Sample records for immune system behavior

  1. The Immune System and Developmental Programming of Brain and Behavior

    PubMed Central

    Bilbo, Staci D.; Schwarz, Jaclyn M.

    2012-01-01

    The brain, endocrine, and immune systems are inextricably linked. Immune molecules have a powerful impact on neuroendocrine function, including hormone-behavior interactions, during health as well as sickness. Similarly, alterations in hormones, such as during stress, can powerfully impact immune function or reactivity. These functional shifts are evolved, adaptive responses that organize changes in behavior and mobilize immune resources, but can also lead to pathology or exacerbate disease if prolonged or exaggerated. The developing brain in particular is exquisitely sensitive to both endogenous and exogenous signals, and increasing evidence suggests the immune system has a critical role in brain development and associated behavioral outcomes for the life of the individual. Indeed, there are associations between many neuropsychiatric disorders and immune dysfunction, with a distinct etiology in neurodevelopment. The goal of this review is to describe the important role of the immune system during brain development, and to discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, mood and cognition. PMID:22982535

  2. Behavioral Immunity in Insects

    PubMed Central

    de Roode, Jacobus C.; Lefèvre, Thierry

    2012-01-01

    Parasites can dramatically reduce the fitness of their hosts, and natural selection should favor defense mechanisms that can protect hosts against disease. Much work has focused on understanding genetic and physiological immunity against parasites, but hosts can also use behaviors to avoid infection, reduce parasite growth or alleviate disease symptoms. It is increasingly recognized that such behaviors are common in insects, providing strong protection against parasites and parasitoids. We review the current evidence for behavioral immunity in insects, present a framework for investigating such behavior, and emphasize that behavioral immunity may act through indirect rather than direct fitness benefits. We also discuss the implications for host-parasite co-evolution, local adaptation, and the evolution of non-behavioral physiological immune systems. Finally, we argue that the study of behavioral immunity in insects has much to offer for investigations in vertebrates, in which this topic has traditionally been studied. PMID:26466629

  3. Identification of an immune-responsive mesolimbocortical serotonergic system: Potential role in regulation of emotional behavior

    PubMed Central

    Lowry, C.A.; Hollis, J.H.; de Vries, A.; Pan, B.; Brunet, L.R.; Hunt, J.R.F.; Paton, J.F.R.; van Kampen, E.; Knight, D.M.; Evans, A.K.; Rook, G.A.W.; Lightman, S.L.

    2007-01-01

    Peripheral immune activation can have profound physiological and behavioral effects including induction of fever and sickness behavior. One mechanism through which immune activation or immunomodulation may affect physiology and behavior is via actions on brainstem neuromodulatory systems, such as serotonergic systems. We have found that peripheral immune activation with antigens derived from the nonpathogenic, saprophytic bacterium, Mycobacterium vaccae, activated a specific subset of serotonergic neurons in the interfascicular part of the dorsal raphe nucleus (DRI) of mice, as measured by quantification of c-Fos expression following intratracheal (12 h) or s.c. (6 h) administration of heat-killed, ultrasonically disrupted M. vaccae, or heat-killed, intact M. vaccae, respectively. These effects were apparent after immune activation by M. vaccae or its components but not by ovalbumin, which induces a qualitatively different immune response. The effects of immune activation were associated with increases in serotonin metabolism within the ventromedial prefrontal cortex, consistent with an effect of immune activation on mesolimbocortical serotonergic systems. The effects of M. vaccae administration on serotonergic systems were temporally associated with reductions in immobility in the forced swim test, consistent with the hypothesis that the stimulation of mesolimbocortical serotonergic systems by peripheral immune activation alters stress-related emotional behavior. These findings suggest that the immune-responsive subpopulation of serotonergic neurons in the DRI is likely to play an important role in the neural mechanisms underlying regulation of the physiological and pathophysiological responses to both acute and chronic immune activation, including regulation of mood during health and disease states. Together with previous studies, these findings also raise the possibility that immune stimulation activates a functionally and anatomically distinct subset of

  4. Immune System as a Sensory System

    PubMed Central

    Dozmorov, Igor M.; Dresser, D.

    2010-01-01

    As suggested by the well-known gestalt concept the immune system can be regarded as an integrated complex system, the functioning of which cannot be fully characterized by the behavior of its constituent elements. Similar approaches to the immune system in particular and sensory systems in general allows one to discern similarities and differences in the process of distinguishing informative patterns in an otherwise random background, thus initiating an appropriate and adequate response. This may lead to a new interpretation of difficulties in the comprehension of some immunological phenomena. PMID:21686066

  5. A gut feeling: Microbiome-brain-immune interactions modulate social and affective behaviors.

    PubMed

    Sylvia, Kristyn E; Demas, Gregory E

    2018-03-01

    The expression of a wide range of social and affective behaviors, including aggression and investigation, as well as anxiety- and depressive-like behaviors, involves interactions among many different physiological systems, including the neuroendocrine and immune systems. Recent work suggests that the gut microbiome may also play a critical role in modulating behavior and likely functions as an important integrator across physiological systems. Microbes within the gut may communicate with the brain via both neural and humoral pathways, providing numerous avenues of research in the area of the gut-brain axis. We are now just beginning to understand the intricate relationships among the brain, microbiome, and immune system and how they work in concert to influence behavior. The effects of different forms of experience (e.g., changes in diet, immune challenge, and psychological stress) on the brain, gut microbiome, and the immune system have often been studied independently. Though because these systems do not work in isolation, it is essential to shift our focus to the connections among them as we move forward in our investigations of the gut-brain axis, the shaping of behavioral phenotypes, and the possible clinical implications of these interactions. This review summarizes the recent progress the field has made in understanding the important role the gut microbiome plays in the modulation of social and affective behaviors, as well as some of the intricate mechanisms by which the microbiome may be communicating with the brain and immune system. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. An immunity-based anomaly detection system with sensor agents.

    PubMed

    Okamoto, Takeshi; Ishida, Yoshiteru

    2009-01-01

    This paper proposes an immunity-based anomaly detection system with sensor agents based on the specificity and diversity of the immune system. Each agent is specialized to react to the behavior of a specific user. Multiple diverse agents decide whether the behavior is normal or abnormal. Conventional systems have used only a single sensor to detect anomalies, while the immunity-based system makes use of multiple sensors, which leads to improvements in detection accuracy. In addition, we propose an evaluation framework for the anomaly detection system, which is capable of evaluating the differences in detection accuracy between internal and external anomalies. This paper focuses on anomaly detection in user's command sequences on UNIX-like systems. In experiments, the immunity-based system outperformed some of the best conventional systems.

  7. Network representations of immune system complexity

    PubMed Central

    Subramanian, Naeha; Torabi-Parizi, Parizad; Gottschalk, Rachel A.; Germain, Ronald N.; Dutta, Bhaskar

    2015-01-01

    The mammalian immune system is a dynamic multi-scale system composed of a hierarchically organized set of molecular, cellular and organismal networks that act in concert to promote effective host defense. These networks range from those involving gene regulatory and protein-protein interactions underlying intracellular signaling pathways and single cell responses to increasingly complex networks of in vivo cellular interaction, positioning and migration that determine the overall immune response of an organism. Immunity is thus not the product of simple signaling events but rather non-linear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multi-scale spatial and temporal interactions, permitting development of computational models that can be used to predict responses to perturbation. Recent technological advances permit collection of comprehensive datasets at multiple molecular and cellular levels while advances in network biology support representation of the relationships of components at each level as physical or functional interaction networks. The latter facilitate effective visualization of patterns and recognition of emergent properties arising from the many interactions of genes, molecules, and cells of the immune system. We illustrate the power of integrating ‘omics’ and network modeling approaches for unbiased reconstruction of signaling and transcriptional networks with a focus on applications involving the innate immune system. We further discuss future possibilities for reconstruction of increasingly complex cellular and organism-level networks and development of sophisticated computational tools for prediction of emergent immune behavior arising from the concerted action of these networks. PMID:25625853

  8. The S(c)ensory Immune System Theory.

    PubMed

    Veiga-Fernandes, Henrique; Freitas, António A

    2017-10-01

    Viewpoints on the immune system have evolved across different paradigms, including the clonal selection theory, the idiotypic network, and the danger and tolerance models. Herein, we propose that in multicellular organisms, where panoplies of cells from different germ layers interact and immune cells are constantly generated, the behavior of the immune system is defined by the rules governing cell survival, systems physiology and organismic homeostasis. Initially, these rules were imprinted at the single cell-protist level, but supervened modifications in the transition to multicellular organisms. This context determined the emergence of the 'sensory immune system', which operates in a s(c)ensor mode to ensure systems physiology, organismic homeostasis, and perpetuation of its replicating molecules. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Systems-Level Analysis of Innate Immunity

    PubMed Central

    Zak, Daniel E.; Tam, Vincent C.; Aderem, Alan

    2014-01-01

    Systems-level analysis of biological processes strives to comprehensively and quantitatively evaluate the interactions between the relevant molecular components over time, thereby enabling development of models that can be employed to ultimately predict behavior. Rapid development in measurement technologies (omics), when combined with the accessible nature of the cellular constituents themselves, is allowing the field of innate immunity to take significant strides toward this lofty goal. In this review, we survey exciting results derived from systems biology analyses of the immune system, ranging from gene regulatory networks to influenza pathogenesis and systems vaccinology. PMID:24655298

  10. Probiotics Improve Inflammation-Associated Sickness Behavior by Altering Communication between the Peripheral Immune System and the Brain.

    PubMed

    D'Mello, Charlotte; Ronaghan, Natalie; Zaheer, Raza; Dicay, Michael; Le, Tai; MacNaughton, Wallace K; Surrette, Michael G; Swain, Mark G

    2015-07-29

    Patients with systemic inflammatory diseases (e.g., rheumatoid arthritis, inflammatory bowel disease, chronic liver disease) commonly develop debilitating symptoms (i.e., sickness behaviors) that arise from changes in brain function. The microbiota-gut-brain axis alters brain function and probiotic ingestion can influence behavior. However, how probiotics do this remains unclear. We have previously described a novel periphery-to-brain communication pathway in the setting of peripheral organ inflammation whereby monocytes are recruited to the brain in response to systemic TNF-α signaling, leading to microglial activation and subsequently driving sickness behavior development. Therefore, we investigated whether probiotic ingestion (i.e., probiotic mixture VSL#3) alters this periphery-to-brain communication pathway, thereby reducing subsequent sickness behavior development. Using a well characterized mouse model of liver inflammation, we now show that probiotic (VSL#3) treatment attenuates sickness behavior development in mice with liver inflammation without affecting disease severity, gut microbiota composition, or gut permeability. Attenuation of sickness behavior development was associated with reductions in microglial activation and cerebral monocyte infiltration. These events were paralleled by changes in markers of systemic immune activation, including decreased circulating TNF-α levels. Our observations highlight a novel pathway through which probiotics mediate cerebral changes and alter behavior. These findings allow for the potential development of novel therapeutic interventions targeted at the gut microbiome to treat inflammation-associated sickness behaviors in patients with systemic inflammatory diseases. This research shows that probiotics, when eaten, can improve the abnormal behaviors (including social withdrawal and immobility) that are commonly associated with inflammation. Probiotics are able to cause this effect within the body by changing how

  11. Behavioral Immunity Suppresses an Epizootic in Caribbean Spiny Lobsters.

    PubMed

    Butler, Mark J; Behringer, Donald C; Dolan, Thomas W; Moss, Jessica; Shields, Jeffrey D

    2015-01-01

    Sociality has evolved in a wide range of animal taxa but infectious diseases spread rapidly in populations of aggregated individuals, potentially negating the advantages of their social interactions. To disengage from the coevolutionary struggle with pathogens, some hosts have evolved various forms of "behavioral immunity"; yet, the effectiveness of such behaviors in controlling epizootics in the wild is untested. Here we show how one form of behavioral immunity (i.e., the aversion of diseased conspecifics) practiced by Caribbean spiny lobsters (Panulirus argus) when subject to the socially transmitted PaV1 virus, appears to have prevented an epizootic over a large seascape. We capitalized on a "natural experiment" in which a die-off of sponges in the Florida Keys (USA) resulted in a loss of shelters for juvenile lobsters over a ~2500km2 region. Lobsters were thus concentrated in the few remaining shelters, presumably increasing their exposure to the contagious virus. Despite this spatial reorganization of the population, viral prevalence in lobsters remained unchanged after the sponge die-off and for years thereafter. A field experiment in which we introduced either a healthy or PaV1-infected lobster into lobster aggregations in natural dens confirmed that spiny lobsters practice behavioral immunity. Healthy lobsters vacated dens occupied by PaV1-infected lobsters despite the scarcity of alternative shelters and the higher risk of predation they faced when searching for a new den. Simulations from a spatially-explicit, individual-based model confirmed our empirical results, demonstrating the efficacy of behavioral immunity in preventing epizootics in this system.

  12. Streptozotocin induced oxidative stress, innate immune system responses and behavioral abnormalities in male mice.

    PubMed

    Amiri, Shayan; Haj-Mirzaian, Arya; Momeny, Majid; Amini-Khoei, Hossein; Rahimi-Balaei, Maryam; Poursaman, Simin; Rastegar, Mojgan; Nikoui, Vahid; Mokhtari, Tahmineh; Ghazi-Khansari, Mahmoud; Hosseini, Mir-Jamal

    2017-01-06

    Recent evidence indicates the involvement of inflammatory factors and mitochondrial dysfunction in the etiology of psychiatric disorders such as anxiety and depression. To investigate the possible role of mitochondrial-induced sterile inflammation in the co-occurrence of anxiety and depression, in this study, we treated adult male mice with the intracerebroventricular (i.c.v.) infusion of a single low dose of streptozotocin (STZ, 0.2mg/mouse). Using valid and qualified behavioral tests for the assessment of depressive and anxiety-like behaviors, we showed that STZ-treated mice exhibited behaviors relevant to anxiety and depression 24h following STZ treatment. We observed that the co-occurrence of anxiety and depressive-like behaviors in animals were associated with abnormal mitochondrial function, nitric oxide overproduction and, the increased activity of cytosolic phospholipase A 2 (cPLA 2 ) in the hippocampus. Further, STZ-treated mice had a significant upregulation of genes associated with the innate immune system such as toll-like receptors 2 and 4. Pathological evaluations showed no sign of neurodegeneration in the hippocampus of STZ-treated mice. Results of this study revealed that behavioral abnormalities provoked by STZ, as a cytotoxic agent that targets mitochondria and energy metabolism, are associated with abnormal mitochondrial activity and, consequently the initiation of innate-inflammatory responses in the hippocampus. Our findings highlight the role of mitochondria and innate immunity in the formation of sterile inflammation and behaviors relevant to anxiety and depression. Also, we have shown that STZ injection (i.c.v.) might be an animal model for depression and anxiety disorders based on sterile inflammation. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  13. Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring.

    PubMed

    Bauman, Melissa D; Iosif, Ana-Maria; Smith, Stephen E P; Bregere, Catherine; Amaral, David G; Patterson, Paul H

    2014-02-15

    Maternal infection during pregnancy is associated with an increased risk of schizophrenia and autism in the offspring. Supporting this correlation, experimentally activating the maternal immune system during pregnancy in rodents produces offspring with abnormal brain and behavioral development. We have developed a nonhuman primate model to bridge the gap between clinical populations and rodent models of maternal immune activation (MIA). A modified form of the viral mimic, synthetic double-stranded RNA (polyinosinic:polycytidylic acid stabilized with poly-L-lysine) was delivered to two separate groups of pregnant rhesus monkeys to induce MIA: 1) late first trimester MIA (n = 6), and 2) late second trimester MIA (n = 7). Control animals (n = 11) received saline injections at the same first or second trimester time points or were untreated. Sickness behavior, temperature, and cytokine profiles of the pregnant monkeys confirmed a strong inflammatory response to MIA. Behavioral development of the offspring was studied for 24 months. Following weaning at 6 months of age, MIA offspring exhibited abnormal responses to separation from their mothers. As the animals matured, MIA offspring displayed increased repetitive behaviors and decreased affiliative vocalizations. When evaluated with unfamiliar conspecifics, first trimester MIA offspring deviated from species-typical macaque social behavior by inappropriately approaching and remaining in immediate proximity of an unfamiliar animal. In this rhesus monkey model, MIA yields offspring with abnormal repetitive behaviors, communication, and social interactions. These results extended the findings in rodent MIA models to more human-like behaviors resembling those in both autism and schizophrenia. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Immune System Activation and Depression: Roles of Serotonin in the Central Nervous System and Periphery.

    PubMed

    Robson, Matthew J; Quinlan, Meagan A; Blakely, Randy D

    2017-05-17

    Serotonin (5-hydroxytryptamine, 5-HT) has long been recognized as a key contributor to the regulation of mood and anxiety and is strongly associated with the etiology of major depressive disorder (MDD). Although more known for its roles within the central nervous system (CNS), 5-HT is recognized to modulate several key aspects of immune system function that may contribute to the development of MDD. Copious amounts of research have outlined a connection between alterations in immune system function, inflammation status, and MDD. Supporting this connection, peripheral immune activation results in changes in the function and/or expression of many components of 5-HT signaling that are associated with depressive-like phenotypes. How 5-HT is utilized by the immune system to effect CNS function and ultimately behaviors related to depression is still not well understood. This Review summarizes the evidence that immune system alterations related to depression affect CNS 5-HT signaling that can alter MDD-relevant behaviors and that 5-HT regulates immune system signaling within the CNS and periphery. We suggest that targeting the interrelationships between immune and 5-HT signaling may provide more effective treatments for subsets of those suffering from inflammation-associated MDD.

  15. The Immune System, Cytokines, and Biomarkers in Autism Spectrum Disorder.

    PubMed

    Masi, Anne; Glozier, Nicholas; Dale, Russell; Guastella, Adam J

    2017-04-01

    Autism Spectrum Disorder (ASD) is a pervasive neurodevelopmental condition characterized by variable impairments in communication and social interaction as well as restricted interests and repetitive behaviors. Heterogeneity of presentation is a hallmark. Investigations of immune system problems in ASD, including aberrations in cytokine profiles and signaling, have been increasing in recent times and are the subject of ongoing interest. With the aim of establishing whether cytokines have utility as potential biomarkers that may define a subgroup of ASD, or function as an objective measure of response to treatment, this review summarizes the role of the immune system, discusses the relationship between the immune system, the brain, and behavior, and presents previously-identified immune system abnormalities in ASD, specifically addressing the role of cytokines in these aberrations. The roles and identification of biomarkers are also addressed, particularly with respect to cytokine profiles in ASD.

  16. The effects of early life adversity on the immune system.

    PubMed

    Elwenspoek, Martha M C; Kuehn, Annette; Muller, Claude P; Turner, Jonathan D

    2017-08-01

    Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the 'ELA immune phenotype', characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Behavioral immune system and ingroup derogation: the effects of infectious diseases on ingroup derogation attitudes.

    PubMed

    Wu, Qi; Tan, Chuan; Wang, Bo; Zhou, Ping

    2015-01-01

    From evolutionary reasoning, we derived a novel hypothesis that ingroup derogation is an evolved response of behavioral immune system which follows the smoke detector principle and the functional flexibility principle. This hypothesis was tested and supported across three experiments. In Experiment 1, participants' group membership was manipulated by using a minimal group paradigm. The results indicated that mere social categorization alone - a heuristic cue that implies the differentiation between "us" and "them" - was sufficient to elicit ingroup derogation among Chinese participants, and, such an intergroup bias was positively associated with the perceived vulnerability to diseases, which was also more consistently associated with ingroup attitudes. Experiment 2 extended and partially replicated Experiment 1 by showing that when there were cues of diseases in the immediate physical environment, Chinese participants exaggerated their attitudes of ingroup derogation. The results also showed that this effect was mainly driven by outgroup attraction. Experiment 3 changed the method of disease manipulation, and found that Chinese participants responded more strongly to disease cues originating from ingroup members and that they endorsed more ingroup derogation attitudes even when the ingroup and outgroup members were both displaying cues of diseases. Taken together, these results reveal the previously unexplored effects of infectious diseases on ingroup derogation attitudes, and suggest an interesting linkage between the evolved behavioral immune system and the ingroup derogation.

  18. Behavioral Immunity Suppresses an Epizootic in Caribbean Spiny Lobsters

    PubMed Central

    Butler, Mark J.; Behringer, Donald C.; Dolan, Thomas W.; Moss, Jessica; Shields, Jeffrey D.

    2015-01-01

    Sociality has evolved in a wide range of animal taxa but infectious diseases spread rapidly in populations of aggregated individuals, potentially negating the advantages of their social interactions. To disengage from the coevolutionary struggle with pathogens, some hosts have evolved various forms of “behavioral immunity”; yet, the effectiveness of such behaviors in controlling epizootics in the wild is untested. Here we show how one form of behavioral immunity (i.e., the aversion of diseased conspecifics) practiced by Caribbean spiny lobsters (Panulirus argus) when subject to the socially transmitted PaV1 virus, appears to have prevented an epizootic over a large seascape. We capitalized on a "natural experiment" in which a die-off of sponges in the Florida Keys (USA) resulted in a loss of shelters for juvenile lobsters over a ~2500km2 region. Lobsters were thus concentrated in the few remaining shelters, presumably increasing their exposure to the contagious virus. Despite this spatial reorganization of the population, viral prevalence in lobsters remained unchanged after the sponge die-off and for years thereafter. A field experiment in which we introduced either a healthy or PaV1-infected lobster into lobster aggregations in natural dens confirmed that spiny lobsters practice behavioral immunity. Healthy lobsters vacated dens occupied by PaV1-infected lobsters despite the scarcity of alternative shelters and the higher risk of predation they faced when searching for a new den. Simulations from a spatially-explicit, individual-based model confirmed our empirical results, demonstrating the efficacy of behavioral immunity in preventing epizootics in this system. PMID:26061629

  19. Microbes, Immunity, and Behavior: Psychoneuroimmunology Meets the Microbiome

    PubMed Central

    Dinan, Timothy G; Cryan, John F

    2017-01-01

    There is now a large volume of evidence to support the view that the immune system is a key communication pathway between the gut and brain, which plays an important role in stress-related psychopathologies and thus provides a potentially fruitful target for psychotropic intervention. The gut microbiota is a complex ecosystem with a diverse range of organisms and a sophisticated genomic structure. Bacteria within the gut are estimated to weigh in excess of 1 kg in the adult human and the microbes within not only produce antimicrobial peptides, short chain fatty acids, and vitamins, but also most of the common neurotransmitters found in the human brain. That the microbial content of the gut plays a key role in immune development is now beyond doubt. Early disruption of the host-microbe interplay can have lifelong consequences, not just in terms of intestinal function but in distal organs including the brain. It is clear that the immune system and nervous system are in continuous communication in order to maintain a state of homeostasis. Significant gaps in knowledge remain about the effect of the gut microbiota in coordinating the immune-nervous systems dialogue. However, studies using germ-free animals, infective models, prebiotics, probiotics, and antibiotics have increased our understanding of the interplay. Early life stress can have a lifelong impact on the microbial content of the intestine and permanently alter immune functioning. That early life stress can also impact adult psychopathology has long been appreciated in psychiatry. The challenge now is to fully decipher the molecular mechanisms that link the gut microbiota, immune, and central nervous systems in a network of communication that impacts behavior patterns and psychopathology, to eventually translate these findings to the human situation both in health and disease. Even at this juncture, there is evidence to pinpoint key sites of communication where gut microbial interventions either with drugs

  20. Immune System Quiz

    MedlinePlus

    ... Videos for Educators Search English Español Quiz: Immune System KidsHealth / For Kids / Quiz: Immune System Print How much do you know about your immune system? Find out by taking this quiz! About Us ...

  1. Immune system gene dysregulation in autism and schizophrenia.

    PubMed

    Michel, Maximilian; Schmidt, Martin J; Mirnics, Karoly

    2012-10-01

    Gene*environment interactions play critical roles in the emergence of autism and schizophrenia pathophysiology. In both disorders, recent genetic association studies have provided evidence for disease-linked variation in immune system genes and postmortem gene expression studies have shown extensive chronic immune abnormalities in brains of diseased subjects. Furthermore, peripheral biomarker studies revealed that both innate and adaptive immune systems are dysregulated. In both disorders symptoms of the disease correlate with the immune system dysfunction; yet, in autism this process appears to be chronic and sustained, while in schizophrenia it is exacerbated during acute episodes. Furthermore, since immune abnormalities endure into adulthood and anti-inflammatory agents appear to be beneficial, it is likely that these immune changes actively contribute to disease symptoms. Modeling these changes in animals provided further evidence that prenatal maternal immune activation alters neurodevelopment and leads to behavioral changes that are relevant for autism and schizophrenia. The converging evidence strongly argues that neurodevelopmental immune insults and genetic background critically interact and result in increased risk for either autism or schizophrenia. Further research in these areas may improve prenatal health screening in genetically at-risk families and may also lead to new preventive and/or therapeutic strategies. Copyright © 2012 Wiley Periodicals, Inc.

  2. Do infant behaviors following immunization predict attachment? An exploratory study.

    PubMed

    Horton, Rachel; Pillai Riddell, Rebecca; Moran, Greg; Lisi, Diana

    2016-01-01

    The relationship between infant behaviors during routine immunization, pre- and post-needle, and infant attachment was explored. A total of 130 parent-infant dyads were recruited from a larger longitudinal study and videotaped during routine immunization at 12 months and the Strange Situation Procedure (SSP) at 14 months. Six infant behaviors were coded for 1-minute pre-needle and 3-minutes post-needle. Attachment was operationalized according to the secure/avoidant/resistant/disorganized categories. As expected, none of the pre-needle behaviors predicted attachment. Proximity-seeking post-needle significantly discriminated attachment categorizations. Secure infants were more likely to seek proximity to caregivers post-needle in comparison with avoidant and disorganized infants. Proximity-seeking following immunization was positively correlated with proximity-seeking during the SSP and negatively correlated with avoidance and disorganization during the SSP. Infant proximity-seeking during immunization is associated with attachment security and parallels behaviors observed during the SSP. More research is needed to identify behavioral markers of disorganization.

  3. [Immune system and tumors].

    PubMed

    Terme, Magali; Tanchot, Corinne

    2017-02-01

    Despite having been much debated, it is now well established that the immune system plays an essential role in the fight against cancer. In this article, we will highlight the implication of the immune system in the control of tumor growth and describe the major components of the immune system involved in the antitumoral immune response. The immune system, while exerting pressure on tumor cells, also will play a pro-tumoral role by sculpting the immunogenicity of tumors cells as they develop. Finally, we will illustrate the numerous mechanisms of immune suppression that take place within the tumoral microenvironment which allow tumor cells to escape control from the immune system. The increasingly precise knowledge of the brakes to an effective antitumor immune response allows the development of immunotherapy strategies more and more innovating and promising of hope. Copyright © 2016. Published by Elsevier Masson SAS.

  4. Behavioral Fever Drives Epigenetic Modulation of the Immune Response in Fish.

    PubMed

    Boltana, Sebastian; Aguilar, Andrea; Sanhueza, Nataly; Donoso, Andrea; Mercado, Luis; Imarai, Monica; Mackenzie, Simon

    2018-01-01

    Ectotherms choose the best thermal conditions to mount a successful immune response, a phenomenon known as behavioral fever. The cumulative evidence suggests that behavioral fever impacts positively upon lymphocyte proliferation, inflammatory cytokine expression, and other immune functions. In this study, we have explored how thermal choice during infection impacts upon underpinning molecular processes and how temperature increase is coupled to the immune response. Our results show that behavioral fever results in a widespread, plastic imprint on gene regulation, and lymphocyte proliferation. We further explored the possible contribution of histone modification and identified global associations between temperature and histone changes that suggest epigenetic remodeling as a result of behavioral fever. Together, these results highlight the critical importance of thermal choice in mobile ectotherms, particularly in response to an infection, and demonstrate the key role of epigenetic modification to orchestrate the thermocoupling of the immune response during behavioral fever.

  5. Relations among Functional Systems in Behavior Analysis

    ERIC Educational Resources Information Center

    Thompson, Travis

    2007-01-01

    This paper proposes that an organism's integrated repertoire of operant behavior has the status of a biological system, similar to other biological systems, like the nervous, cardiovascular, or immune systems. Evidence from a number of sources indicates that the distinctions between biological and behavioral events is often misleading, engendering…

  6. Immune system

    USDA-ARS?s Scientific Manuscript database

    This chapter is an update on the swine Immune System. It will be Chapter 16 in the 11th Edition (2018) of Diseases of Swine. The chapter outlines all aspects of the swine immune system in development and in responses to infection and vaccination. It illustrates the tremendous influence that the immu...

  7. Assessing providers' vaccination behaviors during routine immunization in India.

    PubMed

    Cohen, Megan A; Gargano, Lisa M; Thacker, Naveen; Choudhury, Panna; Weiss, Paul S; Arora, Manisha; Orenstein, Walter A; Omer, Saad B; Hughes, James M

    2015-08-01

    Progress has been made toward improving routine immunization coverage in India, but universal coverage has not been achieved. Little is known about how providers' vaccination behaviors affect coverage rates. The purpose of this study was to identify provider behaviors that served as barriers to vaccination that could lead to missed opportunities to vaccinate. We conducted a study of health-care providers' vaccination behaviors during clinic visits for children <3 years of age. Information on provider behaviors was collected through parent report and direct observation. Compared with illness visits, parents were eight times more likely to report vaccination status was verified (p < 0.001) and three times more likely to report receiving counseling on immunization (p = 0.022) during vaccination visits. Training of all vaccination practitioners should focus on behaviors such as the necessity of verifying vaccination status regardless of visit type, stressing the importance of counseling parents on immunization and emphasizing what is a valid contraindication to vaccination. © The Author [2015]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Testicular defense systems: immune privilege and innate immunity

    PubMed Central

    Zhao, Shutao; Zhu, Weiwei; Xue, Shepu; Han, Daishu

    2014-01-01

    The mammalian testis possesses a special immunological environment because of its properties of remarkable immune privilege and effective local innate immunity. Testicular immune privilege protects immunogenic germ cells from systemic immune attack, and local innate immunity is important in preventing testicular microbial infections. The breakdown of local testicular immune homeostasis may lead to orchitis, an etiological factor of male infertility. The mechanisms underlying testicular immune privilege have been investigated for a long time. Increasing evidence shows that both a local immunosuppressive milieu and systemic immune tolerance are involved in maintaining testicular immune privilege status. The mechanisms underlying testicular innate immunity are emerging based on the investigation of the pattern recognition receptor-mediated innate immune response in testicular cells. This review summarizes our current understanding of testicular defense mechanisms and identifies topics that merit further investigation. PMID:24954222

  9. How Psychological States Affect the Immune System: Implications for Interventions in the Context of HIV.

    ERIC Educational Resources Information Center

    Littrell, Jill

    1996-01-01

    Discusses the psychological states associated with enhanced immune system functioning and those associated with suppressed immune functioning. Reviews studies of psychological and behavioral interventions to boost the immune systems of people who are HIV positive. Suggests that group interventions can enhance psychological states associated with…

  10. Intranasal Immune Challenge Induces Sex-Dependent Depressive-Like Behavior and Cytokine Expression in the Brain

    PubMed Central

    Tonelli, Leonardo H; Holmes, Andrew; Postolache, Teodor T

    2007-01-01

    The association between activation of the immune system and mood disorders has been reported by several studies. However, the mechanisms by which the immune system affects mood are only partially understood. In the present study, we detected depressive-like behavior in a rat animal model which involves the induction of inflammation in the nasal cavities by intranasal (i.n.) instillation of bacterial lipopolysaccharides (LPS). Female rats showed depressive-like behavior as evidenced by the forced swim test after repeated i.n. administration of LPS. These responses were not paralleled by alterations in motor activity as measured by the open field test. In the same animals, corticosterone responses after the swimming sessions were the highest of all the groups evaluated. Real-time RT PCR was used to analyze the transcriptional regulation of the cytokines interleukin-1β, tumor necrosis factor-α, and interleukin-6 in several brain regions. Increased tumor necrosis factor-α was detected in the hippocampus and brainstem of female rats challenged with i.n. LPS. These results suggest that peripheral inflammation in the upper respiratory tract is an immune challenge capable of inducing depressive-like behavior, promoting exaggerated glucocorticoid responses to stress, and increasing cytokine transcription in the brain. These results further our understanding of the role that the immune system may play in the pathophysiology of depression. PMID:17593929

  11. Artificial Immune System for Recognizing Patterns

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terrance

    2005-01-01

    A method of recognizing or classifying patterns is based on an artificial immune system (AIS), which includes an algorithm and a computational model of nonlinear dynamics inspired by the behavior of a biological immune system. The method has been proposed as the theoretical basis of the computational portion of a star-tracking system aboard a spacecraft. In that system, a newly acquired star image would be treated as an antigen that would be matched by an appropriate antibody (an entry in a star catalog). The method would enable rapid convergence, would afford robustness in the face of noise in the star sensors, would enable recognition of star images acquired in any sensor or spacecraft orientation, and would not make an excessive demand on the computational resources of a typical spacecraft. Going beyond the star-tracking application, the AIS-based pattern-recognition method is potentially applicable to pattern- recognition and -classification processes for diverse purposes -- for example, reconnaissance, detecting intruders, and mining data.

  12. Immunity-Based Aircraft Fault Detection System

    NASA Technical Reports Server (NTRS)

    Dasgupta, D.; KrishnaKumar, K.; Wong, D.; Berry, M.

    2004-01-01

    In the study reported in this paper, we have developed and applied an Artificial Immune System (AIS) algorithm for aircraft fault detection, as an extension to a previous work on intelligent flight control (IFC). Though the prior studies had established the benefits of IFC, one area of weakness that needed to be strengthened was the control dead band induced by commanding a failed surface. Since the IFC approach uses fault accommodation with no detection, the dead band, although it reduces over time due to learning, is present and causes degradation in handling qualities. If the failure can be identified, this dead band can be further A ed to ensure rapid fault accommodation and better handling qualities. The paper describes the application of an immunity-based approach that can detect a broad spectrum of known and unforeseen failures. The approach incorporates the knowledge of the normal operational behavior of the aircraft from sensory data, and probabilistically generates a set of pattern detectors that can detect any abnormalities (including faults) in the behavior pattern indicating unsafe in-flight operation. We developed a tool called MILD (Multi-level Immune Learning Detection) based on a real-valued negative selection algorithm that can generate a small number of specialized detectors (as signatures of known failure conditions) and a larger set of generalized detectors for unknown (or possible) fault conditions. Once the fault is detected and identified, an adaptive control system would use this detection information to stabilize the aircraft by utilizing available resources (control surfaces). We experimented with data sets collected under normal and various simulated failure conditions using a piloted motion-base simulation facility. The reported results are from a collection of test cases that reflect the performance of the proposed immunity-based fault detection algorithm.

  13. Control of adaptive immunity by the innate immune system.

    PubMed

    Iwasaki, Akiko; Medzhitov, Ruslan

    2015-04-01

    Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting adaptive immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of adaptive immunity.

  14. Immune System

    EPA Science Inventory

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  15. Embracing Complexity beyond Systems Medicine: A New Approach to Chronic Immune Disorders

    PubMed Central

    te Velde, Anje A.; Bezema, Tjitske; van Kampen, Antoine H. C.; Kraneveld, Aletta D.; 't Hart, Bert A.; van Middendorp, Henriët; Hack, Erik C.; van Montfrans, Joris M.; Belzer, Clara; Jans-Beken, Lilian; Pieters, Raymond H.; Knipping, Karen; Huber, Machteld; Boots, Annemieke M. H.; Garssen, Johan; Radstake, Tim R.; Evers, Andrea W. M.; Prakken, Berent J.; Joosten, Irma

    2016-01-01

    In order to combat chronic immune disorders (CIDs), it is an absolute necessity to understand the bigger picture, one that goes beyond insights at a one-disease, molecular, cellular, and static level. To unravel this bigger picture we advocate an integral, cross-disciplinary approach capable of embracing the complexity of the field. This paper discusses the current knowledge on common pathways in CIDs including general psychosocial and lifestyle factors associated with immune functioning. We demonstrate the lack of more in-depth psychosocial and lifestyle factors in current research cohorts and most importantly the need for an all-encompassing analysis of these factors. The second part of the paper discusses the challenges of understanding immune system dynamics and effectively integrating all key perspectives on immune functioning, including the patient’s perspective itself. This paper suggests the use of techniques from complex systems science in describing and simulating healthy or deviating behavior of the immune system in its biopsychosocial surroundings. The patient’s perspective data are suggested to be generated by using specific narrative techniques. We conclude that to gain more insight into the behavior of the whole system and to acquire new ways of combatting CIDs, we need to construct and apply new techniques in the field of computational and complexity science, to an even wider variety of dynamic data than used in today’s systems medicine. PMID:28018353

  16. Pattern dynamics of the reaction-diffusion immune system.

    PubMed

    Zheng, Qianqian; Shen, Jianwei; Wang, Zhijie

    2018-01-01

    In this paper, we will investigate the effect of diffusion, which is ubiquitous in nature, on the immune system using a reaction-diffusion model in order to understand the dynamical behavior of complex patterns and control the dynamics of different patterns. Through control theory and linear stability analysis of local equilibrium, we obtain the optimal condition under which the system loses stability and a Turing pattern occurs. By combining mathematical analysis and numerical simulation, we show the possible patterns and how these patterns evolve. In addition, we establish a bridge between the complex patterns and the biological mechanism using the results from a previous study in Nature Cell Biology. The results in this paper can help us better understand the biological significance of the immune system.

  17. Neuroendocrine-Immune Circuits, Phenotypes, and Interactions

    PubMed Central

    Ashley, Noah T.; Demas, Gregory E.

    2016-01-01

    Multidirectional interactions among the immune, endocrine, and nervous systems have been demonstrated in humans and non-human animal models for many decades by the biomedical community, but ecological and evolutionary perspectives are lacking. Neuroendocrine-immune interactions can be conceptualized using a series of feedback loops, which culminate into distinct neuroendocrine-immune phenotypes. Behavior can exert profound influences on these phenotypes, which can in turn reciprocally modulate behavior. For example, the behavioral aspects of reproduction, including courtship, aggression, mate selection and parental behaviors can impinge upon neuroendocrine-immune interactions. One classic example is the immunocompetence handicap hypothesis (ICHH), which proposes that steroid hormones act as mediators of traits important for female choice while suppressing the immune system. Reciprocally, neuroendocrine-immune pathways can promote the development of altered behavioral states, such as sickness behavior. Understanding the energetic signals that mediate neuroendocrine-immune crosstalk is an active area of research. Although the field of psychoneuroimmunology (PNI) has begun to explore this crosstalk from a biomedical standpoint, the neuroendocrine-immune-behavior nexus has been relatively underappreciated in comparative species. The field of ecoimmunology, while traditionally emphasizing the study of non-model systems from an ecological evolutionary perspective, often under natural conditions, has focused less on the physiological mechanisms underlying behavioral responses. This review summarizes neuroendocrine-immune interactions using a comparative framework to understand the ecological and evolutionary forces that shape these complex physiological interactions. PMID:27765499

  18. Neuroendocrine-immune circuits, phenotypes, and interactions.

    PubMed

    Ashley, Noah T; Demas, Gregory E

    2017-01-01

    Multidirectional interactions among the immune, endocrine, and nervous systems have been demonstrated in humans and non-human animal models for many decades by the biomedical community, but ecological and evolutionary perspectives are lacking. Neuroendocrine-immune interactions can be conceptualized using a series of feedback loops, which culminate into distinct neuroendocrine-immune phenotypes. Behavior can exert profound influences on these phenotypes, which can in turn reciprocally modulate behavior. For example, the behavioral aspects of reproduction, including courtship, aggression, mate selection and parental behaviors can impinge upon neuroendocrine-immune interactions. One classic example is the immunocompetence handicap hypothesis (ICHH), which proposes that steroid hormones act as mediators of traits important for female choice while suppressing the immune system. Reciprocally, neuroendocrine-immune pathways can promote the development of altered behavioral states, such as sickness behavior. Understanding the energetic signals that mediate neuroendocrine-immune crosstalk is an active area of research. Although the field of psychoneuroimmunology (PNI) has begun to explore this crosstalk from a biomedical standpoint, the neuroendocrine-immune-behavior nexus has been relatively underappreciated in comparative species. The field of ecoimmunology, while traditionally emphasizing the study of non-model systems from an ecological evolutionary perspective, often under natural conditions, has focused less on the physiological mechanisms underlying behavioral responses. This review summarizes neuroendocrine-immune interactions using a comparative framework to understand the ecological and evolutionary forces that shape these complex physiological interactions. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Immunization Information System and Informatics to Promote Immunizations: Perspective From Minnesota Immunization Information Connection.

    PubMed

    Muscoplat, Miriam Halstead; Rajamani, Sripriya

    2017-01-01

    The vision for management of immunization information is availability of real-time consolidated data and services for all ages, to clinical, public health, and other stakeholders. This is being executed through Immunization Information Systems (IISs), which are population-based and confidential computerized systems present in most US states and territories. Immunization Information Systems offer many functionalities, such as immunization assessment reports, client follow-up, reminder/recall feature, vaccine management tools, state-supplied vaccine ordering, comprehensive immunization history, clinical decision support/vaccine forecasting and recommendations, data processing, and data exchange. This perspective article will present various informatics tools in an IIS, in the context of the Minnesota Immunization Information Connection.

  20. Self-organizing behavior in a lattice model for co-evolution of virus and immune systems

    NASA Astrophysics Data System (ADS)

    Izmailian, N. Sh.; Papoyan, Vl. V.; Priezzhev, V. B.; Hu, Chin-Kun

    2007-04-01

    We propose a lattice model for the co-evolution of a virus population and an adaptive immune system. We show that, under some natural assumptions, both probability distribution of the virus population and the distribution of activity of the immune system tend during the evolution to a self-organized critical state.

  1. Aggression, Social Stress, and the Immune System in Humans and Animal Models

    PubMed Central

    Takahashi, Aki; Flanigan, Meghan E.; McEwen, Bruce S.; Russo, Scott J.

    2018-01-01

    Social stress can lead to the development of psychological problems ranging from exaggerated anxiety and depression to antisocial and violence-related behaviors. Increasing evidence suggests that the immune system is involved in responses to social stress in adulthood. For example, human studies show that individuals with high aggression traits display heightened inflammatory cytokine levels and dysregulated immune responses such as slower wound healing. Similar findings have been observed in patients with depression, and comorbidity of depression and aggression was correlated with stronger immune dysregulation. Therefore, dysregulation of the immune system may be one of the mediators of social stress that produces aggression and/or depression. Similar to humans, aggressive animals also show increased levels of several proinflammatory cytokines, however, unlike humans these animals are more protected from infectious organisms and have faster wound healing than animals with low aggression. On the other hand, subordinate animals that receive repeated social defeat stress have been shown to develop escalated and dysregulated immune responses such as glucocorticoid insensitivity in monocytes. In this review we synthesize the current evidence in humans, non-human primates, and rodents to show a role for the immune system in responses to social stress leading to psychiatric problems such as aggression or depression. We argue that while depression and aggression represent two fundamentally different behavioral and physiological responses to social stress, it is possible that some overlapped, as well as distinct, pattern of immune signaling may underlie both of them. We also argue the necessity of studying animal models of maladaptive aggression induced by social stress (i.e., social isolation) for understanding neuro-immune mechanism of aggression, which may be relevant to human aggression. PMID:29623033

  2. Aggression, Social Stress, and the Immune System in Humans and Animal Models.

    PubMed

    Takahashi, Aki; Flanigan, Meghan E; McEwen, Bruce S; Russo, Scott J

    2018-01-01

    Social stress can lead to the development of psychological problems ranging from exaggerated anxiety and depression to antisocial and violence-related behaviors. Increasing evidence suggests that the immune system is involved in responses to social stress in adulthood. For example, human studies show that individuals with high aggression traits display heightened inflammatory cytokine levels and dysregulated immune responses such as slower wound healing. Similar findings have been observed in patients with depression, and comorbidity of depression and aggression was correlated with stronger immune dysregulation. Therefore, dysregulation of the immune system may be one of the mediators of social stress that produces aggression and/or depression. Similar to humans, aggressive animals also show increased levels of several proinflammatory cytokines, however, unlike humans these animals are more protected from infectious organisms and have faster wound healing than animals with low aggression. On the other hand, subordinate animals that receive repeated social defeat stress have been shown to develop escalated and dysregulated immune responses such as glucocorticoid insensitivity in monocytes. In this review we synthesize the current evidence in humans, non-human primates, and rodents to show a role for the immune system in responses to social stress leading to psychiatric problems such as aggression or depression. We argue that while depression and aggression represent two fundamentally different behavioral and physiological responses to social stress, it is possible that some overlapped, as well as distinct, pattern of immune signaling may underlie both of them. We also argue the necessity of studying animal models of maladaptive aggression induced by social stress (i.e., social isolation) for understanding neuro-immune mechanism of aggression, which may be relevant to human aggression.

  3. The effects of stress hormones on immune function may be vital for the adaptive reconfiguration of the immune system during fight-or-flight behavior.

    PubMed

    Adamo, Shelley A

    2014-09-01

    Intense, short-term stress (i.e., robust activation of the fight-or-flight response) typically produces a transient decline in resistance to disease in animals across phyla. Chemical mediators of the stress response (e.g., stress hormones) help induce this decline, suggesting that this transient immunosuppression is an evolved response. However, determining the function of stress hormones on immune function is difficult because of their complexity. Nevertheless, evidence suggests that stress hormones help maintain maximal resistance to disease during the physiological changes needed to optimize the body for intense physical activity. Work on insects demonstrates that stress hormones both shunt resources away from the immune system during fight-or-flight responses as well as reconfigure the immune system. Reconfiguring the immune system minimizes the impact of the loss of these resources and reduces the increased costs of some immune functions due to the physiological changes demanded by the fight-or-flight response. For example, during the stress response of the cricket Gryllus texensis, some molecular resources are shunted away from the immune system and toward lipid transport, resulting in a reduction in resistance to disease. However, insects' immune cells (hemocytes) have receptors for octopamine (the insect stress neurohormone). Octopamine increases many hemocyte functions, such as phagocytosis, and these changes would tend to mitigate the decline in immunity due to the loss of molecular resources. Moreover, because the stress response generates oxidative stress, some immune responses are probably more costly when activated during a stress response (e.g., those that produce reactive molecules). Some of these immune responses are depressed during stress in crickets, while others, whose costs are probably not increased during a stress response, are enhanced. Some effects of stress hormones on immune systems may be better understood as examples of reconfiguration

  4. The twilight of immunity: emerging concepts in aging of the immune system.

    PubMed

    Nikolich-Žugich, Janko

    2018-01-01

    Immunosenescence is a series of age-related changes that affect the immune system and, with time, lead to increased vulnerability to infectious diseases. This Review addresses recent developments in the understanding of age-related changes that affect key components of immunity, including the effect of aging on cells of the (mostly adaptive) immune system, on soluble molecules that guide the maintenance and function of the immune system and on lymphoid organs that coordinate both the maintenance of lymphocytes and the initiation of immune responses. I further address the effect of the metagenome and exposome as key modifiers of immune-system aging and discuss a conceptual framework in which age-related changes in immunity might also affect the basic rules by which the immune system operates.

  5. Systems vaccinology: probing humanity's diverse immune systems with vaccines.

    PubMed

    Pulendran, Bali

    2014-08-26

    Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic changes during the past century have created further diversification with respect to age, nutritional status, and the incidence of associated chronic inflammatory disorders and chronic infections. These shifting demographics pose new challenges for vaccination, as emerging evidence suggests that age, the metabolic state, and chronic infections can exert major influences on the immune system. Thus, a key public health challenge is learning how to reprogram suboptimal immune systems to induce effective vaccine immunity. Recent advances have applied systems biological analysis to define molecular signatures induced early after vaccination that correlate with and predict the later adaptive immune responses in humans. Such "systems vaccinology" approaches offer an integrated picture of the molecular networks driving vaccine immunity, and are beginning to yield novel insights about the immune system. Here we discuss the promise of systems vaccinology in probing humanity's diverse immune systems, and in delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. Such insights will be critical in reengineering suboptimal immune systems in immunocompromised populations.

  6. [Chronobiology of immune system].

    PubMed

    Trufakin, V A; Shurlygina, A V; Dergacheva, T I; Litvinenko, G I; Verbitskaia, L V

    1999-01-01

    The biological rhythmological programme of the immune system is a constituent of the body's common biological rhythmological programme. Its pattern seems to be genetically determined and reflects the functional status of the system. The chronobiological mechanisms responsible for the regulation of immune functions lie in the presence of certain phasic interrelations between the biological rhythms of the synthesis and production of regulatory agents on the one hand, and those of the receptor system and metabolic potential of immunocompetent cells on the other. The facts given in the paper may be a basis for a chronobiological approach to better understanding the mechanisms of the physiology and pathology of the immune system. The medical significance of study of the structural and temporal pattern of the immune system consists in the development of new techniques for diagnosis, prognosis, therapy, and assessment of risk factors in immunopathological conditions.

  7. Immune System and Disorders

    MedlinePlus

    Your immune system is a complex network of cells, tissues, and organs that work together to defend against germs. It helps ... to find and destroy them. If your immune system cannot do its job, the results can be ...

  8. Immune System Dysfunction in the Elderly.

    PubMed

    Fuentes, Eduardo; Fuentes, Manuel; Alarcón, Marcelo; Palomo, Iván

    2017-01-01

    Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

  9. Organizational culture influences health care workers' influenza immunization behavior.

    PubMed

    Isaacson, Nicole; Roemheld-Hamm, Beatrix; Crosson, Jesse C; Dicicco-Bloom, Barbara; Winston, Carla A

    2009-03-01

    Low rates of influenza immunization among health care workers (HCWs) pose a potential health risk to patients in primary care practices. Despite previous educational efforts and programs to reduce financial barriers, HCW influenza immunization rates remain low. Variation in practice-level organizational culture may affect immunization rates. To explore this relationship, we examined organizational cultures and HCWs' influenza immunization behaviors in three family medicine practices. We used a multi-method comparative case study. A field researcher used participant observation, in-depth interviews, and key informant interviews to collect data in each practice in November-December 2003. A diverse team used grounded theory to analyze text data. Organizational culture varied among practices and differing HCW immunization rates were observed. The most structured and business-like practice achieved immunization of all HCWs, while the other two practices exhibited greater variation in HCW immunization rates. Physicians in the practices characterized as chaotic/disorganized or divided were immunized at higher rates than other members of the practices. In these practices, organizational culture was associated with varying rates of influenza immunization for HCWs, especially among nonphysicians. Addressing elements of organizational culture such as beliefs regarding influenza immunization and office policies may facilitate the immunization of all staff members.

  10. Contrasting invertebrate immune defense behaviors caused by a single gene, the Caenorhabditis elegans neuropeptide receptor gene npr-1.

    PubMed

    Nakad, Rania; Snoek, L Basten; Yang, Wentao; Ellendt, Sunna; Schneider, Franziska; Mohr, Timm G; Rösingh, Lone; Masche, Anna C; Rosenstiel, Philip C; Dierking, Katja; Kammenga, Jan E; Schulenburg, Hinrich

    2016-04-11

    The invertebrate immune system comprises physiological mechanisms, physical barriers and also behavioral responses. It is generally related to the vertebrate innate immune system and widely believed to provide nonspecific defense against pathogens, whereby the response to different pathogen types is usually mediated by distinct signalling cascades. Recent work suggests that invertebrate immune defense can be more specific at least at the phenotypic level. The underlying genetic mechanisms are as yet poorly understood. We demonstrate in the model invertebrate Caenorhabditis elegans that a single gene, a homolog of the mammalian neuropeptide Y receptor gene, npr-1, mediates contrasting defense phenotypes towards two distinct pathogens, the Gram-positive Bacillus thuringiensis and the Gram-negative Pseudomonas aeruginosa. Our findings are based on combining quantitative trait loci (QTLs) analysis with functional genetic analysis and RNAseq-based transcriptomics. The QTL analysis focused on behavioral immune defense against B. thuringiensis, using recombinant inbred lines (RILs) and introgression lines (ILs). It revealed several defense QTLs, including one on chromosome X comprising the npr-1 gene. The wildtype N2 allele for the latter QTL was associated with reduced defense against B. thuringiensis and thus produced an opposite phenotype to that previously reported for the N2 npr-1 allele against P. aeruginosa. Analysis of npr-1 mutants confirmed these contrasting immune phenotypes for both avoidance behavior and nematode survival. Subsequent transcriptional profiling of C. elegans wildtype and npr-1 mutant suggested that npr-1 mediates defense against both pathogens through p38 MAPK signaling, insulin-like signaling, and C-type lectins. Importantly, increased defense towards P. aeruginosa seems to be additionally influenced through the induction of oxidative stress genes and activation of GATA transcription factors, while the repression of oxidative stress genes

  11. Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system.

    PubMed

    Godbout, Jonathan P; Moreau, Maïté; Lestage, Jacques; Chen, Jing; Sparkman, Nathan L; O'Connor, Jason; Castanon, Nathalie; Kelley, Keith W; Dantzer, Robert; Johnson, Rodney W

    2008-09-01

    Exposure to peripheral infections may be permissive to cognitive and behavioral complications in the elderly. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness behavior in aged BALB/c mice. Because LPS also causes depressive behavior, the purpose of this study was to determine whether aging is associated with an exacerbated depressive-like response. We confirmed that LPS (0.33 mg/kg intraperitoneal) induced a protracted sickness response in aged mice with reductions in locomotor and feeding activities 24 and 48 h postinjection, when young adults had fully recovered. When submitted to the forced swim test 24 h post-LPS, both young adult and aged mice exhibited an increased duration of immobility. However, when submitted to either the forced swim test or the tail suspension test 72 h post-LPS, an increased duration of immobility was evident only in aged mice. This prolonged depressive-like behavior in aged LPS-treated mice was associated with a more pronounced induction of peripheral and brain indoleamine 2,3-dioxygenase and a markedly higher turnover rate of brain serotonin (as measured by the ratio of 5-hydroxy-indoleacetic acid over 5-hydroxy-tryptamine) compared to young adult mice at 24 post-LPS injection. These results provide the first evidence that age-associated reactivity of the brain cytokine system could play a pathophysiological role in the increased prevalence of depression observed in the elderly.

  12. Conceptual Spaces of the Immune System.

    PubMed

    Fierz, Walter

    2016-01-01

    The immune system can be looked at as a cognitive system. This is often done in analogy to the neuro-psychological system. Here, it is demonstrated that the cognitive functions of the immune system can be properly described within a new theory of cognitive science. Gärdenfors' geometrical framework of conceptual spaces is applied to immune cognition. Basic notions, like quality dimensions, natural properties and concepts, similarities, prototypes, saliences, etc., are related to cognitive phenomena of the immune system. Constraints derived from treating the immune system within a cognitive theory, like Gärdenfors' conceptual spaces, might well prove to be instrumental for the design of vaccines, immunological diagnostic tests, and immunotherapy.

  13. Immune System and Kidney Transplantation.

    PubMed

    Shrestha, Badri Man

    2017-01-01

    The immune system recognises a transplanted kidney as foreign body and mounts immune response through cellular and humoral mechanisms leading to acute or chronic rejection, which ultimately results in graft loss. Over the last five decades, there have been significant advances in the understanding of the immune responses to transplanted organs in both experimental and clinical transplant settings. Modulation of the immune response by using immunosuppressive agents has led to successful outcomes after kidney transplantation. The paper provides an overview of the general organisation and function of human immune system, immune response to kidney transplantation, and the current practice of immunosuppressive therapy in kidney transplantation in the United Kingdom.

  14. The Immune System: Basis of so much Health and Disease: 2. Innate Immunity.

    PubMed

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-03-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covering innate immunity. Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  15. The Immune System: Basis of so much Health and Disease: 3. Adaptive Immunity.

    PubMed

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-04-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system; this article covers adaptive immunity. Clinical relevance: Dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  16. Evolution of immune systems from self/not self to danger to artificial immune systems (AIS).

    PubMed

    Cooper, Edwin L

    2010-03-01

    This review will examine the evolution of immune mechanisms by emphasizing information from animal groups exclusive of all vertebrates. There will be a focus on concepts that propelled the immune system into prominent discourse in the life sciences. The self/not self hypothesis was crucial and so was the concern for immunologic memory or anamnesia, development of cancer, autoimmunity, and clonal selection. Now we may be able to deconstruct clonal selection since it is not applicable in the sense that it is not applicable to invertebrate mechanisms. Clonal selection seems to be purely as all evidence indicates a vertebrate strategy and therefore irrelevant to invertebrates. Some views may insist that anthropocentric mammalian immunologists utilized a tool to propel: the universal innate immune system of ubiquitous and plentiful invertebrates as an essential system for vertebrates. This was advantageous for all immunology; moreover innate immunity acquired an extended raison d'être. Innate immunity should help if there would be a failure of the adaptive immune system. Still to be answered are questions concerning immunologic surveillance that includes clonal selection. We can then ask does immunologic surveillance play a role in the survival of invertebrates that most universally seem to not develop cancer of vertebrates especially mammals; invertebrates only develop benign tumor. A recent proposal concerns an alternative explanation that is all embracing. Danger hypothesis operates in striking contrast to the self/not self hypothesis. This view holds that the immune system is adapted to intervene not because self is threatened but because of the system's sense of danger. This perception occurs by means of signals other than recognition of microbial pattern recognition molecules characteristic of invertebrates. Response to danger may be another way of analyzing innate immunity that does not trigger the production of clones and therefore does not rely entirely on the

  17. Evolution of immune systems from self/not self to danger to artificial immune systems (AIS)

    NASA Astrophysics Data System (ADS)

    Cooper, Edwin L.

    2010-03-01

    This review will examine the evolution of immune mechanisms by emphasizing information from animal groups exclusive of all vertebrates. There will be a focus on concepts that propelled the immune system into prominent discourse in the life sciences. The self/not self hypothesis was crucial and so was the concern for immunologic memory or anamnesia, development of cancer, autoimmunity, and clonal selection. Now we may be able to deconstruct clonal selection since it is not applicable in the sense that it is not applicable to invertebrate mechanisms. Clonal selection seems to be purely as all evidence indicates a vertebrate strategy and therefore irrelevant to invertebrates. Some views may insist that anthropocentric mammalian immunologists utilized a tool to propel: the universal innate immune system of ubiquitous and plentiful invertebrates as an essential system for vertebrates. This was advantageous for all immunology; moreover innate immunity acquired an extended raison d'être. Innate immunity should help if there would be a failure of the adaptive immune system. Still to be answered are questions concerning immunologic surveillance that includes clonal selection. We can then ask does immunologic surveillance play a role in the survival of invertebrates that most universally seem to not develop cancer of vertebrates especially mammals; invertebrates only develop benign tumor. A recent proposal concerns an alternative explanation that is all embracing. Danger hypothesis operates in striking contrast to the self/not self hypothesis. This view holds that the immune system is adapted to intervene not because self is threatened but because of the system's sense of danger. This perception occurs by means of signals other than recognition of microbial pattern recognition molecules characteristic of invertebrates. Response to danger may be another way of analyzing innate immunity that does not trigger the production of clones and therefore does not rely entirely on the

  18. Prenatal maternal immune activation increases anxiety- and depressive-like behaviors in offspring with experimental autoimmune encephalomyelitis.

    PubMed

    Majidi-Zolbanin, J; Doosti, M-H; Kosari-Nasab, M; Salari, A-A

    2015-05-21

    Multiple sclerosis (MS) is thought to result from a combination of genetics and environmental factors. Several lines of evidence indicate that significant prevalence of anxiety and depression-related disorders in MS patients can influence the progression of the disease. Although we and others have already reported the consequences of prenatal maternal immune activation on anxiety and depression, less is known about the interplay between maternal inflammation, MS and gender. We here investigated the effects of maternal immune activation with Poly I:C during mid-gestation on the progression of clinical symptoms of experimental autoimmune encephalomyelitis (EAE; a mouse model of MS), and then anxiety- and depressive-like behaviors in non-EAE and EAE-induced offspring were evaluated. Stress-induced corticosterone and tumor necrosis factor-alpha (TNF-α) levels in EAE-induced offspring were also measured. Maternal immune activation increased anxiety and depression in male offspring, but not in females. This immune challenge also resulted in an earlier onset of the EAE clinical signs in male offspring and enhanced the severity of the disease in both male and female offspring. Interestingly, the severity of the disease was associated with increased anxiety/depressive-like behaviors and elevated corticosterone or TNF-α levels in both sexes. Overall, these data suggest that maternal immune activation with Poly I:C during mid-pregnancy increases anxiety- and depressive-like behaviors, and the clinical symptoms of EAE in a sex-dependent manner in non-EAE or EAE-induced offspring. Finally, the progression of EAE in offspring seems to be linked to maternal immune activation-induced dysregulation in neuro-immune-endocrine system. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  19. The Immune System Game

    ERIC Educational Resources Information Center

    Work, Kirsten A.; Gibbs, Melissa A.; Friedman, Erich J.

    2015-01-01

    We describe a card game that helps introductory biology students understand the basics of the immune response to pathogens. Students simulate the steps of the immune response with cards that represent the pathogens and the cells and molecules mobilized by the immune system. In the process, they learn the similarities and differences between the…

  20. Interaction of entomopathogenic fungi with the host immune system.

    PubMed

    Qu, Shuang; Wang, Sibao

    2018-06-01

    Entomopathogenic fungi can invade wide range of insect hosts in the natural world and have been used as environmentally friendly alternatives to chemical insecticides for pest control. Studies of host-pathogen interactions provide valuable insights into the coevolutionay arms race between fungal pathogens and their hosts. Entomopathogenic fungi have evolved a series of sophisticated strategies to counter insect immune defenses. In response to fungal infection, insect hosts rely on behavior avoidance, physical barrier and innate immune defenses in the fight against invading pathogens. The insect cuticle acts as the first physical barrier against pathogens. It is an inhospitable physiological environment that contains chemicals (e.g., antimicrobial peptides and reactive oxygen species), which inhibit fungal growth. In addition, innate immune responses, including cellular immunity and humoral immunity, play critical roles in preventing fungal infection. In this review, we outline the current state of our knowledge of insect defenses to fungal infection and discuss the strategies by which entomopathogenic fungi counter the host immune system. Increased knowledge regarding the molecular interactions between entomopathogenic fungi and the insect host could provide new strategies for pest management. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Local and systemic tumor immune dynamics

    NASA Astrophysics Data System (ADS)

    Enderling, Heiko

    Tumor-associated antigens, stress proteins, and danger-associated molecular patterns are endogenous immune adjuvants that can both initiate and continually stimulate an immune response against a tumor. In retaliation, tumors can hijack intrinsic immune regulatory programs that are intended to prevent autoimmune disease, thereby facilitating continued growth despite the activated antitumor immune response. In metastatic disease, this ongoing tumor-immune battle occurs at each site. Adding an additional layer of complexity, T cells activated at one tumor site can cycle through the blood circulation system and extravasate in a different anatomic location to surveil a distant metastasis. We propose a mathematical modeling framework that incorporates the trafficking of activated T cells between metastatic sites. We extend an ordinary differential equation model of tumor-immune system interactions to multiple metastatic sites. Immune cells are activated in response to tumor burden and tumor cell death, and are recruited from tumor sites elsewhere in the body. A model of T cell trafficking throughout the circulatory system can inform the tumor-immune interaction model about the systemic distribution and arrival of T cells at specific tumor sites. Model simulations suggest that metastases not only contribute to immune surveillance, but also that this contribution varies between metastatic sites. Such information may ultimately help harness the synergy of focal therapy with the immune system to control metastatic disease.

  2. Do entheogen-induced mystical experiences boost the immune system? Psychedelics, peak experiences, and wellness.

    PubMed

    Roberts, T B

    1999-01-01

    Daily events that boost the immune system (as indicated by levels of salivary immunoglobulin A), some instances of spontaneous remission, and mystical experiences seem to share a similar cluster of thoughts, feelings, moods, perceptions, and behaviors. Entheogens--psychedelic drugs used in a religious context--can also produce mystical experiences (peak experiences, states of unitive consciousness, intense primary religious experiences) with the same cluster of effects. When this happens, is it also possible that such entheogen-induced mystical experiences strengthen the immune system? Might spontaneous remissions occur more frequently under such conditions? This article advances the so called "Emxis hypothesis"--that entheogen-induced mystical experiences influence the immune system.

  3. Systems vaccinology: Probing humanity’s diverse immune systems with vaccines

    PubMed Central

    Pulendran, Bali

    2014-01-01

    Homo sapiens are genetically diverse, but dramatic demographic and socioeconomic changes during the past century have created further diversification with respect to age, nutritional status, and the incidence of associated chronic inflammatory disorders and chronic infections. These shifting demographics pose new challenges for vaccination, as emerging evidence suggests that age, the metabolic state, and chronic infections can exert major influences on the immune system. Thus, a key public health challenge is learning how to reprogram suboptimal immune systems to induce effective vaccine immunity. Recent advances have applied systems biological analysis to define molecular signatures induced early after vaccination that correlate with and predict the later adaptive immune responses in humans. Such “systems vaccinology” approaches offer an integrated picture of the molecular networks driving vaccine immunity, and are beginning to yield novel insights about the immune system. Here we discuss the promise of systems vaccinology in probing humanity’s diverse immune systems, and in delineating the impact of genes, the environment, and the microbiome on protective immunity induced by vaccination. Such insights will be critical in reengineering suboptimal immune systems in immunocompromised populations. PMID:25136102

  4. Immune evasion, immunopathology and the regulation of the immune system.

    PubMed

    Sorci, Gabriele; Cornet, Stéphane; Faivre, Bruno

    2013-02-13

    Costs and benefits of the immune response have attracted considerable attention in the last years among evolutionary biologists. Given the cost of parasitism, natural selection should favor individuals with the most effective immune defenses. Nevertheless, there exists huge variation in the expression of immune effectors among individuals. To explain this apparent paradox, it has been suggested that an over-reactive immune system might be too costly, both in terms of metabolic resources and risks of immune-mediated diseases, setting a limit to the investment into immune defenses. Here, we argue that this view neglects one important aspect of the interaction: the role played by evolving pathogens. We suggest that taking into account the co-evolutionary interactions between the host immune system and the parasitic strategies to overcome the immune response might provide a better picture of the selective pressures that shape the evolution of immune functioning. Integrating parasitic strategies of host exploitation can also contribute to understand the seemingly contradictory results that infection can enhance, but also protect from, autoimmune diseases. In the last decades, the incidence of autoimmune disorders has dramatically increased in wealthy countries of the northern hemisphere with a concomitant decrease of most parasitic infections. Experimental work on model organisms has shown that this pattern may be due to the protective role of certain parasites (i.e., helminths) that rely on the immunosuppression of hosts for their persistence. Interestingly, although parasite-induced immunosuppression can protect against autoimmunity, it can obviously favor the spread of other infections. Therefore, we need to think about the evolution of the immune system using a multidimensional trade-off involving immunoprotection, immunopathology and the parasitic strategies to escape the immune response.

  5. A Dialogue between the Immune System and Brain, Spoken in the Language of Serotonin

    PubMed Central

    2012-01-01

    Neuropsychiatric disorders have long been linked to both immune system activation and alterations in serotonin (5-HT) signaling. In the CNS, the contributions of 5-HT modulate a broad range of targets, most notably, hypothalamic, limbic and cortical circuits linked to the control of mood and mood disorders. In the periphery, many are aware of the production and actions of 5-HT in the gut but are unaware that the molecule and its receptors are also present in the immune system where evidence suggests they contribute to the both innate and adaptive responses. In addition, there is clear evidence that the immune system communicates to the brain via both humoral and neuronal mechanisms, and that CNS 5-HT neurons are a direct or indirect target for these actions. Following a brief primer on the immune system, we describe our current understanding of the synthesis, release, and actions of 5-HT in modulating immune function, including the expression of 5-HT biosynthetic enzymes, receptors, and transporters that are typically studied with respect to the roles in the CNS. We then orient our presentation to recent findings that pro-inflammatory cytokines can modulate CNS 5-HT signaling, leading to a conceptualization that among the many roles of 5-HT in the body is an integrated physiological and behavioral response to inflammatory events and pathogens. From this perspective, altered 5-HT/immune conversations are likely to contribute to risk for neurobehavioral disorders historically linked to compromised 5-HT function or ameliorated by 5-HT targeted medications, including depression and anxiety disorders, obsessive-compulsive disorder (OCD), and autism. Our review raises the question as to whether genetic variation impacting 5-HT signaling genes may contribute to maladaptive behavior as much through perturbed immune system modulation as through altered brain mechanisms. Conversely, targeting the immune system for therapeutic development may provide an important opportunity

  6. Caregiver Soothing Behaviors After Immunization and Infant Attachment: A Longitudinal Analysis.

    PubMed

    Hillgrove-Stuart, Jessica; Pillai Riddell, Rebecca; Flora, David B; Greenberg, Saul; Garfield, Hartley

    2015-01-01

    There were 2 primary objectives to the current study: (1) to relate caregiver behavior trajectories across immunization appointments over the first year of life to subsequent infant attachment and (2) to relate caregiver behavior trajectories within each immunization appointment over the first year of life to subsequent infant attachment. A subsample of 130 caregivers and their infants were recruited from a sample of 760 caregivers who were part of an ongoing longitudinal cohort that videotaped infants' 2-, 4-, 6-, and 12-month immunization appointments. This subsample of caregivers and their infants (n = 130) were invited to participate in an assessment of attachment when infants were between 12 and 18 months of age at the local children's hospital. Caregiver proximal soothing behaviors were the only caregiver behaviors postimmunization that were related to subsequent infant attachment. Higher frequencies of caregiver proximal soothing at 12 months were related to infants' organized attachment, whereas steeper decreases in proximal soothing across the first year were associated with disorganized infant attachment. In addition, when caregivers engaged in proximal soothing for longer after their 12 month olds' immunizations, these infants were more likely to be secure or organized in their attachment. These results provide empirical support for the ecological validity of studying infant attachment in a pediatric pain context. The pediatric "well-baby" visit may provide a potential opportunity to feasibly integrate brief infant mental health screening and intervention.

  7. [Plant immune system: the basal immunity].

    PubMed

    Shamraĭ, S N

    2014-01-01

    Plants have an efficient system of innate immunity which is based on the effective detection of potentially harmful microorganisms and rapid induction of defense responses. The first level of plant immunity is the basal immunity which is induced by the conserved molecular structures of microbes such as bacterial flagellins or fungal chitin, or molecules that result from the interaction of plants with pathogens, for example oligosaccharides and peptides ("danger signals"). Plants recognize these inducers through receptors localized to the plasma membrane, represented mainly receptor-like protein kinases or receptor-like proteins. Activation of the receptor by a ligand triggers a complex network of signaling events which eventually cause an array of plant defense responses to prevent further spread of the pathogen.

  8. Gender-Dependent Effects of Maternal Immune Activation on the Behavior of Mouse Offspring

    PubMed Central

    Xuan, Ingrid C. Y.; Hampson, David R.

    2014-01-01

    Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the “maternal immune activation” model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior. PMID:25111339

  9. The Role of the Immune System in Autism Spectrum Disorder

    PubMed Central

    Meltzer, Amory; Van de Water, Judy

    2017-01-01

    Autism is a neurodevelopmental disorder characterized by deficits in communication and social skills as well as repetitive and stereotypical behaviors. While much effort has focused on the identification of genes associated with autism, research emerging within the past two decades suggests that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in autism spectrum disorders (ASD). Further, it is the heterogeneity within this disorder that has brought to light much of the current thinking regarding the subphenotypes within ASD and how the immune system is associated with these distinctions. This review will focus on the two main axes of immune involvement in ASD, namely dysfunction in the prenatal and postnatal periods. During gestation, prenatal insults including maternal infection and subsequent immunological activation may increase the risk of autism in the child. Similarly, the presence of maternally derived anti-brain autoantibodies found in ~20% of mothers whose children are at risk for developing autism has defined an additional subphenotype of ASD. The postnatal environment, on the other hand, is characterized by related but distinct profiles of immune dysregulation, inflammation, and endogenous autoantibodies that all persist within the affected individual. Further definition of the role of immune dysregulation in ASD thus necessitates a deeper understanding of the interaction between both maternal and child immune systems, and the role they have in diagnosis and treatment. PMID:27534269

  10. Timing of Maternal Immunization Affects Immunological and Behavioral Outcomes of Adult Offspring in Siberian Hamsters (Phodopus sungorus)

    PubMed Central

    French, Susannah S.; Chester, Emily M.; Demas, Gregory E.

    2016-01-01

    Maternal influences are an important contributing factor to offspring survival, development, and behavior. Common environmental pathogens can induce maternal immune responses and affect subsequent development of offspring. There are likely sensitive periods during pregnancy when animals are particularly vulnerable to environmental disruption. Here we characterize the effects of maternal immunization across pregnancy and postpartum on offspring physiology and behavior in Siberian hamsters (Phodopus sungorus). Hamsters were injected with the antigen keyhole limpet hemocyanin (KLH) 1) prior to pairing with a male (pre-mating), 2) at separation (post-mating), 3) at mid-pregnancy, or 4) after birth (lactation). Maternal food intake, body mass, and immunity were monitored throughout gestation, and litters were measured weekly for growth until adulthood when social behavior, hormone concentrations, and immune responses were determined. We found that immunizations altered maternal immunity throughout pregnancy and lactation. The effects of maternal treatment differed between male and female offspring. Aggressive behavior was enhanced in offspring of both sexes born to mothers treated post-mating and thus early in pregnancy relative to other stages. In contrast, maternal treatment and maternal stage differentially affected innate immunity in males and females. Offspring cortisol, however, was unaffected by maternal treatment. Collectively, these data demonstrate that maternal immunization affects offspring physiology and behavior in a time-dependent and sex-specific manner. More broadly, these findings contribute to our understanding of the effects of maternal immune activation, whether it be from environmental exposure or immunization, on immunological and behavioral responses of offspring. PMID:27320639

  11. In immune defense: redefining the role of the immune system in chronic disease.

    PubMed

    Rubinow, Katya B; Rubinow, David R

    2017-03-01

    The recognition of altered immune system function in many chronic disease states has proven to be a pivotal advance in biomedical research over the past decade. For many metabolic and mood disorders, this altered immune activity has been characterized as inflammation, with the attendant assumption that the immune response is aberrant. However, accumulating evidence challenges this assumption and suggests that the immune system may be mounting adaptive responses to chronic stressors. Further, the inordinate complexity of immune function renders a simplistic, binary model incapable of capturing critical mechanistic insights. In this perspective article, we propose alternative paradigms for understanding the role of the immune system in chronic disease. By invoking allostasis or systems biology rather than inflammation, we can ascribe greater functional significance to immune mediators, gain newfound appreciation of the adaptive facets of altered immune activity, and better avoid the potentially disastrous effects of translating erroneous assumptions into novel therapeutic strategies.

  12. Sex, the aging immune system, and chronic disease.

    PubMed

    Gubbels Bupp, Melanie R

    2015-04-01

    The immune systems of men and women differ in significant ways, especially after puberty. In particular, females are generally more prone to autoimmunity, but experience lower rates of infections and chronic inflammatory disease. Sex hormones, genes encoded on the sex chromosomes, and gender-specific behaviors likely contribute to these differences. The aging process is associated with changes in the composition and function of the immune system and these changes may occur at an accelerated rate in men as compared to women. Moreover, after the age of menopause, the incidence of chronic inflammatory disease in women approaches or exceeds that observed in males. At the same time, the incidence of autoimmunity in post-menopausal women is decreased or equivalent to the rates observed in similarly-aged men. Additional studies addressing the influence of sex on the pathogenesis of chronic and autoimmune diseases in the aged are warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Approaches Mediating Oxytocin Regulation of the Immune System.

    PubMed

    Li, Tong; Wang, Ping; Wang, Stephani C; Wang, Yu-Feng

    2016-01-01

    The hypothalamic neuroendocrine system is mainly composed of the neural structures regulating hormone secretion from the pituitary gland and has been considered as the higher regulatory center of the immune system. Recently, the hypothalamo-neurohypophysial system (HNS) emerged as an important component of neuroendocrine-immune network, wherein the oxytocin (OT)-secreting system (OSS) plays an essential role. The OSS, consisting of OT neurons in the supraoptic nucleus, paraventricular nucleus, their several accessory nuclei and associated structures, can integrate neural, endocrine, metabolic, and immune information and plays a pivotal role in the development and functions of the immune system. The OSS can promote the development of thymus and bone marrow, perform immune surveillance, strengthen immune defense, and maintain immune homeostasis. Correspondingly, OT can inhibit inflammation, exert antibiotic-like effect, promote wound healing and regeneration, and suppress stress-associated immune disorders. In this process, the OSS can release OT to act on immune system directly by activating OT receptors or through modulating activities of other hypothalamic-pituitary-immune axes and autonomic nervous system indirectly. However, our understandings of the role of the OSS in neuroendocrine regulation of immune system are largely incomplete, particularly its relationship with other hypothalamic-pituitary-immune axes and the vasopressin-secreting system that coexists with the OSS in the HNS. In addition, it remains unclear about the relationship between the OSS and peripherally produced OT in immune regulation, particularly intrathymic OT that is known to elicit central immunological self-tolerance of T-cells to hypophysial hormones. In this work, we provide a brief review of current knowledge of the features of OSS regulation of the immune system and of potential approaches that mediate OSS coordination of the activities of entire neuroendocrine-immune network.

  14. Immune System Toxicity and Immunotoxicity Hazard Identification

    EPA Science Inventory

    Exposure to chemicals may alter immune system health, increasing the risk of infections, allergy and autoimmune diseases. The chapter provides a concise overview of the immune system, host factors that affect immune system heal, and the effects that xenobiotic exposure may have ...

  15. Miming the cancer-immune system competition by kinetic Monte Carlo simulations

    NASA Astrophysics Data System (ADS)

    Bianca, Carlo; Lemarchand, Annie

    2016-10-01

    In order to mimic the interactions between cancer and the immune system at cell scale, we propose a minimal model of cell interactions that is similar to a chemical mechanism including autocatalytic steps. The cells are supposed to bear a quantity called activity that may increase during the interactions. The fluctuations of cell activity are controlled by a so-called thermostat. We develop a kinetic Monte Carlo algorithm to simulate the cell interactions and thermalization of cell activity. The model is able to reproduce the well-known behavior of tumors treated by immunotherapy: the first apparent elimination of the tumor by the immune system is followed by a long equilibrium period and the final escape of cancer from immunosurveillance.

  16. [Immune system and influenza virus].

    PubMed

    Wierzbicka-Woś, Anna; Tokarz-Deptuła, Beata; Deptuła, Wiesław

    2015-02-15

    Influenza viruses are a significant cause of respiratory infections, causing 3-5 million clinical infections and 250-500 thousand deaths per year. Infections caused by the influenza virus induce a host immune response at the non-specific and specific level (defined as natural and acquired), which leads to limitation of virus replication. Moreover the elements of immunological memory are induced so that they can protect against subsequent infection by the influenza virus. However, there is still no effective way for the total elimination of this virus, and the only effective method to combat this pathogen appears to be vaccination, which through immune system activation greatly limits its spread. The present paper presents the immune reaction at different levels in response to the influenza virus after entering the body and the mechanisms of the influenza virus for avoiding reactions of the immune system, which correspond to its high variability at the molecular level. Moreover, in this paper we describe various methods of stimulating the organism's immune systems with different generations of vaccines and their effectiveness in the fight against this pathogen.

  17. Feeding Immunity: Physiological and Behavioral Responses to Infection and Resource Limitation

    PubMed Central

    Budischak, Sarah A.; Hansen, Christina B.; Caudron, Quentin; Garnier, Romain; Kartzinel, Tyler R.; Pelczer, István; Cressler, Clayton E.; van Leeuwen, Anieke; Graham, Andrea L.

    2018-01-01

    Resources are a core currency of species interactions and ecology in general (e.g., think of food webs or competition). Within parasite-infected hosts, resources are divided among the competing demands of host immunity and growth as well as parasite reproduction and growth. Effects of resources on immune responses are increasingly understood at the cellular level (e.g., metabolic predictors of effector function), but there has been limited consideration of how these effects scale up to affect individual energetic regimes (e.g., allocation trade-offs), susceptibility to infection, and feeding behavior (e.g., responses to local resource quality and quantity). We experimentally rewilded laboratory mice (strain C57BL/6) in semi-natural enclosures to investigate the effects of dietary protein and gastrointestinal nematode (Trichuris muris) infection on individual-level immunity, activity, and behavior. The scale and realism of this field experiment, as well as the multiple physiological assays developed for laboratory mice, enabled us to detect costs, trade-offs, and potential compensatory mechanisms that mice employ to battle infection under different resource conditions. We found that mice on a low-protein diet spent more time feeding, which led to higher body fat stores (i.e., concentration of a satiety hormone, leptin) and altered metabolite profiles, but which did not fully compensate for the effects of poor nutrition on albumin or immune defenses. Specifically, immune defenses measured as interleukin 13 (IL13) (a primary cytokine coordinating defense against T. muris) and as T. muris-specific IgG1 titers were lower in mice on the low-protein diet. However, these reduced defenses did not result in higher worm counts in mice with poorer diets. The lab mice, living outside for the first time in thousands of generations, also consumed at least 26 wild plant species occurring in the enclosures, and DNA metabarcoding revealed that the consumption of different wild foods

  18. Immune system and melanoma biology: a balance between immunosurveillance and immune escape.

    PubMed

    Passarelli, Anna; Mannavola, Francesco; Stucci, Luigia Stefania; Tucci, Marco; Silvestris, Francesco

    2017-12-01

    Melanoma is one of the most immunogenic tumors and its relationship with host immune system is currently under investigation. Many immunomodulatory mechanisms, favoring melanomagenesis and progression, have been described to interfere with the disablement of melanoma recognition and attack by immune cells resulting in immune resistance and immunosuppression. This knowledge produced therapeutic advantages, such as immunotherapy, aiming to overcome the immune evasion. Here, we review the current advances in cancer immunoediting and focus on melanoma immunology, which involves a dynamic interplay between melanoma and immune system, as well as on effects of "targeted therapies" on tumor microenvironment for combination strategies.

  19. Relations among Functional Systems in Behavior Analysis

    PubMed Central

    Thompson, Travis

    2007-01-01

    This paper proposes that an organism's integrated repertoire of operant behavior has the status of a biological system, similar to other biological systems, like the nervous, cardiovascular, or immune systems. Evidence from a number of sources indicates that the distinctions between biological and behavioral events is often misleading, engendering counterproductive explanatory controversy. A good deal of what is viewed as biological (often thought to be inaccessible or hypothetical) can become publicly measurable variables using currently available and developing technologies. Moreover, such endogenous variables can serve as establishing operations, discriminative stimuli, conjoint mediating events, and maintaining consequences within a functional analysis of behavior and need not lead to reductionistic explanation. I suggest that explanatory misunderstandings often arise from conflating different levels of analysis and that behavior analysis can extend its reach by identifying variables operating within a functional analysis that also serve functions in other biological systems. PMID:17575907

  20. Portable Immune-Assessment System

    NASA Technical Reports Server (NTRS)

    Pierson, Duane L.; Stowe, Raymond P.; Mishra, Saroj K.

    1995-01-01

    Portable immune-assessment system developed for use in rapidly identifying infections or contaminated environment. System combines few specific fluorescent reagents for identifying immune-cell dysfunction, toxic substances, buildup of microbial antigens or microbial growth, and potential identification of pathogenic microorganisms using fluorescent microplate reader linked to laptop computer. By using few specific dyes for cell metabolism, DNA/RNA conjugation, specific enzyme activity, or cell constituents, one makes immediate, onsite determination of person's health or of contamination of environment.

  1. Maternal immunity enhances systemic recall immune responses upon oral immunization of piglets with F4 fimbriae.

    PubMed

    Nguyen, Ut V; Melkebeek, Vesna; Devriendt, Bert; Goetstouwers, Tiphanie; Van Poucke, Mario; Peelman, Luc; Goddeeris, Bruno M; Cox, Eric

    2015-06-23

    F4 enterotoxigenic Escherichia coli (ETEC) cause diarrhoea and mortality in piglets leading to severe economic losses. Oral immunization of piglets with F4 fimbriae induces a protective intestinal immune response evidenced by an F4-specific serum and intestinal IgA response. However, successful oral immunization of pigs with F4 fimbriae in the presence of maternal immunity has not been demonstrated yet. In the present study we aimed to evaluate the effect of maternal immunity on the induction of a systemic immune response upon oral immunization of piglets. Whereas F4-specific IgG and IgA could be induced by oral immunization of pigs without maternal antibodies and by intramuscular immunization of pigs with maternal antibodies, no such response was seen in the orally immunized animals with maternal antibodies. Since maternal antibodies can mask an antibody response, we also looked by ELIspot assays for circulating F4-specific antibody secreting cells (ASCs). Enumerating the F4-specific ASCs within the circulating peripheral blood mononuclear cells, and the number of F4-specific IgA ASCs within the circulating IgA(+) B-cells revealed an F4-specific immune response in the orally immunized animals with maternal antibodies. Interestingly, results suggest a more robust IgA booster response by oral immunization of pigs with than without maternal antibodies. These results demonstrate that oral immunization of piglets with F4-specific maternal antibodies is feasible and that these maternal antibodies seem to enhance the secondary systemic immune response. Furthermore, our ELIspot assay on enriched IgA(+) B-cells could be used as a screening procedure to optimize mucosal immunization protocols in pigs with maternal immunity.

  2. Monocyte trafficking to the brain with stress and inflammation: a novel axis of immune-to-brain communication that influences mood and behavior

    PubMed Central

    Wohleb, Eric S.; McKim, Daniel B.; Sheridan, John F.; Godbout, Jonathan P.

    2015-01-01

    HIGHLIGHTS Psychological stress activates neuroendocrine pathways that alter immune responses.Stress-induced alterations in microglia phenotype and monocyte priming leads to aberrant peripheral and central inflammation.Elevated pro-inflammatory cytokine levels caused by microglia activation and recruitment of monocytes to the brain contribute to development and persistent anxiety-like behavior.Mechanisms that mediate interactions between microglia, endothelial cells, and macrophages and how these contribute to changes in behavior are discussed.Sensitization of microglia and re-distribution of primed monocytes are implicated in re-establishment of anxiety-like behavior. Psychological stress causes physiological, immunological, and behavioral alterations in humans and rodents that can be maladaptive and negatively affect quality of life. Several lines of evidence indicate that psychological stress disrupts key functional interactions between the immune system and brain that ultimately affects mood and behavior. For example, activation of microglia, the resident innate immune cells of the brain, has been implicated as a key regulator of mood and behavior in the context of prolonged exposure to psychological stress. Emerging evidence implicates a novel neuroimmune circuit involving microglia activation and sympathetic outflow to the peripheral immune system that further reinforces stress-related behaviors by facilitating the recruitment of inflammatory monocytes to the brain. Evidence from various rodent models, including repeated social defeat (RSD), revealed that trafficking of monocytes to the brain promoted the establishment of anxiety-like behaviors following prolonged stress exposure. In addition, new evidence implicates monocyte trafficking from the spleen to the brain as key regulator of recurring anxiety following exposure to prolonged stress. The purpose of this review is to discuss mechanisms that cause stress-induced monocyte re-distribution in the brain

  3. Weakened Immune System and Adult Vaccination

    MedlinePlus

    ... Adult Vaccination Resources for Healthcare Professionals Weakened Immune System and Adult Vaccination Recommend on Facebook Tweet Share ... with health conditions such as a weakened immune system. If you have cancer or other immunocompromising conditions, ...

  4. The immune system

    PubMed Central

    2016-01-01

    All organisms are connected in a complex web of relationships. Although many of these are benign, not all are, and everything alive devotes significant resources to identifying and neutralizing threats from other species. From bacteria through to primates, the presence of some kind of effective immune system has gone hand in hand with evolutionary success. This article focuses on mammalian immunity, the challenges that it faces, the mechanisms by which these are addressed, and the consequences that arise when it malfunctions. PMID:27784777

  5. Role of immune system in tumor progression and carcinogenesis.

    PubMed

    Upadhyay, Shishir; Sharma, Nidhi; Gupta, Kunj Bihari; Dhiman, Monisha

    2018-07-01

    Tumor micro-environment has potential to customize the behavior of the immune cell according to their need. In immune-eliminating phase, immune cells eliminate transformed cells but after tumor establishment innate and adaptive immune cells synergistically provide shelter as well as fulfill their requirement that helps in progression. In between eliminating and establishment phase, equilibrium and escaping phase regulate the immune cells response. During immune-escaping, (1) the antigenic response generated is either inadequate, or focused entirely on tolerance, and (2) immune response generated is specific and effective, but the tumor skips immune recognition. In this review, we are discussing the critical role of immune cells and their cytokines before and after the establishment of tumor which might play a critical role during immunotherapy. © 2018 Wiley Periodicals, Inc.

  6. Agent-based modeling of the immune system: NetLogo, a promising framework.

    PubMed

    Chiacchio, Ferdinando; Pennisi, Marzio; Russo, Giulia; Motta, Santo; Pappalardo, Francesco

    2014-01-01

    Several components that interact with each other to evolve a complex, and, in some cases, unexpected behavior, represents one of the main and fascinating features of the mammalian immune system. Agent-based modeling and cellular automata belong to a class of discrete mathematical approaches in which entities (agents) sense local information and undertake actions over time according to predefined rules. The strength of this approach is characterized by the appearance of a global behavior that emerges from interactions among agents. This behavior is unpredictable, as it does not follow linear rules. There are a lot of works that investigates the immune system with agent-based modeling and cellular automata. They have shown the ability to see clearly and intuitively into the nature of immunological processes. NetLogo is a multiagent programming language and modeling environment for simulating complex phenomena. It is designed for both research and education and is used across a wide range of disciplines and education levels. In this paper, we summarize NetLogo applications to immunology and, particularly, how this framework can help in the development and formulation of hypotheses that might drive further experimental investigations of disease mechanisms.

  7. The immune system as a biomonitor: explorations in innate and adaptive immunity

    PubMed Central

    Thomas, Niclas; Heather, James; Pollara, Gabriel; Simpson, Nandi; Matjeka, Theres; Shawe-Taylor, John; Noursadeghi, Mahdad; Chain, Benjamin

    2013-01-01

    The human immune system has a highly complex, multi-layered structure which has evolved to detect and respond to changes in the internal microenvironment of the body. Recognition occurs at the molecular or submolecular scale, via classical reversible receptor–ligand interactions, and can lead to a response with great sensitivity and speed. Remarkably, recognition is coupled to memory, such that responses are modulated by events which occurred years or even decades before. Although the immune system in general responds differently and more vigorously to stimuli entering the body from the outside (e.g. infections), this is an emergent property of the system: many of the recognition molecules themselves have no inherent bias towards external stimuli (non-self) but also bind targets found within the body (self). It is quite clear that the immune response registers pathophysiological changes in general. Cancer, wounding and chronic tissue injury are some obvious examples. Against this background, the immune system ‘state’ tracks the internal processes of the body, and is likely to encode information regarding both current and past disease processes. Moreover, the distributed nature of most immune responses (e.g. typically involving lymphoid tissue, non-lymphoid tissue, bone marrow, blood, extracellular interstitial spaces, etc.) means that many of the changes associated with immune responses are manifested systemically, and specifically can be detected in blood. This provides a very convenient route to sampling immune cells. We consider two different and complementary ways of querying the human immune ‘state’ using high-dimensional genomic screening methodologies, and discuss the potentials of these approaches and some of the technological and computational challenges to be overcome. PMID:24427535

  8. Recent Advances in Aptamers Targeting Immune System.

    PubMed

    Hu, Piao-Ping

    2017-02-01

    The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

  9. A Model of an Integrated Immune System Pathway in Homo sapiens and Its Interaction with Superantigen Producing Expression Regulatory Pathway in Staphylococcus aureus: Comparing Behavior of Pathogen Perturbed and Unperturbed Pathway

    PubMed Central

    Tomar, Namrata; De, Rajat K.

    2013-01-01

    Response of an immune system to a pathogen attack depends on the balance between the host immune defense and the virulence of the pathogen. Investigation of molecular interactions between the proteins of a host and a pathogen helps in identifying the pathogenic proteins. It is necessary to understand the dynamics of a normally behaved host system to evaluate the capacity of its immune system upon pathogen attack. In this study, we have compared the behavior of an unperturbed and pathogen perturbed host system. Moreover, we have developed a formalism under Flux Balance Analysis (FBA) for the optimization of conflicting objective functions. We have constructed an integrated pathway system, which includes Staphylococcal Superantigen (SAg) expression regulatory pathway and TCR signaling pathway of Homo sapiens. We have implemented the method on this pathway system and observed the behavior of host signaling molecules upon pathogen attack. The entire study has been divided into six different cases, based on the perturbed/unperturbed conditions. In other words, we have investigated unperturbed and pathogen perturbed human TCR signaling pathway, with different combinations of optimization of concentrations of regulatory and signaling molecules. One of these cases has aimed at finding out whether minimization of the toxin production in a pathogen leads to the change in the concentration levels of the proteins coded by TCR signaling pathway genes in the infected host. Based on the computed results, we have hypothesized that the balance between TCR signaling inhibitory and stimulatory molecules can keep TCR signaling system into resting/stimulating state, depending upon the perturbation. The proposed integrated host-pathogen interaction pathway model has accurately reflected the experimental evidences, which we have used for validation purpose. The significance of this kind of investigation lies in revealing the susceptible interaction points that can take back the

  10. Chronic infection and the origin of adaptive immune system.

    PubMed

    Usharauli, David

    2010-08-01

    It has been speculated that the rise of the adaptive immune system in jawed vertebrates some 400 million years ago gave them a superior protection to detect and defend against pathogens that became more elusive and/or virulent to the host that had only innate immune system. First, this line of thought implies that adaptive immune system was a new, more sophisticated layer of host defense that operated independently of the innate immune system. Second, the natural consequence of this scenario would be that pathogens would have exercised so strong an evolutionary pressure that eventually no host could have afforded not to have an adaptive immune system. Neither of these arguments is supported by the facts. First, new experimental evidence has firmly established that operation of adaptive immune system is critically dependent on the ability of the innate immune system to detect invader-pathogens and second, the absolute majority of animal kingdom survives just fine with only an innate immune system. Thus, these data raise the dilemma: If innate immune system was sufficient to detect and protect against pathogens, why then did adaptive immune system develop in the first place? In contrast to the innate immune system, the adaptive immune system has one important advantage, precision. By precision I mean the ability of the defense system to detect and remove the target, for example, infected cells, without causing unwanted bystander damage of surrounding tissue. While the target precision per se is not important for short-term immune response, it becomes a critical factor when the immune response is long-lasting, as during chronic infection. In this paper I would like to propose new, "toxic index" hypothesis where I argue that the need to reduce the collateral damage to the tissue during chronic infection(s) was the evolutionary pressure that led to the development of the adaptive immune system. Copyright 2010 Elsevier Ltd. All rights reserved.

  11. Synthetic immunology: modulating the human immune system.

    PubMed

    Geering, Barbara; Fussenegger, Martin

    2015-02-01

    Humans have manipulated the immune system to dampen or boost the immune response for thousands of years. As our understanding of fundamental immunology and biotechnological methodology accumulates, we can capitalize on this combined knowledge to engineer biological devices with the aim of rationally manipulating the immune response. We address therapeutic approaches based on the principles of synthetic immunology that either ameliorate disorders of the immune system by interfering with the immune response, or improve diverse pathogenic conditions by exploiting immune cell effector functions. We specifically highlight synthetic proteins investigated in preclinical and clinical trials, summarize studies that have used engineered immune cells, and finish with a discussion of possible future therapeutic concepts. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Melatonin: Buffering the Immune System

    PubMed Central

    Carrillo-Vico, Antonio; Lardone, Patricia J.; Álvarez-Sánchez, Nuria; Rodríguez-Rodríguez, Ana; Guerrero, Juan M.

    2013-01-01

    Melatonin modulates a wide range of physiological functions with pleiotropic effects on the immune system. Despite the large number of reports implicating melatonin as an immunomodulatory compound, it still remains unclear how melatonin regulates immunity. While some authors argue that melatonin is an immunostimulant, many studies have also described anti-inflammatory properties. The data reviewed in this paper support the idea of melatonin as an immune buffer, acting as a stimulant under basal or immunosuppressive conditions or as an anti-inflammatory compound in the presence of exacerbated immune responses, such as acute inflammation. The clinical relevance of the multiple functions of melatonin under different immune conditions, such as infection, autoimmunity, vaccination and immunosenescence, is also reviewed. PMID:23609496

  13. Unique aspects of the perinatal immune system.

    PubMed

    Zhang, Xiaoming; Zhivaki, Dania; Lo-Man, Richard

    2017-08-01

    The early stages of life are associated with increased susceptibility to infection, which is in part due to an ineffective immune system. In the context of infection, the immune system must be stimulated to provide efficient protection while avoiding insufficient or excessive activation. Yet, in early life, age-dependent immune regulation at molecular and cellular levels contributes to a reduced immunological fitness in terms of pathogen clearance and response to vaccines. To enable microbial colonization to be tolerated at birth, epigenetic immune cell programming and early life-specific immune regulatory and effector mechanisms ensure that vital functions and organ development are supported and that tissue damage is avoided. Advancement in our understanding of age-related remodelling of immune networks and the consequent tuning of immune responsiveness will open up new possibilities for immune intervention and vaccine strategies that are designed specifically for early life.

  14. Brain mast cells link the immune system to anxiety-like behavior

    PubMed Central

    Nautiyal, Katherine M.; Ribeiro, Ana C.; Pfaff, Donald W.; Silver, Rae

    2008-01-01

    Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient KitW−sh/W−sh (sash−/−) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links. PMID:19004805

  15. Brain mast cells link the immune system to anxiety-like behavior.

    PubMed

    Nautiyal, Katherine M; Ribeiro, Ana C; Pfaff, Donald W; Silver, Rae

    2008-11-18

    Mast cells are resident in the brain and contain numerous mediators, including neurotransmitters, cytokines, and chemokines, that are released in response to a variety of natural and pharmacological triggers. The number of mast cells in the brain fluctuates with stress and various behavioral and endocrine states. These properties suggest that mast cells are poised to influence neural systems underlying behavior. Using genetic and pharmacological loss-of-function models we performed a behavioral screen for arousal responses including emotionality, locomotor, and sensory components. We found that mast cell deficient Kit(W-sh/W-sh) (sash(-/-)) mice had a greater anxiety-like phenotype than WT and heterozygote littermate control animals in the open field arena and elevated plus maze. Second, we show that blockade of brain, but not peripheral, mast cell activation increased anxiety-like behavior. Taken together, the data implicate brain mast cells in the modulation of anxiety-like behavior and provide evidence for the behavioral importance of neuroimmune links.

  16. Weakened Immune Systems

    MedlinePlus

    ... Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... Español Text Size Email Print Share Weakened Immune Systems Page Content Article Body Some children have weakened ...

  17. Review of the systems biology of the immune system using agent-based models.

    PubMed

    Shinde, Snehal B; Kurhekar, Manish P

    2018-06-01

    The immune system is an inherent protection system in vertebrate animals including human beings that exhibit properties such as self-organisation, self-adaptation, learning, and recognition. It interacts with the other allied systems such as the gut and lymph nodes. There is a need for immune system modelling to know about its complex internal mechanism, to understand how it maintains the homoeostasis, and how it interacts with the other systems. There are two types of modelling techniques used for the simulation of features of the immune system: equation-based modelling (EBM) and agent-based modelling. Owing to certain shortcomings of the EBM, agent-based modelling techniques are being widely used. This technique provides various predictions for disease causes and treatments; it also helps in hypothesis verification. This study presents a review of agent-based modelling of the immune system and its interactions with the gut and lymph nodes. The authors also review the modelling of immune system interactions during tuberculosis and cancer. In addition, they also outline the future research directions for the immune system simulation through agent-based techniques such as the effects of stress on the immune system, evolution of the immune system, and identification of the parameters for a healthy immune system.

  18. Association of Childhood Obesity and the Immune System: A Systematic Review of Reviews.

    PubMed

    Kelishadi, Roya; Roufarshbaf, Mohammad; Soheili, Sina; Payghambarzadeh, Farzaneh; Masjedi, Mohsen

    2017-08-01

    The growing prevalence of childhood obesity has become a serious health problem over the past decades. As the immune system is greatly affected by excess weight, in this review of reviews, we discuss the findings of review articles about the relationship between childhood/maternal obesity and children's immune system. We searched English-language articles in PubMed, Scopus, ISI Thomson Reuters, and Google Scholar databases. All relevant reviews, either systematic or narrative, were retrieved. Then their quality was assessed by using the Assessment of Multiple Systematic Reviews and International Narrative Systematic Assessment tools, respectively. In the final step, 26 reviews were included. Our review suggests that childhood obesity is associated with extensive changes in the serum levels of inflammatory and anti-inflammatory cytokines and proteins, as well as the number of immune cells and their behavior. Therefore, it might cause or exacerbate diseases such as asthma, allergy, atopic dermatitis (AD), and obstructive sleep apnea syndrome. Moreover, childhood obesity may reduce the immune system responsiveness to vaccines and microorganisms. Furthermore, studies suggest that maternal obesity increases the risk of asthma in offspring. Future studies are needed to determine different associations of childhood obesity with allergy, atophic dermatitis, and autoimmune diseases.

  19. Primer on the Immune System.

    PubMed

    Spiering, Martin J

    2015-01-01

    The human body regularly encounters and combats many pathogenic organisms and toxic molecules. Its ensuing responses to these disease-causing agents involve two interrelated systems: innate immunity and adaptive (or acquired) immunity. Innate immunity is active at several levels, both at potential points of entry and inside the body (see figure). For example, the skin represents a physical barrier preventing pathogens from invading internal tissues. Digestive enzymes destroy microbes that enter the stomach with food. Macrophages and lymphocytes, equipped with molecular detectors, such as Toll-like receptors (TLRs), which latch onto foreign structures and activate cellular defenses, patrol the inside of the body. These immune cells sense and devour microbes, damaged cells, and other foreign materials in the body. Certain proteins in the blood (such as proteins of the complement system and those released by natural killer cells, along with antimicrobial host-defense peptides) attach to foreign organisms and toxins to initiate their destruction.

  20. Ageing and the immune system: focus on macrophages.

    PubMed

    Linehan, E; Fitzgerald, D C

    2015-03-01

    A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population.

  1. Immunotherapy: How the Immune System Fights Cancer

    Cancer.gov

    Immunotherapy uses the body’s immune system to fight cancer. This animation explains three types of immunotherapy used to treat cancer: nonspecific immune stimulation, T-cell transfer therapy, and immune checkpoint inhibitors.

  2. Evaluation of immunization data completeness within a large community health care system exchanging data with a state immunization information system.

    PubMed

    Hendrickson, Bryan K; Panchanathan, Sarada S; Petitti, Diana

    2015-01-01

    Information systems are used by most states to maintain registries of immunization data both for monitoring population-level adherence and for use in clinical practice and research. Direct data exchange between such systems and electronic health record systems presents an opportunity to improve the completeness and quality of information available. Our goals were to describe and compare the completeness of the Arizona State Immunization System, the electronic health record at a large community health provider in Arizona exchanging electronic data with the Arizona system, and personal immunization records in an effort to contribute to the discussion on the completeness of state-run immunization registries and data exchange with these registries. Immunization histories from these sources were collected and reviewed sequentially. Unique dates of vaccination administrations were counted for each patient and tagged on the basis of comparisons across sources. We quantified completeness by combining information from all 3 sources and comparing each source with the complete set. We determined that the state registry was 71.8% complete, the hospital electronic health record was 81.9% complete, and personal records were 87.8% complete. Of the 2017 unique vaccination administrations, 65% were present in all 3 sources, 24.6% in 2 of the 3 sources, and 10.4% in only 1 source. Only 11% of patients had records in complete agreement across the 3 sources. This study highlights issues related to data completeness, exchange, and reporting of immunization information to state registries and suggests that there is some degree of deficiency in completeness of immunization registries and other sources. This study indicates that there is a need to strengthen links between electronic data sources with immunization information and describes potential improvements in completeness that such efforts could provide, enabling providers to better rely on state immunization registries and to

  3. Artificial Immune System Approaches for Aerospace Applications

    NASA Technical Reports Server (NTRS)

    KrishnaKumar, Kalmanje; Koga, Dennis (Technical Monitor)

    2002-01-01

    Artificial Immune Systems (AIS) combine a priori knowledge with the adapting capabilities of biological immune system to provide a powerful alternative to currently available techniques for pattern recognition, modeling, design, and control. Immunology is the science of built-in defense mechanisms that are present in all living beings to protect against external attacks. A biological immune system can be thought of as a robust, adaptive system that is capable of dealing with an enormous variety of disturbances and uncertainties. Biological immune systems use a finite number of discrete "building blocks" to achieve this adaptiveness. These building blocks can be thought of as pieces of a puzzle which must be put together in a specific way-to neutralize, remove, or destroy each unique disturbance the system encounters. In this paper, we outline AIS models that are immediately applicable to aerospace problems and identify application areas that need further investigation.

  4. A Brief Journey through the Immune System

    PubMed Central

    Yatim, Karim M.

    2015-01-01

    This review serves as an introduction to an Immunology Series for the Nephrologist published in CJASN. It provides a brief overview of the immune system, how it works, and why it matters to kidneys. This review describes in broad terms the main divisions of the immune system (innate and adaptive), their cellular and tissue components, and the ways by which they function and are regulated. The story is told through the prism of evolution in order to relay to the reader why the immune system does what it does and why imperfections in the system can lead to renal disease. Detailed descriptions of cell types, molecules, and other immunologic curiosities are avoided as much as possible in an effort to not detract from the importance of the broader concepts that define the immune system and its relationship to the kidney. PMID:25845377

  5. Uniform Persistence and Global Stability for a Brain Tumor and Immune System Interaction

    NASA Astrophysics Data System (ADS)

    Khajanchi, Subhas

    This paper describes the synergistic interaction between the growth of malignant gliomas and the immune system interactions using a system of coupled ordinary differential equations (ODEs). The proposed mathematical model comprises the interaction of glioma cells, macrophages, activated Cytotoxic T-Lymphocytes (CTLs), the immunosuppressive factor TGF-β and the immuno-stimulatory factor IFN-γ. The dynamical behavior of the proposed system both analytically and numerically is investigated from the point of view of stability. By constructing Lyapunov functions, the global behavior of the glioma-free and the interior equilibrium point have been analyzed under some assumptions. Finally, we perform numerical simulations in order to illustrate our analytical findings by varying the system parameters.

  6. Learning and Memory... and the Immune System

    ERIC Educational Resources Information Center

    Marin, Ioana; Kipnis, Jonathan

    2013-01-01

    The nervous system and the immune system are two main regulators of homeostasis in the body. Communication between them ensures normal functioning of the organism. Immune cells and molecules are required for sculpting the circuitry and determining the activity of the nervous system. Within the parenchyma of the central nervous system (CNS),…

  7. Food supplementation and testosterone interact to influence reproductive behavior and immune function in Sceloporus graciosus.

    PubMed

    Ruiz, Mayté; French, Susannah S; Demas, Gregory E; Martins, Emília P

    2010-02-01

    The energetic resources in an organism's environment are essential for executing a wide range of life-history functions, including immunity and reproduction. Most energetic budgets, however, are limited, which can lead to trade-offs among competing functions. Increasing reproductive effort tends to decrease immunity in many cases, and increasing total energy via supplemental feedings can eliminate this effect. Testosterone (T), an important regulator of reproduction, and food availability are thus both potential factors regulating life-history processes, yet they are often tested in isolation of each other. In this study, we considered the effect of both food availability and elevated T on immune function and reproductive behavior in sagebrush lizards, Sceloporus graciosus, to assess how T and energy availability affect these trade-offs. We experimentally manipulated diet (via supplemental feedings) and T (via dermal patches) in males from a natural population. We determined innate immune response by calculating the bacterial killing capability of collected plasma exposed to Escherichia coli ex vivo. We measured reproductive behavior by counting the number of courtship displays produced in a 20-min sampling period. We observed an interactive effect of food availability and T-patch on immune function, with food supplementation increasing immunity in T-patch lizards. Additionally, T increased courtship displays in control food lizards. Lizards with supplemental food had higher circulating T than controls. Collectively, this study shows that the energetic state of the animal plays a critical role in modulating the interactions among T, behavior and immunity in sagebrush lizards and likely other species. Copyright 2009 Elsevier Inc. All rights reserved.

  8. Food supplementation and testosterone interact to influence reproductive behavior and immune function in Sceloporous graciosus

    PubMed Central

    Ruiz, Mayté; French, Susannah S.; Demas, Gregory E.; Martins, Emília P.

    2009-01-01

    The energetic resources in an organism’s environment are essential for executing a wide range of life history functions, including immunity and reproduction. Most energetic budgets, however, are limited, which can lead to trade-offs among competing functions. Increasing reproductive effort tends to decrease immunity in many cases; and increasing total energy via supplemental feedings can eliminate this effect. Testosterone (T), an important regulator of reproduction, and food availability are thus both potential factors regulating life-history processes, yet they are often tested in isolation of each other. In this study, we considered the effect of both food availability and elevated T on immune function and reproductive behavior in sagebrush lizards, Sceloporus graciosus, to assess how T and energy availability affect these trade-offs. We experimentally manipulated diet (via supplemental feedings) and T (via dermal patches) in males from a natural population. We determined innate immune response by calculating the bacterial killing capability of collected plasma exposed to E. coli ex vivo. We measured reproductive behavior by counting the number of courtship displays produced in a 20-min sampling period. We observed an interactive effect of food availability and T-patch on immune function, with food supplementation increasing immunity in T-patch lizards. Additionally, T increased courtship displays in control food lizards. Lizards with supplemental food had higher circulating T than controls. Collectively, this study shows that the energetic state of the animal plays a critical role in modulating the interactions among T, behavior and immunity in sagebrush lizards and likely other species. PMID:19800885

  9. Diffuse endocrine system, neuroendocrine tumors and immunity: what's new?

    PubMed

    Ameri, Pietro; Ferone, Diego

    2012-01-01

    During the last two decades, research into the modulation of immunity by the neuroendocrine system has flourished, unravelling significant effects of several neuropeptides, including somatostatin (SRIH), and especially cortistatin (CST), on immune cells. Scientists have learnt that the diffuse neuroendocrine system can regulate the immune system at all its levels: innate immunity, adaptive immunity, and maintenance of immune tolerance. Compelling studies with animal models have demonstrated that some neuropeptides may be effective in treating inflammatory disorders, such as sepsis, and T helper 1-driven autoimmune diseases, like Crohn's disease and rheumatoid arthritis. Here, the latest findings concerning the neuroendocrine control of the immune system are discussed, with emphasis on SRIH and CST. The second part of the review deals with the immune response to neuroendocrine tumors (NETs). The anti-NET immune response has been described in the last years and it is still being characterized, similarly to what is happening for several other types of cancer. In parallel with investigations addressing the mechanisms by which the immune system contrasts NET growth and spreading, ground-breaking clinical trials of dendritic cell vaccination as immunotherapy for metastatic NETs have shown in principle that the immune reaction to NETs can be exploited for treatment. Copyright © 2012 S. Karger AG, Basel.

  10. Insect Immunity to Entomopathogenic Fungi.

    PubMed

    Lu, H-L; St Leger, R J

    2016-01-01

    The study of infection and immunity in insects has achieved considerable prominence with the appreciation that their host defense mechanisms share many fundamental characteristics with the innate immune system of vertebrates. Studies on the highly tractable model organism Drosophila in particular have led to a detailed understanding of conserved innate immunity networks, such as Toll. However, most of these studies have used opportunistic human pathogens and may not have revealed specialized immune strategies that have arisen through evolutionary arms races with natural insect pathogens. Fungi are the commonest natural insect pathogens, and in this review, we focus on studies using Metarhizium and Beauveria spp. that have addressed immune system function and pathogen virulence via behavioral avoidance, the use of physical barriers, and the activation of local and systemic immune responses. In particular, we highlight studies on the evolutionary genetics of insect immunity and discuss insect-pathogen coevolution. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Visceral Inflammation and Immune Activation Stress the Brain

    PubMed Central

    Holzer, Peter; Farzi, Aitak; Hassan, Ahmed M.; Zenz, Geraldine; Jačan, Angela; Reichmann, Florian

    2017-01-01

    Stress refers to a dynamic process in which the homeostasis of an organism is challenged, the outcome depending on the type, severity, and duration of stressors involved, the stress responses triggered, and the stress resilience of the organism. Importantly, the relationship between stress and the immune system is bidirectional, as not only stressors have an impact on immune function, but alterations in immune function themselves can elicit stress responses. Such bidirectional interactions have been prominently identified to occur in the gastrointestinal tract in which there is a close cross-talk between the gut microbiota and the local immune system, governed by the permeability of the intestinal mucosa. External stressors disturb the homeostasis between microbiota and gut, these disturbances being signaled to the brain via multiple communication pathways constituting the gut–brain axis, ultimately eliciting stress responses and perturbations of brain function. In view of these relationships, the present article sets out to highlight some of the interactions between peripheral immune activation, especially in the visceral system, and brain function, behavior, and stress coping. These issues are exemplified by the way through which the intestinal microbiota as well as microbe-associated molecular patterns including lipopolysaccharide communicate with the immune system and brain, and the mechanisms whereby overt inflammation in the GI tract impacts on emotional-affective behavior, pain sensitivity, and stress coping. The interactions between the peripheral immune system and the brain take place along the gut–brain axis, the major communication pathways of which comprise microbial metabolites, gut hormones, immune mediators, and sensory neurons. Through these signaling systems, several transmitter and neuropeptide systems within the brain are altered under conditions of peripheral immune stress, enabling adaptive processes related to stress coping and resilience

  12. Promoting tissue regeneration by modulating the immune system.

    PubMed

    Julier, Ziad; Park, Anthony J; Briquez, Priscilla S; Martino, Mikaël M

    2017-04-15

    The immune system plays a central role in tissue repair and regeneration. Indeed, the immune response to tissue injury is crucial in determining the speed and the outcome of the healing process, including the extent of scarring and the restoration of organ function. Therefore, controlling immune components via biomaterials and drug delivery systems is becoming an attractive approach in regenerative medicine, since therapies based on stem cells and growth factors have not yet proven to be broadly effective in the clinic. To integrate the immune system into regenerative strategies, one of the first challenges is to understand the precise functions of the different immune components during the tissue healing process. While remarkable progress has been made, the immune mechanisms involved are still elusive, and there is indication for both negative and positive roles depending on the tissue type or organ and life stage. It is well recognized that the innate immune response comprising danger signals, neutrophils and macrophages modulates tissue healing. In addition, it is becoming evident that the adaptive immune response, in particular T cell subset activities, plays a critical role. In this review, we first present an overview of the basic immune mechanisms involved in tissue repair and regeneration. Then, we highlight various approaches based on biomaterials and drug delivery systems that aim at modulating these mechanisms to limit fibrosis and promote regeneration. We propose that the next generation of regenerative therapies may evolve from typical biomaterial-, stem cell-, or growth factor-centric approaches to an immune-centric approach. Most regenerative strategies have not yet proven to be safe or reasonably efficient in the clinic. In addition to stem cells and growth factors, the immune system plays a crucial role in the tissue healing process. Here, we propose that controlling the immune-mediated mechanisms of tissue repair and regeneration may support

  13. The immune system: a target for functional foods?

    PubMed

    Calder, Philip C; Kew, Samantha

    2002-11-01

    The immune system acts to protect the host from infectious agents that exist in the environment (bacteria, viruses, fungi, parasites) and from other noxious insults. The immune system is constantly active, acting to discriminate 'non-self' from 'self'. The immune system has two functional divisions: the innate and the acquired. Both components involve various blood-borne factors (complement, antibodies, cytokines) and cells. A number of methodologies exist to assess aspects of immune function; many of these rely upon studying cells in culture ex vivo. There are large inter-individual variations in many immune functions even among the healthy. Genetics, age, gender, smoking habits, habitual levels of exercise, alcohol consumption, diet, stage in the female menstrual cycle, stress, history of infections and vaccinations, and early life experiences are likely to be important contributors to the observed variation. While it is clear that individuals with immune responses significantly below 'normal' are more susceptible to infectious agents and exhibit increased infectious morbidity and mortality, it is not clear how the variation in immune function among healthy individuals relates to variation in susceptibility to infection. Nutrient status is an important factor contributing to immune competence: undernutrition impairs the immune system, suppressing immune functions that are fundamental to host protection. Undernutrition leading to impairment of immune function can be due to insufficient intake of energy and macronutrients and/or due to deficiencies in specific micronutrients. Often these occur in combination. Nutrients that have been demonstrated (in either animal or human studies) to be required for the immune system to function efficiently include essential amino acids, the essential fatty acid linoleic acid, vitamin A, folic acid, vitamin B6, vitamin B12, vitamin C, vitamin E, Zn, Cu, Fe and Se. Practically all forms of immunity may be affected by deficiencies

  14. Measuring the immune system: a comprehensive approach for the analysis of immune functions in humans.

    PubMed

    Claus, Maren; Dychus, Nicole; Ebel, Melanie; Damaschke, Jürgen; Maydych, Viktoriya; Wolf, Oliver T; Kleinsorge, Thomas; Watzl, Carsten

    2016-10-01

    The immune system is essential to provide protection from infections and cancer. Disturbances in immune function can therefore directly affect the health of the affected individual. Many extrinsic and intrinsic factors such as exposure to chemicals, stress, nutrition and age have been reported to influence the immune system. These influences can affect various components of the immune system, and we are just beginning to understand the causalities of these changes. To investigate such disturbances, it is therefore essential to analyze the different components of the immune system in a comprehensive fashion. Here, we demonstrate such an approach which provides information about total number of leukocytes, detailed quantitative and qualitative changes in the composition of lymphocyte subsets, cytokine levels in serum and functional properties of T cells, NK cells and monocytes. Using samples from a cohort of 24 healthy volunteers, we demonstrate the feasibility of our approach to detect changes in immune functions.

  15. Vitamin D, the immune system and asthma

    PubMed Central

    Lange, Nancy E; Litonjua, Augusto; Hawrylowicz, Catherine M; Weiss, Scott

    2010-01-01

    The effects of vitamin D on bone metabolism and calcium homeostasis have long been recognized. Emerging evidence has implicated vitamin D as a critical regulator of immunity, playing a role in both the innate and cell-mediated immune systems. Vitamin D deficiency has been found to be associated with several immune-mediated diseases, susceptibility to infection and cancer. Recently, there has been increasing interest in the possible link between vitamin D and asthma. Further elucidation of the role of vitamin D in lung development and immune system function may hold profound implications for the prevention and treatment of asthma. PMID:20161622

  16. Natural evolution, disease, and localization in the immune system

    NASA Astrophysics Data System (ADS)

    Deem, Michael

    2004-03-01

    Adaptive vertebrate immune system is a wonder of modern evolution. Under most circumstances, the dynamics of the immune system is well-matched to the dynamics of pathogen growth during a typical infection. Some pathogens, however, have evolved escape mechanisms that interact in subtle ways with the immune system dynamics. In addition, negative interactions the immune system, which has evolved over 400 000 000 years, and vaccination,which has been practiced for only 200 years, are possible. For example,vaccination against the flu can actually increase susceptibility to the flu in the next year. As another example, vaccination against one of the four strains of dengue fever typically increases susceptibility against the other three strains. Immunodominance also arises in the immune system control of nascent tumors--the immune system recognizes only a small subset of the tumor specific antigens, and the rest are free to grow and cause tumor growth. In this talk, I present a physical theory of original antigenic sin and immunodominance. How localization in the immune system leads to the observed phenomena is discussed. 1) M. W. Deem and H. Y. Lee, ``Sequence Space Localization in the Immune System Response to Vaccination and Disease,'' Phys. Rev. Lett. 91 (2003) 068101

  17. The role of the immune system in kidney disease.

    PubMed

    Tecklenborg, J; Clayton, D; Siebert, S; Coley, S M

    2018-05-01

    The immune system and the kidneys are closely linked. In health the kidneys contribute to immune homeostasis, while components of the immune system mediate many acute forms of renal disease and play a central role in progression of chronic kidney disease. A dysregulated immune system can have either direct or indirect renal effects. Direct immune-mediated kidney diseases are usually a consequence of autoantibodies directed against a constituent renal antigen, such as collagen IV in anti-glomerular basement membrane disease. Indirect immune-mediated renal disease often follows systemic autoimmunity with immune complex formation, but can also be due to uncontrolled activation of the complement pathways. Although the range of mechanisms of immune dysregulation leading to renal disease is broad, the pathways leading to injury are similar. Loss of immune homeostasis in renal disease results in perpetual immune cell recruitment and worsening damage to the kidney. Uncoordinated attempts at tissue repair, after immune-mediated disease or non-immune mediated injury, result in fibrosis of structures important for renal function, leading eventually to kidney failure. As renal disease often manifests clinically only when substantial damage has already occurred, new diagnostic methods and indeed treatments must be identified to inhibit further progression and promote appropriate tissue repair. Studying cases in which immune homeostasis is re-established may reveal new treatment possibilities. © 2018 British Society for Immunology.

  18. Invited essay: Cognitive influences on the psychological immune system.

    PubMed

    Rachman, S J

    2016-12-01

    The construct of the psychological immune system is described and analysed. The direct and indirect cognitive influences on the system are discussed, and the implications of adding a cognitive construal to the influential model of a behavioural immune system are considered. The psychological immune system has two main properties: defensive and healing. It encompasses a good amount of health-related phenomena that is outside the scope of the behavioural model or the biological immune system. Evidence pertaining to the psychological immune system includes meta-analyses of the associations between psychological variables such as positive affect/wellbeing and diseases and mortality, and associations between wellbeing and positive health. The results of long-term prospective studies are consistent with the conclusions drawn from the meta-analyses. Laboratory investigations of the effects of psychological variables on the biological immune system show that negative affect can slow wound-healing, and positive affect can enhance resistance to infections, for example in experiments involving the introduction of the rhinovirus and the influenza A virus. A number of problems concerning the assessment of the functioning of the psychological immune system are considered, and the need to develop techniques for determining when the system is active or not, is emphasized. This problem is particularly challenging when trying to assess the effects of the psychological immune system during a prolonged psychological intervention, such as a course of resilience training. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Sleep and immune function: glial contributions and consequences of aging.

    PubMed

    Ingiosi, Ashley M; Opp, Mark R; Krueger, James M

    2013-10-01

    The reciprocal interactions between sleep and immune function are well-studied. Insufficient sleep induces innate immune responses as evidenced by increased expression of pro-inflammatory mediators in the brain and periphery. Conversely, immune challenges upregulate immunomodulator expression, which alters central nervous system-mediated processes and behaviors, including sleep. Recent studies indicate that glial cells, namely microglia and astrocytes, are active contributors to sleep and immune system interactions. Evidence suggests glial regulation of these interactions is mediated, in part, by adenosine and adenosine 5'-triphosphate actions at purinergic type 1 and type 2 receptors. Furthermore, microglia and astrocytes may modulate declines in sleep-wake behavior and immunity observed in aging. Copyright © 2013. Published by Elsevier Ltd.

  20. Sleep and immune function: glial contributions and consequences of aging

    PubMed Central

    Ingiosi, Ashley M.; Opp, Mark R.; Krueger, James M.

    2013-01-01

    The reciprocal interactions between sleep and immune function are well-studied. Insufficient sleep induces innate immune responses as evidenced by increased expression of pro-inflammatory mediators in the brain and periphery. Conversely, immune challenges upregulate immunomodulator expression, which alters central nervous system-mediated processes and behaviors, including sleep. Recent studies indicate that glial cells, namely microglia and astrocytes, are active contributors to sleep and immune system interactions. Evidence suggests glial regulation of these interactions is mediated, in part, by adenosine and adenosine 5′-triphosphate actions at purinergic type 1 and type 2 receptors. Furthermore, microglia and astrocytes may modulate declines in sleep-wake behavior and immunity observed in aging. PMID:23452941

  1. Evaluation of Mucosal and Systemic Immune Responses Elicited by GPI-0100- Adjuvanted Influenza Vaccine Delivered by Different Immunization Strategies

    PubMed Central

    Liu, Heng; Patil, Harshad P.; de Vries-Idema, Jacqueline; Wilschut, Jan; Huckriede, Anke

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery often results in poor systemic immunity. In order to find an immunization strategy which satisfies the need for induction of both mucosal and systemic immunity, we compared local and systemic immune responses elicited by two mucosal immunizations, given either by the intranasal (IN) or the intrapulmonary (IPL) route, with responses elicited by a mucosal prime followed by a systemic boost immunization. The study was conducted in BALB/c mice and the vaccine formulation was an influenza subunit vaccine supplemented with GPI-0100, a saponin-derived adjuvant. While optimal mucosal antibody titers were obtained after two intrapulmonary vaccinations, optimal systemic antibody responses were achieved by intranasal prime followed by intramuscular boost. The latter strategy also resulted in the best T cell response, yet, it was ineffective in inducing nose or lung IgA. Successful induction of secretory IgA, IgG and T cell responses was only achieved with prime-boost strategies involving intrapulmonary immunization and was optimal when both immunizations were given via the intrapulmonary route. Our results underline that immunization via the lungs is particularly effective for priming as well as boosting of local and systemic immune responses. PMID:23936066

  2. Architecture for an artificial immune system.

    PubMed

    Hofmeyr, S A; Forrest, S

    2000-01-01

    An artificial immune system (ARTIS) is described which incorporates many properties of natural immune systems, including diversity, distributed computation, error tolerance, dynamic learning and adaptation, and self-monitoring. ARTIS is a general framework for a distributed adaptive system and could, in principle, be applied to many domains. In this paper, ARTIS is applied to computer security in the form of a network intrusion detection system called LISYS. LISYS is described and shown to be effective at detecting intrusions, while maintaining low false positive rates. Finally, similarities and differences between ARTIS and Holland's classifier systems are discussed.

  3. Brief Report: Dysregulated Immune System in Children with Autism: Beneficial Effects of Intravenous Immune Globulin on Autistic Characteristics.

    ERIC Educational Resources Information Center

    Gupta, Sudhir; And Others

    1996-01-01

    Children (ages 3-12) with autism (n=25) were given intravenous immune globulin (IVIG) treatments at 4-week intervals for at least 6 months. Marked abnormality of immune parameters was observed in subjects, compared to age-matched controls. IVIG treatment resulted in improved eye contact, speech, behavior, echolalia, and other autistic features.…

  4. Effects of engineered nanoparticles on the innate immune system.

    PubMed

    Liu, Yuanchang; Hardie, Joseph; Zhang, Xianzhi; Rotello, Vincent M

    2017-12-01

    Engineered nanoparticles (NPs) have broad applications in industry and nanomedicine. When NPs enter the body, interactions with the immune system are unavoidable. The innate immune system, a non-specific first line of defense against potential threats to the host, immediately interacts with introduced NPs and generates complicated immune responses. Depending on their physicochemical properties, NPs can interact with cells and proteins to stimulate or suppress the innate immune response, and similarly activate or avoid the complement system. NPs size, shape, hydrophobicity and surface modification are the main factors that influence the interactions between NPs and the innate immune system. In this review, we will focus on recent reports about the relationship between the physicochemical properties of NPs and their innate immune response, and their applications in immunotherapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Gap junction-mediated intercellular communication in the immune system.

    PubMed

    Neijssen, Joost; Pang, Baoxu; Neefjes, Jacques

    2007-01-01

    Immune cells are usually considered non-attached blood cells, which would exclude the formation of gap junctions. This is a misconception since many immune cells express connexin 43 (Cx43) and other connexins and are often residing in tissue. The role of gap junctions is largely ignored by immunologists as is the immune system in the field of gap junction research. Here, the current knowledge of the distribution of connexins and the function of gap junctions in the immune system is discussed. Gap junctions appear to play many roles in antibody productions and specific immune responses and may be important in sensing danger in tissue by the immune system. Gap junctions not only transfer electrical and metabolical but also immunological information in the form of peptides for a process called cross-presentation. This is essential for proper immune responses to viruses and possibly tumours. Until now only 40 research papers on gap junctions in the immune system appeared and this will almost certainly expand with the increased mutual interest between the fields of immunology and gap junction research.

  6. The Concordance of Parent and Child Immunization.

    PubMed

    Robison, Steve G; Osborn, Andrew W

    2017-05-01

    A substantial body of work has related survey-based parental vaccine hesitancy to noncompliant childhood immunization. However little attention has been paid to the connection between parents' own immunization behavior and the immunizations their children receive. Using the Oregon ALERT Immunization Information System, we identified adult caregiver-child pairs for children between 9 months and 17 years of age. The likelihood of adult-child concordance of influenza immunization per influenza season from 2010-2011 through 2014-2015 was assessed. The utility of adult immunization as a predictor was also assessed for other, noninfluenza recommended immunizations for children and adolescents. A total of 450 687 matched adult caregiver-child pairs were included in the study. The children of immunizing adults were 2.77 times more likely to also be immunized for seasonal influenza across all seasons (95% confidence interval, 2.74-2.79), with similar results applying within each season. Adult immunization status was also significantly associated with the likelihood of children and adolescents getting other noninfluenza immunizations, such as the human papillomavirus vaccine (HPV). When adults improved their own behavior from nonimmunizing to immunizing across influenza seasons, their children if not immunized in the previous season were 5.44 times (95% confidence interval, 5.35-5.53) more likely to become immunized for influenza. Children's likelihood of following immunization recommendations is associated with the immunization behavior of their parents. Encouraging parental immunization is a potential tool for increasing children's immunization rates. Copyright © 2017 by the American Academy of Pediatrics.

  7. Role of Osmolytes in Regulating Immune System.

    PubMed

    Kumar, Tarun; Yadav, Manisha; Singh, Laishram Rajendrakumar

    2016-01-01

    The immune system has evolved to protect the host organism from diverse range of pathogenic microbes that are themselves constantly evolving. It is a complex network of cells, humoral factors, chemokines and cytokines. Dysregulation of immune system results in various kinds of immunological disorders. There are several external agents which govern the regulation of immune system. Recent studies have indicated the role of osmolytes in regulation of various immunological processes such as Ag-Ab interaction, Ig assembly, Ag presentation etc. In this present review, we have systematically discussed the role of osmolytes involved in regulation of several key immunological processes. Osmolytes are involved in the regulation of several key immunological processes such as immunoglobulin assembly and folding, immune cells proliferation, regulation of immune cells function, Ag-Ab interaction, antigen presentation, inflammatory response and protection against photo-immunosuppression. Hence, osmolytes and their transporters might be used as potential drug and drug targets respectively. This review is therefore designed to help clinicians in development of osmolyte based therapeutic strategies in the treatment of various immunological disorders. Appropriate future perspectives have also been included.

  8. Exploring the Homeostatic and Sensory Roles of the Immune System.

    PubMed

    Marques, Rafael Elias; Marques, Pedro Elias; Guabiraba, Rodrigo; Teixeira, Mauro Martins

    2016-01-01

    Immunology developed under the notion of the immune system exists to fight pathogens. Recently, the discovery of interactions with commensal microbiota that are essential to human health initiated a change in this old paradigm. Here, we argue that the immune system has major physiological roles extending far beyond defending the host. Immune and inflammatory responses share the core property of sensing, defining the immune system also as a sensory system. The inference with the immune system collects, interprets, and stores information, while creating an identity of self, places it in close relationship to the nervous system, which suggests that these systems may have a profound evolutionary connection.

  9. Pneumonia - weakened immune system

    MedlinePlus

    ... gov/ency/article/000093.htm Pneumonia - weakened immune system To use the sharing features on this page, ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  10. Strengthening health system to improve immunization for migrants in China.

    PubMed

    Fang, Hai; Yang, Li; Zhang, Huyang; Li, Chenyang; Wen, Liankui; Sun, Li; Hanson, Kara; Meng, Qingyue

    2017-07-01

    Immunization is the most cost-effective method to prevent and control vaccine-preventable diseases. Migrant population in China has been rising rapidly, and their immunization status is poor. China has tried various strategies to strengthen its health system, which has significantly improved immunization for migrants. This study applied a qualitative retrospective review method aiming to collect, analyze and synthesize health system strengthening experiences and practices about improving immunizations for migrants in China. A conceptual framework of Theory of Change was used to extract the searched literatures. 11 searched literatures and 4 national laws and policies related to immunizations for migrant children were carefully studied. China mainly employed 3 health system strengthening strategies to significantly improve immunization for migrant population: stop charging immunization fees or immunization insurance, manage immunization certificates well, and pay extra attentions on immunization for special children including migrant children. These health system strengthening strategies were very effective, and searched literatures show that up-to-date and age-appropriate immunization rates were significantly improved for migrant children. Economic development led to higher migrant population in China, but immunization for migrants, particularly migrant children, were poor. Fortunately various health system strengthening strategies were employed to improve immunization for migrants in China and they were rather successful. The experiences and lessons of immunization for migrant population in China might be helpful for other developing countries with a large number of migrant population.

  11. Crosstalk between cancer and the neuro-immune system.

    PubMed

    Kuol, Nyanbol; Stojanovska, Lily; Apostolopoulos, Vasso; Nurgali, Kulmira

    2018-02-15

    In the last decade, understanding of cancer initiation and progression has been given much attention with studies mainly focusing on genetic abnormalities. Importantly, cancer cells can influence their microenvironment and bi-directionally communicate with other systems such as the immune system. The nervous system plays a fundamental role in regulating immune responses to a range of disease states including cancer. Its dysfunction influences the progression of cancer. The role of the immune system in tumor progression is of relevance to the nervous system since they can bi-directionally communicate via neurotransmitters and neuropeptides, common receptors, and, cytokines. However, cross-talk between these cells is highly complex in nature, and numerous variations are possible according to the type of cancer involved. The neuro-immune interaction is essential in influencing cancer development and progression. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Artificial immune system approach for air combat maneuvering

    NASA Astrophysics Data System (ADS)

    Kaneshige, John; Krishnakumar, Kalmanje

    2007-04-01

    Since future air combat missions will involve both manned and unmanned aircraft, the primary motivation for this research is to enable unmanned aircraft with intelligent maneuvering capabilities. During air combat maneuvering, pilots use their knowledge and experience of maneuvering strategies and tactics to determine the best course of action. As a result, we try to capture these aspects using an artificial immune system approach. The biological immune system protects the body against intruders by recognizing and destroying harmful cells or molecules. It can be thought of as a robust adaptive system that is capable of dealing with an enormous variety of disturbances and uncertainties. However, another critical aspect of the immune system is that it can remember how previous encounters were successfully defeated. As a result, it can respond faster to similar encounters in the future. This paper describes how an artificial immune system is used to select and construct air combat maneuvers. These maneuvers are composed of autopilot mode and target commands, which represent the low-level building blocks of the parameterized system. The resulting command sequences are sent to a tactical autopilot system, which has been enhanced with additional modes and an aggressiveness factor for enabling high performance maneuvers. Just as vaccinations train the biological immune system how to combat intruders, training sets are used to teach the maneuvering system how to respond to different enemy aircraft situations. Simulation results are presented, which demonstrate the potential of using immunized maneuver selection for the purposes of air combat maneuvering.

  13. Network intrusion detection by the coevolutionary immune algorithm of artificial immune systems with clonal selection

    NASA Astrophysics Data System (ADS)

    Salamatova, T.; Zhukov, V.

    2017-02-01

    The paper presents the application of the artificial immune systems apparatus as a heuristic method of network intrusion detection for algorithmic provision of intrusion detection systems. The coevolutionary immune algorithm of artificial immune systems with clonal selection was elaborated. In testing different datasets the empirical results of evaluation of the algorithm effectiveness were achieved. To identify the degree of efficiency the algorithm was compared with analogs. The fundamental rules based of solutions generated by this algorithm are described in the article.

  14. An immune-related gene expression atlas of the shrimp digestive system in response to two major pathogens brings insights into the involvement of hemocytes in gut immunity.

    PubMed

    Silveira, Amanda S; Matos, Gabriel M; Falchetti, Marcelo; Ribeiro, Fabio S; Bressan, Albert; Bachère, Evelyne; Perazzolo, Luciane M; Rosa, Rafael D

    2018-02-01

    Much of our current knowledge on shrimp immune system is restricted to the defense reactions mediated by the hemocytes and little is known about gut immunity. Here, we have investigated the transcriptional profile of immune-related genes in different organs of the digestive system of the shrimp Litopenaeus vannamei. First, the tissue distribution of 52 well-known immune-related genes has been assessed by semiquantitative analysis in the gastrointestinal tract (foregut, midgut and hindgut) and in the hepatopancreas and circulating hemocytes of shrimp stimulated or not with heat-killed bacteria. Then, the expression levels of 18 genes from key immune functional categories were quantified by fluorescence-based quantitative PCR in the midgut of animals experimentally infected with the Gram-negative Vibrio harveyi or the White spot syndrome virus (WSSV). Whereas the expression of some genes was induced at 48 h after the bacterial infection, any of the analyzed genes showed to be modulated in response to the virus. Whole-mount immunofluorescence assays confirmed the presence of infiltrating hemocytes in the intestines, indicating that the expression of some immune-related genes in gut is probably due to the migratory behavior of these circulating cells. This evidence suggests the participation of hemocytes in the delivery of antimicrobial molecules into different portions of the digestive system. Taken all together, our results revealed that gut is an important immune organ in L. vannamei with intimate association with hemocytes. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Alcohol and HIV Effects on the Immune System.

    PubMed

    Bagby, Gregory J; Amedee, Angela M; Siggins, Robert W; Molina, Patricia E; Nelson, Steve; Veazey, Ronald S

    2015-01-01

    HIV disease and alcohol independently influence the human immune system, so it stands to reason that, together, their influence may be additive. Here, we review the evidence that alcohol can exacerbate HIV's influence on the immune system, thereby affecting disease progression and transmission. We focus particularly on alcohol's effect on the mucosal immune system in the tissues of the gastrointestinal tract, the genital tract and the lungs, all of which play a role in transmission and progression of HIV disease.

  16. Reciprocal Interactions of the Intestinal Microbiota and Immune System

    PubMed Central

    Maynard, Craig L.; Elson, Charles O.; Hatton, Robin D.; Weaver, Casey T.

    2013-01-01

    Preface Emergence of the adaptive immune system in vertebrates set the stage for evolution of an advanced symbiotic relationship with the intestinal microbiota. The defining features of specificity and memory that characterize adaptive immunity have afforded vertebrates mechanisms for efficiently tailoring immune responses to diverse types of microbes, whether to promote mutualism or host defense. These same attributes carry risk for immune-mediated diseases that are increasingly linked to the intestinal microbiota. Understanding how the adaptive immune system copes with the remarkable number and diversity of microbes that colonize the digestive tract, and how it integrates with more primitive innate immune mechanisms to maintain immune homeostasis, holds considerable promise for new approaches to modulate immune networks in order to treat and prevent disease. PMID:22972296

  17. Continuous Dual Resetting of the Immune Repertoire as a Basic Principle of the Immune System Function.

    PubMed

    Balzar, Silvana

    2017-01-01

    Idiopathic chronic inflammatory conditions (ICIC) such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR) of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system's thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way) resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system's compartmentalization in the pathogenesis of ICIC. The CDR concept's relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function.

  18. The Molecules of the Immune System.

    ERIC Educational Resources Information Center

    Tonegawa, Susumu

    1985-01-01

    The immune system includes the most diverse proteins known because they are encoded by hundreds of scattered gene fragments which can be combined in millions or billions of ways. Events of immune response, binding of antigens, antibody structure, T-cell receptors, and other immunologically-oriented topics are discussed. (DH)

  19. The influence of pregnancy on systemic immunity.

    PubMed

    Pazos, Michael; Sperling, Rhoda S; Moran, Thomas M; Kraus, Thomas A

    2012-12-01

    Adaptations in maternal systemic immunity are presumed to be responsible for observed alterations in disease susceptibility and severity as pregnancy progresses. Epidemiological evidence as well as animal studies have shown that influenza infections are more severe during the second and third trimesters of pregnancy, resulting in greater morbidity and mortality, although the reason for this is still unclear. Our laboratory has taken advantage of 20 years of experience studying the murine immune response to respiratory viruses to address questions of altered immunity during pregnancy. With clinical studies and unique animal model systems, we are working to define the mechanisms responsible for altered immune responses to influenza infection during pregnancy and what roles hormones such as estrogen or progesterone play in these alterations.

  20. The mucosal immune system: From dentistry to vaccine development

    PubMed Central

    KIYONO, Hiroshi; AZEGAMI, Tatsuhiko

    2015-01-01

    The oral cavity is the beginning of the aero-digestive tract, which is covered by mucosal epithelium continuously under the threat of invasion of pathogens, it is thus protected by the mucosal immune system. In the early phase of our scientific efforts for the demonstration of mucosal immune system, dental science was one of major driving forces due to their foreseeability to use oral immunity for the control of oral diseases. The mucosal immune system is divided functionally into, but interconnected inductive and effector sites. Intestinal Peyer’s patches (PPs) are an inductive site containing antigen-sampling M cells and immunocompetent cells required to initiate antigen-specific immune responses. At effector sites, PP-originated antigen-specific IgA B cells become plasma cells to produce polymeric IgA and form secretory IgA by binding to poly-Ig receptor expressed on epithelial cells for protective immunity. The development of new-generation mucosal vaccines, including the rice-based oral vaccine MucoRice, on the basis of the coordinated mucosal immune system is a promising strategy for the control of mucosal infectious diseases. PMID:26460320

  1. The Role of the Immune System Beyond the Fight Against Infection.

    PubMed

    Sattler, Susanne

    2017-01-01

    The immune system was identified as a protective factor during infectious diseases over a century ago. Current definitions and textbook information are still largely influenced by these early observations, and the immune system is commonly presented as a defence machinery. However, host defence is only one manifestation of the immune system's overall function in the maintenance of tissue homeostasis and system integrity. In fact, the immune system is integral part of fundamental physiological processes such as development, reproduction and wound healing, and a close crosstalk between the immune system and other body systems such as metabolism, the central nervous system and the cardiovascular system is evident. Research and medical professionals in an expanding range of areas start to recognise the implications of the immune system in their respective fields.This chapter provides a brief historical perspective on how our understanding of the immune system has evolved from a defence system to an overarching surveillance machinery to maintain tissue integrity. Current perspectives on the non-defence functions of classical immune cells and factors will also be discussed.

  2. [The liver and the immune system].

    PubMed

    Jakab, Lajos

    2015-07-26

    The liver is known to be the metabolic centre of the organism and is under the control of the central nervous system. It has a peculiar tissue structure and its anatomic localisation defines it as part of the immune system having an individual role in the defence of the organism. The determinant of its particular tissue build-up is the sinusoid system. In addition to hepatocytes, one cell row "endothelium", stellate cells close to the external surface, Kupffer cells tightly to its inner surface, as well as dendritic cells and other cell types (T and B lymphocytes, natural killer and natural killer T-cells, mast cells, granulocytes) are present. The multitudes and variety of cells make it possible to carry out the tasks according to the assignment of the organism. The liver is a member of the immune system having immune cells largely in an activated state. Its principal tasks are the assurance of the peripheral immune tolerance of the organism with the help of the haemopoetic cells and transforming growth factor-β. The liver takes part in the determination of the manner of the non-specific immune response of the organism. In addition to acute phase reaction of the organism, the liver has a role in the adaptive/specific immune response. These functions include retardation of the T and B lymphocytes and the defence against harmful pathogens. With the collaboration of transforming growth factor-β, immunoglobulins and their subclasses are inhibited just as the response of the T lymphocytes. The only exception is the undisturbed immunoglobulin A production. Particularly important is the intensive participation of the liver in the acute phase reaction of the organism, which is organised and guided by the coordinated functions of the cortico-hypothalamo-hypophysis-adrenal axis. Beside cellular elements, hormones, adhesion molecules, chemokines and cytokines are also involved in the cooperation with the organs. Acute phase reactants play a central role in these processes

  3. The developing immune system - from foetus to toddler.

    PubMed

    Ygberg, Sofia; Nilsson, Anna

    2012-02-01

    During foetal development, neonatal period and childhood, the immune system is constantly maturing. In the foetus, infection responsiveness is low and associates with spontaneous abortion. During the neonatal period, the infection response shifts towards a more pro-inflammatory response. The immune system of the newborn acquires adaptive features as a result of exposure to microbes. The development of the human immune system is a continuous process where both accelerated and retarded development is deleterious. © 2011 The Author(s)/Acta Paediatrica © 2011 Foundation Acta Paediatrica.

  4. Alcohol and HIV Effects on the Immune System

    PubMed Central

    Bagby, Gregory J.; Amedee, Angela M.; Siggins, Robert W.; Molina, Patricia E.; Nelson, Steve; Veazey, Ronald S.

    2015-01-01

    HIV disease and alcohol independently influence the human immune system, so it stands to reason that, together, their influence may be additive. Here, we review the evidence that alcohol can exacerbate HIV’s influence on the immune system, thereby affecting disease progression and transmission. We focus particularly on alcohol’s effect on the mucosal immune system in the tissues of the gastrointestinal tract, the genital tract and the lungs, all of which play a role in transmission and progression of HIV disease. PMID:26695751

  5. The deconvolution of complex spectra by artificial immune system

    NASA Astrophysics Data System (ADS)

    Galiakhmetova, D. I.; Sibgatullin, M. E.; Galimullin, D. Z.; Kamalova, D. I.

    2017-11-01

    An application of the artificial immune system method for decomposition of complex spectra is presented. The results of decomposition of the model contour consisting of three components, Gaussian contours, are demonstrated. The method of artificial immune system is an optimization method, which is based on the behaviour of the immune system and refers to modern methods of search for the engine optimization.

  6. Maternal immune activation with staphylococcal enterotoxin A produces unique behavioral changes in C57BL/6 mouse offspring.

    PubMed

    Glass, Ruthy; Norton, Sara; Fox, Nicholas; Kusnecov, Alexander W

    2018-05-14

    Stimulation of the immune system during pregnancy, known as maternal immune activation (MIA), can cause long-lasting neurobiological and behavioral changes in the offspring. This phenomenon has been implicated in the etiology of developmental psychiatric disorders, such as autism and schizophrenia. Much of this evidence is predicated on animal models using bacterial agents such as LPS and/or viral mimics such as Poly I:C, both of which act through toll-like receptors. However, fewer studies have examined the role of direct activation of maternal T-cells during pregnancy using microbial agents. Bacterial superantigens, such as Staphylococcal Enterotoxin A and B (SEA; SEB), are microbial proteins that activate CD4 + T-cells and cause prominent T-cell proliferation and cytokine production. We injected pregnant and non-pregnant adult female C57BL/6 mice with 200 μg/Kg of SEA, SEB, or 0.9% saline, and measured splenic T-cell-derived cytokine concentrations (viz., IL-2, IFN-γ, IL-6, and IL-4) 2 h later; animals injected with SEA were also measured for splenic concentrations of TNF-α and IL-17A. Half of the injected pregnant animals were brought to term, and their offspring were tested on a series of behavioral tasks starting at six weeks of age (postnatal day 42 [P42]). These tasks included social interaction, the elevated plus maze (EPM), an open field and object recognition (OR) task, prepulse inhibition (PPI) of sensorimotor gating, and the Morris water maze (MWM). Results showed that SEA and SEB induced significant concentrations of all measured cytokines, and in particular IFN-γ, although cytokine responses were greater following SEA exposure. In addition, pregnancy induced an inhibitory effect on cytokine production. Behavioral results showed distinct phenotypes among offspring from SEA- or SEB-injected mothers, very likely due to differences in the magnitude of cytokines generated in response to each toxin. Offspring from SEA-injected mothers displayed

  7. Immune Abnormalities in Autism Spectrum Disorder-Could They Hold Promise for Causative Treatment?

    PubMed

    Gładysz, Dominika; Krzywdzińska, Amanda; Hozyasz, Kamil K

    2018-01-06

    Autism spectrum disorders (ASD) are characterized by impairments in language and communication development, social behavior, and the occurrence of stereotypic patterns of behavior and interests. Despite substantial speculation about causes of ASD, its exact etiology remains unknown. Recent studies highlight a link between immune dysfunction and behavioral traits. Various immune anomalies, including humoral and cellular immunity along with abnormalities at the molecular level, have been reported. There is evidence of altered immune function both in cerebrospinal fluid and peripheral blood. Several studies hypothesize a role for neuroinflammation in ASD and are supported by brain tissue and cerebrospinal fluid analysis, as well as evidence of microglial activation. It has been shown that immune abnormalities occur in a substantial number of individuals with ASD. Identifying subgroups with immune system dysregulation and linking specific cellular immunophenotypes to different symptoms would be key to defining a group of patients with immune abnormalities as a major etiology underlying behavioral symptoms. These determinations would provide the opportunity to investigate causative treatments for a defined patient group that may specifically benefit from such an approach. This review summarizes recent insights into immune system dysfunction in individuals with ASD and discusses the potential implications for future therapies.

  8. (Neuro)transmitter systems in circulating immune cells: a target of immunopharmacological interventions?

    PubMed

    Tayebati, Seyed Khosrow; Amenta, Francesco

    2008-01-01

    Increasing evidence indicates the existence of an association between nervous and immune systems. The two systems communicate with each-other to maintain immune homeostasis. Activated immune cells secrete cytokines that influence central nervous system activity. Nervous system, through its peripheral and/or autonomic divisions activates output regulating levels of immune cell activity and the subsequent magnitude of an immune response. On the other hand, neurotransmitters, which represent the main substances involved in nerve cell communications, can influence immune function. Immune organs and circulating immune cells express several (neuro)transmitter systems that can be involved in regulating their activity. The expression of neurotransmitter systems by different subsets of circulating immune cells was reviewed. The regulatory role of different families of (neuro)transmitters (catecholamines, 5-hydroxytryptamine, acetylcholine, histamine and neuropeptides) in modulating levels of immune mediators or specific immune responses is discussed.

  9. The immune self: a selectionist theory of recognition, learning, and remembering within the immune system.

    PubMed

    Kradin, R L

    1995-01-01

    In this paper, I have briefly explored metaphors shared by the immune and nervous systems and shown that this exercise can lead to the elucidation of common principles of organization, as well as to predictions concerning how the immune system functions. Metaphor itself undoubtedly reflects the way in which we categorize and retrieve information 44], so it is not surprising that the deep processes of language tend to sample information from related data categories. Although the nervous and immune systems are obviously not the same and metaphors are indeed just that, my primary goal has been to suggest that by virtue of their having evolved in parallel over millions of years, the nervous and immune systems currently use the same archetypal principles and strategies to address related challenges in information processing and retrieval. Ultimately, nature is conservative. One need only look at a tree, a river, the airways, or the vascular bed in order to see how a fractal pattern of repetitive dichotomous branching has been used by each, in order to optimize the transport of fluids over large distances [45]. While each system has had to adopt different materials in order to solve the problem, the shape of their solutions is remarkably alike. In the immune and nervous systems, the elements used to produce optimal functional responses are also quite different, but again the solutions have been achieved by comparable strategies. I am certain that these two great systems of information processing, each responding with vastly different kinetics, will prove to be far more integrally interdependent than has been previously recognized. For example, should a swift response by the immune system be required in an overwhelming invasion by microbial pathogens, the immune system may be able to cooperate with the rapidly reacting nervous system to rid the host of the invaders. In this regard, we have shown that the beta-adrenergic hormone epinephrine rapidly increases the traffic of

  10. The University Immune System: Overcoming Resistance to Change

    ERIC Educational Resources Information Center

    Gilley, Ann; Godek, Marisha; Gilley, Jerry W.

    2009-01-01

    A university, similar to any other organization, has an immune system that erects a powerful barrier against change. This article discusses the university immune system and what can be done to counteract its negative effects and thereby allow change to occur.

  11. An Immunized Aircraft Maneuver Selection System

    NASA Technical Reports Server (NTRS)

    Karr, Charles L.

    2003-01-01

    The objective of this project, as stated in the original proposal, was to develop an immunized aircraft maneuver selection (IAMS) system. The IAMS system was to be composed of computational and informational building blocks that resemble structures in natural immune systems. The ultimate goal of the project was to develop a software package that could be flight tested on aircraft models. This report describes the work performed in the first year of what was to have been a two year project. This report also describes efforts that would have been made in the final year to have completed the project, had it been continued for the final year. After introductory material is provided in Section 2, the end-of-year-one status of the effort is discussed in Section 3. The remainder of the report provides an accounting of first year efforts. Section 4 provides background information on natural immune systems while Section 5 describes a generic ar&itecture developed for use in the IAMS. Section 6 describes the application of the architecture to a system identification problem. Finally, Section 7 describes steps necessary for completing the project.

  12. Effects of microgravity on the immune system

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald; Taylor, Gerald R.

    1991-01-01

    Changes in resistance to bacterial and viral infections in Apollo crew members has stimulated interest in the study of immunity and space flight. Results of studies from several laboratories in both humans and rodents have indicated alterations after space flight that include the following immunological parameters: thymus size, lymphocyte blastogenesis, interferon and interleukin production, natural killer cell activity, cytotoxic T-cell activity, leukocyte subset population distribution, response of bone marrow cells to colony stimulating factors, and delayed hypersensitivity skin test reactivity. The interactions of the immune system with other physiological systems, including muscle, bone, and the nervous system, may play a major role in the development of these immunological parameters during and after flight. There may also be direct effects of space flight on immune responses.

  13. Aging of the Immune System. Mechanisms and Therapeutic Targets.

    PubMed

    Weyand, Cornelia M; Goronzy, Jörg J

    2016-12-01

    Beginning with the sixth decade of life, the human immune system undergoes dramatic aging-related changes, which continuously progress to a state of immunosenescence. The aging immune system loses the ability to protect against infections and cancer and fails to support appropriate wound healing. Vaccine responses are typically impaired in older individuals. Conversely, inflammatory responses mediated by the innate immune system gain in intensity and duration, rendering older individuals susceptible to tissue-damaging immunity and inflammatory disease. Immune system aging functions as an accelerator for other age-related pathologies. It occurs prematurely in some clinical conditions, most prominently in patients with the autoimmune syndrome rheumatoid arthritis (RA); and such patients serve as an informative model system to study molecular mechanisms of immune aging. T cells from patients with RA are prone to differentiate into proinflammatory effector cells, sustaining chronic-persistent inflammatory lesions in the joints and many other organ systems. RA T cells have several hallmarks of cellular aging; most importantly, they accumulate damaged DNA. Because of deficiency of the DNA repair kinase ataxia telangiectasia mutated, RA T cells carry a higher burden of DNA double-strand breaks, triggering cell-indigenous stress signals that shift the cell's survival potential and differentiation pattern. Immune aging in RA T cells is also associated with metabolic reprogramming; specifically, with reduced glycolytic flux and diminished ATP production. Chronic energy stress affects the longevity and the functional differentiation of older T cells. Altered metabolic patterns provide opportunities to therapeutically target the immune aging process through metabolic interference.

  14. Impact of aging immune system on neurodegeneration and potential immunotherapies.

    PubMed

    Liang, Zhanfeng; Zhao, Yang; Ruan, Linhui; Zhu, Linnan; Jin, Kunlin; Zhuge, Qichuan; Su, Dong-Ming; Zhao, Yong

    2017-10-01

    The interaction between the nervous and immune systems during aging is an area of avid interest, but many aspects remain unclear. This is due, not only to the complexity of the aging process, but also to a mutual dependency and reciprocal causation of alterations and diseases between both the nervous and immune systems. Aging of the brain drives whole body systemic aging, including aging-related changes of the immune system. In turn, the immune system aging, particularly immunosenescence and T cell aging initiated by thymic involution that are sources of chronic inflammation in the elderly (termed inflammaging), potentially induces brain aging and memory loss in a reciprocal manner. Therefore, immunotherapeutics including modulation of inflammation, vaccination, cellular immune therapies and "protective autoimmunity" provide promising approaches to rejuvenate neuroinflammatory disorders and repair brain injury. In this review, we summarize recent discoveries linking the aging immune system with the development of neurodegeneration. Additionally, we discuss potential rejuvenation strategies, focusing aimed at targeting the aging immune system in an effort to prevent acute brain injury and chronic neurodegeneration during aging. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. A methodological approach for using high-level Petri Nets to model the immune system response.

    PubMed

    Pennisi, Marzio; Cavalieri, Salvatore; Motta, Santo; Pappalardo, Francesco

    2016-12-22

    Mathematical and computational models showed to be a very important support tool for the comprehension of the immune system response against pathogens. Models and simulations allowed to study the immune system behavior, to test biological hypotheses about diseases and infection dynamics, and to improve and optimize novel and existing drugs and vaccines. Continuous models, mainly based on differential equations, usually allow to qualitatively study the system but lack in description; conversely discrete models, such as agent based models and cellular automata, permit to describe in detail entities properties at the cost of losing most qualitative analyses. Petri Nets (PN) are a graphical modeling tool developed to model concurrency and synchronization in distributed systems. Their use has become increasingly marked also thanks to the introduction in the years of many features and extensions which lead to the born of "high level" PN. We propose a novel methodological approach that is based on high level PN, and in particular on Colored Petri Nets (CPN), that can be used to model the immune system response at the cellular scale. To demonstrate the potentiality of the approach we provide a simple model of the humoral immune system response that is able of reproducing some of the most complex well-known features of the adaptive response like memory and specificity features. The methodology we present has advantages of both the two classical approaches based on continuous and discrete models, since it allows to gain good level of granularity in the description of cells behavior without losing the possibility of having a qualitative analysis. Furthermore, the presented methodology based on CPN allows the adoption of the same graphical modeling technique well known to life scientists that use PN for the modeling of signaling pathways. Finally, such an approach may open the floodgates to the realization of multi scale models that integrate both signaling pathways (intra

  16. Roles of microRNA in the immature immune system of neonates.

    PubMed

    Yu, Hong-Ren; Huang, Lien-Hung; Li, Sung-Chou

    2018-06-13

    Neonates have an immature immune system; therefore, their immune activities are different from the activities of adult immune systems. Such differences between neonates and adults are reflected by cell population constitutions, immune responses, cytokine production, and the expression of cellular/humoral molecules, which contribute to the specific neonatal microbial susceptibility and atopic properties. MicroRNAs (miRNAs) have been discovered to modulate many aspects of immune responses. Herein, we summarize the distinct manifestations of the neonatal immune system, including cellular and non-cellular components. We also review the current findings on the modulatory effects of miRNAs on the neonatal immune system. These findings suggest that miRNAs have the potential to be useful therapeutic targets for certain infection or inflammatory conditions by modulating the neonatal immune system. In the future, we need a more comprehensive understanding in regard to miRNAs and how they modulate specific immune cells in neonates. Copyright © 2018. Published by Elsevier B.V.

  17. Cancer immunoediting by the innate immune system in the absence of adaptive immunity

    PubMed Central

    O’Sullivan, Timothy; Saddawi-Konefka, Robert; Vermi, William; Koebel, Catherine M.; Arthur, Cora; White, J. Michael; Uppaluri, Ravi; Andrews, Daniel M.; Ngiow, Shin Foong; Teng, Michele W.L.; Smyth, Mark J.; Schreiber, Robert D.

    2012-01-01

    Cancer immunoediting is the process whereby immune cells protect against cancer formation by sculpting the immunogenicity of developing tumors. Although the full process depends on innate and adaptive immunity, it remains unclear whether innate immunity alone is capable of immunoediting. To determine whether the innate immune system can edit tumor cells in the absence of adaptive immunity, we compared the incidence and immunogenicity of 3′methylcholanthrene-induced sarcomas in syngeneic wild-type, RAG2−/−, and RAG2−/−x γc−/− mice. We found that innate immune cells could manifest cancer immunoediting activity in the absence of adaptive immunity. This activity required natural killer (NK) cells and interferon γ (IFN-γ), which mediated the induction of M1 macrophages. M1 macrophages could be elicited by administration of CD40 agonists, thereby restoring editing activity in RAG2−/−x γc−/− mice. Our results suggest that in the absence of adaptive immunity, NK cell production of IFN-γ induces M1 macrophages, which act as important effectors during cancer immunoediting. PMID:22927549

  18. Systems integration of innate and adaptive immunity.

    PubMed

    Zak, Daniel E; Aderem, Alan

    2015-09-29

    The pathogens causing AIDS, malaria, and tuberculosis have proven too complex to be overcome by classical approaches to vaccination. The complexities of human immunology and pathogen-induced modulation of the immune system mandate new approaches to vaccine discovery and design. A new field, systems vaccinology, weds holistic analysis of innate and adaptive immunity within a quantitative framework to enable rational design of new vaccines that elicit tailored protective immune responses. A key step in the approach is to discover relationships between the earliest innate inflammatory responses to vaccination and the subsequent vaccine-induced adaptive immune responses and efficacy. Analysis of these responses in clinical studies is complicated by the inaccessibility of relevant tissue compartments (such as the lymph node), necessitating reliance upon peripheral blood responses as surrogates. Blood transcriptomes, although indirect to vaccine mechanisms, have proven very informative in systems vaccinology studies. The approach is most powerful when innate and adaptive immune responses are integrated with vaccine efficacy, which is possible for malaria with the advent of a robust human challenge model. This is more difficult for AIDS and tuberculosis, given that human challenge models are lacking and efficacy observed in clinical trials has been low or highly variable. This challenge can be met by appropriate clinical trial design for partially efficacious vaccines and by analysis of natural infection cohorts. Ultimately, systems vaccinology is an iterative approach in which mechanistic hypotheses-derived from analysis of clinical studies-are evaluated in model systems, and then used to guide the development of new vaccine strategies. In this review, we will illustrate the above facets of the systems vaccinology approach with case studies. Copyright © 2015. Published by Elsevier Ltd.

  19. Transportation Planning with Immune System Derived Approach

    NASA Astrophysics Data System (ADS)

    Sugiyama, Kenji; Yaji, Yasuhito; Ootsuki, John Takuya; Fujimoto, Yasutaka; Sekiguchi, Takashi

    This paper presents an immune system derived approach for planning transportation of materials between manufacturing processes in the factory. Transportation operations are modeled by Petri Net, and divided into submodels. Transportation orders are derived from the firing sequences of those submodels through convergence calculation by the immune system derived excitation and suppression operations. Basic evaluation of this approach is conducted by simulation-based investigation.

  20. Overview of fish immune system and infectious diseases

    USDA-ARS?s Scientific Manuscript database

    A brief overview of the fish immune system and the emerging or re-emerging bacterial, viral, parasitic and fungal diseases considered to currently have a negative impact on aquaculture is presented. The fish immune system has evolved with both innate (natural resistance) and adaptive (acquired) immu...

  1. The immune system and skin cancer.

    PubMed

    Yu, Sherry H; Bordeaux, Jeremy S; Baron, Elma D

    2014-01-01

    Carcinogenesis involves multiple mechanisms that disturb genomic integrity and encourage abnormal proliferation. The immune system plays an integral role in maintaining homeostasis and these mechanisms may arrest or enhance dysplasia. There exists a large body of evidence from organ transplantation literature supporting the significance of the immune suppression in the development of skin cancer. Nonmelanoma skin cancers are the most frequent neoplasms after organ transplantation, with organ transplant recipients having a 65-fold increase in squamous cell carcinoma incidence and 10-fold increase in basal cell carcinoma incidence. Similarly, UV-radiation (UVR) induced immunosuppression is correlated with the development of cutaneous malignancies in a dose-dependent manner. This was first shown several decades ago by Margaret Kripke, when transplanted tumors were rejected in mice with competent immune systems, but grew unchecked in immunosuppressed specimens. After UV exposure, chromophores initiate a cascade that leads to immunosuppression via derangement of Langerhans cells' antigen-presenting capacity. UV-irradiated Langerhans cells present antigens to Th2 cells, but fail to stimulate Th1 cells. A subset of T regulatory cells, specific for the antigen encountered after UVR, is also stimulated to proliferate. In general UV irradiation leads to a greater number of T regulatory cells and fewer effector T cells in the skin, shiftingthe balance from T-cell-mediated immunity to immunosuppression. These regulatory cells have the phenotype CD4+, CD25+, Foxp3+, CTLA-4+. These and many other changes in local immunity lead to a suppressed immune state, which allow for skin cancer development.

  2. [Relationship between BCG immunization coverage and the immunization delivery system in the Tama area of Tokyo].

    PubMed

    Sugishita, Yoshiyuki; Hayashi, Kunihiko; Mori, Toru; Horiguchi, Itsuko; Marui, Eiji

    2012-03-01

    The BCG immunization has long been performed in Japan. Although the BCG immunization service is the responsibility of the municipality, the manner in which the BCG immunization is delivered differs from municipality to municipality. The purpose of this study was to clarify how the different manner of the BCG immunization delivery systems influenced the BCG immunization coverage. The study of BCG immunization coverage was conducted in the Tama area located in the western suburbs of Tokyo in 2004. The birth data and the immunization history by the age of 3 years were collected in the three-year-old health check-up from a total of 2,341 children residing in the Tama area. Based on the age at immunization for each child, the BCG immunization coverage was calculated according to the types of the BCG immunization delivery system. The immunization types were defined as follows; the BCG immunization given on the occasion of the mass health check-up (Group 1); the exclusive mass BCG immunization in a monthly service (Group 2); the exclusive mass BCG immunization in a bimonthly service (Group 3); the exclusive mass BCG immunization in services of fewer than every two months (Group 4); and the immunization given on an individual basis by a general practitioner (Group 5). A univariate analysis was performed to examine the relationship between the BCG immunization coverage by the age of 6 months and the difference among the BCG immunization delivery systems, followed by a multivariate regression analysis to adjust for the factors related to the demography, health care services and the socio-economic status of the municipalities. Unadjusted odds ratios and adjusted odds ratios for BCG unimmunized children under the age of 6 months by the BCG immunization delivery manner groups were OR 1 reference, adj. OR 1 reference in Group 1; OR 1.42 CI 0.87-2.29, adj. OR 4.01 CI 2.24-7.11 in Group 2; OR 4.96 CI 3.66-6.82, adj. OR 15.59 CI 10.10-24.49 in Group 3;OR 18.60 CI 13.77-25.49, adj

  3. CMV immune evasion and manipulation of the immune system with aging.

    PubMed

    Jackson, Sarah E; Redeker, Anke; Arens, Ramon; van Baarle, Debbie; van den Berg, Sara P H; Benedict, Chris A; Čičin-Šain, Luka; Hill, Ann B; Wills, Mark R

    2017-06-01

    Human cytomegalovirus (HCMV) encodes numerous proteins and microRNAs that function to evade the immune response and allow the virus to replicate and disseminate in the face of a competent innate and acquired immune system. The establishment of a latent infection by CMV, which if completely quiescent at the level of viral gene expression would represent an ultimate in immune evasion strategies, is not sufficient for lifelong persistence and dissemination of the virus. CMV needs to reactivate and replicate in a lytic cycle of infection in order to disseminate further, which occurs in the face of a fully primed secondary immune response. Without reactivation, latency itself would be redundant for the virus. It is also becoming clear that latency is not a totally quiescent state, but is characterized by limited viral gene expression. Therefore, the virus also needs immune evasion strategies during latency. An effective immune response to CMV is required or viral replication will cause morbidity and ultimately mortality in the host. There is clearly a complex balance between virus immune evasion and host immune recognition over a lifetime. This poses the important question of whether long-term evasion or manipulation of the immune response driven by CMV is detrimental to health. In this meeting report, three groups used the murine model of CMV (MCMV) to examine if the contribution of the virus to immune senescence is set by the (i) initial viral inoculum, (ii) inflation of T cell responses, (iii) or the balance between functionally distinct effector CD4+ T cells. The work of other groups studying the CMV response in humans is discussed. Their work asks whether the ability to make immune responses to new antigens is compromised by (i) age and HCMV carriage, (ii) long-term exposure to HCMV giving rise to an overall immunosuppressive environment and increased levels of latent virus, or (iii) adapted virus mutants (used as potential vaccines) that have the capacity to

  4. The Immune System: Basis of so much Health and Disease: 4. Immunocytes.

    PubMed

    Scully, Crispian; Georgakopoulou, Eleni A; Hassona, Yazan

    2017-05-01

    The immune system is the body’s primary defence mechanism against infections, and disturbances in the system can cause disease if the system fails in defence functions (in immunocompromised people), or if the activity is detrimental to the host (as in auto-immune and auto-inflammatory states). A healthy immune system is also essential to normal health of dental and oral tissues. This series presents the basics for the understanding of the immune system, this article covers cells of the immune system (immunocytes). Clinical relevance: Modern dental clinicians need a basic understanding of the immune system as it underlies health and disease.

  5. How (and why) the immune system makes us sleep.

    PubMed

    Imeri, Luca; Opp, Mark R

    2009-03-01

    Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value.

  6. [Regulatory role of the immune system in the organism].

    PubMed

    Alekseev, L P; Khaitov, R M

    2010-08-01

    The paper presents modern idea of regulatory role of the human immune system in performing a number of physiological functions including intercellular interactions, reproductive process, and forming of protection against external and internal aggression. Significance of the immune system is considered and substantiated, that of genes of the human immune response in particular in provision of human survival as a biological species.

  7. Human adaptive immune system Rag2-/-gamma(c)-/- mice.

    PubMed

    Chicha, Laurie; Tussiwand, Roxane; Traggiai, Elisabetta; Mazzucchelli, Luca; Bronz, Lucio; Piffaretti, Jean-Claude; Lanzavecchia, Antonio; Manz, Markus G

    2005-06-01

    Although many biologic principles are conserved in mice and humans, species-specific differences exist, for example, in susceptibility and response to pathogens, that often do not allow direct implementation of findings in experimental mice to humans. Research in humans, however, for ethical and practical reasons, is largely restricted to in vitro assays that lack components and the complexity of a living organism. To nevertheless study the human hematopoietic and immune system in vivo, xenotransplantation assays have been developed that substitute human components to small animals. Here, we summarize our recent findings that transplantation of human cord blood CD34(+) cells to newborn Rag2(-/-)gamma(c)(-/-) mice leads to de novo development of major functional components of the human adaptive immune system. These human adaptive immune system Rag2(-/-)gamma(c)(-/-) (huAIS-RG) mice can now be used as a technically straightforward preclinical model to evaluate in vivo human adaptive immune system development as well as immune responses, for example, to vaccines or live infectious pathogens.

  8. Nutritionally mediated programming of the developing immune system.

    PubMed

    Palmer, Amanda C

    2011-09-01

    A growing body of evidence highlights the importance of a mother's nutrition from preconception through lactation in programming the emerging organ systems and homeostatic pathways of her offspring. The developing immune system may be particularly vulnerable. Indeed, examples of nutrition-mediated immune programming can be found in the literature on intra-uterine growth retardation, maternal micronutrient deficiencies, and infant feeding. Current models of immune ontogeny depict a "layered" expansion of increasingly complex defenses, which may be permanently altered by maternal malnutrition. One programming mechanism involves activation of the maternal hypothalamic-pituitary-adrenal axis in response to nutritional stress. Fetal or neonatal exposure to elevated stress hormones is linked in animal studies to permanent changes in neuroendocrine-immune interactions, with diverse manifestations such as an attenuated inflammatory response or reduced resistance to tumor colonization. Maternal malnutrition may also have a direct influence, as evidenced by nutrient-driven epigenetic changes to developing T regulatory cells and subsequent risk of allergy or asthma. A 3rd programming pathway involves placental or breast milk transfer of maternal immune factors with immunomodulatory functions (e.g. cytokines). Maternal malnutrition can directly affect transfer mechanisms or influence the quality or quantity of transferred factors. The public health implications of nutrition-mediated immune programming are of particular importance in the developing world, where prevalent maternal undernutrition is coupled with persistent infectious challenges. However, early alterations to the immune system, resulting from either nutritional deficiencies or excesses, have broad relevance for immune-mediated diseases, such as asthma, and chronic inflammatory conditions like cardiovascular disease.

  9. The Immune System in Hypertension

    ERIC Educational Resources Information Center

    Trott, Daniel W.; Harrison, David G.

    2014-01-01

    While hypertension has predominantly been attributed to perturbations of the vasculature, kidney, and central nervous system, research for almost 50 yr has shown that the immune system also contributes to this disease. Inflammatory cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension and likely…

  10. The Immune System of HIV-Exposed Uninfected Infants.

    PubMed

    Abu-Raya, Bahaa; Kollmann, Tobias R; Marchant, Arnaud; MacGillivray, Duncan M

    2016-01-01

    Infants born to human immunodeficiency virus (HIV) infected women are HIV-exposed but the majority remains uninfected [i.e., HIV-exposed uninfected (HEU)]. HEU infants suffer greater morbidity and mortality from infections compared to HIV-unexposed (HU) peers. The reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. This review comprehensively summarizes the current literature investigating the adaptive and innate immune system of HEU infants. HEU infants have altered cell-mediated immunity, including impaired T-cell maturation with documented hypo- as well as hyper-responsiveness to T-cell activation. And although prevaccination vaccine-specific antibody levels are often lower in HEU than HU, most HEU infants mount adequate humoral immune response following primary vaccination with diphtheria toxoid, haemophilus influenzae type b, whole cell pertussis, measles, hepatitis B, tetanus toxoid, and pneumococcal conjugate vaccines. However, HEU infants are often found to have lower absolute neutrophil counts as compared to HU infants. On the other hand, an increase of innate immune cytokine production and expression of co-stimulatory markers has been noted in HEU infants, but this increase appears to be restricted to the first few weeks of life. The immune system of HEU children beyond infancy remains largely unexplored.

  11. Neuroimmune Interactions: From the Brain to the Immune System and Vice Versa.

    PubMed

    Dantzer, Robert

    2018-01-01

    Because of the compartmentalization of disciplines that shaped the academic landscape of biology and biomedical sciences in the past, physiological systems have long been studied in isolation from each other. This has particularly been the case for the immune system. As a consequence of its ties with pathology and microbiology, immunology as a discipline has largely grown independently of physiology. Accordingly, it has taken a long time for immunologists to accept the concept that the immune system is not self-regulated but functions in close association with the nervous system. These associations are present at different levels of organization. At the local level, there is clear evidence for the production and use of immune factors by the central nervous system and for the production and use of neuroendocrine mediators by the immune system. Short-range interactions between immune cells and peripheral nerve endings innervating immune organs allow the immune system to recruit local neuronal elements for fine tuning of the immune response. Reciprocally, immune cells and mediators play a regulatory role in the nervous system and participate in the elimination and plasticity of synapses during development as well as in synaptic plasticity at adulthood. At the whole organism level, long-range interactions between immune cells and the central nervous system allow the immune system to engage the rest of the body in the fight against infection from pathogenic microorganisms and permit the nervous system to regulate immune functioning. Alterations in communication pathways between the immune system and the nervous system can account for many pathological conditions that were initially attributed to strict organ dysfunction. This applies in particular to psychiatric disorders and several immune-mediated diseases. This review will show how our understanding of this balance between long-range and short-range interactions between the immune system and the central nervous

  12. Assessment of geometry in 2D immune systems using high accuracy laser-based bioprinting techniques (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Lauzurica, Sara; Márquez, Andrés.; Molpeceres, Carlos; Notario, Laura; Gómez-Fontela, Miguel; Lauzurica, Pilar

    2017-02-01

    The immune system is a very complex system that comprises a network of genetic and signaling pathways subtending a network of interacting cells. The location of the cells in a network, along with the gene products they interact with, rules the behavior of the immune system. Therefore, there is a great interest in understanding properly the role of a cell in such networks to increase our knowledge of the immune system response. In order to acquire a better understanding of these processes, cell printing with high spatial resolution emerges as one of the promising approaches to organize cells in two and three-dimensional patterns to enable the study the geometry influence in these interactions. In particular, laser assisted bio-printing techniques using sub-nanosecond laser sources have better characteristics for application in this field, mainly due to its higher spatial resolution, cell viability percentage and process automation. This work presents laser assisted bio-printing of antigen-presenting cells (APCs) in two-dimensional geometries, placing cellular components on a matrix previously generated on demand, permitting to test the molecular interactions between APCs and lymphocytes; as well as the generation of two-dimensional structures designed ad hoc in order to study the mechanisms of mobilization of immune system cells. The use of laser assisted bio-printing, along with APCs and lymphocytes emulate the structure of different niches of the immune system so that we can analyse functional requirement of these interaction.

  13. Immune system alterations in amyotrophic lateral sclerosis.

    PubMed

    Hovden, H; Frederiksen, J L; Pedersen, S W

    2013-11-01

    Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might give more insight into the disease. Markers from the classical complement pathway are elevated where its initiator C1q appears to derive primarily from motor neurons. Activated microglia and astrocytes are found in close proximity to dying motor neurons. Their activation status and proliferation seemingly increases with disease progression. Infiltrating monocytes, macrophages and T cells are associated with these areas, although with mixed reports regarding T cell composition. This literature review will provide evidence supporting the immune system as an important part of ALS disease mechanism and present a hypothesis to direct the way for further studies. © 2013 John Wiley & Sons A/S.

  14. The Immune System in Obesity: Developing Paradigms Amidst Inconvenient Truths.

    PubMed

    Agrawal, Madhur; Kern, Philip A; Nikolajczyk, Barbara S

    2017-08-15

    Adipose tissue (AT) houses both innate and adaptive immune systems that are crucial for preserving AT function and metabolic homeostasis. In this review, we summarize recent information regarding progression of obesity-associated AT inflammation and insulin resistance. We additionally consider alterations in AT distribution and the immune system in males vs. females and among different racial populations. Innate and adaptive immune cell-derived inflammation drives insulin resistance both locally and systemically. However, new evidence also suggests that the immune system is equally vital for adipocyte differentiation and protection from ectopic lipid deposition. Furthermore, roles of anti-inflammatory immune cells such as regulatory T cells, "M2-like" macrophages, eosinophils, and mast cells are being explored, primarily due to promise of immunotherapeutic applications. Both immune responses and AT distribution are strongly influenced by factors like sex and race, which have been largely underappreciated in the field of metabolically-associated inflammation, or meta-flammation. More studies are required to recognize factors that switch inflammation from controlled to uncontrolled in obesity-associated pathogenesis and to integrate the combined effects of meta-flammation and immunometabolism. It is critical to recognize that the AT-associated immune system can be alternately beneficial and destructive; therefore, simply blocking immune responses early in obesity may not be the best clinical approach. The dearth of information on gender and race-associated disparities in metabolism, AT distribution, and the immune system suggest that a greater understanding of such differences will be critical to develop personalized treatments for obesity and the associated metabolic dysfunction.

  15. Activation of the immune system by bacterial CpG-DNA

    PubMed Central

    Häcker, Georg; Redecke, Vanessa; Häcker, Hans

    2002-01-01

    The past decade has seen a remarkable process of refocusing in immunology. Cells of the innate immune system, especially macrophages and dendritic cells, have been at the centre of this process. These cells had been regarded by some scientists as non-specific, sometimes perhaps even confined to the menial job of serving T cells by scavenging antigen and presenting it to the sophisticated adaptive immune system. Only over the last few years has it become unequivocally clear that cells of the innate immunity hold, by variation of context and mode of antigen presentation, the power of shaping an adaptive immune response. The innate immune response, in turn, is to a significant degree the result of stimulation by so-called pathogen-associated molecular patterns (PAMPs). One compound with high stimulatory potential for the innate immune system is bacterial DNA. Here we will review recent evidence that bacterial DNA should be ranked with other PAMPs such as lipopolysaccharide (LPS) and lipoteichoic acid. We will further review our present knowledge of DNA recognition and DNA-dependent signal transduction in cells of the immune system. PMID:11918685

  16. The immunization data quality audit: verifying the quality and consistency of immunization monitoring systems.

    PubMed Central

    Ronveaux, O.; Rickert, D.; Hadler, S.; Groom, H.; Lloyd, J.; Bchir, A.; Birmingham, M.

    2005-01-01

    OBJECTIVE: To evaluate the consistency and quality of immunization monitoring systems in 27 countries during 2002-03 using standardized data quality audits (DQAs) that had been launched within the framework of the Global Alliance for Vaccines and Immunization. METHODS: The consistency of reporting systems was estimated by determining the proportion of third doses of diphtheria-tetanuspertussis (DTP-3) vaccine reported as being administered that could be verified by written documentation at health facilities and districts. The quality of monitoring systems was measured using quality indices for different components of the monitoring systems. These indices were applied to each level of the health service (health unit, district and national). FINDINGS: The proportion of verified DTP-3 doses was lower than 85% in 16 countries. Difficulties in verifying the doses administered often arose at the peripheral level of the health service, usually as the result of discrepancies in information between health units and their corresponding districts or because completed recording forms were not available from health units. All countries had weaknesses in their monitoring systems; these included the inconsistent use of monitoring charts; inadequate monitoring of vaccine stocks, injection supplies and adverse events; unsafe computer practices; and poor monitoring of completeness and timeliness of reporting. CONCLUSION: Inconsistencies in immunization data occur in many countries, hampering their ability to manage their immunization programmes. Countries should use these findings to strengthen monitoring systems so that data can reliably guide programme activities. The DQA is an innovative tool that provides a way to independently assess the quality of immunization monitoring systems at all levels of a health service and serves as a point of entry to make improvements. It provides a useful example for other global health initiatives. PMID:16175824

  17. Robustness trade-offs and host–microbial symbiosis in the immune system

    PubMed Central

    Kitano, Hiroaki; Oda, Kanae

    2006-01-01

    The immune system provides organisms with robustness against pathogen threats, yet it also often adversely affects the organism as in autoimmune diseases. Recently, the molecular interactions involved in the immune system have been uncovered. At the same time, the role of the bacterial flora and its interactions with the host immune system have been identified. In this article, we try to reconcile these findings to draw a consistent picture of the host defense system. Specifically, we first argue that the network of molecular interactions involved in immune functions has a bow-tie architecture that entails inherent trade-offs among robustness, fragility, resource limitation, and performance. Second, we discuss the possibility that commensal bacteria and the host immune system constitute an integrated defense system. This symbiotic association has evolved to optimize its robustness against pathogen attacks and nutrient perturbations by harboring a broad range of microorganisms. Owing to the inherent propensity of a host immune system toward hyperactivity, maintenance of bacterial flora homeostasis might be particularly important in the development of preventive strategies against immune disorders such as autoimmune diseases. PMID:16738567

  18. How (and why) the immune system makes us sleep

    PubMed Central

    Imeri, Luca; Opp, Mark R.

    2010-01-01

    Good sleep is necessary for physical and mental health. For example, sleep loss impairs immune function, and sleep is altered during infection. Immune signalling molecules are present in the healthy brain, where they interact with neurochemical systems to contribute to the regulation of normal sleep. Animal studies have shown that interactions between immune signalling molecules (such as the cytokine interleukin 1) and brain neurochemical systems (such as the serotonin system) are amplified during infection, indicating that these interactions might underlie the changes in sleep that occur during infection. Why should the immune system cause us to sleep differently when we are sick? We propose that the alterations in sleep architecture during infection are exquisitely tailored to support the generation of fever, which in turn imparts survival value. PMID:19209176

  19. Modulating the immune system through nanotechnology.

    PubMed

    Dacoba, Tamara G; Olivera, Ana; Torres, Dolores; Crecente-Campo, José; Alonso, María José

    2017-12-01

    Nowadays, nanotechnology-based modulation of the immune system is presented as a cutting-edge strategy, which may lead to significant improvements in the treatment of severe diseases. In particular, efforts have been focused on the development of nanotechnology-based vaccines, which could be used for immunization or generation of tolerance. In this review, we highlight how different immune responses can be elicited by tuning nanosystems properties. In addition, we discuss specific formulation approaches designed for the development of anti-infectious and anti-autoimmune vaccines, as well as those intended to prevent the formation of antibodies against biologicals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Reactions of immune system to physical exercises.

    PubMed

    Pershin, Boris B; Geliev, Anatoly B; Tolstov, Dmitry V; Kovalchuk, Leonid V; Medvedev, Vladimir Ya

    2002-04-01

    The great attention to reactions of immune system to the physical exercises in sportsmen is linked to the growth of training volumes, to the increase of competition numbers and to the elevation of morbidity. Immune deficiency may be considered as the detonator of pathological processes among which acute respiratory diseases (ARD) are investigated most completely in sports medicine. Other pathologies require long-term observations, but it is not so simple to do due to the frequent renewal of sports groups. Besides ARD, there are reports about the growth of cases of poliomyelitis, endotoxemia, allergic and autoimmune disorders. Immune reactions in sportsmen are developed at the background of fever, impaired balance of ergotrophic hormone activity and in a number of cases under conditions of systemic endotoxemia. We have described the extreme type of immune deficiency in sportsmen, in which we could not determine different isotypes of Ig. The phenomenon of Ig disappearance is reproduced under the experimental conditions that opened the way to study its mechanisms. Physical exercises decrease function of immunocompetent cells, their antiviral resistance, antigen presentation and expression of class II MHC molecules. With the involvement of macrophages hyperproduction of IL-6 is developed in muscle tissues. After physical exercises other cytokines also change the state of immunity. Also, neuropeptides getting in touch the links between endocrine and immune systems may make a contribution to immunosuppression. The immunosuppression may be prevented by use of special carbohydrate diets and by administration of complexed preparations. The prophylaxis is capable to control the morbidity, profoundly to increase the training volumes and to enhance the labor efficiency.

  1. Interactions of cnidarian toxins with the immune system.

    PubMed

    Suput, Dusan

    2011-10-01

    Cnidarians comprise four classes of toxic marine animals: Anthozoa, Cubozoa, Scyphozoa and Hydrozoa. They are the largest and probably the oldest phylum of toxic marine animals. Any contact with a cnidarian, especially the box jellyfish (Chironex fleckeri), can be fatal, but most cnidarians do not possess sufficiently strong venomous apparatus to penetrate the human skin, whereas others rarely come into contact with human beings. Only a small, almost negligible percentage of the vast wealth of cnidarian toxins has been studied in detail. Many polypeptide cnidarian toxins are immunogenic, and cross-reactivity between several jellyfish venoms has been reported. Cnidarians also possess components of innate immunity, and some of those components have been preserved in evolution. On the other hand, cnidarian toxins have already been used for the design of immunotoxins to treat cancer, whereas other cnidarian toxins can modulate the immune system in mammals, including man. This review will focus on a short overview of cnidarian toxins, on the innate immunity of cnidarians, and on the mode of action of cnidarian toxins which can modulate the immune system in mammals. Emphasis is palced on those toxins which block voltage activated potassium channels in the cells of the immune system.

  2. Dissecting innate immune responses with the tools of systems biology.

    PubMed

    Smith, Kelly D; Bolouri, Hamid

    2005-02-01

    Systems biology strives to derive accurate predictive descriptions of complex systems such as innate immunity. The innate immune system is essential for host defense, yet the resulting inflammatory response must be tightly regulated. Current understanding indicates that this system is controlled by complex regulatory networks, which maintain homoeostasis while accurately distinguishing pathogenic infections from harmless exposures. Recent studies have used high throughput technologies and computational techniques that presage predictive models and will be the foundation of a systems level understanding of innate immunity.

  3. Direct and Electronic Health Record Access to the Clinical Decision Support for Immunizations in the Minnesota Immunization Information System.

    PubMed

    Rajamani, Sripriya; Bieringer, Aaron; Wallerius, Stephanie; Jensen, Daniel; Winden, Tamara; Muscoplat, Miriam Halstead

    2016-01-01

    Immunization information systems (IIS) are population-based and confidential computerized systems maintained by public health agencies containing individual data on immunizations from participating health care providers. IIS hold comprehensive vaccination histories given across providers and over time. An important aspect to IIS is the clinical decision support for immunizations (CDSi), consisting of vaccine forecasting algorithms to determine needed immunizations. The study objective was to analyze the CDSi presentation by IIS in Minnesota (Minnesota Immunization Information Connection [MIIC]) through direct access by IIS interface and by access through electronic health records (EHRs) to outline similarities and differences. The immunization data presented were similar across the three systems examined, but with varying ability to integrate data across MIIC and EHR, which impacts immunization data reconciliation. Study findings will lead to better understanding of immunization data display, clinical decision support, and user functionalities with the ultimate goal of promoting IIS CDSi to improve vaccination rates.

  4. Effects of prebiotics on immune system and cytokine expression.

    PubMed

    Shokryazdan, Parisa; Faseleh Jahromi, Mohammad; Navidshad, Bahman; Liang, Juan Boo

    2017-02-01

    Nowadays, use of prebiotics as feed and food additives has received increasing interest because of the beneficial effects of prebiotics on the health of animals and humans. One of the beneficial effects of prebiotics is stimulation of immune system, which can be direct or indirect through increasing population of beneficial microbes or probiotics, especially lactic acid bacteria and bifidobacteria, in the gut. An important mechanism of action of probiotics and prebiotics, by which they can affect the immune system, is changing the expression of cytokines. The present review tried to summarize the findings of studies that investigated the effects of prebiotics on immune system with focusing on their effects on cytokine expression. Generally, most of reviewed studies indicated beneficial effects for prebiotics in terms of improving immune system, by increasing the expression of anti-inflammatory cytokines, while reducing the expressions of proinflammatory cytokines. However, most of studies mainly considered the indirect effects of prebiotics on the immune system (through changing the composition and population of gut microbiota), and their direct effects still need to be further studied using prebiotics with different degree of polymerization in different hosts.

  5. Prenatal immune activation in mice blocks the effects of environmental enrichment on exploratory behavior and microglia density.

    PubMed

    Buschert, Jens; Sakalem, Marna E; Saffari, Roja; Hohoff, Christa; Rothermundt, Matthias; Arolt, Volker; Zhang, Weiqi; Ambrée, Oliver

    2016-06-03

    Adverse environmental factors including prenatal maternal infection are capable of inducing long-lasting behavioral and neural alterations which can enhance the risk to develop schizophrenia. It is so far not clear whether supportive postnatal environments are able to modify such prenatally-induced alterations. In rodent models, environmental enrichment influences behavior and cognition, for instance by affecting endocrinologic, immunologic, and neuroplastic parameters. The current study was designed to elucidate the influence of postnatal environmental enrichment on schizophrenia-like behavioral alterations induced by prenatal polyI:C immune stimulation at gestational day 9 in mice. Adult offspring were tested for amphetamine-induced locomotion, social interaction, and problem-solving behavior as well as expression of dopamine D1 and D2 receptors and associated molecules, microglia density and adult neurogenesis. Prenatal polyI:C treatment resulted in increased dopamine sensitivity and dopamine D2 receptor expression in adult offspring which was not reversed by environmental enrichment. Prenatal immune activation prevented the effects of environmental enrichment which increased exploratory behavior and microglia density in NaCl treated mice. Problem-solving behavior as well as the number of immature neurons was affected by neither prenatal immune stimulation nor postnatal environmental enrichment. The behavioral and neural alterations that persist into adulthood could not generally be modified by environmental enrichment. This might be due to early neurodevelopmental disturbances which could not be rescued or compensated for at a later developmental stage. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Single-cell technologies to study the immune system.

    PubMed

    Proserpio, Valentina; Mahata, Bidesh

    2016-02-01

    The immune system is composed of a variety of cells that act in a coordinated fashion to protect the organism against a multitude of different pathogens. The great variability of existing pathogens corresponds to a similar high heterogeneity of the immune cells. The study of individual immune cells, the fundamental unit of immunity, has recently transformed from a qualitative microscopic imaging to a nearly complete quantitative transcriptomic analysis. This shift has been driven by the rapid development of multiple single-cell technologies. These new advances are expected to boost the detection of less frequent cell types and transient or intermediate cell states. They will highlight the individuality of each single cell and greatly expand the resolution of current available classifications and differentiation trajectories. In this review we discuss the recent advancement and application of single-cell technologies, their limitations and future applications to study the immune system. © 2015 The Authors. Immunology Published by John Wiley & Sons Ltd.

  7. Vaccination, herd behavior, and herd immunity.

    PubMed

    Cohen, Matan J; Brezis, Mayer; Block, Colin; Diederich, Adele; Chinitz, David

    2013-11-01

    During the 2009 outbreak of novel influenza AH1N1, insufficient data were available to adequately inform decision makers about benefits and risks of vaccination and disease. We hypothesized that individuals would opt to mimic their peers, having no better decision anchor. We used Game Theory, decision analysis, and transmission models to simulate the impact of subjective risks and preference estimates on vaccination behavior. We asked 95 students to provide estimates of risk and health state valuations with regard to AH1N1 infection, complications, and expectations of vaccine benefits and risks. These estimates were included in a sequential chain of models: a dynamic epidemic model, a decision tree, and a population-level model. Additionally, participants' intentions to vaccinate or not at varying vaccination rates were documented. The model showed that at low vaccination rates, vaccination dominated. When vaccination rates increased above 78%, nonvaccination was the dominant strategy. We found that vaccination intentions did not correspond to the shift in strategy dominance and segregated to 3 types of intentions: regardless of what others do 29/95 (31%) intended to vaccinate while 27/95 (28%) did not; among 39 of 95 (41%) intention was positively associated with putative vaccination rates. Some people conform to the majority's choice, either shifting epidemic dynamics toward herd immunity or, conversely, limiting societal goals. Policy leaders should use models carefully, noting their limitations and theoretical assumptions. Behavior drivers were not explicitly explored in this study, and the discrepant results beg further investigation. Models including real subjective perceptions with empiric or subjective probabilities can provide insight into deviations from expected rational behavior and suggest interventions in order to provide better population outcomes.

  8. Stochastic dynamics for idiotypic immune networks

    NASA Astrophysics Data System (ADS)

    Barra, Adriano; Agliari, Elena

    2010-12-01

    In this work we introduce and analyze the stochastic dynamics obeyed by a model of an immune network recently introduced by the authors. We develop Fokker-Planck equations for the single lymphocyte behavior and coarse grained Langevin schemes for the averaged clone behavior. After showing agreement with real systems (as a short path Jerne cascade), we suggest, both with analytical and numerical arguments, explanations for the generation of (metastable) memory cells, improvement of the secondary response (both in the quality and quantity) and bell shaped modulation against infections as a natural behavior. The whole emerges from the model without being postulated a-priori as it often occurs in second generation immune networks: so the aim of the work is to present some out-of-equilibrium features of this model and to highlight mechanisms which can replace a-priori assumptions in view of further detailed analysis in theoretical systemic immunology.

  9. Modeling Systems-Level Regulation of Host Immune Responses

    PubMed Central

    Thakar, Juilee; Pilione, Mylisa; Kirimanjeswara, Girish; Harvill, Eric T; Albert, Réka

    2007-01-01

    Many pathogens are able to manipulate the signaling pathways responsible for the generation of host immune responses. Here we examine and model a respiratory infection system in which disruption of host immune functions or of bacterial factors changes the dynamics of the infection. We synthesize the network of interactions between host immune components and two closely related bacteria in the genus Bordetellae. We incorporate existing experimental information on the timing of immune regulatory events into a discrete dynamic model, and verify the model by comparing the effects of simulated disruptions to the experimental outcome of knockout mutations. Our model indicates that the infection time course of both Bordetellae can be separated into three distinct phases based on the most active immune processes. We compare and discuss the effect of the species-specific virulence factors on disrupting the immune response during their infection of naive, antibody-treated, diseased, or convalescent hosts. Our model offers predictions regarding cytokine regulation, key immune components, and clearance of secondary infections; we experimentally validate two of these predictions. This type of modeling provides new insights into the virulence, pathogenesis, and host adaptation of disease-causing microorganisms and allows systems-level analysis that is not always possible using traditional methods. PMID:17559300

  10. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.

    PubMed

    Hodes, Georgia E; Pfau, Madeline L; Leboeuf, Marylene; Golden, Sam A; Christoffel, Daniel J; Bregman, Dana; Rebusi, Nicole; Heshmati, Mitra; Aleyasin, Hossein; Warren, Brandon L; Lebonté, Benoit; Horn, Sarah; Lapidus, Kyle A; Stelzhammer, Viktoria; Wong, Erik H F; Bahn, Sabine; Krishnan, Vaishnav; Bolaños-Guzman, Carlos A; Murrough, James W; Merad, Miriam; Russo, Scott J

    2014-11-11

    Depression and anxiety disorders are associated with increased release of peripheral cytokines; however, their functional relevance remains unknown. Using a social stress model in mice, we find preexisting individual differences in the sensitivity of the peripheral immune system that predict and promote vulnerability to social stress. Cytokine profiles were obtained 20 min after the first social stress exposure. Of the cytokines regulated by stress, IL-6 was most highly up-regulated only in mice that ultimately developed a susceptible behavioral phenotype following a subsequent chronic stress, and levels remained elevated for at least 1 mo. We confirmed a similar elevation of serum IL-6 in two separate cohorts of patients with treatment-resistant major depressive disorder. Before any physical contact in mice, we observed individual differences in IL-6 levels from ex vivo stimulated leukocytes that predict susceptibility versus resilience to a subsequent stressor. To shift the sensitivity of the peripheral immune system to a pro- or antidepressant state, bone marrow (BM) chimeras were generated by transplanting hematopoietic progenitor cells from stress-susceptible mice releasing high IL-6 or from IL-6 knockout (IL-6(-/-)) mice. Stress-susceptible BM chimeras exhibited increased social avoidance behavior after exposure to either subthreshold repeated social defeat stress (RSDS) or a purely emotional stressor termed witness defeat. IL-6(-/-) BM chimeric and IL-6(-/-) mice, as well as those treated with a systemic IL-6 monoclonal antibody, were resilient to social stress. These data establish that preexisting differences in stress-responsive IL-6 release from BM-derived leukocytes functionally contribute to social stress-induced behavioral abnormalities.

  11. A cognitive computational model inspired by the immune system response.

    PubMed

    Abdo Abd Al-Hady, Mohamed; Badr, Amr Ahmed; Mostafa, Mostafa Abd Al-Azim

    2014-01-01

    The immune system has a cognitive ability to differentiate between healthy and unhealthy cells. The immune system response (ISR) is stimulated by a disorder in the temporary fuzzy state that is oscillating between the healthy and unhealthy states. However, modeling the immune system is an enormous challenge; the paper introduces an extensive summary of how the immune system response functions, as an overview of a complex topic, to present the immune system as a cognitive intelligent agent. The homogeneity and perfection of the natural immune system have been always standing out as the sought-after model we attempted to imitate while building our proposed model of cognitive architecture. The paper divides the ISR into four logical phases: setting a computational architectural diagram for each phase, proceeding from functional perspectives (input, process, and output), and their consequences. The proposed architecture components are defined by matching biological operations with computational functions and hence with the framework of the paper. On the other hand, the architecture focuses on the interoperability of main theoretical immunological perspectives (classic, cognitive, and danger theory), as related to computer science terminologies. The paper presents a descriptive model of immune system, to figure out the nature of response, deemed to be intrinsic for building a hybrid computational model based on a cognitive intelligent agent perspective and inspired by the natural biology. To that end, this paper highlights the ISR phases as applied to a case study on hepatitis C virus, meanwhile illustrating our proposed architecture perspective.

  12. Behavioural conditioning of immune functions: how the central nervous system controls peripheral immune responses by evoking associative learning processes.

    PubMed

    Riether, Carsten; Doenlen, Raphaël; Pacheco-López, Gustavo; Niemi, Maj-Britt; Engler, Andrea; Engler, Harald; Schedlowski, Manfred

    2008-01-01

    During the last 30 years of psychoneuroimmunology research the intense bi-directional communication between the central nervous system (CNS) and the immune system has been demonstrated in studies on the interaction between the nervous-endocrine-immune systems. One of the most intriguing examples of such interaction is the capability of the CNS to associate an immune status with specific environmental stimuli. In this review, we systematically summarize experimental evidence demonstrating the behavioural conditioning of peripheral immune functions. In particular, we focus on the mechanisms underlying the behavioural conditioning process and provide a theoretical framework that indicates the potential feasibility of behaviourally conditioned immune changes in clinical situations.

  13. Behavioral determinants of immunization service utilization in Ethiopia: a cross-sectional community-based survey

    PubMed Central

    Ababu, Yohannes; Braka, Fiona; Teka, Aschalew; Getachew, Kinde; Tadesse, Tefera; Michael, Yohannes; Birhanu, Zewdie; Nsubuga, Peter; Assefa, Tersit; Gallagher, Kathleen

    2017-01-01

    Introduction According to the Ethiopian Health Sector Development Plan IV annual performance report (HSDP IV), Ethiopia targeted to reach 90% coverage with DPT-Hib-HepB 3 (Pentavalent3) vaccine and 86% coverage with measles vaccine in 2010- 2011. However, the actual performance fell-short of the intended targets due to several reasons. Therefore, a nationwide comprehensive study was conducted to examine the behavioral determinants of immunization practices in the Ethiopian context. The study employed the Modified Steps of Behavioral Change (SBC) Model as a theoretical lens. Methods A cross-sectional study was conducted in May 2012 in all the nine regions and the two city administrations of Ethiopia. The study used a community-based quantitative survey design comprising of multistage cluster sampling to draw relevant data from a sample of 2,328 caretakers whose children were 12-23 months of age at the time of data collection. Results Overall, the multivariate analysis findings revealed that caretakers, who had high knowledge were 2.24 times more likely to vaccinate their children than participants had low knowledge (OR= 2.24, 95%CI: 1.68-2.98). Participants who had high approval were 2.45 times more likely to vaccinate their children than participants who had unfavorable approval (OR= 2.45, 95%CI: 1.67-3.59); and participants who had high intention were 6.49 times more likely to vaccinate their children with pentavalent3 vaccines than participants who had low intention(OR= 6.49, 95%CI: 4.83-8). Also, it was clear from the regression analysis that aspects of caretakers' demographic characteristics were significant predictors of their immunization practice for the sample group. Conclusion We identified that caretakers' knowledge, approval, intention, parents' residence, and religious backgrounds were associated with immunization service utilization. To achieve sustainable behavioral change on immunization service utilization of the caretakers in Ethiopia, this study

  14. Behavioral determinants of immunization service utilization in Ethiopia: a cross-sectional community-based survey.

    PubMed

    Ababu, Yohannes; Braka, Fiona; Teka, Aschalew; Getachew, Kinde; Tadesse, Tefera; Michael, Yohannes; Birhanu, Zewdie; Nsubuga, Peter; Assefa, Tersit; Gallagher, Kathleen

    2017-01-01

    According to the Ethiopian Health Sector Development Plan IV annual performance report (HSDP IV), Ethiopia targeted to reach 90% coverage with DPT-Hib-HepB 3 (Pentavalent3) vaccine and 86% coverage with measles vaccine in 2010- 2011. However, the actual performance fell-short of the intended targets due to several reasons. Therefore, a nationwide comprehensive study was conducted to examine the behavioral determinants of immunization practices in the Ethiopian context. The study employed the Modified Steps of Behavioral Change (SBC) Model as a theoretical lens. A cross-sectional study was conducted in May 2012 in all the nine regions and the two city administrations of Ethiopia. The study used a community-based quantitative survey design comprising of multistage cluster sampling to draw relevant data from a sample of 2,328 caretakers whose children were 12-23 months of age at the time of data collection. Overall, the multivariate analysis findings revealed that caretakers, who had high knowledge were 2.24 times more likely to vaccinate their children than participants had low knowledge (OR= 2.24, 95%CI: 1.68-2.98). Participants who had high approval were 2.45 times more likely to vaccinate their children than participants who had unfavorable approval (OR= 2.45, 95%CI: 1.67-3.59); and participants who had high intention were 6.49 times more likely to vaccinate their children with pentavalent3 vaccines than participants who had low intention(OR= 6.49, 95%CI: 4.83-8). Also, it was clear from the regression analysis that aspects of caretakers' demographic characteristics were significant predictors of their immunization practice for the sample group. We identified that caretakers' knowledge, approval, intention, parents' residence, and religious backgrounds were associated with immunization service utilization. To achieve sustainable behavioral change on immunization service utilization of the caretakers in Ethiopia, this study suggests investing in activities that

  15. Changes in the immune system are conditioned by nutrition.

    PubMed

    Marcos, A; Nova, E; Montero, A

    2003-09-01

    Undernutrition due to insufficient intake of energy and macronutrients and/or due to deficiencies in specific micronutrients impairs the immune system, suppressing immune functions that are fundamental to host protection. The most consistent abnormalities are seen in cell-mediated immunity, complement system, phagocyte function, cytokine production, mucosal secretory antibody response, and antibody affinity. There is a number of physiological situations such as ageing and performance of intense physical exercise associated with an impairment of some immune parameters' response. Nutrition can influence the extent of immune alteration in both of them. There are also numerous pathological situations in which nutrition plays a role as a primary or secondary determinant of some underlying immunological impairments. This includes obesity, eating disorders (anorexia nervosa and bulimia nervosa), food hypersensitivity and gastrointestinal disorders as some examples. The implications of nutrition on immune function in these disorders are briefly reviewed.

  16. Electronic immunization data collection systems: application of an evaluation framework.

    PubMed

    Heidebrecht, Christine L; Kwong, Jeffrey C; Finkelstein, Michael; Quan, Sherman D; Pereira, Jennifer A; Quach, Susan; Deeks, Shelley L

    2014-01-14

    Evaluating the features and performance of health information systems can serve to strengthen the systems themselves as well as to guide other organizations in the process of designing and implementing surveillance tools. We adapted an evaluation framework in order to assess electronic immunization data collection systems, and applied it in two Ontario public health units. The Centers for Disease Control and Prevention's Guidelines for Evaluating Public Health Surveillance Systems are broad in nature and serve as an organizational tool to guide the development of comprehensive evaluation materials. Based on these Guidelines, and informed by other evaluation resources and input from stakeholders in the public health community, we applied an evaluation framework to two examples of immunization data collection and examined several system attributes: simplicity, flexibility, data quality, timeliness, and acceptability. Data collection approaches included key informant interviews, logic and completeness assessments, client surveys, and on-site observations. Both evaluated systems allow high-quality immunization data to be collected, analyzed, and applied in a rapid fashion. However, neither system is currently able to link to other providers' immunization data or provincial data sources, limiting the comprehensiveness of coverage assessments. We recommended that both organizations explore possibilities for external data linkage and collaborate with other jurisdictions to promote a provincial immunization repository or data sharing platform. Electronic systems such as the ones described in this paper allow immunization data to be collected, analyzed, and applied in a rapid fashion, and represent the infostructure required to establish a population-based immunization registry, critical for comprehensively assessing vaccine coverage.

  17. The role of immune system exhaustion on cancer cell escape and anti-tumor immune induction after irradiation.

    PubMed

    Mendes, Fernando; Domingues, Cátia; Rodrigues-Santos, Paulo; Abrantes, Ana Margarida; Gonçalves, Ana Cristina; Estrela, Jéssica; Encarnação, João; Pires, Ana Salomé; Laranjo, Mafalda; Alves, Vera; Teixo, Ricardo; Sarmento, Ana Bela; Botelho, Maria Filomena; Rosa, Manuel Santos

    2016-04-01

    Immune surveillance seems to represent an effective tumor suppressor mechanism. However, some cancer cells survive and become variants, being poorly immunogenic and able to enter a steady-state phase. These cells become functionally dormant or remain hidden clinically throughout. Neoplastic cells seem to be able to instruct immune cells to undergo changes promoting malignancy. Radiotherapy may act as a trigger of the immune response. After radiotherapy a sequence of reactions occurs, starting in the damage of oncogenic cells by multiple mechanisms, leading to the immune system positive feedback against the tumor. The link between radiotherapy and the immune system is evident. T cells, macrophages, Natural Killer cells and other immune cells seem to have a key role in controlling the tumor. T cells may be dysfunctional and remain in a state of T cell exhaustion, nonetheless, they often retain a high potential for successful defense against cancer, being able to be mobilized to become highly functional. The lack of clinical trials on a large scale makes data a little robust, in spite of promising information, there are still many variables in the studies relating to radiation and immune system. The clarification of the mechanisms underlying immune response to radiation exposure may contribute to treatment improvement, gain of life quality and span of patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Immunization information systems in Canada: Attributes, functionality, strengths and challenges. A Canadian Immunization Research Network study.

    PubMed

    Wilson, Sarah E; Quach, Susan; MacDonald, Shannon E; Naus, Monika; Deeks, Shelley L; Crowcroft, Natasha S; Mahmud, Salaheddin M; Tran, Dat; Kwong, Jeffrey C; Tu, Karen; Johnson, Caitlin; Desai, Shalini

    2017-03-01

    Canada does not have a national immunization registry. Diverse systems to record vaccine uptake exist, but these have not been systematically described. Our objective was to describe the immunization information systems (IISs) and non-IIS processes used to record childhood and adolescent vaccinations, and to outline the strengths and limitations of the systems and processes. We collected information from key informants regarding their provincial, territorial or federal organization's surveillance systems for assessing immunization coverage. Information collection consisted of a self-administered questionnaire and a follow-up interview. We evaluated systems against attributes derived from the literature using content analysis. Twenty-six individuals across 16 public health organizations participated over the period of April to August 2015. Twelve of Canada's 13 provinces and territories (P/Ts) and two organizations involved in health service delivery for on-reserve First Nations people participated. Across systems, there were differences in data collection processes, reporting capabilities and advanced functionality. Commonly cited challenges included timeliness and data completeness of records, particularly for physician-administered immunizations. Privacy considerations and the need for data standards were stated as challenges to the goal of information sharing across P/T systems. Many P/Ts have recently implemented new systems and, in some cases, legislation to improve timeliness and/or completeness. Considerable variability exists among IISs and non-IIS processes used to assess immunization coverage in Canada. Although some P/Ts have already pursued legislative or policy initiatives to address the completeness and timeliness of information, many additional opportunities exist in the information technology realm.

  19. Country Immunization Information System Assessments - Kenya, 2015 and Ghana, 2016.

    PubMed

    Scott, Colleen; Clarke, Kristie E N; Grevendonk, Jan; Dolan, Samantha B; Ahmed, Hussein Osman; Kamau, Peter; Ademba, Peter Aswani; Osadebe, Lynda; Bonsu, George; Opare, Joseph; Diamenu, Stanley; Amenuvegbe, Gregory; Quaye, Pamela; Osei-Sarpong, Fred; Abotsi, Francis; Ankrah, Joseph Dwomor; MacNeil, Adam

    2017-11-10

    The collection, analysis, and use of data to measure and improve immunization program performance are priorities for the World Health Organization (WHO), global partners, and national immunization programs (NIPs). High quality data are essential for evidence-based decision-making to support successful NIPs. Consistent recording and reporting practices, optimal access to and use of health information systems, and rigorous interpretation and use of data for decision-making are characteristics of high-quality immunization information systems. In 2015 and 2016, immunization information system assessments (IISAs) were conducted in Kenya and Ghana using a new WHO and CDC assessment methodology designed to identify root causes of immunization data quality problems and facilitate development of plans for improvement. Data quality challenges common to both countries included low confidence in facility-level target population data (Kenya = 50%, Ghana = 53%) and poor data concordance between child registers and facility tally sheets (Kenya = 0%, Ghana = 3%). In Kenya, systemic challenges included limited supportive supervision and lack of resources to access electronic reporting systems; in Ghana, challenges included a poorly defined subdistrict administrative level. Data quality improvement plans (DQIPs) based on assessment findings are being implemented in both countries. IISAs can help countries identify and address root causes of poor immunization data to provide a stronger evidence base for future investments in immunization programs.

  20. Mice with Reconstituted Human Immune System Components as a Tool to Study Immune Cell Interactions in EBV Infection.

    PubMed

    Heuts, Frank; Nagy, Noemi

    2017-01-01

    Recent developments in mouse models that harbor part of a human immune system have proved extremely valuable to study the in vivo immune response to human specific pathogens such as Epstein-Barr virus. Over the last decades, advances in immunodeficient mouse strains that can be used as recipients for human immune cells have greatly enhanced the use of these models. Here, we describe the generation of mice with reconstituted human immune system (HIS mice) using immunocompromised mice transplanted with human CD34 + hematopoietic stem cells. We will also describe how such mice, in which human immune cells are generated de novo, can be used to study EBV infection.

  1. Artificial immune system algorithm in VLSI circuit configuration

    NASA Astrophysics Data System (ADS)

    Mansor, Mohd. Asyraf; Sathasivam, Saratha; Kasihmuddin, Mohd Shareduwan Mohd

    2017-08-01

    In artificial intelligence, the artificial immune system is a robust bio-inspired heuristic method, extensively used in solving many constraint optimization problems, anomaly detection, and pattern recognition. This paper discusses the implementation and performance of artificial immune system (AIS) algorithm integrated with Hopfield neural networks for VLSI circuit configuration based on 3-Satisfiability problems. Specifically, we emphasized on the clonal selection technique in our binary artificial immune system algorithm. We restrict our logic construction to 3-Satisfiability (3-SAT) clauses in order to outfit with the transistor configuration in VLSI circuit. The core impetus of this research is to find an ideal hybrid model to assist in the VLSI circuit configuration. In this paper, we compared the artificial immune system (AIS) algorithm (HNN-3SATAIS) with the brute force algorithm incorporated with Hopfield neural network (HNN-3SATBF). Microsoft Visual C++ 2013 was used as a platform for training, simulating and validating the performances of the proposed network. The results depict that the HNN-3SATAIS outperformed HNN-3SATBF in terms of circuit accuracy and CPU time. Thus, HNN-3SATAIS can be used to detect an early error in the VLSI circuit design.

  2. A Cognitive Computational Model Inspired by the Immune System Response

    PubMed Central

    Abdo Abd Al-Hady, Mohamed; Badr, Amr Ahmed; Mostafa, Mostafa Abd Al-Azim

    2014-01-01

    The immune system has a cognitive ability to differentiate between healthy and unhealthy cells. The immune system response (ISR) is stimulated by a disorder in the temporary fuzzy state that is oscillating between the healthy and unhealthy states. However, modeling the immune system is an enormous challenge; the paper introduces an extensive summary of how the immune system response functions, as an overview of a complex topic, to present the immune system as a cognitive intelligent agent. The homogeneity and perfection of the natural immune system have been always standing out as the sought-after model we attempted to imitate while building our proposed model of cognitive architecture. The paper divides the ISR into four logical phases: setting a computational architectural diagram for each phase, proceeding from functional perspectives (input, process, and output), and their consequences. The proposed architecture components are defined by matching biological operations with computational functions and hence with the framework of the paper. On the other hand, the architecture focuses on the interoperability of main theoretical immunological perspectives (classic, cognitive, and danger theory), as related to computer science terminologies. The paper presents a descriptive model of immune system, to figure out the nature of response, deemed to be intrinsic for building a hybrid computational model based on a cognitive intelligent agent perspective and inspired by the natural biology. To that end, this paper highlights the ISR phases as applied to a case study on hepatitis C virus, meanwhile illustrating our proposed architecture perspective. PMID:25003131

  3. Systemic lupus erythematosus following HPV immunization or infection?

    PubMed

    Soldevilla, H F; Briones, S F R; Navarra, S V

    2012-02-01

    The link between autoimmunity and infectious agents has been strongly suggested by reports of lupus or lupus-like syndromes following immunization. This report describes three patients with either newly diagnosed systemic lupus erythematosus (SLE) or SLE flare, following vaccination for human papilloma virus (HPV). CASE 1: A 17-year-old female completed two doses of HPV vaccine uneventfully. Two months later, she developed arthralgias with pruritic rashes on both lower extremities, later accompanied by livedo reticularis, bipedal edema with proteinuria, anemia, leucopenia, hypocomplementemia and high titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA). Kidney biopsy showed International Society of Nephrology/Renal Pathology Society Class III lupus nephritis. She was started on high dose steroids followed by pulse cyclophosphamide therapy protocol for lupus nephritis, and subsequently went into remission. CASE 2: A 45-year-old housewife, previously managed for 11 years as having rheumatoid arthritis, had been in clinical remission for a year when she received two doses of HPV immunization. Four months later, she developed fever accompanied by arthritis, malar rash, oral ulcers, recurrent ascites with intestinal pseudo-obstruction, and behavioral changes. Cranial MRI showed vasculitic lesions on the frontal and parietal lobes. Laboratory tests showed anemia with leucopenia, hypocomplementemia, proteinuria, ANA positive at 1:320, and antibodies against dsDNA, Ro/SSA, La/SSB and histone. She improved following pulse methylprednisolone with subsequent oral prednisone combined with hydroxychloroquine. CASE 3: A 58-year-old housewife diagnosed with SLE had been in clinical remission for 8 years when she received two doses of HPV immunization. Three months later, she was admitted to emergency because of a 1-week history of fever, malar rash, easy fatigability, cervical lymph nodes, gross hematuria and pallor. Laboratory exams showed severe

  4. A nonlinear delayed model for the immune response in the presence of viral mutation

    NASA Astrophysics Data System (ADS)

    Messias, D.; Gleria, Iram; Albuquerque, S. S.; Canabarro, Askery; Stanley, H. E.

    2018-02-01

    We consider a delayed nonlinear model of the dynamics of the immune system against a viral infection that contains a wild-type virus and a mutant. We consider the finite response time of the immune system and find sustained oscillatory behavior as well as chaotic behavior triggered by the presence of delays. We present a numeric analysis and some analytical results.

  5. New insights into innate immune control of systemic candidiasis

    PubMed Central

    Lionakis, Michail S.

    2014-01-01

    Systemic infection caused by Candida species is the fourth leading cause of nosocomial bloodstream infection in modern hospitals and carries high morbidity and mortality despite antifungal therapy. A recent surge of immunological studies in the mouse models of systemic candidiasis and the parallel discovery and phenotypic characterization of inherited genetic disorders in antifungal immune factors that are associated with enhanced susceptibility or resistance to the infection have provided new insights into the cellular and molecular basis of protective innate immune responses against Candida. In this review, the new developments in our understanding of how the mammalian immune system responds to systemic Candida challenge are synthesized and important future research directions are highlighted. PMID:25023483

  6. HIV-1 and hijacking of the host immune system: the current scenario.

    PubMed

    Imran, Muhammad; Manzoor, Sobia; Saalim, Muhammad; Resham, Saleha; Ashraf, Javed; Javed, Aneela; Waqar, Ahmed Bilal

    2016-10-01

    Human immunodeficiency virus (HIV) infection is a major health burden across the world which leads to the development of acquired immune deficiency syndrome (AIDS). This review article discusses the prevalence of HIV, its major routes of transmission, natural immunity, and evasion from the host immune system. HIV is mostly prevalent in Sub-Saharan Africa and low income countries. It is mostly transmitted by sharing syringe needles, blood transfusion, and sexual routes. The host immune system is categorized into three main types; the innate, the adaptive, and the intrinsic immune system. Regarding the innate immune system against HIV, the key players are mucosal membrane, dendritic cells (DCs), complement system, interferon, and host Micro RNAs. The major components of the adaptive immune system exploited by HIV are T cells mainly CD4+ T cells and B cells. The intrinsic immune system confronted by HIV involves (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) APOBEC3G, tripartite motif 5-α (TRIM5a), terherin, and (SAM-domain HD-domain containing protein) SAMHD1. HIV-1 efficiently interacts with the host immune system, exploits the host machinery, successfully replicates and transmits from one cell to another. Further research is required to explore evasion strategies of HIV to develop novel therapeutic approaches against HIV. © 2016 APMIS. Published by John Wiley & Sons Ltd.

  7. IMMUNE SYSTEM MATURITY AND SENSITIVITY TO CHEMICAL EXPOSURE

    EPA Science Inventory

    It is well established that human diseases associated with abnormal immune function, including some common infectious diseases and asthma, are considerably more prevalent at younger ages. The immune system continues to mature after birth, and functional immaturity accounts for m...

  8. Recognition of bacterial plant pathogens: local, systemic and transgenerational immunity.

    PubMed

    Henry, Elizabeth; Yadeta, Koste A; Coaker, Gitta

    2013-09-01

    Bacterial pathogens can cause multiple plant diseases and plants rely on their innate immune system to recognize and actively respond to these microbes. The plant innate immune system comprises extracellular pattern recognition receptors that recognize conserved microbial patterns and intracellular nucleotide binding leucine-rich repeat (NLR) proteins that recognize specific bacterial effectors delivered into host cells. Plants lack the adaptive immune branch present in animals, but still afford flexibility to pathogen attack through systemic and transgenerational resistance. Here, we focus on current research in plant immune responses against bacterial pathogens. Recent studies shed light onto the activation and inactivation of pattern recognition receptors and systemic acquired resistance. New research has also uncovered additional layers of complexity surrounding NLR immune receptor activation, cooperation and sub-cellular localizations. Taken together, these recent advances bring us closer to understanding the web of molecular interactions responsible for coordinating defense responses and ultimately resistance. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  9. Effects of the space flight environment on the immune system

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald; Butel, Janet S.; Shearer, William T.

    2003-01-01

    Space flight conditions have a dramatic effect on a variety of physiologic functions of mammals, including muscle, bone, and neurovestibular function. Among the physiological functions that are affected when humans or animals are exposed to space flight conditions is the immune response. The focus of this review is on the function of the immune system in space flight conditions during actual space flights, as well as in models of space flight conditions on the earth. The experiments were carried out in tissue culture systems, in animal models, and in human subjects. The results indicate that space flight conditions alter cell-mediated immune responses, including lymphocyte proliferation and subset distribution, and cytokine production. The mechanism(s) of space flight-induced alterations in immune system function remain(s) to be established. It is likely, however, that multiple factors, including microgravity, stress, neuroendocrine factors, sleep disruption, and nutritional factors, are involved in altering certain functions of the immune system. Such alterations could lead to compromised defenses against infections and tumors.

  10. Chronic grouped social restriction triggers long-lasting immune system adaptations.

    PubMed

    Tian, Rui; Hou, Gonglin; Song, Liuwei; Zhang, Jianming; Yuan, Ti-Fei

    2017-05-16

    Chronic stress triggers rigorous psychological and physiological changes, including immunological system adaptations. However, the effects of long-term social restriction on human immune system have not been investigated. The present study is to investigate the effect of chronic stress on immune changes in human blood, with the stress stimuli controlled.10 male volunteers were group isolated from the modern society in a 50-meter-square room for 150 days, with enriched nutrition and good living conditions provided. Serum examination of immune system markers demonstrated numerous changes in different aspects of the immune functions. The changes were observed as early as 30 days and could last for another 150 days after the termination of the restriction period (300 days' time point). The results strongly argued for the adaptation of immunological system under chronic social restriction stress in adult human, preceding a clear change in psychological conditions. The changes of these immune system factors could as well act as the serum biomarkers in clinical early-diagnosis of stress-related disorders.

  11. Targeting the immune system in cancer.

    PubMed

    Chaudhuri, Devyani; Suriano, Robert; Mittelman, Abraham; Tiwari, Raj K

    2009-02-01

    The concept of cancer immunotherapy provides a fresh perspective as it is not associated with many of the drawbacks of conventional therapies such as chemotherapy, radiotherapy and surgery. When fully activated the immune system has immense potential as is evident from mis-matched transplanted organs undergoing rapid immunological attack and rejection. However, the development of immune strategies for cancer therapy has been associated with challenges of their own. Early attempts at cancer vaccination were carried out in an empirical manner that did not always lead to reproducibility. This led to a search of tumor associated antigens with the belief that specific targeting of these antigens would lead to successful tumor elimination. Active vaccination with TAA peptides or passive vaccination with specific lymphocytes against these TAAs did not however demonstrate encouraging results in clinical trials. This was mainly because of the lack of an activating immune response which is required for continuous stimulation of lymphocytes and also because of the selection of tumor escape variants that did not express the particular TAA. On the positive side, attempts at characterizing TAAs illuminated the molecular changes that attribute a malignant phenotype to cancer cells. Attempts at cytokine therapy were also met with challenges of high systemic toxicity and a lack of specific lymphocyte activation. It was therefore realized that an ideal vaccinating agent should be able to combine the effects of both these therapeutic strategies, i.e., it should be able to induce an innate immune response which can be tailored to a tumor specific adaptive immune response. By this, the immunosuppressive tumor environment can be altered to become immune activating, thus facilitating the infiltration of myeloid and lymphoid cells that can act in concert leading to tumor regression. In this regard, immunotherapeutic approaches such as DNA vaccines, dendritic cell based vaccines, HSP based

  12. A basic mathematical model of the immune response

    NASA Astrophysics Data System (ADS)

    Mayer, H.; Zaenker, K. S.; an der Heiden, U.

    1995-03-01

    Interaction of the immune system with a target population of, e.g., bacteria, viruses, antigens, or tumor cells must be considered as a dynamic process. We describe this process by a system of two ordinary differential equations. Although the model is strongly idealized it demonstrates how the combination of a few proposed nonlinear interaction rules between the immune system and its targets are able to generate a considerable variety of different kinds of immune responses, many of which are observed both experimentally and clinically. In particular, solutions of the model equations correspond to states described by immunologists as ``virgin state,'' ``immune state'' and ``state of tolerance.'' The model successfully replicates the so-called primary and secondary response. Moreover, it predicts the existence of a threshold level for the amount of pathogen germs or of transplanted tumor cells below which the host is able to eliminate the infectious organism or to reject the tumor graft. We also find a long time coexistence of targets and immune competent cells including damped and undamped oscillations of both. Plausibly the model explains that if the number of transformed cells or pathogens exeeds definable values (poor antigenicity, high reproduction rate) the immune system fails to keep the disease under control. On the other hand, the model predicts apparently paradoxical situations including an increased chance of target survival despite enhanced immune activity or therapeutically achieved target reduction. A further obviously paradoxical behavior consists of a positive effect for the patient up to a complete cure by adding an additional target challenge where the benefit of the additional targets depends strongly on the time point and on their amount. Under periodically pulsed stimulation the model may show a chaotic time behavior of both target growth and immune response.

  13. Graphene and the immune system: Challenges and potentiality.

    PubMed

    Orecchioni, Marco; Ménard-Moyon, Cécilia; Delogu, Lucia Gemma; Bianco, Alberto

    2016-10-01

    In the growing area of nanomedicine, graphene-based materials (GBMs) are some of the most recent explored nanomaterials. For the majority of GBM applications in nanomedicine, the immune system plays a fundamental role. It is necessary to well understand the complexity of the interactions between GBMs, the immune cells, and the immune components and how they could be of advantage for novel effective diagnostic and therapeutic approaches. In this review, we aimed at painting the current picture of GBMs in the background of the immune system. The picture we have drawn looks like a cubist image, a sort of Picasso-like portrait looking at the topic from all perspectives: the challenges (due to the potential toxicity) and the potentiality like the conjugation of GBMs to biomolecules to develop advanced nanomedicine tools. In this context, we have described and discussed i) the impact of graphene on immune cells, ii) graphene as immunobiosensor, and iii) antibodies conjugated to graphene for tumor targeting. Thanks to the huge advances on graphene research, it seems realistic to hypothesize in the near future that some graphene immunoconjugates, endowed of defined immune properties, can go through preclinical test and be successfully used in nanomedicine. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Nutritionally Mediated Programming of the Developing Immune System12

    PubMed Central

    Palmer, Amanda C.

    2011-01-01

    A growing body of evidence highlights the importance of a mother’s nutrition from preconception through lactation in programming the emerging organ systems and homeostatic pathways of her offspring. The developing immune system may be particularly vulnerable. Indeed, examples of nutrition-mediated immune programming can be found in the literature on intra-uterine growth retardation, maternal micronutrient deficiencies, and infant feeding. Current models of immune ontogeny depict a “layered” expansion of increasingly complex defenses, which may be permanently altered by maternal malnutrition. One programming mechanism involves activation of the maternal hypothalamic-pituitary-adrenal axis in response to nutritional stress. Fetal or neonatal exposure to elevated stress hormones is linked in animal studies to permanent changes in neuroendocrine-immune interactions, with diverse manifestations such as an attenuated inflammatory response or reduced resistance to tumor colonization. Maternal malnutrition may also have a direct influence, as evidenced by nutrient-driven epigenetic changes to developing T regulatory cells and subsequent risk of allergy or asthma. A 3rd programming pathway involves placental or breast milk transfer of maternal immune factors with immunomodulatory functions (e.g. cytokines). Maternal malnutrition can directly affect transfer mechanisms or influence the quality or quantity of transferred factors. The public health implications of nutrition-mediated immune programming are of particular importance in the developing world, where prevalent maternal undernutrition is coupled with persistent infectious challenges. However, early alterations to the immune system, resulting from either nutritional deficiencies or excesses, have broad relevance for immune-mediated diseases, such as asthma, and chronic inflammatory conditions like cardiovascular disease. PMID:22332080

  15. Strain-dependent effects of prenatal maternal immune activation on anxiety- and depression-like behaviors in offspring.

    PubMed

    Babri, Shirin; Doosti, Mohammad-Hossein; Salari, Ali-Akbar

    2014-03-01

    There is converging evidence that prenatal maternal infection can increase the risk of occurrence of neuropsychiatric disorders like schizophrenia, autism, anxiety and depression in later life. Experimental studies have shown conflicting effects of prenatal maternal immune activation on anxiety-like behavior and hypothalamic-pituitary-adrenal (HPA) axis development in offspring. We investigated the effects of maternal immune activation during pregnancy on anxiety- and depression-like behaviors in pregnant mice and their offspring to determine whether these effects are dependent on strain. NMRI and C57BL/6 pregnant mice were treated with either saline or lipopolysaccharide on gestational day 17 and then interleukin (IL)-6 and corticosterone (COR) levels; anxiety or depression in the pregnant mice and their offspring were evaluated. The results indicate that maternal inflammation increased the levels of COR and anxiety-like behavior in NMRI pregnant mice, but not in C57BL/6 dams. Our data also demonstrate that maternal inflammation elevated the levels of anxiety-and depression-like behaviors in NMRI offspring on the elevated plus-maze, elevated zero-maze, tail suspension test and forced swimming test respectively, but not in the open field and light-dark box. In addition, we did not find any significant change in anxiety- and depression-like behaviors of adult C57BL/6 offspring. Our findings suggest that prenatal maternal immune activation can alter the HPA axis activity, anxiety- and depression-like behaviors in a strain- and task-dependent manner in offspring and further comprehensive studies are needed to prove the causal relationship between the findings found here and to validate their relevance to neuropsychiatric disorders in humans. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Molecular mechanisms of aging and immune system regulation in Drosophila.

    PubMed

    Eleftherianos, Ioannis; Castillo, Julio Cesar

    2012-01-01

    Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span.

  17. Cancer-Targeted Oncolytic Adenoviruses for Modulation of the Immune System.

    PubMed

    Cerullo, Vincenzo; Capasso, Cristian; Vaha-Koskela, Markus; Hemminki, Otto; Hemminki, Akseli

    2018-01-01

    Adenovirus is one of the most commonly used vectors for gene therapy and it is the first approved virus-derived drug for treatment of cancer. As an oncolytic agent, it can induce lysis of infected cells, but it can also engage the immune system, promoting activation and maturation of antigen- presenting cells (APCs). In essence, oncolysis combined with the associated immunostimulatory actions result in a "personalized in situ vaccine" for each patient. In order to take full advantage of these features, we should try to understand how adenovirus interacts with the immune system, what are the receptors involved in triggering subsequent signals and which kind of responses they elicit. Tackling these questions will give us further insight in how to manipulate adenovirus-mediated immune responses for enhancement of anti-tumor efficacy. In this review, we first highlight how oncolytic adenovirus interacts with the innate immune system and its receptors such as Toll-like receptors, nucleotide-binding and oligomerization domain (NOD)- like receptors and other immune sensors. Then we describe the effect of these interactions on the adaptive immune system and its cells, especially B and T lymphocytes. Finally, we summarize the most significant preclinical and clinical results in the field of gene therapy where researchers have engineered adenovirus to manipulate the host immune system by expressing cytokines and signalingmediators. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. An evolutionary perspective on the systems of adaptive immunity.

    PubMed

    Müller, Viktor; de Boer, Rob J; Bonhoeffer, Sebastian; Szathmáry, Eörs

    2018-02-01

    We propose an evolutionary perspective to classify and characterize the diverse systems of adaptive immunity that have been discovered across all major domains of life. We put forward a new function-based classification according to the way information is acquired by the immune systems: Darwinian immunity (currently known from, but not necessarily limited to, vertebrates) relies on the Darwinian process of clonal selection to 'learn' by cumulative trial-and-error feedback; Lamarckian immunity uses templated targeting (guided adaptation) to internalize heritable information on potential threats; finally, shotgun immunity operates through somatic mechanisms of variable targeting without feedback. We argue that the origin of Darwinian (but not Lamarckian or shotgun) immunity represents a radical innovation in the evolution of individuality and complexity, and propose to add it to the list of major evolutionary transitions. While transitions to higher-level units entail the suppression of selection at lower levels, Darwinian immunity re-opens cell-level selection within the multicellular organism, under the control of mechanisms that direct, rather than suppress, cell-level evolution for the benefit of the individual. From a conceptual point of view, the origin of Darwinian immunity can be regarded as the most radical transition in the history of life, in which evolution by natural selection has literally re-invented itself. Furthermore, the combination of clonal selection and somatic receptor diversity enabled a transition from limited to practically unlimited capacity to store information about the antigenic environment. The origin of Darwinian immunity therefore comprises both a transition in individuality and the emergence of a new information system - the two hallmarks of major evolutionary transitions. Finally, we present an evolutionary scenario for the origin of Darwinian immunity in vertebrates. We propose a revival of the concept of the 'Big Bang' of

  19. The role of the immune system in Alzheimer disease: Etiology and treatment.

    PubMed

    Jevtic, Stefan; Sengar, Ameet S; Salter, Michael W; McLaurin, JoAnne

    2017-11-01

    The immune system is now considered a major factor in Alzheimer Disease (AD). This review seeks to demonstrate how various aspects of the immune system, both in the brain and peripherally, interact to contribute to AD. We highlight classical nervous system immune components, such as complement and microglia, as well as novel aspects of the peripheral immune system that can influence disease, such as monocytes and lymphocytes. By detailing the roles of various immune cells in AD, we summarize an emerging perspective for disease etiology and future therapeutic targets. Copyright © 2017. Published by Elsevier B.V.

  20. Impact of the Innate Immune Response in the Actions of Ethanol on the Central Nervous System.

    PubMed

    Montesinos, Jorge; Alfonso-Loeches, Silvia; Guerri, Consuelo

    2016-11-01

    The innate immune response in the central nervous system (CNS) participates in both synaptic plasticity and neural damage. Emerging evidence from human and animal studies supports the role of the neuroimmune system response in many actions of ethanol (EtOH) on the CNS. Research studies have shown that alcohol stimulates brain immune cells, microglia, and astrocytes, by activating innate immune receptors Toll-like receptors (TLRs) and NOD-like receptors (inflammasome NLRs) triggering signaling pathways, which culminate in the production of pro-inflammatory cytokines and chemokines that lead to neuroinflammation. This review focuses on evidence that indicates the participation of TLRs and the inflammasome NLRs signaling response in many effects of EtOH on the CNS, such as neuroinflammation associated with brain damage, cognitive and behavioral dysfunction, and adolescent brain development alterations. It also reviews findings that indicate the role of TLR4-dependent signaling immune molecules in alcohol consumption, reward, and addiction. The research data suggest that overactivation of TLR4 or NLRs increases pro-inflammatory cytokines and mediators to cause neural damage in the cerebral cortex and hippocampus, while modest TLR4 activation, along with the generation of certain cytokines and chemokines in specific brain areas (e.g., amygdala, ventral tegmental area), modulate neurotransmission, alcohol drinking, and alcohol rewards. Elimination of TLR4 and NLRP3 abolishes many neuroimmune effects of EtOH. Despite much progress being made in this area, there are some research gaps and unanswered questions that this review discusses. Finally, potential therapies that target neuroimmune pathways to treat neuropathological and behavioral consequences of alcohol abuse are also evaluated. Copyright © 2016 by the Research Society on Alcoholism.

  1. Systemic bacterial infection and immune defense phenotypes in Drosophila melanogaster.

    PubMed

    Khalil, Sarah; Jacobson, Eliana; Chambers, Moria C; Lazzaro, Brian P

    2015-05-13

    The fruit fly Drosophila melanogaster is one of the premier model organisms for studying the function and evolution of immune defense. Many aspects of innate immunity are conserved between insects and mammals, and since Drosophila can readily be genetically and experimentally manipulated, they are powerful for studying immune system function and the physiological consequences of disease. The procedure demonstrated here allows infection of flies by introduction of bacteria directly into the body cavity, bypassing epithelial barriers and more passive forms of defense and allowing focus on systemic infection. The procedure includes protocols for the measuring rates of host mortality, systemic pathogen load, and degree of induction of the host immune system. This infection procedure is inexpensive, robust and quantitatively repeatable, and can be used in studies of functional genetics, evolutionary life history, and physiology.

  2. Immunoadolescence: Neuroimmune development and adolescent behavior

    PubMed Central

    Brenhouse, Heather C.; Schwarz, Jaclyn M.

    2016-01-01

    The brain is increasingly appreciated to be a constantly rewired organ that yields age-specific behaviors and responses to the environment. Adolescence in particular is a unique period characterized by continued brain maturation, superimposed with transient needs of the organism to traverse a leap from parental dependence to independence. Here we describe how these needs require immune maturation, as well as brain maturation. Our immune system, which protects us from pathogens and regulates inflammation, is in constant communication with our nervous system. Together, neuro-immune signaling regulates our behavioral responses to the environment, making this interaction a likely substrate for adolescent development. We review here the identified as well as understudied components of neuro-immune interactions during adolescence. Synaptic pruning, neurite outgrowth, and neurotransmitter release during adolescence all regulate—and are regulated by—immune signals, which occur via blood-brain barrier dynamics and glial activity. We discuss these processes, as well as how immune signaling during this transitional period of development confers differential effects on behavior and vulnerability to mental illness. PMID:27260127

  3. Recognising promoter sequences using an artificial immune system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cooke, D.E.; Hunt, J.E.

    1995-12-31

    We have developed an artificial immune system (AIS) which is based on the human immune system. The AIS possesses an adaptive learning mechanism which enables antibodies to emerge which can be used for classification tasks. In this paper, we describe how the AIS has been used to evolve antibodies which can classify promoter containing and promoter negative DNA sequences. The DNA sequences used for teaching were 57 nucleotides in length and contained procaryotic promoters. The system classified previously unseen DNA sequences with an accuracy of approximately 90%.

  4. Neural Control of the Immune System

    ERIC Educational Resources Information Center

    Sundman, Eva; Olofsson, Peder S.

    2014-01-01

    Neural reflexes support homeostasis by modulating the function of organ systems. Recent advances in neuroscience and immunology have revealed that neural reflexes also regulate the immune system. Activation of the vagus nerve modulates leukocyte cytokine production and alleviates experimental shock and autoimmune disease, and recent data have…

  5. Clonal Selection Based Artificial Immune System for Generalized Pattern Recognition

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terry

    2011-01-01

    The last two decades has seen a rapid increase in the application of AIS (Artificial Immune Systems) modeled after the human immune system to a wide range of areas including network intrusion detection, job shop scheduling, classification, pattern recognition, and robot control. JPL (Jet Propulsion Laboratory) has developed an integrated pattern recognition/classification system called AISLE (Artificial Immune System for Learning and Exploration) based on biologically inspired models of B-cell dynamics in the immune system. When used for unsupervised or supervised classification, the method scales linearly with the number of dimensions, has performance that is relatively independent of the total size of the dataset, and has been shown to perform as well as traditional clustering methods. When used for pattern recognition, the method efficiently isolates the appropriate matches in the data set. The paper presents the underlying structure of AISLE and the results from a number of experimental studies.

  6. The effects of central pro-and anti-inflammatory immune challenges on depressive-like behavior induced by chronic forced swim stress in rats.

    PubMed

    Pan, Yuqin; Lin, Wenjuan; Wang, Weiwen; Qi, Xiaoli; Wang, Donglin; Tang, Mingming

    2013-06-15

    Although increasing evidence demonstrates that both chronic stressors and inflammatory immune activation contribute to pathophysiology and behavioral alterations associated with major depression, little is known about the interaction effect of central inflammatory immune activation and stress on depressive-like behavior. Our previous work has shown that 14-day chronic forced swim stress induces significant depressive-like behavior. The present investigation assessed whether pro-inflammatory cytokine and anti-inflammatory cytokine challenges have differential interaction effect on depressive-like behavior induced by chronic forced swim stress in rats. The pro-inflammatory and anti-inflammatory immune challenges were achieved respectively by central administration of lipopolysaccharide (LPS), a pro-inflammatory cytokine inducer, and interleukin-10 (IL-10), an anti-inflammatory cytokine. It was found that either central LPS treatment alone or chronic forced swim stress alone significantly induced depressive-like behavior, including reduced body weight gain, reduced saccharin preference and reduced locomotor activity. However, there was no significant synergistic or additive effect of central LPS treatment and stress on depressive-like behavior. LPS treatment did not exacerbate the depressive-like behavior induced by forced swim stress. Nevertheless, IL-10 reversed depressive-like behavior induced by forced swim stress, a finding indicating that IL-10 has antidepressant effect on behavioral depression induced by stress. The present findings provide new insight into the complexity of the immunity-inflammation hypothesis of depression. Copyright © 2013 Elsevier B.V. All rights reserved.

  7. Evolution of complement as an effector system in innate and adaptive immunity.

    PubMed

    Sunyer, J Oriol; Boshra, Hani; Lorenzo, Gema; Parra, David; Freedman, Bruce; Bosch, Nina

    2003-01-01

    For a long time, the complement system in mammals has been regarded as a biological system that plays an essential role in innate immunity. More recently, it has been recognized that the complement system contributes heavily to the generation and development of an acquired immune response. In fact, this ancient mechanism of defense has evolved from a primitive mechanism of innate immune recognition in invertebrate species to that of an effector system that bridges the innate with the adaptive immune response in vertebrate species. When and how did complement evolve into a shared effector system between innate and adaptive immunity? To answer this question, our group is interested in understanding the role of complement in innate and adaptive immune responses in an evolutionary relevant species: the teleost fish. The attractiveness of this species as an animal model is based on two important facts. First, teleost fish are one of the oldest animal species to have developed an adaptive immune response. Second, the complement system of teleost fish offers a unique feature, which is the structural and functional diversity of its main effector protein, C3, the third component of the complement system.

  8. Prolonged protection against Intranasal challenge with influenza virus following systemic immunization or combinations of mucosal and systemic immunizations with a heat-labile toxin mutant.

    PubMed

    Zhou, Fengmin; Goodsell, Amanda; Uematsu, Yasushi; Vajdy, Michael

    2009-04-01

    Seasonal influenza virus infections cause considerable morbidity and mortality in the world, and there is a serious threat of a pandemic influenza with the potential to cause millions of deaths. Therefore, practical influenza vaccines and vaccination strategies that can confer protection against intranasal infection with influenza viruses are needed. In this study, we demonstrate that using LTK63, a nontoxic mutant of the heat-labile toxin from Escherichia coli, as an adjuvant for both mucosal and systemic immunizations, systemic (intramuscular) immunization or combinations of mucosal (intranasal) and intramuscular immunizations protected mice against intranasal challenge with a lethal dose of live influenza virus at 3.5 months after the second immunization.

  9. CRISPR-Cas systems: prokaryotes upgrade to adaptive immunity

    PubMed Central

    Barrangou, Rodolphe; Marraffini, Luciano A.

    2014-01-01

    Summary Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing, and can be repurposed for numerous DNA targeting applications including transcriptional control. PMID:24766887

  10. CRISPR-Cas systems: Prokaryotes upgrade to adaptive immunity.

    PubMed

    Barrangou, Rodolphe; Marraffini, Luciano A

    2014-04-24

    Clustered regularly interspaced short palindromic repeats (CRISPR), and associated proteins (Cas) comprise the CRISPR-Cas system, which confers adaptive immunity against exogenic elements in many bacteria and most archaea. CRISPR-mediated immunization occurs through the uptake of DNA from invasive genetic elements such as plasmids and viruses, followed by its integration into CRISPR loci. These loci are subsequently transcribed and processed into small interfering RNAs that guide nucleases for specific cleavage of complementary sequences. Conceptually, CRISPR-Cas shares functional features with the mammalian adaptive immune system, while also exhibiting characteristics of Lamarckian evolution. Because immune markers spliced from exogenous agents are integrated iteratively in CRISPR loci, they constitute a genetic record of vaccination events and reflect environmental conditions and changes over time. Cas endonucleases, which can be reprogrammed by small guide RNAs have shown unprecedented potential and flexibility for genome editing and can be repurposed for numerous DNA targeting applications including transcriptional control. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. A Service Oriented Architecture Approach to Achieve Interoperability between Immunization Information Systems in Iran.

    PubMed

    Hosseini, Masoud; Ahmadi, Maryam; Dixon, Brian E

    2014-01-01

    Clinical decision support (CDS) systems can support vaccine forecasting and immunization reminders; however, immunization decision-making requires data from fragmented, independent systems. Interoperability and accurate data exchange between immunization information systems (IIS) is an essential factor to utilize Immunization CDS systems. Service oriented architecture (SOA) and Health Level 7 (HL7) are dominant standards for web-based exchange of clinical information. We implemented a system based on SOA and HL7 v3 to support immunization CDS in Iran. We evaluated system performance by exchanging 1500 immunization records for roughly 400 infants between two IISs. System turnaround time is less than a minute for synchronous operation calls and the retrieved immunization history of infants were always identical in different systems. CDS generated reports were accordant to immunization guidelines and the calculations for next visit times were accurate. Interoperability is rare or nonexistent between IIS. Since inter-state data exchange is rare in United States, this approach could be a good prototype to achieve interoperability of immunization information.

  12. Molecular Mechanisms of Aging and Immune System Regulation in Drosophila

    PubMed Central

    Eleftherianos, Ioannis; Castillo, Julio Cesar

    2012-01-01

    Aging is a complex process that involves the accumulation of deleterious changes resulting in overall decline in several vital functions, leading to the progressive deterioration in physiological condition of the organism and eventually causing disease and death. The immune system is the most important host-defense mechanism in humans and is also highly conserved in insects. Extensive research in vertebrates has concluded that aging of the immune function results in increased susceptibility to infectious disease and chronic inflammation. Over the years, interest has grown in studying the molecular interaction between aging and the immune response to pathogenic infections. The fruit fly Drosophila melanogaster is an excellent model system for dissecting the genetic and genomic basis of important biological processes, such as aging and the innate immune system, and deciphering parallel mechanisms in vertebrate animals. Here, we review the recent advances in the identification of key players modulating the relationship between molecular aging networks and immune signal transduction pathways in the fly. Understanding the details of the molecular events involved in aging and immune system regulation will potentially lead to the development of strategies for decreasing the impact of age-related diseases, thus improving human health and life span. PMID:22949833

  13. Policing of gut microbiota by the adaptive immune system.

    PubMed

    Dollé, Laurent; Tran, Hao Q; Etienne-Mesmin, Lucie; Chassaing, Benoit

    2016-02-12

    The intestinal microbiota is a large and diverse microbial community that inhabits the intestine, containing about 100 trillion bacteria of 500-1000 distinct species that, collectively, provide benefits to the host. The human gut microbiota composition is determined by a myriad of factors, among them genetic and environmental, including diet and medication. The microbiota contributes to nutrient absorption and maturation of the immune system. As reciprocity, the host immune system plays a central role in shaping the composition and localization of the intestinal microbiota. Secretory immunoglobulins A (sIgAs), component of the adaptive immune system, are important player in the protection of epithelium, and are known to have an important impact on the regulation of microbiota composition. A recent study published in Immunity by Fransen and colleagues aimed to mechanistically decipher the interrelationship between sIgA and microbiota diversity/composition. This commentary will discuss these important new findings, as well as how future therapies can ultimately benefit from such discovery.

  14. The immune system in space and microgravity

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    2002-01-01

    Space flight and models that created conditions similar to those that occur during space flight have been shown to affect a variety of immunological responses. These have primarily been cell-mediated immune responses including leukocyte proliferation, cytokine production, and leukocyte subset distribution. The mechanisms and biomedical consequences of these changes remain to be established. Among the possible causes of space flight-induced alterations in immune responses are exposure to microgravity, exposure to stress, exposure to radiation, and many more as yet undetermined causes. This review chronicles the known effects of space flight on the immune system and explores the possible role of stress in contributing to these changes.

  15. Effects of sheltering on physiology, immune function, behavior, and the welfare of dogs.

    PubMed

    Protopopova, Alexandra

    2016-05-15

    Approximately 4 million dogs live in animal shelters each year. However, understanding and measuring the welfare of these kenneled dogs presents a challenge. One way to determine welfare is by assessing how stay at the shelter influences physiology, immune function, and behavior of the dogs. Prior research, from all of these domains, has not resulted in clear conclusions on how the animal shelter influences the well-being of dogs. One robust finding is that, when placed into a kennel environment, dogs experience a spike in cortisol levels followed by a decrease to original at-home levels. Current evidence cannot differentiate between several proposed hypotheses that may be responsible for this pattern. In addition, very few studies have assessed the effects of kenneling on immune function of dogs, and of these, no consistent findings have emerged. However, this line of inquiry can have a large impact as infectious diseases are rampant in animal shelters. The ability of behavioral measures to inform us about the welfare of dogs is discussed by reviewing published and new data on the effects of kenneling on dog behavior. Prior research has suffered from a lack of consistent operational definitions when defining abnormal behavior in dogs, resulting in difficult to interpret results. Research on the well-being of individual dogs, rather than on group averages, may be a fruitful next step in determining and improving the welfare of dogs housed in shelters. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Tuberculosis disease diagnosis using artificial immune recognition system.

    PubMed

    Shamshirband, Shahaboddin; Hessam, Somayeh; Javidnia, Hossein; Amiribesheli, Mohsen; Vahdat, Shaghayegh; Petković, Dalibor; Gani, Abdullah; Kiah, Miss Laiha Mat

    2014-01-01

    There is a high risk of tuberculosis (TB) disease diagnosis among conventional methods. This study is aimed at diagnosing TB using hybrid machine learning approaches. Patient epicrisis reports obtained from the Pasteur Laboratory in the north of Iran were used. All 175 samples have twenty features. The features are classified based on incorporating a fuzzy logic controller and artificial immune recognition system. The features are normalized through a fuzzy rule based on a labeling system. The labeled features are categorized into normal and tuberculosis classes using the Artificial Immune Recognition Algorithm. Overall, the highest classification accuracy reached was for the 0.8 learning rate (α) values. The artificial immune recognition system (AIRS) classification approaches using fuzzy logic also yielded better diagnosis results in terms of detection accuracy compared to other empirical methods. Classification accuracy was 99.14%, sensitivity 87.00%, and specificity 86.12%.

  17. Oncolytic Viral Therapy and the Immune System: A Double-Edged Sword Against Cancer.

    PubMed

    Marelli, Giulia; Howells, Anwen; Lemoine, Nicholas R; Wang, Yaohe

    2018-01-01

    Oncolytic viral therapy is a new promising strategy against cancer. Oncolytic viruses (OVs) can replicate in cancer cells but not in normal cells, leading to lysis of the tumor mass. Beside this primary effect, OVs can also stimulate the immune system. Tumors are an immuno-suppressive environment in which the immune system is silenced in order to avoid the immune response against cancer cells. The delivery of OVs into the tumor wakes up the immune system so that it can facilitate a strong and durable response against the tumor itself. Both innate and adaptive immune responses contribute to this process, producing an immune response against tumor antigens and facilitating immunological memory. However, viruses are recognized by the immune system as pathogens and the consequent anti-viral response could represent a big hurdle for OVs. Finding a balance between anti-tumor and anti-viral immunity is, under this new light, a priority for researchers. In this review, we provide an overview of the various ways in which different components of the immune system can be allied with OVs. We have analyzed the different immune responses in order to highlight the new and promising perspectives leading to increased anti-tumor response and decreased immune reaction to the OVs.

  18. Evaluation of Baby Advocate, a childhood immunization reminder system.

    PubMed

    Ludwig-Beymer, P; Hefferan, C

    2001-10-01

    Childhood immunizations, based on CDC recommendations, are recognized as a cost effective and health promoting practice. However, ensuring full immunization requires a long-term commitment on the part of parents and providers. This article describes a program at Advocate Health care to increase the percentage of children fully immunized at two years to 90%. Termed Baby Advocate, the program uses a mailed reminder system that includes vaccine and growth and development information along with gifts and incentives. Volume, satisfaction and immunization status data are presented.

  19. Immune–neural connections: how the immune system’s response to infectious agents influences behavior

    PubMed Central

    McCusker, Robert H.; Kelley, Keith W.

    2013-01-01

    Summary Humans and animals use the classical five senses of sight, sound, touch, smell and taste to monitor their environment. The very survival of feral animals depends on these sensory perception systems, which is a central theme in scholarly research on comparative aspects of anatomy and physiology. But how do all of us sense and respond to an infection? We cannot see, hear, feel, smell or taste bacterial and viral pathogens, but humans and animals alike are fully aware of symptoms of sickness that are caused by these microbes. Pain, fatigue, altered sleep pattern, anorexia and fever are common symptoms in both sick animals and humans. Many of these physiological changes represent adaptive responses that are considered to promote animal survival, and this constellation of events results in sickness behavior. Infectious agents display a variety of pathogen-associated molecular patterns (PAMPs) that are recognized by pattern recognition receptors (PRRs). These PRR are expressed on both the surface [e.g. Toll-like receptor (TLR)-4] and in the cytoplasm [e.g. nucleotide-binding oligomerization domain (Nod)-like receptors] of cells of the innate immune system, primarily macrophages and dendritic cells. These cells initiate and propagate an inflammatory response by stimulating the synthesis and release of a variety of cytokines. Once an infection has occurred in the periphery, both cytokines and bacterial toxins deliver this information to the brain using both humoral and neuronal routes of communication. For example, binding of PRR can lead to activation of the afferent vagus nerve, which communicates neuronal signals via the lower brain stem (nucleus tractus solitarius) to higher brain centers such as the hypothalamus and amygdala. Blood-borne cytokines initiate a cytokine response from vascular endothelial cells that form the blood–brain barrier (BBB). Cytokines can also reach the brain directly by leakage through the BBB via circumventricular organs or by being

  20. Immune defects caused by mutations in the ubiquitin system.

    PubMed

    Etzioni, Amos; Ciechanover, Aaron; Pikarsky, Eli

    2017-03-01

    The importance of the ubiquitin system in health and disease has been widely recognized in recent decades, with better understanding of the various components of the system and their function. Ubiquitination, which is essential to almost all biological processes in eukaryotes, was also found to play an important role in innate and adaptive immune responses. Thus it is not surprising that mutations in genes coding for components of the ubiquitin system cause immune dysregulation. The first defect in the system was described 30 years ago and is due to mutations in the nuclear factor κB (NF-κB) essential modulator, a key regulator of the NF-κB pathway. With use of novel sequencing techniques, many additional mutations in different genes involved in ubiquitination and related to immune system function were identified. This can be clearly illustrated in mutations in the different activation pathways of NF-κB, which result in aberrations in production of various proinflammatory cytokines. The inherited diseases typically manifest with immunodeficiency, autoimmunity, or autoinflammation. In this perspective we provide a short description of the ubiquitin system, with specific emphasis given to its role in the immune system. The various immunodeficiency conditions identified thus far in association with defective ubiquitination are discussed in more detail. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  1. A Service Oriented Architecture Approach to Achieve Interoperability between Immunization Information Systems in Iran

    PubMed Central

    Hosseini, Masoud; Ahmadi, Maryam; Dixon, Brian E.

    2014-01-01

    Clinical decision support (CDS) systems can support vaccine forecasting and immunization reminders; however, immunization decision-making requires data from fragmented, independent systems. Interoperability and accurate data exchange between immunization information systems (IIS) is an essential factor to utilize Immunization CDS systems. Service oriented architecture (SOA) and Health Level 7 (HL7) are dominant standards for web-based exchange of clinical information. We implemented a system based on SOA and HL7 v3 to support immunization CDS in Iran. We evaluated system performance by exchanging 1500 immunization records for roughly 400 infants between two IISs. System turnaround time is less than a minute for synchronous operation calls and the retrieved immunization history of infants were always identical in different systems. CDS generated reports were accordant to immunization guidelines and the calculations for next visit times were accurate. Interoperability is rare or nonexistent between IIS. Since inter-state data exchange is rare in United States, this approach could be a good prototype to achieve interoperability of immunization information. PMID:25954452

  2. Innate immune system and tissue regeneration in planarians: an area ripe for exploration.

    PubMed

    Peiris, T Harshani; Hoyer, Katrina K; Oviedo, Néstor J

    2014-08-01

    The immune system has been implicated as an important modulator of tissue regeneration. However, the mechanisms driving injury-induced immune response and tissue repair remain poorly understood. For over 200 years, planarians have been a classical model for studies on tissue regeneration, but the planarian immune system and its potential role in repair is largely unknown. We found through comparative genomic analysis and data mining that planarians contain many potential homologs of the innate immune system that are activated during injury and repair of adult tissues. These findings support the notion that the relationship between adult tissue repair and the immune system is an ancient feature of basal Bilateria. Further analysis of the planarian immune system during regeneration could potentially add to our understanding of how the innate immune system and inflammatory responses interplay with regenerative signals to induce scar-less tissue repair in the context of the adult organism. Copyright © 2014 Elsevier Ltd. All rights reserved.

  3. Morphostructure of Immune System Organs in Cattle of Different Age.

    PubMed

    Gasisova, A I; Atkenova, A B; Ahmetzhanova, N B; Murzabekova, L M; Bekenova, A C

    2017-04-01

    This article provides comprehensive consideration of the age-dependent morphofunctional state of organs and tissues of the immune system (thymus, spleen, superficial and deep lymph nodes) in cattle. The morphofunctional maturity of organs and tissues of the immune system in cattle will be taken into account in various experimental studies, preventive and therapeutic measures. Performed analysis provides description of the spleen formation as well as the thymus and lymph nodes in post-natal ontogenesis and the macro- and microscopic structure of lymphoid cells and macrophages. The obtained results can be used to study immune responses of the thymus, spleen, lymph nodes in the pathological immunogenesis and may serve as a basis for development of recommendations related to diagnosis and treatment of diseases of the cattle immune system. The morphofunctional state of organs and tissues of the immune system in cattle was first studied with regard to the age dynamics. Based on the immunohistological studies, this article described the distribution and topography of immunocompetent cells (T lymphocytes, B lymphocytes and macrophages) and proliferative activity of lymphoid cells in the lymphoid organs and tissues in cattle. © 2016 Blackwell Verlag GmbH.

  4. CHECKPOINT INHIBITOR IMMUNE THERAPY: Systemic Indications and Ophthalmic Side Effects.

    PubMed

    Dalvin, Lauren A; Shields, Carol L; Orloff, Marlana; Sato, Takami; Shields, Jerry A

    2018-06-01

    To review immune checkpoint inhibitor indications and ophthalmic side effects. A literature review was performed using a PubMed search for publications between 1990 and 2017. Immune checkpoint inhibitors are designed to treat system malignancies by targeting one of three ligands, leading to T-cell activation for attack against malignant cells. These ligands (and targeted drug) include cytotoxic T-lymphocyte antigen-4 (CTLA-4, ipilimumab), programmed death protein 1 (PD-1, pembrolizumab, nivolumab), and programmed death ligand-1 (PD-L1, atezolizumab, avelumab, durvalumab). These medications upregulate the immune system and cause autoimmune-like side effects. Ophthalmic side effects most frequently manifest as uveitis (1%) and dry eye (1-24%). Other side effects include myasthenia gravis (n = 19 reports), inflammatory orbitopathy (n = 11), keratitis (n = 3), cranial nerve palsy (n = 3), optic neuropathy (n = 2), serous retinal detachment (n = 2), extraocular muscle myopathy (n = 1), atypical chorioretinal lesions (n = 1), immune retinopathy (n = 1), and neuroretinitis (n = 1). Most inflammatory side effects are managed with topical or periocular corticosteroids, but advanced cases require systemic corticosteroids and cessation of checkpoint inhibitor therapy. Checkpoint inhibitors enhance the immune system by releasing inhibition on T cells, with risk of autoimmune-like side effects. Ophthalmologists should include immune-related adverse events in their differential when examining cancer patients with new ocular symptoms.

  5. A cleanroom sleeping environment's impact on markers of oxidative stress, immune dysregulation, and behavior in children with autism spectrum disorders.

    PubMed

    Faber, Scott; Zinn, Gregory M; Boggess, Andrew; Fahrenholz, Timothy; Kern, John C; Kingston, H M Skip

    2015-03-19

    An emerging paradigm suggests children with autism display a unique pattern of environmental, genetic, and epigenetic triggers that make them susceptible to developing dysfunctional heavy metal and chemical detoxification systems. These abnormalities could be caused by alterations in the methylation, sulfation, and metalloprotein pathways. This study sought to evaluate the physiological and behavioral effects of children with autism sleeping in an International Organization for Standardization Class 5 cleanroom. Ten children with autism, ages 3-12, slept in a cleanroom for two weeks to evaluate changes in toxin levels, oxidative stress, immune dysregulation, and behavior. Before and after the children slept in the cleanroom, samples of blood and hair and rating scale scores were obtained to assess these changes. Five children significantly lowered their concentration of oxidized glutathione, a biomarker of oxidative stress. The younger cohort, age 5 and under, showed significantly greater mean decreases in two markers of immune dysregulation, CD3% and CD4%, than the older cohort. Changes in serum magnesium, influencing neuronal regulation, correlated negatively while changes in serum iron, affecting oxygenation of tissues, correlated positively with age. Changes in serum benzene and PCB 28 concentrations showed significant negative correlations with age. The younger children demonstrated significant improvements on behavioral rating scales compared to the older children. In a younger pair of identical twins, one twin showed significantly greater improvements in 4 out of 5 markers of oxidative stress, which corresponded with better overall behavioral rating scale scores than the other twin. Younger children who slept in the cleanroom altered elemental levels, decreased immune dysregulation, and improved behavioral rating scales, suggesting that their detoxification metabolism was briefly enhanced. The older children displayed a worsening in behavioral rating scale

  6. Inactivated Influenza Vaccine That Provides Rapid, Innate-Immune-System-Mediated Protection and Subsequent Long-Term Adaptive Immunity.

    PubMed

    Chua, Brendon Y; Wong, Chinn Yi; Mifsud, Edin J; Edenborough, Kathryn M; Sekiya, Toshiki; Tan, Amabel C L; Mercuri, Francesca; Rockman, Steve; Chen, Weisan; Turner, Stephen J; Doherty, Peter C; Kelso, Anne; Brown, Lorena E; Jackson, David C

    2015-10-27

    The continual threat to global health posed by influenza has led to increased efforts to improve the effectiveness of influenza vaccines for use in epidemics and pandemics. We show in this study that formulation of a low dose of inactivated detergent-split influenza vaccine with a Toll-like receptor 2 (TLR2) agonist-based lipopeptide adjuvant (R4Pam2Cys) provides (i) immediate, antigen-independent immunity mediated by the innate immune system and (ii) significant enhancement of antigen-dependent immunity which exhibits an increased breadth of effector function. Intranasal administration of mice with vaccine formulated with R4Pam2Cys but not vaccine alone provides protection against both homologous and serologically distinct (heterologous) viral strains within a day of administration. Vaccination in the presence of R4Pam2Cys subsequently also induces high levels of systemic IgM, IgG1, and IgG2b antibodies and pulmonary IgA antibodies that inhibit hemagglutination (HA) and neuraminidase (NA) activities of homologous but not heterologous virus. Improved primary virus nucleoprotein (NP)-specific CD8(+) T cell responses are also induced by the use of R4Pam2Cys and are associated with robust recall responses to provide heterologous protection. These protective effects are demonstrated in wild-type and antibody-deficient animals but not in those depleted of CD8(+) T cells. Using a contact-dependent virus transmission model, we also found that heterologous virus transmission from vaccinated mice to naive mice is significantly reduced. These results demonstrate the potential of adding a TLR2 agonist to an existing seasonal influenza vaccine to improve its utility by inducing immediate short-term nonspecific antiviral protection and also antigen-specific responses to provide homologous and heterologous immunity. The innate and adaptive immune systems differ in mechanisms, specificities, and times at which they take effect. The innate immune system responds within hours of

  7. Impact of Pharmacist Immunization Authority on Seasonal Influenza Immunization Rates Across States.

    PubMed

    Drozd, Edward M; Miller, Laura; Johnsrud, Michael

    2017-08-01

    The goal of this study was to investigate the impact on immunization rates of policy changes that allowed pharmacists to administer influenza immunizations across the United States. Influenza immunization rates across states were compared before and after policy changes permitting pharmacists to administer influenza immunizations. The study used Behavioral Risk Factor Surveillance System (BRFSS) survey data on influenza immunization rates between 2003 and 2013. Logistic regression models were constructed and incorporated adjustments for the complex sample design of the BRFSS to predict the likelihood of a person receiving an influenza immunization based on various patient health, demographic, and access to care factors. Overall, as states moved to allow pharmacists to administer influenza immunizations, the odds that an adult resident received an influenza immunization rose, with the effect increasing over time. The average percentage of people receiving influenza immunizations in states was 35.1%, rising from 32.2% in 2003 to 40.3% in 2013. The policy changes were associated with a long-term increase of 2.2% to 7.6% in the number of adults aged 25 to 59 years receiving an influenza immunization (largest for those aged 35-39 years) and no significant change for those younger or older. These findings suggest that pharmacies and other nontraditional settings may offer accessible venues for patients when implementing other public health initiatives. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. Immune Cell Metabolism in Systemic Lupus Erythematosus.

    PubMed

    Choi, Seung-Chul; Titov, Anton A; Sivakumar, Ramya; Li, Wei; Morel, Laurence

    2016-11-01

    Cellular metabolism represents a newly identified checkpoint of effector functions in the immune system. A solid body of work has characterized the metabolic requirements of normal T cells during activation and differentiation into polarized effector subsets. Similar studies have been initiated to characterize the metabolic requirements for B cells and myeloid cells. Only a few studies though have characterized the metabolism of immune cells in the context of autoimmune diseases. Here, we review what is known on the altered metabolic patterns of CD4 + T cells, B cells, and myeloid cells in lupus patients and lupus-prone mice and how they contribute to lupus pathogenesis. We also discuss how defects in immune metabolism in lupus can be targeted therapeutically.

  9. Protective and Pathological Immunity during Central Nervous System Infections.

    PubMed

    Klein, Robyn S; Hunter, Christopher A

    2017-06-20

    The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection. Advances in these areas have broadened our comprehension of how the immune system functions in the brain and can readily overcome immune privilege. Copyright © 2017. Published by Elsevier Inc.

  10. 'Order from disorder sprung': recognition and regulation in the immune system

    NASA Astrophysics Data System (ADS)

    Mak, Tak W.

    2003-06-01

    Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen

  11. 'Order from disorder sprung': recognition and regulation in the immune system.

    PubMed

    Mak, Tak W

    2003-06-15

    Milton's epic poem Paradise lost supplies a colourful metaphor for the immune system and its responses to pathogens. With the role of Satan played by pathogens seeking to destroy the paradise of human health, GOD intervenes and imposes order out of chaos. In this context, GOD means 'generation of diversity': the capacity of the innate and specific immune responses to recognize and eliminate a universe of pathogens. Thus, the immune system can be thought of as an entity that self-assembles the elements required to combat bodily invasion and injury. In so doing, it brings to bear the power of specific recognition: the ability to distinguish self from non-self, and the threatening from the benign. This ability to define and protect self is evolutionarily very old. Self-recognition and biochemical and barrier defences can be detected in primitive organisms, and elements of these mechanisms are built upon in an orderly way to establish the mammalian immune system. Innate immune responses depend on the use of a limited number of germline-encoded receptors to recognize conserved molecular patterns that occur on the surfaces of a broad range of pathogens. The B and T lymphocytes of the specific immune response use complex gene-rearrangement machinery to generate a diversity of antigen receptors capable of recognizing any pathogen in the universe. Binding to receptors on both innate and specific immune-system cells triggers intricate intracellular signalling pathways that lead to new gene transcription and effector-cell activation. And yet, regulation is imposed on these responses so that Paradise is not lost to the turning of the immune system onto self-tissues, the spectre of autoimmunity. Lymphocyte activation requires multiple signals and intercellular interactions. Mechanisms exist to establish tolerance to self by the selection and elimination of cells recognizing self-antigens. Immune system cell populations are reduced by programmed cell death once the pathogen

  12. Alcohol, aging, and innate immunity.

    PubMed

    Boule, Lisbeth A; Kovacs, Elizabeth J

    2017-07-01

    The global population is aging: in 2010, 8% of the population was older than 65 y, and that is expected to double to 16% by 2050. With advanced age comes a heightened prevalence of chronic diseases. Moreover, elderly humans fair worse after acute diseases, namely infection, leading to higher rates of infection-mediated mortality. Advanced age alters many aspects of both the innate and adaptive immune systems, leading to impaired responses to primary infection and poor development of immunologic memory. An often overlooked, yet increasingly common, behavior in older individuals is alcohol consumption. In fact, it has been estimated that >40% of older adults consume alcohol, and evidence reveals that >10% of this group is drinking more than the recommended limit by the National Institute on Alcohol Abuse and Alcoholism. Alcohol consumption, at any level, alters host immune responses, including changes in the number, phenotype, and function of innate and adaptive immune cells. Thus, understanding the effect of alcohol ingestion on the immune system of older individuals, who are already less capable of combating infection, merits further study. However, there is currently almost nothing known about how drinking alters innate immunity in older subjects, despite innate immune cells being critical for host defense, resolution of inflammation, and maintenance of immune homeostasis. Here, we review the effects of aging and alcohol consumption on innate immune cells independently and highlight the few studies that have examined the effects of alcohol ingestion in aged individuals. © Society for Leukocyte Biology.

  13. [The immune system and the eye].

    PubMed

    Faber, Carsten; Nissen, Mogens Holst

    2008-09-15

    The special relationship between the eye and the immune system rests on a number of anatomical, physiological and immunological mechanisms. These mechanisms prevent the delicate structures of the eye from potentially damaging immunogenic inflammation while protecting against pathogens. Rather than inflammation, antigen induces a form of systemic and antigen-specific immunological tolerance. Owing to its systemic nature, this tolerance may be utilised to achieve successful treatment of immunological disorders.

  14. The respiratory immune system of pigs.

    PubMed

    Pabst, R

    1996-11-01

    Respiratory tract infections with bacteria like Actinobacillus pleuropneumoniae are extremely common in pigs and are of major veterinary relevance. The respiratory tract can be divided into the upper part, consisting of the nose, pharynx, larynx and trachea, and the lower part, consisting of the different parts of the lung. After bronchoscopy and bronchoalveolar lavage (BAL) had been established for pigs, interest grew in the unspecific parts of the immune system of the respiratory tract (such as macrophages, mast cells, the mucociliary function) and the specific immune system, consisting of the different lymphocyte subsets. In contrast to the rodent and human lung, the lung of the pig contains large numbers of intravascular macrophages with a high clearance capacity. The main focus of this paper is the localization, subset composition and quantification of lymphocytes in the pig lung: the intravascular and interstitial pool and the lymphocytes in the bronchial epithelium and lamina propria including bronchus-associated lymphoid tissue form the major compartments. In the BAL only a small proportion of nucleated cells are lymphocytes. The effects of age, antigen exposition, immunization and infection on the lymphocyte distribution in the pig lung are presented. In addition to veterinary aspects, the lung of pigs can also serve as a model for diseases in humans.

  15. Endocrine and Local IGF-I in the Bony Fish Immune System.

    PubMed

    Franz, Anne-Constance; Faass, Oliver; Köllner, Bernd; Shved, Natallia; Link, Karl; Casanova, Ayako; Wenger, Michael; D'Cotta, Helena; Baroiller, Jean-François; Ullrich, Oliver; Reinecke, Manfred; Eppler, Elisabeth

    2016-01-26

    A role for GH and IGF-I in the modulation of the immune system has been under discussion for decades. Generally, GH is considered a stimulator of innate immune parameters in mammals and teleost fish. The stimulatory effects in humans as well as in bony fish often appear to be correlated with elevated endocrine IGF-I (liver-derived), which has also been shown to be suppressed during infection in some studies. Nevertheless, data are still fragmentary. Some studies point to an important role of GH and IGF-I particularly during immune organ development and constitution. Even less is known about the potential relevance of local (autocrine/paracrine) IGF-I within adult and developing immune organs, and the distinct localization of IGF-I in immune cells and tissues of mammals and fish has not been systematically defined. Thus far, IGF-I has been localized in different mammalian immune cell types, particularly macrophages and granulocytes, and in supporting cells, but not in T-lymphocytes. In the present study, we detected IGF-I in phagocytic cells isolated from rainbow trout head kidney and, in contrast to some findings in mammals, in T-cells of a channel catfish cell line. Thus, although numerous analogies among mammals and teleosts exist not only for the GH/IGF-system, but also for the immune system, there are differences that should be further investigated. For instance, it is unclear whether the primarily reported role of GH/IGF-I in the innate immune response is due to the lack of studies focusing on the adaptive immune system, or whether it truly preferentially concerns innate immune parameters. Infectious challenges in combination with GH/IGF-I manipulations are another important topic that has not been sufficiently addressed to date, particularly with respect to developmental and environmental influences on fish growth and health.

  16. A human tissue-based functional assay platform to evaluate the immune function impact of small molecule inhibitors that target the immune system.

    PubMed

    St Pierre, Cristina; Guo, Jane; Shin, John D; Engstrom, Laura W; Lee, Hyun-Hee; Herbert, Alan; Surdi, Laura; Baker, James; Salmon, Michael; Shah, Sanjiv; Ellis, J Michael; Houshyar, Hani; Crackower, Michael A; Kleinschek, Melanie A; Jones, Dallas C; Hicks, Alexandra; Zaller, Dennis M; Alves, Stephen E; Ramadas, Ravisankar A

    2017-01-01

    While the immune system is essential for the maintenance of the homeostasis, health and survival of humans, aberrant immune responses can lead to chronic inflammatory and autoimmune disorders. Pharmacological modulation of drug targets in the immune system to ameliorate disease also carry a risk of immunosuppression that could lead to adverse outcomes. Therefore, it is important to understand the 'immune fingerprint' of novel therapeutics as they relate to current and, clinically used immunological therapies to better understand their potential therapeutic benefit as well as immunosuppressive ability that might lead to adverse events such as infection risks and cancer. Since the mechanistic investigation of pharmacological modulators in a drug discovery setting is largely compound- and mechanism-centric but not comprehensive in terms of immune system impact, we developed a human tissue based functional assay platform to evaluate the impact of pharmacological modulators on a range of innate and adaptive immune functions. Here, we demonstrate that it is possible to generate a qualitative and quantitative immune system impact of pharmacological modulators, which might help better understand and predict the benefit-risk profiles of these compounds in the treatment of immune disorders.

  17. Addiction, Adolescence, and Innate Immune Gene Induction

    PubMed Central

    Crews, Fulton T.; Vetreno, Ryan Peter

    2011-01-01

    Repeated drug use/abuse amplifies psychopathology, progressively reducing frontal lobe behavioral control, and cognitive flexibility while simultaneously increasing limbic temporal lobe negative emotionality. The period of adolescence is a neurodevelopmental stage characterized by poor behavioral control as well as strong limbic reward and thrill seeking. Repeated drug abuse and/or stress during this stage increase the risk of addiction and elevate activator innate immune signaling in the brain. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a key glial transcription factor that regulates proinflammatory chemokines, cytokines, oxidases, proteases, and other innate immune genes. Induction of innate brain immune gene expression (e.g., NF-κB) facilitates negative affect, depression-like behaviors, and inhibits hippocampal neurogenesis. In addition, innate immune gene induction alters cortical neurotransmission consistent with loss of behavioral control. Studies with anti-oxidant, anti-inflammatory, and anti-depressant drugs as well as opiate antagonists link persistent innate immune gene expression to key behavioral components of addiction, e.g., negative affect-anxiety and loss of frontal–cortical behavioral control. This review suggests that persistent and progressive changes in innate immune gene expression contribute to the development of addiction. Innate immune genes may represent a novel new target for addiction therapy. PMID:21629837

  18. The Immune System in the Pathogenesis of Ovarian Cancer

    PubMed Central

    Charbonneau, Bridget; Goode, Ellen L.; Kalli, Kimberly R.; Knutson, Keith L.; DeRycke, Melissa S.

    2014-01-01

    Clinical outcomes in ovarian cancer are heterogeneous even when considering common features such as stage, response to therapy, and grade. This disparity in outcomes warrants further exploration into tumor and host characteristics. One compelling host characteristic is the immune response to ovarian cancer. While several studies have confirmed a prominent role for the immune system in modifying the clinical course of the disease, recent genetic and protein analyses also suggest a role in disease incidence. Recent studies also show that anti-tumor immunity is often negated by immune suppressive cells present in the tumor microenvironment. These suppressive immune cells also directly enhance the pathogenesis through the release of various cytokines and chemokines, which together form an integrated pathologic network. Thus, future research into immunotherapy targeting ovarian cancer will likely become increasingly focused on combination approaches that simultaneously augment immunity while preventing local immune suppression or by disrupting critical cytokine networks. PMID:23582060

  19. Epilepsy and the immune system: is there a link?

    PubMed

    Billiau, An D; Wouters, Carine H; Lagae, Lieven G

    2005-01-01

    The concept that the immune system plays a role in the epileptogenic process of some epileptic syndromes was first proposed more than 20 years ago. Since then, numerous studies have reported on the existence of a variety of immunological alterations in epileptic patients, on the observation of favourable responses of refractory epilepsy syndromes to immunomodulatory treatment, and on the association of certain well-known immune-mediated disease states with epilepsy. This review comprehensively recapitulates the currently available evidence supporting or arguing against the possible involvement of the immune system in the pathogenesis of certain types of epilepsy. It is concluded that an abundance of facts is in support of this concept and that further studies should be directed at substantiating the pathogenic significance of (auto)immune responses in certain types of epilepsy. Current progress in the functional and molecular immunological research techniques will indisputably contribute to the elucidation of this link.

  20. Aging of immune system: Immune signature from peripheral blood lymphocyte subsets in 1068 healthy adults.

    PubMed

    Qin, Ling; Jing, Xie; Qiu, Zhifeng; Cao, Wei; Jiao, Yang; Routy, Jean-Pierre; Li, Taisheng

    2016-05-01

    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation.

  1. Web-based e-learning and virtual lab of human-artificial immune system.

    PubMed

    Gong, Tao; Ding, Yongsheng; Xiong, Qin

    2014-05-01

    Human immune system is as important in keeping the body healthy as the brain in supporting the intelligence. However, the traditional models of the human immune system are built on the mathematics equations, which are not easy for students to understand. To help the students to understand the immune systems, a web-based e-learning approach with virtual lab is designed for the intelligent system control course by using new intelligent educational technology. Comparing the traditional graduate educational model within the classroom, the web-based e-learning with the virtual lab shows the higher inspiration in guiding the graduate students to think independently and innovatively, as the students said. It has been found that this web-based immune e-learning system with the online virtual lab is useful for teaching the graduate students to understand the immune systems in an easier way and design their simulations more creatively and cooperatively. The teaching practice shows that the optimum web-based e-learning system can be used to increase the learning effectiveness of the students.

  2. How do plants achieve immunity? Defence without specialized immune cells.

    PubMed

    Spoel, Steven H; Dong, Xinnian

    2012-01-25

    Vertebrates have evolved a sophisticated adaptive immune system that relies on an almost infinite diversity of antigen receptors that are clonally expressed by specialized immune cells that roam the circulatory system. These immune cells provide vertebrates with extraordinary antigen-specific immune capacity and memory, while minimizing self-reactivity. Plants, however, lack specialized mobile immune cells. Instead, every plant cell is thought to be capable of launching an effective immune response. So how do plants achieve specific, self-tolerant immunity and establish immune memory? Recent developments point towards a multilayered plant innate immune system comprised of self-surveillance, systemic signalling and chromosomal changes that together establish effective immunity.

  3. Modulating the function of the immune system by thyroid hormones and thyrotropin.

    PubMed

    Jara, Evelyn L; Muñoz-Durango, Natalia; Llanos, Carolina; Fardella, Carlos; González, Pablo A; Bueno, Susan M; Kalergis, Alexis M; Riedel, Claudia A

    2017-04-01

    Accumulating evidence suggests a close bidirectional communication and regulation between the neuroendocrine and immune systems. Thyroid hormones (THs) can exert responses in various immune cells, e.g., monocytes, macrophages, natural killer cells, and lymphocytes, affecting several inflammation-related processes (such as, chemotaxis, phagocytosis, reactive oxygen species generation, and cytokines production). The interactions between the endocrine and immune systems have been shown to contribute to pathophysiological conditions, including sepsis, inflammation, autoimmune diseases and viral infections. Under these conditions, TH therapy could contribute to restoring normal physiological functions. Here we discuss the effects of THs and thyroid stimulating hormone (TSH) on the immune system and the contribution to inflammation and pathogen clearance, as well as the consequences of thyroid pathologies over the function of the immune system. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  4. The influence of immune system stimulation on encapsulated islet graft survival.

    PubMed

    Orłowski, Tadeusz M; Godlewska, Ewa; Tarchalska, Magda; Kinasiewicz, Joanna; Antosiak, Magda; Sabat, Marek

    2005-01-01

    The aim of this study was to determine the influence activating of the recipient immune system on the function of microencapsulated islet xenografts. The skin of WAG or Fisher rats and WAG free or encapsulated (APA) Langerhans islets were transplanted to healthy or to streptozotocin diabetic BALB/c mice. Skin grafts were performed following the method of Billingham and Medawar. Rat islets were isolated from pancreas by the Lacy and Kostianovsy method and encapsulated with calcium alginate-poly-L-lysine-alginate according to the 3-step coating method of Sun. The transplantation of encapsulated WAG islets, despite activation of the host immune system, restored euglycemia for over 180 +/-100 days. A subsequent skin graft taken from the same donor was rejected in the second set mode, but euglycemia persisted. In diabetic recipients, impaired immune response was corrected by successful encapsulated islet transplantation. In diabetic mice, strong stimulation with 2-fold skin transplantation induced primary non-function of grafted islets despite their encapsulation. The survival of an islet xenograft depends on the level of activation of the recipient immune system. The immune response of diabetic mice was impaired, but increased after post-transplant restitution of euglycemia. Microencapsulation sufficiently protected grafted islets, and remission of diabetes was preserved. However, after strong specific or non-specific stimulation of the host immune system, non-function of xenografted islets developed despite their encapsulation. Therefore, islet graft recipients should avoid procedures which could stimulate their immune systems. If absolutely necessary, the graft should be protected by exogenous insulin therapy at that time.

  5. The Neuromodulation of the Intestinal Immune System and Its Relevance in Inflammatory Bowel Disease.

    PubMed

    Di Giovangiulio, Martina; Verheijden, Simon; Bosmans, Goele; Stakenborg, Nathalie; Boeckxstaens, Guy E; Matteoli, Gianluca

    2015-01-01

    One of the main tasks of the immune system is to discriminate and appropriately react to "danger" or "non-danger" signals. This is crucial in the gastrointestinal tract, where the immune system is confronted with a myriad of food antigens and symbiotic microflora that are in constant contact with the mucosa, in addition to any potential pathogens. This large number of antigens and commensal microflora, which are essential for providing vital nutrients, must be tolerated by the intestinal immune system to prevent aberrant inflammation. Hence, the balance between immune activation versus tolerance should be tightly regulated to maintain intestinal homeostasis and to prevent immune activation indiscriminately against all luminal antigens. Loss of this delicate equilibrium can lead to chronic activation of the intestinal immune response resulting in intestinal disorders, such as inflammatory bowel diseases (IBD). In order to maintain homeostasis, the immune system has evolved diverse regulatory strategies including additional non-immunological actors able to control the immune response. Accumulating evidence strongly indicates a bidirectional link between the two systems in which the brain modulates the immune response via the detection of circulating cytokines and via direct afferent input from sensory fibers and from enteric neurons. In the current review, we will highlight the most recent findings regarding the cross-talk between the nervous system and the mucosal immune system and will discuss the potential use of these neuronal circuits and neuromediators as novel therapeutic tools to reestablish immune tolerance and treat intestinal chronic inflammation.

  6. Endocrine, immune, and behavioral effects of aldicarb (carbamate), atrazine (triazine) and nitrate (fertilizer) mixtures at groundwater concentrations.

    PubMed

    Porter, W P; Jaeger, J W; Carlson, I H

    1999-01-01

    This paper describes the results of 5 years of research on interactive effects of mixtures of aldicarb, atrazine, and nitrate on endocrine, immune, and nervous system function. The concentrations of chemicals used were the same order of magnitude as current maximum contaminant levels (MCLs) for all three compounds. Such levels occur in groundwater across the United States. Dosing was through voluntary consumption of drinking water. We used fractional and full factorial designs with center replicates to determine multifactor effects. We used chronic doses in experiments that varied in duration from 22 to 103 days. We tested for changes in thyroid hormone levels, ability to make antibodies to foreign proteins, and aggression in wild deer mice, Peromyscus maniculatus, and white outbred Swiss Webster mice, Mus musculus, ND4 strain. Endocrine, immune, and behavior changes occurred due to doses of mixtures, but rarely due to single compounds at the same concentrations. Immune assay data suggest the possibility of seasonal effects at low doses. We present a multiple-level model to help interpret the data in the context of human health and biological conservation concerns. We discuss six testing deficiencies of currently registered pesticides, and suggest areas of human health concerns if present trends in pesticide use continue.

  7. Social immunity and the superorganism: Behavioral defenses protecting honey bee colonies from pathogens and parasites

    USDA-ARS?s Scientific Manuscript database

    Honey bees (Apis mellifera) have a number of traits that effectively reduce the spread of pathogens and parasites throughout the colony. These mechanisms of social immunity are often analogous to the individual immune system. As such social immune defences function to protect the colony or superorga...

  8. The Microbiota, the Immune System and the Allograft

    PubMed Central

    Alegre, Maria-Luisa; Mannon, Roslyn B.; Mannon, Peter J.

    2015-01-01

    The microbiota represents the complex collections of microbial communities that colonize a host. In health, the microbiota is essential for metabolism, protection against pathogens and maturation of the immune system. In return, the immune system determines the composition of the microbiota. Altered microbial composition (dysbiosis) has been correlated with a number of diseases in humans. The tight reciprocal immune/microbial interactions complicate determining whether dysbiosis is a cause and/or a consequence of immune dysregulation and disease initiation or progression. However, a number of studies in germ-free and antibiotic-treated animal models support causal roles for intestinal bacteria in disease susceptibility. The role of the microbiota in transplant recipients is only starting to be investigated and its study is further complicated by putative contributions of both recipient and donor microbiota. Moreover, both flora may be affected directly or indirectly by immunosuppressive drugs and anti-microbial prophylaxis taken by transplant patients, as well as by inflammatory processes secondary to ischemia/reperfusion and allorecognition, and the underlying cause of end-organ failure. Whether the ensuing dysbiosis affects alloresponses and whether therapies aimed at correcting dysbiosis should be considered in transplant patients constitutes an exciting new field of research. PMID:24840316

  9. Long-Range Activation of Systemic Immunity through Peptidoglycan Diffusion in Drosophila

    PubMed Central

    Gendrin, Mathilde; Welchman, David P.; Poidevin, Mickael; Hervé, Mireille; Lemaitre, Bruno

    2009-01-01

    The systemic immune response of Drosophila is known to be induced both by septic injury and by oral infection with certain bacteria, and is characterized by the secretion of antimicrobial peptides (AMPs) into the haemolymph. To investigate other possible routes of bacterial infection, we deposited Erwinia carotovora (Ecc15) on various sites of the cuticle and monitored the immune response via expression of the AMP gene Diptericin. A strong response was observed to deposition on the genital plate of males (up to 20% of a septic injury response), but not females. We show that the principal response to genital infection is systemic, but that some AMPs, particularly Defensin, are induced locally in the genital tract. At late time points we detected bacteria in the haemolymph of immune deficient RelishE20 flies, indicating that the genital plate can be a route of entry for pathogens, and that the immune response protects flies against the progression of genital infection. The protective role of the immune response is further illustrated by our observation that RelishE20 flies exhibit significant lethality in response to genital Ecc15 infections. We next show that a systemic immune response can be induced by deposition of the bacterial elicitor peptidoglycan (PGN), or its terminal monomer tracheal cytotoxin (TCT), on the genital plate. This immune response is downregulated by PGRP-LB and Pirk, known regulators of the Imd pathway, and can be suppressed by the overexpression of PGRP-LB in the haemolymph compartment. Finally, we provide strong evidence that TCT can activate a systemic response by crossing epithelia, by showing that radiolabelled TCT deposited on the genital plate can subsequently be detected in the haemolymph. Genital infection is thus an intriguing new model for studying the systemic immune response to local epithelial infections and a potential route of entry for naturally occurring pathogens of Drosophila. PMID:20019799

  10. Long-range activation of systemic immunity through peptidoglycan diffusion in Drosophila.

    PubMed

    Gendrin, Mathilde; Welchman, David P; Poidevin, Mickael; Hervé, Mireille; Lemaitre, Bruno

    2009-12-01

    The systemic immune response of Drosophila is known to be induced both by septic injury and by oral infection with certain bacteria, and is characterized by the secretion of antimicrobial peptides (AMPs) into the haemolymph. To investigate other possible routes of bacterial infection, we deposited Erwinia carotovora (Ecc15) on various sites of the cuticle and monitored the immune response via expression of the AMP gene Diptericin. A strong response was observed to deposition on the genital plate of males (up to 20% of a septic injury response), but not females. We show that the principal response to genital infection is systemic, but that some AMPs, particularly Defensin, are induced locally in the genital tract. At late time points we detected bacteria in the haemolymph of immune deficient Relish(E20) flies, indicating that the genital plate can be a route of entry for pathogens, and that the immune response protects flies against the progression of genital infection. The protective role of the immune response is further illustrated by our observation that Relish(E20) flies exhibit significant lethality in response to genital Ecc15 infections. We next show that a systemic immune response can be induced by deposition of the bacterial elicitor peptidoglycan (PGN), or its terminal monomer tracheal cytotoxin (TCT), on the genital plate. This immune response is downregulated by PGRP-LB and Pirk, known regulators of the Imd pathway, and can be suppressed by the overexpression of PGRP-LB in the haemolymph compartment. Finally, we provide strong evidence that TCT can activate a systemic response by crossing epithelia, by showing that radiolabelled TCT deposited on the genital plate can subsequently be detected in the haemolymph. Genital infection is thus an intriguing new model for studying the systemic immune response to local epithelial infections and a potential route of entry for naturally occurring pathogens of Drosophila.

  11. Strengthening routine immunization systems to improve global vaccination coverage.

    PubMed

    Sodha, S V; Dietz, V

    2015-03-01

    Global coverage with the third dose of diphtheria-tetanus-pertussis vaccine among children under 1 year of age stagnated at ∼ 83-84% during 2008-13. Annual World Health Organization and UNICEF-derived national vaccination coverage estimates. Incomplete vaccination is associated with poor socioeconomic status, lower education, non-use of maternal-child health services, living in conflict-affected areas, missed immunization opportunities and cancelled vaccination sessions. Vaccination platforms must expand to include older ages including the second year of life. Immunization programmes, including eradication and elimination initiatives such as those for polio and measles, must integrate within the broader health system. The Global Vaccine Action Plan (GVAP) 2011-20 is a framework for strengthening immunization systems, emphasizing country ownership, shared responsibility, equity, integration, sustainability and innovation. Immunization programmes should identify, monitor and evaluate gaps and interventions within the GVAP framework. Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Domestication drive the changes of immune and digestive system of Eurasian perch (Perca fluviatilis).

    PubMed

    Chen, Xiaowen; Wang, Jun; Qian, Long; Gaughan, Sarah; Xiang, Wei; Ai, Tao; Fan, Zhenming; Wang, Chenghui

    2017-01-01

    Domestication has altered a variety of traits within the Eurasian perch (Perca fluviatilis), including phenotypic, physiological and behavioral traits of Eurasian perch (Perca fluviatilis). Little is known, however, about the genetic changes between domesticated and wild Eurasian perch. In this study, we assembled a high-quality de novo reference transcriptome and identified differentially expressed genes between wild and domesticated Eurasian perch. A total of 113,709 transcripts were assembled, and 58,380 transcripts were annotated. Transcriptomic comparison revealed 630 differentially expressed genes between domesticated and wild Eurasian perch. Within domesticated Eurasian perch there were 412 genes that were up-regulated including MHCI, MHCII, chia, ighm within immune system development. There were 218 genes including try1, ctrl, ctrb, cela3b, cpa1 and cpb1, which were down-regulated that were associated with digestive processes. Our results indicated domestication drives the changes of immune and digestive system of Eurasian perch. Our study not only provide valuable genetic resources for further studies in Eurasian perch, but also provide novel insights into the genetic basis of physiological changes in Eurasian perch during domestication process.

  13. Hypo-gravity and immune system effects

    NASA Technical Reports Server (NTRS)

    Carter, Paul D.; Barnes, Frank

    1990-01-01

    Recent studies on the effects of hypo-gravity on astronauts have shown depressed response of the immune system component cells (e.g. T-lymphocytes activity) and associated bone-mass loss due to demineralization. The widespread use of various electrical stimulation techniques in fracture repair and bone growth make use of the inherent piezoelectric and streaming potentials in Ca(2++) depositation. In-vitro and in-vivo experiments were designed to determine if these potentials, absent or greatly reduced in space, could be artificially enhanced to advantageously effect the bone marrow and, consequently, immune system cells. The bone marrow plays an extremely important role in the development and maturation of all blood cells and, specifically, T- and B-lymphocytes. It is our belief that simulated E-fields will enhance this development when 'ambient' physiological fields are absent during spaceflight or extended bedrest. Our investigation began with a look at the component immune system cells and their growth patterns in vitro. The first chamber will induce E-fields by current densities produced from an agar-bridge electrode arrangement. The cells are immersed in a nutrient agar and isolated from the electrodes by an agar bridge to prevent electrolytic contamination. The second chamber induces current densities by mutual induction from a magnetic field produced by a solenoid coil. Cells are isolated in a small radial area to reduce (1/r) effects and for accurate field calculations. We anticipate inducing currents in the nano- and microampere range as indicated by our calculations of physiological fields.

  14. Digital immunization registry: evidence for the impact of mHealth on enhancing the immunization system and improving immunization coverage for children under one year old in Vietnam.

    PubMed

    Nguyen, Nga Tuyet; Vu, Huong Minh; Dao, Sang Dinh; Tran, Hieu Trung; Nguyen, Tu Xuan Cam

    2017-01-01

    The Vietnam National Expanded Program on Immunization (NEPI) has been successfully implementing a nationwide immunization system since 1985. From the start, the program has increased the immunization coverage rate; however, data on immunization coverage in Vietnam are gathered and aggregated from commune health centers in routine, paper-based reports, which have shortcomings. Also, calculations of coverage are inconsistent at subnational levels, which lead to uncertainty about the size of the target population used as the denominator in coverage calculations. The growth of mobile networks in Vietnam provides an opportunity to apply mHealth to improve the immunization program. In 2012, PATH and the Vietnam NEPI developed and piloted a digital immunization registry, ImmReg, to overcome the challenges of the paper system. A final evaluation was conducted in 2015 to assess the impact of ImmReg, including its use of SMS reminders, on improving the immunization program. The study population comprised all children born in Ben Tre province in September and October of 2013, 2014, and 2015, representing pre-intervention, post-intervention, and one year post-intervention, respectively. Data exported from ImmReg were used to compare the immunization rate, dropout rate, and timeliness of vaccination before and after the intervention. Additionally, a rapid survey was conducted to understand the willingness of parents with children due for vaccination to pay for SMS reminder messages on the immunization schedule. Timely administration of oral polio vaccine, Quinvaxem, and measles 1 vaccine significantly increased over time from baseline to post-intervention to one year post-intervention. In particular, the timeliness of vaccination with the third dose of Quinvaxem increased from 53.6% to 65.8% to 77.2%. For measles 1 vaccine, the rate increased from 70.4% to 76.2% to 92.3%. In addition, the dropout rate from Quinvaxem 1 to Quinvaxem 3 declined from 4.2% in 2013 to 0% in 2015, and

  15. Interactions between adipose tissue and the immune system in health and malnutrition.

    PubMed

    Wensveen, Felix M; Valentić, Sonja; Šestan, Marko; Wensveen, Tamara Turk; Polić, Bojan

    2015-09-01

    Adipose tissue provides the body with a storage depot of nutrients that is drained during times of starvation and replenished when food sources are abundant. As such, it is the primary sensor for nutrient availability in the milieu of an organism, which it communicates to the body through the excretion of hormones. Adipose tissue regulates a multitude of body functions associated with metabolism, such as gluconeogenesis, feeding and nutrient uptake. The immune system forms a vital layer of protection against micro-organisms that try to gain access to the nutrients contained in the body. Because infections need to be resolved as quickly as possible, speed is favored over energy-efficiency in an immune response. Especially when immune cells are activated, they switch to fast, but energy-inefficient anaerobic respiration to fulfill their energetic needs. Despite the necessity for an effective immune system, it is not given free rein in its energy expenditure. Signals derived from adipose tissue limit immune cell numbers and activity under conditions of nutrient shortage, whereas they allow proper immune cell activity when food sources are sufficiently available. When excessive fat accumulation occurs, such as in diet-induced obesity, adipose tissue becomes the site of pathological immune cell activation, causing chronic low-grade systemic inflammation. Obesity is therefore associated with a number of disorders in which the immune system plays a central role, such as atherosclerosis and non-alcoholic steatohepatitis. In this review, we will discuss the way in which adipose tissue regulates activity of the immune system under healthy and pathological conditions. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. A minimal model for multiple epidemics and immunity spreading.

    PubMed

    Sneppen, Kim; Trusina, Ala; Jensen, Mogens H; Bornholdt, Stefan

    2010-10-18

    Pathogens and parasites are ubiquitous in the living world, being limited only by availability of suitable hosts. The ability to transmit a particular disease depends on competing infections as well as on the status of host immunity. Multiple diseases compete for the same resource and their fate is coupled to each other. Such couplings have many facets, for example cross-immunization between related influenza strains, mutual inhibition by killing the host, or possible even a mutual catalytic effect if host immunity is impaired. We here introduce a minimal model for an unlimited number of unrelated pathogens whose interaction is simplified to simple mutual exclusion. The model incorporates an ongoing development of host immunity to past diseases, while leaving the system open for emergence of new diseases. The model exhibits a rich dynamical behavior with interacting infection waves, leaving broad trails of immunization in the host population. This obtained immunization pattern depends only on the system size and on the mutation rate that initiates new diseases.

  17. At the crossroads between tolerance and aggression: Revisiting the "layered immune system" hypothesis.

    PubMed

    Mold, Jeff E; McCune, Joseph M

    2011-04-01

    "We do not grow absolutely, chronologically. We grow sometimes in one dimension, and not in another; unevenly. We grow partially. We are relative. We are mature in one realm, childish in another. The past, present and future mingle and pull us backward, forward, or fix us in the present. We are made up of layers, cells, constellations."-Anaïs NinIt has long been recognized that the developing immune system exhibits certain peculiarities when compared to the adult immune system. Nonetheless, many still regard the fetal immune system as simply being an immature version of the adult immune system. Here we discuss historical evidence as well as recent findings, which suggest that the human immune system may develop in distinct layers with specific functions at different stages of development.

  18. Molecular architecture of the fruit fly's airway epithelial immune system.

    PubMed

    Wagner, Christina; Isermann, Kerstin; Fehrenbach, Heinz; Roeder, Thomas

    2008-09-29

    Airway epithelial cells not only constitute a physical barrier, but also the first line of defence against airborne pathogens. At the same time, they are constantly exposed to reactive oxygen species. Therefore, airway epithelia cells have to possess a sophisticated innate immune system and a molecular armamentarium to detoxify reactive oxygen species. It has become apparent that deregulation of epithelial innate immunity is a major reason for the development of chronic inflammatory lung diseases. To elucidate the molecular architecture of the innate immune system of airway epithelial cells, we choose the fruit fly Drosophila melanogaster as a model, because it has the simplest type of airways, consisting of epithelial cells only. Elucidating the structure of the innate immune system of this "airway epithelial cell culture" might enable us to understand why deregulatory processes in innate immune signalling cascades lead to long lasting inflammatory events. All airway epithelial cells of the fruit fly are able to launch an immune response. They contain only one functional signal transduction pathway that converges onto NF-kappaB factors, namely the IMD-pathway, which is homologous to the TNF-alpha receptor pathway. Although vital parts of the Toll-pathway are missing, dorsal and dif, the NF-kappaB factors dedicated to this signalling system, are present. Other pathways involved in immune regulation, such as the JNK- and the JAK/STAT-pathway, are completely functional in these cells. In addition, most peptidoglycan recognition proteins, representing the almost complete collection of pattern recognition receptors, are part of the epithelial cells equipment. Potential effector molecules are different antimicrobial peptides and lysozymes, but also transferrin that can inhibit bacterial growth through iron-depletion. Reactive oxygen species can be inactivated through the almost complete armamentarium of enzymatic antioxidants that has the fly to its disposal. The innate

  19. Regulation of bone by the adaptive immune system in arthritis

    PubMed Central

    2011-01-01

    Studies on the immune regulation of osteoclasts in rheumatoid arthritis have promoted the new research field of 'osteoimmunology', which investigates the interplay between the skeletal and immune systems at the molecular level. Accumulating evidence lends support to the theory that bone destruction associated with rheumatoid arthritis is caused by the enhanced activity of osteoclasts, resulting from the activation of a unique helper T cell subset, 'Th17 cells'. Understanding the interaction between osteoclasts and the adaptive immune system in rheumatoid arthritis and the molecular mechanisms of Th17 development will lead to the development of potentially effective therapeutic strategies. PMID:21635718

  20. Memory and Specificity in the Insect Immune System: Current Perspectives and Future Challenges.

    PubMed

    Cooper, Dustin; Eleftherianos, Ioannis

    2017-01-01

    The immune response of a host to a pathogen is typically described as either innate or adaptive. The innate form of the immune response is conserved across all organisms, including insects. Previous and recent research has focused on the nature of the insect immune system and the results imply that the innate immune response of insects is more robust and specific than previously thought. Priming of the insect innate immune system involves the exposure of insects to dead or a sublethal dose of microbes in order to elicit an initial response. Comparing subsequent infections in primed insects to non-primed individuals indicates that the insect innate immune response may possess some of the qualities of an adaptive immune system. Although some studies demonstrate that the protective effects of priming are due to a "loitering" innate immune response, others have presented more convincing elements of adaptivity. While an immune mechanism capable of producing the same degree of recognition specificity as seen in vertebrates has yet to be discovered in insects, a few interesting cases have been identified and discussed.

  1. Apoptosis in the homeostasis of the immune system and in human immune mediated diseases.

    PubMed

    Giovannetti, A; Pierdominici, M; Di Iorio, A; Cianci, R; Murdaca, G; Puppo, F; Pandolfi, F; Paganelli, R

    2008-01-01

    The immune system has evolved sophisticated mechanisms controlling the development of responses to dangerous antigens while avoiding unnecessary attacks to innocuous, commensal or self antigens. The risk of autoimmunity is continuously checked and balanced against the risk of succumbing to exogenous infectious agents. It is therefore of paramount importance to understand the molecular events linking the breakdown of tolerance and the development of immunodeficiency. Apoptotic mechanisms are used to regulate the development of thymocytes, the shaping of T cell repertoire, its selection and the coordinate events leading to immune responses in the periphery. Moreover, they are at the heart of the homeostatic controls restoring T cell numbers and establishing T cell memory. T lymphocytes shift continuously from survival to death signals to ensure immune responsiveness without incurring in autoimmune damage. In this review we shall consider some key facts on the relationship of lymphopenia to autoreactivity, the mechanisms controlling positive and negative selection in the thymus, the role of apoptosis in selected primary immunodeficiency states and in systemic and organ-specific autoimmunity, with examples from human diseases and their animal models.

  2. A benign helminth alters the host immune system and the gut microbiota in a rat model system.

    PubMed

    Wegener Parfrey, Laura; Jirků, Milan; Šíma, Radek; Jalovecká, Marie; Sak, Bohumil; Grigore, Karina; Jirků Pomajbíková, Kateřina

    2017-01-01

    Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs) in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome. We tested the impact of a benign tapeworm, Hymenolepis diminuta, in a rat model system. We find that H. diminuta infection results in increased interleukin 10 gene expression in the beginning of the prepatent period, consistent with induction of a type 2 immune response. We also find induction of humoral immunity during the patent period, shown here by increased IgA in feces. Further, we see an immuno-modulatory effect in the small intestine and spleen in patent period, as measured by reductions in tissue immune cells. We observed shifts in microbiota community composition during the patent period (beta-diversity) in response to H. diminuta infection. However, these compositional changes appear to be minor; they occur within families and genera common to both treatment groups. There was no change in alpha diversity. Hymenolepis diminuta is a promising model for helminth therapy because it establishes long-term, stable colonization in rats and modulates the immune system without causing bacterial dysbiosis. These results suggest that the goal of engineering a therapeutic helminth that can safely manipulate the mammalian immune system without disrupting the rest of the gut ecosystem is in reach.

  3. A benign helminth alters the host immune system and the gut microbiota in a rat model system

    PubMed Central

    Wegener Parfrey, Laura; Jirků, Milan; Šíma, Radek; Jalovecká, Marie; Sak, Bohumil; Grigore, Karina; Jirků Pomajbíková, Kateřina

    2017-01-01

    Helminths and bacteria are major players in the mammalian gut ecosystem and each influences the host immune system and health. Declines in helminth prevalence and bacterial diversity appear to play a role in the dramatic rise of immune mediated inflammatory diseases (IMIDs) in western populations. Helminths are potent modulators of immune system and their reintroduction is a promising therapeutic avenue for IMIDs. However, the introduction of helminths represents a disturbance for the host and it is important to understand the impact of helminth reintroduction on the host, including the immune system and gut microbiome. We tested the impact of a benign tapeworm, Hymenolepis diminuta, in a rat model system. We find that H. diminuta infection results in increased interleukin 10 gene expression in the beginning of the prepatent period, consistent with induction of a type 2 immune response. We also find induction of humoral immunity during the patent period, shown here by increased IgA in feces. Further, we see an immuno-modulatory effect in the small intestine and spleen in patent period, as measured by reductions in tissue immune cells. We observed shifts in microbiota community composition during the patent period (beta-diversity) in response to H. diminuta infection. However, these compositional changes appear to be minor; they occur within families and genera common to both treatment groups. There was no change in alpha diversity. Hymenolepis diminuta is a promising model for helminth therapy because it establishes long-term, stable colonization in rats and modulates the immune system without causing bacterial dysbiosis. These results suggest that the goal of engineering a therapeutic helminth that can safely manipulate the mammalian immune system without disrupting the rest of the gut ecosystem is in reach. PMID:28771620

  4. Infection-Induced Interaction between the Mosquito Circulatory and Immune Systems

    PubMed Central

    King, Jonas G.; Hillyer, Julián F.

    2012-01-01

    Insects counter infection with innate immune responses that rely on cells called hemocytes. Hemocytes exist in association with the insect's open circulatory system and this mode of existence has likely influenced the organization and control of anti-pathogen immune responses. Previous studies reported that pathogens in the mosquito body cavity (hemocoel) accumulate on the surface of the heart. Using novel cell staining, microdissection and intravital imaging techniques, we investigated the mechanism of pathogen accumulation in the pericardium of the malaria mosquito, Anopheles gambiae, and discovered a novel insect immune tissue, herein named periostial hemocytes, that sequesters pathogens as they flow with the hemolymph. Specifically, we show that there are two types of endocytic cells that flank the heart: periostial hemocytes and pericardial cells. Resident periostial hemocytes engage in the rapid phagocytosis of pathogens, and during the course of a bacterial or Plasmodium infection, circulating hemocytes migrate to the periostial regions where they bind the cardiac musculature and each other, and continue the phagocytosis of invaders. Periostial hemocyte aggregation occurs in a time- and infection dose-dependent manner, and once this immune process is triggered, the number of periostial hemocytes remains elevated for the lifetime of the mosquito. Finally, the soluble immune elicitors peptidoglycan and β-1,3-glucan also induce periostial hemocyte aggregation, indicating that this is a generalized and basal immune response that is induced by diverse immune stimuli. These data describe a novel insect cellular immune response that fundamentally relies on the physiological interaction between the insect circulatory and immune systems. PMID:23209421

  5. Mind-Body Medicine and Immune System Outcomes: A Systematic Review.

    PubMed

    Wahbeh, Helané; Haywood, Ashley; Kaufman, Karen; Zwickey, Heather

    2009-01-01

    This study is a systematic review of mind-body interventions that used immune outcomes in order to: 1) characterize mind-body medicine studies that assessed immune outcomes, 2) evaluate the quality of mind-body medicine studies measuring immune system effects, and 3) systematically evaluate the evidence for mind-body interventions effect on immune system outcomes using existing formal tools. 111 studies with 4,777 subjects were reviewed. The three largest intervention type categories were Relaxation Training (n=25), Cognitive Based Stress Management (n=22), and Hypnosis (n=21). Half the studies were conducted with healthy subjects (n=51). HIV (n=18), cancer (n=13) and allergies (n=7) were the most prominent conditions examined in the studies comprising of non-healthy subjects. Natural killer cell and CD4 T lymphocyte measures were the most commonly studied outcomes. Most outcome and modality categories had limited or inconclusive evidence. Relaxation training had the strongest scientific evidence of a mind-body medicine affecting immune outcomes. Immunoglobulin A had the strongest scientific evidence for positive effects from mind-body medicine. Issues for mind-body medicine studies with immune outcomes are discussed and recommendations are made to help improve future clinical trials.

  6. Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function.

    PubMed

    Lenz, Kathryn M; Nelson, Lars H

    2018-01-01

    Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

  7. A Behavioral Systems Analysis of Behavior Analysis as a Scientific System

    ERIC Educational Resources Information Center

    Hayes, Linda J.; Dubuque, Erick M.; Fryling, Mitch J.; Pritchard, Joshua K.

    2009-01-01

    Behavioral systems analyses typically address organizational problems in business and industry. However, to the extent that a behavioral system is an entity comprised of interdependent elements formed by individuals interacting toward a common goal, a scientific enterprise constitutes a behavioral system to which a behavioral systems analysis may…

  8. The Interplay between the Intestinal Microbiota and the Immune System

    PubMed Central

    Lei, Yuk Man Kevin; Nair, Lekha; Alegre, Maria-Luisa

    2015-01-01

    Summary The relationship between commensal microbes and their hosts has been studied for many years. Commensal microorganisms are known to have a significant role in regulating the physiology of their hosts and preventing pathogenic infections while the hosts’ immune system is important in determining the composition of the microbiota. More recently, specific effects of the intestinal microbiota on the local and distal immune systems have been uncovered with important consequences for health and disease, and alterations in intestinal microbial composition has been associated with various disease states. Here, we will review the current understanding of the microbiota/immune system crosstalk, highlight the clinical consequences of changes in the microbiota and consider how to harness this symbiotic relationship to improve public health. PMID:25481240

  9. [THE SYSTEMIC IMMUNITY CELLULAR LINK REACTION IN PATIENTS WITH TRAUMATIC ILLNESS].

    PubMed

    Plehutsa, I M; Sydorchuk, R I; Plehutsa, O M

    2015-01-01

    The effect of trauma on parameters of cellular immunity changes is studied. The study includes 52 patients with various forms of traumatic illness, aged 18-69 years (37.91-4.28). The control group consisted of 16 patients who underwent routine surgery not related to the pathology of musculoskeletal system. All patients of the main group were divided into 3 groups according to severity of the condition. Analysis of parameters of cellular link of immune system was performed by defining subpopulations of T-lymphocytes in indirect immunofluorescence method using a panel of monoclonal antibodies for CD3, CD4, CD8, CD22 lymphocytes' receptors and calculation of integrated indicators. The highest expression (immune disorders of II-III grades) of changes of cellular immunity observed in patients with severe traumatic: illness (expand clinical picture). Surgical intervention, even without traumatic injury significantly impact cellular immunity, but in patients with traumatic illness immunity violation were significantly higher than in comparison groups patients except immunoregulatory index.

  10. Accelerated aging versus rejuvenation of the immune system in heterochronic parabiosis.

    PubMed

    Pishel, Iryna; Shytikov, Dmytro; Orlova, Tatiana; Peregudov, Alex; Artyuhov, Igor; Butenko, Gennadij

    2012-04-01

    The emergence of immune disorders in aging is explained by many factors, including thymus dysfunction, decrease in the proportion and function of naïve T cells, and so forth. There are several approaches to preventing these changes, such as thymus rejuvenation, stem cells recovery, modulation of hormone production, and others. Our investigations of heterochronic parabiosis have shown that benefits of a young immune system, e.g., actively working thymus and regular migration of young hematopoietic stem cells between parabiotic partners, appeared unable to restore the immune system of the old partner. At the same time, we have established a progressive immune impairment in the young heterochronic partners. The mechanism of age changes in the immune system in this model, which may lead to reduced life expectancy, has not been fully understood. The first age-related manifestation in the young partners observed 3 weeks after the surgery was a dramatic increase of CD8(+)44(+) cells population in the spleen. A detailed analysis of further changes revealed a progressive decline of most immunological functions observable for up to 3 months after the surgery. This article reviews possible mechanisms of induction of age-related changes in the immune system of young heterochronic partners. The data obtained suggest the existence of certain factors in the old organisms that trigger aging, thus preventing the rejuvenation process.

  11. [The role of immune system in the control of cancer development and growth].

    PubMed

    Sütő, Gábor

    2016-06-01

    The role of immune system is the maintenace of the integritiy of the living organism. The elements of the immune system are connected by several ways forming a complex biological network. This network senses the changes of the inner and outer environment and works out the most effective response against infections and tumors. Dysfunction of the immune system leads to the development of cancer development and chronic inflammatory diseases. Modulation of the checkpoints of the immune system opened new perspecitves in the treatment of rheumatological and oncological diseases as well. Beside the potent antiinflammatory activity, new therapies are able to stimulate anticancer activity of the immune system. The result of these recent developments is a better outcome of malignant diseases, which had an unfavorable outcome in the past. Orv. Hetil., 2016, 157(Suppl. 2), 3-8.

  12. Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders

    PubMed Central

    Saviano, A.; Newton, E. E.; Serricchio, M. L.; Dal Lago, A. A.

    2018-01-01

    Gut microbiota is key to the development and modulation of the mucosal immune system. It plays a central role in several physiological functions, in the modulation of inflammatory signaling and in the protection against infections. In healthy states, there is a perfect balance between commensal and pathogens, and microbiota and the immune system interact to maintain gut homeostasis. The alteration of such balance, called dysbiosis, determines an intestinal bacterial overgrowth which leads to the disruption of the intestinal barrier with systemic translocation of pathogens. The pancreas does not possess its own microbiota, and it is believed that inflammatory and neoplastic processes affecting the gland may be linked to intestinal dysbiosis. Increasing research evidence testifies a correlation between intestinal dysbiosis and various pancreatic disorders, but it remains unclear whether dysbiosis is the cause or an effect. The analysis of specific alterations in the microbiome profile may permit to develop novel tools for the early detection of several pancreatic disorders, utilizing samples, such as blood, saliva, and stools. Future studies will have to elucidate the mechanisms by which gut microbiota is modulated and how it tunes the immune system, in order to be able to develop innovative treatment strategies for pancreatic disorders. PMID:29563853

  13. The neonate versus adult mammalian immune system in cardiac repair and regeneration.

    PubMed

    Sattler, Susanne; Rosenthal, Nadia

    2016-07-01

    The immune system is a crucial player in tissue homeostasis and wound healing. A sophisticated cascade of events triggered upon injury ensures protection from infection and initiates and orchestrates healing. While the neonatal mammal can readily regenerate damaged tissues, adult regenerative capacity is limited to specific tissue types, and in organs such as the heart, adult wound healing results in fibrotic repair and loss of function. Growing evidence suggests that the immune system greatly influences the balance between regeneration and fibrotic repair. The neonate mammalian immune system has impaired pro-inflammatory function, is prone to T-helper type 2 responses and has an immature adaptive immune system skewed towards regulatory T cells. While these characteristics make infants susceptible to infection and prone to allergies, it may also provide an immunological environment permissive of regeneration. In this review we will give a comprehensive overview of the immune cells involved in healing and regeneration of the heart and explore differences between the adult and neonate immune system that may explain differences in regenerative ability. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Why AIDS? The Mystery of How HIV Attacks the Immune System.

    ERIC Educational Resources Information Center

    Christensen, Damaris

    1999-01-01

    Reviews differing theories surrounding the mystery of how human immunodeficiency virus (HIV) attacks the immune system. Claims that understanding how HIV triggers immune-cell depletion may enable researchers to block its effects. New knowledge could reveal strategies for acquired immune deficiency syndrome (AIDS) therapies that go beyond the drugs…

  15. The Immune Phenotype of Three Drosophila Leukemia Models.

    PubMed

    Arefin, Badrul; Kunc, Martin; Krautz, Robert; Theopold, Ulrich

    2017-07-05

    Many leukemia patients suffer from dysregulation of their immune system, making them more susceptible to infections and leading to general weakening (cachexia). Both adaptive and innate immunity are affected. The fruit fly Drosophila melanogaster has an innate immune system, including cells of the myeloid lineage (hemocytes). To study Drosophila immunity and physiology during leukemia, we established three models by driving expression of a dominant-active version of the Ras oncogene ( Ras V12 ) alone or combined with knockdowns of tumor suppressors in Drosophila hemocytes. Our results show that phagocytosis, hemocyte migration to wound sites, wound sealing, and survival upon bacterial infection of leukemic lines are similar to wild type. We find that in all leukemic models the two major immune pathways (Toll and Imd) are dysregulated. Toll-dependent signaling is activated to comparable extents as after wounding wild-type larvae, leading to a proinflammatory status. In contrast, Imd signaling is suppressed. Finally, we notice that adult tissue formation is blocked and degradation of cell masses during metamorphosis of leukemic lines, which is akin to the state of cancer-dependent cachexia. To further analyze the immune competence of leukemic lines, we used a natural infection model that involves insect-pathogenic nematodes. We identified two leukemic lines that were sensitive to nematode infections. Further characterization demonstrates that despite the absence of behavioral abnormalities at the larval stage, leukemic larvae show reduced locomotion in the presence of nematodes. Taken together, this work establishes new Drosophila models to study the physiological, immunological, and behavioral consequences of various forms of leukemia. Copyright © 2017 Arefin et al.

  16. Influence of Melatonin on the Immune System of Fish: A Review

    PubMed Central

    Esteban, M. Ángeles; Cuesta, Alberto; Chaves-Pozo, Elena; Meseguer, José

    2013-01-01

    Endocrine-immune system interactions have been widely demonstrated in mammals, whereas in fish, these relationships remain unclear. Of the organs that constitute the endocrine system, the pineal gland and its secretory product melatonin act in the synchronization of daily and seasonal rhythms in most vertebrates, including fish. Seasonal differences in immunocompetence and disease prevalence have been well documented in humans. Seasonality also strongly influences the life history of fish by controlling the timing of physiological events, such as reproduction, food intake, locomotor activity, and growth performance. Apart from its synchronizing capabilities, the role of melatonin in physiological processes in fish is not thoroughly understood. The purpose of this review is to summarize current studies on the effects of melatonin on the fish immune system. These studies suggest that melatonin represents an important component of fish endocrine-immune system interactions. The elucidation of the defense mechanisms of fish will facilitate the development of health management tools to support the growing finfish aquaculture industry as well as address questions concerning the origins and evolution of the immune system in vertebrates. PMID:23579958

  17. Influence of melatonin on the immune system of fish: a review.

    PubMed

    Esteban, M Ángeles; Cuesta, Alberto; Chaves-Pozo, Elena; Meseguer, José

    2013-04-11

    Endocrine-immune system interactions have been widely demonstrated in mammals, whereas in fish, these relationships remain unclear. Of the organs that constitute the endocrine system, the pineal gland and its secretory product melatonin act in the synchronization of daily and seasonal rhythms in most vertebrates, including fish. Seasonal differences in immunocompetence and disease prevalence have been well documented in humans. Seasonality also strongly influences the life history of fish by controlling the timing of physiological events, such as reproduction, food intake, locomotor activity, and growth performance. Apart from its synchronizing capabilities, the role of melatonin in physiological processes in fish is not thoroughly understood. The purpose of this review is to summarize current studies on the effects of melatonin on the fish immune system. These studies suggest that melatonin represents an important component of fish endocrine-immune system interactions. The elucidation of the defense mechanisms of fish will facilitate the development of health management tools to support the growing finfish aquaculture industry as well as address questions concerning the origins and evolution of the immune system in vertebrates.

  18. Osteoimmunology: The Conceptual Framework Unifying the Immune and Skeletal Systems.

    PubMed

    Okamoto, Kazuo; Nakashima, Tomoki; Shinohara, Masahiro; Negishi-Koga, Takako; Komatsu, Noriko; Terashima, Asuka; Sawa, Shinichiro; Nitta, Takeshi; Takayanagi, Hiroshi

    2017-10-01

    The immune and skeletal systems share a variety of molecules, including cytokines, chemokines, hormones, receptors, and transcription factors. Bone cells interact with immune cells under physiological and pathological conditions. Osteoimmunology was created as a new interdisciplinary field in large part to highlight the shared molecules and reciprocal interactions between the two systems in both heath and disease. Receptor activator of NF-κB ligand (RANKL) plays an essential role not only in the development of immune organs and bones, but also in autoimmune diseases affecting bone, thus effectively comprising the molecule that links the two systems. Here we review the function, gene regulation, and signal transduction of osteoimmune molecules, including RANKL, in the context of osteoclastogenesis as well as multiple other regulatory functions. Osteoimmunology has become indispensable for understanding the pathogenesis of a number of diseases such as rheumatoid arthritis (RA). We review the various osteoimmune pathologies, including the bone destruction in RA, in which pathogenic helper T cell subsets [such as IL-17-expressing helper T (Th17) cells] induce bone erosion through aberrant RANKL expression. We also focus on cellular interactions and the identification of the communication factors in the bone marrow, discussing the contribution of bone cells to the maintenance and regulation of hematopoietic stem and progenitors cells. Thus the time has come for a basic reappraisal of the framework for understanding both the immune and bone systems. The concept of a unified osteoimmune system will be absolutely indispensable for basic and translational approaches to diseases related to bone and/or the immune system. Copyright © 2017 the American Physiological Society.

  19. Geometric Distribution-Based Readers Scheduling Optimization Algorithm Using Artificial Immune System.

    PubMed

    Duan, Litian; Wang, Zizhong John; Duan, Fu

    2016-11-16

    In the multiple-reader environment (MRE) of radio frequency identification (RFID) system, multiple readers are often scheduled to interrogate the randomized tags via operating at different time slots or frequency channels to decrease the signal interferences. Based on this, a Geometric Distribution-based Multiple-reader Scheduling Optimization Algorithm using Artificial Immune System (GD-MRSOA-AIS) is proposed to fairly and optimally schedule the readers operating from the viewpoint of resource allocations. GD-MRSOA-AIS is composed of two parts, where a geometric distribution function combined with the fairness consideration is first introduced to generate the feasible scheduling schemes for reader operation. After that, artificial immune system (including immune clone, immune mutation and immune suppression) quickly optimize these feasible ones as the optimal scheduling scheme to ensure that readers are fairly operating with larger effective interrogation range and lower interferences. Compared with the state-of-the-art algorithm, the simulation results indicate that GD-MRSOA-AIS could efficiently schedules the multiple readers operating with a fairer resource allocation scheme, performing in larger effective interrogation range.

  20. Geometric Distribution-Based Readers Scheduling Optimization Algorithm Using Artificial Immune System

    PubMed Central

    Duan, Litian; Wang, Zizhong John; Duan, Fu

    2016-01-01

    In the multiple-reader environment (MRE) of radio frequency identification (RFID) system, multiple readers are often scheduled to interrogate the randomized tags via operating at different time slots or frequency channels to decrease the signal interferences. Based on this, a Geometric Distribution-based Multiple-reader Scheduling Optimization Algorithm using Artificial Immune System (GD-MRSOA-AIS) is proposed to fairly and optimally schedule the readers operating from the viewpoint of resource allocations. GD-MRSOA-AIS is composed of two parts, where a geometric distribution function combined with the fairness consideration is first introduced to generate the feasible scheduling schemes for reader operation. After that, artificial immune system (including immune clone, immune mutation and immune suppression) quickly optimize these feasible ones as the optimal scheduling scheme to ensure that readers are fairly operating with larger effective interrogation range and lower interferences. Compared with the state-of-the-art algorithm, the simulation results indicate that GD-MRSOA-AIS could efficiently schedules the multiple readers operating with a fairer resource allocation scheme, performing in larger effective interrogation range. PMID:27854342

  1. Leptin in the interplay of inflammation, metabolism and immune system disorders.

    PubMed

    Abella, Vanessa; Scotece, Morena; Conde, Javier; Pino, Jesús; Gonzalez-Gay, Miguel Angel; Gómez-Reino, Juan J; Mera, Antonio; Lago, Francisca; Gómez, Rodolfo; Gualillo, Oreste

    2017-02-01

    Leptin is one of the most relevant factors secreted by adipose tissue and the forerunner of a class of molecules collectively called adipokines. Initially discovered in 1994, its crucial role as a central regulator in energy homeostasis has been largely described during the past 20 years. Once secreted into the circulation, leptin reaches the central and peripheral nervous systems and acts by binding and activating the long form of leptin receptor (LEPR), regulating appetite and food intake, bone mass, basal metabolism, reproductive function and insulin secretion, among other processes. Research on the regulation of different adipose tissues has provided important insights into the intricate network that links nutrition, metabolism and immune homeostasis. The neuroendocrine and immune systems communicate bi-directionally through common ligands and receptors during stress responses and inflammation, and control cellular immune responses in several pathological situations including immune-inflammatory rheumatic diseases. This Review discusses the latest findings regarding the role of leptin in the immune system and metabolism, with particular emphasis on its effect on autoimmune and/or inflammatory rheumatic diseases, such as rheumatoid arthritis and osteoarthritis.

  2. Vaccines and the infant's immune system--what nurses need to know.

    PubMed

    Heurter, Helen; Langman, Eileen

    2005-01-01

    Vaccines prevent serious infections by stimulating the immune system to identify and destroy invading organisms rapidly before they have a chance to cause disease. Armed with the scientific facts to refute current misconceptions surrounding vaccines and the infant's immune system, nurses can provide parents with the answers they need.

  3. Organization of an optimal adaptive immune system

    NASA Astrophysics Data System (ADS)

    Walczak, Aleksandra; Mayer, Andreas; Balasubramanian, Vijay; Mora, Thierry

    The repertoire of lymphocyte receptors in the adaptive immune system protects organisms from a diverse set of pathogens. A well-adapted repertoire should be tuned to the pathogenic environment to reduce the cost of infections. I will discuss a general framework for predicting the optimal repertoire that minimizes the cost of infections contracted from a given distribution of pathogens. The theory predicts that the immune system will have more receptors for rare antigens than expected from the frequency of encounters and individuals exposed to the same infections will have sparse repertoires that are largely different, but nevertheless exploit cross-reactivity to provide the same coverage of antigens. I will show that the optimal repertoires can be reached by dynamics that describes the competitive binding of antigens by receptors, and selective amplification of stimulated receptors.

  4. [Impairment of the immune system caused by drugs].

    PubMed

    Pichler, W J

    1987-03-21

    The immune response and the ensuing inflammation relies on a complex interaction of cells and mediators. Various drugs can interfere with individual steps of the immune response, and in so doing they often imitate regulatory mechanisms of the immune system itself. The immunosuppressive effect of corticosteroids is based on changes in cell migration, reduced responsiveness of monocytes/macrophages to various stimuli and diminished production of interleukin-2. Cyclosporin A appears to block prolactin binding to prolactin receptors on lymphocytes, thus interfering with the immunostimulatory effect of prolactin. It also appears to have a Calmodulin antagonism and might thus block lymphokine production. Anticoagulants may block delayed type hypersensitivity reactions, since activation of the coagulation cascade is involved in this type of immune reaction. Attempts to use calcium channel blockers as immunosuppressive agents, or to take advantage of the immunoregulatory effects of adrenergic substances/blockers or other neurotransmitters, are of experimental value only.

  5. Role of the immune system in cardiac tissue damage and repair following myocardial infarction.

    PubMed

    Saparov, Arman; Ogay, Vyacheslav; Nurgozhin, Talgat; Chen, William C W; Mansurov, Nurlan; Issabekova, Assel; Zhakupova, Jamilya

    2017-09-01

    The immune system plays a crucial role in the initiation, development, and resolution of inflammation following myocardial infarction (MI). The lack of oxygen and nutrients causes the death of cardiomyocytes and leads to the exposure of danger-associated molecular patterns that are recognized by the immune system to initiate inflammation. At the initial stage of post-MI inflammation, the immune system further damages cardiac tissue to clear cell debris. The excessive production of reactive oxygen species (ROS) by immune cells and the inability of the anti-oxidant system to neutralize ROS cause oxidative stress that further aggravates inflammation. On the other hand, the cells of both innate and adaptive immune system and their secreted factors are critically instrumental in the very dynamic and complex processes of regulating inflammation and mediating cardiac repair. It is important to decipher the balance between detrimental and beneficial effects of the immune system in MI. This enables us to identify better therapeutic targets for reducing the infarct size, sustaining the cardiac function, and minimizing the likelihood of heart failure. This review discusses the role of both innate and adaptive immune systems in cardiac tissue damage and repair in experimental models of MI.

  6. Physical Theory of the Competition that Allows HIV to Escape from the Immune System

    NASA Astrophysics Data System (ADS)

    Wang, Guanyu; Deem, Michael W.

    2006-11-01

    Competition within the immune system may degrade immune control of viral infections. We formalize the evolution that occurs in both HIV-1 and the immune system quasispecies. Inclusion of competition in the immune system leads to a novel balance between the immune response and HIV-1, in which the eventual outcome is HIV-1 escape rather than control. The analytical model reproduces the three stages of HIV-1 infection. We propose a vaccine regimen that may be able to reduce competition between T cells, potentially eliminating the third stage of HIV-1.

  7. Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy

    PubMed Central

    Fragiadakis, Gabriela K.; Baca, Quentin J.; Gherardini, Pier Federico; Ganio, Edward A.; Gaudilliere, Dyani K.; Tingle, Martha; Lancero, Hope L.; McNeil, Leslie S.; Spitzer, Matthew H.; Wong, Ronald J.; Shaw, Gary M.; Darmstadt, Gary L.; Sylvester, Karl G.; Winn, Virginia D.; Carvalho, Brendan; Lewis, David B.; Stevenson, David K.; Nolan, Garry P.; Aghaeepour, Nima; Angst, Martin S.; Gaudilliere, Brice L.

    2016-01-01

    Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus are critical for the maintenance of pregnancy and the delivery of an immuno-competent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyper-responsiveness of CD4+ and CD8+ T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPKAPK2, rpS6, and CREB phosphorylation in fetal Tbet+CD4+ T cells, CD8+ T cells, B cells and CD56loCD16+ NK cells and decreased ERK1/2, MAPKAPK2, and STAT1 phosphorylation in fetal intermediate and non-classical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes. PMID:27793998

  8. Individual differences in maternal response to immune challenge predict offspring behavior: Contribution of environmental factors

    PubMed Central

    Bronson, Stefanie L.; Ahlbrand, Rebecca; Horn, Paul S.; Kern, Joseph R.; Richtand, Neil M.

    2011-01-01

    Maternal infection during pregnancy elevates risk for schizophrenia and related disorders in offspring. Converging evidence suggests the maternal inflammatory response mediates the interaction between maternal infection, altered brain development, and behavioral outcome. The extent to which individual differences in the maternal response to immune challenge influence the development of these abnormalities is unknown. The present study investigated the impact of individual differences in maternal response to the viral mimic polyinosinic:polycytidylic acid (poly I:C) on offspring behavior. We observed significant variability in body weight alterations of pregnant rats induced by administration of poly I:C on gestational day 14. Furthermore, the presence or absence of maternal weight loss predicted MK-801 and amphetamine stimulated locomotor abnormalities in offspring. MK-801 stimulated locomotion was altered in offspring of all poly I:C treated dams; however, the presence or absence of maternal weight loss resulted in decreased and modestly increased locomotion, respectively. Adult offspring of poly I:C treated dams that lost weight exhibited significantly decreased amphetamine stimulated locomotion, while offspring of poly I:C treated dams without weight loss performed similarly to vehicle controls. Social isolation and increased maternal age predicted weight loss in response to poly I:C but not vehicle injection. In combination, these data identify environmental factors associated with the maternal response to immune challenge and functional outcome of offspring exposed to maternal immune activation. PMID:21255612

  9. Complement System Part II: Role in Immunity

    PubMed Central

    Merle, Nicolas S.; Noe, Remi; Halbwachs-Mecarelli, Lise; Fremeaux-Bacchi, Veronique; Roumenina, Lubka T.

    2015-01-01

    The complement system has been considered for a long time as a simple lytic cascade, aimed to kill bacteria infecting the host organism. Nowadays, this vision has changed and it is well accepted that complement is a complex innate immune surveillance system, playing a key role in host homeostasis, inflammation, and in the defense against pathogens. This review discusses recent advances in the understanding of the role of complement in physiology and pathology. It starts with a description of complement contribution to the normal physiology (homeostasis) of a healthy organism, including the silent clearance of apoptotic cells and maintenance of cell survival. In pathology, complement can be a friend or a foe. It acts as a friend in the defense against pathogens, by inducing opsonization and a direct killing by C5b–9 membrane attack complex and by triggering inflammatory responses with the anaphylatoxins C3a and C5a. Opsonization plays also a major role in the mounting of an adaptive immune response, involving antigen presenting cells, T-, and B-lymphocytes. Nevertheless, it can be also an enemy, when pathogens hijack complement regulators to protect themselves from the immune system. Inadequate complement activation becomes a disease cause, as in atypical hemolytic uremic syndrome, C3 glomerulopathies, and systemic lupus erythematosus. Age-related macular degeneration and cancer will be described as examples showing that complement contributes to a large variety of conditions, far exceeding the classical examples of diseases associated with complement deficiencies. Finally, we discuss complement as a therapeutic target. PMID:26074922

  10. Ecosystem and immune systems: Hierarchial response provides resilience against invasions

    USGS Publications Warehouse

    Allen, Craig R.

    2001-01-01

    Janssen (2001) provides the stimulus for thoughtful comparison and consideration of the ranges of responses exhibited by immune systems and ecological systems in the face of perturbations such as biological invasions. It may indeed be informative to consider the similarities of the responses to invasions exhibited by immune systems and ecological systems. Clearly, both types of systems share a general organizational structure with all other complex hierarchical systems. Their organization provides these systems with resilience. However, when describing the response of ecological-economic systems to invasions, Janssen emphasizes the human-economic response. I would like to expand on his comparison by focusing on how resilience is maintained in complex systems under the threat of invasion.

  11. The role of the immune system in central nervous system plasticity after acute injury.

    PubMed

    Peruzzotti-Jametti, Luca; Donegá, Matteo; Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano

    2014-12-26

    Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. State-Level Immunization Information Systems: Potential for Childhood Immunization Data Linkages.

    PubMed

    Fuller, Jill E; Walter, Emmanuel B; Dole, Nancy; O'Hara, Richard; Herring, Amy H; Durkin, Maureen S; Specker, Bonny; Wey, Betty

    2017-01-01

    Objectives Sources of immunization data include state registries or immunization information systems (IIS), medical records, and surveys. Little is known about the quality of these data sources or the feasibility of using IIS data for research. We assessed the feasibility of collecting immunization information for a national children's health study by accessing existing IIS data and comparing the completeness of these data against medical record abstractions (MRA) and parent report. Staff time needed to obtain IIS and MRA data was assessed. Methods We administered a questionnaire to state-level IIS representatives to ascertain availability and completeness of their data for research and gather information about data formats. We evaluated quality of data from IIS, medical records, and reports from parents of 119 National Children's Study participants at three locations. Results IIS data were comparable to MRA data and both were more complete than parental report. Agreement between IIS and MRA data was greater than between parental report and MRA, suggesting IIS and MRA are better sources than parental report. Obtaining IIS data took less staff time than chart review, making IIS data linkage for research a preferred choice. Conclusions IIS survey results indicate data can be obtained by researchers using data linkages. IIS are an accessible and feasible child immunization information source and these registries reduce reliance on parental report or medical record abstraction. Researchers seeking to link IIS data with large multi-site studies should consider acquiring IIS data, but may need strategies to overcome barriers to data completeness and linkage.

  13. [IMMUNE SYSTEM INTERNSHIP WITH SYMBIOTIC MICROORGANISMS IN GNOTOBIOTIC ANIMAL'S INTESTINUM ILEUM].

    PubMed

    Kochlamasashvili, B; Gogiashvili, L; Jandieri, K

    2017-11-01

    Structures, responsible for acceptive (comensaling relation) and protective (pathogenic defense) immunity, were studied and compared in small intestine - to ileum mucosa. Data shown, that main application of the both domains of immune system is to support the correlation between body and foreign microbes, but they response is different. Most significant differences are as follows: in acceptive reactions presented only in aseptic animals - gnotobionts, inflammatory changes absent, so immune reaction complex develops into physiological condition. Symbiotic reactions release in mucosa epithelial cells, also in cells, responsible for adaptive and congenital immune reactivity. Thus, acceptive immune reactions contribute symbiotic biocenosis versus elimination; which is function of protective immunity.

  14. Immunization information system progress--United States, 2004.

    PubMed

    2005-11-18

    One of the national health objectives for 2010 is to increase to at least 95% the proportion of children aged <6 years who participate in fully operational, population-based immunization registries (objective no. 14-26). Immunization registries are confidential, computerized information systems that collect and consolidate vaccination data from multiple health-care providers, generate reminder and recall notifications, and assess vaccination coverage within a defined geographic area. A registry with added capabilities, such as vaccine management, adverse event reporting, lifespan vaccination histories, and linkages with electronic data sources, is called an immunization information system (IIS). This report summarizes data from CDC's 2004 IIS Annual Report, a survey of 56 grantees in 50 states, five cities, and the District of Columbia (DC) that receive funding under section 317b of the Public Health Service Act. The findings indicate that approximately 48% of U.S. children aged <6 years participated in an IIS. Moreover, 76% of public vaccination provider sites and 39% of private vaccination provider sites submitted immunization data to an IIS during the last 6 months of 2004. Overcoming challenges and barriers to increasing the number of provider sites and the percentage of children aged <6 years participating in an IIS is critical to achieving the national health objective. CDC has developed a plan of action to address those challenges. Major components of the plan include, but are not limited to, a multiyear IIS business plan for each grantee and enhanced technical assistance to grantees with unresolved challenges.

  15. Abnormal Epigenetic Regulation of Immune System during Aging.

    PubMed

    Jasiulionis, Miriam G

    2018-01-01

    Epigenetics refers to the study of mechanisms controlling the chromatin structure, which has fundamental role in the regulation of gene expression and genome stability. Epigenetic marks, such as DNA methylation and histone modifications, are established during embryonic development and epigenetic profiles are stably inherited during mitosis, ensuring cell differentiation and fate. Under the effect of intrinsic and extrinsic factors, such as metabolic profile, hormones, nutrition, drugs, smoke, and stress, epigenetic marks are actively modulated. In this sense, the lifestyle may affect significantly the epigenome, and as a result, the gene expression profile and cell function. Epigenetic alterations are a hallmark of aging and diseases, such as cancer. Among biological systems compromised with aging is the decline of immune response. Different regulators of immune response have their promoters and enhancers susceptible to the modulation by epigenetic marks, which is fundamental to the differentiation and function of immune cells. Consistent evidence has showed the regulation of innate immune cells, and T and B lymphocytes by epigenetic mechanisms. Therefore, age-dependent alterations in epigenetic marks may result in the decline of immune function and this might contribute to the increased incidence of diseases in old people. In order to maintain health, we need to better understand how to avoid epigenetic alterations related to immune aging. In this review, the contribution of epigenetic mechanisms to the loss of immune function during aging will be discussed, and the promise of new means of disease prevention and management will be pointed.

  16. Role of the immune system in regeneration and its dynamic interplay with adult stem cells.

    PubMed

    Abnave, Prasad; Ghigo, Eric

    2018-04-09

    The immune system plays an indispensable role in the process of tissue regeneration following damage as well as during homeostasis. Inflammation and immune cell recruitment are signs of early onset injury. At the wound site, immune cells not only help to clear debris but also secrete numerous signalling molecules that induce appropriate cell proliferation and differentiation programmes essential for successful regeneration. However, the immune system does not always perform a complementary role in regeneration and several reports have suggested that increased inflammation can inhibit the regeneration process. Successful regeneration requires a balanced immune cell response, with the recruitment of accurately polarised immune cells in an appropriate quantity. The regulatory interactions of the immune system with regeneration are not unidirectional. Stem cells, as key players in regeneration, can also modulate the immune system in several ways to facilitate regeneration. In this review, we will focus on recent research demonstrating the key role of immune system in the regeneration process as well as the immunomodulatory effects of stem cells. Finally, we propose that research investigating the interplay between the immune system and stem cells within highly regenerating animals can benefit the identification of the key interactions and molecules required for successful regeneration. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Protein phylogenies provide evidence of a radical discontinuity between arthropod and vertebrate immune systems.

    PubMed

    Hughes, A L

    1998-03-01

    Protein phylogenies were used to test the hypothesis that aspects of the innate immune system of vertebrates have been conserved since the last common ancestor of vertebrates and arthropods. The phylogeny of lysozymes showed evidence of conservation of function, but phylogenies of seven other protein families did not. Natural resistance-associated macrophage protein, nitric oxide synthetase, and serine protease families all showed a pattern of gene duplication within vertebrates after their divergence from arthropods, giving rise to immune system-expressed genes in vertebrates. Insect hemolin, a member of the immunoglobulin superfamily, was found not to be closely related to members of that family having an immune system role in vertebrates; rather, it appeared most closely related to both arthropod and vertebrate molecules expressed in the nervous system. Thus, hemolin seems to have evolved its role independently in insects, probably through duplication of a neuroglian-like ancestor. Furthermore, vertebrate immune system-expressed serpins, chitinases, and pentraxins were found to lack orthologous relationships with arthropod members of the same families also functioning in immunity. Therefore members of these families have evolved immune system functions independently in the two phyla. It is now widely recognized that the specific immune system of vertebrates has no counterpart in invertebrates; these phylogenetic analyses suggest that there is a similar evolutionary discontinuity with respect to innate immunity as well.

  18. Nonlinear response of the immune system to power-frequency magnetic fields.

    PubMed

    Marino, A A; Wolcott, R M; Chervenak, R; Jourd'Heuil, F; Nilsen, E; Frilot, C

    2000-09-01

    Studies of the effects of power-frequency electromagnetic fields (EMFs) on the immune and other body systems produced positive and negative results, and this pattern was usually interpreted to indicate the absence of real effects. However, if the biological effects of EMFs were governed by nonlinear laws, deterministic responses to fields could occur that were both real and inconsistent, thereby leading to both types of results. The hypothesis of real inconsistent effects due to EMFs was tested by exposing mice to 1 G, 60 Hz for 1-105 days and observing the effect on 20 immune parameters, using flow cytometry and functional assays. The data were evaluated by means of a novel statistical procedure that avoided averaging away oppositely directed changes in different animals, which we perceived to be the problem in some of the earlier EMF studies. The reliability of the procedure was shown using appropriate controls. In three independent experiments involving exposure for 21 or more days, the field altered lymphoid phenotype even though the changes in individual immune parameters were inconsistent. When the data were evaluated using traditional linear statistical methods, no significant difference in any immune parameter was found. We were able to mimic the results by sampling from known chaotic systems, suggesting that deterministic chaos could explain the effect of fields on the immune system. We conclude that exposure to power-frequency fields produced changes in the immune system that were both real and inconsistent.

  19. Exosomes and nanotubes: control of immune cell communication

    PubMed Central

    McCoy-Simandle, Kessler; Hanna, Samer J.; Cox, Dianne

    2015-01-01

    Cell-cell communication is critical to coordinate the activity and behavior of a multicellular organism. The cells of the immune system not only must communicate with similar cells, but also with many other cell types in the body. Therefore, the cells of the immune system have evolved multiple ways to communicate. Exosomes and tunneling nanotubes (TNTs) are two means of communication used by immune cells that contribute to immune functions. Exosomes are small membrane vesicles secreted by most cell types that can mediate intercellular communication and in the immune system they are proposed to play a role in antigen presentation and modulation of gene expression. TNTs are membranous structures that mediate direct cell-cell contact over several cell diameters in length (and possibly longer) and facilitate the interaction and/or the transfer of signals, material and other cellular organelles between connected cells. Recent studies have revealed additional, but sometimes conflicting, structural and functional features of both exosomes and TNTs. Despite the new and exciting information in exosome and TNT composition, origin and in vitro function, biologically significant functions are still being investigated and determined. In this review, we discuss the current field regarding exosomes and TNTs in immune cells providing evaluation and perspectives of the current literature. PMID:26704468

  20. The eye: A window to the soul of the immune system.

    PubMed

    Perez, V L; Saeed, A M; Tan, Y; Urbieta, M; Cruz-Guilloty, F

    2013-09-01

    The eye is considered as an immune privileged site, and with good reason. It has evolved a variety of molecular and cellular mechanisms that limit immune responses to preserve vision. For example, the cornea is mainly protected from autoimmunity by the lack of blood and lymphatic vessels, whereas the retina-blood barrier is maintained in an immunosuppressive state by the retinal pigment epithelium. However, there are several scenarios in which immune privilege is altered and the eye becomes susceptible to immune attack. In this review, we highlight the role of the immune system in two clinical conditions that affect the anterior and posterior segments of the eye: corneal transplantation and age-related macular degeneration. Interestingly, crosstalk between the innate and adaptive immune systems is critical in both acute and chronic inflammatory responses in the eye, with T cells playing a central role in combination with neutrophils and macrophages. In addition, we emphasize the advantage of using the eye as a model for in vivo longitudinal imaging of the immune system in action. Through this technique, it has been possible to identify functionally distinct intra-graft motility patterns of responding T cells, as well as the importance of chemokine signaling in situ for T cell activation. The detailed study of ocular autoimmunity could provide novel therapeutic strategies for blinding diseases while also providing more general information on acute versus chronic inflammation. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. A Large Scale Dynamical System Immune Network Modelwith Finite Connectivity

    NASA Astrophysics Data System (ADS)

    Uezu, T.; Kadono, C.; Hatchett, J.; Coolen, A. C. C.

    We study a model of an idiotypic immune network which was introduced by N. K. Jerne. It is known that in immune systems there generally exist several kinds of immune cells which can recognize any particular antigen. Taking this fact into account and assuming that each cell interacts with only a finite number of other cells, we analyze a large scale immune network via both numerical simulations and statistical mechanical methods, and show that the distribution of the concentrations of antibodies becomes non-trivial for a range of values of the strength of the interaction and the connectivity.

  2. Effects of LPS-induced immune activation prior to trauma exposure on PTSD-like symptoms in mice.

    PubMed

    Deslauriers, Jessica; van Wijngaarde, Myrthe; Geyer, Mark A; Powell, Susan; Risbrough, Victoria B

    2017-04-14

    The prevalence of posttraumatic stress disorder (PTSD) is high in the armed services, with a rate up to 20%. Multiple studies have associated markers of inflammatory signaling prior to trauma with increased risk of PTSD, suggesting a potential role of the immune system in the development of this psychiatric disorder. One question that arises is if "priming" the immune system before acute trauma alters the stress response and increases enduring effects of trauma. We investigated the time course of inflammatory response to predator stress, a robust stressor that induces enduring PTSD-like behaviors, and the modulation of these effects via prior immune activation with the bacterial endotoxin, lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) agonist. Mice exposed to predator stress exhibited decreased pro-/anti-inflammatory balance in the brain 6h after stress, suggesting that predator exposure acutely suppressed the immune system by increasing anti-inflammatory cytokines levels. Acute immune activation with LPS before a single predator stress did not alter the enduring avoidance behavior in stressed mice. Our findings suggest that acute inflammation, at least via TLR4 activation, is not sufficient to increase susceptibility for PTSD-like behaviors in this model. Future studies will examine if chronic inflammation is required to induce similar immune changes to those observed in PTSD patients in this model. Published by Elsevier B.V.

  3. The role of the immune system in neurofibromatosis type 1-associated nervous system tumors.

    PubMed

    Karmakar, Souvik; Reilly, Karlyne M

    2017-01-01

    With the recent development of new anticancer therapies targeting the immune system, it is important to understand which immune cell types and cytokines play critical roles in suppressing or promoting tumorigenesis. The role of mast cells in promoting neurofibroma growth in neurofibromatosis type 1 (NF1) patients was hypothesized decades ago. More recent experiments in mouse models have demonstrated the causal role of mast cells in neurofibroma development and of microglia in optic pathway glioma development. We review here what is known about the role of NF1 mutation in immune cell function and the role of immune cells in promoting tumorigenesis in NF1. We also review the therapies targeting immune cell pathways and their promise in NF1 tumors.

  4. How Ebola and Marburg viruses battle the immune system.

    PubMed

    Mohamadzadeh, Mansour; Chen, Lieping; Schmaljohn, Alan L

    2007-07-01

    The filoviruses Ebola and Marburg have emerged in the past decade from relative obscurity to serve now as archetypes for some of the more intriguing and daunting challenges posed by such agents. Public imagination is captured by deadly outbreaks of these viruses and reinforced by the specter of bioterrorism. As research on these agents has accelerated, it has been found increasingly that filoviruses use a combination of familiar and apparently new ways to baffle and battle the immune system. Filoviruses have provided thereby a new lens through which to examine the immune system itself.

  5. Adolescent fluoxetine treatment decreases the effects of neonatal immune activation on anxiety-like behavior in mice.

    PubMed

    Majidi-Zolbanin, Jafar; Azarfarin, Maryam; Samadi, Hanieh; Enayati, Mohsen; Salari, Ali-Akbar

    2013-08-01

    Experimental studies have shown conflicting effects of neonatal infection on anxiety-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis activity in adult rats. We investigated for the first time whether neonatal exposure to lipopolysaccharide (LPS) is associated with increased levels of anxiety-like behaviors in mice. Moreover, there have been several studies showing that adolescent fluoxetine (FLX) treatment can influence HPA axis development and prevent occurrence of psychiatric disorders induced by common early-life insults. In the present study, we also investigated the effects of adolescent FLX exposure following neonatal immune activation on anxiety-like behavior in mice. Neonatal mice were treated to LPS (50μg/kg) or saline on postnatal days (PND) 3 and 5, then male and female mice of both neonatal intervention groups received oral administration of FLX (5 and 10mg/kg/day) or water via regular drinking bottles during the adolescent period (PNDs 35-65). The results showed that postnatal immune challenge increased anxiety-like behavior in the open field, elevated plus-maze and light-dark box in adult mice (PND 90). Furthermore, the adolescent FLX treatment inhibited the anxiety-like behavior induced by neonatal infection in both sexes. However, this study indicates the negative effects of the FLX on normal behavioral symptoms in male control mice. Taken together, the current data provide experimental evidence that neonatal infection increases anxiety levels in male and female mice in adulthood. Additionally, the findings of this study support the hypothesis that an early pharmacological intervention with FLX may be an effective treatment for reducing the behavioral abnormalities induced by common early-life insults. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Triggering the adaptive immune system with commensal gut bacteria protects against insulin resistance and dysglycemia.

    PubMed

    Pomié, Céline; Blasco-Baque, Vincent; Klopp, Pascale; Nicolas, Simon; Waget, Aurélie; Loubières, Pascale; Azalbert, Vincent; Puel, Anthony; Lopez, Frédéric; Dray, Cédric; Valet, Philippe; Lelouvier, Benjamin; Servant, Florence; Courtney, Michael; Amar, Jacques; Burcelin, Rémy; Garidou, Lucile

    2016-06-01

    To demonstrate that glycemia and insulin resistance are controlled by a mechanism involving the adaptive immune system and gut microbiota crosstalk. We triggered the immune system with microbial extracts specifically from the intestinal ileum contents of HFD-diabetic mice by the process of immunization. 35 days later, immunized mice were fed a HFD for up to two months in order to challenge the development of metabolic features. The immune responses were quantified. Eventually, adoptive transfer of immune cells from the microbiota-immunized mice to naïve mice was performed to demonstrate the causality of the microbiota-stimulated adaptive immune system on the development of metabolic disease. The gut microbiota of the immunized HFD-fed mice was characterized in order to demonstrate whether the manipulation of the microbiota to immune system interaction reverses the causal deleterious effect of gut microbiota dysbiosis on metabolic disease. Subcutaneous injection (immunization procedure) of ileum microbial extracts prevented hyperglycemia and insulin resistance in a dose-dependent manner in response to a HFD. The immunization enhanced the proliferation of CD4 and CD8 T cells in lymphoid organs, also increased cytokine production and antibody secretion. As a mechanism explaining the metabolic improvement, the immunization procedure reversed gut microbiota dysbiosis. Finally, adoptive transfer of immune cells from immunized mice improved metabolic features in response to HFD. Glycemia and insulin sensitivity can be regulated by triggering the adaptive immunity to microbiota interaction. This reduces the gut microbiota dysbiosis induced by a fat-enriched diet.

  7. Dynamical properties of a tumor growth system in the presence of immunization and colored cross-correlated noises

    NASA Astrophysics Data System (ADS)

    Jia, Zheng-Lin; Mei, Dong-Cheng

    2010-05-01

    We investigate the effects of the noise parameters and immunization strength β on the dynamical properties of a tumor growth system with both immunization and colored cross-correlated noises. The analytical expressions for the associated relaxation time TC and the normalized correlation function C(s) are derived by means of the projection operator method. The results indicate that: (i) TC as a function of the multiplicative noise intensity α shows resonance-like behavior, i.e. the curves of TC versus α exhibit a single-peak structure and its peak position changes with increasing correlation strength between noises λ, the autocorrelation time of multiplicative noise τ1, the autocorrelation time of additive noise τ2 and the cross-correlation time τ3. This behavior can be understood in terms of the noise-enhanced stability effect and the influence of the memory effects on it. (ii) The increasing λ, τ1, τ2 and the additive noise intensity D slow down the fluctuation decay of the tumor population, whereas the increasing τ3 and β speed it up. (iii) C(s) increases as λ, τ1, τ2 and β increase, while it decreases with τ3 increasing. Our study shows that the effects of some noise parameters on tumor growth can be modified due to the presence of the immunization effect.

  8. Live Music Therapy as an Active Focus of Attention for Pain and Behavioral Symptoms of Distress During Pediatric Immunization.

    PubMed

    Sundar, Sumathy; Ramesh, Bhuvaneswari; Dixit, Priyanka B; Venkatesh, Soma; Das, Prarthana; Gunasekaran, Dhandapany

    2016-07-01

    A total of 100 children coming for routine immunization to pediatric outpatient department were included and were divided into experiment (n = 50) and control (n = 50) groups. Experiment group received live music therapy during immunization procedure. Control group received no intervention. The Modified Behavior Pain Scale (MBPS), 10-point pain levels, and 10-point distress levels were documented by parents. Duration of crying was recorded by investigators. Pre- and postimmunization blood pressures and heart rates of parents holding the children were also measured and recorded by investigators. Independent and paired t tests were used for analysis. All 3 domains of the Modified Behavior Pain Scale and duration of crying showed significant improvement (P < .05) in the experiment group. Pain and distress levels also showed statistically nonsignificant improvement in experiment group. Blood pressure and heart rate of parents showed no difference. Music therapy could be helpful to children, parents, and health care providers by reducing discomfort of the child during pediatric immunization. © The Author(s) 2015.

  9. Liver-inherent immune system: its role in blood-stage malaria

    PubMed Central

    Wunderlich, Frank; Al-Quraishy, Saleh; Dkhil, Mohamed A.

    2014-01-01

    The liver is well known as that organ which is obligately required for the intrahepatocyte development of the pre-erythrocytic stages of the malaria-causative agent Plasmodium. However, largely neglected is the fact that the liver is also a central player of the host defense against the morbidity- and mortality-causing blood stages of the malaria parasites. Indeed, the liver is equipped with a unique immune system that acts locally, however, with systemic impact. Its main “antipodal” functions are to recognize and to generate effective immunoreactivity against pathogens on the one hand, and to generate tolerance to avoid immunoreactivity with “self” and harmless substances as dietary compounds on the other hand. This review provides an introductory survey of the liver-inherent immune system: its pathogen recognition receptors including Toll-like receptors (TLRs) and its major cell constituents with their different facilities to fight and eliminate pathogens. Then, evidence is presented that the liver is also an essential organ to overcome blood-stage malaria. Finally, we discuss effector responses of the liver-inherent immune system directed against blood-stage malaria: activation of TLRs, acute phase response, phagocytic activity, cytokine-mediated pro- and anti-inflammatory responses, generation of “protective” autoimmunity by extrathymic T cells and B-1 cells, and T cell-mediated repair of liver injuries mainly produced by malaria-induced overreactions of the liver-inherent immune system. PMID:25408684

  10. Effects of psycho-behavioral interventions on immune functioning in cancer patients: a systematic review.

    PubMed

    Tong, Guixian; Geng, Qingqing; Cheng, Jing; Chai, Jing; Xia, Yi; Feng, Rui; Zhang, Lu; Wang, Debin

    2014-01-01

    This study aimed at summarizing evidence about effects of psycho-behavioral interventions (PBIs) on immune responses among cancer patients and analyzing quality of published studies so as to inform future researches. Literature retrieval utilized both highly inclusive algorithms searching randomized controlled studies published in English and Chinese and manual searching of eligible studies from references of relevant review papers. Two researchers examined the articles selected separately and extracted the information using a pre-designed form for soliciting data about the trials (e.g., sample size, disease status, intervention, immune responses) and quality ratings of the studies. Both narrative descriptions and meta-analysis (via Review manager 5) were used synthesizing the effects of PBIs on immune responses among cancer patients and state of art of the researches in this area. Seventy-six RCTs met inclusion criteria. PBIs implemented were divided into three major categories including psychological state adjustment, physical activity and dietary modification. Immune indicators measured included CD4+ cells, CD8+ cells, CD4/CDC8+ ratio, CD3+ cells, NK cell activity, etc. Effects of PBIs on immune responses documented in individual papers were mixed and pooled analysis of CD4+ cells, CD4+/CD8+ ratio, CD3+ cells, NKCA, IgG, IgM and IL-2 showed modest effects. However, there were huge discrepancies in intervention effects between studies published in English and Chinese and the results should be interpreted with caution. Besides, most studies suffer from some quality flaws concerning blinding, randomization procedures, compliance, attrition and intention-to-treat analyses, etc. Although there are considerable evidences of PBI effects on some immune indicators, the effect sizes are modest and it is still premature to conclude whether PBIs have effects on immune functions among cancer patients. There is a clear need for much more rigorous efforts in this area

  11. Mapping the Fetomaternal Peripheral Immune System at Term Pregnancy.

    PubMed

    Fragiadakis, Gabriela K; Baca, Quentin J; Gherardini, Pier Federico; Ganio, Edward A; Gaudilliere, Dyani K; Tingle, Martha; Lancero, Hope L; McNeil, Leslie S; Spitzer, Matthew H; Wong, Ronald J; Shaw, Gary M; Darmstadt, Gary L; Sylvester, Karl G; Winn, Virginia D; Carvalho, Brendan; Lewis, David B; Stevenson, David K; Nolan, Garry P; Aghaeepour, Nima; Angst, Martin S; Gaudilliere, Brice L

    2016-12-01

    Preterm labor and infections are the leading causes of neonatal deaths worldwide. During pregnancy, immunological cross talk between the mother and her fetus is critical for the maintenance of pregnancy and the delivery of an immunocompetent neonate. A precise understanding of healthy fetomaternal immunity is the important first step to identifying dysregulated immune mechanisms driving adverse maternal or neonatal outcomes. This study combined single-cell mass cytometry of paired peripheral and umbilical cord blood samples from mothers and their neonates with a graphical approach developed for the visualization of high-dimensional data to provide a high-resolution reference map of the cellular composition and functional organization of the healthy fetal and maternal immune systems at birth. The approach enabled mapping of known phenotypical and functional characteristics of fetal immunity (including the functional hyperresponsiveness of CD4 + and CD8 + T cells and the global blunting of innate immune responses). It also allowed discovery of new properties that distinguish the fetal and maternal immune systems. For example, examination of paired samples revealed differences in endogenous signaling tone that are unique to a mother and her offspring, including increased ERK1/2, MAPK-activated protein kinase 2, rpS6, and CREB phosphorylation in fetal Tbet + CD4 + T cells, CD8 + T cells, B cells, and CD56 lo CD16 + NK cells and decreased ERK1/2, MAPK-activated protein kinase 2, and STAT1 phosphorylation in fetal intermediate and nonclassical monocytes. This highly interactive functional map of healthy fetomaternal immunity builds the core reference for a growing data repository that will allow inferring deviations from normal associated with adverse maternal and neonatal outcomes. Copyright © 2016 by The American Association of Immunologists, Inc.

  12. Inorganic nanoparticles and the immune system: detection, selective activation and tolerance

    NASA Astrophysics Data System (ADS)

    Bastús, Neus G.; Sánchez-Tilló, Ester; Pujals, Silvia; Comenge, Joan; Giralt, Ernest; Celada, Antonio; Lloberas, Jorge; Puntes, Victor F.

    2012-03-01

    The immune system is the responsible for body integrity and prevention of external invasion. On one side, nanoparticles are no triggers that the immune system is prepared to detect, on the other side it is known that foreign bodies, not only bacteria, viruses and parasites, but also inorganic matter, can cause various pathologies such as silicosis, asbestosis or inflammatory reactions. Therefore, nanoparticles entering the body, after interaction with proteins, will be either recognized as self-agents or detected by the immune system, encompassing immunostimulation or immunosuppression responses. The nature of these interactions seems to be dictated not specially by the composition of the material but by modifications of NP coating (composition, surface charge and structure). Herein, we explore the use of gold nanoparticles as substrates to carry multifunctional ligands to manipulate the immune system in a controlled manner, from undetection to immunostimulation. Murine bone marrow macrophages can be activated with artificial nanometric objects consisting of a gold nanoparticle functionalized with peptides. In the presence of some conjugates, macrophage proliferation was stopped and pro-inflammatory cytokines were induced. The biochemical type of response depended on the type of conjugated peptide and was correlated with the degree of ordering in the peptide coating. These findings help to illustrate the basic requirements involved in medical NP conjugate design to either activate the immune system or hide from it, in order to reach their targets before being removed by phagocytes. Additionally, it opens up the possibility to modulate the immune response in order to suppress unwanted responses resulting from autoimmunity, or allergy or to stimulate protective responses against pathogens.

  13. Dietary docosahexaenoic acid alleviates autistic-like behaviors resulting from maternal immune activation in mice.

    PubMed

    Weiser, Michael J; Mucha, Brittany; Denheyer, Heather; Atkinson, Devon; Schanz, Norman; Vassiliou, Evros; Benno, Robert H

    2016-03-01

    The prevalence of autism spectrum disorders over the last several decades has risen at an alarming rate. Factors such as broadened clinical definitions and increased parental age only partially account for this precipitous increase, suggesting that recent changes in environmental factors may also be responsible. One such factor could be the dramatic decrease in consumption of anti-inflammatory dietary omega-3 (n-3) polyunsaturated fatty acids (PUFAs) relative to the amount of pro-inflammatory omega-6 (n-6) PUFAs and saturated fats in the Western diet. Docosahexaenoic acid (DHA) is the principle n-3 PUFA found in neural tissue and is important for optimal brain development, especially during late gestation when DHA rapidly and preferentially accumulates in the brain. In this study, we tested whether supplementation of a low n-3 PUFA diet with DHA throughout development could improve measures related to autism in a mouse model of maternal immune activation. We found that dietary DHA protected offspring from the deleterious effects of gestational exposure to the viral mimetic polyriboinosinic-polyribocytidilic acid on behavioral measures of autism and subsequent adulthood immune system reactivity. These data suggest that elevated dietary levels of DHA, especially during pregnancy and nursing, may help protect normal neurodevelopment from the potentially adverse consequences of environmental insults like maternal infection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Postmenopausal Osteoporosis: The Role of Immune System Cells

    PubMed Central

    Faienza, Maria Felicia; Ventura, Annamaria; Marzano, Flaviana; Cavallo, Luciano

    2013-01-01

    In the last years, new evidences of the relationship between immune system and bone have been accumulated both in animal models and in humans affected by bone disease, such as rheumatoid arthritis, bone metastasis, periodontitis, and osteoporosis. Osteoporosis is characterized by low bone mass and microarchitectural deterioration of bone tissue with a subsequent increase in bone fragility and susceptibility to fractures. The combined effects of estrogen deprivation and raising of FSH production occurring in menopause cause a marked stimulation of bone resorption and a rapid bone loss which is central for the onset of postmenopausal osteoporosis. This review focuses on the role of immune system in postmenopausal osteoporosis and on therapeutic strategies targeting osteoimmunology pathways. PMID:23762093

  15. Seasonal benefits of a natural propolis envelope to honey bee immunity and colony health.

    PubMed

    Borba, Renata S; Klyczek, Karen K; Mogen, Kim L; Spivak, Marla

    2015-11-01

    Honey bees, as social insects, rely on collective behavioral defenses that produce a colony-level immune phenotype, or social immunity, which in turn impacts the immune response of individuals. One behavioral defense is the collection and deposition of antimicrobial plant resins, or propolis, in the nest. We tested the effect of a naturally constructed propolis envelope within standard beekeeping equipment on the pathogen and parasite load of large field colonies, and on immune system activity, virus and storage protein levels of individual bees over the course of a year. The main effect of the propolis envelope was a decreased and more uniform baseline expression of immune genes in bees during summer and autumn months each year, compared with the immune activity in bees with no propolis envelope in the colony. The most important function of the propolis envelope may be to modulate costly immune system activity. As no differences were found in levels of bacteria, pathogens and parasites between the treatment groups, the propolis envelope may act directly on the immune system, reducing the bees' need to activate the physiologically costly production of humoral immune responses. Colonies with a natural propolis envelope had increased colony strength and vitellogenin levels after surviving the winter in one of the two years of the study, despite the fact that the biological activity of the propolis diminished over the winter. A natural propolis envelope acts as an important antimicrobial layer enshrouding the colony, benefiting individual immunity and ultimately colony health. © 2015. Published by The Company of Biologists Ltd.

  16. Domestication drive the changes of immune and digestive system of Eurasian perch (Perca fluviatilis)

    PubMed Central

    Chen, Xiaowen; Wang, Jun; Qian, Long; Gaughan, Sarah; Xiang, Wei; Ai, Tao; Fan, Zhenming; Wang, Chenghui

    2017-01-01

    Domestication has altered a variety of traits within the Eurasian perch (Perca fluviatilis), including phenotypic, physiological and behavioral traits of Eurasian perch (Perca fluviatilis). Little is known, however, about the genetic changes between domesticated and wild Eurasian perch. In this study, we assembled a high-quality de novo reference transcriptome and identified differentially expressed genes between wild and domesticated Eurasian perch. A total of 113,709 transcripts were assembled, and 58,380 transcripts were annotated. Transcriptomic comparison revealed 630 differentially expressed genes between domesticated and wild Eurasian perch. Within domesticated Eurasian perch there were 412 genes that were up-regulated including MHCI, MHCII, chia, ighm within immune system development. There were 218 genes including try1, ctrl, ctrb, cela3b, cpa1 and cpb1, which were down-regulated that were associated with digestive processes. Our results indicated domestication drives the changes of immune and digestive system of Eurasian perch. Our study not only provide valuable genetic resources for further studies in Eurasian perch, but also provide novel insights into the genetic basis of physiological changes in Eurasian perch during domestication process. PMID:28257494

  17. Countermeasure for space flight effects on immune system: nutritional nucleotides

    NASA Technical Reports Server (NTRS)

    Kulkarni, A. D.; Yamauchi, K.; Sundaresan, A.; Ramesh, G. T.; Pellis, N. R.

    2005-01-01

    Microgravity and its environment have adverse effects on the immune system. Abnormal immune responses observed in microgravity may pose serious consequences, especially for the recent directions of NASA for long-term space missions to Moon, Mars and deep Space exploration. The study of space flight immunology is limited due to relative inaccessibility, difficulty of performing experiments in space, and inadequate provisions in this area in the United States and Russian space programs (Taylor 1993). Microgravity and stress experienced during space flights results in immune system aberration (Taylor 1993). In ground-based mouse models for some of the microgravity effects on the human body, hindlimb unloading (HU) has been reported to cause abnormal cell proliferation and cytokine production (Armstrong et al., 1993, Chapes et al. 1993). In this report, we document that a nutritional nucleotide supplementation as studied in ground-based microgravity analogs, has potential to serve as a countermeasure for the immune dysfunction observed in space travel.

  18. Vascular, glial, and lymphatic immune gateways of the central nervous system.

    PubMed

    Engelhardt, Britta; Carare, Roxana O; Bechmann, Ingo; Flügel, Alexander; Laman, Jon D; Weller, Roy O

    2016-09-01

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer's disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

  19. The trenbolone acetate affects the immune system in rainbow trout, Oncorhynchus mykiss.

    PubMed

    Massart, Sophie; Redivo, Baptiste; Flamion, Enora; Mandiki, S N M; Falisse, Elodie; Milla, Sylvain; Kestemont, Patrick

    2015-06-01

    In aquatic systems, the presence of endocrine-disrupting chemicals (EDC) can disrupt the reproductive function but also the immune system of wildlife. Some studies have investigated the effects of androgens on the fish immune parameters but the mechanisms by which the xenoandrogens alter the immunity are not well characterized. In order to test the effects of trenbolone acetate (TbA) on fish immune system, we exposed rainbow trout male juveniles during three weeks to TbA levels at 0.1 and 1μg/L. The present results suggest that TbA impacts, in a tissue-dependent manner, the rainbow trout immunity by affecting primarily the humoral immunity. Indeed, TbA inhibited lysozyme activity in plasma and liver and enhanced the alternative complement pathway activity (ACH50) in kidney. In plasma, the modulation of the complement system was time-dependent. The mRNA expression of genes encoding some cytokines such as renal TGF-β1, TNF-α in skin and hepatic IL-1β was also altered in fish exposed to TbA. Regarding the cellular immunity, no effect was observed on the leucocyte population. However, the expression of genes involved in the development and maturation of lymphoid cells (RAG-1 and RAG-2) was decreased in TbA-treated fish. Among those effects, we suggest that the modulation of RAG-1 and mucus apolipoprotein-A1 gene expression as well as plasma and hepatic lysozyme activities are mediated through the action of the androgen receptor. All combined, we conclude that trenbolone affects the rainbow trout immunity. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. The interplay between the immune system and chemotherapy: emerging methods for optimizing therapy.

    PubMed

    Ghiringhelli, François; Apetoh, Lionel

    2014-01-01

    Preclinical studies have revealed an unexpected ability of the immune system to contribute to the success of chemotherapy and radiotherapy. Anticancer therapies can trigger immune system activation by promoting the release of danger signals from dying tumor cells and/or the elimination of immunosuppressive cells. We have, however, recently discovered that some chemotherapies, such as 5-fluorouracil and gemcitabine, exert conflicting effects on anticancer immune responses. Although 5-fluorouracil and Gem selectively eliminated myeloid-derived suppressive cells in tumor-bearing rodents, these chemotherapies promoted the release of IL-1β and the development of pro-angiogenic IL-17-producing CD4 T cells. The ambivalent effects of chemotherapy on immune responses should thus be carefully considered to design effective combination therapies based on chemotherapy and immune modulators. Herein, we discuss how the initial findings underscoring the key role of the immune system in mediating the antitumor efficacy of anticancer agents could begin to translate into effective therapies in humans.

  1. Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology.

    PubMed

    Pulendran, Bali

    2009-10-01

    Despite their great success, we understand little about how effective vaccines stimulate protective immune responses. Two recent developments promise to yield such understanding: the appreciation of the crucial role of the innate immune system in sensing microorganisms and tuning immune responses, and advances in systems biology. Here I review how these developments are yielding insights into the mechanism of action of the yellow fever vaccine, one of the most successful vaccines ever developed, and the broader implications for vaccinology.

  2. Periodic and chaotic oscillations in a tumor and immune system interaction model with three delays

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bi, Ping; Center for Partial Differential Equations, East China Normal University, 500 Dongchuan Rd., Shanghai 200241; Ruan, Shigui, E-mail: ruan@math.miami.edu

    2014-06-15

    In this paper, a tumor and immune system interaction model consisted of two differential equations with three time delays is considered in which the delays describe the proliferation of tumor cells, the process of effector cells growth stimulated by tumor cells, and the differentiation of immune effector cells, respectively. Conditions for the asymptotic stability of equilibria and existence of Hopf bifurcations are obtained by analyzing the roots of a second degree exponential polynomial characteristic equation with delay dependent coefficients. It is shown that the positive equilibrium is asymptotically stable if all three delays are less than their corresponding critical valuesmore » and Hopf bifurcations occur if any one of these delays passes through its critical value. Numerical simulations are carried out to illustrate the rich dynamical behavior of the model with different delay values including the existence of regular and irregular long periodic oscillations.« less

  3. Overview on experimental models of interactions between nanoparticles and the immune system.

    PubMed

    Najafi-Hajivar, Saeedeh; Zakeri-Milani, Parvin; Mohammadi, Hamed; Niazi, Mehri; Soleymani-Goloujeh, Mehdi; Baradaran, Behzad; Valizadeh, Hadi

    2016-10-01

    Nanotechnology increasingly plays a significant role in modern medicine development. The clear benefits of using nanomaterials in various biomedical applications are often challenged by concerns about the lack of adequate data regarding their toxicity. Two decades of nanotoxicology research have shown that the interactions between nanoparticles (NPs) and biosystem are remarkably complex. This complexity derives from NPs' ability to bind and interact with biological cells and change their surface characteristics. One area of interest involves the interactions between NPs and the immune component. Immune system's function in the maintenance of tissue homeostasis is to protect the host from unfamiliar agents. This is done through effective surveillance and elimination of foreign substances and abnormal self cells from the body. Research shows that nanomaterials can stimulate and/or suppress the immune responses, and that their compatibility with the immune system is largely determined by their surface properties. NP size, shape, composition, protein binding and administration routes seem to be the main factors that contribute to the interactions of NPs with the immune system. In the present article, we focus on the relationship between effective physiochemical properties of NPs and their immunogenic effects. In addition, we review more details about immunological responses of different types of NPs. Understanding the interactions of nanomaterials with the immune system is essential for the engineering of new NP-based systems for medical applications. Copyright © 2016. Published by Elsevier Masson SAS.

  4. The Anopheles innate immune system in the defense against malaria infection

    PubMed Central

    Clayton, April M.; Dong, Yuemei; Dimopoulos, George

    2014-01-01

    The multifaceted innate immune system of insects is capable of fighting infection by a variety of pathogens including those causing human malaria. Malaria transmission by the Anopheles mosquito depends on the Plasmodium parasite’s successful completion of its lifecycle in the insect vector, a process that involves interactions with several tissues and cell types as well as with the mosquito’s innate immune system. This review will discuss our current understanding of the Anopheles mosquito’s innate immune responses against the malaria parasite Plasmodium and the influence of the insect’s intestinal microbiota on parasite infection. PMID:23988482

  5. Human immune system mouse models of Ebola virus infection.

    PubMed

    Spengler, Jessica R; Prescott, Joseph; Feldmann, Heinz; Spiropoulou, Christina F

    2017-08-01

    Human immune system (HIS) mice, immunodeficient mice engrafted with human cells (with or without donor-matched tissue), offer a unique opportunity to study pathogens that cause disease predominantly or exclusively in humans. Several HIS mouse models have recently been used to study Ebola virus (EBOV) infection and disease. The results of these studies are encouraging and support further development and use of these models in Ebola research. HIS mice provide a small animal model to study EBOV isolates, investigate early viral interactions with human immune cells, screen vaccines and therapeutics that modulate the immune system, and investigate sequelae in survivors. Here we review existing models, discuss their use in pathogenesis studies and therapeutic screening, and highlight considerations for study design and analysis. Finally, we point out caveats to current models, and recommend future efforts for modeling EBOV infection in HIS mice. Published by Elsevier B.V.

  6. ImmunoScenarios: A Game for the Immune System.

    ERIC Educational Resources Information Center

    Taylor, Mark F.; Jackson, Sally W.

    1996-01-01

    Describes a board game, ImmunoScenarios, which was developed to reinforce the ideas about the immune system discussed in lecture classes. Emphasizes important characteristics of the body's specific defense system including specificity, cooperation among various cells, and memory. Includes directions for playing, student handouts, and scenarios.…

  7. Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology.

    PubMed

    Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N

    2015-08-18

    Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

  8. Improving vaccine registries through mobile technologies: a vision for mobile enhanced Immunization information systems.

    PubMed

    Wilson, Kumanan; Atkinson, Katherine M; Deeks, Shelley L; Crowcroft, Natasha S

    2016-01-01

    Immunization registries or information systems are critical to improving the quality and evaluating the ongoing success of immunization programs. However, the completeness of these systems is challenged by a myriad of factors including the fragmentation of vaccine administration, increasing mobility of individuals, new vaccine development, use of multiple products, and increasingly frequent changes in recommendations. Mobile technologies could offer a solution, which mitigates some of these challenges. Engaging individuals to have more control of their own immunization information using their mobile devices could improve the timeliness and accuracy of data in central immunization information systems. Other opportunities presented by mobile technologies that could be exploited to improve immunization information systems include mobile reporting of adverse events following immunization, the capacity to scan 2D barcodes, and enabling bidirectional communication between individuals and public health officials. Challenges to utilizing mobile solutions include ensuring privacy of data, access, and equity concerns, obtaining consent and ensuring adoption of technology at sufficiently high rates. By empowering individuals with their own health information, mobile technologies can also serve as a mechanism to transfer immunization information as individuals cross local, regional, and national borders. Ultimately, mobile enhanced immunization information systems can help realize the goal of the individual, the healthcare provider, and public health officials always having access to the same immunization information. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. Mechanisms for eco-immunity in a changing enviroment: how does the coral innate immune system contend with climate change?

    NASA Astrophysics Data System (ADS)

    Traylor-Knowles, N. G.

    2016-02-01

    Innate immunity plays a central role in maintaining homeostasis, and within the context of impending climate change scenarios, understanding how this system works is critical. However, the actual mechanisms involved in the evolution of the innate immune system are largely unknown. Cnidaria (including corals, sea anemones and jellyfish) are well suited for studying the fundamental functions of innate immunity because they share a common ancestor with bilaterians. This study will highlight the transcriptomic changes during a heat shock in the coral Acropora hyacinthus of American Samoa, examining the temporal changes, every half an hour for 5 hours. We hypothesize that genes involved in innate immunity, and extracellular matrix maintenance will be key components to the heat stress response. This presentation will highlight the novel role of the tumor necrosis factor receptor gene family as a responder to heat stress and present future directions for this developing field in coral reef research.

  10. Immune System Dysregulation and Herpesvirus Reactivation Persist During Long-Duration Spaceflight

    NASA Technical Reports Server (NTRS)

    Crucian, B. E.; Mehta, S.; Stowe, R. P.; Uchakin, P.; Quiriarte, H.; Pierson, D.; Sams, C. F.

    2011-01-01

    This poster presentation reviews a study that is designed to address immune system dysregulation and the risk to crewmembers in long duration exploration class missions. This study will address these objectives: (1) Determine the status of adaptive immunity physiological stress, viral immunity, latent herpesvirus reactivation in astronauts during 6 month missions to the International Space Station; (2) determine the clinical risk related to immune dysregulation for exploration class spaceflight; and (3) determine an appropriate monitoring strategy for spaceflight-associated immune dysfunction that could be used for the evaluation of countermeasures. The study anticipates 17 subjects, and for this presentation, (midpoint study data) 10 subjects are reviewed.

  11. Development and analysis of a novel cytokine biosensor concept for astronaut immune system monitoring

    NASA Astrophysics Data System (ADS)

    Aponte, Vanessa M.

    The dynamics of how astronauts' immune systems respond to space flight have been studied extensively, but the complex process has not to date been thoroughly characterized, nor have the underlying principles of what causes the immune system to change in microgravity been fully determined. To obtain statistically significant results regarding overall immunological effects in space, collecting in vivo data during flight is desirable, but no sensor is currently capable of performing such function in this environment. The aims of this research were to establish appropriate markers for in-flight monitoring of the immune system and develop a novel approach for a benchtop sensor to measure them. Quartz Crystal Microbalances (QCMs) were used as platforms to study a surface biochemistry process selective towards cytokines, which are used as stress-related immune markers in space and ground medicine. Pilot studies elucidated that a thiolated streptavidin-biotinylated antibody surface assembly did not form the protein monolayer necessary for stable cytokine sensing. Improved experiments incorporated self-assembled monolayers (SAMs) by using di-thiol tethers at the base of a dual antibody sandwich and fluorophore assembly. The goals of the improved experiments were to achieve a stable monolayer of covalently bound tethers, to enhance sensitivity by the addition of a second monoclonal antibody, and to have a fluorescence tether attached to the last antibody layer as a way to corroborate the amount of proteins attached to the surface by using confocal fluorescence microscopy (CFM). Atomic Force Microscopy (AFM) results confirmed the formation of an even protein monolayer at the surface of the QCM, while CFM corroborated that the entire sandwich assembly had been achieved. Frequency changes increased directly proportional to concentration of cytokines, adhering to non-linear behavior explained by viscoelastic fluid models. Results point to the promising use of this surface

  12. The intersection of cancer, cancer stem cells, and the immune system: therapeutic opportunities.

    PubMed

    Silver, Daniel J; Sinyuk, Maksim; Vogelbaum, Michael A; Ahluwalia, Manmeet S; Lathia, Justin D

    2016-02-01

    During brain neoplasia, malignant cells subjugate the immune system to provide an environment that favors tumor growth. These mechanisms capitalize on tumor-promoting functions of various immune cell types and typically result in suppression of tumor immune rejection. Immunotherapy efforts are underway to disrupt these mechanisms and turn the immune system against developing tumors. While many of these therapies are already in early-stage clinical trials, understanding how these therapies impact various tumor cell populations, including self-renewing cancer stem cells, may help to predict their efficacy and clarify their mechanisms of action. Moreover, interrogating the biology of glioma cell, cancer stem cell, and immune cell interactions may provide additional therapeutic targets to leverage against disease progression. In this review, we begin by highlighting a series of investigations into immune cell-mediated tumor promotion that do not parse the tumor into stem and non-stem components. We then take a closer look at the immune-suppressive mechanisms derived specifically from cancer stem cell interactions with the immune system and end with an update on immunotherapy and cancer stem cell-directed clinical trials in glioblastoma. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. [Environmental pollutants as adjuvant factors of immune system derived diseases].

    PubMed

    Lehmann, Irina

    2017-06-01

    The main task of the immune system is to protect the body against invading pathogens. To be able to do so, immune cells must be able to recognize and combat exogenous challenges and at the same time tolerate body-borne structures. A complex regulatory network controls the sensitive balance between defense and tolerance. Perturbation of this network ultimately leads to the development of chronic inflammation, such as allergies, autoimmune reactions, and infections, because the immune system is no longer able to efficiently eliminate invading pathogens. Environmental pollutants can cause such perturbations by affecting the function of immune cells in such a way that they would react hypersensitively against allergens and the body's own structures, respectively, or that they would be no longer able to adequately combat pathogens. This indirect effect is also known as adjuvant effect. For pesticides, heavy metals, wood preservatives, or volatile organic compounds such adjuvant effects are well known. Examples of the mechanism by which environmental toxins contribute to chronic inflammatory diseases are manifold and will be discussed along asthma and allergies.While the immune system of healthy adults is typically well able to distinguish between foreign and endogenous substances even under adverse environmental conditions, that of children would react much more sensible upon comparable environmental challenges. To prevent priming for diseases by environmental cues during that highly sensitive period of early childhood children are to be particularly protected.

  14. Cyclic Dinucleotides in the Scope of the Mammalian Immune System.

    PubMed

    Mankan, Arun K; Müller, Martina; Witte, Gregor; Hornung, Veit

    2017-01-01

    First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system. In this regard, our main focus is the role of the cGAS-STING axis in the context of microbial infection and sterile inflammation and its implications for therapeutic applications.

  15. [Indicators of the persistent pro-inflammatory activation of the immune system in depression].

    PubMed

    Cubała, Wiesław Jerzy; Godlewska, Beata; Trzonkowski, Piotr; Landowski, Jerzy

    2006-01-01

    The aetiology of depression remains tentative. Current hypotheses on the aetiology of the depressive disorder tend to integrate monoaminoergic, neuroendocrine and immunological concepts of depression. A number of research papers emphasise the altered hormonal and immune status of patients with depression with pronounced cytokine level variations. Those studies tend to link the variable course of depression in relation to the altered proinflammatory activity of the immune system. The results of the studies on the activity of the selected elements of the immune system are ambiguous indicating both increased and decreased activities of its selected elements. However, a number of basic and psychopharmacological studies support the hypothesis of the increased proinflammatory activity of the immune system in the course of depression which is the foundation for the immunological hypothesis of depression. The aim of this paper is to review the functional abnormalities that are observed in depression focusing on the monoaminoergic deficiency and increased immune activation as well as endocrine dysregulation. This paper puts together and discusses current studies related to this subject with a detailed insight into interactions involving nervous, endocrine and immune systems.

  16. [Saccharomyces boulardii CNCM I-745 influences the gut-associated immune system].

    PubMed

    Stier, Heike; Bischoff, Stephan C

    2017-06-01

    The impact of the intestinal microbiome is increasing steadily with regard to the immune function und the defense against pathogens. The medicinal yeast Saccharomyces boulardii CNCM I-745 (S. boulardii) has been used as probiotic for the prevention and treatment of infectious diarrhea since more than 50 years. Meta-analyses confirm the clinical efficacy of S. boulardii to treat diarrhea of various origins in children and adults. This review article summarizes experimental studies on molecular and immunological mechanisms which explain the proven clinical efficacy of S. boulardii. Thereby the focus is on the gut-associated immune system. S. boulardii stimulates the release of immunoglobulins and cytokines and also induces the maturation of immune cells. This suggests that S. boulardii is capable of activating the unspecific immune system. In case of an infection, S. boulardii is able to bind pathogenic bacteria and to neutralize their toxins. Moreover, the medicinal yeast can attenuate the overreacting inflammatory immune response, by interfering with the signaling cascade, which is induced by the infection, and that way influences the innate and adaptive immune system. Thanks to these mechanisms the pathogens' potential of adhesion is lessened. Thus the intestinal epithelial layer is protected and diarrhea-induced fluid loss is reduced. The different molecular and immunological mechanisms investigated in the experimental studies prove the already confirmed very good clinical efficacy of S. boulardii in infectious diarrhea caused by pathogens such as bacteria, viruses, and fungi.

  17. Studying the Impact of Spaceflight Environment on Immune Functions Using New Molecular Diagnostics System

    NASA Astrophysics Data System (ADS)

    Cohen, Luchino

    Immune functions are altered during space flights. Latent virus reactivation, reduction in the number of immune cells, decreased cell activation and increased sensitivity of astronauts to infections following their return on Earth demonstrate that the immune system is less efficient during space flight. The causes of this immune deficiency are not fully understood and this dysfunction during long-term missions could result in the appearance of opportunistic infections or a decrease in the immuno-surveillance mechanisms that eradicate cancer cells. Therefore, the immune functions of astronauts will have to be monitored continuously during long-term missions in space, using miniature and semi-automated diagnostic systems. The objectives of this project are to study the causes of space-related immunodeficiency, to develop countermeasures to maintain an optimal immune function and to improve our capacity to detect infectious diseases during space missions through the monitoring of astronauts' immune system. In order to achieve these objectives, an Immune Function Diagnostic System (IFDS) will be designed to perform a set of immunological assays on board spacecrafts or on planet-bound bases. Through flow cytometric assays and molecular biology analyses, this diagnostic system could improve medical surveillance of astronauts and could be used to test countermeasures aimed at preventing immune deficiency during space missions. The capacity of the instrument to assess cellular fluorescence and to quantify the presence of soluble molecules in biological samples would support advanced molecular studies in space life sciences. Finally, such diagnostic system could also be used on Earth in remote areas or in mobile hospitals following natural disasters to fight against infectious diseases and other pathologies.

  18. Progress in immunization information systems--United States, 2011.

    PubMed

    2013-01-25

    Immunization information systems (IIS) are confidential, computerized, population-based systems that collect and consolidate vaccination data from vaccination providers and provide important tools for designing and sustaining effective immunization strategies. A Healthy People 2020 objective (IID-18) is to increase to 95% the proportion of children aged <6 years whose immunization records are in fully operational, population-based IIS. The National Vaccine Advisory Committee (NVAC) has published goals for IIS, including required and optional core data elements for which IIS should collect information. Two of the required core data elements are vaccine manufacturer and vaccine lot number. To monitor progress toward achieving these and other program goals, CDC annually surveys 56 immunization program grantees using the IIS Annual Report (IISAR). Results from the 2011 IISAR (completed by 54 grantees) indicate that 84% (19.2 million) of U.S. children aged <6 years participated in IIS, as defined by having at least two recorded vaccinations, an increase from 82% (18.8 million) in 2010. Grantees reported that an average of 63% of vaccination records for these children contained data in the field for vaccine manufacturer and 60% contained data in the field for lot number. A new project under way to capture vaccine product information, expiration date, and lot number on two-dimensional (2D) barcodes on vaccine vials might increase completeness, accuracy, and availability of these data elements in patient medical records and IIS, which in turn might enhance vaccine safety and support vaccine inventory management.

  19. Leveraging the immune system to treat advanced thyroid cancers.

    PubMed

    French, Jena D; Bible, Keith; Spitzweg, Christine; Haugen, Bryan R; Ryder, Mabel

    2017-06-01

    Inflammation has long been associated with the thyroid and with thyroid cancers, raising seminal questions about the role of the immune system in the pathogenesis of advanced thyroid cancers. With a growing understanding of dynamic tumour-immune cell interactions and the mechanisms by which tumour cells evade antitumour immunity, the field of cancer immunotherapy has been revolutionised. In this Review, we provide evidence to support the presence of an antitumour immune response in advanced thyroid cancers linked to cytotoxic T cells and NK cells. This antitumour response, however, is likely blunted by the presence of immunosuppressive pathways within the microenvironment, facilitated by tumour-associated macrophages or increased expression of negative regulators of cytotoxic T-cell function. Current and future efforts to incorporate immune-based therapies into existing tumour cell or endothelial-derived therapies-eg, with kinase inhibitors targeting tumour-associated macrophages or antibodies blocking negative regulators on T cells-could provide improved and durable responses for patients with disease that is otherwise refractory to treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Simulating the decentralized processes of the human immune system in a virtual anatomy model.

    PubMed

    Sarpe, Vladimir; Jacob, Christian

    2013-01-01

    Many physiological processes within the human body can be perceived and modeled as large systems of interacting particles or swarming agents. The complex processes of the human immune system prove to be challenging to capture and illustrate without proper reference to the spatial distribution of immune-related organs and systems. Our work focuses on physical aspects of immune system processes, which we implement through swarms of agents. This is our first prototype for integrating different immune processes into one comprehensive virtual physiology simulation. Using agent-based methodology and a 3-dimensional modeling and visualization environment (LINDSAY Composer), we present an agent-based simulation of the decentralized processes in the human immune system. The agents in our model - such as immune cells, viruses and cytokines - interact through simulated physics in two different, compartmentalized and decentralized 3-dimensional environments namely, (1) within the tissue and (2) inside a lymph node. While the two environments are separated and perform their computations asynchronously, an abstract form of communication is allowed in order to replicate the exchange, transportation and interaction of immune system agents between these sites. The distribution of simulated processes, that can communicate across multiple, local CPUs or through a network of machines, provides a starting point to build decentralized systems that replicate larger-scale processes within the human body, thus creating integrated simulations with other physiological systems, such as the circulatory, endocrine, or nervous system. Ultimately, this system integration across scales is our goal for the LINDSAY Virtual Human project. Our current immune system simulations extend our previous work on agent-based simulations by introducing advanced visualizations within the context of a virtual human anatomy model. We also demonstrate how to distribute a collection of connected simulations over a

  1. Immunization Information Systems: A Decade of Progress in Law and Policy

    PubMed Central

    Martin, Daniel W.; Lowery, N. Elaine; Brand, Bill; Gold, Rebecca; Horlick, Gail

    2015-01-01

    This article reports on a study of laws, regulations, and policies governing Immunization Information Systems (IIS, also known as “immunization registries”) in states and selected urban areas of the United States. The study included a search of relevant statutes, administrative codes and published attorney general opinions/findings, an online questionnaire completed by immunization program managers and/or their staff, and follow-up telephone interviews. The legal/regulatory framework for IIS has changed considerably since 2000, largely in ways that improve IIS’ ability to perform their public health functions while continuing to maintain strict confidentiality and privacy controls. Nevertheless, the exchange of immunization data and other health information between care providers and public health and between entities in different jurisdictions remains difficult due in part to ongoing regulatory diversity. To continue to be leaders in health information exchange and facilitate immunization of children and adults, IIS will need to address the challenges presented by the interplay of federal and state legislation, regulations, and policies and continue to move toward standardized data collection and sharing necessary for interoperable systems. PMID:24402434

  2. Integrated Immune

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarnece

    2010-01-01

    This slide presentation reviews the program to replace several recent studies about astronaut immune systems with one comprehensive study that will include in-flight sampling. The study will address lack of in-flight data to determine the inflight status of immune systems, physiological stress, viral immunity, to determine the clinical risk related to immune dysregulation for exploration class spaceflight, and to determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  3. Immune malfunction in the GPR39 zinc receptor of knockout mice: Its relationship to depressive disorder.

    PubMed

    Młyniec, Katarzyna; Trojan, Ewa; Ślusarczyk, Joanna; Głombik, Katarzyna; Basta-Kaim, Agnieszka; Budziszewska, Bogusława; Skrzeszewski, Jakub; Siwek, Agata; Holst, Birgitte; Nowak, Gabriel

    2016-02-15

    Depression is a serious psychiatric disorder affecting not only the monaminergic, glutamatergic, and GABAergic neurosystems, but also the immune system. Patients suffering from depression show disturbance in the immune parameters as well as increased susceptibility to infections. Zinc is well known as an anti-inflammatory agent, and its link with depression has been proved, zinc deficiency causing depression- and anxiety-like behavior with immune malfunction. It has been discovered that trace-element zinc acts as a neurotransmitter in the central nervous system via zinc receptor GPR39. In this study we investigated whether GPR39 knockout would cause depressive-like behavior as measured by the forced swim test, and whether these changes would coexist with immune malfunction. In GPR39 knockout mice versus a wild-type control we found: i) depressive-like behavior; ii) significantly reduced thymus weight; (iii) reduced cell viability of splenocytes; iv) reduced proliferative response of splenocytes; and v) increased IL-6 production of splenocytes after ConA stimulation and decreased IL-1b and IL-6 release after LPS stimulation. The results indicate depressive-like behavior in GPR39 KO animals with an immune response similar to that observed in depressive disorder. Here for the first time we show immunological changes under GPR39-deficient conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. From immunotoxicity to carcinogenicity: the effects of carbamate pesticides on the immune system.

    PubMed

    Dhouib, Ines; Jallouli, Manel; Annabi, Alya; Marzouki, Soumaya; Gharbi, Najoua; Elfazaa, Saloua; Lasram, Mohamed Montassar

    2016-05-01

    The immune system can be the target of many chemicals, with potentially severe adverse effects on the host's health. In the literature, carbamate (CM) pesticides have been implicated in the increasing prevalence of diseases associated with alterations of the immune response, such as hypersensitivity reactions, some autoimmune diseases and cancers. CMs may initiate, facilitate, or exacerbate pathological immune processes, resulting in immunotoxicity by induction of mutations in genes coding for immunoregulatory factors and modifying immune tolerance. In the present study, direct immunotoxicity, endocrine disruption and inhibition of esterases activities have been introduced as the main mechanisms of CMs-induced immune dysregulation. Moreover, the evidence on the relationship between CM pesticide exposure, dysregulation of the immune system and predisposition to different types of cancers, allergies, autoimmune and infectious diseases is criticized. In addition, in this review, we will discuss the relationship between immunotoxicity and cancer, and the advances made toward understanding the basis of cancer immune evasion.

  5. Current understanding of interactions between nanoparticles and the immune system

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dobrovolskaia, Marina A., E-mail: marina@mail.nih.

    2016-05-15

    The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure–activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guidemore » safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle–immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15 years of research on the immunotoxicity of engineered nanomaterials. - Graphical abstract: API — active pharmaceutical ingredient; NP — nanoparticles; PCP — physicochemical properties, CARPA — complement activation-related pseudoallergy, ICH — International Conference on Harmonization. Display Omitted - Highlights: • Achievements, disappointments and lessons learned over past decade are reviewed. • Areas in focus include characterization, immunotoxicity and utility in drug delivery. • Future direction focusing on mechanistic immunotoxicity studies is proposed.« less

  6. Immune System Dysregulation, Viral Reactivation and Stress During Short-Duration Space Flight

    NASA Technical Reports Server (NTRS)

    Crucian, Brian; Mehta, Satish; Stowe, Raymond; Uchakin, Peter; Quiriarte, Heather; Pierson, Duane; Sams, Clarence

    2010-01-01

    This slide presentation reviews a study that was conducted to ascertain if the immune system dysregulation, viral reactivation and stress from short duration space flight were a result of the stress of landing and readjustment to gravity. The objectives of the study were to replace several recent immune studies with one comprehensive study that will include in-flight sampling; address lack of in-flight data: (i.e., determine the in-flight status of immunity, physiological stress, viral immunity/reactivation); determine the clinical risk related to immune dysregulation for exploration class spaceflight; and determine the appropriate monitoring strategy for spaceflight-associated immune dysfunction, that could be used for the evaluation of countermeasures.

  7. Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System

    PubMed Central

    Symowski, Cornelia; Voehringer, David

    2017-01-01

    Type 2 innate lymphoid cells (ILC2s) are a major source of cytokines, which are also produced by Th2 cells and several cell types of the innate immune system. Work over the past few years indicates that ILC2s play a central role in regulating type 2 immune responses against allergens and helminths. ILC2s can interact with a variety of cells types of the innate and adaptive immune system by cell–cell contacts or by communication via soluble factors. In this review, we provide an overview about recent advances in our understanding how ILC2s orchestrate type 2 immune responses with focus on direct interactions between ILC2s and other cells of the immune system. PMID:29163497

  8. Interactions between Innate Lymphoid Cells and Cells of the Innate and Adaptive Immune System.

    PubMed

    Symowski, Cornelia; Voehringer, David

    2017-01-01

    Type 2 innate lymphoid cells (ILC2s) are a major source of cytokines, which are also produced by Th2 cells and several cell types of the innate immune system. Work over the past few years indicates that ILC2s play a central role in regulating type 2 immune responses against allergens and helminths. ILC2s can interact with a variety of cells types of the innate and adaptive immune system by cell-cell contacts or by communication via soluble factors. In this review, we provide an overview about recent advances in our understanding how ILC2s orchestrate type 2 immune responses with focus on direct interactions between ILC2s and other cells of the immune system.

  9. Immune system changes during simulated planetary exploration on Devon Island, high arctic

    PubMed Central

    Crucian, Brian; Lee, Pascal; Stowe, Raymond; Jones, Jeff; Effenhauser, Rainer; Widen, Raymond; Sams, Clarence

    2007-01-01

    Background Dysregulation of the immune system has been shown to occur during spaceflight, although the detailed nature of the phenomenon and the clinical risks for exploration class missions have yet to be established. Also, the growing clinical significance of immune system evaluation combined with epidemic infectious disease rates in third world countries provides a strong rationale for the development of field-compatible clinical immunology techniques and equipment. In July 2002 NASA performed a comprehensive immune assessment on field team members participating in the Haughton-Mars Project (HMP) on Devon Island in the high Canadian Arctic. The purpose of the study was to evaluate the effect of mission-associated stressors on the human immune system. To perform the study, the development of techniques for processing immune samples in remote field locations was required. Ten HMP-2002 participants volunteered for the study. A field protocol was developed at NASA-JSC for performing sample collection, blood staining/processing for immunophenotype analysis, whole-blood mitogenic culture for functional assessments and cell-sample preservation on-location at Devon Island. Specific assays included peripheral leukocyte distribution; constitutively activated T cells, intracellular cytokine profiles, plasma cortisol and EBV viral antibody levels. Study timepoints were 30 days prior to mission start, mid-mission and 60 days after mission completion. Results The protocol developed for immune sample processing in remote field locations functioned properly. Samples were processed on Devon Island, and stabilized for subsequent analysis at the Johnson Space Center in Houston. The data indicated that some phenotype, immune function and stress hormone changes occurred in the HMP field participants that were largely distinct from pre-mission baseline and post-mission recovery data. These immune changes appear similar to those observed in astronauts following spaceflight. Conclusion

  10. Effect of Bedding Material on Flies, and Behavior and Innate Immunity of Calves Reared in Hutches

    USDA-ARS?s Scientific Manuscript database

    Dairy calf hutches are often bedded with straw (STR), but sand (SND) and wood shavings (SHV) are becoming more common. The objective was to compare 3 beddings for presence of flies and measures of innate immunity and behavior of calves. Hutches were blocked by location and each of 3 hutches in a blo...

  11. Effect of Bedding Material on Flies, and Behavior and Innate Immunity of Calves Reared in Hutches.

    USDA-ARS?s Scientific Manuscript database

    Dairy calf hutches are often bedded with straw (STR), but sand (SND) and wood shavings (SHV) are becoming more common. The objective was to compare 3 beddings for presence of flies and measures of innate immunity and behavior of calves. Hutches were blocked by location and each of 3 hutches in a blo...

  12. Linking the microbiota, chronic disease and the immune system

    PubMed Central

    Hand, Timothy W.; Vujkovic-Cvijin, Ivan; Ridaura, Vanessa K.; Belkaid, Yasmine

    2016-01-01

    Chronic inflammatory diseases are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many chronic inflammatory diseases are associated with significant shifts in the microbiota towards inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites. This review discusses recent findings suggesting that shifts in the microbiota may contribute to chronic disease via effects on the immune system. PMID:27623245

  13. The role of immune dysfunction in the pathophysiology of autism

    PubMed Central

    Onore, Charity; Careaga, Milo; Ashwood, Paul

    2012-01-01

    Autism spectrum disorders (ASD) are a complex group of neurodevelopmental disorders encompassing impairments in communication, social interactions and restricted stereotypical behaviors. Although a link between altered immune responses and ASD was first recognized nearly 40 years ago, only recently has new evidence started to shed light on the complex multifaceted relationship between immune dysfunction and behavior in ASD. Neurobiological research in ASD has highlighted pathways involved in neural development, synapse plasticity, structural brain abnormalities, cognition and behavior. At the same time, several lines of evidence point to altered immune dysfunction in ASD that directly impacts some or all these neurological processes. Extensive alterations in immune function have now been described in both children and adults with ASD, including ongoing inflammation in brain specimens, elevated pro-inflammatory cytokine profiles in the CSF and blood, increased presence of brain-specific auto-antibodies and altered immune cell function. Furthermore, these dysfunctional immune responses are associated with increased impairments in behaviors characteristic of core features of ASD, in particular, deficits in social interactions and communication. This accumulating evidence suggests that immune processes play a key role in the pathophysiology of ASD. This review will discuss the current state of our knowledge of immune dysfunction in ASD, how these findings may impact on underlying neuro-immune mechanisms and implicate potential areas where the manipulation of the immune response could have an impact on behavior and immunity in ASD. PMID:21906670

  14. Crosstalk between bone niche and immune system: osteoimmunology signaling as a potential target for cancer treatment.

    PubMed

    Criscitiello, Carmen; Viale, Giulia; Gelao, Lucia; Esposito, Angela; De Laurentiis, Michele; De Placido, Sabino; Santangelo, Michele; Goldhirsch, Aron; Curigliano, Giuseppe

    2015-02-01

    There is a well recognized link between the bone and the immune system and in recent years there has been a major effort to elucidate the multiple functions of the molecules expressed in both bone and immune cells. Several molecules that were initially identified and studied in the immune system have been shown to have essential functions also in the bone. An interdisciplinary field embracing immune and bone biology has been brought together and called "osteoimmunology". The co-regulation of the skeletal and immune systems strikingly exemplifies the extreme complexity of such an interaction. Their interdependency must be considered in designing therapeutic approaches for either of the two systems. In other words, it is necessary to think of the osteoimmune system as a complex physiological unit. Denosumab was originally introduced to specifically target bone resorption, but it is now under evaluation for its effect on the long term immune response. Similarly, our current and still growing knowledge of the intimate link between the immune system and bone will be beneficial for the safety of drugs targeting either of these integrated systems. Given the large number of molecules exerting functions on both the skeletal and immune systems, osteoimmunological understanding is becoming increasingly important. Both bone and immune systems are frequently disrupted in cancer; and they may be crucial in regulating tumor growth and progression. Some therapies - such as bisphosphonates and receptor activator of NF-κB ligand (RANKL) targeted drugs - that aim at reducing pathologic osteolysis in cancer may interact with the immune system, thus providing potential favorable effects on survival. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. The mucosal immune system in health and disease, with an emphasis on parasitic infection

    PubMed Central

    Allardyce, R. A.; Bienenstock, J.

    1984-01-01

    This article briefly describes the network of immunity involving selected humoral and cellular elements shared between mucosal surfaces that are both exposed to and remote from antigen challenge. The mechanisms promoting the production, concentration, and secretion of specific antibody isotypes, as well as the migration and localization of various lymphoid cell populations, have been discussed with regard to host mucosal protection against pathogenic agents and other potentially harmful macromolecules. Although certain aspects of the mucosal immune system may be viewed as separate from the systemic immune system, they are not exclusively so. We have drawn attention to their interactions with systemic immune reactants and other, nonimmunological, cellular and humoral constituents of mucosal surfaces and tissues such as the liver. At another level of interaction we have considered the teleological translation of host defence and immunoregulation from one generation to the next through the medium of colostrum and breast milk. The manipulation of the mucosal immune system in order to enhance host resistance, modulate autoimmune and allergic systemic reactivity, or even modify fertility holds great promise. Achievement of these goals depends on gaining further insight into the mechanisms that contribute to mucosal immunity and their interactions with the systemic immune system. Much of our current knowledge is based upon experimental animal models or human populations living in relative prosperity. However, the results of oral vaccination, for example, are known to differ considerably in populations that suffer from parasitic infestations, lack adequate nutrition, and are very old or very young. We have chosen to focus attention on these groups because they constitute a large proportion of the world's population and because mucosal infections are a common cause of illness and death among them. Lastly, the recent discovery that immune deficiencies due to insufficient

  16. Controlled progressive innate immune stimulation regimen prevents the induction of sickness behavior in the open field test

    PubMed Central

    Chen, Qun; Tarr, Andrew J; Liu, Xiaoyu; Wang, Yufen; Reed, Nathaniel S; DeMarsh, Cameron P; Sheridan, John F; Quan, Ning

    2013-01-01

    Peripheral immune activation by bacterial mimics or live replicating pathogens is well known to induce central nervous system activation. Sickness behavior alterations are often associated with inflammation-induced increases in peripheral proinflammatory cytokines (eg, interleukin [IL]-1β and IL-6). However, most researchers have used acute high dose endotoxin/bacterial challenges to observe these outcomes. Using this methodology may pose inherent risks in the translational interpretation of the experimental data in these studies. Studies using Escherichia coli have yet to establish the full kinetics of repeated E. coli peripheral injections. Therefore, we sought to examine the effects of repeated low dose E. coli on sickness behavior and local peripheral inflammation in the open field test. Results from the current experiments showed a behavioral dose response, where increased amounts of E. coli resulted in correspondingly increased sickness behavior. Furthermore, animals that received a subthreshold dose (ie, one that did not cause sickness behavior) of E. coli 24 hours prior were able to withstand a larger dose of E. coli on the second day (a dose that would normally cause sickness behavior in mice without prior exposure) without inducing sickness behavior. In addition, animals that received escalating subthreshold doses of E. coli on days 1 and 2 behaviorally tolerated a dose of E. coli 25 times higher than what would normally cause sickness behavior if given acutely. Lastly, increased levels of E. coli caused increased IL-6 and IL-1β protein expression in the peritoneal cavity, and this increase was blocked by administering a subthreshold dose of E. coli 24 hours prior. These data show that progressive challenges with subthreshold levels of E. coli may obviate the induction of sickness behavior and proinflammatory cytokine expression. PMID:23950656

  17. Controlled progressive innate immune stimulation regimen prevents the induction of sickness behavior in the open field test.

    PubMed

    Chen, Qun; Tarr, Andrew J; Liu, Xiaoyu; Wang, Yufen; Reed, Nathaniel S; Demarsh, Cameron P; Sheridan, John F; Quan, Ning

    2013-01-01

    Peripheral immune activation by bacterial mimics or live replicating pathogens is well known to induce central nervous system activation. Sickness behavior alterations are often associated with inflammation-induced increases in peripheral proinflammatory cytokines (eg, interleukin [IL]-1β and IL-6). However, most researchers have used acute high dose endotoxin/bacterial challenges to observe these outcomes. Using this methodology may pose inherent risks in the translational interpretation of the experimental data in these studies. Studies using Escherichia coli have yet to establish the full kinetics of repeated E. coli peripheral injections. Therefore, we sought to examine the effects of repeated low dose E. coli on sickness behavior and local peripheral inflammation in the open field test. Results from the current experiments showed a behavioral dose response, where increased amounts of E. coli resulted in correspondingly increased sickness behavior. Furthermore, animals that received a subthreshold dose (ie, one that did not cause sickness behavior) of E. coli 24 hours prior were able to withstand a larger dose of E. coli on the second day (a dose that would normally cause sickness behavior in mice without prior exposure) without inducing sickness behavior. In addition, animals that received escalating subthreshold doses of E. coli on days 1 and 2 behaviorally tolerated a dose of E. coli 25 times higher than what would normally cause sickness behavior if given acutely. Lastly, increased levels of E. coli caused increased IL-6 and IL-1β protein expression in the peritoneal cavity, and this increase was blocked by administering a subthreshold dose of E. coli 24 hours prior. These data show that progressive challenges with subthreshold levels of E. coli may obviate the induction of sickness behavior and proinflammatory cytokine expression.

  18. A peroxidase/dual oxidase system modulates midgut epithelial immunity in Anopheles gambiae.

    PubMed

    Kumar, Sanjeev; Molina-Cruz, Alvaro; Gupta, Lalita; Rodrigues, Janneth; Barillas-Mury, Carolina

    2010-03-26

    Extracellular matrices in diverse biological systems are cross-linked by dityrosine covalent bonds catalyzed by the peroxidase/oxidase system. We show that a peroxidase, secreted by the Anopheles gambiae midgut, and dual oxidase form a dityrosine network that decreases gut permeability to immune elicitors. This network protects the microbiota by preventing activation of epithelial immunity. It also provides a suitable environment for malaria parasites to develop within the midgut lumen without inducing nitric oxide synthase expression. Disruption of this barrier results in strong and effective pathogen-specific immune responses.

  19. Effects of chromium on the immune system.

    PubMed

    Shrivastava, Richa; Upreti, R K; Seth, P K; Chaturvedi, U C

    2002-09-06

    Chromium is a naturally occurring heavy metal found commonly in the environment in trivalent, Cr(III), and hexavalent, Cr(VI), forms. Cr(VI) compounds have been declared as a potent occupational carcinogen among workers in chrome plating, stainless steel, and pigment industries. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that together with oxidative stress oxidative tissue damage and a cascade of cellular events including modulation of apoptosis regulatory gene p53, contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. On the other hand, chromium is an essential nutrient required to promote the action of insulin in body tissues so that the body can use sugars, proteins and fats. Chromium is of significant importance in altering the immune response by immunostimulatory or immunosuppressive processes as shown by its effects on T and B lymphocytes, macrophages, cytokine production and the immune response that may induce hypersensitivity reactions. This review gives an overview of the effects of chromium on the immune system of the body. Copyright 2002 Federation of European Microbiological Societies

  20. Collectivism/individualism and its relationship to behavioral and physiological immunity

    PubMed Central

    Brown, Susan G.; Ikeuchi, Ryan K.M.; Lucas, Daniel Reed

    2014-01-01

    The interaction between the behavioral and physiological immune systems provides fertile ground for research. Here, we examine the interactions between fear of disease, collectivism/individualism, disgust, visual perception and salivary IgA. First, we parsed collectivism/individualism into ancestry and psychological processes and examined their relationships to fear of disease. Both ancestral and psychological collectivists scored higher on a test of hypochondria than individualists. Additionally, in two studies we exposed participants to slides of diseased, injured or healthy individuals. Diseased and injured stimuli were rated as equally disgusting, while diseased stimuli were rated as more disgusting than healthy stimuli. We measured salivary IgA in participants before and after they viewed the stimuli. Participants provided information on their ancestral collectivism or individualism. Salivary IgA levels increased after participants viewed images of diseased or injured individuals. Participants with collectivist ancestry tended to react to the diseased and injured images with an increase in IgA, while levels of IgA remained the same or decreased in individualists in one study but we failed to replicate the effect in the second study. An increased salivary IgA response to potentially diseased individuals is adaptive, because salivary IgA plays an important role in protecting individuals from contracting an infection. The response may be related to increased preoccupation with disease states. PMID:25750808

  1. Collectivism/individualism and its relationship to behavioral and physiological immunity.

    PubMed

    Brown, Susan G; Ikeuchi, Ryan K M; Lucas, Daniel Reed

    2014-01-01

    The interaction between the behavioral and physiological immune systems provides fertile ground for research. Here, we examine the interactions between fear of disease, collectivism/individualism, disgust, visual perception and salivary IgA. First, we parsed collectivism/individualism into ancestry and psychological processes and examined their relationships to fear of disease. Both ancestral and psychological collectivists scored higher on a test of hypochondria than individualists. Additionally, in two studies we exposed participants to slides of diseased, injured or healthy individuals. Diseased and injured stimuli were rated as equally disgusting, while diseased stimuli were rated as more disgusting than healthy stimuli. We measured salivary IgA in participants before and after they viewed the stimuli. Participants provided information on their ancestral collectivism or individualism. Salivary IgA levels increased after participants viewed images of diseased or injured individuals. Participants with collectivist ancestry tended to react to the diseased and injured images with an increase in IgA, while levels of IgA remained the same or decreased in individualists in one study but we failed to replicate the effect in the second study. An increased salivary IgA response to potentially diseased individuals is adaptive, because salivary IgA plays an important role in protecting individuals from contracting an infection. The response may be related to increased preoccupation with disease states.

  2. The Innate Immune System in Acute and Chronic Wounds

    PubMed Central

    MacLeod, Amanda S.; Mansbridge, Jonathan N.

    2016-01-01

    Significance: This review article provides an overview of the critical roles of the innate immune system to wound healing. It explores aspects of dysregulation of individual innate immune elements known to compromise wound repair and promote nonhealing wounds. Understanding the key mechanisms whereby wound healing fails will provide seed concepts for the development of new therapeutic approaches. Recent Advances: Our understanding of the complex interactions of the innate immune system in wound healing has significantly improved, particularly in our understanding of the role of antimicrobials and peptides and the nature of the switch from inflammatory to reparative processes. This takes place against an emerging understanding of the relationship between human cells and commensal bacteria in the skin. Critical Issues: It is well established and accepted that early local inflammatory mediators in the wound bed function as an immunological vehicle to facilitate immune cell infiltration and microbial clearance upon injury to the skin barrier. Both impaired and excessive innate immune responses can promote nonhealing wounds. It appears that the switch from the inflammatory to the proliferative phase is tightly regulated and mediated, at least in part, by a change in macrophages. Defining the factors that initiate the switch in such macrophage phenotypes and functions is the subject of multiple investigations. Future Directions: The review highlights processes that may be useful targets for further investigation, particularly the switch from M1 to M2 macrophages that appears to be critical as dysregulation of this switch occurs during defective wound healing. PMID:26862464

  3. CRISPR-Cas: evolution of an RNA-based adaptive immunity system in prokaryotes.

    PubMed

    Koonin, Eugene V; Makarova, Kira S

    2013-05-01

    The CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR-associated genes) is an adaptive immunity system in bacteria and archaea that functions via a distinct self-non-self recognition mechanism that is partially analogous to the mechanism of eukaryotic RNA interference (RNAi). The CRISPR-Cas system incorporates fragments of virus or plasmid DNA into the CRISPR repeat cassettes and employs the processed transcripts of these spacers as guide RNAs to cleave the cognate foreign DNA or RNA. The Cas proteins, however, are not homologous to the proteins involved in RNAi and comprise numerous, highly diverged families. The majority of the Cas proteins contain diverse variants of the RNA recognition motif (RRM), a widespread RNA-binding domain. Despite the fast evolution that is typical of the cas genes, the presence of diverse versions of the RRM in most Cas proteins provides for a simple scenario for the evolution of the three distinct types of CRISPR-cas systems. In addition to several proteins that are directly implicated in the immune response, the cas genes encode a variety of proteins that are homologous to prokaryotic toxins that typically possess nuclease activity. The predicted toxins associated with CRISPR-Cas systems include the essential Cas2 protein, proteins of COG1517 that, in addition to a ligand-binding domain and a helix-turn-helix domain, typically contain different nuclease domains and several other predicted nucleases. The tight association of the CRISPR-Cas immunity systems with predicted toxins that, upon activation, would induce dormancy or cell death suggests that adaptive immunity and dormancy/suicide response are functionally coupled. Such coupling could manifest in the persistence state being induced and potentially providing conditions for more effective action of the immune system or in cell death being triggered when immunity fails.

  4. Living off a fish: a trade-off between parasites and the immune system.

    PubMed

    Sitjà-Bobadilla, A

    2008-10-01

    Research in fish immune system and parasite invasion mechanisms has advanced the knowledge of the mechanisms whereby parasites evade or cope with fish immune response. The main mechanisms of immune evasion employed by fish parasites are reviewed and considered under ten headings. 1) Parasite isolation: parasites develop in immuno-privileged host tissues, such as brain, gonads, or eyes, where host barriers prevent or limit the immune response. 2) Host isolation: the host cellular immune response isolates and encapsulates the parasites in a dormant stage without killing them. 3) Intracellular disguise: typical of intracellular microsporidians, coccidians and some myxosporeans. 4) Parasite migration, behavioural and environmental strategies: parasites migrate to host sites the immune response has not yet reached or where it is not strong enough to kill them, or they accommodate their life cycles to the season or the age in which the host immune system is down-regulated. 5) Antigen-based strategies such as mimicry or masking, variation and sharing of parasite antigens. 6) Anti-immune mechanisms: these allow parasites to resist innate humoral factors, to neutralize host antibodies or to scavenge reactive oxygen species within macrophages. 7) Immunodepression: parasites either suppress the fish immune systems by reducing the proliferative capacity of lymphocytes or the phagocytic activity of macrophages, or they induce apoptosis of host leucocytes. 8) Immunomodulation: parasites secrete or excrete substances which modulate the secretion of host immune factors, such as cytokines, to their own benefit. 9) Fast development: parasites proliferate faster than the ability of the host to mount a defence response. 10) Exploitation of the host immune reaction. Knowledge of the evasion strategies adopted by parasites will help us to understand host-parasite interactions and may therefore help in the discovery of novel immunotherapeutic agents or targeted vaccines, and permit the

  5. Mining the human gut microbiota for effector strains that shape the immune system

    PubMed Central

    Ahern, Philip P.; Faith, Jeremiah J.; Gordon, Jeffrey I.

    2014-01-01

    Summary The gut microbiota co-develops with the immune system beginning at birth. Mining the microbiota for bacterial strains responsible for shaping the structure and dynamic operations of the innate and adaptive arms of the immune system represents a formidable combinatorial problem but one that needs to be overcome to advance mechanistic understanding of microbial community-immune system co-regulation, and in order to develop new diagnostic and therapeutic approaches that promote health. Here, we discuss a scalable, less biased approach for identifying effector strains in complex microbial communities that impact immune function. The approach begins by identifying uncultured human fecal microbiota samples that transmit immune phenotypes to germ-free mice. Clonally-arrayed sequenced collections of bacterial strains are constructed from representative donor microbiota. If the collection transmits phenotypes, effector strains are identified by testing randomly generated subsets with overlapping membership in individually-housed germ-free animals. Detailed mechanistic studies of effector strain-host interactions can then be performed. PMID:24950201

  6. Hormones in the immune system and their possible role. A critical review.

    PubMed

    Csaba, György

    2014-09-01

    Immune cells synthesize, store and secrete hormones, which are identical with the hormones of the endocrine glands. These are: the POMC hormones (ACTH, endorphin), the thyroid system hormones (TRH, TSH, T3), growth hormone (GH), prolactin, melatonin, histamine, serotonin, catecholamines, GnRH, LHRH, hCG, renin, VIP, ANG II. This means that the immune cells contain all of the hormones, which were searched at all and they also have receptors for these hormones. From this point of view the immune cells are similar to the unicells (Tetrahymena), so it can be supposed that these cells retained the properties characteristic at a low level of phylogeny while other cells during the evolution accumulated to form endocrine glands. In contrast to the glandular endocrine cells, immune cells are polyproducers and polyreceivers. As they are mobile cells, they are able to transport the stored hormone to different places (packed transport) or attracted by local factors, accumulate in the neighborhood of the target, synthesizing and secreting hormones locally. This is taking place, e.g. in the case of endorphin, where the accumulating immune cells calms pain caused by the inflammation. The targeted packed transport is more economical than the hormone-pouring to the blood circulation of glandular endocrines and the targeting also cares the other receptor-bearing cells timely not needed the effect. Mostly the immune-effects of immune-cell derived hormones were studied (except endorphin), however, it is not exactly cleared, while the system could have scarcely studied important roles in other cases. The evolutionary aspects and the known as well, as possible roles of immune-endocrine system and their hormones are listed and discussed.

  7. Recovery of the immune system after exercise.

    PubMed

    Peake, Jonathan M; Neubauer, Oliver; Walsh, Neil P; Simpson, Richard J

    2017-05-01

    The notion that prolonged, intense exercise causes an "open window" of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8 + T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes. Copyright © 2017 the American Physiological Society.

  8. A Physical Theory of the Competition that Allows HIV to Escape from the Immune System

    NASA Astrophysics Data System (ADS)

    Deem, Michael

    2007-03-01

    Competition within the immune system may degrade immune control of viral infections. We formalize the evolution that occurs in both HIV-1 and the immune system quasispecies [1]. Inclusion of competition in the immune system leads to a novel balance between the immune response and HIV-1, in which the eventual outcome is HIV-1 escape rather than control. The analytical model reproduces the three stages of HIV-1 infection. We propose a vaccine regimen that may be able to reduce competition between T cells, potentially eliminating the third stage of HIV-1. 1) G. Wang and M. W. Deem, Phys. Rev. Lett. 97 (2006) 188106.

  9. Neuroinflammation, immune system and Alzheimer disease: searching for the missing link.

    PubMed

    Guerriero, F; Sgarlata, C; Francis, M; Maurizi, N; Faragli, A; Perna, S; Rondanelli, M; Rollone, M; Ricevuti, G

    2017-10-01

    Due to an increasingly aging population, Alzheimer disease (AD) represents a crucial issue for the healthcare system because of its widespread prevalence and the burden of its care needs. Several hypotheses on AD pathogenesis have been proposed and current therapeutical strategies have shown limited effectiveness. In the last decade, more evidence has supported a role for neuroinflammation and immune system dysregulation in AD. It remains unclear whether astrocytes, microglia and immune cells influence disease onset, progression or both. Amyloid-β peptides that aggregate extracellularly in the typical neuritic plaques generate a constant inflammatory environment. This causes a prolonged activation of microglial and astroglial cells that potentiate neuronal damage and provoke the alteration of the blood brain barrier (BBB), damaging the permeability of blood vessels. Recent data support the role of the BBB as a link between neuroinflammation, the immune system and AD. Hence, a thorough investigation of the neuroinflammatory and immune system pathways that impact neurodegeneration and novel exciting findings such as microglia-derived microvesicles, inflammasomes and signalosomes will ultimately enhance our understanding of the pathological process. Eventually, we should proceed with caution in defining a causal or consequential role of neuroinflammation in AD, but rather focus on identifying its exact pathological contribution.

  10. Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System

    PubMed Central

    Díaz-Muñoz, Manuel D.; Turner, Martin

    2018-01-01

    Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and translation are the other key steps for final gene expression, and they are all controlled by RNA-binding proteins (RBPs). Nowadays we have a deep understanding of how transcription factors control the immune system but recent evidences suggest that post-transcriptional regulation by RBPs is equally important for both development and activation of immune responses. Here, we review current knowledge about how post-transcriptional control by RBPs shapes our immune system and discuss the perspective of RBPs being the key players of a hidden immune cell epitranscriptome. PMID:29875770

  11. Uncovering the Role of RNA-Binding Proteins in Gene Expression in the Immune System.

    PubMed

    Díaz-Muñoz, Manuel D; Turner, Martin

    2018-01-01

    Fighting external pathogens requires an ever-changing immune system that relies on tight regulation of gene expression. Transcriptional control is the first step to build efficient responses while preventing immunodeficiencies and autoimmunity. Post-transcriptional regulation of RNA editing, location, stability, and translation are the other key steps for final gene expression, and they are all controlled by RNA-binding proteins (RBPs). Nowadays we have a deep understanding of how transcription factors control the immune system but recent evidences suggest that post-transcriptional regulation by RBPs is equally important for both development and activation of immune responses. Here, we review current knowledge about how post-transcriptional control by RBPs shapes our immune system and discuss the perspective of RBPs being the key players of a hidden immune cell epitranscriptome.

  12. Comparative genomic analysis of the Tribolium immune system

    PubMed Central

    Zou, Zhen; Evans, Jay D; Lu, Zhiqiang; Zhao, Picheng; Williams, Michael; Sumathipala, Niranji; Hetru, Charles; Hultmark, Dan; Jiang, Haobo

    2007-01-01

    Background Tribolium castaneum is a species of Coleoptera, the largest and most diverse order of all eukaryotes. Components of the innate immune system are hardly known in this insect, which is in a key phylogenetic position to inform us about genetic innovations accompanying the evolution of holometabolous insects. We have annotated immunity-related genes and compared them with homologous molecules from other species. Results Around 300 candidate defense proteins are identified based on sequence similarity to homologs known to participate in immune responses. In most cases, paralog counts are lower than those of Drosophila melanogaster or Anopheles gambiae but are substantially higher than those of Apis mellifera. The genome contains probable orthologs for nearly all members of the Toll, IMD, and JAK/STAT pathways. While total numbers of the clip-domain serine proteinases are approximately equal in the fly (29), mosquito (32) and beetle (30), lineage-specific expansion of the family is discovered in all three species. Sixteen of the thirty-one serpin genes form a large cluster in a 50 kb region that resulted from extensive gene duplications. Among the nine Toll-like proteins, four are orthologous to Drosophila Toll. The presence of scavenger receptors and other related proteins indicates a role of cellular responses in the entire system. The structures of some antimicrobial peptides drastically differ from those in other orders of insects. Conclusion A framework of information on Tribolium immunity is established, which may serve as a stepping stone for future genetic analyses of defense responses in a nondrosophiline genetic model insect. PMID:17727709

  13. Influence of breast milk polyamines on suckling rat immune system maturation.

    PubMed

    Pérez-Cano, Francisco J; González-Castro, Ana; Castellote, Cristina; Franch, Angels; Castell, Margarida

    2010-02-01

    The aim of this study was to ascertain whether the supplementation of polyamines present in breast milk, i.e. spermine (SPM) and spermidine (SPD), influenced the post-natal maturation of the systemic and intestinal immune system in rats. From birth, pups daily received SPM or SPD. At 5, 11 and 18 days old, small intestine intraepithelial lymphocytes (IEL), lamina propria lymphocytes (LPL) and splenocytes were phenotypically characterized. SPM and, less evidently, SPD accelerated the maturation of CD8+ IEL, and enhanced the presence of intraepithelial NK cells and IEL related with specific immune responses on the proximal and distal small intestine, respectively. Polyamines increased the percentage of more mature CD4+ LPL and enhanced the early presence of splenic B cells and, later, that of NK cells. However, no effect on Ig-secretory function was detected. These results suggest that breast milk polyamines improve the maturation of the rat intestinal and systemic immune system.

  14. The role of cortistatin in the human immune system.

    PubMed

    van Hagen, P Martin; Dalm, Virgil A; Staal, Frank; Hofland, Leo J

    2008-05-14

    Cortistatin (CST) is a recently described neuropeptide that shares high homology with somatostatin (somatotropin release-inhibiting factor, SRIF) and binds with high affinity to all somatostatin (sst) receptor subtypes. CST is currently known to have a widespread distribution in many human organs including the immune system. The activities specific to CST may be partially attributable to its binding to the growth hormone secretagogue (GHS)-receptor (GHS-R) and the orphan G-protein-coupled receptor MrgX2. Human immune cells produce CST, whereas macrophage lineage and activated endothelium express sst2, and human lymphocytes express sst3. The human thymus expresses sst1, 2, 3, MrgX2 and almost all immune cells express GHS-R. Moreover, at this very moment promising research with CST in experimental animal models is being performed. On the basis of these promising results, studies aiming to further evaluate the possibilities of CST as a therapeutic agent in human immune-mediated inflammatory diseases are warranted.

  15. The immune system in space, including Earth-based benefits of space-based research.

    PubMed

    Sonnenfeld, Gerald

    2005-08-01

    Exposure to space flight conditions has been shown to result in alterations in immune responses. Changes in immune responses of humans and experimental animals have been shown to be altered during and after space flight of humans and experimental animals or cell cultures of lymphoid cells. Exposure of subjects to ground-based models of space flight conditions, such as hindlimb unloading of rodents or chronic bed rest of humans, has also resulted in changes in the immune system. The relationship of these changes to compromised resistance to infection or tumors in space flight has not been fully established, but results from model systems suggest that alterations in the immune system that occur in space flight conditions may be related to decreases in resistance to infection. The establishment of such a relationship could lead to the development of countermeasures that could prevent or ameliorate any compromises in resistance to infection resulting from exposure to space flight conditions. An understanding of the mechanisms of space flight conditions effects on the immune response and development of countermeasures to prevent them could contribute to the development of treatments for compromised immunity on earth.

  16. Endocannabinoids and the Immune System in Health and Disease.

    PubMed

    Cabral, Guy A; Ferreira, Gabriela A; Jamerson, Melissa J

    2015-01-01

    Endocannabinoids are bioactive lipids that have the potential to signal through cannabinoid receptors to modulate the functional activities of a variety of immune cells. Their activation of these seven-transmembranal, G protein-coupled receptors sets in motion a series of signal transductional events that converge at the transcriptional level to regulate cell migration and the production of cytokines and chemokines. There is a large body of data that supports a functional relevance for 2-arachidonoylglycerol (2-AG) as acting through the cannabinoid receptor type 2 (CB2R) to inhibit migratory activities for a diverse array of immune cell types. However, unequivocal data that supports a functional linkage of anandamide (AEA) to a cannabinoid receptor in immune modulation remains to be obtained. Endocannabinoids, as typical bioactive lipids, have a short half-life and appear to act in an autocrine and paracrine fashion. Their immediate effective action on immune function may be at localized sites in the periphery and within the central nervous system. It is speculated that endocannabinoids play an important role in maintaining the overall "fine-tuning" of the immune homeostatic balance within the host.

  17. Evolution of JAK-STAT Pathway Components: Mechanisms and Role in Immune System Development

    PubMed Central

    Liongue, Clifford; O'Sullivan, Lynda A.; Trengove, Monique C.; Ward, Alister C.

    2012-01-01

    Background Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK) – Signal transducer and activator of transcription (STAT) pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP), Protein inhibitors against Stats (PIAS), and Suppressor of cytokine signaling (SOCS) proteins across a diverse range of organisms. Results Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components. Conclusion Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity. PMID:22412924

  18. Follicular helper T cells in immunity and systemic autoimmunity.

    PubMed

    Craft, Joseph E

    2012-05-01

    Follicular helper T (T(FH)) cells are essential for B-cell maturation and immunoglobulin production after immunization with thymus-dependent antigens. Nevertheless, the development and function of T(FH) cells have been less clearly defined than classic CD4(+) effector T-cell subsets, including T-helper-1 (T(H)1), T(H)2 and T(H)17 cells. As such, our understanding of the genesis of T(FH) cells in humans and their role in the development of autoimmunity remains incomplete. However, evidence from animal models of systemic lupus erythematosus (SLE) and patients with systemic autoimmune diseases suggests that these cells are necessary for pathogenic autoantibody production, in a manner analogous to their role in promotion of B-cell maturation during normal immune responses. In this Review, I discuss the findings that have increased our knowledge of T(FH)-cell development and function in normal and aberrant immune responses. Such information might improve our understanding of autoimmune diseases, such as SLE, and highlights the potential of T(FH) cells as therapeutic targets in these diseases.

  19. The interplay between the gut microbiota and the immune system.

    PubMed

    Geuking, Markus B; Köller, Yasmin; Rupp, Sandra; McCoy, Kathy D

    2014-01-01

    The impact of the gut microbiota on immune homeostasis within the gut and, importantly, also at systemic sites has gained tremendous research interest over the last few years. The intestinal microbiota is an integral component of a fascinating ecosystem that interacts with and benefits its host on several complex levels to achieve a mutualistic relationship. Host-microbial homeostasis involves appropriate immune regulation within the gut mucosa to maintain a healthy gut while preventing uncontrolled immune responses against the beneficial commensal microbiota potentially leading to chronic inflammatory bowel diseases (IBD). Furthermore, recent studies suggest that the microbiota composition might impact on the susceptibility to immune-mediated disorders such as autoimmunity and allergy. Understanding how the microbiota modulates susceptibility to these diseases is an important step toward better prevention or treatment options for such diseases.

  20. Novel Therapeutic Strategies for Solid Tumor Based on Body's Intrinsic Antitumor Immune System.

    PubMed

    Duan, Haifeng

    2018-05-22

    The accumulation of mutated somatic cells due to the incompetency of body's immune system may lead to tumor onset. Therefore, enhancing the ability of the system to eliminate such cells should be the core of tumor therapy. The intrinsic antitumor immunity is triggered by tumor-specific antigens (TSA) or TSA-sensitized dendritic cells (DC). Once initiated, specific anti-tumor antibodies are produced and tumor-specific killer immune cells, including cytotoxic T lymphocytes (CTL), NK cells, and macrophages, are raised or induced. Several strategies may enhance antitumor action of immune system, such as supplying tumor-targeted antibody, activating T cells, enhancing the activity and tumor recognition of NK cells, promoting tumor-targeted phagocytosis of macrophages, and eliminating the immunosuppressive myeloid-derived suppressor cells (MDSCs) and Treg cells. Apart from the immune system, the removal of tumor burden still needs to be assisted by drugs, surgery or radiation. And the body's internal environment and tumor microenvironment should be improved to recover immune cell function and prevent tumor growth. Multiple microenvironment modulatory therapies may be applied, including addressing hypoxia and oxidative stress, correcting metabolic disorders, and controlling chronic inflammation. Finally, to cure tumor and prevent tumor recurrence, repairing or supporting therapy that consist of tissue repair and nutritional supplement should be applied properly. © 2018 The Author(s). Published by S. Karger AG, Basel.

  1. HIV Immune Recovery Inflammatory Syndrome and Central Nervous System Paracoccidioidomycosis.

    PubMed

    de Almeida, Sérgio Monteiro; Roza, Thiago Henrique

    2017-04-01

    The immune reconstitution inflammatory syndrome (IRIS) is a deregulated inflammatory response to invading microorganisms. It is manifested when there is an abrupt change in host immunity from an anti-inflammatory and immunosuppressive state to a pro-inflammatory state as a result of rapid depletion or removal of factors that promote immune suppression or inhibition of inflammation. The aim of this paper is to discuss and re-interpret the possibility of association of paracoccidioidomycosis (PCM) with IRIS in the central nervous system (CNS) in a case from Brazil published by Silva-Vergara ML. et al. (Mycopathologia 177:137-141, 6). An AIDS patient who was not receiving medical care developed pulmonary PCM successfully treated with itraconazole. The patient developed central nervous system PCM (NPCM) after starting the ARV therapy with recovery of immunity and control of HIV viral load, although it was not interpreted as IRIS by the authors, it fulfills the criteria for CNS IRIS. This could be the first case of NPCM associated with IRIS described. Although not frequent, IRIS must be considered in PCM patients and HIV, from endemic areas or patients that traveled to endemic areas, receiving ARV treatment and with worsening symptoms.

  2. Immunity by equilibrium.

    PubMed

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  3. Anatomy of the immune system: facts and problems.

    PubMed

    Grossi, C E; Ciccone, E; Tacchetti, C; Santoro, G; Anastasi, G

    2000-01-01

    In the introductory section of this report, the anatomy of the immune system, from organs and tissues to molecules, will be reviewed briefly. Cell proliferation and differentiation in the central lymphoid organs (thymus and bone marrow) yield a repertoire of T- and B-cell clones that seed into peripheral lymphoid organs (spleen, lymph nodes and Mucosa-Associated Lymphoid Tissue, MALT), where humoral and cell-mediated antigen-specific immune responses occur. The stringent process of clonal selection in the central lymphoid organs implies deletion of inappropriate cells via apoptosis. In the peripheral lymphoid organs, the potential of unlimited activation and expansion of lymphocytes in response to antigens is primarily regulated by apoptosis and anergy. These events, on the one hand, are relevant to prevent autoimmunity and lymphoproliferative disorders; on the other hand, clonal deletion and anergy provide a detrimental escape to immune recognition of malignant cells. Two major inhibitory mechanisms of the immune response have emerged recently. One is linked to the existence of bona fide suppressor cells and cytokines; the other relies on the existence of inhibitory molecules expressed by T, B and NK cells, as well as by other leukocytes. In the studies herein reported, emphasis will be given to surface membrane molecules that down-regulate T-cell-mediated immune responses. These molecules control interactions between T cells and antigen presenting cells (APC's) or target (virus-infected or mutated) cells that have to be killed. Two sets of molecules exist that either upregulate (coactivation molecules) or down-regulate (inhibitory molecules) T-cell mediated responses. The latter aspect of the immune regulation, i.e. molecules that limit the expansion of T-cell clones following specific recognition of antigens will be considered in depth. Two inhibitory molecules, CD152 (CTLA-4) and CD85/LIR-1/ILT2 are expressed in all T cells, being largely confined within

  4. An Investigation of the Memory Response of the Local Immune System to Shigella Antigens.

    DTIC Science & Technology

    1985-12-31

    kAD-A±75 215 AN INVESTIOATION OF THE MEMORY RESPONSE OF THE LOCAL L/1 I IMMUNE SYSTEM TO SHIGELLA ANTIGENS(U) MICHIGAN UNIV ANN I RBOR D F KEREN 31...IMMUNE SYSTEM TO SHIGELLA ANTIGENS ANNUAL REPORT DAVID F. KEREN, M.D. DECEMBER 31, 1985 FOR THE PERIOD DECEMBER 1, 1984 - NOVEMBER 30, 1985 SUPPORTED...Security Classification) An Investigation of the Memory Response of the Local Immune System to Shigella Antigens 12 PERSONAL AUTHOR(S) Keren, David F

  5. Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex.

    PubMed

    Rizzetto, Lisa; Fava, Francesca; Tuohy, Kieran M; Selmi, Carlo

    2018-05-31

    Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in

  6. Effect of Pain Management on Immunization Efficacy in Mice

    PubMed Central

    Kolstad, April M; Rodriguiz, Ramona M; Kim, Caroline J; Hale, Laura P

    2012-01-01

    Immunization with complete Freund adjuvant (CFA) or incomplete Freund adjuvant (IFA) is commonly viewed as painful, yet rodents may not receive analgesics due to concerns that these drugs affect the desired immune responses. Here we tested the hypothesis that pain associated with immunization with CFA or IFA in mice can be relieved without compromising the effectiveness of the immune response. After subcutaneous immunization in the leg with antigen in CFA or IFA, mice were assessed for signs of pain by using behavioral tests, including unrestricted locomotion in an open field, forced running on an automated treadmill, and voluntary wheel running. Effects of the analgesics acetaminophen, meloxicam, and buprenorphine on behavioral and antibody responses were assessed after primary and secondary immunization with the model antigen ovalbumin and after repeated immunization with a limiting dose of recombinant protective antigen from Bacillus anthracis. Open field activity and the distance traveled during forced gait analysis and voluntary wheel running both decreased after immunization. Treatment with each of the analgesics normalized some but not all of these behaviors but did not decrease the mean or maximal antibody titer after primary or repeated immunization with a moderate dose of ovalbumin or after repeated immunization with a limiting dose of protective antigen. In summary, after immunization with CFA or IFA, mice showed behavioral responses suggestive of pain. Acetaminophen, meloxicam, and buprenorphine attenuated these effects without decreasing antibody responses. Therefore, the use of these analgesics for managing rodent pain associated with CFA- or IFA-containing vaccines can be encouraged. PMID:23043810

  7. Mucosal Vaccination Overcomes the Barrier to Recombinant Vaccinia Immunization Caused by Preexisting Poxvirus Immunity

    NASA Astrophysics Data System (ADS)

    Belyakov, Igor M.; Moss, Bernard; Strober, Warren; Berzofsky, Jay A.

    1999-04-01

    Overcoming preexisting immunity to vaccinia virus in the adult population is a key requirement for development of otherwise potent recombinant vaccinia vaccines. Based on our observation that s.c. immunization with vaccinia induces cellular and antibody immunity to vaccinia only in systemic lymphoid tissue and not in mucosal sites, we hypothesized that the mucosal immune system remains naive to vaccinia and therefore amenable to immunization with recombinant vaccinia vectors despite earlier vaccinia exposure. We show that mucosal immunization of vaccinia-immune BALB/c mice with recombinant vaccinia expressing HIV gp160 induced specific serum antibody and strong HIV-specific cytotoxic T lymphocyte responses. These responses occurred not only in mucosal but also in systemic lymphoid tissue, whereas systemic immunization was ineffective under these circumstances. In this context, intrarectal immunization was more effective than intranasal immunization. Boosting with a second dose of recombinant vaccinia was also more effective via the mucosal route. The systemic HIV-specific cytotoxic T lymphocyte response was enhanced by coadministration of IL-12 at the mucosal site. These results also demonstrate the independent compartmentalization of the mucosal versus systemic immune systems and the asymmetric trafficking of lymphocytes between them. This approach to circumvent previous vaccinia immunity may be useful for induction of protective immunity against infectious diseases and cancer in the sizable populations with preexisting immunity to vaccinia from smallpox vaccination.

  8. Effect of simulated weightlessness on the immune system in rats

    NASA Technical Reports Server (NTRS)

    Caren, L. D.; Mandel, A. D.; Nunes, J. A.

    1980-01-01

    Rats suspended in a model system designed to simulate many aspects of weightlessness were immunized with sheep red blood cells. Parameters measured on these and control rats included titers of anti-sheep red blood cell antibodies, serum immunoglobulin levels, spleen and thymus weights, hematocrits, and leukocyte differential counts on peripheral blood. No significant differences were found between test and weight-bearing, harnessed controls; however, the thymuses of animals in both these groups were significantly smaller than untreated cage controls. The lack of an effect of simulated weightlessness on the immune system is an interesting result, and its significance is discussed.

  9. Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system.

    PubMed

    Monzón-Sandoval, Jimena; Castillo-Morales, Atahualpa; Crampton, Sean; McKelvey, Laura; Nolan, Aoife; O'Keeffe, Gerard; Gutierrez, Humberto

    2015-01-01

    During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune-related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS.

  10. Role of leptin as a link between metabolism and the immune system.

    PubMed

    Pérez-Pérez, Antonio; Vilariño-García, Teresa; Fernández-Riejos, Patricia; Martín-González, Jenifer; Segura-Egea, Juan José; Sánchez-Margalet, Víctor

    2017-06-01

    Leptin is an adipocyte-derived hormone not only with an important role in the central control of energy metabolism, but also with many pleiotropic effects in different physiological systems. One of these peripheral functions of leptin is a regulatory role in the interplay between energy metabolism and the immune system, being a cornerstone of the new field of immunometabolism. Leptin receptor is expressed throughout the immune system and the regulatory effects of leptin include cells from both the innate and adaptive immune system. Leptin is one of the adipokines responsible for the inflammatory state found in obesity that predisposes not only to type 2 diabetes, metabolic syndrome and cardiovascular disease, but also to autoimmune and allergic diseases. Leptin is an important mediator of the immunosuppressive state in undernutrition status. Placenta is the second source of leptin and it may play a role in the immunomodulation during pregnancy. Finally, recent work has pointed to the participation of leptin and leptin receptor in the pathophysiology of inflammation in oral biology. Therefore, leptin and leptin receptor should be considered for investigation as a marker of inflammation and immune activation in the frontier of innate-adaptive system, and as possible targets for intervention in the immunometabolic mediated pathophysiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations.

    PubMed

    Marchandeau, Stéphane; Pontier, Dominique; Guitton, Jean-Sébastien; Letty, Jérôme; Fouchet, David; Aubineau, Jacky; Berger, Francis; Léonard, Yves; Roobrouck, Alain; Gelfi, Jacqueline; Peralta, Brigitte; Bertagnoli, Stéphane

    2014-03-04

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen.

  12. Early infections by myxoma virus of young rabbits (Oryctolagus cuniculus) protected by maternal antibodies activate their immune system and enhance herd immunity in wild populations

    PubMed Central

    2014-01-01

    The role of maternal antibodies is to protect newborns against acute early infection by pathogens. This can be achieved either by preventing any infection or by allowing attenuated infections associated with activation of the immune system, the two strategies being based on different cost/benefit ratios. We carried out an epidemiological survey of myxomatosis, which is a highly lethal infectious disease, in two distant wild populations of rabbits to describe the epidemiological pattern of the disease. Detection of specific IgM and IgG enabled us to describe the pattern of immunity. We show that maternal immunity attenuates early infection of juveniles and enables activation of their immune system. This mechanism associated with steady circulation of the myxoma virus in both populations, which induces frequent reinfections of immune rabbits, leads to the maintenance of high immunity levels within populations. Thus, myxomatosis has a low impact, with most infections being asymptomatic. This work shows that infection of young rabbits protected by maternal antibodies induces attenuated disease and activates their immune system. This may play a major role in reducing the impact of a highly lethal disease when ecological conditions enable permanent circulation of the pathogen. PMID:24589193

  13. Materials to Engineer the Immune System

    DTIC Science & Technology

    2011-04-01

    alone (Lysate), or with GM-CSF and lysate (GM+Lys), and 14 days later 200,000 NT1 cells were injected into the mammary pad. Mice survival was...followed over time. Fig. 2. Therapeutic vaccination against NT1 transplantable tumors. NT1 cells (200,000) were injected into the mammary...Engineer the Immune System David Mooney Harvard College Cambridge, MA 02136 Dendritic cells , GM-CSF, CpG, poly(lactide-co-glycolide) The

  14. Association of psychosis, affective disorders and diseases affecting the immune system.

    PubMed

    Larsen, Jeanette Brun; Iversen, Valentina Cabral; Reitan, Solveig Klæbo

    2018-02-01

    Purpose of the article: There are indications of altered immune activity in depressed and psychotic patients compared to healthy controls in several studies. To explore the clinical importance of this phenomenon we examined the relation between different disorders affecting the immune system and psychoses and depression, respectively. A total of 276 patients consecutively admitted to a psychiatric acute ward were included in the study. Of these 41 patients fulfilled the criteria for ICD-10 F20-29 (psychotic) diagnosis and 157 patients a F30-39 (affective) diagnosis. Information on diseases affecting the immune system in patients themselves and family members of the patients were obtained by a self-report questionnaire. Comparing the two groups showed a significant correlation between the F20-29 group and eczema (r = -0.116, p = .037). Comparing what patients reported for family members showed a significantly higher frequency of epilepsy (p = .033) in the F20-29 group. Summarizing all immunological diseases for family members showed a significantly higher frequency in the F30-39 group compared to the F20-29 group (χ 2  = 4, 82, df = 1, p = .028). There may be differences between the F20-29 and F30-39 groups and their family members regarding risk for diseases affecting the immune system. This is in line with different activity of the immune system measured in blood for the disorders and may add information regarding etiology and pathology of these psychiatric diseases. Further studies including a greater number of subjects, as well as confirmation of the immunological diseases through blood samples are needed.

  15. Exercise and the Regulation of Immune Functions.

    PubMed

    Simpson, Richard J; Kunz, Hawley; Agha, Nadia; Graff, Rachel

    2015-01-01

    Exercise has a profound effect on the normal functioning of the immune system. It is generally accepted that prolonged periods of intensive exercise training can depress immunity, while regular moderate intensity exercise is beneficial. Single bouts of exercise evoke a striking leukocytosis and a redistribution of effector cells between the blood compartment and the lymphoid and peripheral tissues, a response that is mediated by increased hemodynamics and the release of catecholamines and glucocorticoids following the activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis. Single bouts of prolonged exercise may impair T-cell, NK-cell, and neutrophil function, alter the Type I and Type II cytokine balance, and blunt immune responses to primary and recall antigens in vivo. Elite athletes frequently report symptoms associated with upper respiratory tract infections (URTI) during periods of heavy training and competition that may be due to alterations in mucosal immunity, particularly reductions in secretory immunoglobulin A. In contrast, single bouts of moderate intensity exercise are "immuno-enhancing" and have been used to effectively increase vaccine responses in "at-risk" patients. Improvements in immunity due to regular exercise of moderate intensity may be due to reductions in inflammation, maintenance of thymic mass, alterations in the composition of "older" and "younger" immune cells, enhanced immunosurveillance, and/or the amelioration of psychological stress. Indeed, exercise is a powerful behavioral intervention that has the potential to improve immune and health outcomes in the elderly, the obese, and patients living with cancer and chronic viral infections such as HIV. © 2015 Elsevier Inc. All rights reserved.

  16. Effect of Compassion Meditation on Neuroendocrine, Innate Immune and Behavioral Responses to Psychosocial Stress

    PubMed Central

    Pace, Thaddeus W.W.; Negi, Lobsang Tenzin; Adame, Daniel D.; Cole, Steven P.; Sivilli, Teresa I.; Brown, Timothy D.; Issa, Michael J.; Raison, Charles L.

    2009-01-01

    Summary Meditation practices may impact physiological pathways that are modulated by stress and relevant to disease. While much attention has been paid to meditation practices that emphasize calming the mind, improving focused attention, or developing mindfulness, less is known about meditation practices that foster compassion. Accordingly, the current study examined the effect of compassion meditation on innate immune, neuroendocrine and behavioral responses to psychosocial stress and evaluated the degree to which engagement in meditation practice influenced stress-reactivity. Sixty-one healthy adults were randomized to 6 weeks of training in compassion meditation (n=33) or participation in a health discussion control group (n=28) followed by exposure to a standardized laboratory stressor (Trier Social Stress Test [TSST]). Physiologic and behavioral responses to the TSST were determined by repeated assessments of plasma concentrations of interleukin (IL)-6 and cortisol as well as total distress scores on the Profile of Mood States (POMS). No main effect of group assignment on TSST responses was found for IL-6, cortisol or POMS scores. However, within the meditation group, increased meditation practice was correlated with decreased TSST-induced IL-6 (rp =-0.46, p=0.008) and POMS distress scores (rp =-0.43, p=0.014). Moreover, individuals with meditation practice times above the median exhibited lower TSST-induced IL-6 and POMS distress scores compared to individuals below the median, who did not differ from controls. These data suggest that engagement in compassion meditation may reduce stress-induced immune and behavioral responses, although future studies are required to determine whether individuals who engage in compassion meditation techniques are more likely to exhibit reduced stress reactivity. PMID:18835662

  17. Control of an automated mobile manipulator using artificial immune system

    NASA Astrophysics Data System (ADS)

    Deepak, B. B. V. L.; Parhi, Dayal R.

    2016-03-01

    This paper addresses the coordination and control of a wheeled mobile manipulator (WMM) using artificial immune system. The aim of the developed methodology is to navigate the system autonomously and transport jobs and tools in manufacturing environments. This study integrates the kinematic structures of a four-axis manipulator and a differential wheeled mobile platform. The motion of the developed WMM is controlled by the complete system of parametric equation in terms of joint velocities and makes the robot to follow desired trajectories by the manipulator and platform within its workspace. The developed robot system performs its action intelligently according to the sensed environmental criteria within its search space. To verify the effectiveness of the proposed immune-based motion planner for WMM, simulations as well as experimental results are presented in various unknown environments.

  18. Comprehensive Transcriptome Profiling and Functional Analysis of the Frog (Bombina maxima) Immune System

    PubMed Central

    Zhao, Feng; Yan, Chao; Wang, Xuan; Yang, Yang; Wang, Guangyin; Lee, Wenhui; Xiang, Yang; Zhang, Yun

    2014-01-01

    Amphibians occupy a key phylogenetic position in vertebrates and evolution of the immune system. But, the resources of its transcriptome or genome are still little now. Bombina maxima possess strong ability to survival in very harsh environment with a more mature immune system. We obtained a comprehensive transcriptome by RNA-sequencing technology. 14.3% of transcripts were identified to be skin-specific genes, most of which were not isolated from skin secretion in previous works or novel non-coding RNAs. 27.9% of transcripts were mapped into 242 predicted KEGG pathways and 6.16% of transcripts related to human disease and cancer. Of 39 448 transcripts with the coding sequence, at least 1501 transcripts (570 genes) related to the immune system process. The molecules of immune signalling pathway were almost presented, several transcripts with high expression in skin and stomach. Experiments showed that lipopolysaccharide or bacteria challenge stimulated pro-inflammatory cytokine production and activation of pro-inflammatory caspase-1. These frog's data can remarkably expand the existing genome or transcriptome resources of amphibians, especially immunity data. The entity of the data provides a valuable platform for further investigation on more detailed immune response in B. maxima and a comparative study with other amphibians. PMID:23942912

  19. HIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation

    PubMed Central

    Heron, Samantha E.; Elahi, Shokrollah

    2017-01-01

    Mucosal surfaces account for the vast majority of HIV transmission. In adults, HIV transmission occurs mainly by vaginal and rectal routes but rarely via oral route. By contrast, pediatric HIV infections could be as the result of oral route by breastfeeding. As such mucosal surfaces play a crucial role in HIV acquisition, and spread of the virus depends on its ability to cross a mucosal barrier. HIV selectively infects, depletes, and/or dysregulates multiple arms of the human immune system particularly at the mucosal sites and causes substantial irreversible damage to the mucosal barriers. This leads to microbial products translocation and subsequently hyper-immune activation. Although introduction of antiretroviral therapy (ART) has led to significant reduction in morbidity and mortality of HIV-infected patients, viral replication persists. As a result, antigen presence and immune activation are linked to “inflammaging” that attributes to a pro-inflammatory environment and the accelerated aging process in HIV patients. HIV infection is also associated with the prevalence of oral mucosal infections and dysregulation of oral microbiota, both of which may compromise the oral mucosal immunity of HIV-infected individuals. In addition, impaired oral immunity in HIV infection may predispose the patients to periodontal diseases that are associated with systemic inflammation and increased risk of cardiovascular diseases. The purpose of this review is to examine existing evidence regarding the role of innate and cellular components of the oral cavity in HIV infection and how HIV infection may drive systemic hyper-immune activation in these patients. We will also discuss current knowledge on HIV oral transmission, HIV immunosenescence in relation to the oral mucosal alterations during the course of HIV infection and periodontal disease. Finally, we discuss oral manifestations associated with HIV infection and how HIV infection and ART influence the oral microbiome

  20. HIV Infection and Compromised Mucosal Immunity: Oral Manifestations and Systemic Inflammation.

    PubMed

    Heron, Samantha E; Elahi, Shokrollah

    2017-01-01

    Mucosal surfaces account for the vast majority of HIV transmission. In adults, HIV transmission occurs mainly by vaginal and rectal routes but rarely via oral route. By contrast, pediatric HIV infections could be as the result of oral route by breastfeeding. As such mucosal surfaces play a crucial role in HIV acquisition, and spread of the virus depends on its ability to cross a mucosal barrier. HIV selectively infects, depletes, and/or dysregulates multiple arms of the human immune system particularly at the mucosal sites and causes substantial irreversible damage to the mucosal barriers. This leads to microbial products translocation and subsequently hyper-immune activation. Although introduction of antiretroviral therapy (ART) has led to significant reduction in morbidity and mortality of HIV-infected patients, viral replication persists. As a result, antigen presence and immune activation are linked to "inflammaging" that attributes to a pro-inflammatory environment and the accelerated aging process in HIV patients. HIV infection is also associated with the prevalence of oral mucosal infections and dysregulation of oral microbiota, both of which may compromise the oral mucosal immunity of HIV-infected individuals. In addition, impaired oral immunity in HIV infection may predispose the patients to periodontal diseases that are associated with systemic inflammation and increased risk of cardiovascular diseases. The purpose of this review is to examine existing evidence regarding the role of innate and cellular components of the oral cavity in HIV infection and how HIV infection may drive systemic hyper-immune activation in these patients. We will also discuss current knowledge on HIV oral transmission, HIV immunosenescence in relation to the oral mucosal alterations during the course of HIV infection and periodontal disease. Finally, we discuss oral manifestations associated with HIV infection and how HIV infection and ART influence the oral microbiome. Therefore

  1. Bovine whey protein concentrate supplementation modulates maturation of immune system in suckling rats.

    PubMed

    Pérez-Cano, Francisco J; Marín-Gallén, Silvia; Castell, Margarida; Rodríguez-Palmero, María; Rivero, Montserrat; Franch, Angels; Castellote, Cristina

    2007-10-01

    During neonatal life, challenges from breast milk and microbial flora promote immune system maturation. Immunonutrition in these stages may become an important way to increase natural defence systems. The aim of this study was to determine the effect of a daily bovine milk whey protein concentrate (WPC) supplement on the intestinal and systemic immune systems in suckling rats. The composition of intraepithelial and lamina propria lymphocytes (IEL and LPL) was analysed by flow cytometry. Systemic and intestinal humoral immune responses were determined by sera Ig levels and Ig-secreting cell quantification by ELISA and ELISPOT, respectively. From birth, suckling Wistar rats were supplemented with WPC or standard infant formula (SIF). The WPC group showed the same proportion of most of the main mucosal cell subsets as the reference animals. However, in the first days of life WPC enhanced the innate immunity by increasing the NK cell proportion in both epithelial and lamina propria (LP) compartments. A rise in intestinal CD8alphaalpha+ IEL was also induced by WPC supplementation. A time-course of sera Ig levels and spontaneous IgA, IgM and IgG production by LPL and mononuclear cells from blood and spleen, in the WPC group, exhibited a similar pattern to those pups fed only by dam's milk. In summary, the present results show the effects of WPC on enhancing mucosal innate immunity during early life.

  2. Beneficial influences of systemic cooperation and sociological behavior on longevity.

    PubMed

    Mountz, John D; Zant, Gary Van; Allison, David B; Zhang, Huang-Ge; Hsu, Hui-Chen

    2002-04-30

    During his long research career in the field of aging, Dr Bernard Strehler developed a series of theories concerning the identity of genes that can promote longevity and their role in natural selection. As a tribute to Dr Strehler, we have taken this opportunity to summarize a selection of these theories and to illustrate how these insights have influenced our search for longevity genes within the immune system. The identification of longevity genes has proven difficult. We believe that, at least in part, this reflects the emphasis on the concept of survival of the 'physically' fittest. We have used the immune system as a model to demonstrate that, over and above the self-evident advantage of those genes that contribute the attributes commonly associated with survival of the 'physically' fittest, those genes that lead to a predisposition to cooperate also confer a competitive survival advantage. As the acquisition of cooperativity in a society is linked to support mechanisms provided by older individuals, the search for longevity genes should not be limited to those genes that are associated with extended expression of a youthful phenotype. Rather these studies should be expanded to include identification of those genes that regulate physiologic parameters that affect individual longevity, even if they do not correspond with the traditional view of reproductive competitiveness. At the societal level, longevity genes may encode attributes that regulate sociologic or psychological parameters that may contribute to a tendency to non-aggressive or cooperative behavior that leads to achievement of common goals necessary for the survival of the species. This view of the selection for longevity impacts the analysis of longevity genes and aging at the organismal level. Dr Strehler viewed organismal aging as an integrated functional state, in which he conceived the outcome as reflecting the net balance of functional decrementers and evolved compensatory features. We propose

  3. The Effect of Microbiota and the Immune System on the Development and Organization of the Enteric Nervous System.

    PubMed

    Obata, Yuuki; Pachnis, Vassilis

    2016-11-01

    The gastrointestinal (GI) tract is essential for the absorption of nutrients, induction of mucosal and systemic immune responses, and maintenance of a healthy gut microbiota. Key aspects of gastrointestinal physiology are controlled by the enteric nervous system (ENS), which is composed of neurons and glial cells. The ENS is exposed to and interacts with the outer (microbiota, metabolites, and nutrients) and inner (immune cells and stromal cells) microenvironment of the gut. Although the cellular blueprint of the ENS is mostly in place by birth, the functional maturation of intestinal neural networks is completed within the microenvironment of the postnatal gut, under the influence of gut microbiota and the mucosal immune system. Recent studies have shown the importance of molecular interactions among microbiota, enteric neurons, and immune cells for GI homeostasis. In addition to its role in GI physiology, the ENS has been associated with the pathogenesis of neurodegenerative disorders, such as Parkinson's disease, raising the possibility that microbiota-ENS interactions could offer a viable strategy for influencing the course of brain diseases. Here, we discuss recent advances on the role of microbiota and the immune system on the development and homeostasis of the ENS, a key relay station along the gut-brain axis. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

  4. Immune and Neuroendocrine Mechanisms of Stress Vulnerability and Resilience

    PubMed Central

    Ménard, Caroline; Pfau, Madeline L; Hodes, Georgia E; Russo, Scott J

    2017-01-01

    Diagnostic criteria for mood disorders including major depressive disorder (MDD) largely ignore biological factors in favor of behavioral symptoms. Compounding this paucity of psychiatric biomarkers is a need for therapeutics to adequately treat the 30–50% of MDD patients who are unresponsive to traditional antidepressant medications. Interestingly, MDD is highly prevalent in patients suffering from chronic inflammatory conditions, and MDD patients exhibit higher levels of circulating pro-inflammatory cytokines. Together, these clinical findings suggest a role for the immune system in vulnerability to stress-related psychiatric illness. A growing body of literature also implicates the immune system in stress resilience and coping. In this review, we discuss the mechanisms by which peripheral and central immune cells act on the brain to affect stress-related neurobiological and neuroendocrine responses. We specifically focus on the roles of pro-inflammatory cytokine signaling, peripheral monocyte infiltration, microglial activation, and hypothalamic-pituitary-adrenal axis hyperactivity in stress vulnerability. We also highlight recent evidence suggesting that adaptive immune responses and treatment with immune modulators (exogenous glucocorticoids, humanized antibodies against cytokines) may decrease depressive symptoms and thus represent an attractive alternative to the current antidepressant treatments. PMID:27291462

  5. The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy

    PubMed Central

    Law, Andrew M K; Lim, Elgene; Ormandy, Christopher J

    2017-01-01

    A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy. Among these cell types, immune cells have emerged as a promising target for therapy. The adaptive and the innate immune system play an important role in normal mammary development and breast cancer. The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily, T lymphocytes, is lower in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression. A consideration of components of both the innate and the adaptive immune system is essential for the design and development of immunotherapies in breast cancer. In this review, we focus on the importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) as potential targets for breast cancer therapy. PMID:28193698

  6. The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy.

    PubMed

    Law, Andrew M K; Lim, Elgene; Ormandy, Christopher J; Gallego-Ortega, David

    2017-04-01

    A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy. Among these cell types, immune cells have emerged as a promising target for therapy. The adaptive and the innate immune system play an important role in normal mammary development and breast cancer. The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily, T lymphocytes, is lower in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression. A consideration of components of both the innate and the adaptive immune system is essential for the design and development of immunotherapies in breast cancer. In this review, we focus on the importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) as potential targets for breast cancer therapy. © 2017 The authors.

  7. Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system

    PubMed Central

    Lukasch, Barbara; Westerdahl, Helena; Strandh, Maria; Winkler, Hans; Moodley, Yoshan; Knauer, Felix

    2017-01-01

    Background A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important. Methods To do this we used captive house sparrows (Passer domesticus) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Results Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles. Discussion We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic. PMID:28875066

  8. Genes of the major histocompatibility complex highlight interactions of the innate and adaptive immune system.

    PubMed

    Lukasch, Barbara; Westerdahl, Helena; Strandh, Maria; Winkler, Hans; Moodley, Yoshan; Knauer, Felix; Hoi, Herbert

    2017-01-01

    A well-functioning immune defence is crucial for fitness, but our knowledge about the immune system and its complex interactions is still limited. Major histocompatibility complex (MHC) molecules are involved in T-cell mediated adaptive immune responses, but MHC is also highly upregulated during the initial innate immune response. The aim of our study was therefore to determine to what extent the highly polymorphic MHC is involved in interactions of the innate and adaptive immune defence and if specific functional MHC alleles (FA) or heterozygosity at the MHC are more important. To do this we used captive house sparrows ( Passer domesticus ) to survey MHC diversity and immune function controlling for several environmental factors. MHC class I alleles were identified using parallel amplicon sequencing and to mirror immune function, several immunological tests that correspond to the innate and adaptive immunity were conducted. Our results reveal that MHC was linked to all immune tests, highlighting its importance for the immune defence. While all innate responses were associated with one single FA, adaptive responses (cell-mediated and humoral) were associated with several different alleles. We found that repeated injections of an antibody in nestlings and adults were linked to different FA and hence might affect different areas of the immune system. Also, individuals with a higher number of different FA produced a smaller secondary response, indicating a disadvantage of having numerous MHC alleles. These results demonstrate the complexity of the immune system in relation to the MHC and lay the foundation for other studies to further investigate this topic.

  9. Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection

    PubMed Central

    Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

    2015-01-01

    Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close “neighborhood” of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa. PMID:26327290

  10. Sensitivity Analysis of an ENteric Immunity SImulator (ENISI)-Based Model of Immune Responses to Helicobacter pylori Infection.

    PubMed

    Alam, Maksudul; Deng, Xinwei; Philipson, Casandra; Bassaganya-Riera, Josep; Bisset, Keith; Carbo, Adria; Eubank, Stephen; Hontecillas, Raquel; Hoops, Stefan; Mei, Yongguo; Abedi, Vida; Marathe, Madhav

    2015-01-01

    Agent-based models (ABM) are widely used to study immune systems, providing a procedural and interactive view of the underlying system. The interaction of components and the behavior of individual objects is described procedurally as a function of the internal states and the local interactions, which are often stochastic in nature. Such models typically have complex structures and consist of a large number of modeling parameters. Determining the key modeling parameters which govern the outcomes of the system is very challenging. Sensitivity analysis plays a vital role in quantifying the impact of modeling parameters in massively interacting systems, including large complex ABM. The high computational cost of executing simulations impedes running experiments with exhaustive parameter settings. Existing techniques of analyzing such a complex system typically focus on local sensitivity analysis, i.e. one parameter at a time, or a close "neighborhood" of particular parameter settings. However, such methods are not adequate to measure the uncertainty and sensitivity of parameters accurately because they overlook the global impacts of parameters on the system. In this article, we develop novel experimental design and analysis techniques to perform both global and local sensitivity analysis of large-scale ABMs. The proposed method can efficiently identify the most significant parameters and quantify their contributions to outcomes of the system. We demonstrate the proposed methodology for ENteric Immune SImulator (ENISI), a large-scale ABM environment, using a computational model of immune responses to Helicobacter pylori colonization of the gastric mucosa.

  11. The Spleen: A Hub Connecting Nervous and Immune Systems in Cardiovascular and Metabolic Diseases

    PubMed Central

    Lori, Andrea; Perrotta, Marialuisa; Lembo, Giuseppe; Carnevale, Daniela

    2017-01-01

    Metabolic disorders have been identified as major health problems affecting a large portion of the world population. In addition, obesity and insulin resistance are principal risk factors for the development of cardiovascular diseases. Altered immune responses are common features of both hypertension and obesity and, moreover, the involvement of the nervous system in the modulation of immune system is gaining even more attention in both pathophysiological contexts. For these reasons, during the last decades, researches focused their efforts on the comprehension of the molecular mechanisms connecting immune system to cardiovascular and metabolic diseases. On the other hand, it has been reported that in these pathological conditions, central neural pathways modulate the activity of the peripheral nervous system, which is strongly involved in onset and progression of the disease. It is interesting to notice that neural reflex can also participate in the modulation of immune functions. In this scenario, the spleen becomes the crucial hub allowing the interaction of different systems differently involved in metabolic and cardiovascular diseases. Here, we summarize the major findings that dissect the role of the immune system in disorders related to metabolic and cardiovascular dysfunctions, and how this could also be influenced by neural reflexes. PMID:28590409

  12. Parameters of the Immune System and Vitamin D Levels in Old Individuals.

    PubMed

    Alves, Amanda Soares; Ishimura, Mayari Eika; Duarte, Yeda Aparecida de Oliveira; Bueno, Valquiria

    2018-01-01

    The increased number of individuals older than 80 years, centenarians, and supercentenarians is not a synonym for healthy aging, since severe infections, hospitalization, and disability are frequently observed. In this context, a possible strategy is to preserve the main characteristics/functions of the immune system with the aim to cause less damage to the organism during the aging process. Vitamin D acts on bone marrow, brain, breast, malignant cells, and immune system and has been recommended as a supplement. We aimed to evaluate whether immune parameters and vitamin D serum levels are correlated. We evaluated some features of the immune system using the peripheral blood of individuals older than 80 years ( n  = 12) compared to young subjects ( n  = 10). In addition, we correlated these findings with vitamin D serum levels. Old individuals presented metabolic parameters of healthy aging and maintained preserved some features of immunity such as CD4/CD8 ratio, and low production of pro-inflammatory cytokines after stimulus. On the other hand, we observed increase in the frequency of myeloid-derived suppressor cells, reduction in circulating leukocytes, in the percentage of total CD8+, and in CD8+ Naïve T cells, in addition to increase in the percentage of CD8+ effector memory re-expressing CD45RA (EMRA) T cells. We found seropositivity for CMV in 97.7%, which was correlated with the decrease of CD8+ Naïve T cells and increase in CD8+ EMRA T cells. Vitamin D levels were insufficient in 50% of old individuals and correlated positively with total CD8+ T cells and negatively with CD8+ EMRA T cells. In the studied population, longevity was correlated to maintenance of some immune parameters. Considering the limitations of the study as size of the sample and lack of functional assays, it was found that vitamin D in old individuals was correlated to some features of the immune system, mainly in the CD8 compartment.

  13. Immune system stimulation in rats by Lactobacillus sp. isolates from Raffia wine (Raphia vinifera).

    PubMed

    Flore, Tiepma N E; François, Zambou N; Félicité, Tchouanguep M

    2010-01-01

    The immune system consists of organs and several cell types. Antigen interaction with these cells induces a cellular immune response mediated by activated cells. The effects of lactic acid bacteria on the systemic immune response and on the secretory immune system are described. The current investigation sets out to examine the possible effects of isolated wine lacto-bacilli upon various hematologic and immunologic parameters in rats. We have fed rats with probiotic isolates from Raffia wine and challenged with castor oil; two control groups were fed with castor oil and others were not. We counted blood cells at the end of the experiment; all isolates seemed to cause a decrease of circulating white blood cells. The percentage of lymphocytes and the total protein in the spleen increased in the treated animals; also a normal aspect of faeces was observed compared to the control. These isolates of Lactobacillus seem to occur to immune cell-mediated responses in rats.

  14. Early Peritoneal Immune Response during Echinococcus granulosus Establishment Displays a Biphasic Behavior

    PubMed Central

    Mourglia-Ettlin, Gustavo; Marqués, Juan Martín; Chabalgoity, José Alejandro; Dematteis, Sylvia

    2011-01-01

    Background Cystic echinococcosis is a worldwide distributed helminth zoonosis caused by the larval stage of Echinococcus granulosus. Human secondary cystic echinococcosis is caused by dissemination of protoscoleces after accidental rupture of fertile cysts and is due to protoscoleces ability to develop into new metacestodes. In the experimental model of secondary cystic echinococcosis mice react against protoscoleces producing inefficient immune responses, allowing parasites to develop into cysts. Although the chronic phase of infection has been analyzed in depth, early immune responses at the site of infection establishment, e.g., peritoneal cavity, have not been well studied. Because during early stages of infection parasites are thought to be more susceptible to immune attack, this work focused on the study of cellular and molecular events triggered early in the peritoneal cavity of infected mice. Principal Findings Data obtained showed disparate behaviors among subpopulations within the peritoneal lymphoid compartment. Regarding B cells, there is an active molecular process of plasma cell differentiation accompanied by significant local production of specific IgM and IgG2b antibodies. In addition, peritoneal NK cells showed a rapid increase with a significant percentage of activated cells. Peritoneal T cells showed a substantial increase, with predominance in CD4+ T lymphocytes. There was also a local increase in Treg cells. Finally, cytokine response showed local biphasic kinetics: an early predominant induction of Th1-type cytokines (IFN-γ, IL-2 and IL-15), followed by a shift toward a Th2-type profile (IL-4, IL-5, IL-6, IL-10 and IL-13). Conclusions Results reported here open new ways to investigate the involvement of immune effectors players in E. granulosus establishment, and also in the sequential promotion of Th1- toward Th2-type responses in experimental secondary cystic echinococcosis. These data would be relevant for designing rational therapies

  15. Distinct alterations in motor & reward seeking behavior are dependent on the gestational age of exposure to LPS-induced maternal immune activation.

    PubMed

    Straley, Megan E; Van Oeffelen, Wesley; Theze, Sarah; Sullivan, Aideen M; O'Mahony, Siobhain M; Cryan, John F; O'Keeffe, Gerard W

    2017-07-01

    The dopaminergic system is involved in motivation, reward and the associated motor activities. Mesodiencephalic dopaminergic neurons in the ventral tegmental area (VTA) regulate motivation and reward, whereas those in the substantia nigra (SN) are essential for motor control. Defective VTA dopaminergic transmission has been implicated in schizophrenia, drug addiction and depression whereas dopaminergic neurons in the SN are lost in Parkinson's disease. Maternal immune activation (MIA) leading to in utero inflammation has been proposed to be a risk factor for these disorders, yet it is unclear how this stimulus can lead to the diverse disturbances in dopaminergic-driven behaviors that emerge at different stages of life in affected offspring. Here we report that gestational age is a critical determinant of the subsequent alterations in dopaminergic-driven behavior in rat offspring exposed to lipopolysaccharide (LPS)-induced MIA. Behavioral analysis revealed that MIA on gestational day 16 but not gestational day 12 resulted in biphasic impairments in motor behavior. Specifically, motor impairments were evident in early life, which were resolved by adolescence, but subsequently re-emerged in adulthood. In contrast, reward seeking behaviors were altered in offspring exposed MIA on gestational day 12. These changes were not due to a loss of dopaminergic neurons per se in the postnatal period, suggesting that they reflect functional changes in dopaminergic systems. This highlights that gestational age may be a key determinant of how MIA leads to distinct alterations in dopaminergic-driven behavior across the lifespan of affected offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. The effect of tonsillectomy on the immune system: A systematic review and meta-analysis.

    PubMed

    Bitar, Mohamad A; Dowli, Alexander; Mourad, Marc

    2015-08-01

    The immunological sequelae of tonsillectomy in children have been a source of debate among physicians and a continuous concern for parents. Contradictory pertinent results exist in the literature. To understand the real effect of tonsillectomy on the immune system. MEDLINE, EMBASE and COCHRANE. Articles addressing the effect of tonsillectomy on the immune system, up to Dec 2014. Related keywords and medical subject headings were used during the search. The abstracts were reviewed to determine suitability for inclusion based on a set of criteria. Manual crosscheck of references was performed. We checked the tests results and the conclusion of each study to classify it as supporting or refuting the hypothesis of a negative effect of tonsillectomy on the immune system. We reviewed 35 articles, published between 1971 and 2014, including 1997 patients. Only Four studies (11.4%), including 406 patients (20.3%) found that tonsillectomy negatively affects the immune system. We performed a separate meta-analysis on various reviewed humoral and cellular immunological parameters (e.g. total and specific serum Ig's, SecIgA, cellular immunity, and Ag specific Ig). There is more evidence to suggest that tonsillectomy has no negative clinical or immunological sequalae on the immune system. Study limitations included heterogeneity in the diagnostic tools, timing of testing, indication for tonsillectomy and patients' age. It is reasonable to say that there is enough evidence to conclude that tonsillectomy has no clinically significant negative effect on the immune system. It will be important for future studies to uniformly use both preoperative and control laboratory tests' levels to compare the postoperative levels with, to have short and long term follow-up levels, and to include both humoral and cellular immunity in their measurements. The results should reassure both surgeons and parents that tonsillectomy has no proven clinical sequalae. If more research is to be done in the

  17. Mucosal and systemic immune modulation by Trichuris trichiura in a self-infected individual.

    PubMed

    Dige, A; Rasmussen, T K; Nejsum, P; Hagemann-Madsen, R; Williams, A R; Agnholt, J; Dahlerup, J F; Hvas, C L

    2017-01-01

    Helminthic therapy of immune-mediated diseases has gained attention in recent years, but we know little of how helminths modulate human immunity. In this study, we investigated how self-infection with Trichuris (T.) trichiura in an adult man without intestinal disease affected mucosal and systemic immunity. Colonic mucosal biopsies were obtained at baseline, during T. trichiura infection, and after its clearance following mebendazole treatment. Unexpectedly, the volunteer experienced a Campylobacter colitis following T. trichiura clearance, and this served as a positive infectious control. Trichuris trichiura colonization induced equally increased expressions of T-helper (h)1-, Th2-, Th17- and Treg-associated cytokines and transcription factors, measured by quantitative polymerase chain reaction. We observed several indicators of modulation of systemic immunity during the T. trichiura infection. Plasma eosinophils and anti-Trichuris antibodies rose markedly during the inoculation phase, and a shift towards a Th2-dominated T cell response at the expense of the Th1-response was observed in circulating T cells. Taken together, our findings corroborate that helminths modulate regional and systemic human immunity. © 2016 John Wiley & Sons Ltd.

  18. Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease.

    PubMed

    Masliah, Eliezer; Rockenstein, Edward; Mante, Michael; Crews, Leslie; Spencer, Brian; Adame, Anthony; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Rohn, Troy T; Mueller-Steiner, Sarah; Seubert, Peter; Barbour, Robin; McConlogue, Lisa; Buttini, Manuel; Games, Dora; Schenk, Dale

    2011-04-29

    Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB.

  19. An automated diagnosis system of liver disease using artificial immune and genetic algorithms.

    PubMed

    Liang, Chunlin; Peng, Lingxi

    2013-04-01

    The rise of health care cost is one of the world's most important problems. Disease prediction is also a vibrant research area. Researchers have approached this problem using various techniques such as support vector machine, artificial neural network, etc. This study typically exploits the immune system's characteristics of learning and memory to solve the problem of liver disease diagnosis. The proposed system applies a combination of two methods of artificial immune and genetic algorithm to diagnose the liver disease. The system architecture is based on artificial immune system. The learning procedure of system adopts genetic algorithm to interfere the evolution of antibody population. The experiments use two benchmark datasets in our study, which are acquired from the famous UCI machine learning repository. The obtained diagnosis accuracies are very promising with regard to the other diagnosis system in the literatures. These results suggest that this system may be a useful automatic diagnosis tool for liver disease.

  20. TV synchronization system features stability and noise immunity

    NASA Technical Reports Server (NTRS)

    Landauer, F. P.

    1967-01-01

    Horizontal jitter in the video presentation in television systems is prevented by using an additional sync level. This circuitry uses simultaneous signals at both sync and porch frequencies, providing a sync identification from which a coincidence circuit can generate pulses having the required stability and noise immunity.

  1. Construction of an integrated gene regulatory network link to stress-related immune system in cattle.

    PubMed

    Behdani, Elham; Bakhtiarizadeh, Mohammad Reza

    2017-10-01

    The immune system is an important biological system that is negatively impacted by stress. This study constructed an integrated regulatory network to enhance our understanding of the regulatory gene network used in the stress-related immune system. Module inference was used to construct modules of co-expressed genes with bovine leukocyte RNA-Seq data. Transcription factors (TFs) were then assigned to these modules using Lemon-Tree algorithms. In addition, the TFs assigned to each module were confirmed using the promoter analysis and protein-protein interactions data. Therefore, our integrated method identified three TFs which include one TF that is previously known to be involved in immune response (MYBL2) and two TFs (E2F8 and FOXS1) that had not been recognized previously and were identified for the first time in this study as novel regulatory candidates in immune response. This study provides valuable insights on the regulatory programs of genes involved in the stress-related immune system.

  2. Chapter 2: Innate Immunity

    PubMed Central

    Turvey, Stuart E.; Broide, David H.

    2009-01-01

    Recent years have witnessed an explosion of interest in the innate immune system. Questions about how the innate immune system senses infection and empowers a protective immune response are being answered at the molecular level. These basic science discoveries are being translated into a more complete understanding of the central role innate immunity plays in the pathogenesis of many human infectious and inflammatory diseases. It is particularly exciting that we are already seeing a return on these scientific investments with the emergence of novel therapies to harness the power of the innate immune system. In this review we explore the defining characteristics of the innate immune system, and through more detailed examples, we highlight recent breakthroughs that have advanced our understanding of the role of innate immunity in human health and disease. PMID:19932920

  3. Studies of Cell-Mediated Immunity Against Immune Disorders Using Synthetic Peptides and Rotating Bioreactor System

    NASA Technical Reports Server (NTRS)

    Sastry, Jagannadha K.

    1998-01-01

    We conducted a series of experiments using mouse immune-precursor cells, and observed that bioreactor culturing results in the loss of antigen-specific cytotoxic T lymphocyte (CTL) function. The reason for the abrogation of CTL function is microgravity conditions in the bioreactor, but not the antigen per se or its MHC restriction. Similarly, we observed that allostimulation of human PBMC in the bioreactor, but not in the T flask, resulted in the blunting of both allo-CTL function and the NK activity, indicating that the microgravity-associated functional defects are not unique to the mouse system. These results provide further confirmation to the microgravity-associated immune dysfunction, and constitute ground-based confirmatory data for those related to space-travel.

  4. Selfish brain and selfish immune system interplay: A theoretical framework for metabolic comorbidities of mood disorders.

    PubMed

    Yamagata, Ana Sayuri; Mansur, Rodrigo Barbachan; Rizzo, Lucas Bortolotto; Rosenstock, Tatiana; McIntyre, Roger S; Brietzke, Elisa

    2017-01-01

    According to the "selfish brain" theory, the brain regulates its own energy supply influencing the peripheral metabolism and food intake according to its needs. The immune system has been likewise "selfish" due to independent energy consumption; and it may compete with the brain (another high energy-consumer) for glucose. In mood disorders, stress in mood episodes or physiological stress activate homeostasis mechanisms from the brain and the immune system to solve the imbalance. The interaction between the selfish brain and the selfish immune system may explain various conditions of medical impairment in mood disorders, such as Metabolic Syndrome (MetS), obesity, type 2 diabetes mellitus (T2DM) and immune dysregulation. The objective of this study is to comprehensively review the literature regarding the competition between the brain and the immune system for energy substrate. Targeting the energetic regulation of the brain and the immune system and their cross-talk open alternative treatments and a different approach in the study of general medical comorbidities in mood disorders, although more investigation is needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. The roles of the immune system in women's reproduction: evolutionary constraints and life history trade-offs.

    PubMed

    Abrams, Elizabeth T; Miller, Elizabeth M

    2011-01-01

    Life history theory posits that, as long as survival is assured, finite resources are available for reproduction, maintenance, and growth/storage. To maximize lifetime reproductive success, resources are subject to trade-offs both within individuals and between current and future investment. For women, reproducing is costly and time-consuming; the bulk of available resources must be allocated to reproduction at the expense of more flexible systems like immune function. When reproducing women contract infectious diseases, the resources required for immune activation can fundamentally shift the patterns of resource allocation. Adding to the complexity of the reproductive-immune trade-offs in women are the pleiotropic effects of many immune factors, which were modified to serve key roles in mammalian reproduction. In this review, we explore the complex intersections between immune function and female reproduction to situate proximate immunological processes within a life history framework. After a brief overview of the immune system, we discuss some important physiological roles of immune factors in women's reproduction and the conflicts that may arise when these factors must play dual roles. We then discuss the influence of reproductive-immune trade-offs on the patterning of lifetime reproductive success: (1) the effect of immune activation/infectious disease on the timing of life history events; (2) the role of the immune system, immune activation, and infectious disease on resource allocation within individual reproductive events, particularly pregnancy; and (3) the role of the immune system in shaping the offspring's patterns of future life history trade-offs. We close with a discussion of future directions in reproductive immunology for anthropologists. Copyright © 2011 Wiley Periodicals, Inc.

  6. The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease.

    PubMed

    Holleran, Grainne; Lopetuso, Loris; Petito, Valentina; Graziani, Cristina; Ianiro, Gianluca; McNamara, Deirdre; Gasbarrini, Antonio; Scaldaferri, Franco

    2017-09-21

    Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date.

  7. The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease

    PubMed Central

    Holleran, Grainne; Lopetuso, Loris; Petito, Valentina; Graziani, Cristina; Ianiro, Gianluca; McNamara, Deirdre; Gasbarrini, Antonio; Scaldaferri, Franco

    2017-01-01

    Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date. PMID:28934123

  8. Methods for increasing noise immunity of radio electronic systems with redundancy

    NASA Astrophysics Data System (ADS)

    Orlov, P. E.; Medvedev, A. V.; Sharafutdinov, V. R.; Gazizov, T. R.; Ubaichin, A. V.

    2018-05-01

    The idea of increasing the noise immunity of radioelectronic systems with redundancy is presented. Specific technical solutions based on this idea of modal redundancy are described. An estimation of noise immunity improvement was performed by the example of implementation of modal redundancy with the broad-side electromagnetic coupling for a printed circuit board of the digital signal processing unit for an autonomous navigation system of a spacecraft. It is shown that the implementation of modal redundancy can provide an attenuation coefficient for the interference signal up to 12 dB.

  9. MicroRNAs (MiRs) Precisely Regulate Immune System Development and Function in Immunosenescence Process.

    PubMed

    Aalaei-Andabili, Seyed Hossein; Rezaei, Nima

    2016-01-01

    Human aging is a complex process with pivotal changes in gene expression of biological pathways. Immune system dysfunction has been recognized as one of the most important abnormalities induced by senescent names immunosenescence. Emerging evidences suggest miR role in immunosenescence. We aimed to systemically review all relevant reports to clearly state miR effects on immunosenescence process. Sensitive electronic searches carried out. Quality assessment has been performed. Since majority of the included studies were laboratory works, and therefore heterogen, we discussed miR effects on immunological aging process nonstatically. Forty-six articles were found in the initial search. After exclusion of 34 articles, 12 studies enrolled to the final stage. We found that miRs have crucial roles in exact function of immune system. MiRs are involved in the regulation of the aging process in the immune system components and target certain genes, promoting or inhibiting immune system reaction to invasion. Also, miRs control life span of the immune system members by regulation of the genes involved in the apoptosis. Interestingly, we found that immunosenescence is controllable by proper manipulation of the various miRs expression. DNA methylation and histone acetylation have been discovered as novel strategies, altering NF-κB binding ability to the miR promoter sites. Effect of miRs on impairment of immune system function due to the aging is emerging. Although it has been accepted that miRs have determinant roles in the regulation of the immunosenescence; however, most of the reports are concluded from animal/laboratory works, suggesting the necessity of more investigations in human.

  10. Hygiene and other early childhood influences on the subsequent function of the immune system.

    PubMed

    Rook, Graham A W; Lowry, Christopher A; Raison, Charles L

    2015-08-18

    The immune system influences brain development and function. Hygiene and other early childhood influences impact the subsequent function of the immune system during adulthood, with consequences for vulnerability to neurodevelopmental and psychiatric disorders. Inflammatory events during pregnancy can act directly to cause developmental problems in the central nervous system (CNS) that have been implicated in schizophrenia and autism. The immune system also acts indirectly by "farming" the intestinal microbiota, which then influences brain development and function via the multiple pathways that constitute the gut-brain axis. The gut microbiota also regulates the immune system. Regulation of the immune system is crucial because inflammatory states in pregnancy need to be limited, and throughout life inflammation needs to be terminated completely when not required; for example, persistently raised levels of background inflammation during adulthood (in the presence or absence of a clinically apparent inflammatory stimulus) correlate with an increased risk of depression. A number of factors in the perinatal period, notably immigration from rural low-income to rich developed settings, caesarean delivery, breastfeeding and antibiotic abuse have profound effects on the microbiota and on immunoregulation during early life that persist into adulthood. Many aspects of the modern western environment deprive the infant of the immunoregulatory organisms with which humans co-evolved, while encouraging exposure to non-immunoregulatory organisms, associated with more recently evolved "crowd" infections. Finally, there are complex interactions between perinatal psychosocial stressors, the microbiota, and the immune system that have significant additional effects on both physical and psychiatric wellbeing in subsequent adulthood. This article is part of a Special Issue entitled Neuroimmunology in Health And Disease. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights

  11. Innate immune memory in plants.

    PubMed

    Reimer-Michalski, Eva-Maria; Conrath, Uwe

    2016-08-01

    The plant innate immune system comprises local and systemic immune responses. Systemic plant immunity develops after foliar infection by microbial pathogens, upon root colonization by certain microbes, or in response to physical injury. The systemic plant immune response to localized foliar infection is associated with elevated levels of pattern-recognition receptors, accumulation of dormant signaling enzymes, and alterations in chromatin state. Together, these systemic responses provide a memory to the initial infection by priming the remote leaves for enhanced defense and immunity to reinfection. The plant innate immune system thus builds immunological memory by utilizing mechanisms and components that are similar to those employed in the trained innate immune response of jawed vertebrates. Therefore, there seems to be conservation, or convergence, in the evolution of innate immune memory in plants and vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations.

    PubMed

    Ramirez, Karol; Niraula, Anzela; Sheridan, John F

    2016-01-01

    Psychosocial stress is associated with altered immunity, anxiety, and depression. Repeated social defeat (RSD), a model of social stress, triggers egress of inflammatory myeloid progenitor cells (MPCs; CD11b(+)/Ly6C(hi)) that traffic to the brain, promoting anxiety-like behavior. In parallel, RSD enhances neuroinflammatory signaling and long-lasting social avoidant behavior. Lorazepam and clonazepam are routinely prescribed anxiolytics that act by enhancing GABAergic activity in the brain. Besides binding to the central benzodiazepine binding site (CBBS) in the central nervous system (CNS), lorazepam binds to the translocator protein (TSPO) with high affinity causing immunomodulation. Clonazepam targets the CBBS and has low affinity for the TSPO. Here the aims were to determine if lorazepam and clonazepam would: (1) prevent stress-induced peripheral and central inflammatory responses, and (2) block anxiety and social avoidance behavior in mice subjected to RSD. C57/BL6 mice were divided into experimental groups, and treated with either lorazepam (0.10mg/kg), clonazepam (0.25mg/kg) or vehicle (0.9% NaCl). Behavioral data and tissues were collected the morning after the last cycle of RSD. Lorazepam and clonazepam were effective in attenuating mRNA expression of CRH in the hypothalamus and corticosterone in plasma in mice subjected to RSD. Both drugs blocked stress-induced levels of IL-6 in plasma. Lorazepam and clonazepam had different effects on stress-induced enhancement of myelopoiesis and inhibited trafficking of monocytes and granulocytes in circulation. Furthermore, lorazepam, but not clonazepam, inhibited splenomegaly and the production of pro-inflammatory cytokines in the spleen following RSD. Additionally, lorazepam and clonazepam, blocked stress-induced accumulation of macrophages (CD11b(+)/CD45(high)) in the CNS. In a similar manner, both lorazepam and clonazepam prevented neuroinflammatory signaling and reversed anxiety-like and depressive-like behavior

  13. GABAergic modulation with classical benzodiazepines prevent stress-induced neuro-immune dysregulation and behavioral alterations

    PubMed Central

    Ramirez, Karol; Niraula, Anzela; Sheridan, John F.

    2015-01-01

    Objective Psychosocial stress is associated with altered immunity, anxiety, and depression. Repeated social defeat (RSD), a model of social stress, triggers egress of inflammatory myeloid progenitor cells (MPCs; CD11b+ /Ly6Chi) that traffic to the brain, promoting anxiety-like behavior. In parallel, RSD enhances neuroinflammatory signaling and long-lasting social avoidant behavior. Lorazepam and clonazepam are routinely prescribed anxiolytics that act by enhancing GABAergic activity in the brain. Besides binding to the central benzodiazepine binding site (CBBS) in the central nervous system (CNS), lorazepam binds to the translocator protein (TSPO) with high affinity causing immunomodulation. Clonazepam targets the CBBS and has low affinity for the TSPO. Here the aims were to determine if lorazepam and clonazepam would: 1) prevent stress-induced peripheral and central inflammatory responses, and 2) block anxiety and social avoidance behavior in mice subjected to RSD. Methods C57/BL6 mice were divided into experimental groups, and treated with either lorazepam (0.10mg/kg), clonazepam (0.25 mg/kg) or vehicle (0.9%NaCl). Behavioral data and tissues were collected the morning after the last cycle of RSD. Results Lorazepam and clonazepam were effective in attenuating mRNA expression of CRH in the hypothalamus and corticosterone in plasma in mice subjected to RSD. Both drugs blocked stress-induced levels of IL-6 in plasma. Lorazepam and clonazepam had different effects on stress-induced enhancement of myelopoiesis and inhibited trafficking of monocytes and granulocytes in circulation. Furthermore, lorazepam, but not clonazepam, inhibited splenomegaly and the production of pro-inflammatory cytokines in the spleen following RSD. Additionally, lorazepam and clonazepam, blocked stress-induced accumulation of macrophages (CD11b+/CD45high) in the CNS. In a similar manner, both lorazepam and clonazepam prevented neuroinflammatory signaling and reversed anxiety-like and

  14. Candidate innate immune system gene expression in the ecological model Daphnia

    PubMed Central

    Decaestecker, Ellen; Labbé, Pierrick; Ellegaard, Kirsten; Allen, Judith E.; Little, Tom J.

    2011-01-01

    The last ten years have witnessed increasing interest in host–pathogen interactions involving invertebrate hosts. The invertebrate innate immune system is now relatively well characterised, but in a limited range of genetic model organisms and under a limited number of conditions. Immune systems have been little studied under real-world scenarios of environmental variation and parasitism. Thus, we have investigated expression of candidate innate immune system genes in the water flea Daphnia, a model organism for ecological genetics, and whose capacity for clonal reproduction facilitates an exceptionally rigorous control of exposure dose or the study of responses at many time points. A unique characteristic of the particular Daphnia clones and pathogen strain combinations used presently is that they have been shown to be involved in specific host–pathogen coevolutionary interactions in the wild. We choose five genes, which are strong candidates to be involved in Daphnia–pathogen interactions, given that they have been shown to code for immune effectors in related organisms. Differential expression of these genes was quantified by qRT-PCR following exposure to the bacterial pathogen Pasteuria ramosa. Constitutive expression levels differed between host genotypes, and some genes appeared to show correlated expression. However, none of the genes appeared to show a major modification of expression level in response to Pasteuria exposure. By applying knowledge from related genetic model organisms (e.g. Drosophila) to models for the study of evolutionary ecology and coevolution (i.e. Daphnia), the candidate gene approach is temptingly efficient. However, our results show that detection of only weak patterns is likely if one chooses target genes for study based on previously identified genome sequences by comparison to homologues from other related organisms. Future work on the Daphnia–Pasteuria system will need to balance a candidate gene approach with more

  15. Candidate innate immune system gene expression in the ecological model Daphnia.

    PubMed

    Decaestecker, Ellen; Labbé, Pierrick; Ellegaard, Kirsten; Allen, Judith E; Little, Tom J

    2011-10-01

    The last ten years have witnessed increasing interest in host-pathogen interactions involving invertebrate hosts. The invertebrate innate immune system is now relatively well characterised, but in a limited range of genetic model organisms and under a limited number of conditions. Immune systems have been little studied under real-world scenarios of environmental variation and parasitism. Thus, we have investigated expression of candidate innate immune system genes in the water flea Daphnia, a model organism for ecological genetics, and whose capacity for clonal reproduction facilitates an exceptionally rigorous control of exposure dose or the study of responses at many time points. A unique characteristic of the particular Daphnia clones and pathogen strain combinations used presently is that they have been shown to be involved in specific host-pathogen coevolutionary interactions in the wild. We choose five genes, which are strong candidates to be involved in Daphnia-pathogen interactions, given that they have been shown to code for immune effectors in related organisms. Differential expression of these genes was quantified by qRT-PCR following exposure to the bacterial pathogen Pasteuria ramosa. Constitutive expression levels differed between host genotypes, and some genes appeared to show correlated expression. However, none of the genes appeared to show a major modification of expression level in response to Pasteuria exposure. By applying knowledge from related genetic model organisms (e.g. Drosophila) to models for the study of evolutionary ecology and coevolution (i.e. Daphnia), the candidate gene approach is temptingly efficient. However, our results show that detection of only weak patterns is likely if one chooses target genes for study based on previously identified genome sequences by comparison to homologues from other related organisms. Future work on the Daphnia-Pasteuria system will need to balance a candidate gene approach with more comprehensive

  16. From inflammation to sickness and depression: when the immune system subjugates the brain.

    PubMed

    Dantzer, Robert; O'Connor, Jason C; Freund, Gregory G; Johnson, Rodney W; Kelley, Keith W

    2008-01-01

    In response to a peripheral infection, innate immune cells produce pro-inflammatory cytokines that act on the brain to cause sickness behaviour. When activation of the peripheral immune system continues unabated, such as during systemic infections, cancer or autoimmune diseases, the ensuing immune signalling to the brain can lead to an exacerbation of sickness and the development of symptoms of depression in vulnerable individuals. These phenomena might account for the increased prevalence of clinical depression in physically ill people. Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.

  17. Influence of Hesperidin on the Systemic and Intestinal Rat Immune Response.

    PubMed

    Camps-Bossacoma, Mariona; Franch, Àngels; Pérez-Cano, Francisco J; Castell, Margarida

    2017-06-06

    Polyphenols, widely found in edible plants, influence the immune system. Nevertheless, the immunomodulatory properties of hesperidin, the predominant flavanone in oranges, have not been deeply studied. To establish the effect of hesperidin on in vivo immune response, two different conditions of immune system stimulations in Lewis rats were applied. In the first experimental design, rats were intraperitoneally immunized with ovalbumin (OVA) plus Bordetella pertussis toxin and alum as the adjuvants, and orally given 100 or 200 mg/kg hesperidin. In the second experimental design, rats were orally sensitized with OVA together with cholera toxin and fed a diet containing 0.5% hesperidin. In the first approach, hesperidin administration changed mesenteric lymph node lymphocyte (MLNL) composition, increasing the TCRαβ+ cell percentage and decreasing that of B lymphocytes. Furthermore, hesperidin enhanced the interferon (IFN)-γ production in stimulated MLNL. In the second approach, hesperidin intake modified the lymphocyte composition in the intestinal epithelium (TCRγδ+ cells) and the lamina propria (TCRγδ+, CD45RA+, natural killer, natural killer T, TCRαβ+CD4+, and TCRαβ+CD8+ cells). Nevertheless, hesperidin did not modify the level of serum anti-OVA antibodies in either study. In conclusion, hesperidin does possess immunoregulatory properties in the intestinal immune response, but this effect is not able to influence the synthesis of specific antibodies.

  18. Influence of Hesperidin on the Systemic and Intestinal Rat Immune Response

    PubMed Central

    Camps-Bossacoma, Mariona; Franch, Àngels; Pérez-Cano, Francisco J.; Castell, Margarida

    2017-01-01

    Polyphenols, widely found in edible plants, influence the immune system. Nevertheless, the immunomodulatory properties of hesperidin, the predominant flavanone in oranges, have not been deeply studied. To establish the effect of hesperidin on in vivo immune response, two different conditions of immune system stimulations in Lewis rats were applied. In the first experimental design, rats were intraperitoneally immunized with ovalbumin (OVA) plus Bordetella pertussis toxin and alum as the adjuvants, and orally given 100 or 200 mg/kg hesperidin. In the second experimental design, rats were orally sensitized with OVA together with cholera toxin and fed a diet containing 0.5% hesperidin. In the first approach, hesperidin administration changed mesenteric lymph node lymphocyte (MLNL) composition, increasing the TCRαβ+ cell percentage and decreasing that of B lymphocytes. Furthermore, hesperidin enhanced the interferon (IFN)-γ production in stimulated MLNL. In the second approach, hesperidin intake modified the lymphocyte composition in the intestinal epithelium (TCRγδ+ cells) and the lamina propria (TCRγδ+, CD45RA+, natural killer, natural killer T, TCRαβ+CD4+, and TCRαβ+CD8+ cells). Nevertheless, hesperidin did not modify the level of serum anti-OVA antibodies in either study. In conclusion, hesperidin does possess immunoregulatory properties in the intestinal immune response, but this effect is not able to influence the synthesis of specific antibodies. PMID:28587283

  19. The lymphocytic cholinergic system and its contribution to the regulation of immune activity.

    PubMed

    Kawashima, Koichiro; Fujii, Takeshi

    2003-12-26

    Lymphocytes express most of the cholinergic components found in the nervous system, including acetylcholine (ACh), choline acetyltransferase (ChAT), high affinity choline transporter, muscarinic and nicotinic ACh receptors (mAChRs and nAChRs, respectively), and acetylcholinesterase. Stimulation of T and B cells with ACh or another mAChR agonist elicits intracellular Ca2+ signaling, up-regulation of c-fos expression, increased nitric oxide synthesis and IL-2-induced signal transduction, probably via M3 and M5 mAChR-mediated pathways. Acute stimulation of nAChRs with ACh or nicotine causes rapid and transient Ca2+ signaling in T and B cells, probably via alpha7 nAChR subunit-mediated pathways. Chronic nicotine stimulation, by contrast, down-regulates nAChR expression and suppresses T cell activity. Activation of T cells with phytohemagglutinin or antibodies against cell surface molecules enhances lymphocytic cholinergic transmission by activating expression of ChAT and M5 mAChR, which is suggestive of local cholinergic regulation of immune system activity. This idea is supported by the facts that lymphocytic cholinergic activity reflects well the changes in immune system function seen in animal models of immune deficiency and immune acceleration. Collectively, these data provide a compelling picture in which lymphocytes constitute a cholinergic system that is independent of cholinergic nerves, and which is involved in the regulation of immune function.

  20. Immune regulation of systemic hypertension, pulmonary arterial hypertension, and preeclampsia: shared disease mechanisms and translational opportunities.

    PubMed

    Jafri, Salema; Ormiston, Mark L

    2017-12-01

    Systemic hypertension, preeclampsia, and pulmonary arterial hypertension (PAH) are diseases of high blood pressure in the systemic or pulmonary circulation. Beyond the well-defined contribution of more traditional pathophysiological mechanisms, such as changes in the renin-angiotensin-aldosterone system, to the development of these hypertensive disorders, there is substantial clinical evidence supporting an important role for inflammation and immunity in the pathogenesis of each of these three conditions. Over the last decade, work in small animal models, bearing targeted deficiencies in specific cytokines or immune cell subsets, has begun to clarify the immune-mediated mechanisms that drive changes in vascular structure and tone in hypertensive disease. By summarizing the clinical and experimental evidence supporting a contribution of the immune system to systemic hypertension, preeclampsia, and PAH, the current review highlights the cellular and molecular pathways that are common to all three hypertensive disorders. These mechanisms are centered on an imbalance in CD4 + helper T cell populations, defined by excessive Th17 responses and impaired T reg activity, as well as the excessive activation or impairment of additional immune cell types, including macrophages, dendritic cells, CD8 + T cells, B cells, and natural killer cells. The identification of common immune mechanisms in systemic hypertension, preeclampsia, and PAH raises the possibility of new therapeutic strategies that target the immune component of hypertension across multiple disorders. Copyright © 2017 the American Physiological Society.

  1. From immunotoxicity to nanotherapy: the effects of nanomaterials on the immune system.

    PubMed

    Smith, Matthew J; Brown, Jared M; Zamboni, William C; Walker, Nigel J

    2014-04-01

    The potential for human exposure to the diverse and ever-changing world of nanoscale materials has raised concerns about their influence on health and disease. The novel physical and chemical properties of these materials, which are associated with their small size, complicate toxicological evaluations. Further, these properties may make engineered nanomaterials (ENMs) a prime target for interaction with the immune system following uptake by phagocytes. Undesired effects on antigen-presenting cells and other phagocytic cells are of concern due to the high likelihood of ENM uptake by these cells. In addition, ENM interactions with lymphocytes and other cell types can contribute to a varied spectrum of possible effects, including inflammation, hypersensitivity, and immunomodulation. Furthermore, the mast cell (a type of immune cell traditionally associated with allergy) appears to contribute to certain inflammatory and toxic effects associated with some ENMs. Although incidental exposure may be undesirable, nanomedicines engineered for various clinical applications provide opportunities to develop therapies that may or may not intentionally target the immune system. The interaction between ENMs and the immune system and the resulting pharmacokinetic and phenotypic responses are critical factors that dictate the balance between toxicity and clinical efficacy of nanotherapeutics.

  2. Nutritional modulation of age-related changes in the immune system and risk of infection

    USDA-ARS?s Scientific Manuscript database

    The immune system undergoes some adverse alterations during aging, many of which have been implicated in the increased morbidity and mortality associated with infection in the elderly. In addition to intrinsic changes to the immune system with aging, the elderly are more likely to have poor nutritio...

  3. Effects of chalcone derivatives on players of the immune system

    PubMed Central

    Lee, Jian Sian; Bukhari, Syed Nasir Abbas; Fauzi, Norsyahida Mohd

    2015-01-01

    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells. PMID:26316713

  4. Pineal-adrenal-immune system relationship under thermal stress: effect on physiological, endocrine, and non-specific immune response in goats.

    PubMed

    Sejian, Veerasamy; Srivastava, Rajendra Swaroop

    2010-12-01

    The purpose of the investigation was to observe the pineal-adrenal-immune system relationships and their influence on non-specific immune response in female goats under short-term thermal stress. Six female goats had been exposed to 40°C and 60% relative humidity in the psychrometric chamber for 17 days. Blood samples were obtained on days 0 and 10 to establish control and thermal stress effects, respectively. Chemical adrenalectomy was achieved by injecting metyrapone (100 mg/kg body weight) followed by exogenous melatonin treatment (0.1 mg/kg body weight) from 11th to 17th day of experiment. Thermal stress significantly (P≤0.05) altered the physiological responses. Metyrapone and melatonin treatment significantly (P≤0.05) reduced the thermal-stress-induced increase in plasma concentrations of cortisol and corticosterone while significantly (P≤0.05) increased the plasma melatonin on days 11 and 17. Furthermore, these treatments significantly (P<0.05) increased the phagocytic activity of neutrophils as compared to both control and thermal exposure values from 11-17 days of experiment. The data generated from this study help us to understand the functional relationship between pineal, adrenal, and immune system, and how this relationship modifies the non-specific immune response for the well being of goats during thermal stress.

  5. How simple autonomous decisions evolve into robust behaviours? A review from neurorobotics, cognitive, self-organized and artificial immune systems fields.

    PubMed

    Fernandez-Leon, Jose A; Acosta, Gerardo G; Rozenfeld, Alejandro

    2014-10-01

    Researchers in diverse fields, such as in neuroscience, systems biology and autonomous robotics, have been intrigued by the origin and mechanisms for biological robustness. Darwinian evolution, in general, has suggested that adaptive mechanisms as a way of reaching robustness, could evolve by natural selection acting successively on numerous heritable variations. However, is this understanding enough for realizing how biological systems remain robust during their interactions with the surroundings? Here, we describe selected studies of bio-inspired systems that show behavioral robustness. From neurorobotics, cognitive, self-organizing and artificial immune system perspectives, our discussions focus mainly on how robust behaviors evolve or emerge in these systems, having the capacity of interacting with their surroundings. These descriptions are twofold. Initially, we introduce examples from autonomous robotics to illustrate how the process of designing robust control can be idealized in complex environments for autonomous navigation in terrain and underwater vehicles. We also include descriptions of bio-inspired self-organizing systems. Then, we introduce other studies that contextualize experimental evolution with simulated organisms and physical robots to exemplify how the process of natural selection can lead to the evolution of robustness by means of adaptive behaviors. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. Systems analysis of protective immune responses to RTS,S malaria vaccination in humans

    PubMed Central

    Kazmin, Dmitri; Nakaya, Helder I.; Lee, Eva K.; Johnson, Matthew J.; van der Most, Robbert; van den Berg, Robert A.; Ballou, W. Ripley; Jongert, Erik; Wille-Reece, Ulrike; Ockenhouse, Christian; Aderem, Alan; Zak, Daniel E.; Sadoff, Jerald; Hendriks, Jenny; Wrammert, Jens; Ahmed, Rafi; Pulendran, Bali

    2017-01-01

    RTS,S is an advanced malaria vaccine candidate and confers significant protection against Plasmodium falciparum infection in humans. Little is known about the molecular mechanisms driving vaccine immunity. Here, we applied a systems biology approach to study immune responses in subjects receiving three consecutive immunizations with RTS,S (RRR), or in those receiving two immunizations of RTS,S/AS01 following a primary immunization with adenovirus 35 (Ad35) (ARR) vector expressing circumsporozoite protein. Subsequent controlled human malaria challenge (CHMI) of the vaccinees with Plasmodium-infected mosquitoes, 3 wk after the final immunization, resulted in ∼50% protection in both groups of vaccinees. Circumsporozoite protein (CSP)-specific antibody titers, prechallenge, were associated with protection in the RRR group. In contrast, ARR-induced lower antibody responses, and protection was associated with polyfunctional CD4+ T-cell responses 2 wk after priming with Ad35. Molecular signatures of B and plasma cells detected in PBMCs were highly correlated with antibody titers prechallenge and protection in the RRR cohort. In contrast, early signatures of innate immunity and dendritic cell activation were highly associated with protection in the ARR cohort. For both vaccine regimens, natural killer (NK) cell signatures negatively correlated with and predicted protection. These results suggest that protective immunity against P. falciparum can be achieved via multiple mechanisms and highlight the utility of systems approaches in defining molecular correlates of protection to vaccination. PMID:28193898

  7. Neuroendocrine mechanisms for immune system regulation during stress in fish.

    PubMed

    Nardocci, Gino; Navarro, Cristina; Cortés, Paula P; Imarai, Mónica; Montoya, Margarita; Valenzuela, Beatriz; Jara, Pablo; Acuña-Castillo, Claudio; Fernández, Ricardo

    2014-10-01

    In the last years, the aquaculture crops have experienced an explosive and intensive growth, because of the high demand for protein. This growth has increased fish susceptibility to diseases and subsequent death. The constant biotic and abiotic changes experienced by fish species in culture are challenges that induce physiological, endocrine and immunological responses. These changes mitigate stress effects at the cellular level to maintain homeostasis. The effects of stress on the immune system have been studied for many years. While acute stress can have beneficial effects, chronic stress inhibits the immune response in mammals and teleost fish. In response to stress, a signaling cascade is triggered by the activation of neural circuits in the central nervous system because the hypothalamus is the central modulator of stress. This leads to the production of catecholamines, corticosteroid-releasing hormone, adrenocorticotropic hormone and glucocorticoids, which are the essential neuroendocrine mediators for this activation. Because stress situations are energetically demanding, the neuroendocrine signals are involved in metabolic support and will suppress the "less important" immune function. Understanding the cellular mechanisms of the neuroendocrine regulation of immunity in fish will allow the development of new pharmaceutical strategies and therapeutics for the prevention and treatment of diseases triggered by stress at all stages of fish cultures for commercial production. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. The stress response and immune system share, borrow, and reconfigure their physiological network elements: Evidence from the insects.

    PubMed

    Adamo, Shelley A

    2017-02-01

    The classic biomedical view is that stress hormone effects on the immune system are largely pathological, especially if the stress is chronic. However, more recent interpretations have focused on the potential adaptive function of these effects. This paper examines stress response-immune system interactions from a physiological network perspective, using insects because of their simpler physiology. For example, stress hormones can reduce disease resistance, yet activating an immune response results in the release of stress hormones in both vertebrates and invertebrates. From a network perspective, this phenomenon is consistent with the 'sharing' of the energy-releasing ability of stress hormones by both the stress response and the immune system. Stress-induced immunosuppression is consistent with the stress response 'borrowing' molecular components from the immune system to increase the capacity of stress-relevant physiological processes (i.e. a trade off). The insect stress hormones octopamine and adipokinetic hormone can also 'reconfigure' the immune system to help compensate for the loss of some of the immune system's molecular resources (e.g. apolipophorin III). This view helps explain seemingly maladaptive interactions between the stress response and immune system. The adaptiveness of stress hormone effects on individual immune components may be apparent only from the perspective of the whole organism. These broad principles will apply to both vertebrates and invertebrates. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Immunity's fourth dimension: approaching the circadian-immune connection.

    PubMed

    Arjona, Alvaro; Silver, Adam C; Walker, Wendy E; Fikrig, Erol

    2012-12-01

    The circadian system ensures the generation and maintenance of self-sustained ~24-h rhythms in physiology that are linked to internal and environmental changes. In mammals, daily variations in light intensity and other cues are integrated by a hypothalamic master clock that conveys circadian information to peripheral molecular clocks that orchestrate physiology. Multiple immune parameters also vary throughout the day and disruption of circadian homeostasis is associated with immune-related disease. Here, we discuss the molecular links between the circadian and immune systems and examine their outputs and disease implications. Understanding the mechanisms that underlie circadian-immune crosstalk may prove valuable for devising novel prophylactic and therapeutic interventions. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Interactions of the innate and adaptive arms of the immune system in the pathogenesis of spondyloarthritis

    PubMed Central

    Stoll, Matthew L

    2011-01-01

    The immune system can be divided into the innate and adaptive arms. Historically, most of the research into the pathogenesis of spondyloarthritis (SpA) and other types of chronic arthritis focused on the adaptive immune system. Recently, the pendulum has shifted, and much current work in SpA focuses on innate immunity. Herein, I summarize evidence demonstrating that both the innate and the adaptive arms of the immune system are involved in the pathogenesis of SpA, propose a mechanism in which both arms interact to maintain chronic arthritis, and discuss potential research directions. PMID:21269576

  11. Old and new facts about hyperthermia-induced modulations of the immune system.

    PubMed

    Frey, Benjamin; Weiss, Eva-Maria; Rubner, Yvonne; Wunderlich, Roland; Ott, Oliver J; Sauer, Rolf; Fietkau, Rainer; Gaipl, Udo S

    2012-01-01

    Hyperthermia (HT) is a potent sensitiser for radiotherapy (RT) and chemotherapy (CT) and has been proven to modulate directly or indirectly cells of the innate and adaptive immune system. We will focus in this article on how anti-tumour immunity can be induced by HT. In contrast to some in vitro assays, in vivo examinations showed that natural killer cells and phagocytes like granulocytes are directly activated against the tumour by HT. Since heat also activates dendritic cells (DCs), HT should be combined with further death stimuli (RT, CT or immune therapy) to allocate tumour antigen, derived from, for example, necrotic tumour cells, for uptake by DCs. We will outline that induction of immunogenic tumour cells and direct tumour cell killing by HT in combination with other therapies contributes to immune activation against the tumour. Studies will be presented showing that non-beneficial effects of HT on immune cells are mostly timely restricted. A special focus is set on immune activation mediated by extracellular present heat shock proteins (HSPs) carrying tumour antigens and further danger signals released by dying tumour cells. Local HT treatment in addition to further stress stimuli exerts abscopal effects and might be considered as in situ tumour vaccination. An increased natural killer (NK) cell activity, lymphocyte infiltration and HSP-mediated induction of immunogenic tumour cells have been observed in patients. Treatments with the addition of HT therefore can be considered as a personalised cancer treatment approach by specifically activating the immune system against the individual unique tumour.

  12. Interaction Between Familial Transmission and a Constitutively Active Immune System Shapes Gut Microbiota in Drosophila melanogaster

    PubMed Central

    Mistry, Rupal; Kounatidis, Ilias; Ligoxygakis, Petros

    2017-01-01

    Resident gut bacteria are constantly influencing the immune system, yet the role of the immune system in shaping microbiota composition during an organism’s life span has remained unclear. Experiments in mice have been inconclusive due to differences in husbandry schemes that led to conflicting results. We used Drosophila as a genetically tractable system with a simpler gut bacterial population structure streamlined genetic backgrounds and established cross schemes to address this issue. We found that, depending on their genetic background, young flies had microbiota of different diversities that converged with age to the same Acetobacteraceae-dominated pattern in healthy flies. This pattern was accelerated in immune-compromised flies with higher bacterial load and gut cell death. Nevertheless, immune-compromised flies resembled their genetic background, indicating that familial transmission was the main force regulating gut microbiota. In contrast, flies with a constitutively active immune system had microbiota readily distinguishable from their genetic background with the introduction and establishment of previously undetectable bacterial families. This indicated the influence of immunity over familial transmission. Moreover, hyperactive immunity and increased enterocyte death resulted in the highest bacterial load observed starting from early adulthood. Cohousing experiments showed that the microenvironment also played an important role in the structure of the microbiota where flies with constitutive immunity defined the gut microbiota of their cohabitants. Our data show that, in Drosophila, constitutively active immunity shapes the structure and density of gut microbiota. PMID:28413160

  13. Stability of Lentiviral Vector-Mediated Transgene Expression in the Brain in the Presence of Systemic Antivector Immune Responses

    PubMed Central

    ABORDO-ADESIDA, EVELYN; FOLLENZI, ANTONIA; BARCIA, CARLOS; SCIASCIA, SANDRA; CASTRO, MARIA G.; NALDINI, LUIGI; LOWENSTEIN, PEDRO R.

    2009-01-01

    Lentiviral vectors are promising tools for gene therapy in the CNS. It is therefore important to characterize their interactions with the immune system in the CNS. This work characterizes transgene expression and brain inflammation in the presence or absence of immune responses generated after systemic immunization with lentiviral vectors. We characterized transduction with SIN-LV vectors in the CNS. A dose—response curve using SIN-LV-GFP demonstrated detectable transgene expression in the striatum at a dose of 102, and maximum expression at 106, transducing units of lentiviral vector, with minimal increase in inflammatory markers between the lowest and highest dose of vector injected. Our studies demonstrate that injection of a lentiviral vector into the CNS did not cause a measurable inflammatory response. Systemic immunization after CNS injection, with the lentiviral vector expressing the same transgene as a vector injected into the CNS, caused a decrease in transgene expression in the CNS, concomitantly with an infiltration of inflammatory cells into the CNS parenchyma at the injection site. However, peripheral immunization with a lentiviral vector carrying a different transgene did not diminish transgene expression, or cause CNS inflammation. Systemic immunization preceding injection of lentiviral vectors into the CNS determined that preexisting antilentiviral immunity, regardless of the transgene, did not affect transgene expression. Furthermore, we showed that the transgene, but not the virion or vector components, is responsible for providing antigenic epitopes to the activated immune system, on systemic immunization with lentivirus. Low immunogenicity and prolonged transgene expression in the presence of preexisting lentiviral immunity are encouraging data for the future use of lentiviral vectors in CNS gene therapy. In summary, the lentiviral vectors tested induced undetectable activation of innate immune responses, and stimulation of adaptive immune

  14. The aryl hydrocarbon receptor: multitasking in the immune system.

    PubMed

    Stockinger, Brigitta; Di Meglio, Paola; Gialitakis, Manolis; Duarte, João H

    2014-01-01

    The aryl hydrocarbon receptor (AhR), for many years almost exclusively studied by the pharmacology/toxicology field for its role in mediating the toxicity of xenobiotics such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), has more recently attracted the attention of immunologists. The evolutionary conservation of this transcription factor and its widespread expression in the immune system point to important physiological functions that are slowly being unraveled. In particular, the emphasis is now shifting from the role of AhR in the xenobiotic pathway toward its mode of action in response to physiological ligands. In this article, we review the current understanding of the molecular interactions and functions of AhR in the immune system in steady state and in the presence of infection and inflammation, with a focus on barrier organs such as the skin, the gut, and the lung.

  15. The Functional Impact of the Intestinal Microbiome on Mucosal Immunity and Systemic Autoimmunity

    PubMed Central

    Longman, Randy S.; Littman, Dan R.

    2016-01-01

    Purpose of Review This review will highlight recent advances functionally linking the gut microbiome with mucosal and systemic immune cell activation potentially underlying autoimmunity. Recent Findings Dynamic interactions between the gut microbiome and environmental cues (including diet and medicines) shape the effector potential of the microbial organ. Key bacteria and viruses have emerged, that, in defined microenvironments, play a critical role in regulating effector lymphocyte functions. The coordinated interactions between these different microbial kingdoms—including bacteria, helminths, and viruses (termed transkingdom interactions)—play a critical role in shaping immunity. Emerging strategies to identify immunologically-relevant microbes with the potential to regulate immune cell functions both at mucosal sites and systemically will likely define key diagnostic and therapeutic targets. Summary The microbiome constitutes a critical microbial organ with coordinated interactions that shape host immunity. PMID:26002030

  16. Osteoimmunology: Influence of the Immune System on Bone Regeneration and Consumption.

    PubMed

    Limmer, Andreas; Wirtz, Dieter C

    2017-06-01

    Background Stimulating bone regeneration is a central aim in orthopaedic and trauma surgery. Although the replacement of bone with artificial materials like cement or apatite helps to keep up bone stability, new bone often cannot be regenerated. Increasing research efforts have led to the clinical application of growth factors stimulating bone growth (e.g. bone morphogenic protein, BMP) and inhibitors preventing bone consumption (e.g. RANKL blocking antibodies). These factors mostly concentrate on stimulating osteoblast or preventing osteoclast activity. Current Situation It is widely accepted that osteoblasts and osteoclasts are central players in bone regeneration. This concept assumes that osteoblasts are responsible for bone growth while osteoclasts cause bone consumption by secreting matrix-degrading enzymes such as cathepsin K and matrix metalloproteinases (MMP). However, according to new research results, bone growth or consumption are not regulated by single cell types. It is rather the interaction of various cell types that regulates bone metabolism. While factors secreted by osteoblasts are essential for osteoclast differentiation and activation, factors secreted by activated osteoclasts are essential for osteoblast activity. In addition, recent research results imply that the influence of the immune system on bone metabolism has long been neglected. Factors secreted by macrophages or T cells strongly influence bone growth or degradation, depending on the bone microenvironment. Infections, sterile inflammation or tumour metastases not only affect bone cells directly, but also influence immune cells such as T cells indirectly. Furthermore, immune cells and bone are mechanistically regulated by similar factors such as cytokines, chemokines and transcription factors, suggesting that the definition of bone and immune cells has to be thought over. Outlook Bone and the immune system are regulated by similar mechanisms. These newly identified similarities

  17. Immune Organs and Haemopoietic System Under Modelling of the Mission Factors

    NASA Astrophysics Data System (ADS)

    Sapin, M. R.; Grigoriev, A. I.; Erofeeva, L. M.; Grigorenko, D. E.; Fedorenko, B. S.

    1997-07-01

    Literary and experimental data on the character of changes in immune organs and lymphoid tissue of respiratory system and digestive system in laboratory animals during the mission factors model are given. Inhibition of reproductive function in bone marrow, thymus and spleen under irradiation of gamma-rays and accelerated carbon ions, tensity of immune response in the lymphoid structures of larynx, trachea and bronchi under the influence of acetaldehyde vapors and decrease of lymphoid tissue square on histological series in spleen and small intestine with an increase of concentration of microbial bodies in the drinking water were estimated.

  18. Development of a human adaptive immune system in cord blood cell-transplanted mice.

    PubMed

    Traggiai, Elisabetta; Chicha, Laurie; Mazzucchelli, Luca; Bronz, Lucio; Piffaretti, Jean-Claude; Lanzavecchia, Antonio; Manz, Markus G

    2004-04-02

    Because ethical restrictions limit in vivo studies of the human hemato-lymphoid system, substitute human to small animal xenotransplantation models have been employed. Existing models, however, sustain only limited development and maintenance of human lymphoid cells and rarely produce immune responses. Here we show that intrahepatic injection of CD34+ human cord blood cells into conditioned newborn Rag2-/-gammac-/- mice leads to de novo development of B, T, and dendritic cells; formation of structured primary and secondary lymphoid organs; and production of functional immune responses. This provides a valuable model to study development and function of the human adaptive immune system in vivo.

  19. Influence of Photoperiod on Hormones, Behavior, and Immune Function

    PubMed Central

    Walton, James C.; Weil, Zachary M.; Nelson, Randy J.

    2011-01-01

    Photoperiodism is the ability of plants and animals to measure environmental day length to ascertain time of year. Central to the evolution of photoperiodism in animals is the adaptive distribution of energetically challenging activities across the year to optimize reproductive fitness while balancing the energetic tradeoffs necessary for seasonally- appropriate survival strategies. The ability to accurately predict future events requires endogenous mechanisms to permit physiological anticipation of annual conditions. Day length provides a virtually noise free environmental signal to monitor and accurately predict time of the year. In mammals, melatonin provides the hormonal signal transducing day length. Duration of pineal melatonin is inversely related to day length and its secretion drives enduring changes in many physiological systems, including the HPA, HPG, and brain-gut axes, the autonomic nervous system, and the immune system. Thus, melatonin is the fulcrum mediating redistribution of energetic investment among physiological processes to maximize fitness and survival. PMID:21156187

  20. Vitamin effects on the immune system: vitamins A and D take centre stage.

    PubMed

    Mora, J Rodrigo; Iwata, Makoto; von Andrian, Ulrich H

    2008-09-01

    Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity.

  1. Enhanced systemic immune reactivity to a Basal cell carcinoma associated antigen following photodynamic therapy.

    PubMed

    Kabingu, Edith; Oseroff, Allan R; Wilding, Gregory E; Gollnick, Sandra O

    2009-07-01

    Numerous preclinical studies have shown that local photodynamic therapy (PDT) of tumors enhances systemic antitumor immunity. However, other than single-case and anecdotal reports, this phenomenon has not been examined following clinical PDT. To determine whether PDT in a clinical setting enhances systemic recognition of tumor cells, we examined whether PDT of basal cell carcinoma resulted in an increased systemic immune response to Hip1, a tumor antigen associated with basal cell carcinoma. Basal cell carcinoma lesions were either treated with PDT or surgically removed. Blood was collected from patients immediately before or 7 to 10 days following treatment. Peripheral blood leukocytes were isolated from HLA-A2-expressing patients and reactivity to a HLA-A2-restricted Hip1 peptide was measured by INF-gamma ELISpot assay. Immune recognition of Hip1 increased in patients whose basal cell carcinoma lesions were treated with PDT. This increase in reactivity was significantly greater than reactivity observed in patients whose lesions were surgically removed. Patients with superficial lesions exhibited greater enhancement of reactivity compared with patients with nodular lesions. Immune reactivity following PDT was inversely correlated with treatment area and light dose. These findings show for the first time that local tumor PDT can enhance systemic immune responses to tumors in patients, and validate previous preclinical findings.

  2. Can investments in health systems strategies lead to changes in immunization coverage?

    PubMed

    Brenzel, Logan

    2014-04-01

    National immunization programs in developing countries have made major strides to immunize the world's children, increasing full coverage to 83% of children. However, the World Health Organization estimates that 22 million children less than five years of age are left unvaccinated, and coverage levels have been plateauing for nearly a decade. This paper describes the evidence on factors contributing to low vaccination uptake, and describes the connection between these factors and the documented strategies and interventions that can lead to changes in immunization outcomes. The author suggests that investments in these areas may contribute more effectively to immunization coverage and also have positive spill-over benefits for health systems. The paper concludes that while some good quality evidence exists of what works and may contribute to immunization outcomes, the quality of evidence needs to improve and major gaps need to be addressed.

  3. Linking autoimmunity to the origin of the adaptive immune system.

    PubMed

    Bayersdorf, Robert; Fruscalzo, Arrigo; Catania, Francesco

    2018-01-01

    In jawed vertebrates, the adaptive immune system (AIS) cooperates with the innate immune system (IIS) to protect hosts from infections. Although targeting non-self-components, the AIS also generates self-reactive antibodies which, when inadequately counter-selected, can give rise to autoimmune diseases (ADs). ADs are on the rise in western countries. Why haven't ADs been eliminated during the evolution of a ∼500 million-year old system? And why have they become more frequent in recent decades? Self-recognition is an attribute of the phylogenetically more ancient IIS and empirical data compellingly show that some self-reactive antibodies, which are classifiable as elements of the IIS rather then the AIS, may protect from (rather than cause) ADs. Here, we propose that the IIS's self-recognition system originally fathered the AIS and, as a consequence of this relationship, its activity is dampened in hygienic environments. Rather than a mere breakdown or failure of the mechanisms of self-tolerance, ADs might thus arise from architectural constraints.

  4. Breast-fed and bottle-fed infant rhesus macaques develop distinct gut microbiotas and immune systems

    PubMed Central

    Ardeshir, Amir; Narayan, Nicole R.; Méndez-Lagares, Gema; Lu, Ding; Rauch, Marcus; Huang, Yong; Van Rompay, Koen K. A.; Lynch, Susan V.; Hartigan-O'Connor, Dennis J.

    2015-01-01

    Diet has a strong influence on the intestinal microbiota in both humans and animal models. It is well established that microbial colonization is required for normal development of the immune system and that specific microbial constituents prompt the differentiation or expansion of certain immune cell subsets. Nonetheless, it has been unclear how profoundly diet might shape the primate immune system or how durable the influence might be. We show that breast-fed and bottle-fed infant rhesus macaques develop markedly different immune systems, which remain different 6 months after weaning when the animals begin receiving identical diets. In particular, breast-fed infants develop robust populations of memory T cells as well as T helper 17 (TH17) cells within the memory pool, whereas bottle-fed infants do not. These findings may partly explain the variation in human susceptibility to conditions with an immune basis, as well as the variable protection against certain infectious diseases. PMID:25186175

  5. Neonatal immune activation by lipopolysaccharide causes inadequate emotional responses to novel situations but no changes in anxiety or cognitive behavior in Wistar rats.

    PubMed

    Vojtechova, Iveta; Petrasek, Tomas; Maleninska, Kristyna; Brozka, Hana; Tejkalova, Hana; Horacek, Jiri; Stuchlik, Ales; Vales, Karel

    2018-05-02

    Infection during the prenatal or neonatal stages of life is considered one of the major risk factors for the development of mental diseases such as schizophrenia or autism. However, the impacts of such an immune challenge on adult behavior are still not clear. In our study, we used a model of early postnatal immune activation by the application of bacterial endotoxin lipopolysaccharide (LPS) to rat pups at a dose of 2 mg/kg from postnatal day (PD) 5 to PD 9. In adulthood, the rats were tested in a battery of tasks probing various aspects of behavior: spontaneous activity (open field test), social behavior (social interactions and female bedding exploration), anxiety (elevated plus maze), cognition (active place avoidance in Carousel) and emotional response (ultrasonic vocalization recording). Moreover, we tested sensitivity to acute challenge with MK-801, a psychotomimetic drug. Our results show that the application of LPS led to increased self-grooming in the female bedding exploration test and inadequate emotional reactions in Carousel maze displayed by ultrasonic vocalizations. However, it did not have serious consequences on exploration, locomotion, social behavior or cognition. Furthermore, exposition to MK-801 did not trigger social or cognitive deficits in the LPS-treated rats. We conclude that the emotional domain is the most sensitive to the changes induced by neonatal immune activation in rats, including a disrupted response to novel and stressful situations in early adulthood (similar to that observed in human patients suffering from schizophrenia or autism), while other aspects of tested behavior remain unaffected. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. A systems model for immune cell interactions unravels the mechanism of inflammation in human skin.

    PubMed

    Valeyev, Najl V; Hundhausen, Christian; Umezawa, Yoshinori; Kotov, Nikolay V; Williams, Gareth; Clop, Alex; Ainali, Crysanthi; Ouzounis, Christos; Tsoka, Sophia; Nestle, Frank O

    2010-12-02

    Inflammation is characterized by altered cytokine levels produced by cell populations in a highly interdependent manner. To elucidate the mechanism of an inflammatory reaction, we have developed a mathematical model for immune cell interactions via the specific, dose-dependent cytokine production rates of cell populations. The model describes the criteria required for normal and pathological immune system responses and suggests that alterations in the cytokine production rates can lead to various stable levels which manifest themselves in different disease phenotypes. The model predicts that pairs of interacting immune cell populations can maintain homeostatic and elevated extracellular cytokine concentration levels, enabling them to operate as an immune system switch. The concept described here is developed in the context of psoriasis, an immune-mediated disease, but it can also offer mechanistic insights into other inflammatory pathologies as it explains how interactions between immune cell populations can lead to disease phenotypes.

  7. The transition between immune and disease states in a cellular automaton model of clonal immune response

    NASA Astrophysics Data System (ADS)

    Bezzi, Michele; Celada, Franco; Ruffo, Stefano; Seiden, Philip E.

    1997-02-01

    In this paper we extend the Celada-Seiden (CS) model of the humoral immune response to include infections virus and killer T cells (cellular response). The model represents molecules and cells with bitstrings. The response of the system to virus involves a competition between the ability of the virus to kill the host cells and the host's ability to eliminate the virus. We find two basins of attraction in the dynamics of this system, one is identified with disease and the other with the immune state. There is also an oscillating state that exists on the border of these two stable states. Fluctuations in the population of virus or antibody can end the oscillation and drive the system into one of the stable states. The introduction of mechanisms of cross-regulation between the two responses can bias the system towards one of them. We also study a mean field model, based on coupled maps, to investigate virus-like infections. This simple model reproduces the attractors for average populations observed in the cellular automaton. All the dynamical behavior connected to spatial extension is lost, as is the oscillating feature. Thus the mean field approximation introduced with coupled maps destroys oscillations.

  8. Immune system responses and fitness costs associated with consumption of bacteria in larvae of Trichoplusia ni

    PubMed Central

    Freitak, Dalial; Wheat, Christopher W; Heckel, David G; Vogel, Heiko

    2007-01-01

    Background Insects helped pioneer, and persist as model organisms for, the study of specific aspects of immunity. Although they lack an adaptive immune system, insects possess an innate immune system that recognizes and destroys intruding microorganisms. Its operation under natural conditions has not been well studied, as most studies have introduced microbes to laboratory-reared insects via artificial mechanical wounding. One of the most common routes of natural exposure and infection, however, is via food; thus, the role of dietary microbial communities in herbivorous insect immune system evolution invites study. Here, we examine the immune system response and consequences of exposing a lepidopteran agricultural pest to non-infectious microorganisms via simple oral consumption. Results Immune system response was compared between Trichoplusia ni larvae reared on diets with or without non-pathogenic bacteria (Escherichia coli and Micrococcus luteus). Two major immune response-related enzymatic activities responded to diets differently – phenoloxidase activity was inhibited in the bacteria-fed larvae, whereas general antibacterial activity was enhanced. Eight proteins were highly expressed in the hemolymph of the bacteria fed larvae, among them immune response related proteins arylphorin, apolipophorin III and gloverin. Expression response among 25 putative immune response-related genes were assayed via RT-qPCR. Seven showed more than fivefold up regulation in the presence of bacterial diet, with 22 in total being differentially expressed, among them apolipophorin III, cecropin, gallerimycin, gloverin, lysozyme, and phenoloxidase inhibiting enzyme. Finally, potential life-history trade-offs were studied, with pupation time and pupal mass being negatively affected in bacteria fed larvae. Conclusion The presence of bacteria in food, even if non-pathogenic, can trigger an immune response cascade with life history tradeoffs. Trichoplusia ni larvae are able to detect

  9. Innate immune system and inflammation in Alzheimer's disease: from pathogenesis to treatment.

    PubMed

    Serpente, Maria; Bonsi, Rossana; Scarpini, Elio; Galimberti, Daniela

    2014-01-01

    Immune activation and inflammation, likely triggered by amyloid-beta (Aβ) deposition, play a remarkable role in the pathogenesis of Alzheimer's disease (AD), which is the most frequent cause of dementia in the elderly. The principal cellular elements of the brain innate immune system likely to be involved in such processes are microglia. In an attempt to search for new disease-modifying drugs, the immune system has been addressed, with the aim of removing deposition of Aβ or tau by developing vaccines and humanized monoclonal antibodies. The aim of this review is to summarize the current evidence regarding the role played by microglia and inflammatory molecules in the pathogenesis of AD. In addition, we will discuss the main active and passive immunotherapeutic approaches. © 2014 S. Karger AG, Basel.

  10. Using information technology to improve adult immunization delivery in an integrated urban health system.

    PubMed

    Swenson, Carolyn J; Appel, Alicia; Sheehan, Moira; Hammer, Anne; Fenner, Zita; Phibbs, Stephanie; Harbrecht, Marjie; Main, Deborah S

    2012-01-01

    Adult immunizations prevent morbidity and mortality yet coverage remains suboptimal, in part due to missed opportunities. Clinical decision support systems (CDSSs) can improve immunization rates when integrated into routine work flow, implemented wherever care is delivered, and used by staff who can act on the recommendation. An adult immunization improvement project was undertaken in a large integrated, safety-net health care system. A CDSS was developed to query patient records and identify patients eligible for pneumococcal, influenza, or tetanus immunization and then generate a statement that recommends immunization or indicates a previous refusal. A new agency policy authorized medical assistants and nurses in clinics, and nurses in the hospital, to use the CDSS as a standing order. Immunization delivery work flow was standardized, and staff received feedback on immunization rates. The CDSS identified more patients than a typical paper standing order and can be easily modified to incorporate changes in vaccine indications. The intervention led to a 10% improvement in immunization rates in adults 65 years of age or older and in younger adults with diabetes or chronic obstructive pulmonary disease. Overall, the improvements were sustained beyond the project period. The CDSS was expanded to encompass additional vaccines. Interdepartmental collaboration was critical to identify needs, challenges, and solutions. Implementing the standing order policy in clinics and the hospital usually allowed immunizations to be taken out of the hands of clinicians. As an on-demand tool, CDSS must be used at each patient encounter to avoid missed opportunities. Staff retraining accompanied by ongoing assessment of immunization rates, work flow, and missed opportunities to immunize patients are critical to sustain and enhance improvements.

  11. Systemic Immune Activation and HIV Shedding in the Female Genital Tract.

    PubMed

    Spencer, LaShonda Y; Christiansen, Shawna; Wang, Chia-Hao H; Mack, Wendy J; Young, Mary; Strickler, Howard D; Anastos, Kathryn; Minkoff, Howard; Cohen, Mardge; Geenblatt, Ruth M; Karim, Roksana; Operskalski, Eva; Frederick, Toni; Homans, James D; Landay, Alan; Kovacs, Andrea

    2016-02-01

    Plasma HIV RNA is the most significant determinant of cervical HIV shedding. However, shedding is also associated with sexually transmitted infections (STIs) and cervical inflammation. The mechanism by which this occurs is poorly understood. There is evidence that systemic immune activation promotes viral entry, replication, and HIV disease progression. We hypothesized that systemic immune activation would be associated with an increase in HIV genital shedding. Clinical assessments, HIV RNA in plasma and genital secretions, and markers of immune activation (CD38(+)DR(+) and CD38(-)DR(-)) on CD4(+) and CD8(+) T cells in blood were evaluated in 226 HIV+ women enrolled in the Women's Interagency HIV Study. There were 569 genital evaluations of which 159 (28%) exhibited HIV RNA shedding, defined as HIV viral load >80 copies per milliliter. We tested associations between immune activation and shedding using generalized estimating equations with logit link function. In the univariate model, higher levels of CD4(+) and CD8(+) T-cell activation in blood were significantly associated with genital tract shedding. However, in the multivariate model adjusting for plasma HIV RNA, STIs, and genital tract infections, only higher levels of resting CD8(+) T cells (CD38(-)DR(-)) were significantly inversely associated with HIV shedding in the genital tract (odds ratios = 0.44, 95% confidence interval: 0.21 to 0.9, P = 0.02). The association of systemic immune activation with genital HIV shedding is multifactorial. Systemic T-cell activation is associated with genital tract shedding in univariate analysis but not when adjusting for plasma HIV RNA, STIs, and genital tract infections. In addition, women with high percentage of resting T cells are less likely to have HIV shedding compared with those with lower percentages. These findings suggest that a higher percentage of resting cells, as a result of maximal viral suppression with treatment, may decrease local genital activation, HIV

  12. [Progress of childhood immunization information management system in China in 2008].

    PubMed

    Cao, Ling-Sheng; Liu, Da-Wei; Guo, Biao

    2009-08-01

    To evaluate the coverage of childhood immunization information management system (CIIMS) in China (not include HongKong, Macao, and Taiwan) in 2008. Analyzing immunization cases and users' file record archives in CIIMS for china in 2008. These data indicated that 87.10% (27/31) of provinces and 30.36% (891/2935) of county level and 26.63% (11,512/43,231) of vaccination points of township level submitted immunization data to an CIIMS in 2008. The rate of implementation of the county > or = 90% are Fujian and Hubei. The rate of implementation of the township > or = 90% are Hubei, Fujian and Hebei. Coverage of eastern areas, middle areas and western areas were 28.91%, 43.20%, and 18.41% by county, 26.15%, 37.69%, and 16.44% by township respectively. The upload permissions against cases is in a total of 15,014 units, and the client software collect a total of 42,956,214 cases of immunization. 44.46% chinese children aged < 6 years old participated in an CIIMS in 2008. The vaccination point of township level submitted 8,793,334 cases to CIIMS, it accounted for 20.47% of client collection cases. To achieve the national CIIMS objectives for 2010, the extensive implementation must be promoted, the funding for system-building should be increased, an independent platform of CIIMS must be established, and admission of the issue of data exchange with the local information systems must be accelerated.

  13. Immune system development during early childhood in tropical Latin America: evidence for the age-dependent down regulation of the innate immune response.

    PubMed

    Teran, Rommy; Mitre, Edward; Vaca, Maritza; Erazo, Silvia; Oviedo, Gisela; Hübner, Marc P; Chico, Martha E; Mattapallil, Joseph J; Bickle, Quentin; Rodrigues, Laura C; Cooper, Philip J

    2011-03-01

    The immune response that develops in early childhood underlies the development of inflammatory diseases such as asthma and there are few data from tropical Latin America (LA). This study investigated the effects of age on the development of immunity during the first 5 years of life by comparing innate and adaptive immune responses in Ecuadorian children aged 6-9 months, 22-26 months, and 48-60 months. Percentages of naïve CD4+ T cells declined with age while those of memory CD4(+) and CD8(+) T cells increased indicating active development of the immune system throughout the first five years. Young infants had greater innate immune responses to TLR agonists compared to older children while regulatory responses including SEB-induced IL-10 and percentages of FoxP3(+) T-regulatory cells decreased with age. Enhanced innate immunity in early life may be important for host defense against pathogens but may increase the risk of immunopathology. Copyright © 2010 Elsevier Inc. All rights reserved.

  14. The Effects of Environment and Physiological Cyclicity on the Immune System of Viperinae

    PubMed Central

    Kobolkuti, Lorand; Cadar, Daniel; Czirjak, Gabor; Niculae, Mihaela; Kiss, Timea; Sandru, Carmen; Spinu, Marina

    2012-01-01

    One of the important aspects of species' survival is connected with global climate changes, which also conditions the epidemiology of infectious diseases. Poikilotherms are exposed, as other species, to climatic influence, especially due to their physiological peculiarities such as important stages of their life cycle: hibernation, shedding, and active phase. The immune system serves as an accurate indicator of the health status and stress levels in these species. This study aimed to monitor the changes of innate (leukocyte subpopulations and total immune globulins) and adaptive immunity (in vitro leukocyte blast transformation) of two viper species, V. berus berus and V. ammodytes ammodytes, endemic in Europe and spread in different regions of Romania during their three major life cycles, hibernation, shedding, and active phase. The results indicated that seasonal variance and cycle rather than species and regional distribution influence the functionality of the immune system. PMID:22547989

  15. The evaluation of a standardized call/recall system for childhood immunizations in Wandsworth, England.

    PubMed

    Atchison, Christina; Zvoc, Miro; Balakrishnan, Ravikumar

    2013-06-01

    To improve uptake of childhood immunizations in Wandsworth we developed a standardized call/recall system based on parents being sent three reminders and defaulters being referred to a Health Visitor. Thirty-two out of 44 primary care practices in the area implemented the intervention in September 2011. The aim of this study was to evaluate the implementation, delivery and impact on immunization uptake of the new call/recall system. To assess implementation and delivery, a mixed method approach was used including qualitative (structured interviews) and quantitative (data collected at three months post-implementation) assessment. To assess the impact, we used Student's t test to compare the difference in immunization uptake rates between intervention and non-intervention practices before and after implementation. The call/recall system was viewed positively by both parents and staff. Most children due or overdue immunizations were successfully captured by the 1st invitation reminder. After three invitations, between 87.3 % (MMR1) and 92.2 % (pre-school booster) of children identified as due or overdue immunizations successfully responded. Prior to implementation there was no difference in uptake rates between intervention and non-intervention practices. Post-implementation uptake rates for DTaP/IPV/Hib, MMR1, MMR2 and the pre-school booster were significantly greater in the intervention practices. Similar findings were seen for PCV and Hib/MenC boosters, although the differences were not statistically significant at the 5 % level. Following the successful implementation of a standardized call/recall system in Wandsworth, other regions or primary care practices may wish to consider introducing a similar system to help improve their immunization coverage levels.

  16. Understanding the immune response to seasonal influenza vaccination in older adults: a systems biology approach.

    PubMed

    Lambert, Nathaniel D; Ovsyannikova, Inna G; Pankratz, V Shane; Jacobson, Robert M; Poland, Gregory A

    2012-08-01

    Annual vaccination against seasonal influenza is recommended to decrease disease-related mortality and morbidity. However, one population that responds suboptimally to influenza vaccine is adults over the age of 65 years. The natural aging process is associated with a complex deterioration of multiple components of the host immune system. Research into this phenomenon, known as immunosenescence, has shown that aging alters both the innate and adaptive branches of the immune system. The intricate mechanisms involved in immune response to influenza vaccine, and how these responses are altered with age, have led us to adopt a more encompassing systems biology approach to understand exactly why the response to vaccination diminishes with age. Here, the authors review what changes occur with immunosenescence, and some immunogenetic factors that influence response, and outline the systems biology approach to understand the immune response to seasonal influenza vaccination in older adults.

  17. Passive Immunization Reduces Behavioral and Neuropathological Deficits in an Alpha-Synuclein Transgenic Model of Lewy Body Disease

    PubMed Central

    Masliah, Eliezer; Rockenstein, Edward; Mante, Michael; Crews, Leslie; Spencer, Brian; Adame, Anthony; Patrick, Christina; Trejo, Margarita; Ubhi, Kiren; Rohn, Troy T.; Mueller-Steiner, Sarah; Seubert, Peter; Barbour, Robin; McConlogue, Lisa; Buttini, Manuel; Games, Dora; Schenk, Dale

    2011-01-01

    Dementia with Lewy bodies (DLB) and Parkinson's Disease (PD) are common causes of motor and cognitive deficits and are associated with the abnormal accumulation of alpha-synuclein (α-syn). This study investigated whether passive immunization with a novel monoclonal α-syn antibody (9E4) against the C-terminus (CT) of α-syn was able to cross into the CNS and ameliorate the deficits associated with α-syn accumulation. In this study we demonstrate that 9E4 was effective at reducing behavioral deficits in the water maze, moreover, immunization with 9E4 reduced the accumulation of calpain-cleaved α-syn in axons and synapses and the associated neurodegenerative deficits. In vivo studies demonstrated that 9E4 traffics into the CNS, binds to cells that display α-syn accumulation and promotes α-syn clearance via the lysosomal pathway. These results suggest that passive immunization with monoclonal antibodies against the CT of α-syn may be of therapeutic relevance in patients with PD and DLB. PMID:21559417

  18. Re-thinking our understanding of immunity: Robustness in the tissue reconstruction system.

    PubMed

    Truchetet, Marie-Elise; Pradeu, Thomas

    2018-04-01

    Robustness, understood as the maintenance of specific functionalities of a given system against internal and external perturbations, is pervasive in today's biology. Yet precise applications of this notion to the immune system have been scarce. Here we show that the concept of robustness sheds light on tissue repair, and particularly on the crucial role the immune system plays in this process. We describe the specific mechanisms, including plasticity and redundancy, by which robustness is achieved in the tissue reconstruction system (TRS). In turn, tissue repair offers a very important test case for assessing the usefulness of the concept of robustness, and identifying different varieties of robustness. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. The human immune system's response to carcinogenic and other infectious agents transmitted by mosquito vectors.

    PubMed

    Johansson, Olle; Ward, Martin

    2017-01-01

    It has been hypothesised that mosquitoes [Diptera: Culicidae] may play more of a role in certain cancers than is currently appreciated. Research links 33 infectious agents to cancer, 27 of which have a presence in mosquitoes, and that, in addition, mosquito saliva downregulates the immune system. The objective of this paper is to review the literature on the immune system and cancer-causing infectious agents, particularly those present in mosquitoes, with a view to establishing whether such infectious agents can, in the long run, defeat the immune system or be defeated by it. Many of the viruses, bacteria and parasites recognised by the International Agency for Research on Cancer (IARC) as carcinogenic and suspected by others as being involved in cancer have evolved numerous complex ways of avoiding, suppressing or altering the immune system's responses. These features, coupled with the multiplicity and variety of serious infectious agents carried by some species of mosquitoes and the adverse effects on the immune system of mosquito saliva, suggest that post-mosquito bite the immune system is likely to be overwhelmed. In such a situation, immunisation strategies offer little chance of cancer prevention, unless a single or limited number of critical infectious agents can be isolated from the 'mosquito' cocktail. If that proves to be impossible cancer prevention will, therefore, if the hypothesis proves to be correct, rest on the twin strategies of environmentally controlling the mosquito population and humans avoiding being bitten. The latter strategy will involve determining the factors that demark those being bitten from those that are not.

  20. Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis

    PubMed Central

    López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C.; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

    2016-01-01

    Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen