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Sample records for modulates immune system

  1. Sympathetic neural modulation of the immune system

    SciTech Connect

    Madden, K.S.

    1989-01-01

    One route by which the central nervous system communicates with lymphoid organs in the periphery is through the sympathetic nervous system (SNS). To study SNS regulation of immune activity in vivo, selective removal of peripheral noradrenergic nerve fibers was achieved by administration of the neurotoxic drug, 6-hydroxydopamine (6-OHDA), to adult mice. To assess SNS influence on lymphocyte proliferation in vitro, uptake of {sup 125}iododeoxyuridine ({sup 125}IUdR), a DNA precursor, was measured following 6-OHDA treatment. Sympathectomy prior to epicutaneous immunization with TNCB did not alter draining lymph nodes (LN) cell proliferation, whereas 6-OHDA treatment before footpad immunization with KLH reduced DNA synthesis in popliteal LN by 50%. In mice which were not deliberately immunized, sympathectomy stimulated {sup 125}IUdR uptake inguinal and axillary LN, spleen, and bone marrow. In vitro, these LN and spleen cells exhibited decreased proliferation responses to the T cell mitogen, concanavalin A (Con A), whereas lipopolysaccharide (LPS)-stimulated IgG secretion was enhanced. Studies examining {sup 51}Cr-labeled lymphocyte trafficking to LN suggested that altered cell migration may play a part in sympathectomy-induced changes in LN cell function.

  2. Opioid System Modulates the Immune Function: A Review

    PubMed Central

    Liang, Xuan; Liu, Renyu; Chen, Chunhua; Ji, Fang; Li, Tianzuo

    2016-01-01

    Opioid receptors and their ligands produce powerful analgesia that is effective in perioperative period and chronic pain managements accompanied with various side effects including respiratory depression, constipation and addiction etc. Opioids can also interfere with the immune system, not only participating in the function of the immune cells, but also modulating innate and acquired immune responses. The traditional notion of opioids is immunosuppressive. Recent studies indicate that the role of opioid receptors on immune function is complicated, working through various different mechanisms. Different opioids or opioids administrations show various effects on the immune system: immunosuppressive, immunostimulatory, or dual effect. It is important to elucidate the relationship between opioids and immune function, since immune system plays critical role in various physiological and pathophysiological processes, including the inflammation, tumor growth and metastasis, drug abuse, and so on. This review article tends to have an overview of the recent work and perspectives on opioids and the immune function. PMID:26985446

  3. Opioid System Modulates the Immune Function: A Review.

    PubMed

    Liang, Xuan; Liu, Renyu; Chen, Chunhua; Ji, Fang; Li, Tianzuo

    Opioid receptors and their ligands produce powerful analgesia that is effective in perioperative period and chronic pain managements accompanied with various side effects including respiratory depression, constipation and addiction etc. Opioids can also interfere with the immune system, not only participating in the function of the immune cells, but also modulating innate and acquired immune responses. The traditional notion of opioids is immunosuppressive. Recent studies indicate that the role of opioid receptors on immune function is complicated, working through various different mechanisms. Different opioids or opioids administrations show various effects on the immune system: immunosuppressive, immunostimulatory, or dual effect. It is important to elucidate the relationship between opioids and immune function, since immune system plays critical role in various physiological and pathophysiological processes, including the inflammation, tumor growth and metastasis, drug abuse, and so on. This review article tends to have an overview of the recent work and perspectives on opioids and the immune function.

  4. Promoting tissue regeneration by modulating the immune system.

    PubMed

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

    2017-01-22

    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.

  5. The immune system and its modulation mechanism in scallop.

    PubMed

    Song, Linsheng; Wang, Lingling; Zhang, Huan; Wang, Mengqiang

    2015-09-01

    Scallops are a cosmopolitan family of bivalves, and some of them are highly prized as dominant aquaculture species. In the past decades, there have been increasing studies on the basic biology and immunology of scallops, and this review summarizes the research progresses of immune system and its modulation mechanism in scallop. As invertebrate, scallops lack adaptive immunity and they have evolved an array of sophisticated strategies to recognize and eliminate various invaders by employing a set of molecules and cells. It is evident that basic immune reactions such as immune recognition, signal transduction, and effector synthesis involved in immune response are accomplished in a variety of ways. They rely upon an extensive repertoire of phagocytosis, apoptosis and encapsulation of the circulating hemocytes for eliminating invasive pathogens, as well as the production of immune effectors that are active against a large range of pathogens or sensitive for the environmental stress. Furthermore, the molecular constitutions, metabolic pathways and immunomodulation mechanisms of the primitive catecholaminergic, cholinergic, enkephalinergic system and NO system in scallop are also discussed, which can be taken as an entrance to better understand the origin and evolution of the neuroendocrine-immune regulatory network in lower invertebrates.

  6. How photons modulate wound healing via the immune system

    NASA Astrophysics Data System (ADS)

    Dyson, Mary

    2009-02-01

    The immune system is a diverse group of cells that recognize and attack foreign substances, pathogenic organisms and cancer cells. It also produces inflammation, an essential component of the wound healing process and, following the resolution of inflammation, plays a crucial role in the control of granulation tissue formation. Granulation tissue is the precursor of scar tissue. Injured skin and mucous membranes generally heal rapidly. However, some wounds are either slow to heal or fail to heal while in others overgrowth of scar tissue occurs, resulting in the production of either hypertophic or keloid scars. The modulation of wound healing in such conditions is clinically important and may even be vital. Evidence will be presented that phototherapy can modulate wound healing, and that changes induced in the immune system, in particular the secretion of soluble protein mediators including cytokines, may be involved in this modulation. The immune system has peripheral and deep components. The former, being located mainly in the skin and mucous membranes, are readily accessible to photons, which can affect them directly. The components of the immune system are linked by lymphatic vessels and blood vessels, which include many capillaries located in the sub-epithelial connective tissues of the skin and mucous membranes. The superficial location of these capillaries provides the immune cells and molecules in transit through them with ready access to photons. When these cells and molecules, some modified by exposure to photons, reach susceptible cells such as lymphocytes in the deeper parts of the immune system and cells of injured tissues, they can modify their activity. In addition to having direct effects on peripheral cells, photons can thus also produce indirect effects on cells too distant for the photons to reach them. For example, cytokines released from peripheral macrophages in response to the direct action of photons can be transported to and affect other

  7. Immune System Modulators with Antidepressant Effects: Evidence from Animal Models.

    PubMed

    Abelaira, Helena M; Maciel, Amanda L; Quevedo, Joao; Reus, Gislaine Z

    2017-01-01

    Major depressive disorder (MDD) is associated with high mortality and morbidity rates, and currently, approximately 340 million people worldwide suffer from depression at some point in life. In view of the growing socio-economic and clinical impact, several studies have focused on the etiopathology of MDD, suggesting that not only the monoaminergic system but also other brain mechanisms may be involved in the pathophysiology of MDD. Recent studies have shown a link between inflammation and MDD and have also demonstrated that antidepressants and antiinflammatory drugs can act to reduce inflammation, thereby improving depressive symptoms. Animal models of depression are indispensable for studying the pathophysiology of this disorder and new treatments for it. Further, studies have shown that rodent models of depression are also associated with elevated levels of inflammation in the periphery and brain. This review will highlight the role of immune inflammation in MDD and the significance of immune system modulators with antidepressant effects in the treatment of MDD, based on studies using animal models of depression. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Materials that harness and modulate the immune system

    PubMed Central

    Lewis, Jamal S.; Roy, Krishnendu; Keselowsky, Benjamin G.

    2016-01-01

    Recently, biomaterial scientists have married materials engineering and immunobiology to conceptualize new immunomodulatory materials. This special class of biomaterials can modulate and harness the innate properties of immune functionality for enhanced therapeutic efficacy. Generally, two fundamental strategies are followed in the design of immunomodulatory biomaterials: (1) immuno-evasive (immuno-mimetic, immuno-suppressing, or immuno-inert) biomaterials and (2) immuno-activating or immuno-enhancing biomaterials. This article highlights the development and application of a number of immunomodulatory materials, categorized by these two general approaches. PMID:26997752

  9. Acupuncture and immune modulation.

    PubMed

    Kim, Sun Kwang; Bae, Hyunsu

    2010-10-28

    Acupuncture is probably the most popular alternative therapy practiced in the United States, Europe and many Asian countries. It has been applied clinically for more than 5 thousand years according to the ancient oriental medical theory. A great deal of acupuncture research has been achieved, with particular efforts toward understanding the pain control effects. In addition to the analgesic effect of acupuncture, an increasing number of studies have demonstrated that acupuncture treatment can control autonomic nerve system functions such as blood pressure regulation, sphincter Oddi relaxation, and immune modulation. Although only a limited number of controlled studies have assessed the efficacy of acupuncture, increasing clinical evidences support that EA treatment is effective for various immunological diseases including allergic disorders, infections, autoimmune diseases and immunodifficiency-syndromes. This review will address the mechanism of acupuncture in modulating various immune responses and the relationship between acupuncture mediated immune regulation and neurological involvement.

  10. Regenerative function of immune system: Modulation of muscle stem cells.

    PubMed

    Saini, Jasdeep; McPhee, Jamie S; Al-Dabbagh, Sarah; Stewart, Claire E; Al-Shanti, Nasser

    2016-05-01

    Ageing is characterised by progressive deterioration of physiological systems and the loss of skeletal muscle mass is one of the most recognisable, leading to muscle weakness and mobility impairments. This review highlights interactions between the immune system and skeletal muscle stem cells (widely termed satellite cells or myoblasts) to influence satellite cell behaviour during muscle regeneration after injury, and outlines deficits associated with ageing. Resident neutrophils and macrophages in skeletal muscle become activated when muscle fibres are damaged via stimuli (e.g. contusions, strains, avulsions, hyperextensions, ruptures) and release high concentrations of cytokines, chemokines and growth factors into the microenvironment. These localised responses serve to attract additional immune cells which can reach in excess of 1×10(5) immune cell/mm(3) of skeletal muscle in order to orchestrate the repair process. T-cells have a delayed response, reaching peak activation roughly 4 days after the initial damage. The cytokines and growth factors released by activated T-cells play a key role in muscle satellite cell proliferation and migration, although the precise mechanisms of these interactions remain unclear. T-cells in older people display limited ability to activate satellite cell proliferation and migration which is likely to contribute to insufficient muscle repair and, consequently, muscle wasting and weakness. If the factors released by T-cells to activate satellite cells can be identified, it may be possible to develop therapeutic agents to enhance muscle regeneration and reduce the impact of muscle wasting during ageing and disease.

  11. Lentivirus technologies for modulation of the immune system.

    PubMed

    Houghton, Benjamin C; Booth, Claire; Thrasher, Adrian J

    2015-10-01

    Lentiviral vectors (LVV) are important tools for the treatment of immune system disorders. Integration of therapeutic genetic material into the haematopoietic stem cell compartment using LVV can mediate long-term correction of haematopoietic lineages, thereby correcting disease phenotypes. Twenty years of vector development have successfully brought LVV to the clinic, with follow up studies of clinical trials treating primary immunodeficiencies now being reported. Results have demonstrated clear improvements in the quality of life for patients with a number of conditions in the absence of the severe adverse events observed in earlier retroviral gene therapy trials. Growing interest in gene modified adoptive T cell transfer as an alternative strategy has driven further technology innovation, including characterisation of novel viral envelopes. We will also discuss the progression of gene editing technology to preclinical investigations in models of immune deficiency. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies.

    PubMed

    Sideras, K; Braat, H; Kwekkeboom, J; van Eijck, C H; Peppelenbosch, M P; Sleijfer, S; Bruno, M

    2014-05-01

    Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Chronic schistosome infection leads to modulation of granuloma formation and systemic immune suppression

    PubMed Central

    Lundy, Steven K.; Lukacs, Nicholas W.

    2012-01-01

    Schistosome worms have been infecting humans for millennia, but it is only in the last half century that we have begun to understand the complexities of this inter-relationship. As our sophistication about the inner workings of every aspect of the immune system has increased, it has also become obvious that schistosome infections have broad ranging effects on nearly all of the innate and adaptive immune response mechanisms. Selective pressures on both the worms and their hosts, has no doubt led to co-evolution of protective mechanisms, particularly those that favor granuloma formation around schistosome eggs and immune suppression during chronic infection. The immune modulatory effects that chronic schistosome infection and egg deposition elicit have been intensely studied, not only because of their major implications to public health issues, but also due to the emerging evidence that schistosome infection may protect humans from severe allergies and autoimmunity. Mouse models of schistosome infection have been extremely valuable for studying immune modulation and regulation, and in the discovery of novel aspects of immunity. A progression of immune reactions occurs during granuloma formation ranging from innate inflammation, to activation of each branch of adaptive immune response, and culminating in systemic immune suppression and granuloma fibrosis. Although molecular factors from schistosome eggs have been identified as mediators of immune modulation and suppressive functions of T and B cells, much work is still needed to define the mechanisms of the immune alteration and determine whether therapies for asthma or autoimmunity could be developed from these pathways. PMID:23429492

  14. Iloprost modulates the immune response in systemic sclerosis

    PubMed Central

    2010-01-01

    Background Iloprost has been suggested to possess anti-inflammatory and immunomodulating actions and it is widely use as a vasodilatator in systemic sclerosis (SSc). In this study we evaluate the effect of iloprost on immune response in SSc patients. To this extend we enrolled 15 women affected by SSc and infused iloprost for 5 days. The effect of iloprost on T cells and monocytes was measured by flow cytometry, Real time PCR and measuring cytokines production in vivo and in vitro by ELISA. Results Our results demonstrate that Iloprost reduces T cell and TNF alpha production both in vivo and in vitro. It reduces T regulatory cells number, but increases their activity after immune stimulation. It increases serum IL-2 and this increase persists 28 days after the last infusion, also RANKL was increased both in vivo and in vitro. We observed no effect on IFN gamma production. Conclusions These results suggest that iloprost has anti-inflammatory and immunomodulating effects, reducing TNF alpha production by T cells and the number of T regulatory cells and increasing IL-2 and RANKL. PMID:21159177

  15. Immune System

    MedlinePlus

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Immune System KidsHealth > For Teens > Immune System A A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  16. Photodynamic immune modulation (PIM)

    NASA Astrophysics Data System (ADS)

    North, John R.; Hunt, David W. C.; Simkin, Guillermo O.; Ratkay, Leslie G.; Chan, Agnes H.; Lui, Harvey; Levy, Julia G.

    1999-09-01

    Photodynamic Therapy (PDT) is accepted for treatment of superficial and lumen-occluding tumors in regions accessible to activating light and is now known to be effective in closure of choroidal neovasculature in Age Related Macular Degeneration. PDT utilizes light absorbing drugs (photosensitizers) that generate the localized formation of reactive oxygen species after light exposure. In a number of systems, PDT has immunomodulatory effects; Photodynamic Immune Modulation (PIM). Using low- intensity photodynamic regimens applied over a large body surface area, progression of mouse autoimmune disease could be inhibited. Further, this treatment strongly inhibited the immunologically- medicated contact hypersensitivity response to topically applied chemical haptens. Immune modulation appears to result from selective targeting of activated T lymphocytes and reduction in immunostimulation by antigen presenting cells. Psoriasis, an immune-mediated skin condition, exhibits heightened epidermal cell proliferation, epidermal layer thickening and plaque formation at different body sites. In a recent clinical trial, approximately one-third of patients with psoriasis and arthritis symptoms (psoriatic arthritis) displayed a significant clinical improvement in several psoriasis-related parameters after four weekly whole-body PIM treatments with verteporfin. The safety profile was favorable. The capacity of PIM to influence other human immune disorders including rheumatoid arthritis is under extensive evaluation.

  17. Encapsulated Cellular Implants for Recombinant Protein Delivery and Therapeutic Modulation of the Immune System

    PubMed Central

    Lathuilière, Aurélien; Mach, Nicolas; Schneider, Bernard L.

    2015-01-01

    Ex vivo gene therapy using retrievable encapsulated cellular implants is an effective strategy for the local and/or chronic delivery of therapeutic proteins. In particular, it is considered an innovative approach to modulate the activity of the immune system. Two recently proposed therapeutic schemes using genetically engineered encapsulated cells are discussed here: the chronic administration of monoclonal antibodies for passive immunization against neurodegenerative diseases and the local delivery of a cytokine as an adjuvant for anti-cancer vaccines. PMID:26006227

  18. Vitamin D and molecular actions on the immune system: modulation of innate and autoimmunity

    PubMed Central

    Kamen, Diane L.

    2010-01-01

    Vitamin D has received increased attention recently for its pleiotropic actions on many chronic diseases. The importance of vitamin D on the regulation of cells of the immune system has gained increased appreciation over the past decade with the discovery of the vitamin D receptor (VDR) and key vitamin D metabolizing enzymes expressed by cells of the immune system. Animal studies, early epidemiologic and clinical studies have supported a potential role for vitamin D in maintaining immune system balance. The hormonal form of vitamin D up-regulates anti-microbial peptides, namely cathelicidin, to enhance clearance of bacteria at various barrier sites and in immune cells. Vitamin D modulates the adaptive immune system by direct effects on T cell activation and on the phenotype and function of antigen-presenting cells (APCs), particularly of DCs. The purpose of this manuscript is to review the molecular and clinical evidence for vitamin D as a modulator of the innate and adaptive immune system. PMID:20119827

  19. Immune Response Modulation by Vitamin D: Role in Systemic Lupus Erythematosus

    PubMed Central

    Iruretagoyena, Mirentxu; Hirigoyen, Daniela; Naves, Rodrigo; Burgos, Paula Isabel

    2015-01-01

    Vitamin D plays key roles as a natural immune modulator and has been implicated in the pathophysiology of autoimmune diseases, including systemic lupus erythematosus (SLE). This review presents a summary and analysis of the recent literature regarding immunoregulatory effects of vitamin D as well as its importance in SLE development, clinical severity, and possible effects of supplementation in disease treatment. PMID:26528285

  20. Systemic immune modulation induced by alcoholic beverage intake in obese-diabetes (db/db) mice.

    PubMed

    Lee, Hyunah; Jang, Ik-Soon; Park, Junsoo; Kim, Seol-Hee; Baek, So-Young; Go, Sung-Ho; Lee, Seung-Hoon

    2013-03-01

    Alcohol over-consumption is generally immunosuppressive. In this study, the effects of single or repetitive alcohol administration on the systemic immunity of db/db mice were observed to clarify the possible mechanisms for the increased susceptibility of obese individuals to alcohol-related immunological health problems. Alcohol (as a form of commercially available 20% distilled-alcoholic beverage) was orally administered one-time or seven times over 2 weeks to db/db mice and normal C57BL/6J mice. Immunologic alterations were analyzed by observation of body weight and animal activity, along with proportional changes of splenocytes for natural killer cells, macrophages, and T and B lymphocytes. Modulation of plasma cytokine level and immune-related genes were also ascertained by micro-bead assay and a microarray method, respectively. The immune micro-environment of db/db mice was an inflammatory state and adaptive cellular immunity was significantly suppressed. Low-dose alcohol administration reversed the immune response, decreasing inflammatory responses and the increment of adaptive immunity mainly related to CD4(+) T cells, but not CD8(+) T cells, to normal background levels. Systemic immune modulation due to alcohol administration in the obese-diabetic mouse model may be useful in the understanding of the induction mechanism, which will aid the development of therapeutics for related secondary diseases.

  1. 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.

  2. Immune Modulation in Hematologic Malignancies

    PubMed Central

    Dhodapkar, Madhav V.; Dhodapkar, Kavita M.

    2015-01-01

    The therapeutic potential of the immune system in the context of hematologic malignancies has long been appreciated particularly due to the curative impact of allogeneic hematopoietic stem cell transplantation. The role of immune system in shaping the biology and evolution of these tumors is now well recognized. While the contribution of the immune system in anti-tumor effects of certain therapies such as immune-modulatory drugs and monoclonal antibodies active in hematologic malignancies is quite evident, the immune system has also been implicated in anti-tumor effects of other targeted therapies. The horizon of immune-based therapies in hematologic malignancies is rapidly expanding with promising results from immune-modulatory drugs, immune-checkpoint blockade and adoptive cellular therapies, including genetically-modified T cells. Hematologic malignancies present distinct issues (relative to solid tumors) for the application of immune therapies due to differences in cell of origin/developmental niche of tumor cells, and patterns of involvement such as common systemic involvement of secondary lymphoid tissues. This article discusses the rapidly changing landscape of immune modulation in hematologic malignancies and emphasizes areas wherein hematologic malignancies present distinct opportunities for immunologic approaches to prevent or treat cancer. PMID:26320065

  3. Sympathetic Modulation of Immunity: Relevance to Disease

    PubMed Central

    Bellinger, Denise L.; Millar, Brooke A.; Perez, Sam; Carter, Jeff; Wood, Carlo; ThyagaRajan, Srinivasan; Molinaro, Christine; Lubahn, Cheri; Lorton, Dianne

    2008-01-01

    Optimal host defense against pathogens requires cross-talk between the nervous and immune systems. This paper reviews sympathetic-immune interaction, one major communication pathway, and its importance for health and disease. Sympathetic innervation of primary and secondary immune organs is described, as well as evidence for neurotransmission with cells of the immune system as targets. Most research thus far as focused on neural-immune modulation in secondary lymphoid organs, and have revealed complex sympathetic modulation resulting in both potentiation and inhibition of immune functions. SNS-immune interaction may enhance immune readiness during disease- or injury-induced ‘fight’ responses. Research also indicate that dysregulation of the SNS can significantly affect the progression of immune-mediated diseases. However, a better understanding of neural-immune interactions is needed to develop strategies for treatment of immune-mediated diseases that are designed to return homeostasis and restore normal functioning neural-immune networks. PMID:18308299

  4. Innate immune interactions within the central nervous system modulate pathogenesis of viral infections

    PubMed Central

    Nair, Sharmila; Diamond, Michael S.

    2015-01-01

    The innate immune system mediates protection against neurotropic viruses that replicate in the central nervous system (CNS). Virus infection within specific cells of the CNS triggers activation of several families of pattern recognition receptors including Toll-like receptors, retinoic acid-inducible gene 1 like receptors, nucleotide-binding oligomerization domain-like receptors, and cytosolic DNA sensors. In this review, we highlight recent advances in our understanding of how cell-intrinsic host defenses within the CNS modulate infection of different DNA and RNA viruses. PMID:26163762

  5. Effects of the modulation of microbiota on the gastrointestinal immune system and bowel function.

    PubMed

    Kanauchi, Osamu; Andoh, Akira; Mitsuyama, Keiichi

    2013-10-23

    The gastrointestinal tract harbors a tremendous number and variety of commensal microbiota. The intestinal mucosa simultaneously absorbs essential nutrients and protects against detrimental antigens or pathogenic microbiota as the first line of defense. Beneficial interactions between the host and microbiota are key requirements for host health. Although the gut microbiota has been previously studied in the context of inflammatory diseases, it has recently become clear that this microbial environment has a beneficial role during normal homeostasis, by modulating the immune system or bowel motor function. Recent studies revealed that microbiota, including their metabolites, modulate key signaling pathways involved in the inflammation of the mucosa or the neurotransmitter system in the gut-brain axis. The underlying molecular mechanisms of host-microbiota interactions are still unclear; however, manipulation of microbiota by probiotics or prebiotics is becoming increasingly recognized as an important therapeutic option, especially for the treatment of the dysfunction or inflammation of the intestinal tract.

  6. Strategies to modulate the immune system in breast cancer: checkpoint inhibitors and beyond

    PubMed Central

    Migali, Cristina; Milano, Monica; Trapani, Dario; Criscitiello, Carmen; Esposito, Angela; Locatelli, Marzia; Minchella, Ida; Curigliano, Giuseppe

    2016-01-01

    Is breast cancer (BC) immunogenic? Many data suggest that it is. Many observations demonstrated the prognostic role of tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2 (HER-2)-positive BC. TNBCs are poorly differentiated tumors with high genetic instability and very high heterogeneity. This heterogeneity enhances the ‘danger signals’ and select clone variants that could be more antigenic or, in other words, that could more strongly stimulate a host immune antitumor response. The response to chemotherapy is at least partly dependent on an immunological reaction against those tumor cells that are dying during the chemotherapy. One of the mechanisms whereby chemotherapy can stimulate the immune system to recognize and destroy malignant cells is commonly known as immunogenic cell death (ICD). ICD elicits an adaptive immune response. Which are the clinical implications of all ‘immunome’ data produced in the last years? First, validate prognostic or predictive role of TILs. Second, validate immune genomic signatures that may be predictive and prognostic in patients with TN disease. Third, incorporate an ‘immunoscore’ into traditional classification of BC, thus providing an essential prognostic and potentially predictive tool in the pathology report. Fourth, implement clinical trials for BC in the metastatic setting with drugs that target immune-cell–intrinsic checkpoints. Blockade of one of these checkpoints, cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) or the programmed cell death 1 (PD-1) receptor may provide proof of concepts for the activity of an immune-modulation approach in the treatment of a BC. PMID:27583028

  7. Photosensitizers for photodynamic immune modulation

    NASA Astrophysics Data System (ADS)

    North, John R.; Boch, Ronald; Hunt, David W. C.; Ratkay, Leslie G.; Simkin, Guillermo O.; Tao, Jing-Song; Richter, Anna M.; Levy, Julia G.

    2000-06-01

    PDT may be an effective treatment for certain immune-mediated disorders. The immunomodulatory action of PDT is likely a consequence of effects exerted at a number of levels including stimulation of specific cell signaling pathways, selective depletion of activated immune cells, alteration of receptor expression by immune and non-immune cells, and the modulation of cytokine availability. QLT0074, a potent photosensitizer that exhibits rapid clearance kinetics in vivo, is in development for the treatment of immune disorders. In comparison to the well-characterized and structurally related photosensitizer verteporfin, lower concentrations of QLT0074 were required to induce apoptosis in human blood T cells and keratinocytes using blue light for photoactivation. Both photosensitizers triggered the stress activated protein kinase (SAPK) and p38 (HOG1) pathways but not extracellularly regulated kinase (ERK) activity in mouse Pam212 keratinocytes. In cell signaling responses, QLT0074 was active at lower concentrations than verteporfin. For all in vitro test systems, the stronger photodynamic activity of QLT0074 was associated with a greater cell uptake of this photosensitize than verteporfin. In mouse immune models, sub-erythemogenic doses of QLT0074 in combination with whole body blue light irradiation inhibited the contact hypersensitivity response and limited the development of adjuvant-induced arthritis. QLT0074 exhibits activities that indicate it may be a favorable agent for the photodynamic treatment of human immune disease.

  8. Tinospora species: An overview of their modulating effects on the immune system.

    PubMed

    Haque, Md Areeful; Jantan, Ibrahim; Abbas Bukhari, Syed Nasir

    2017-07-31

    Studies on the effects of natural immunomodulators to heal various diseases related to the immune system have been a growing interest in recent years. Amongst the medicinal plants, Tinospora species (family; Menispermaceae) have been one of the widely investigated plants for their modulating effects on the immune system due to their wide use in ethnomedicine to treat various ailments related to immune-related diseases. However, their ethnopharmacological uses are mainly with limited or without scientific basis. In this article, we have reviewed the literature on the phytochemicals of several Tinospora species, which have shown strong immunomodulatory effects and critically analyzed the reports to provide perspectives and instructions for future research for the plants as a potential source of new immunomodulators for use as medicinal agents or dietary supplements. Electronic search on worldwide accepted scientific databases (Google Scholar, Science Direct, SciFinder, Web of Science, PubMed, Wiley Online Library, ACS Publications Today) was performed to compile the relevant information. Some information was obtained from books, database on medicinal plants used in Ayurveda, MSc dissertations and herbal classics books written in various languages. T. cordifolia, T. crispa, T. sinensis, T. smilacina, T. bakis, and T. sagittata have been reported to possess significant immunomodulatory effects. For a few decades, initiatives in molecular research on the effects of these species on the immune system have been carried out. However, most of the biological and pharmacological studies were carried out using the crude extracts of plants. The bioactive compounds contributing to the bioactivities have not been properly identified, and mechanistic studies to understand the immunomodulatory effects of the plants are limited by many considerations with regard to design, conduct, and interpretation. The plant extracts and their active constituents should be subjected to more

  9. Rational modulation of the innate immune system for neuroprotection in ischemic stroke

    PubMed Central

    Amantea, Diana; Micieli, Giuseppe; Tassorelli, Cristina; Cuartero, María I.; Ballesteros, Iván; Certo, Michelangelo; Moro, María A.; Lizasoain, Ignacio; Bagetta, Giacinto

    2015-01-01

    The innate immune system plays a dualistic role in the evolution of ischemic brain damage and has also been implicated in ischemic tolerance produced by different conditioning stimuli. Early after ischemia, perivascular astrocytes release cytokines and activate metalloproteases (MMPs) that contribute to blood–brain barrier (BBB) disruption and vasogenic oedema; whereas at later stages, they provide extracellular glutamate uptake, BBB regeneration and neurotrophic factors release. Similarly, early activation of microglia contributes to ischemic brain injury via the production of inflammatory cytokines, including tumor necrosis factor (TNF) and interleukin (IL)-1, reactive oxygen and nitrogen species and proteases. Nevertheless, microglia also contributes to the resolution of inflammation, by releasing IL-10 and tumor growth factor (TGF)-β, and to the late reparative processes by phagocytic activity and growth factors production. Indeed, after ischemia, microglia/macrophages differentiate toward several phenotypes: the M1 pro-inflammatory phenotype is classically activated via toll-like receptors or interferon-γ, whereas M2 phenotypes are alternatively activated by regulatory mediators, such as ILs 4, 10, 13, or TGF-β. Thus, immune cells exert a dualistic role on the evolution of ischemic brain damage, since the classic phenotypes promote injury, whereas alternatively activated M2 macrophages or N2 neutrophils prompt tissue remodeling and repair. Moreover, a subdued activation of the immune system has been involved in ischemic tolerance, since different preconditioning stimuli act via modulation of inflammatory mediators, including toll-like receptors and cytokine signaling pathways. This further underscores that the immuno-modulatory approach for the treatment of ischemic stroke should be aimed at blocking the detrimental effects, while promoting the beneficial responses of the immune reaction. PMID:25972779

  10. 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...

  11. 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...

  12. Poly(lactic acid)-based particulate systems are promising tools for immune modulation.

    PubMed

    Peres, Carina; Matos, Ana I; Conniot, João; Sainz, Vanessa; Zupančič, Eva; Silva, Joana M; Graça, Luís; Sá Gaspar, Rogério; Préat, Véronique; Florindo, Helena F

    2017-01-15

    Poly(lactic acid) (PLA) is one of the most successful and versatile polymers explored for controlled delivery of bioactive molecules. Its attractive properties of biodegradability and biocompatibility in vivo have contributed in a meaningful way to the approval of different products by the FDA and EMA for a wide range of biomedical and pharmaceutical applications, in the past two decades. This polymer has been widely used for the preparation of particles as delivery systems of several therapeutic molecules, including vaccines. These PLA vaccine carriers have shown to induce a sustained and targeted release of different bacterial, viral and tumor-associated antigens and adjuvants in vivo, triggering distinct immune responses. The present review intends to highlight and discuss the major advantages of PLA as a promising polymer for the development of potent vaccine delivery systems against pathogens and cancer. It aims to provide a critical discussion based on preclinical data to better understand the major effect of PLA-based carrier properties on their interaction with immune cells and thus their role in the modulation of host immunity. During the last decades, vaccination has had a great impact on global health with the control of many severe diseases. Polymeric nanosystems have emerged as promising strategies to stabilize vaccine antigens, promoting their controlled release to phagocytic cells, thus avoiding the need for multiple administrations. One of the most promising polymers are the aliphatic polyesters, which include the poly(lactic acid). This is a highly versatile biodegradable and biocompatible polymer. Products containing this polymer have already been approved for all food and some biomedical applications. Despite all favorable characteristics presented above, PLA has been less intensively discussed than other polymers, such as its copolymer PLGA, including regarding its application in vaccination and particularly in tumor immunotherapy. The present

  13. Gastric Adenocarcinoma: An Update on Genomics, Immune System Modulations, and Targeted Therapy.

    PubMed

    Lee, Jeeyun; Bass, Adam J; Ajani, Jaffer A

    2016-01-01

    Gastric adenocarcinoma (GAC) is a global health burden on all societies, and it was the third-leading cause of cancer-related mortality in 2012, causing 723,000 deaths worldwide. The prognosis of patients with metastatic GAC remains poor, with a median overall survival of less than 1 year in patients treated with currently available therapies. A limited number of therapeutic agents is currently available. Recent additions to the armamentarium include trastuzumab and ramucirumab, which have shown some survival advantage when added to cytotoxic(s). Genomic analyses have defined various genotypes of GACs. The novel genomic knowledge can lead to discovery of novel targets and novel therapeutic agents. In this update, we focus on the current genomic data, targeted therapies including immune system modulators, and expand on HER2/neu testing and the use of agents against this target. Several other facets of GAC and its therapy are not to be included in this review but have been discussed elsewhere.

  14. Adjuvant System AS03 containing α-tocopherol modulates innate immune response and leads to improved adaptive immunity.

    PubMed

    Morel, Sandra; Didierlaurent, Arnaud; Bourguignon, Patricia; Delhaye, Sophie; Baras, Benoît; Jacob, Valérie; Planty, Camille; Elouahabi, Abdelatif; Harvengt, Pol; Carlsen, Harald; Kielland, Anders; Chomez, Patrick; Garçon, Nathalie; Van Mechelen, Marcelle

    2011-03-16

    AS03 is an Adjuvant System (AS) containing α-tocopherol and squalene in an oil-in-water (o/w) emulsion. AS03 has been considered for the development of pandemic and seasonal influenza vaccines. Key features of AS03's mode of action were investigated in vivo in mice and ex vivo in human cells. AS03's adjuvant activity was superior to that of aluminium hydroxide and required the spatio-temporal co-localisation of AS03 with the antigen. This requirement coincided with AS03 triggering a transient production of cytokines at the injection site and in the draining lymph nodes (dLNs). The nature of the cytokines produced was consistent with the enhanced recruitment of granulocytes and of antigen-loaded monocytes in the dLNs. The presence of α-tocopherol in AS03 was required for AS03 to achieve the highest antibody response. The presence of α-tocopherol also modulated the expression of some cytokines, including CCL2, CCL3, IL-6, CSF3 and CXCL1; increased the antigen loading in monocytes; and increased the recruitment of granulocytes in the dLNs. Hence, AS03's promotion of monocytes as the principal antigen-presenting cells, and its effects on granulocytes and cytokines, may all contribute to enhancing the antigen-specific adaptive immune response.

  15. Lactobacillus paracasei modulates the immune system of Galleria mellonella and protects against Candida albicans infection

    PubMed Central

    Rossoni, Rodnei Dennis; Fuchs, Beth Burgwyn; de Barros, Patrícia Pimentel; Velloso, Marisol dos Santos; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos; Mylonakis, Eleftherios

    2017-01-01

    Probiotics have been described as a potential strategy to control opportunistic infections due to their ability to stimulate the immune system. Using the non-vertebrate model host Galleria mellonella, we evaluated whether clinical isolates of Lactobacillus spp. are able to provide protection against Candida albicans infection. Among different strains of Lactobacillus paracasei, Lactobacillus rhamnosus and Lactobacillus fermentum, we verified that L. paracasei 28.4 strain had the greatest ability to prolong the survival of larvae infected with a lethal dose of C. albicans. We found that the injection of 107 cells/larvae of L. paracasei into G. mellonella larvae infected by C. albicans increased the survival of these insects compared to the control group (P = 0.0001). After that, we investigated the immune mechanisms involved in the protection against C. albicans infection, evaluating the number of hemocytes and the gene expression of antifungal peptides. We found that L. paracasei increased the hemocyte quantity (2.38 x 106 cells/mL) in relation to the control group (1.29 x 106 cells/mL), indicating that this strain is capable of raising the number of circulating hemocytes into the G. mellonella hemolymph. Further, we found that L. paracasei 28.4 upregulated genes that encode the antifungal peptides galiomicin and gallerymicin. In relation to the control group, L. paracasei 28.4 increased gene expression of galiomicin by 6.67-fold and 17.29-fold for gallerymicin. Finally, we verified that the prophylactic provision of probiotic led to a significant reduction of the number of fungal cells in G. mellonella hemolymph. In conclusion, L. paracasei 28.4 can modulate the immune system of G. mellonella and protect against candidiasis. PMID:28267809

  16. Lactobacillus paracasei modulates the immune system of Galleria mellonella and protects against Candida albicans infection.

    PubMed

    Rossoni, Rodnei Dennis; Fuchs, Beth Burgwyn; de Barros, Patrícia Pimentel; Velloso, Marisol Dos Santos; Jorge, Antonio Olavo Cardoso; Junqueira, Juliana Campos; Mylonakis, Eleftherios

    2017-01-01

    Probiotics have been described as a potential strategy to control opportunistic infections due to their ability to stimulate the immune system. Using the non-vertebrate model host Galleria mellonella, we evaluated whether clinical isolates of Lactobacillus spp. are able to provide protection against Candida albicans infection. Among different strains of Lactobacillus paracasei, Lactobacillus rhamnosus and Lactobacillus fermentum, we verified that L. paracasei 28.4 strain had the greatest ability to prolong the survival of larvae infected with a lethal dose of C. albicans. We found that the injection of 107 cells/larvae of L. paracasei into G. mellonella larvae infected by C. albicans increased the survival of these insects compared to the control group (P = 0.0001). After that, we investigated the immune mechanisms involved in the protection against C. albicans infection, evaluating the number of hemocytes and the gene expression of antifungal peptides. We found that L. paracasei increased the hemocyte quantity (2.38 x 106 cells/mL) in relation to the control group (1.29 x 106 cells/mL), indicating that this strain is capable of raising the number of circulating hemocytes into the G. mellonella hemolymph. Further, we found that L. paracasei 28.4 upregulated genes that encode the antifungal peptides galiomicin and gallerymicin. In relation to the control group, L. paracasei 28.4 increased gene expression of galiomicin by 6.67-fold and 17.29-fold for gallerymicin. Finally, we verified that the prophylactic provision of probiotic led to a significant reduction of the number of fungal cells in G. mellonella hemolymph. In conclusion, L. paracasei 28.4 can modulate the immune system of G. mellonella and protect against candidiasis.

  17. Anti-allergic effects of probiotic Dahi through modulation of the gut immune system.

    PubMed

    Jain, Shalini; Yadav, Hariom; Sinha, P R; Kapila, Suman; Naito, Yasuhiro; Marotta, Francesco

    2010-09-01

    The alarming increase in allergy in the last few decades demands the development of new anti-allergic prevention strategies, and consumption of functional foods (i.e. probiotic Dahi, which has already been proven to enhance immunity by modulation of the gut mucosal immune system) may be one of them. In the present study, we evaluated anti-allergic effects of a Dahi (yogurt) containing probiotic Lactobacillus acidophilus, L. casei and normal Dahi culture Lactococcus lactis biovar diacetylactis (named probiotic Dahi) on ovalbumin induced allergy in mice. Allergy was induced by injecting (i.p.) ovalbumin at 0 and 14 days. Animals were fed with standard diet (control), milk, control Dahi or probiotic Dahi for 21 days. Total and ovalbumin-specific IgE, cytokines and lymphocyte proliferation index were examined after 7, 14 and 21 days. Feeding of probiotic Dahi completely suppressed the elevation of total and ovalbumin-specific IgE in the serum of ovalbumin-injected mice. Similarly, splenocytes collected from mice fed with probiotic Dahi entirely lost the total and ovalbumin-specific IgE production property during in-vitro culture. Production of T helper (Th)-1 cell-specific cytokines, i.e. interferon -γ and interleukin (IL)-2, increased, while Th2-specific cytokines, i.e. IL-4 and IL-6, decreased in the supernatant of cultured splenocytes collected from mice fed with probiotic Dahi compared to the other groups. Moreover, ovalbumin-stimulated lymphocyte proliferation was strongly suppressed by feeding of probiotic Dahi in comparison to milk and control Dahi. Results of the present study indicate that probiotic Dahi suppressed ovalbumin-induced allergic consequences characterized by decreasing levels of total and ovalbumin-specific IgE and lymphocyte proliferation and skewed ovalbumin-induced Th2-specific immune response towards Th1-specific response.

  18. 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...

  19. Engineering vaccines and niches for immune modulation.

    PubMed

    Purwada, Alberto; Roy, Krishnendu; Singh, Ankur

    2014-04-01

    Controlled modulation of immune response, especially the balance between immunostimulatory and immunosuppressive responses, is critical for a variety of clinical applications, including immunotherapies against cancer and infectious diseases, treatment of autoimmune disorders, transplant surgeries, regenerative medicine, prosthetic implants, etc. Our ability to precisely modify both innate and adaptive immune responses could provide new therapeutic directions in a variety of diseases. In the context of vaccines and immunotherapies, the interplay between antigen-presenting cells (e.g. dendritic cells and macrophages), B cells, T helper and killer subtypes, and regulatory T- and B-cell responses is critical for generating effective immunity against cancer, infectious diseases and autoimmune diseases. In recent years, immunoengineering has emerged as a new field that uses quantitative engineering tools to understand molecular-, cellular- and system-level interactions of the immune system and to develop design-driven approaches to control and modulate immune responses. Biomaterials are an integral part of this engineering toolbox and can exploit the intrinsic biological and mechanical cues of the immune system to directly modulate and train immune cells and direct their response to a particular phenotype. A large body of literature exists on strategies to evade or suppress the immune response in implants, transplantation and regenerative medicine. This review specifically focuses on the use of biomaterials for immunostimulation and controlled modulation, especially in the context of vaccines and immunotherapies against cancer, infectious diseases and autoimmune disorders. Bioengineering smart systems that can simultaneously deliver multiple bioactive agents in a controlled manner or can work as a niche for in situ priming and modulation of the immune system could significantly enhance the efficacy of next-generation immunotherapeutics. In this review, we describe our

  20. 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.

  1. Innate immune modulation in EBV infection

    PubMed Central

    2011-01-01

    Epstein-Barr Virus (EBV) belongs to the gammaherpesvirus family, members of which are oncogenic. Compared with other closely related herpesviruses, EBV has developed much more elaborate and sophisticated strategies for subverting host immune system, which may account for its high prevalence in immune competent hosts. Thus, study of EBV-specific immune dysregulation is important for understanding EBV latency and oncogenesis, and will identify potential molecular targets for immunotherapeutic interventions. Here I summarize the recent findings of individual EBV products in regulating host immune responses, with emphasis on the innate immune modulation. PMID:21429244

  2. Cancer-targeted oncolytic adenoviruses for modulation of the immune system.

    PubMed

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

    2017-05-02

    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 signaling mediators. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  3. Modulation of the peripheral immune system after low-dose radon spa therapy: Detailed longitudinal immune monitoring of patients within the RAD-ON01 study.

    PubMed

    Rühle, Paul F; Wunderlich, Roland; Deloch, Lisa; Fournier, Claudia; Maier, Andreas; Klein, Gerhart; Fietkau, Rainer; Gaipl, Udo S; Frey, Benjamin

    2017-03-01

    The pain-relieving effects of low-dose radon therapies on patients suffering from chronic painful inflammatory diseases have been described for centuries. Even though it has been suggested that low doses of radiation may attenuate chronic inflammation, the underlying mechanisms remain elusive. Thus, the RAD-ON01 study was initiated to examine the effects of radon spa therapy and its low doses of alpha radiation on the human immune system. In addition to an evaluation of pain parameters, blood was drawn from 100 patients suffering from chronic painful degenerative musculoskeletal diseases before as well as 6, 12, 18, and 30 weeks after the start of therapy. We verified significant long-term pain reduction for the majority of patients which was accompanied by modulations of the peripheral immune cells. Detailed immune monitoring was performed using a multicolor flow cytometry-based whole blood assay. After therapy, the major immune cells were only marginally affected. Nevertheless, a small but long-lasting increase in T cells and monocytes was observed. Moreover, neutrophils, eosinophils and, in particular, dendritic cells were temporarily modulated after therapy. Regarding the immune cell subsets, cytotoxic T and NK cells, in particular, were altered. However, the most prominent effects were identified in a strong reduction of the activation marker CD69 on T, B, and NK cells. Simultaneously, the percentage of HLA-DR(+) T cells was elevated after therapy. The RAD-ON01 study showed for the first time a modulation of the peripheral immune cells following standard radon spa therapy. These modulations are in line with attenuation of inflammation.

  4. Dawn of antioxidants and immune modulators to stop HIV-progression and boost the immune system in HIV/AIDS patients: An updated comprehensive and critical review.

    PubMed

    Singh, Gurinder; Pai, Roopa S

    2015-06-01

    In the last two decades, human immunodeficiency virus (HIV), the retrovirus responsible for the acquired immunodeficiency syndrome (AIDS), is one of the leading causes of morbidity and mortality, worldwide. Providing the optimum management of HIV/AIDS is a major challenge in the 21st century. Since, HIV-infected persons have an extended lifespan due to the development of effective antiretroviral therapies, malnutrition is becoming central factors of long-term survivors. The nutrition status of AIDS patients has a significant influence on the maintenance and optimal effectiveness of the immune system. Micronutrient therapy in combination with allopathic treatments can extend and improve the quality and quantity of life in individuals infected with HIV/AIDS. HIV infection is thought to lead to augmented oxidative stress which may in turn lead to faster development of HIV disease. Hence, antioxidants might have a significant role in the treatment of HIV/AIDS. An additional approach to treating HIV infection is fortifying the immune response of infected people. Immune modulators help to activate and boost the normal immune function. The present review first describes the boon of antioxidants (especially Vitamin A) and immune modulators (cytolin, resveratrol, murabutide, setarud, tucaresol, AVR118, Immunitin (HE2000), reticulose, and interleukin-7) in the treatment of HIV/AIDS. Then, providing a comparatively succinct outline on updated patents study on antioxidants and immune modulators to treat HIV/AIDS will be discussed. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  5. 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.

  6. The adaptive immune system restrains Alzheimer's disease pathogenesis by modulating microglial function.

    PubMed

    Marsh, Samuel E; Abud, Edsel M; Lakatos, Anita; Karimzadeh, Alborz; Yeung, Stephen T; Davtyan, Hayk; Fote, Gianna M; Lau, Lydia; Weinger, Jason G; Lane, Thomas E; Inlay, Matthew A; Poon, Wayne W; Blurton-Jones, Mathew

    2016-03-01

    The innate immune system is strongly implicated in the pathogenesis of Alzheimer's disease (AD). In contrast, the role of adaptive immunity in AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal role in this disease. To test the hypothesis that adaptive immunity influences AD pathogenesis, we generated an immune-deficient AD mouse model that lacks T, B, and natural killer (NK) cells. The resulting "Rag-5xfAD" mice exhibit a greater than twofold increase in β-amyloid (Aβ) pathology. Gene expression analysis of the brain implicates altered innate and adaptive immune pathways, including changes in cytokine/chemokine signaling and decreased Ig-mediated processes. Neuroinflammation is also greatly exacerbated in Rag-5xfAD mice as indicated by a shift in microglial phenotype, increased cytokine production, and reduced phagocytic capacity. In contrast, immune-intact 5xfAD mice exhibit elevated levels of nonamyloid reactive IgGs in association with microglia, and treatment of Rag-5xfAD mice or microglial cells with preimmune IgG enhances Aβ clearance. Last, we performed bone marrow transplantation studies in Rag-5xfAD mice, revealing that replacement of these missing adaptive immune populations can dramatically reduce AD pathology. Taken together, these data strongly suggest that adaptive immune cell populations play an important role in restraining AD pathology. In contrast, depletion of B cells and their appropriate activation by T cells leads to a loss of adaptive-innate immunity cross talk and accelerated disease progression.

  7. The adaptive immune system restrains Alzheimer’s disease pathogenesis by modulating microglial function

    PubMed Central

    Abud, Edsel M.; Lakatos, Anita; Karimzadeh, Alborz; Yeung, Stephen T.; Davtyan, Hayk; Fote, Gianna M.; Lau, Lydia; Weinger, Jason G.; Lane, Thomas E.; Inlay, Matthew A.; Poon, Wayne W.; Blurton-Jones, Mathew

    2016-01-01

    The innate immune system is strongly implicated in the pathogenesis of Alzheimer’s disease (AD). In contrast, the role of adaptive immunity in AD remains largely unknown. However, numerous clinical trials are testing vaccination strategies for AD, suggesting that T and B cells play a pivotal role in this disease. To test the hypothesis that adaptive immunity influences AD pathogenesis, we generated an immune-deficient AD mouse model that lacks T, B, and natural killer (NK) cells. The resulting “Rag-5xfAD” mice exhibit a greater than twofold increase in β-amyloid (Aβ) pathology. Gene expression analysis of the brain implicates altered innate and adaptive immune pathways, including changes in cytokine/chemokine signaling and decreased Ig-mediated processes. Neuroinflammation is also greatly exacerbated in Rag-5xfAD mice as indicated by a shift in microglial phenotype, increased cytokine production, and reduced phagocytic capacity. In contrast, immune-intact 5xfAD mice exhibit elevated levels of nonamyloid reactive IgGs in association with microglia, and treatment of Rag-5xfAD mice or microglial cells with preimmune IgG enhances Aβ clearance. Last, we performed bone marrow transplantation studies in Rag-5xfAD mice, revealing that replacement of these missing adaptive immune populations can dramatically reduce AD pathology. Taken together, these data strongly suggest that adaptive immune cell populations play an important role in restraining AD pathology. In contrast, depletion of B cells and their appropriate activation by T cells leads to a loss of adaptive–innate immunity cross talk and accelerated disease progression. PMID:26884167

  8. A potent multivalent vaccine for modulation of immune system in atherosclerosis: an in silico approach

    PubMed Central

    2016-01-01

    Purpose Atherosclerosis is classically defined as an immune-mediated disease characterized by accumulation of low-density lipoprotein cholesterol over intima in medium sized and large arteries. Recent studies have demonstrated that both innate and adaptive immune responses are involved in atherosclerosis. In addition, experimental and human models have recognized many autoantigens in pathophysiology of this disease. Oxidized low-density lipoproteins, β2 glycoprotein I (β-2-GPI), and heat shock protein 60 (HSP60) are the best studied of them which can represent promising approach to design worthwhile vaccines for modulation of atherosclerosis. Materials and Methods In silico approaches are the best tools for design and evaluation of the vaccines before initiating the experimental study. In this study, we identified immunogenic epitopes of HSP60, ApoB-100, and β-2-GPI as major antigens to construct a chimeric protein through bioinformatics tools. Additionally, we have evaluated physico-chemical properties, structures, stability, MHC binding properties, humoral and cellular immune responses, and allergenicity of this chimeric protein by means of bioinformatics tools and servers. Results Validation results indicated that 89.1% residues locate in favorite or additional allowed region of Ramachandran plot. Also, based on Ramachandran plot analysis this protein could be classified as a stable fusion protein. In addition, the epitopes in the chimeric protein had strong potential to induce both the B-cell and T-cell mediated immune responses. Conclusion Our results supported that this chimeric vaccine could be effectively utilized as a multivalent vaccine for prevention and modulation of atherosclerosis. PMID:26866024

  9. Role of Immune Cells in the Course of Central Nervous System Injury: Modulation with Natural Products.

    PubMed

    Magrone, Thea; Russo, Matteo Antonio; Jirillo, Emilio

    2016-01-01

    Immune cells actively participate to the central nervous system (CNS) injury either damaging or protecting neural tissue with release of various mediators. Residential microglia and monocyte-derived macrophages play a fundamental role within the injured CNS and, here, special emphasis will be placed on M1 and M2 macrophages for their different functional activities. On the other hand, peripheral T regulatory (Treg) cells exert antiinflammatory activities in the diseased host. In this respect, activation of Treg cells by nutraceuticals may represent a novel approach to treat neuroinflammation. Omega-3 fatty acids and polyphenols will be described as substances endowed with antioxidant and anti-inflammatory activities. However, taking into account that Treg cells act in the later phase of CNS injury, favoring immune suppression, manipulation of host immune system with both substances requires caution to avoid undesired side effects.

  10. BP8, a novel peptide from avian immune system, modulates B cell developments.

    PubMed

    Liu, Xiao-Dong; Zhou, Bin; Feng, Xiu-Li; Cao, Rui-Bing; Chen, Pu-Yan

    2014-12-01

    The bursa of Fabricius (BF) is the key humoral immune organ unique to birds, and is critical for early B-lymphocyte proliferation and differentiation. However, the molecular basis and mechanisms through which the BF regulates B cell development are not fully understood. In this study, we isolated and identified a new bursal peptide (BP8, AGHTKKAP) by RP-HPLC and MALDI-TOF-MS. BP8 promoted colony-forming pre-B formation, bound B cell precursor, regulated B cell development in vitro as well as in vivo, upstream of the EBF-E2A-Pax5 regulatory complex and increased immunoglobulin secretion. These data revealed a bursal-derived multifunctional factor BP8 as a novel biomaterial which is essential for the development of the immune system. This study elucidates further the mechanisms involved in humoral immune system and has implications in treating human diseases.

  11. Platelet serotonin modulates immune functions.

    PubMed

    Mauler, M; Bode, C; Duerschmied, D

    2016-01-01

    This short review addresses immune functions of platelet serotonin. Platelets transport serotonin at a high concentration in dense granules and release it upon activation. Besides haemostatic, vasotonic and developmental modulation, serotonin also influences a variety of immune functions (mediated by different serotonin receptors). First, platelet serotonergic effects are directed against invading pathogens via activation and proliferation of lymphocytes, modulation of cytokine release, and recruitment of neutrophils to sites of acute inflammation by induction of selectin expression on endothelial cells. Second, serotonin levels are elevated in autoimmune diseases, such as asthma or rheumatoid arthritis, and during tissue regeneration after ischemia of myocardium or brain. Specific antagonism of serotonin receptors appears to improve survival after myocardial infarction or sepsis and to attenuate asthmatic attacks in animal models. It will be of great clinical relevance if these findings can be translated into human applications. In conclusion, targeting immune modulatory effects of platelet serotonin may provide novel therapeutic options for common health problems.

  12. Immune System (For Parents)

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Immune System KidsHealth > For Parents > Immune System A A A ... can lead to illness and infection. About the Immune System The immune system is the body's defense against ...

  13. Immune System Modulation with LOFU And HIFU Treatment of Prostate Cancer

    NASA Astrophysics Data System (ADS)

    Guha, C.; Huagang, Z.; Chen, W.; Carlosn, R.; Sanghvi, N. T.

    2011-09-01

    High intensity focused ultrasound (HIFU) results in instantaneous coagulative tissue necrosis. In contrast, "low" energy focused ultrasound (LOFU) induces membrane perturbation while maintaining cell viability. This report explores the tumor immunomodulatory roles of LOFU and HIFU combination treatment. We hypothesized that administration of repeated cycles of LOFU, followed by HIFU would release tumor-derived peptide-heat shock protein complexes in the blood and induce systemic tumor-specific immune response that would enhance tumor control of both local and systemic disease.

  14. Probiotics as an Immune Modulator.

    PubMed

    Kang, Hye-Ji; Im, Sin-Hyeog

    2015-01-01

    Probiotics are nonpathogenic live microorganism that can provide a diverse health benefits on the host when consumed in adequate amounts. Probiotics are consumed in diverse ways including dairy product, food supplements and functional foods with specific health claims. Recently, many reports suggest that certain probiotic strains or multi strain mixture have potent immunomodulatory activity in diverse disorders including allergic asthma, atopic dermatitis and rheumatoid arthritis. However, underlying mechanism of action is still unclear and efficacy of probiotic administration is quite different depending on the type of strains and the amounts of doses. We and others have suggested that live probiotics or their metabolites could interact with diverse immune cells (antigen presenting cells and T cells) and confer them to have immunoregulatory functions. Through this interaction, probiotics could contribute to maintaining immune homeostasis by balancing pro-inflammatory and anti-inflammatory immune responses. However, the effect of probiotics in prevention or modulation of ongoing disease is quite diverse even within a same species. Therefore, identification of functional probiotics with specific immune regulatory property is a certainly important issue. Herein, we briefly review selection methods for immunomodulatory probiotic strains and the mechanism of action of probiotics in immune modulation.

  15. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease.

    PubMed

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD.

  16. Oral immune therapy: targeting the systemic immune system via the gut immune system for the treatment of inflammatory bowel disease

    PubMed Central

    Ilan, Yaron

    2016-01-01

    Inflammatory bowel diseases (IBD) are associated with an altered systemic immune response leading to inflammation-mediated damage to the gut and other organs. Oral immune therapy is a method of systemic immune modulation via alteration of the gut immune system. It uses the inherit ability of the innate system of the gut to redirect the systemic innate and adaptive immune responses. Oral immune therapy is an attractive clinical approach to treat autoimmune and inflammatory disorders. It can induce immune modulation without immune suppression, has minimal toxicity and is easily administered. Targeting the systemic immune system via the gut immune system can serve as an attractive novel therapeutic method for IBD. This review summarizes the current data and discusses several examples of oral immune therapeutic methods for using the gut immune system to generate signals to reset systemic immunity as a treatment for IBD. PMID:26900473

  17. Rhodnius prolixus: from physiology by Wigglesworth to recent studies of immune system modulation by Trypanosoma cruzi and Trypanosoma rangeli.

    PubMed

    Azambuja, P; Garcia, E S; Waniek, P J; Vieira, C S; Figueiredo, M B; Gonzalez, M S; Mello, C B; Castro, D P; Ratcliffe, N A

    This review is dedicated to the memory of Professor Sir Vincent B. Wigglesworth (VW) in recognition of his many pioneering contributions to insect physiology which, even today, form the basis of modern-day research in this field. Insects not only make vital contributions to our everyday lives by their roles in pollination, balancing eco-systems and provision of honey and silk products, but they are also outstanding models for studying the pathogenicity of microorganisms and the functioning of innate immunity in humans. In this overview, the immune system of the triatomine bug, Rhodnius prolixus, is considered which is most appropriate to this dedication as this insect species was the favourite subject of VW's research. Herein are described recent developments in knowledge of the functioning of the R. prolixus immune system. Thus, the roles of the cellular defences, such as phagocytosis and nodule formation, as well as the role of eicosanoids, ecdysone, antimicrobial peptides, reactive oxygen and nitrogen radicals, and the gut microbiota in the immune response of R. prolixus are described. The details of many of these were unknown to VW although his work gives indications of his awareness of the importance to R. prolixus of cellular immunity, antibacterial activity, prophenoloxidase and the gut microbiota. This description of R. prolixus immunity forms a backdrop to studies on the interaction of the parasitic flagellates, Trypanosoma cruzi and Trypanosoma rangeli, with the host defences of this important insect vector. These parasites remarkably utilize different strategies to avoid/modulate the triatomine immune response in order to survive in the extremely hostile host environments present in the vector gut and haemocoel. Much recent information has also been gleaned on the remarkable diversity of the immune system in the R. prolixus gut and its interaction with trypanosome parasites. This new data is reviewed and gaps in our knowledge of R. prolixus immunity are

  18. Salmonella–Host Interactions – Modulation of the Host Innate Immune System

    PubMed Central

    Hurley, Daniel; McCusker, Matthew P.; Fanning, Séamus; Martins, Marta

    2014-01-01

    Salmonella enterica (S. enterica) are Gram-negative bacteria that can invade a broad range of hosts causing both acute and chronic infections. This phenotype is related to its ability to replicate and persist within non-phagocytic host epithelial cells as well as phagocytic dendritic cells and macrophages of the innate immune system. Infection with S. enterica manifests itself through a broad range of clinical symptoms and can result in asymptomatic carriage, gastroenteritis, systemic disease such as typhoid fever and in severe cases, death (1). Exposure to S. enterica serovars Typhi and Paratyphi exhibits clinical symptoms including diarrhea, fatigue, fever, and temperature fluctuations. Other serovars such as the non-typhoidal Salmonella (NTS), of which there are over 2,500, are commonly contracted as, but not limited to, food-borne sources causing gastrointestinal symptoms, which include diarrhea and vomiting. The availability of complete genome sequences for many S. enterica serovars has facilitated research into the genetic determinants of virulence for this pathogen. This work has led to the identification of important bacterial components, including flagella, type III secretion systems, lipopolysaccharides, and Salmonella pathogenicity islands, all of which support the intracellular life cycle of S. enterica. Studies focusing on the host–pathogen interaction have provided insights into receptor activation of the innate immune system. Therefore, characterizing the host–S. enterica interaction is critical to understand the pathogenicity of the bacteria in a clinically relevant context. This review outlines salmonellosis and the clinical manifestations between typhoidal and NTS infections as well as discussing the host immune response to infection and the models that are being used to elucidate the mechanisms involved in Salmonella pathogenicity. PMID:25339955

  19. Immune System 101

    MedlinePlus

    ... Immune System 101 Subscribe Translate Text Size Print Immune System 101 How Does Your Immune System Work? Your immune system works because your body ... tactics to destroy it. Major Players of the Immune System Lymph nodes (also called "lymph glands"): These small, ...

  20. Modulation of the immune system by Boswellia serrata extracts and boswellic acids.

    PubMed

    Ammon, H P T

    2010-09-01

    Extracts from the gum resin of Boswellia serrata and some of is constituents including boswellic acids affect the immune system in different ways. Among the various boswellic acids 11-keto-beta-boswellic acid (KBA) and acetyl-11-keto-beta-boswellic acid have been observed to be active. However, also other boswellic acids may exhibit actions in the immune system. In the humoral defence system a mixture of boswellic acis at higher doses reduced primary antibody titres; on the other hand lower doses enhanced secondary antibody titres following treatment with sheep erythrocytes. In the cellular defence boswellic acides appear to increase lymphocyte proliferation whereas higher concentrations are even inhibitory. Moreover, BAs increase phagocytosis of macrophages. BAs affect the cellular defence system by interaction with production/release of cytokines. Thus, BAs inhibit activation of NFkappaB which is a product of neutrophile granulocytes. Consequently a down regulation of TNF-alpha and decrease of IL-1, IL-2, IL-4, IL-6 and IFN-gamma, which are proinflammatory cytokines by BEs and BAs has been reported. Suppressions of the classic way of the complement system was found to be due to inhibition of the conversion of C3 into C3a and C3b. However, which of these pharmacological actions contribute to the therapeutic effects and which is finally the best dosage of a standardized extract needs further examination. And it is also a question whether or not a single BA will have the same therapeutic effect as a standardized extract. Among the mediators of inflammatory reaction, mast cell stabilisation has been described by a BE. Inhibition of prostaglandin synthesis appears to play only a minor role as far as the anti-inflammatory effect is concerned. On the other hand the inhibitory action of BAs on 5-LO leading to a decreased production of leukotrienes has received high attention by the scientific community since a variety of chronic inflammatory diseases is associatied with

  1. Zoonotic intestinal helminths interact with the canine immune system by modulating T cell responses and preventing dendritic cell maturation.

    PubMed

    Junginger, Johannes; Raue, Katharina; Wolf, Karola; Janecek, Elisabeth; Stein, Veronika M; Tipold, Andrea; Günzel-Apel, Anne-Rose; Strube, Christina; Hewicker-Trautwein, Marion

    2017-09-04

    Parasite co-evolution alongside the mammalian immune system gave rise to several modulatory strategies by which they prevent exaggerated pathology and facilitate a longer worm survival. As little is known about the immunoregulatory potential of the zoonotic canine parasites Ancylostoma caninum and Toxocara canis in the natural host, the present study aimed to investigate whether their larval excretory-secretory (ES) products can modulate the canine immune system. We demonstrated TcES to increase the frequency of CD4+ Foxp3(high) T cells, while both AcES and TcES were associated with elevated Helios expression in Foxp3(high) lymphocytes. ES products were further capable of inducing IL-10 production by lymphocytes, which was mainly attributed to CD8+ T cells. ES treatment of PBMCs prior to mitogen stimulation inhibited polyclonal proliferation of CD4+ and CD8+ T cells. Moreover, monocyte-derived ES-pulsed dendritic cells reduced upregulation of MHC-II and CD80 in response to lipopolysaccharide. The data showed that regulation of the canine immune system by A. caninum and T. canis larvae comprises the modification of antigen-specific and polyclonal T cell responses and dendritic cell maturation.

  2. Modulation of immune homeostasis by commensal bacteria.

    PubMed

    Ivanov, Ivaylo I; Littman, Dan R

    2011-02-01

    Intestinal bacteria form a resident community that has co-evolved with the mammalian host. In addition to playing important roles in digestion and harvesting energy, commensal bacteria are crucial for the proper functioning of mucosal immune defenses. Most of these functions have been attributed to the presence of large numbers of 'innocuous' resident bacteria that dilute or occupy niches for intestinal pathogens or induce innate immune responses that sequester bacteria in the lumen, thus quenching excessive activation of the mucosal immune system. However it has recently become obvious that commensal bacteria are not simply beneficial bystanders, but are important modulators of intestinal immune homeostasis and that the composition of the microbiota is a major factor in pre-determining the type and robustness of mucosal immune responses. Here we review specific examples of individual members of the microbiota that modify innate and adaptive immune responses, and we focus on potential mechanisms by which such species-specific signals are generated and transmitted to the host immune system.

  3. Immune System Quiz

    MedlinePlus

    ... Room? What Happens in the Operating Room? Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System A A A How much do you know about your immune system? Find out by taking this quiz! About KidsHealth ...

  4. Modulations in the Peripheral Immune System of Glioblastoma Patient Is Connected to Therapy and Tumor Progression-A Case Report from the IMMO-GLIO-01 Trial.

    PubMed

    Rühle, Paul F; Goerig, Nicole; Wunderlich, Roland; Fietkau, Rainer; Gaipl, Udo S; Strnad, Annedore; Frey, Benjamin

    2017-01-01

    Immune responses are important for efficient tumor elimination, also in immune privileged organs such as the brain. Fostering antitumor immunity has therefore become an important challenge in cancer therapy. This cannot only be achieved by immunotherapies as already standard treatments such as radiotherapy and chemotherapy modify the immune system. Consequently, the understanding of how the tumor, the tumor microenvironment, and immune system are modulated by cancer therapy is required for prognosis, prediction, and therapy adaption. The prospective, explorative, and observational IMMO-GLIO-01 trial was initiated to examine the detailed immune status and its modulation of about 50 patients suffering from primary glioblastoma multiforme (GBM) or anaplastic astrocytoma during standard therapy. Prior to the study, a flow cytometry-based assay was established allowing the analysis of 34 immune cell subsets and their activation state. Here, we present the case of the first and longest accompanied patient, a 53-year-old woman suffering from GBM in the front left lobe. In context of tumor progression and therapy, we describe the modulation of the peripheral immune status over 17 months. Distinct immune modulations that were connected to therapy response or tumor progression were identified. Inter alia, a shift of CD4:CD8 ratio was observed that correlated with tumor progression. Twice we observed a unique composition of peripheral immune cells that correlated with tumor progression. Thus, following up these immune modulations in a closely-meshed manner is of high prognostic and predictive relevance for supporting personalized therapy and increasing therapy success. Clinical Trial registration: ClinicalTrials.gov, identifier NCT02022384 (registered retrospectively on 13th of December, 2013).

  5. Helminths and mucosal immune modulation.

    PubMed

    Weinstock, Joel V

    2006-08-01

    Geographic and ethnic variations in ulcerative colitis and Crohn's disease frequency suggest that environmental factors affect disease risk. Prevention of parasitic worms (helminths) through improved hygiene may be one factor leading to the increased disease prevalence. Helminths alter host mucosal and systemic immunity. Animals exposed to helminths are protected from experimental colitis and other immunological diseases, and helminthic colonization can be used to treat ongoing murine and human disease. Helminths induce mucosal T cells to make Th2 and regulatory cytokines. Helminth-induced mucosal IL4, TGFbeta, and IL10 likely are part of the protective process. Helminths affect pathways of innate immunity like TLR4 expression and function. Worms also induce various regulatory-type T-cell subsets in the gut that limit effector T-cell growth and function. These effects of once ever-present helminths may have protected people from immune-mediated illnesses like inflammatory bowel disease.

  6. Organic trace mineral supplementation enhances local and systemic innate immune responses and modulates oxidative stress in broiler chickens.

    PubMed

    Echeverry, H; Yitbarek, A; Munyaka, P; Alizadeh, M; Cleaver, A; Camelo-Jaimes, G; Wang, P; O, K; Rodriguez-Lecompte, J C

    2016-03-01

    The effect of organic trace mineral supplementation on performance, intestinal morphology, immune organ weights (bursa of Fabricius and spleen), expression of innate immune response related genes, blood heterophils/lymphocytes ratio, chemical metabolic panel, natural antibodies (IgG), and oxidative stress of broiler chickens was studied. A total of 1,080 day-old male broilers were assigned to 1 of 3 dietary treatments, which included basal diet with Monensin (control), control diet supplemented with bacitracin methylene disalicylate (BMD), and BMD diet supplemented with organic trace minerals (OTM). No difference in feed conversion ratio was observed among treatments; ileum histomorphological analysis showed a lower crypt depth, higher villi height/crypt depth ratio, and lower villi width in the OTM treatment compared to control. Furthermore, OTM treatment resulted in higher uric acid and lower plasma malondehaldehyde (MDA), indicating lower oxidative stress. Gene expression analysis showed that OTM treatment resulted in up-regulations of TLR2 bin the ileum, and TLR2b, TLR4, and IL-12p35 in the bursa of Fabricius, and down-regulation of TLR2b and TLR4 in the cecal tonsils. In the spleen, OTM treatment resulted in up-regulation of IL-10. In conclusion, OTM supplementation to broiler diets may have beneficial effects on intestinal development, immune system status, and survival by improving ileum histomorphological parameters, modulation of Toll-like receptors and anti-inflammatory cytokines, and decreasing level of MDA, which in conjunction could enhance health status.

  7. Dopamine Mediates the Vagal Modulation of the Immune System by Electroacupuncture

    PubMed Central

    Torres-Rosas, Rafael; Yehia, Ghassan; Peña, Geber; Mishra, Priya; del Rocio Thompson-Bonilla, Maria; Moreno-Eutimio, Mario Adán; Arriaga-Pizano, Lourdes Andrea; Isibasi, Armando; Ulloa, Luis

    2014-01-01

    Previous anti-inflammatory strategies against sepsis, a leading cause of death in hospitals, had limited efficacy in clinical trials, in part because they targeted single cytokines and the experimental models failed to mimic clinical settings1-3. Neuronal networks represent physiological mechanisms selected by evolution to control inflammation that can be exploited for the treatment of inflammatory and infectious disorders3. Here, we report that sciatic nerve activation with electroacupuncture controls systemic inflammation and rescues mice from polymicrobial peritonitis. Electroacupuncture at the sciatic nerve controls systemic inflammation by inducing a vagal activation of DOPA decarboxylase leading to the production of dopamine in the adrenal medulla. Experimental models with adrenolectomized animals mimic clinical adrenal insufficiency4, increase the susceptibility to sepsis, and prevent the anti-inflammatory potential of electroacupuncture. Dopamine inhibits cytokine production via dopaminergic type-1 receptors. Dopaminergic D1-agonists suppress systemic inflammation and rescue mice from polymicrobial peritonitis in animals with adrenal insufficiency. Our results suggest a novel anti-inflammatory mechanism mediated by the sciatic and the vagus nerves modulating the production of catecholamines in the adrenal glands. From a pharmacological perspective, selective dopaminergic agonists mimic the anti-inflammatory potential of electroacupuncture and can provide therapeutic advantages to control inflammation in infectious and inflammatory disorders. PMID:24562381

  8. ANALYSIS OF DENDRITIC CELL STIMULATION UTILIZING A MULTI-FACETED NANOPOLYMER DELIVERY SYSTEM AND THE IMMUNE MODULATOR 1-METHYL TRYPTOPHAN.

    PubMed

    Nikitczuk, Kevin P; Lattime, Edmund C; Schloss, Rene S; Yarmush, Martin L

    2010-09-01

    Dendritic cells (DCs) play a pivotal role in immune modulation. Therefore, understanding and regulating the mechanism of DC activation is paramount for functional optimization of any immunotherapy strategy. In particular, the paradoxical ability of DCs to secrete the immune suppressive enzyme indoleamine 2, 3-dioxygenase (IDO) and the suppressive cytokine IL-10 during the course of, and in response to, stimulation is of great interest. 1-Methyl-Tryptophan (1 MT) is a known inhibitor of IDO and has thus been administered in numerous in vitro and in vivo systems to block IDO activity. However, the effect 1 MT has on DCs beyond inhibiting IDO, especially in therapeutic models, has rarely been analyzed. In the current study, we have administered 1 MT via a nanopolymer-based delivery system in conjunction with an antigen (ovalbumin, OVA) and an adjuvant (CpG motif DNA) to determine both the effects of 1 MT on DCs and the resulting efficacy of the polymer-based treatments. 1 MT delivery alone, either via the polymer-based delivery vehicle or dissolved in solution, induced no significant change in DC activation as measured by surface expression of CD80, CD86, and MHCII and several secreted products such as IL-12. These same factors were upregulated however, when 1 MT was delivered in conjunction with OVA and CpG. Although soluble delivery of these components increased the levels of expression and secretion of key proteins, a differential effect of DC stimulation was seen as a result of the polymer delivery system. The T cell suppressive IL-10 secretion was lower with the polymer-based treatments and IL-12 immune-enhancing secretion was increased when 1 MT was supplemented into the polymer system. As a result, including 1 MT in the polymers along with OVA and CpG was seen to have additional effects on DC stimulation and was able to shift DCs to a state more indicative of inducing a Th1-type response.

  9. Transcriptional modulation of the developing immune system by early life social adversity

    PubMed Central

    Cole, Steven W.; Conti, Gabriella; Arevalo, Jesusa M. G.; Ruggiero, Angela M.; Heckman, James J.; Suomi, Stephen J.

    2012-01-01

    To identify molecular mechanisms by which early life social conditions might influence adult risk of disease in rhesus macaques (Macaca mulatta), we analyze changes in basal leukocyte gene expression profiles in 4-mo-old animals reared under adverse social conditions. Compared with the basal condition of maternal rearing (MR), leukocytes from peer-reared (PR) animals and PR animals provided with an inanimate surrogate mother (surrogate/peer reared, SPR) show enhanced expression of genes involved in inflammation, cytokine signaling, and T-lymphocyte activation, and suppression of genes involved in several innate antimicrobial defenses including type I interferon (IFN) antiviral responses. Promoter-based bioinformatic analyses implicate increased activity of CREB and NF-κB transcription factors and decreased activity of IFN response factors (IRFs) in structuring the observed differences in gene expression. Transcript origin analyses identify monocytes and CD4+ T lymphocytes as primary cellular mediators of transcriptional up-regulation and B lymphocytes as major sources of down-regulated genes. These findings show that adverse social conditions can become embedded within the basal transcriptome of primate immune cells within the first 4 mo of life, and they implicate sympathetic nervous system-linked transcription control pathways as candidate mediators of those effects and potential targets for health-protective intervention. PMID:23184974

  10. Radiofrequency radiation alters the immune system. II. Modulation of in vivo lymphocyte circulation

    SciTech Connect

    Liburdy, R.P.

    1980-07-01

    In vivo lymphocyte circulation was significantly altered in mice exposed to whole-body radiofrequency radiation (RFR). In vivo lymphocyte circulation was followed by quantitating activity of sodium chromate-51-labeled lymphocytes in the lung, spleen, liver, and bone marrow of animals at different times after iv spleen lymphocyte injection. Immediately after cell injection, animals were exposed to 2.6-GHz RFR (CW) at 25 or 5 mW/cm/sup 2/ (3.8 W/kg) for 1 h. At 1,6, and 24 h aftr lymphocyte injection target organs were removed, weighed, and counted. Sham RFR, warm-air, and steroid-treated groups were included as controls. Hyperthermic RFR exposure (25 mW/cm/sup 2/, 2.0/sup 0/C increase in core temperature) led to a 37% reduction in lymphocytes leaving the lung to migrate into the spleen. In addition, a threefold increse in spleen lymphocytes entering the bone marrow occurred. Significantly, this pattern was also observed in the steroid-treated group; nonthermogenic RFR exposure (5 mWcm/sup 2/) and warm-air exposures did not lead to altered lymphocyte traffic. These results support the idea that steroid release associated with thermal stress and the process of thermoregulation is a significant operatnt factor responsible for RFR effects on the immune system.

  11. Melatonin Modulates the Immune System Response and Inflammation in Diabetic Rats Experimentally-Induced by Alloxan.

    PubMed

    Ozkanlar, S; Kara, A; Sengul, E; Simsek, N; Karadeniz, A; Kurt, N

    2016-02-01

    Diabetes mellitus (DM) is a metabolic disease, which causes an increase in the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β), and also proliferation of monocyte chemotactic protein. In the present study, the potential effects of melatonin on proinflammatory cytokines, hematological values, and lymphoid tissues were investigated in diabetic rats. In the study, 36 male rats were randomly divided into 4 groups as follows: Control, Mel (melatonin), DM, and DM-Mel. For 15 days, an isotonic saline solution was given to the Control and DM groups; melatonin was administered to the Mel and DM-Mel groups intraperitoneally. At the end of the study, all animals were sacrificed by drawing the blood from their hearts under deep anesthesia. Samples of the spleen, thymus, and lymph nodes were fixed in 10% formaldehyde for histologic analysis. Increases in proinflammatory serum cytokine concentrations, mast cells, and total white blood cell counts as well as tissue destruction in the lymphoid organs were determined in the DM group via biochemical, hematological, and histologic analyses. However, the findings for the DM-Mel group revealed decreases in serum IL-1β concentration and mast cell densities, and destructions in lymphoid tissues by the melatonin administration. The present study suggests that melatonin treatment may control immune system regulation and inhibit the production of proinflammatory cytokines and tissue mast cell accumulation by preventing the destruction of lymphoid organs in the diabetic process.

  12. Advances in immune-modulating therapies to treat atherosclerotic cardiovascular diseases.

    PubMed

    Chyu, Kuang-Yuh; Shah, Prediman K

    2014-03-01

    In addition to hypercholesterolemia, innate and adaptive immune mechanisms play a critical role in atherogenesis, thus making immune-modulation therapy a potentially attractive way of managing atherosclerotic cardiovascular disease. These immune-modulation strategies include both active and passive immunization and confer beneficial reduction in atherosclerosis. Preclinical studies have demonstrated promising results and we review current knowledge on the complex role of the immune system and the potential for immunization as an immune-modulation therapy for atherosclerosis.

  13. Laser modulation of human immune system: inhibition of lymphocyte proliferation by a gallium-arsenide laser at low energy

    SciTech Connect

    Ohta, A.; Abergel, R.P.; Uitto, J.

    1987-01-01

    Cultured human lymphocytes were subjected to irradiation with a gallium-arsenide laser at energy fluence varying from 2.17 to 651 mJ/cm2, and the cell proliferation was assessed by (/sup 3/H)thymidine incorporation. Both mitogenic proliferation in response to phytohemagglutinin and spontaneous cell proliferation were markedly inhibited by the laser irradiation at energy fluence as low as 10.85 mJ/cm2. Similarly, the functional response of cells to antigen stimulation in a one-way mixed-lymphocyte reaction was also diminished as a result of laser irradiation. The results indicate that laser irradiation at low energy can interfere with immune system in vitro, and similar modulation could potentially occur in human subjects exposed to laser irradiation in vivo.

  14. Pericytes: brain-immune interface modulators

    PubMed Central

    Hurtado-Alvarado, Gabriela; Cabañas-Morales, Adrian M.; Gómez-Gónzalez, Beatriz

    2014-01-01

    The premise that the central nervous system is immune-privileged arose from the fact that direct contact between immune and nervous cells is hindered by the blood–brain barrier. However, the blood–brain barrier also comprises the interface between the immune and nervous systems by secreting chemo-attractant molecules and by modulating immune cell entry into the brain. The majority of published studies on the blood–brain barrier focus on endothelial cells (ECs), which are a critical component, but not the only one; other cellular components include astroglia, microglia, and pericytes. Pericytes are poorly studied in comparison with astrocytes or ECs; they are mesenchymal cells that can modify their ultrastructure and gene expression in response to changes in the central nervous system microenvironment. Pericytes have a unique synergistic relationship with brain ECs in the regulation of capillary permeability through secretion of cytokines, chemokines, nitric oxide, matrix metalloproteinases, and by means of capillary contraction. Those pericyte manifestations are related to changes in blood–brain barrier permeability by an increase in endocytosis-mediated transport and by tight junction disruption. In addition, recent reports demonstrate that pericytes control the migration of leukocytes in response to inflammatory mediators by up-regulating the expression of adhesion molecules and releasing chemo-attractants; however, under physiological conditions they appear to be immune-suppressors. Better understanding of the immune properties of pericytes and their participation in the effects of brain infections, neurodegenerative diseases, and sleep loss will be achieved by analyzing pericyte ultrastructure, capillary coverage, and protein expression. That knowledge may provide a mechanism by which pericytes participate in the maintenance of the proper function of the brain-immune interface. PMID:24454281

  15. Our Immune System

    MedlinePlus

    Our Immune System A story for children with primary immunodeficiency diseases Written by Sara LeBien IMMUNE DEFICIENCY FOUNDATION A note ... who are immune deficient to better understand their immune system. What is a “ B-cell, ” a “ T-cell, ” ...

  16. Modulation of the innate immune system in white shrimp Litopenaeus vannamei following long-term low salinity exposure.

    PubMed

    Lin, Yong-Chin; Chen, Jiann-Chu; Li, Chang-Che; Morni, Wan Zabidii W; Suhaili, Awangku Shahrir N A; Kuo, Yi-Hsuan; Chang, Yu-Hsuan; Chen, Li-Li; Tsui, Wen-Ching; Chen, Yu-Yuan; Huang, Chien-Lun

    2012-08-01

    Immune parameters, haemocyte lifespan, and gene expressions of lipopolysaccharide and β-glucan-binding protein (LGBP), peroxinectin (PX), integrin β, and α2-macroglobulin (α2-M) were examined in white shrimp Litopenaeus vannamei juveniles (0.48 ± 0.05 g) which had been reared at different salinity levels of 2.5‰, 5‰, 15‰, 25‰, and 35‰ for 24 weeks. All shrimp survived during the first 6 weeks. The survival rate of shrimp reared at 2.5‰ and 5‰ was much lower (30%) than that of shrimp reared at 15‰, 25‰, and 35‰ (76%~86%) after 24 weeks. Shrimp reared at 25% grew faster. Shrimp reared at 2.5‰ and 5‰ showed lower hyaline cells (HCs), granular cells (GCs), phenoloxidase activity (PO) activity, respiratory bursts (RBs), superoxide dismutase (SOD) activity, and lysozyme activity, but showed a longer haemocyte lifespan, and higher expressions of LGBP, PX, integrin β, and α2-M. In another experiment, shrimp which had been reared at different salinity levels for 24 weeks were challenged with Vibrio alginolyticus (6 × 10(6) cfu shrimp(-1)), and WSSV (10(3) copies shrimp(-1)) and then released to their respective seawater. At 96-144 h, cumulative mortalities of shrimp reared at 2.5‰ and 5‰ were significantly higher than those of shrimp reared at 15‰, 25‰, and 35‰. It was concluded that following long-term exposure to 2.5‰ and 5‰ seawater, white shrimp juveniles exhibited decreased resistance against a pathogen due to reductions in immune parameters. Increases in the haemocyte lifespan and gene expressions of LGBP, integrin β, PX, and α2-M indicated that shrimp had the ability to expend extra energy to modulate the innate immune system to prevent further perturbations at low salinity levels.

  17. Intestinal Microbiota as Modulators of the Immune System and Neuroimmune System: Impact on the Host Health and Homeostasis

    PubMed Central

    Maranduba, Carlos Magno da Costa; De Castro, Sandra Bertelli Ribeiro; de Souza, Gustavo Torres; da Guia, Francisco Carlos; Valente, Maria Anete Santana; Rettore, João Vitor Paes; Maranduba, Claudinéia Pereira; de Souza, Camila Maurmann; do Carmo, Antônio Márcio Resende; Macedo, Gilson Costa; Silva, Fernando de Sá

    2015-01-01

    Many immune-based intestinal disorders, such as ulcerative colitis and Crohn's disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work—gut microbiota, immune system, and their influence in the neuroimmune system. PMID:25759850

  18. Intestinal microbiota as modulators of the immune system and neuroimmune system: impact on the host health and homeostasis.

    PubMed

    Maranduba, Carlos Magno da Costa; De Castro, Sandra Bertelli Ribeiro; de Souza, Gustavo Torres; Rossato, Cristiano; da Guia, Francisco Carlos; Valente, Maria Anete Santana; Rettore, João Vitor Paes; Maranduba, Claudinéia Pereira; de Souza, Camila Maurmann; do Carmo, Antônio Márcio Resende; Macedo, Gilson Costa; Silva, Fernando de Sá

    2015-01-01

    Many immune-based intestinal disorders, such as ulcerative colitis and Crohn's disease, as well as other illnesses, may have the intestines as an initial cause or aggravator in the development of diseases, even apparently not correlating directly to the intestine. Diabetes, obesity, multiple sclerosis, depression, and anxiety are examples of other illnesses discussed in the literature. In parallel, importance of the gut microbiota in intestinal homeostasis and immunologic conflict between tolerance towards commensal microorganisms and combat of pathogens is well known. Recent researches show that the immune system, when altered by the gut microbiota, influences the state in which these diseases are presented in the patient directly and indirectly. At the present moment, a considerable number of investigations about this subject have been performed and published. However, due to difficulties on correlating information, several speculations and hypotheses are generated. Thus, the present review aims at bringing together how these interactions work-gut microbiota, immune system, and their influence in the neuroimmune system.

  19. 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 ... t, to find and destroy them. If your immune system cannot do its job, the results can be ...

  20. ANALYSIS OF DENDRITIC CELL STIMULATION UTILIZING A MULTI-FACETED NANOPOLYMER DELIVERY SYSTEM AND THE IMMUNE MODULATOR 1-METHYL TRYPTOPHAN

    PubMed Central

    NIKITCZUK, KEVIN P.; LATTIME, EDMUND C.; SCHLOSS, RENE S.; YARMUSH, MARTIN L.

    2014-01-01

    Dendritic cells (DCs) play a pivotal role in immune modulation. Therefore, understanding and regulating the mechanism of DC activation is paramount for functional optimization of any immunotherapy strategy. In particular, the paradoxical ability of DCs to secrete the immune suppressive enzyme indoleamine 2, 3-dioxygenase (IDO) and the suppressive cytokine IL-10 during the course of, and in response to, stimulation is of great interest. 1-Methyl-Tryptophan (1 MT) is a known inhibitor of IDO and has thus been administered in numerous in vitro and in vivo systems to block IDO activity. However, the effect 1 MT has on DCs beyond inhibiting IDO, especially in therapeutic models, has rarely been analyzed. In the current study, we have administered 1 MT via a nanopolymer-based delivery system in conjunction with an antigen (ovalbumin, OVA) and an adjuvant (CpG motif DNA) to determine both the effects of 1 MT on DCs and the resulting efficacy of the polymer-based treatments. 1 MT delivery alone, either via the polymer-based delivery vehicle or dissolved in solution, induced no significant change in DC activation as measured by surface expression of CD80, CD86, and MHCII and several secreted products such as IL-12. These same factors were upregulated however, when 1 MT was delivered in conjunction with OVA and CpG. Although soluble delivery of these components increased the levels of expression and secretion of key proteins, a differential effect of DC stimulation was seen as a result of the polymer delivery system. The T cell suppressive IL-10 secretion was lower with the polymer-based treatments and IL-12 immune-enhancing secretion was increased when 1 MT was supplemented into the polymer system. As a result, including 1 MT in the polymers along with OVA and CpG was seen to have additional effects on DC stimulation and was able to shift DCs to a state more indicative of inducing a Th1-type response. PMID:24772192

  1. Immune System Quiz

    MedlinePlus

    ... A Real Lifesaver Kids Talk About: Coaches Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A How much do you know about your immune system? Find out by taking this quiz! About KidsHealth ...

  2. [Modulation of immune response by bacterial lipopolysaccharides].

    PubMed

    Aldapa-Vega, Gustavo; Pastelín-Palacios, Rodolfo; Isibasi, Armando; Moreno-Eutimio, Mario A; López-Macías, Constantino

    2016-01-01

    Lipopolysaccharide (LPS) is a molecule that is profusely found on the outer membrane of Gram-negative bacteria and is also a potent stimulator of the immune response. As the main molecule on the bacterial surface, is also the most biologically active. The immune response of the host is activated by the recognition of LPS through Toll-like receptor 4 (TLR4) and this receptor-ligand interaction is closely linked to LPS structure. Microorganisms have evolved systems to control the expression and structure of LPS, producing structural variants that are used for modulating the host immune responses during infection. Examples of this include Helicobacter pylori, Francisella tularensis, Chlamydia trachomatis and Salmonella spp. High concentrations of LPS can cause fever, increased heart rate and lead to septic shock and death. However, at relatively low concentrations some LPS are highly active immunomodulators, which can induce non-specific resistance to invading microorganisms. The elucidation of the molecular and cellular mechanisms involved in the recognition of LPS and its structural variants has been fundamental to understand inflammation and is currently a pivotal field of research to understand the innate immune response, inflammation, the complex host-pathogen relationship and has important implications for the rational development of new immunomodulators and adjuvants.

  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.

  4. Proton irradiation impacts age-driven modulations of cancer progression influenced by immune system transcriptome modifications from splenic tissue.

    PubMed

    Wage, Justin; Ma, Lili; Peluso, Michael; Lamont, Clare; Evens, Andrew M; Hahnfeldt, Philip; Hlatky, Lynn; Beheshti, Afshin

    2015-09-01

    Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to 'hallmark' processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age.

  5. Proton irradiation impacts age-driven modulations of cancer progression influenced by immune system transcriptome modifications from splenic tissue

    PubMed Central

    Wage, Justin; Ma, Lili; Peluso, Michael; Lamont, Clare; Evens, Andrew M.; Hahnfeldt, Philip; Hlatky, Lynn; Beheshti, Afshin

    2015-01-01

    Age plays a crucial role in the interplay between tumor and host, with additional impact due to irradiation. Proton irradiation of tumors induces biological modulations including inhibition of angiogenic and immune factors critical to ‘hallmark’ processes impacting tumor development. Proton irradiation has also provided promising results for proton therapy in cancer due to targeting advantages. Additionally, protons may contribute to the carcinogenesis risk from space travel (due to the high proportion of high-energy protons in space radiation). Through a systems biology approach, we investigated how host tissue (i.e. splenic tissue) of tumor-bearing mice was altered with age, with or without whole-body proton exposure. Transcriptome analysis was performed on splenic tissue from adolescent (68-day) versus old (736-day) C57BL/6 male mice injected with Lewis lung carcinoma cells with or without three fractionations of 0.5 Gy (1-GeV) proton irradiation. Global transcriptome analysis indicated that proton irradiation of adolescent hosts caused significant signaling changes within splenic tissues that support carcinogenesis within the mice, as compared with older subjects. Increases in cell cycling and immunosuppression in irradiated adolescent hosts with CDK2, MCM7, CD74 and RUVBL2 indicated these were the key genes involved in the regulatory changes in the host environment response (i.e. the spleen). Collectively, these results suggest that a significant biological component of proton irradiation is modulated by host age through promotion of carcinogenesis in adolescence and resistance to immunosuppression, carcinogenesis and genetic perturbation associated with advancing age. PMID:26253138

  6. miRNA-124 in Immune System and Immune Disorders

    PubMed Central

    Qin, Zhen; Wang, Peng-Yuan; Su, Ding-Feng; Liu, Xia

    2016-01-01

    In recent years, miR-124 has emerged as a critical modulator of immunity and inflammation. Here, we summarize studies on the function and mechanism of miR-124 in the immune system and immunity-related diseases. They indicated that miR-124 exerts a crucial role in the development of immune system, regulation of immune responses, and inflammatory disorders. It is evident that miR-124 may serve as an informative diagnostic biomarker and therapeutic target in the future. PMID:27757114

  7. Peyer's patch-mediated intestinal immune system modulating activity of pectic-type polysaccharide from peel of Citrus unshiu.

    PubMed

    Suh, Hyung-Joo; Yang, Hyun-Seuk; Ra, Kyung-Soo; Noh, Dong-Ouk; Kwon, Ki-Han; Hwang, Jong-Hyun; Yu, Kwang-Won

    2013-06-01

    An intestinal immune system modulating polysaccharide (CUI-3IIb-3-2, 18kDa) was purified from Citrus unshiu peel. CUI-3IIb-3-2 mainly comprised GalA, GlcA, Ara, Gal and Rha, and it consisted of 4-linked GalA, terminal Araf, 4- or 5-linked/3,4- or 3,5-branched Ara, terminal Gal, and 2-linked/2,4-branched Rha. After CUI-3IIb-3-2 digestion by endo-α-d-(1→4)-polygalacturonase, its hydrolysate was fractionated into PG-1 and PG-2. Methylation analyses of PG-1 and PG-2 using base-catalysed β-elimination suggested that CUI-3IIb-3-2 be assumed as pectic-type polysaccharide. Since the activities of PG-1 and PG-2 were potently decreased, the whole polysaccharide structure of CUI-3IIb-3-2 would be essential to maintain the activity. Meanwhile, when CUI-3IIb was orally administered in mice, bone marrow cell proliferation and GM-CSF/IL-6 production from Peyer's patch cell were significantly higher (1.76- and 2.03/2.51-fold, respectively) than a saline. Therefore, a pectic-type polysaccharide from citrus peel could stimulate Peyer's patches and produce hematopoietic growth factors resulted in bone marrow cell proliferation.

  8. Immune modulation by dendritic-cell-based cancer vaccines.

    PubMed

    Kumar, Chaitanya; Kohli, Sakshi; Bapsy, Poonamalle Parthasarathy; Vaid, Ashok Kumar; Jain, Minish; Attili, Venkata Sathya Suresh; Sharan, Bandana

    2017-03-01

    The interplay between host immunity and tumour cells has opened the possibility of targeting tumour cells by modulation of the human immune system. Cancer immunotherapy involves the treatment of a tumour by utilizing the recombinant human immune system components to target the pro-tumour microenvironment or by revitalizing the immune system with the ability to kill tumour cells by priming the immune cells with tumour antigens. In this review, current immunotherapy approaches to cancer with special focus on dendritic cell (DC)-based cancer vaccines are discussed. Some of the DC-based vaccines under clinical trials for various cancer types are highlighted. Establishing tumour immunity involves a plethora of immune components and pathways; hence, combining chemotherapy, radiation therapy and various arms of immunotherapy, after analysing the benefits of individual therapeutic agents, might be beneficial to the patient.

  9. Neuroendocrine Factors Alter Host Defense by Modulating Immune Function

    PubMed Central

    Butts, Cherie L.; Sternberg, Estner M.

    2008-01-01

    An increasing body of evidence demonstrates that there is bidirectional communication between the neuroendocrine and immune systems. Interactions between these systems results in a variety of outcomes, including the well documented “sickness behavior” elicited by cytokines of the immune system that can enter the brain or activate second messengers that modify neuronal activity. Crosstalk between the neuroendocrine and immune systems can also result in production of factors by the nervous and endocrine systems that alter immune cell function and subsequent modulation of immune responses against infectious agents and other pathogens. Continued exposure to molecules produced by the neuroendocrine system has also been shown to increase susceptibility and/or severity of disease. Furthermore, neuroendocrine factors are thought to play a major role in the gender-specific difference in development of certain disorders, including autoimmune/inflammatory diseases that have a 2- to 10-fold higher incidence in females compared to males. Neuroendocrine factors can affect immune cells at the level of gene transcription but have also been shown to modify immune cell activity by interacting with intracellular signal transduction molecules, resulting in modified ability of these cells to mount a potent immune response. In this review, we will consider the various effects of the neuroendocrine system and its proteins on specific populations of immune cells and associated responses in host immunity against pathogens. We will further discuss how this modification of immune cell activity by the neuroendocrine system can contribute to susceptibility/severity of development of diseases. PMID:18329009

  10. Modulation of systemic and intestinal immune response by interleukin-2 therapy in gastrointestinal surgical oncology. Personal experience in the context of current knowledge and future perspectives.

    PubMed

    Nespoli, Luca; Uggeri, Fabio; Romano, Fabrizio; Nespoli, Angelo; Brivo, Fernando; Fumagalli, Luca; Sargenti, Manuela; Uggeri, Franco; Gianotti, Luca

    2012-03-01

    Interactions between host and malignant tumor is currently under intensive investigation. The immune system seems to have a key role in cancer development and spread. Novel strategies to actively modulate the immune system have been proposed to improve the outcome of disease in patients with neoplasms. Our experience with systemic immunomodulation by interleukin-2 (IL-2) focused on both systemic and local immunity in surgical gastrointestinal cancer. Preoperative IL-2 subcutaneous injection was effective in counteracting postoperative immunosuppression, with a reduction of serum levels of IL-6 and the maintenance of preoperative levels of IL-12, a higher number of circulating total lymphocytes, and CD3(+) and CD4(+) T-cells, and a smaller decrease in circulating mature and immature dendritic cells (DCs), as well as a reduction in postoperative serum levels of vascular endothelial growth factor. At the intestinal level, in patients with colorectal cancer, preoperative administration of IL-2 affected both phenotype and function of resident dendritic cells and T-cells, skewing local immunity toward a more immunogenic one. Our data showed that immunomodulation by IL-2 was effective in counteracting the systemic postoperative immune suppression related to surgical stress. IL-2 was also active at a local level on intestinal immunity, affecting both phenotype and function of resident T-cells and DCs. Future studies will encompass the possibility of reaching more adequate intratumoral IL-2 concentrations by direct intralesional injection to maximize immunostimulatory effects and minimize adverse effects.

  11. Immune modulation of resistance artery remodelling.

    PubMed

    Schiffrin, Ernesto L

    2012-01-01

    Low-grade inflammation plays a role in cardiovascular disease. The innate and the adaptive immune responses participate in mechanisms that contribute to inflammatory responses. It has been increasingly appreciated that different subsets of lymphocytes and the cytokines they produce modulate the vascular remodelling that occurs in cardiovascular disease. Effector T cells such as T-helper (Th) 1 (interferon-γ-producing) and Th2 lymphocytes (that produce interleukin-4), as well as Th17 (that produce interleukin-17), and T suppressor lymphocytes including regulatory T cells (Treg), which express the transcription factor forkhead box P3 (Foxp3), are involved in the remodelling of small arteries that occurs under the action of angiotensin II, deoxycorticosterone-salt and aldosterone-salt, as well as in models of hypertension such as the Dahl-salt-sensitive rat. The mechanism whereby the immune system is activated is unclear, but it has been suggested that neo-antigens may be generated by the elevation of blood pressure or other stimuli, leading to the activation of the immune response. Activated Th1 may contribute to vascular remodelling directly on blood vessels via effects of the cytokines produced or indirectly by actions on the kidney. The protective effect of Treg may be mediated similarly directly or via renal effects. These data offer promise for the discovery of new therapeutic targets to ameliorate vascular remodelling, which could lead to improved outcome in cardiovascular disease in humans.

  12. 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…

  13. 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…

  14. Retinoic Acid and Its Role in Modulating Intestinal Innate Immunity

    PubMed Central

    Czarnewski, Paulo; Das, Srustidhar; Parigi, Sara M.; Villablanca, Eduardo J.

    2017-01-01

    Vitamin A (VA) is amongst the most well characterized food-derived nutrients with diverse immune modulatory roles. Deficiency in dietary VA has not only been associated with immune dysfunctions in the gut, but also with several systemic immune disorders. In particular, VA metabolite all-trans retinoic acid (atRA) has been shown to be crucial in inducing gut tropism in lymphocytes and modulating T helper differentiation. In addition to the widely recognized role in adaptive immunity, increasing evidence identifies atRA as an important modulator of innate immune cells, such as tolerogenic dendritic cells (DCs) and innate lymphoid cells (ILCs). Here, we focus on the role of retinoic acid in differentiation, trafficking and the functions of innate immune cells in health and inflammation associated disorders. Lastly, we discuss the potential involvement of atRA during the plausible crosstalk between DCs and ILCs. PMID:28098786

  15. 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

  16. Schistosome-Derived Molecules as Modulating Actors of the Immune System and Promising Candidates to Treat Autoimmune and Inflammatory Diseases

    PubMed Central

    Vieira, Anderson Rodrigues Araújo; de Campos, Tatiana Amabile

    2016-01-01

    It is long known that some parasite infections are able to modulate specific pathways of host's metabolism and immune responses. This modulation is not only important in order to understand the host-pathogen interactions and to develop treatments against the parasites themselves but also important in the development of treatments against autoimmune and inflammatory diseases. Throughout the life cycle of schistosomes the mammalian hosts are exposed to several biomolecules that are excreted/secreted from the parasite infective stage, named cercariae, from their tegument, present in adult and larval stages, and finally from their eggs. These molecules can induce the activation and modulation of innate and adaptive responses as well as enabling the evasion of the parasite from host defense mechanisms. Immunomodulatory effects of helminth infections and egg molecules are clear, as well as their ability to downregulate proinflammatory cytokines, upregulate anti-inflammatory cytokines, and drive a Th2 type of immune response. We believe that schistosomes can be used as a model to understand the potential applications of helminths and helminth-derived molecules against autoimmune and inflammatory diseases. PMID:27635405

  17. Human immune system variation

    PubMed Central

    Brodin, Petter; Davis, Mark M.

    2017-01-01

    The human immune system is highly variable between individuals but relatively stable over time within a given person. Recent conceptual and technological advances have enabled systems immunology analyses, which reveal the composition of immune cells and proteins in populations of healthy individuals. The range of variation and some specific influences that shape an individual’s immune system is now becoming clearer. Human immune systems vary as a consequence of heritable and non-heritable influences, but symbiotic and pathogenic microbes and other non-heritable influences explain most of this variation. Understanding when and how such influences shape the human immune system is key for defining metrics of immunological health and understanding the risk of immune-mediated and infectious diseases. PMID:27916977

  18. Modulation of Immune Functions by Foods

    PubMed Central

    2004-01-01

    Evidence is rapidly accumulating as to the beneficial effects of foods. However, it is not always clear whether the information is based on data evaluated impartially in a scientific fashion. Human research into whether foods modulate immune functions in either intervention studies or randomized controlled trials can be classified into three categories according to the physical state of subjects enrolled for investigation: (i) studies examining the effect of foods in healthy individuals; (ii) studies analyzing the effect of foods on patients with hypersensitivity; and (iii) studies checking the effect of foods on immunocompromized subjects, including patients who had undergone surgical resection of cancer and newborns. The systematization of reported studies has made it reasonable to conclude that foods are able to modulate immune functions manifesting as either innate immunity (phagocytic activity, NK cell activity) or acquired immunity (T cell response, antibody production). Moreover, improvement of immune functions by foods can normalize the physical state of allergic patients or cancer patients, and may reduce the risk of diseases in healthy individuals. Therefore, it is valuable to assess the immune-modulating abilities of foods by measuring at least one parameter of either innate or acquired immunity. PMID:15841257

  19. Effect on the immune system of mice exposed chronically to 50 Hz amplitude-modulated 2.45 GHz microwaves

    SciTech Connect

    Elekes, E.; Thuroczy, G.; Szabo, L.D.

    1996-12-01

    The effect of continuous (CW; 2.45 GHz carrier frequency) or amplitude-modulated (AM; 50 Hz square wave) microwave radiation on the immune response was tested. CW exposures (6 days, 3 h/day) induced elevations of the number of antibody-producing cells in the spleen of male Balb/c mice (+37%). AM microwave exposure induced elevation of the spleen index (+15%) and antibody-producing cell number (+55%) in the spleen of male mice. No changes were observed in female mice. It is concluded that both types of exposure conditions induced moderate elevation of antibody production only in male mice.

  20. β2→1-Fructans Modulate the Immune System In Vivo in a Microbiota-Dependent and -Independent Fashion.

    PubMed

    Fransen, Floris; Sahasrabudhe, Neha M; Elderman, Marlies; Bosveld, Margaret; El Aidy, Sahar; Hugenholtz, Floor; Borghuis, Theo; Kousemaker, Ben; Winkel, Simon; van der Gaast-de Jongh, Christa; de Jonge, Marien I; Boekschoten, Mark V; Smidt, Hauke; Schols, Henk A; de Vos, Paul

    2017-01-01

    It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies in vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of β2→1-fructans on immunity via microbiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- or long-chain β2→1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer's patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples. We found that β2→1-fructans modulated immunity by both microbiota and microbiota-independent effects. Moreover, effects were dependent on the chain-length of the β2→1-fructans type polymer. Both short- and long-chain β2→1-fructans enhanced T-helper 1 cells in PPs, whereas only short-chain β2→1-fructans increased regulatory T cells and CD11b(-)CD103(-) dendritic cells (DCs) in the MLN. A common feature after short- and long-chain β2→1-fructan treatment was enhanced 2-alpha-l-fucosyltransferase 2 expression and other IL-22-dependent genes in the ileum of conventional mice. These effects were not associated with shifts in gut microbiota composition, or altered production of short-chain fatty acids. Both short- and long-chain β2→1-fructans also induced immune effects in germ-free animals, demonstrating direct effect independent from the gut microbiota. Also, these effects were dependent on the chain-length of the β2→1-fructans. Short-chain β2→1-fructan induced lower CD80 expression by CD11b(-)CD103(-) DCs in PPs, whereas long-chain β2→1-fructan specifically modulated B cell responses in germ-free mice. In conclusion, support of immunity is determined by the chemical structure of β2→1-fructans and is partially microbiota independent.

  1. β2→1-Fructans Modulate the Immune System In Vivo in a Microbiota-Dependent and -Independent Fashion

    PubMed Central

    Fransen, Floris; Sahasrabudhe, Neha M.; Elderman, Marlies; Bosveld, Margaret; El Aidy, Sahar; Hugenholtz, Floor; Borghuis, Theo; Kousemaker, Ben; Winkel, Simon; van der Gaast-de Jongh, Christa; de Jonge, Marien I.; Boekschoten, Mark V.; Smidt, Hauke; Schols, Henk A.; de Vos, Paul

    2017-01-01

    It has been shown in vitro that only specific dietary fibers contribute to immunity, but studies in vivo are not conclusive. Here, we investigated degree of polymerization (DP) dependent effects of β2→1-fructans on immunity via microbiota-dependent and -independent effects. To this end, conventional or germ-free mice received short- or long-chain β2→1-fructan for 5 days. Immune cell populations in the spleen, mesenteric lymph nodes (MLNs), and Peyer’s patches (PPs) were analyzed with flow cytometry, genome-wide gene expression in the ileum was measured with microarray, and gut microbiota composition was analyzed with 16S rRNA sequencing of fecal samples. We found that β2→1-fructans modulated immunity by both microbiota and microbiota-independent effects. Moreover, effects were dependent on the chain-length of the β2→1-fructans type polymer. Both short- and long-chain β2→1-fructans enhanced T-helper 1 cells in PPs, whereas only short-chain β2→1-fructans increased regulatory T cells and CD11b−CD103− dendritic cells (DCs) in the MLN. A common feature after short- and long-chain β2→1-fructan treatment was enhanced 2-alpha-l-fucosyltransferase 2 expression and other IL-22-dependent genes in the ileum of conventional mice. These effects were not associated with shifts in gut microbiota composition, or altered production of short-chain fatty acids. Both short- and long-chain β2→1-fructans also induced immune effects in germ-free animals, demonstrating direct effect independent from the gut microbiota. Also, these effects were dependent on the chain-length of the β2→1-fructans. Short-chain β2→1-fructan induced lower CD80 expression by CD11b−CD103− DCs in PPs, whereas long-chain β2→1-fructan specifically modulated B cell responses in germ-free mice. In conclusion, support of immunity is determined by the chemical structure of β2→1-fructans and is partially microbiota independent. PMID:28261212

  2. Swine immune system

    USDA-ARS?s Scientific Manuscript database

    Probably no area of veterinary medicine has seen a greater explosion in knowledge then the immune system and its implications in disease and vaccination. In this chapter on the Swine Immune System for the 10th Edition of Diseases of Swine we expand on the information provided in past editions by in...

  3. Enhancement of Microbiota in Healthy Macaques Results in Beneficial Modulation of Mucosal and Systemic Immune Function1

    PubMed Central

    Manuzak, Jennifer A.; Hensley-McBain, Tiffany; Zevin, Alexander S.; Miller, Charlene; Cubas, Rafael; Agricola, Brian; Gile, Jill; Richert-Spuhler, Laura; Patilea, Gabriela; Estes, Jacob D.; Langevin, Stanley; Reeves, R. Keith; Haddad, Elias K.; Klatt, Nichole R.

    2016-01-01

    Given the critical role of mucosal surfaces in susceptibility to infection, it is imperative that effective mucosal responses are induced when developing efficacious vaccines and prevention strategies for infection. Modulating the microbiota in the gastrointestinal (GI) tract through the use of probiotics (PBio) is a safe and well-tolerated approach to enhance mucosal and overall health. We assessed the longitudinal impact of daily treatment with the VSL#3 probiotic on cellular and humoral immunity and inflammation in healthy macaques. PBio therapy resulted in significantly increased frequencies of B cells expressing IgA in the colon and lymph node (LN), likely due to significantly increased LN T follicular helper cell (Tfh) frequencies and LN follicles. Increased frequencies of IL-23+ antigen presenting cells (APCs) in the colon were found post-PBio treatment, which correlated with LN Tfh. Finally, VSL#3 significantly down-modulated the response of TLR2, TLR3, TLR4 and TLR9-expressing HEK293 cells to stimulation with Pam3CSK4, Poly(I:C), LPS and ODN2006, respectively. These data provide a mechanism for the beneficial impact of PBio on mucosal health and implicates the use of PBio therapy in the context of vaccination or preventative approaches to enhance protection from mucosal infection by improving immune defenses at the mucosal portal of entry. PMID:26826246

  4. Immune Regulation by Pericytes: Modulating Innate and Adaptive Immunity

    PubMed Central

    Navarro, Rocío; Compte, Marta; Álvarez-Vallina, Luis; Sanz, Laura

    2016-01-01

    Pericytes (PC) are mural cells that surround endothelial cells in small blood vessels. PC have traditionally been credited with structural functions, being essential for vessel maturation and stabilization. However, an accumulating body of evidence suggests that PC also display immune properties. They can respond to a series of pro-inflammatory stimuli and are able to sense different types of danger due to their expression of functional pattern-recognition receptors, contributing to the onset of innate immune responses. In this context, PC not only secrete a variety of chemokines but also overexpress adhesion molecules such as ICAM-1 and VCAM-1 involved in the control of immune cell trafficking across vessel walls. In addition to their role in innate immunity, PC are involved in adaptive immunity. It has been reported that interaction with PC anergizes T cells, which is attributed, at least in part, to the expression of PD-L1. As components of the tumor microenvironment, PC can also modulate the antitumor immune response. However, their role is complex, and further studies will be required to better understand the crosstalk of PC with immune cells in order to consider them as potential therapeutic targets. In any case, PC will be looked at with new eyes by immunologists from now on. PMID:27867386

  5. Modulation of host immune defenses by Aeromonas and Yersinia species: convergence on toxins secreted by various secretion systems.

    PubMed

    Rosenzweig, Jason A; Chopra, Ashok K

    2013-01-01

    Like other pathogenic bacteria, Yersinia and Aeromonas species have been continuously co-evolving with their respective hosts. Although the former is a bonafide human pathogen, the latter has gained notararity as an emerging disease-causing agent. In response to immune cell challenges, bacterial pathogens have developed diverse mechanism(s) enabling their survival, and, at times, dominance over various host immune defense systems. The bacterial type three secretion system (T3SS) is evolutionarily derived from flagellar subunits and serves as a vehicle by which microbes can directly inject/translocate anti-host factors/effector proteins into targeted host immune cells. A large number of Gram-negative bacterial pathogens possess a T3SS empowering them to disrupt host cell signaling, actin cytoskeleton re-arrangements, and even to induce host-cell apoptotic and pyroptotic pathways. All pathogenic yersiniae and most Aeromonas species possess a T3SS, but they also possess T2- and T6-secreted toxins/effector proteins. This review will focus on the mechanisms by which the T3SS effectors Yersinia outer membrane protein J (YopJ) and an Aeromonas hydrophila AexU protein, isolated from the diarrheal isolate SSU, mollify host immune system defenses. Additionally, the mechanisms that are associated with host cell apoptosis/pyroptosis by Aeromonas T2SS secreted Act, a cytotoxic enterotoxin, and Hemolysin co-regulated protein (Hcp), an A. hydrophila T6SS effector, will also be discussed.

  6. Modulation of macrophage functions by sheeppox virus provides clues to understand interaction of the virus with host immune system.

    PubMed

    Abu-El-Saad, Abdel-Aziz S; Abdel-Moneim, Ahmed S

    2005-03-22

    Poxviruses encode a range of immunomodulatory genes to subvert or evade the challenges posed by the innate and adaptive immune responses. However, the inactivated poxviruses possessed immunostimulating capacity and were used as a prophylactic or metaphylactic application that efficiently reduced susceptibility to infectious diseases in different species. This fact is intensively studied in different genera of poxviruses. However, little is known about the basic mechanisms adopted by sheeppox virus (SPPV). SPPV causes an acute disease of sheep that recently, has been observed to reinfect its host in spite of vaccination. By injecting inactivated or attenuated sheeppox virus SPPV vaccine in adult male Swiss mice, SPPV was found to reduce macrophages' functions in a local event that occurs at the site of application 12 h after vaccine administration as indicated by increased level of IL-10 and decreased level of SOD from cultured peritoneal macrophages. In contrast increased levels of IL-12, and SOD activity from cultured splenic macrophages, lymphocyte response to PHA-P, and in-vivo response to T-dependant Ag were detected. These effects were observed in both attenuated and inactivated SPPV, but more prominent in attenuated one. The results of this study help to elucidate, the phenomenon of existence natural SPPV infections in sheep instead of vaccination and the basic mechanisms responsible for the immunostimulating capacity of sheeppox virus. Locally, SPPV shows evidence for an immune escape mechanism that alleviates the host's immune response. Later and systemically, the virus protects the host from any fatal consequences of the immune system suppression.

  7. Immune-modulating therapy in acute pancreatitis: fact or fiction.

    PubMed

    Akinosoglou, Karolina; Gogos, Charalambos

    2014-11-07

    Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, bearing significant morbidity and mortality worldwide. Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care. As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis, therapeutic approaches have turned towards modulating the systemic inflammatory response. Targets, among others, have included pro- and anti-inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules and platelets. Even though, initial results in experimental models have been encouraging, clinical implementation of immune-regulating therapies in acute pancreatitis has had a slow progress. Main reasons include difficulty in clinical translation of experimental data, poor understanding of inflammatory response time-course, flaws in experimental designs, need for multimodal approaches and commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future.

  8. Immune-modulating therapy in acute pancreatitis: Fact or fiction

    PubMed Central

    Akinosoglou, Karolina; Gogos, Charalambos

    2014-01-01

    Acute pancreatitis (AP) is one of the most common diseases of the gastrointestinal tract, bearing significant morbidity and mortality worldwide. Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care. As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis, therapeutic approaches have turned towards modulating the systemic inflammatory response. Targets, among others, have included pro- and anti-inflammatory modulators, cytokines, chemokines, immune cells, adhesive molecules and platelets. Even though, initial results in experimental models have been encouraging, clinical implementation of immune-regulating therapies in acute pancreatitis has had a slow progress. Main reasons include difficulty in clinical translation of experimental data, poor understanding of inflammatory response time-course, flaws in experimental designs, need for multimodal approaches and commercial drawbacks. Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future. PMID:25386069

  9. The immune response and its therapeutic modulation in bronchiectasis.

    PubMed

    Daheshia, Massoud; Prahl, James D; Carmichael, Jacob J; Parrish, John S; Seda, Gilbert

    2012-01-01

    Bronchiectasis (BC) is a chronic pulmonary disease with tremendous morbidity and significant mortality. As pathogen infection has been advocated as a triggering insult in the development of BC, a central role for the immune response in this process seems obvious. Inflammatory cells are present in both the airways as well as the lung parenchyma, and multiple mediators of immune cells including proteases and cytokines or their humoral products are increased locally or in the periphery. Interestingly, a defect in the immune system or suppression of immune response during conditions such as immunodeficiency may well predispose one to the devastating effects of BC. Thus, the outcome of an active immune response as detrimental or protective in the pathogenesis of BC may be dependent on the state of the patient's immunity, the severity of infection, and the magnitude of immune response. Here we reassess the function of the innate and acquired immunity in BC, the major sites of immune response, and the nature of the bioactive mediators. Furthermore, the potential link(s) between an ongoing immune response and structural alterations accompanying the disease and the success of therapies that can modulate the nature and extent of immune response in BC are elaborated upon.

  10. Intratumoral modulation of the inducible co-stimulator ICOS by recombinant oncolytic virus promotes systemic anti-tumour immunity

    PubMed Central

    Zamarin, Dmitriy; Holmgaard, Rikke B.; Ricca, Jacob; Plitt, Tamar; Palese, Peter; Sharma, Padmanee; Merghoub, Taha; Wolchok, Jedd D.; Allison, James P.

    2017-01-01

    Emerging data suggest that locoregional cancer therapeutic approaches with oncolytic viruses can lead to systemic anti-tumour immunity, although the appropriate targets for intratumoral immunomodulation using this strategy are not known. Here we find that intratumoral therapy with Newcastle disease virus (NDV), in addition to the activation of innate immunity, upregulates the expression of T-cell co-stimulatory receptors, with the inducible co-stimulator (ICOS) being most notable. To explore ICOS as a direct target in the tumour, we engineered a recombinant NDV-expressing ICOS ligand (NDV-ICOSL). In the bilateral flank tumour models, intratumoral administration of NDV-ICOSL results in enhanced infiltration with activated T cells in both virus-injected and distant tumours, and leads to effective rejection of both tumours when used in combination with systemic CTLA-4 blockade. These findings highlight that intratumoral immunomodulation with an oncolytic virus expressing a rationally selected ligand can be an effective strategy to drive systemic efficacy of immune checkpoint blockade. PMID:28194010

  11. Immune Checkpoint Modulators: An Emerging Antiglioma Armamentarium

    PubMed Central

    Kim, Eileen S.; Kim, Jennifer E.; Patel, Mira A.; Mangraviti, Antonella; Ruzevick, Jacob; Lim, Michael

    2016-01-01

    Immune checkpoints have come to the forefront of cancer therapies as a powerful and promising strategy to stimulate antitumor T cell activity. Results from recent preclinical and clinical studies demonstrate how checkpoint inhibition can be utilized to prevent tumor immune evasion and both local and systemic immune suppression. This review encompasses the key immune checkpoints that have been found to play a role in tumorigenesis and, more specifically, gliomagenesis. The review will provide an overview of the existing preclinical and clinical data, antitumor efficacy, and clinical applications for each checkpoint with respect to GBM, as well as a summary of combination therapies with chemotherapy and radiation. PMID:26881264

  12. Modulation of macrophage functions by sheeppox virus provides clues to understand interaction of the virus with host immune system

    PubMed Central

    Abu-EL-Saad, Abdel-Aziz S; Abdel-Moneim, Ahmed S

    2005-01-01

    Background Poxviruses encode a range of immunomodulatory genes to subvert or evade the challenges posed by the innate and adaptive immune responses. However, the inactivated poxviruses possessed immunostimulating capacity and were used as a prophylactic or metaphylactic application that efficiently reduced susceptibility to infectious diseases in different species. This fact is intensively studied in different genera of poxviruses. However, little is known about the basic mechanisms adopted by sheeppox virus (SPPV). SPPV causes an acute disease of sheep that recently, has been observed to reinfect its host in spite of vaccination. Results By injecting inactivated or attenuated sheeppox virus SPPV vaccine in adult male Swiss mice, SPPV was found to reduce macrophages' functions in a local event that occurs at the site of application 12 h after vaccine administration as indicated by increased level of IL-10 and decreased level of SOD from cultured peritoneal macrophages. In contrast increased levels of IL-12, and SOD activity from cultured splenic macrophages, lymphocyte response to PHA-P, and in-vivo response to T-dependant Ag were detected. These effects were observed in both attenuated and inactivated SPPV, but more prominent in attenuated one. Conclusion The results of this study help to elucidate, the phenomenon of existence natural SPPV infections in sheep instead of vaccination and the basic mechanisms responsible for the immunostimulating capacity of sheeppox virus. Locally, SPPV shows evidence for an immune escape mechanism that alleviates the host's immune response. Later and systemically, the virus protects the host from any fatal consequences of the immune system suppression. PMID:15784144

  13. Autonomic nervous system and immune system interactions.

    PubMed

    Kenney, M J; Ganta, C K

    2014-07-01

    The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological, and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines, and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease

  14. Autonomic Nervous System and Immune System Interactions

    PubMed Central

    Kenney, MJ; Ganta, CK

    2015-01-01

    The present review assesses the current state of literature defining integrative autonomic-immune physiological processing, focusing on studies that have employed electrophysiological, pharmacological, molecular biological and central nervous system experimental approaches. Central autonomic neural networks are informed of peripheral immune status via numerous communicating pathways, including neural and non-neural. Cytokines and other immune factors affect the level of activity and responsivity of discharges in sympathetic and parasympathetic nerves innervating diverse targets. Multiple levels of the neuraxis contribute to cytokine-induced changes in efferent parasympathetic and sympathetic nerve outflows, leading to modulation of peripheral immune responses. The functionality of local sympathoimmune interactions depends on the microenvironment created by diverse signaling mechanisms involving integration between sympathetic nervous system neurotransmitters and neuromodulators; specific adrenergic receptors; and the presence or absence of immune cells, cytokines and bacteria. Functional mechanisms contributing to the cholinergic anti-inflammatory pathway likely involve novel cholinergic-adrenergic interactions at peripheral sites, including autonomic ganglion and lymphoid targets. Immune cells express adrenergic and nicotinic receptors. Neurotransmitters released by sympathetic and parasympathetic nerve endings bind to their respective receptors located on the surface of immune cells and initiate immune-modulatory responses. Both sympathetic and parasympathetic arms of the autonomic nervous system are instrumental in orchestrating neuroimmune processes, although additional studies are required to understand dynamic and complex adrenergic-cholinergic interactions. Further understanding of regulatory mechanisms linking the sympathetic nervous, parasympathetic nervous, and immune systems is critical for understanding relationships between chronic disease development

  15. 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…

  16. 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…

  17. The immune system in hypertension.

    PubMed

    Trott, Daniel W; Harrison, David G

    2014-03-01

    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 contribute to end-organ damage. We and others have shown that mice lacking adaptive immune cells, including recombinase-activating gene-deficient mice and rats and mice with severe combined immunodeficiency have blunted hypertension to stimuli such as ANG II, high salt, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Agonistic antibodies to the ANG II receptor, produced by B cells, contribute to hypertension in experimental models of preeclampsia. The central nervous system seems important in immune cell activation, because lesions in the anteroventral third ventricle block hypertension and T cell activation in response to ANG II. Likewise, genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and immune cell activation. Current evidence indicates that the production of cytokines, including tumor necrosis factor-α, interleukin-17, and interleukin-6, contribute to hypertension, likely via effects on both the kidney and vasculature. In addition, the innate immune system also appears to contribute to hypertension. We propose a working hypothesis linking the sympathetic nervous system, immune cells, production of cytokines, and, ultimately, vascular and renal dysfunction, leading to the augmentation of hypertension. Studies of immune cell activation will clearly be useful in understanding this common yet complex disease.

  18. Role of Hcp, a type 6 secretion system effector, of Aeromonas hydrophila in modulating activation of host immune cells.

    PubMed

    Suarez, Giovanni; Sierra, Johanna C; Kirtley, Michelle L; Chopra, Ashok K

    2010-12-01

    Recently, we reported that the type 6 secretion system (T6SS) of Aeromonas hydrophila SSU plays an important role in bacterial virulence in a mouse model, and immunization of animals with the T6SS effector haemolysin co-regulated protein (Hcp) protected them against lethal infections with wild-type bacteria. Additionally, we showed that the mutant bacteria deleted for the vasH gene within the T6SS gene cluster did not express the hcp gene, while the vasK mutant could express and translocate Hcp, but was unable to secrete it into the extracellular milieu. Both of these A. hydrophila SSU mutants were readily phagocytosed by murine macrophages, pointing to the possible role of the secreted form of Hcp in the evasion of the host innate immunity. By using the ΔvasH mutant of A. hydrophila, our in vitro data showed that the addition of exogenous recombinant Hcp (rHcp) reduced bacterial uptake by macrophages. These results were substantiated by increased bacterial virulence when rHcp was added along with the ΔvasH mutant in a septicaemic mouse model of infection. Analysis of the cytokine profiling in the intraperitoneal lavage as well as activation of host cells after 4 h of infection with the ΔvasH mutant supplemented with rHcp indicated that this T6SS effector inhibited production of pro-inflammatory cytokines and induced immunosuppressive cytokines, such as interleukin-10 and transforming growth factor-β, which could circumvent macrophage activation and maturation. This mechanism of innate immune evasion by Hcp possibly inhibited the recruitment of cellular immune components, which allowed bacterial multiplication and dissemination in animals, thereby leading to their mortality.

  19. Role of Hcp, a type 6 secretion system effector, of Aeromonas hydrophila in modulating activation of host immune cells

    PubMed Central

    Suarez, Giovanni; Sierra, Johanna C.; Kirtley, Michelle L.; Chopra, Ashok K.

    2010-01-01

    Recently, we reported that the type 6 secretion system (T6SS) of Aeromonas hydrophila SSU plays an important role in bacterial virulence in a mouse model, and immunization of animals with the T6SS effector haemolysin co-regulated protein (Hcp) protected them against lethal infections with wild-type bacteria. Additionally, we showed that the mutant bacteria deleted for the vasH gene within the T6SS gene cluster did not express the hcp gene, while the vasK mutant could express and translocate Hcp, but was unable to secrete it into the extracellular milieu. Both of these A. hydrophila SSU mutants were readily phagocytosed by murine macrophages, pointing to the possible role of the secreted form of Hcp in the evasion of the host innate immunity. By using the ΔvasH mutant of A. hydrophila, our in vitro data showed that the addition of exogenous recombinant Hcp (rHcp) reduced bacterial uptake by macrophages. These results were substantiated by increased bacterial virulence when rHcp was added along with the ΔvasH mutant in a septicaemic mouse model of infection. Analysis of the cytokine profiling in the intraperitoneal lavage as well as activation of host cells after 4 h of infection with the ΔvasH mutant supplemented with rHcp indicated that this T6SS effector inhibited production of pro-inflammatory cytokines and induced immunosuppressive cytokines, such as interleukin-10 and transforming growth factor-β, which could circumvent macrophage activation and maturation. This mechanism of innate immune evasion by Hcp possibly inhibited the recruitment of cellular immune components, which allowed bacterial multiplication and dissemination in animals, thereby leading to their mortality. PMID:20798163

  20. Interferon Lambda: Modulating Immunity in Infectious Diseases

    PubMed Central

    Syedbasha, Mohammedyaseen; Egli, Adrian

    2017-01-01

    Interferon lambdas (IFN-λs; IFNL1-4) modulate immunity in the context of infections and autoimmune diseases, through a network of induced genes. IFN-λs act by binding to the heterodimeric IFN-λ receptor (IFNLR), activating a STAT phosphorylation-dependent signaling cascade. Thereby hundreds of IFN-stimulated genes are induced, which modulate various immune functions via complex forward and feedback loops. When compared to the well-characterized IFN-α signaling cascade, three important differences have been discovered. First, the IFNLR is not ubiquitously expressed: in particular, immune cells show significant variation in the expression levels of and susceptibilities to IFN-λs. Second, the binding affinities of individual IFN-λs to the IFNLR varies greatly and are generally lower compared to the binding affinities of IFN-α to its receptor. Finally, genetic variation in the form of a series of single-nucleotide polymorphisms (SNPs) linked to genes involved in the IFN-λ signaling cascade has been described and associated with the clinical course and treatment outcomes of hepatitis B and C virus infection. The clinical impact of IFN-λ signaling and the SNP variations may, however, reach far beyond viral hepatitis. Recent publications show important roles for IFN-λs in a broad range of viral infections such as human T-cell leukemia type-1 virus, rotaviruses, and influenza virus. IFN-λ also potentially modulates the course of bacterial colonization and infections as shown for Staphylococcus aureus and Mycobacterium tuberculosis. Although the immunological processes involved in controlling viral and bacterial infections are distinct, IFN-λs may interfere at various levels: as an innate immune cytokine with direct antiviral effects; or as a modulator of IFN-α-induced signaling via the suppressor of cytokine signaling 1 and the ubiquitin-specific peptidase 18 inhibitory feedback loops. In addition, the modulation of adaptive immune functions via macrophage and

  1. 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

  2. Research on Immunotherapy: Using the Immune System to Treat Cancer

    MedlinePlus

    ... Cancers Clinical Trials Global Health Immunotherapy: Using the Immune System to Treat Cancer Scanning electron micrograph of a ... of cancers, including brain, breast, and lung cancer. Immune System Modulators Yet another type of immunotherapy uses proteins ...

  3. Glycan-Based Cell Targeting To Modulate Immune Responses.

    PubMed

    Johannssen, Timo; Lepenies, Bernd

    2017-04-01

    Glycosylation is an integral post-translational modification present in more than half of all eukaryotic proteins. It affects key protein functions, including folding, stability, and immunogenicity. Glycoengineering approaches, such as the use of bacterial N-glycosylation systems, or expression systems, including yeasts, insect cells, and mammalian cells, have enabled access to defined and homogenous glycoproteins. Given that glycan structures on proteins can be recognized by host lectin receptors, they may facilitate cell-specific targeting and immune modulation. Myeloid C-type lectin receptors (CLRs) expressed by antigen-presenting cells are attractive targets to shape immune responses. Multivalent glycan display on nanoparticles, liposomes, or dendrimers has successfully enabled CLR targeting. In this review, we discuss novel strategies to access defined glycan structures and highlight CLR targeting approaches for immune modulation.

  4. Immune Modulation and Treatment of Human Papilloma Virus-Related Warts with Energetics of Living Systems Acupuncture.

    PubMed

    Brustin, Rom; Toledano, Martine; Geffen, Tal; Goona, Raia; Hochberg, Malka; Kreisberg, Bilha; Murad, Sari; Pitcovski, Jacob

    2017-06-01

    Background: Cutaneous warts are small skin lesions formed as a result of infection by the human papilloma virus (HPV). In the lesion, viral manipulation creates a microenvironment that favors virus survival and reproduction. Most lesions eventually regress, probably as a result of a Th1-mediated immune response. However, some warts fail to regress and become persistent. Objective: The efficacy of treatment of persistent HPV-caused warts with Energetics of Living Systems acupuncture and monitored immune system involvement was tested. Methods: Eighteen patients with persistent warts were recruited for the study; 9 received acupuncture treatment and 9 received placebo. Each patient was treated 4 times. Results: Clinical success was defined as total clearance of all lesions with no recurrence for 3 months. In the treatment group, clinical success was 36.6% versus 0% in the placebo group. In the treatment group, the level of interleukin (IL)-10 decreased. In a comparison of patients with cleared warts and overall patients with nonresponding warts, different expression levels of IL-8, IL-10, tumor necrosis factor-α, IL-6, and interferon-γ were found, although these differences were not always statistically significant. Trends of differences (not significant) were observed in leukocyte levels. Acupuncture eliminated persistent warts in some of the patients, along with inducing changes in immunologic parameters. Conclusions: Taking the clinical and immunologic outcomes together, clearance of persistent warts following acupuncture might be due to a shift toward a Th1 immune response, or an anti-inflammatory effect against the lesion-induced microenvironment.

  5. Immune modulation following immunization with polyvalent vaccines in dogs.

    PubMed

    Strasser, Alois; May, Bettina; Teltscher, Andrea; Wistrela, Eva; Niedermüller, Hans

    2003-08-15

    A decline in T-cell-mediated immunity and transient state of immunosuppression after immunization has been reported in dogs. Nevertheless, dogs are still routinely vaccinated with polyvalent live vaccines and severe disease does not generally occur. In order to investigate these effects on the canine immune system and to elucidate possible mechanisms we determined the following immune parameters in the blood of 33 clinically sound German shepherd dogs before and after standard vaccination with a polyvalent vaccine against distemper, parvovirus, viral hepatitis, leptospirosis, kennel cough and rabies: white and differential blood cell count, the serum concentrations and/or activities of IL-1, IL-2, IFN-gamma, TNF-alpha, neopterin and IgG, natural killer (NK) cell activity, bactericidal activity and complement hemolytic activity, lymphocyte proliferation test (LPT) and nitroblue tetrazolium test (NBT). Our major findings were that significant postvaccinal decreases in T-cell mitogenic response to PHA and in neutrophil function and neopterin serum concentration were accompanied by simultaneous increase in plasma IgG and hemolytic complement activity. This suggests a transient shift in the balance between cell-mediated and humoral (T(H)1/T(H)2) immunity rather than immunosuppression. These results do not imply that dogs should not receive live vaccines, as the response to vaccines just seems to create a state of altered homeostasis when immunization elicits protection by humoral and cell-mediated immunity. However, these recognized compromises of immune function should be considered and vaccines still be applied only in healthy animals and strictly according to the rules and regulations given by the manufacturer.

  6. [Prolactin as a modulator of antiparasitic immunity].

    PubMed

    Płociński, Przemysław; Dzitko, Katarzyna; Długońska, Henryka

    2007-01-01

    Prolactin (PRL) is a polypeptide hormone of the pituitary origin, that expresses over 300 separate biological activities, including its involvement in the regulation of immune functions. The hormone's immune capacities are related, among others, to comitogenic activity, prevention of immune cell apoptosis, stimulation of interleukins and antibodies production. Prolactin acts as a potent positive modulator of immunity to some protozoan parasites. It is well established that the hormone stimulates IFN-gamma and many other TH1-type cytokines production during Toxoplasma gondii, Leishmania sp. and Acanthamoeba castellanii infections. Recent studies suggest that human prolactin may be a regulator of antiparasitic activity against Plasmodium falciparum. On the other hand pregnancy-associated hyperprolactinemia may have a relevant contribution to reactivation of latent infections caused by many helminthic parasites, like Ancylostoma sp. or Necator sp. It is possibly connected with the process of transmammary transmission of hookworm infection to breast-fed newborns. Moreover, an increase in endogenous circulating prolactin during late pregnancy and lactation in ewes infected with Haemonchus contortus, promotes the phenomenon of periparturient egg rise. High prolactin levels have also been seen in dairy cattle suffering from other trichostrongylids infections. In this article we have discussed the role of prolactin as an important regulator of immunity to parasites.

  7. Modulating immune responses with probiotic bacteria.

    PubMed

    Matsuzaki, T; Chin, J

    2000-02-01

    For many years, probiotic bacteria have been known to confer health benefits to the consumer. One possible mechanism for this may be the ability of probiotic bacteria to modulate immune responses. Oral administration of Lactobacillus casei strain Shirota (LcS) has been found to enhance innate immunity by stimulating the activity of splenic NK cells. Oral feeding with killed LcS was able to stimulate the production of Th1 cytokines, resulting in repressed production of IgE antibodies against Ovalbumin in experimental mice. The ability to switch mucosal immune responses towards Th1 with probiotic bacteria provides a strategy for treatment of allergic disorders. Growth of Meth A tumour cells in the lungs was also inhibited by intrapleural injection of LcS. Oral administration of other probiotic bacteria, such as Streptococcus thermophilus (St), Lactobacillus fermentum (Lf) and yeast (Y), elicited different immune responses. Mice that were prefed yeast or Lf followed by feeding with ovalbumin (OVA) responded better to vaccination with OVA than mice not given either probiotic or OVA or mice that had been prefed only OVA. However, antibody responses were significantly suppressed in response to vaccination with OVA in mice that had been prefed yeast followed by yeast and OVA as well as mice prefed Lf followed by Lf and OVA. Prefeeding St followed by OVA feeding enhanced cellular immune responses against ovalbumin. In contrast, mice prefed St followed by St + OVA were hyporesponsive against OVA. While antigen feeding alone appears to prime for an immune response, cofeeding antigen with probiotic bacteria can suppress both antibody and cellular immune responses and may provide an efficacious protocol to attenuate autoimmune diseases, such as experimental allergic encephalomyelitis, by jointly dosing with myelin basic protein and probiotic bacteria.

  8. Peroxiredoxin 5 modulates immune response in Drosophila

    PubMed Central

    Radyuk, Svetlana N.; Michalak, Katarzyna; Klichko, Vladimir I.; Benes, Judith; Orr, William C.

    2010-01-01

    Background Peroxiredoxins are redox-sensing enzymes with multiple cellular functions. Previously, we reported on the potent antioxidant function of Drosophila peroxiredoxin 5 (dPrx5). Studies with mammalian and human cells suggest that peroxiredoxins can modulate immune-related signaling. Methods Survivorship studies and bacteriological analysis were used to determine resistance of flies to fungal and bacterial infections. RT-PCR and immunoblot analyses determined expression of dPrx5 and immunity factors in response to bacterial challenge. Double mutants for dprx5 gene and genes comprising the Imd/Relish and dTak1/Basket branches of the immune signaling pathways were used in epistatic analysis. Results The dprx5 mutant flies were more resistant to bacterial infection than controls, while flies overexpressing dPrx5 were more susceptible. The enhanced resistance to bacteria was accompanied by rapid induction of the Imd-dependent antimicrobial peptides, phosphorylation of the JNK kinase Basket and altered transcriptional profiling of the transient response genes, puckered, ets21C and relish, while the opposite effects were observed in flies over-expressing dPrx5. Epistatic analysis of double mutants, using attacin D and Puckered as read outs of activation of the Imd and JNK pathways, implicated dPrx5 function in the control of the dTak1-JNK arm of immune signaling. Conclusions Differential effects on fly survivorship suggested a trade-off between the antioxidant and immune functions of dPrx5. Molecular and epistatic analyses identified dPrx5 as a negative regulator in the dTak1-JNK arm of immune signaling. General significance Our findings suggest that peroxiredoxins play an important modulatory role in the Drosophila immune response. PMID:20600624

  9. [Cystatin C--modulator of immune processes].

    PubMed

    Wittek, Natalia; Majewska, Ewa

    2010-01-01

    Cystatin C is a lowmolecular protein (13 kDa) that inhibits the activity of lysosomal cysteine proteinases with the strongest activity against cathepsin B and H. The recent experiments show that the level of cystatin C is independented of chronic and acute inflammatory process which frequently coexist with end stage renal diseases. Recent studies challange the theory because a higher concentration of cystatin C in serum correlated well with a higher concentration of inflammatory markers such as a CRP and fibrinogen in the patients. In vitro experiments on cultured monocytes and macrophages discovered that after stimulation by LPS and INF the expression of the cystatin C gene and synthesis of this protein was reduced. Cystatin C plays important modulatory function in regulation of the natural immunity, protecting our body against viruses, bacteries and parasites. Moreover, cystatin C binds the C4 component and modulates activation of the classical complement pathway. The experiments also show that cystatin C could influence non-specific immune response through the inhibition of the superoxide anion generation (respiratory burst), phagocytosis, chemotaxis and apoptosis of neutrophils. Similarly, the cystatin C can modulate the specific immune response through the inhibition of cathepsin S, bindining membrane receptors for TGF-beta or increasing MHC class II expression on dendritic cells.

  10. Avian biological clock - Immune system relationship.

    PubMed

    Markowska, Magdalena; Majewski, Paweł M; Skwarło-Sońta, Krystyna

    2017-01-01

    Biological rhythms in birds are driven by the master clock, which includes the suprachiasmatic nucleus, the pineal gland and the retina. Light/dark cycles are the cues that synchronize the rhythmic changes in physiological processes, including immunity. This review summarizes our investigations on the bidirectional relationships between the chicken pineal gland and the immune system. We demonstrated that, in the chicken, the main pineal hormone, melatonin, regulates innate immunity, maintains the rhythmicity of immune reactions and is involved in the seasonal changes in immunity. Using thioglycollate-induced peritonitis as a model, we showed that the activated immune system regulates the pineal gland by inhibition of melatonin production at the level of the key enzyme in its biosynthetic pathway, arylalkylamine-N-acetyltransferase (AANAT). Interleukin 6 and interleukin 18 seem to be the immune mediators influencing the pineal gland, directly inhibiting Aanat gene transcription and modulating expression of the clock genes Bmal1 and Per3, which in turn regulate Aanat.

  11. The immune system.

    PubMed

    Nicholson, Lindsay B

    2016-10-31

    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. © 2016 The Author(s).

  12. Modulation of DNA methylation states and infant immune system by dietary supplementation with ω-3 PUFA during pregnancy in an intervention study12345

    PubMed Central

    Lee, Ho-Sun; Barraza-Villarreal, Albino; Hernandez-Vargas, Hector; Sly, Peter D; Biessy, Carine; Ramakrishnan, Usha; Romieu, Isabelle; Herceg, Zdenko

    2013-01-01

    Background: Early-life exposures to tobacco smoke and some dietary factors have been identified to induce epigenetic changes in genes involved in allergy and asthma development. Omega-3 (n−3) polyunsaturated fatty acid (PUFA) intake during pregnancy could modulate key cytokines and T helper (Th) cell maturation; however, little is known about the mechanism by which ω-3 PUFA could have a beneficial effect in preventing inflammatory disorders. Objective: We sought to test whether prenatal dietary supplementation with ω-3 PUFA during pregnancy may modulate epigenetic states in the infant immune system. Design: This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg docosahexaenoic acid (DHA) or a placebo from 18 to 22 wk of gestation to parturition. We applied quantitative profiling of DNA methylation states in Th1, Th2, Th17, and regulatory T–relevant genes as well as LINE1 repetitive elements of cord blood mononuclear cells (n = 261). Results: No significant difference in promoter methylation levels was shown between ω-3 PUFA–supplemented and control groups for the genes analyzed; however, ω-3 PUFA supplementation was associated with changes in methylation levels in LINE1 repetitive elements (P = 0.03) in infants of mothers who smoked during pregnancy. Furthermore, an association between the promoter methylation levels of IFNγ and IL13 was modulated by ω-3 PUFA supplementation (P = 0.06). Conclusions: Our results indicate that maternal supplementation with ω-3 PUFA during pregnancy may modulate global methylation levels and the Th1/Th2 balance in infants. Therefore, the epigenetic mechanisms could provide attractive targets for prenatal modulation and prevention of inflammatory disorders and potentially other related diseases in childhood and adulthood. PMID:23761484

  13. Modulation of DNA methylation states and infant immune system by dietary supplementation with ω-3 PUFA during pregnancy in an intervention study.

    PubMed

    Lee, Ho-Sun; Barraza-Villarreal, Albino; Hernandez-Vargas, Hector; Sly, Peter D; Biessy, Carine; Ramakrishnan, Usha; Romieu, Isabelle; Herceg, Zdenko

    2013-08-01

    Early-life exposures to tobacco smoke and some dietary factors have been identified to induce epigenetic changes in genes involved in allergy and asthma development. Omega-3 (n-3) polyunsaturated fatty acid (PUFA) intake during pregnancy could modulate key cytokines and T helper (Th) cell maturation; however, little is known about the mechanism by which ω-3 PUFA could have a beneficial effect in preventing inflammatory disorders. We sought to test whether prenatal dietary supplementation with ω-3 PUFA during pregnancy may modulate epigenetic states in the infant immune system. This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg docosahexaenoic acid (DHA) or a placebo from 18 to 22 wk of gestation to parturition. We applied quantitative profiling of DNA methylation states in Th1, Th2, Th17, and regulatory T-relevant genes as well as LINE1 repetitive elements of cord blood mononuclear cells (n = 261). No significant difference in promoter methylation levels was shown between ω-3 PUFA-supplemented and control groups for the genes analyzed; however, ω-3 PUFA supplementation was associated with changes in methylation levels in LINE1 repetitive elements (P = 0.03) in infants of mothers who smoked during pregnancy. Furthermore, an association between the promoter methylation levels of IFNγ and IL13 was modulated by ω-3 PUFA supplementation (P = 0.06). Our results indicate that maternal supplementation with ω-3 PUFA during pregnancy may modulate global methylation levels and the Th1/Th2 balance in infants. Therefore, the epigenetic mechanisms could provide attractive targets for prenatal modulation and prevention of inflammatory disorders and potentially other related diseases in childhood and adulthood.

  14. Stem Cell-Derived Extracellular Vesicles and Immune-Modulation.

    PubMed

    Burrello, Jacopo; Monticone, Silvia; Gai, Chiara; Gomez, Yonathan; Kholia, Sharad; Camussi, Giovanni

    2016-01-01

    Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system.

  15. Stem Cell-Derived Extracellular Vesicles and Immune-Modulation

    PubMed Central

    Burrello, Jacopo; Monticone, Silvia; Gai, Chiara; Gomez, Yonathan; Kholia, Sharad; Camussi, Giovanni

    2016-01-01

    Extra-cellular vesicles (EVs) are bilayer membrane structures enriched with proteins, nucleic acids, and other active molecules and have been implicated in many physiological and pathological processes over the past decade. Recently, evidence suggests EVs to play a more dichotomic role in the regulation of the immune system, whereby an immune response may be enhanced or supressed by EVs depending on their cell of origin and its functional state. EVs derived from antigen (Ag)-presenting cells for instance, have been involved in both innate and acquired (or adaptive) immune responses, as Ag carriers or presenters, or as vehicles for delivering active signaling molecules. On the other hand, tumor and stem cell derived EVs have been identified to exert an inhibitory effect on immune responses by carrying immuno-modulatory effectors, such as transcriptional factors, non-coding RNA (Species), and cytokines. In addition, stem cell-derived EVs have also been reported to impair dendritic cell maturation and to regulate the activation, differentiation, and proliferation of B cells. They have been shown to control natural killer cell activity and to suppress the innate immune response (IIR). Studies reporting the role of EVs on T lymphocyte modulation are controversial. Discrepancy in literature may be due to stem cell culture conditions, methods of EV purification, EV molecular content, and functional state of both parental and target cells. However, mesenchymal stem cell-derived EVs were shown to play a more suppressive role by shifting T cells from an activated to a T regulatory phenotype. In this review, we will discuss how stem cell-derived EVs may contribute toward the modulation of the immune response. Collectively, stem cell-derived EVs mainly exhibit an inhibitory effect on the immune system. PMID:27597941

  16. Technique Selectively Represses Immune System

    MedlinePlus

    ... Research Matters December 3, 2012 Technique Selectively Represses Immune System Myelin (green) encases and protects nerve fibers (brown). A new technique prevents the immune system from attacking myelin in a mouse model of ...

  17. Systemic application of 3-methyladenine markedly inhibited atherosclerotic lesion in ApoE−/− mice by modulating autophagy, foam cell formation and immune-negative molecules

    PubMed Central

    Dai, Shen; Wang, Bo; Li, Wen; Wang, Liyang; Song, Xingguo; Guo, Chun; Li, Yulan; Liu, Fengming; Zhu, Faliang; Wang, Qun; Wang, Xiaoyan; Shi, Yongyu; Wang, Jianing; Zhao, Wei; Zhang, Lining

    2016-01-01

    A growing body of evidence demonstrates that autophagy, an evolutionarily conserved intracellular degradation process, is involved in the pathogenesis of atherosclerosis and has become a potential therapeutic target. Here we tested the effect of two inhibitors of phosphatidylinositol 3-kinase, 3-methyladenine (3-MA) and 2-(4-morpholinyl)-8-phenyl-chromone (LY294002), commonly used as inhibitors of autophagy, in atherosclerosis in apolipoprotein E−/− mice. Systemic application of 3-MA but not LY294002 markedly reduced the size of atherosclerotic plaque and increased the stability of lesions in high-fat diet-fed mice as compared with controls. Furthermore, 3-MA had multiple atheroprotective effects, including modulating macrophage autophagy and foam cell formation and altering the immune microenvironment. Long-term treatment with 3-MA promoted oxidized low-density lipoprotein (oxLDL)-induced macrophage autophagy and suppressed foam cell formation and cell viability in vitro. Furthermore, systemic application of 3-MA promoted lipid droplet breakdown and decreased apoptosis, most likely associated with autophagy. 3-MA treatment strikingly enhanced the expression of immune-negative molecules such as interleukin 10 (IL-10), transforming growth factor β and IL-35, as well as forkhead box P3 (Foxp3), the specific transcriptional factor for regulatory T cells, but did not affect the level of proinflammatory cytokines in the arterial wall. We provide strong evidence for the potential therapeutic benefit of 3-MA in inhibiting atherosclerosis development and improving plaque stability. PMID:27906187

  18. 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.

  19. Immune modulation of learning, memory, neural plasticity and neurogenesis.

    PubMed

    Yirmiya, Raz; Goshen, Inbal

    2011-02-01

    Over the past two decades it became evident that the immune system plays a central role in modulating learning, memory and neural plasticity. Under normal quiescent conditions, immune mechanisms are activated by environmental/psychological stimuli and positively regulate the remodeling of neural circuits, promoting memory consolidation, hippocampal long-term potentiation (LTP) and neurogenesis. These beneficial effects of the immune system are mediated by complex interactions among brain cells with immune functions (particularly microglia and astrocytes), peripheral immune cells (particularly T cells and macrophages), neurons, and neural precursor cells. These interactions involve the responsiveness of non-neuronal cells to classical neurotransmitters (e.g., glutamate and monoamines) and hormones (e.g., glucocorticoids), as well as the secretion and responsiveness of neurons and glia to low levels of inflammatory cytokines, such as interleukin (IL)-1, IL-6, and TNFα, as well as other mediators, such as prostaglandins and neurotrophins. In conditions under which the immune system is strongly activated by infection or injury, as well as by severe or chronic stressful conditions, glia and other brain immune cells change their morphology and functioning and secrete high levels of pro-inflammatory cytokines and prostaglandins. The production of these inflammatory mediators disrupts the delicate balance needed for the neurophysiological actions of immune processes and produces direct detrimental effects on memory, neural plasticity and neurogenesis. These effects are mediated by inflammation-induced neuronal hyper-excitability and adrenocortical stimulation, followed by reduced production of neurotrophins and other plasticity-related molecules, facilitating many forms of neuropathology associated with normal aging as well as neurodegenerative and neuropsychiatric diseases. Copyright © 2010 Elsevier Inc. All rights reserved.

  20. Low Dose Ionizing Radiation Modulates Immune Function

    SciTech Connect

    Nelson, Gregory A.

    2016-01-12

    In order to examine the effects of low dose ionizing radiation on the immune system we chose to examine an amplified adaptive cellular immunity response. This response is Type IV delayed-type hypersensitivity also called contact hypersensitivity. The agent fluorescein isothiocyanate (FITC) is a low molecular weight, lipophilic, reactive, fluorescent molecule that can be applied to the skin where it (hapten) reacts with proteins (carriers) to become a complete antigen. Exposure to FITC leads to sensitization which is easily measured as a hypersensitivity inflammatory reaction following a subsequent exposure to the ear. Ear swelling, eosinophil infiltration, immunoglobulin E production and cytokine secretion patterns characteristic of a “Th2 polarized” immune response are the components of the reaction. The reaction requires successful implementation of antigen processing and presentation by antigen presenting Langerhans cells, communication with naïve T lymphocytes in draining lymph nodes, expansion of activated T cell clones, migration of activated T cells to the circulation, and recruitment of memory T cells, macrophages and eosinophils to the site of the secondary challenge. Using this model our approach was to quantify system function rather than relying only on indirect biomarkers of cell. We measured the FITC-induced hypersensitivity reaction over a range of doses from 2 cGy to 2 Gy. Irradiations were performed during key events or prior to key events to deplete critical cell populations. In addition to quantifying the final inflammatory response, we assessed cell populations in peripheral blood and spleen, cytokine signatures, IgE levels and expression of genes associated with key processes in sensitization and elicitation/recall. We hypothesized that ionizing radiation would produce a biphasic effect on immune system function resulting in an enhancement at low doses and a depression at higher doses and suggested that this transition would occur in the

  1. Neural tube defects, folate, and immune modulation.

    PubMed

    Denny, Kerina J; Jeanes, Angela; Fathe, Kristin; Finnell, Richard H; Taylor, Stephen M; Woodruff, Trent M

    2013-09-01

    Periconceptional supplementation with folic acid has led to a significant worldwide reduction in the incidence of neural tube defects (NTDs). However, despite increasing awareness of the benefits of folic acid supplementation and the implementation of food fortification programs in many countries, NTDs continue to be a leading cause of perinatal morbidity and mortality worldwide. Furthermore, there exists a significant subgroup of women who appear to be resistant to the protective effects of folic acid supplementation. The following review addresses emerging clinical and experimental evidence for a role of the immune system in the etiopathogenesis of NTDs, with the aim of developing novel preventative strategies to further reduce the incidence of NTD-affected pregnancies. In particular, recent studies demonstrating novel roles and interactions between innate immune factors such as the complement cascade, neurulation, and folate metabolism are explored.

  2. Modulation of Primary Immune Response by Different Vaccine Adjuvants

    PubMed Central

    Ciabattini, Annalisa; Pettini, Elena; Fiorino, Fabio; Pastore, Gabiria; Andersen, Peter; Pozzi, Gianni; Medaglini, Donata

    2016-01-01

    Adjuvants contribute to enhancing and shaping the vaccine immune response through different modes of action. Here early biomarkers of adjuvanticity after primary immunization were investigated using four different adjuvants combined with the chimeric tuberculosis vaccine antigen H56. C57BL/6 mice were immunized by the subcutaneous route with different vaccine formulations, and the modulation of primary CD4+ T cell and B cell responses was assessed within draining lymph nodes, blood, and spleen, 7 and 12 days after priming. Vaccine formulations containing the liposome system CAF01 or a squalene-based oil-in-water emulsion (o/w squalene), but not aluminum hydroxide (alum) or CpG ODN 1826, elicited a significant primary antigen-specific CD4+ T cell response compared to antigen alone, 7 days after immunization. The effector function of activated CD4+ T cells was skewed toward a Th1/Th17 response by CAF01, while a Th1/Th2 response was elicited by o/w squalene. Differentiation of B cells in short-lived plasma cells, and subsequent early H56-specific IgG secretion, was observed in mice immunized with o/w squalene or CpG adjuvants. Tested adjuvants promoted the germinal center reaction with different magnitude. These results show that the immunological activity of different adjuvants can be characterized by profiling early immunization biomarkers after primary immunization. These data and this approach could give an important contribution to the rational development of heterologous prime–boost vaccine immunization protocols. PMID:27781036

  3. Modulation of HIV-1 immunity by adjuvants

    PubMed Central

    Moody, M. Anthony

    2014-01-01

    Purpose of review To summarize the role of adjuvants in eliciting desirable antibody responses against HIV-1 with particular emphasis on both historical context and recent developments. Recent findings Increased understanding of the role of pattern recognition receptors such as Toll-like receptors in recruiting and directing the immune system has increased the variety of adjuvant formulations being tested in animal models and humans. Across all vaccine platforms, adjuvant formulations have been shown to enhance desirable immune responses such as higher antibody titers and increased functional activity. Although no vaccine formulation has yet succeeded in eliciting broad neutralizing antibodies against HIV-1, the ability of adjuvants to direct the immune response to immunogens suggests they will be critically important in any successful HIV-1 vaccine. Summary The parallel development of adjuvants along with better HIV-1 immunogens will be needed for a successful AIDS vaccine. Additional comparative testing will be required to determine the optimal adjuvant and immunogen regimen that can elicit antibody responses capable of blocking HIV-1 transmission. PMID:24670321

  4. The immune system in hypertension.

    PubMed

    Harrison, David G

    2014-01-01

    Hypertension is generally attributed to perturbations of the vasculature, the kidney, and the central nervous system. During the past several years, it has become apparent that cells of the innate and adaptive immune system also contribute to this disease. Macrophages and T cells accumulate in the kidneys and vasculature of humans and experimental animals with hypertension, and likely contribute to end-organ damage. We have shown that mice lacking lymphocytes, such as recombinase-activating gene-deficient (RAG-1(-/-)) mice, have blunted hypertension in response to angiotensin II, increased salt levels, and norepinephrine. Adoptive transfer of T cells restores the blood pressure response to these stimuli. Others have shown that mice with severe combined immunodeficiency have blunted hypertension in response to angiotensin II. Deletion of the RAG gene in Dahl salt-sensitive rats reduces the hypertensive response to salt feeding. The central nervous system seems to orchestrate immune cell activation. We produced lesions of the anteroventral third ventricle and showed that these block T cell activation in response to angiotensin II. Likewise, we showed that genetic manipulation of reactive oxygen species in the subfornical organ modulates both hypertension and T cell activation. Current evidence indicates that production of cytokines including tumor necrosis factor alpha, interleukin 17, and interleukin 6 contribute to hypertension, likely by promoting vasoconstriction, production of reactive oxygen species, and sodium reabsorption in the kidney. We propose a working hypothesis linking the sympathetic nervous system, immune cells, the production of cytokines, and ultimately vascular and renal dysfunction, leading to augmentation of hypertension.

  5. Novel Immune Modulating Cellular Vaccine for Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    AWARD NUMBER: W81XWH-13-1-0423 TITLE: Novel immune modulating cellular vaccine for prostate cancer PRINCIPAL INVESTIGATOR: Smita Nair...2014 2. REPORT TYPE Annual 3. DATES COVERED 30 Sept 2013 to 29 Sept 2014 4. TITLE AND SUBTITLE Novel immune modulating cellular vaccine for...that will safely enhance vaccine -mediated immunity. This lead cellular therapy, called DC-PAPvac-C, consists of dendritic cells (DCs) co-transfected

  6. Platelets: essential components of the immune system

    PubMed Central

    Ali, Ramadan A.; Wuescher, Leah M.; Worth, Randall G.

    2016-01-01

    Platelets are anucleate cell fragments known for their central role in coagulation and vascular integrity. However, it is becoming increasingly clear that platelets contribute to diverse immunological processes extending beyond the traditional view of platelets as fragmentary mediators of hemostasis and thrombosis. There is recent evidence that platelets participate in: 1) intervention against microbial threats; 2) recruitment and promotion of innate effector cell functions; 3) modulating antigen presentation; and 4) enhancement of adaptive immune responses. In this way, platelets should be viewed as the underappreciated orchestrator of the immune system. This review will discuss recent and historical evidence regarding how platelets influence both innate and adaptive immune responses. PMID:27818580

  7. Immune modulation by parenteral lipid emulsions.

    PubMed

    Wanten, Geert J A; Calder, Philip C

    2007-05-01

    Total parenteral nutrition is the final option for nutritional support of patients with severe intestinal failure. Lipid emulsions constitute the main source of fuel calories and fatty acids (FAs) in parenteral nutrition formulations. However, adverse effects on patient outcomes have been attributed to the use of lipids, mostly in relation to impaired immune defenses and altered inflammatory responses. Over the years, this issue has remained in the limelight, also because technical advances have provided no safeguard against the most daunting problems, ie, infectious complications. Nevertheless, numerous investigations have failed to produce a clear picture of the immunologic characteristics of the most commonly used soybean oil-derived lipid emulsions, although their high content of n-6 polyunsaturated FAs (PUFAs) has been considered a drawback because of their proinflammatory potential. This concern initiated the development of emulsions in which part of the n-6 FA component is replaced by less bioactive FAs, such as coconut oil (rich in medium-chain saturated FAs) or olive oil (rich in the n-9 monounsaturated FA oleic acid). Another approach has been to use fish oil (rich in n-3 PUFA), the FAs of which have biological activities different from those of n-6 PUFAs. Recent studies on the modulation of host defenses and inflammation by fish-oil emulsions have yielded consistent data, which indicate that these emulsions may provide a tool to beneficially alter the course of immune-mediated conditions. Although most of these lipids have not yet become available on the US market, this review synthesizes available information on immunologic characteristics of the different lipids that currently can be applied via parenteral nutrition support.

  8. [Olive oil, immune system and infection].

    PubMed

    Puertollano, M A; Puertollano, E; Alvarez de Cienfuegos, G; de Pablo Martínez, Manuel Antonio

    2010-01-01

    Polyunsaturated fatty acids contribute to the suppression of immune system functions. For this reason, n-3 polyunsaturated fatty acids have been applied in the resolution of inflammatory disorders. Although the inhibition of several immune functions promotes beneficial effects on the human health, this state may lead to a significant reduction of immune protection against infectious microorganisms (viruses, bacteria, fungi and parasites). Nevertheless, less attention has been paid to the action of olive oil in immunonutrition. Olive oil, a main constituent of the Mediterranean diet, is capable of modulating several immune functions, but it does not reduce host immune resistance to infectious microorganisms. Based on these criteria, we corroborate that olive oil administration may exert beneficial effects on the human health and especially on immune system, because it contributes to the reduction of typical inflammatory activity observed in patients suffering from autoimmune disorders, but without exacerbating the susceptibility to pathogen agents. The administration of olive oil in lipid emulsions may exert beneficial effects on the health and particularly on the immune system of immunocompromised patients. Therefore, this fact acquires a crucial importance in clinical nutrition. This review contributes to clarify the interaction between the administration of diets containing olive oil and immune system, as well as to determine the effect promoted by this essential component of Mediterranean diet in the immunomodulation against an infectious agent.

  9. Structural characterization of an intestinal immune system-modulating arabino-3,6-galactan-like polysaccharide from the above-ground part of Astragalus membranaceus (Bunge).

    PubMed

    Lim, Jung Dae; Yu, Chang Yeon; Kim, Seung Hyun; Chung, Ill Min

    2016-01-20

    Arabino-3,6-galactan (AMA-1-b-PS2), an intestinal immunomodulatory compound, was purified from the above-ground portion of Astragalus membranaceus (Bunge). Its structure was characterized using sequential enzymatic digestion with exo-α-L-arabinofuranosidase (AFase) and exo-β-D-(1 → 3)-galactanase (GNase), producing small amounts of intermediate-sized and shorter oligosaccharide (AF-PS2-G2 and AF-PS2-G3) fractions, and a large GNase-resistant fraction (AF-PS2-G1). Simultaneous AFase and GNase digestion of the enzyme-resistant fraction produced two long fragments (AF3-PS2-G1-1-1 and AF3-PS2-G1-1-2). Products of GNase digestion of the upper fractions showed decreased intestinal immunomodulatory activity; the GNase-resistant fraction (AF-PS2-G1) retained significant activity. Sugar component, methylation, and FAB-MS analyses indicated that the oligosaccharides consisted of hexosyl tri- to hexa-decasaccharides and hexosyl di- to hepta-saccharides mainly comprising 6-linked Gal(f) and Gal(p); some were partially mono- or di-arabinosylated. These oligosaccharide fractions were attached to the non-reducing terminus of the β-D-(1 → 3)-galactan backbone as side chains at position 6. AMA-1-b-PS2 likely modulates both the systemic and gastric mucosal immune systems.

  10. Glycoinositolphospholipids from Leishmania braziliensis and L. infantum: Modulation of Innate Immune System and Variations in Carbohydrate Structure

    PubMed Central

    Assis, Rafael Ramiro; Ibraim, Izabela Coimbra; Noronha, Fátima Soares; Turco, Salvatore Joseph; Soares, Rodrigo Pedro

    2012-01-01

    The essential role of the lipophosphoglycan (LPG) of Leishmania in innate immune response has been extensively reported. However, information about the role of the LPG-related glycoinositolphospholipids (GIPLs) is limited, especially with respect to the New World species of Leishmania. GIPLs are low molecular weight molecules covering the parasite surface and are similar to LPG in sharing a common lipid backbone and a glycan motif containing up to 7 sugars. Critical aspects of their structure and functions are still obscure in the interaction with the vertebrate host. In this study, we evaluated the role of those molecules in two medically important South American species Leishmania infantum and L. braziliensis, causative agents of visceral (VL) and cutaneous Leishmaniasis (CL), respectively. GIPLs derived from both species did not induce NO or TNF-α production by non-primed murine macrophages. Additionally, primed macrophages from mice (BALB/c, C57BL/6, TLR2−/− and TLR4−/−) exposed to GIPLs from both species, with exception to TNF-α, did not produce any of the cytokines analyzed (IL1-β, IL-2, IL-4, IL-5, IL-10, IL-12p40, IFN-γ) or p38 activation. GIPLs induced the production of TNF-α and NO by C57BL/6 mice, primarily via TLR4. Pre incubation of macrophages with GIPLs reduced significantly the amount of NO and IL-12 in the presence of IFN-γ or lipopolysaccharide (LPS), which was more pronounced with L. braziliensis GIPLs. This inhibition was reversed after PI-specific phospholipase C treatment. A structural analysis of the GIPLs showed that L. infantum has manose rich GIPLs, suggestive of type I and Hybrid GIPLs while L. braziliensis has galactose rich GIPLs, suggestive of Type II GIPLs. In conclusion, there are major differences in the structure and composition of GIPLs from L. braziliensis and L. infantum. Also, GIPLs are important inhibitory molecules during the interaction with macrophages. PMID:22389743

  11. Microbial modulation of host immunity with the small molecule phosphorylcholine.

    PubMed

    Clark, Sarah E; Weiser, Jeffrey N

    2013-02-01

    All microorganisms dependent on persistence in a host for survival rely on either hiding from or modulating host responses to infection. The small molecule phosphorylcholine, or choline phosphate (ChoP), is used for both of these purposes by a wide array of bacterial and parasitic microbes. While the mechanisms underlying ChoP acquisition and expression are diverse, a unifying theme is the use of ChoP to reduce the immune response to infection, creating an advantage for ChoP-expressing microorganisms. In this minireview, we discuss several benefits of ChoP expression during infection as well as how the immune system fights back against ChoP-expressing pathogens.

  12. Immune-modulating effects of alpha-1 antitrypsin.

    PubMed

    Ehlers, Mario R

    2014-10-01

    Alpha-1 antitrypsin (AAT) is a circulating serine protease inhibitor (serpin) that inhibits neutrophil elastase in the lung, and AAT deficiency is associated with early-onset emphysema. AAT is also a liver-derived acute-phase protein that, in vitro and in vivo, reduces production of pro-inflammatory cytokines, inhibits apoptosis, blocks leukocyte degranulation and migration, and modulates local and systemic inflammatory responses. In monocytes, AAT has been shown to increase intracellular cAMP, regulate expression of CD14, and suppress NFκB nuclear translocation. These effects may be mediated by AAT's serpin activity or by other protein-binding activities. In preclinical models of autoimmunity and transplantation, AAT therapy prevents or reverses autoimmune disease and graft loss, and these effects are accompanied by tolerogenic changes in cytokine and transcriptional profiles and T cell subsets. This review highlights advances in our understanding of the immune-modulating effects of AAT and their potential therapeutic utility.

  13. Nanoparticles and the Immune System

    PubMed Central

    Zolnik, Banu S.; González-Fernández, África; Sadrieh, Nakissa; Dobrovolskaia, Marina A.

    2010-01-01

    Today nanotechnology is finding growing applications in industry, biology, and medicine. The clear benefits of using nanosized products in various biological and medical applications are often challenged by concerns about the lack of adequate data regarding their toxicity. One area of interest involves the interactions between nanoparticles and the components of the immune system. Nanoparticles can be engineered to either avoid immune system recognition or specifically inhibit or enhance the immune responses. We review herein reported observations on nanoparticle-mediated immunostimulation and immunosuppression, focusing on possible theories regarding how manipulation of particle physicochemical properties can influence their interaction with immune cells to attain desirable immunomodulation and avoid undesirable immunotoxicity. PMID:20016026

  14. Local Delivery System of Immune Modulating Drug for Unresectable Adenocarcinoma: In Vitro Experimental Study and In Vivo Animal Study

    SciTech Connect

    Lee, Don Haeng; Kang, Sung-Gwon Jeong, Seok; Yoon, Chang Jin; Choi, Jung-Ah; Byun, Ju Nam; Park, Jae Hyung; Lee, Kyu Back

    2006-10-15

    The purpose of the study was to evaluate the efficacy and safety of a developed drug delivery system containing OK-432 through in vitro and animal study. An OK-432-impregnated polycarbonate/polyurethane stent membrane was used to develop a drug delivery system (DDS) enabling the locoregional release of OK-432. Polyethyleneglycol was used as a detergent and porosity generator. The stability of OK-432 in solvent, releasing kinetics of drug, and cytotoxicity of the DDS were evaluated. OK-432-impregnated DDS was implanted in mice in which a human adenocarcinoma cell line was injected and grown in their back. Flow cytometry and enzyme-linked immunosorbent assay were used for quantifying the amount of drug. OK-432 exposed to phosphate-buffered saline and OK-432 exposed to N,N-dimethylacetamide showed similar results on dot graphs and histograms. However, OK-432 exposed to tetrahydrofurane showed different dot graphs and histograms, which means that the antigenicity of the drug was changed. The release rate of OK-432 was maintained at a constant level for 6 weeks. The local delivery of OK-432 was found to have an antitumor effect on a human adenocarcinoma cell line in an animal study, but no effect on this cell line in in vitro cell culture. Histologic examination showed minimal inflammatory reaction in surrounding tissue. Our study shows that local treatment using this OK-432 release system is safe and effective in reducing adenocarcinoma in a mouse model.

  15. Immune System (For Parents)

    MedlinePlus

    ... For example, the viruses that cause leukemia in cats or distemper in dogs don't affect humans. ... virus that causes HIV/AIDS — don't make cats or dogs sick. Innate immunity also includes the ...

  16. Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens

    DTIC Science & Technology

    2005-07-01

    AD Award Number: W81XWH-04-1-0668 TITLE: Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens PRINCIPAL INVESTIGATOR: Richard T...AND SUBTITLE 5a. CONTRACT NUMBER Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens 5b. GRANT NUMBER W81XWH-04-!1-0668 5c...neu-N mice can be readily applied to clinical trial development. The goal of the present work is to test the hypothesis that reproductive hormones can

  17. Dynamics of immune system vulnerabilities

    NASA Astrophysics Data System (ADS)

    Stromberg, Sean P.

    The adaptive immune system can be viewed as a complex system, which adapts, over time, to reflect the history of infections experienced by the organism. Understanding its operation requires viewing it in terms of tradeoffs under constraints and evolutionary history. It typically displays "robust, yet fragile" behavior, meaning common tasks are robust to small changes but novel threats or changes in environment can have dire consequences. In this dissertation we use mechanistic models to study several biological processes: the immune response, the homeostasis of cells in the lymphatic system, and the process that normally prevents autoreactive cells from entering the lymphatic system. Using these models we then study the effects of these processes interacting. We show that the mechanisms that regulate the numbers of cells in the immune system, in conjunction with the immune response, can act to suppress autoreactive cells from proliferating, thus showing quantitatively how pathogenic infections can suppress autoimmune disease. We also show that over long periods of time this same effect can thin the repertoire of cells that defend against novel threats, leading to an age correlated vulnerability. This vulnerability is shown to be a consequence of system dynamics, not due to degradation of immune system components with age. Finally, modeling a specific tolerance mechanism that normally prevents autoimmune disease, in conjunction with models of the immune response and homeostasis we look at the consequences of the immune system mistakenly incorporating pathogenic molecules into its tolerizing mechanisms. The signature of this dynamic matches closely that of the dengue virus system.

  18. Immune system stimulation by probiotics.

    PubMed

    Perdigon, G; Alvarez, S; Rachid, M; Agüero, G; Gobbato, N

    1995-07-01

    The immune system consists of organs and several cell types. Antigen interaction with these cells induces a cellular immune response mediated by activated cells and a humoral immune response mediated by antibodies. The cellular interactions are enhanced by adhesion molecules, and the activated cells release different cytokines. These complex cellular interactions induce a systemic immune response. If the antigen penetrates by the oral route, a secretory immune response is obtained, which is mediated by secretory IgA. The determination of the number of T or B cells, the quantitative or qualitative measure of the cytokines, antibody levels, or the study of cellular function such as phagocytic activity is used to evaluate the state of the immune system. The effects of lactic acid bacteria on the systemic immune response and on the secretory immune system are described. Potential health benefits of lactic acid bacteria include protection against enteric infections, use as an oral adjuvant, the immunopotentiator in malnutrition, and the prevention of chemically induced tumors. The results showed that Lactobacillus casei could prevent enteric infections and stimulate secretory IgA in malnourished animals, but could produce bacteria translocation. Yogurt could inhibit the growth of intestinal carcinoma through increased activity of IgA, T cells, and macrophages.

  19. Systems Biology and immune aging.

    PubMed

    O'Connor, José-Enrique; Herrera, Guadalupe; Martínez-Romero, Alicia; de Oyanguren, Francisco Sala; Díaz, Laura; Gomes, Angela; Balaguer, Susana; Callaghan, Robert C

    2014-11-01

    Many alterations of innate and adaptive immunity are common in the aging population, which reflect a deterioration of the immune system, and have lead to the terms "immune aging" or "immunosenescence". Systems Biology aims to the comprehensive knowledge of the structure, dynamics, control and design that define a given biological system. Systems Biology benefits from the continuous advances in the omics sciences, based on high-throughput and high-content technologies, as well as on bioinformatic tools for data mining and integration. The Systems Biology approach is becoming gradually used to propose and to test comprehensive models of aging, both at the level of the immune system and the whole organism. In this way, immune aging may be described by a dynamic view of the states and interactions of every individual cell and molecule of the immune system and their role in the context of aging and longevity. This mini-review presents a panoramics of the current strategies, tools and challenges for applying Systems Biology to immune aging. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. The innate immune system in human systemic lupus erythematosus.

    PubMed

    Weidenbusch, Marc; Kulkarni, Onkar P; Anders, Hans-Joachim

    2017-04-25

    Although the role of adaptive immune mechanisms, e.g. autoantibody formation and abnormal T-cell activation, has been long noted in the pathogenesis of human systemic lupus erythematosus (SLE), the role of innate immunity has been less well characterized. An intricate interplay between both innate and adaptive immune elements exists in protective anti-infective immunity as well as in detrimental autoimmunity. More recently, it has become clear that the innate immune system in this regard not only starts inflammation cascades in SLE leading to disease flares, but also continues to fuel adaptive immune responses throughout the course of the disease. This is why targeting the innate immune system offers an additional means of treating SLE. First trials assessing the efficacy of anti-type I interferon (IFN) therapy or modulators of pattern recognition receptor (PRR) signalling have been attempted. In this review, we summarize the available evidence on the role of several distinct innate immune elements, especially neutrophils and dendritic cells as well as the IFN system, as well as specific innate PRRs along with their signalling pathways. Finally, we highlight recent clinical trials in SLE addressing one or more of the aforementioned components of the innate immune system.

  1. Neural-endocrine-immune complex in the central modulation of tumorigenesis: facts, assumptions, and hypotheses.

    PubMed

    Mravec, Boris; Gidron, Yori; Kukanova, Barbara; Bizik, Jozef; Kiss, Alexander; Hulin, Ivan

    2006-11-01

    For the precise coordination of systemic functions, the nervous system uses a variety of peripherally and centrally localized receptors, which transmit information from internal and external environments to the central nervous system. Tight interconnections between the immune, nervous, and endocrine systems provide a base for monitoring and consequent modulation of immune system functions by the brain and vice versa. The immune system plays an important role in tumorigenesis. On the basis of rich interconnections between the immune, nervous and endocrine systems, the possibility that the brain may be informed about tumorigenesis is discussed in this review article. Moreover, the eventual modulation of tumorigenesis by central nervous system is also considered. Prospective consequences of the interactions between tumor and brain for diagnosis and therapy of cancer are emphasized.

  2. Testicular defense systems: immune privilege and innate immunity.

    PubMed

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

    2014-09-01

    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.

  3. Immune Response Modulation of Conjugated Agonists with Changing Linker Length.

    PubMed

    Ryu, Keun Ah; Slowinska, Katarzyna; Moore, Troy; Esser-Kahn, Aaron

    2016-12-16

    We report immune response modulation with linked Toll-like receptor (TLR) agonists. Conjugating two agonists of synergistic TLRs induce an increase in immune activity compared to equal molarity of soluble agonists. Additionally, varying the distance between the agonists by changing the linker length alters the level of macrophage NF-κB activity as well as primary bone marrow derived dendritic cell IL-6 production. This modulation is effected by the size of the agonists and the pairing of the stimulated TLRs. The sensitivity of linker-length-dependent immune activity of conjugated agonists provides the potential for developing application specific therapeutics.

  4. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota

    PubMed Central

    Peterson, C T; Sharma, V; Elmén, L; Peterson, S N

    2015-01-01

    The distal gut harbours ∼1013 bacteria, representing the most densely populated ecosystem known. The functional diversity expressed by these communities is enormous and relatively unexplored. The past decade of research has unveiled the profound influence that the resident microbial populations bestow to host immunity and metabolism. The evolution of these communities from birth generates a highly adapted and highly personalized microbiota that is stable in healthy individuals. Immune homeostasis is achieved and maintained due in part to the extensive interplay between the gut microbiota and host mucosal immune system. Imbalances of gut microbiota may lead to a number of pathologies such as obesity, type I and type II diabetes, inflammatory bowel disease (IBD), colorectal cancer (CRC) and inflammaging/immunosenscence in the elderly. In-depth understanding of the underlying mechanisms that control homeostasis and dysbiosis of the gut microbiota represents an important step in our ability to reliably modulate the gut microbiota with positive clinical outcomes. The potential of microbiome-based therapeutics to treat epidemic human disease is of great interest. New therapeutic paradigms, including second-generation personalized probiotics, prebiotics, narrow spectrum antibiotic treatment and faecal microbiome transplantation, may provide safer and natural alternatives to traditional clinical interventions for chronic diseases. This review discusses host–microbiota homeostasis, consequences of its perturbation and the associated challenges in therapeutic developments that lie ahead. PMID:25345825

  5. Immune homeostasis, dysbiosis and therapeutic modulation of the gut microbiota.

    PubMed

    Peterson, C T; Sharma, V; Elmén, L; Peterson, S N

    2015-03-01

    The distal gut harbours ∼10(13) bacteria, representing the most densely populated ecosystem known. The functional diversity expressed by these communities is enormous and relatively unexplored. The past decade of research has unveiled the profound influence that the resident microbial populations bestow to host immunity and metabolism. The evolution of these communities from birth generates a highly adapted and highly personalized microbiota that is stable in healthy individuals. Immune homeostasis is achieved and maintained due in part to the extensive interplay between the gut microbiota and host mucosal immune system. Imbalances of gut microbiota may lead to a number of pathologies such as obesity, type I and type II diabetes, inflammatory bowel disease (IBD), colorectal cancer (CRC) and inflammaging/immunosenscence in the elderly. In-depth understanding of the underlying mechanisms that control homeostasis and dysbiosis of the gut microbiota represents an important step in our ability to reliably modulate the gut microbiota with positive clinical outcomes. The potential of microbiome-based therapeutics to treat epidemic human disease is of great interest. New therapeutic paradigms, including second-generation personalized probiotics, prebiotics, narrow spectrum antibiotic treatment and faecal microbiome transplantation, may provide safer and natural alternatives to traditional clinical interventions for chronic diseases. This review discusses host-microbiota homeostasis, consequences of its perturbation and the associated challenges in therapeutic developments that lie ahead.

  6. Overview of the immune system.

    PubMed

    Medina, Kay L

    2016-01-01

    The immune system is designed to execute rapid, specific, and protective responses against foreign pathogens. To protect against the potentially harmful effects of autoreactive escapees that might arise during the course of the immune response, multiple tolerance checkpoints exist in both the primary and secondary lymphoid organs. Regardless, autoantibodies targeting neural antigens exist in multiple neurologic diseases. The goal of this introductory chapter is to provide a foundation of the major principles and components of the immune system as a framework to understanding autoimmunity and autoimmune neurologic disorders. A broad overview of: (1) innate mechanisms of immunity and their contribution in demyelinating diseases; (2) B and T lymphocytes as effector arms of the adaptive immune response and their contribution to the pathophysiology of neurologic diseases; and (3) emerging therapeutic modalities for treatment of autoimmune disease is provided.

  7. Immune modulation by helminth parasites of ruminants: implications for vaccine development and host immune competence.

    PubMed

    McNeilly, Tom N; Nisbet, Alasdair J

    2014-01-01

    Parasitic helminths reside in immunologically-exposed extracellular locations within their hosts, yet they are capable of surviving for extended periods. To enable this survival, these parasites have developed complex and multifaceted mechanisms to subvert or suppress host immunity. This review summarises current knowledge of immune modulation by helminth parasites of ruminants and the parasite-derived molecules involved in driving this modulation. Such immunomodulatory molecules have considerable promise as vaccine targets, as neutralisation of their function is predicted to enhance anti-parasite immunity and, as such, current knowledge in this area is presented herein. Furthermore, we summarise current evidence that, as well as affecting parasite-specific immunity, immune modulation by these parasites may also affect the ability of ruminant hosts to control concurrent diseases or mount effective responses to vaccination.

  8. Immune modulation by helminth parasites of ruminants: implications for vaccine development and host immune competence

    PubMed Central

    McNeilly, Tom N.; Nisbet, Alasdair J.

    2014-01-01

    Parasitic helminths reside in immunologically-exposed extracellular locations within their hosts, yet they are capable of surviving for extended periods. To enable this survival, these parasites have developed complex and multifaceted mechanisms to subvert or suppress host immunity. This review summarises current knowledge of immune modulation by helminth parasites of ruminants and the parasite-derived molecules involved in driving this modulation. Such immunomodulatory molecules have considerable promise as vaccine targets, as neutralisation of their function is predicted to enhance anti-parasite immunity and, as such, current knowledge in this area is presented herein. Furthermore, we summarise current evidence that, as well as affecting parasite-specific immunity, immune modulation by these parasites may also affect the ability of ruminant hosts to control concurrent diseases or mount effective responses to vaccination. PMID:25292481

  9. Modulation of inflammasome-mediated pulmonary immune activation by type I IFNs protects bone marrow homeostasis during systemic responses to Pneumocystis lung infection.

    PubMed

    Searles, Steve; Gauss, Katherine; Wilkison, Michelle; Hoyt, Teri R; Dobrinen, Erin; Meissner, Nicole

    2013-10-01

    Although acquired bone marrow failure (BMF) is considered a T cell-mediated autoimmune disease, possible innate immune defects as a cause for systemic immune deviations in response to otherwise innocuous infections have not been extensively explored. In this regard, we recently demonstrated an important role of type I IFNs in protecting hematopoiesis during systemic stress responses to the opportunistic fungal pathogen Pneumocystis in lymphocyte-deficient mice. Mice deficient in both lymphocytes and type I IFN receptor (IFrag(-/-) mice) develop rapidly progressing BMF due to accelerated bone marrow (BM) cell apoptosis associated with innate immune deviations in the BM in response to Pneumocystis lung infection. However, the communication pathway between lung and BM eliciting the induction of BMF in response to this strictly pulmonary infection has been unclear. In this study, we report that absence of an intact type I IFN system during Pneumocystis lung infection not only causes BMF in lymphocyte-deficient mice but also transient BM stress in lymphocyte-competent mice. This is associated with an exuberant systemic IFN-γ response. IFN-γ neutralization prevented Pneumocystis lung infection-induced BM depression in type I IFN receptor-deficient mice and prolonged neutrophil survival time in BM from IFrag(-/-) mice. IL-1β and upstream regulators of IFN-γ, IL-12, and IL-18 were also upregulated in lung and serum of IFrag(-/-) mice. In conjunction, there was exuberant inflammasome-mediated caspase-1 activation in pulmonary innate immune cells required for processing of IL-18 and IL-1β. Thus, absence of type I IFN signaling during Pneumocystis lung infection may result in deregulation of inflammasome-mediated pulmonary immune activation, causing systemic immune deviations triggering BMF in this model.

  10. Modulation of inflammasome-mediated pulmonary immune activation by type-I-IFNs protects bone marrow homeostasis during systemic responses to Pneumocystis lung infection

    PubMed Central

    Searles, Steve; Gauss, Katherine; Wilkison, Michelle; Hoyt, Teri R.; Dobrinen, Erin; Meissner, Nicole

    2013-01-01

    Although acquired bone marrow failure (BMF) is considered a T cell-mediated autoimmune disease, possible innate immune defects as a cause for systemic immune deviations in response to otherwise innocuous infections, have not been extensively explored. In this regard we recently demonstrated an important role of type-I-IFNs in protecting hematopoiesis during systemic stress responses to the opportunistic fungal pathogen Pneumocystis in lymphocyte-deficient mice. Mice deficient in both lymphocytes and type-I-IFN-receptor (IFrag−/− mice) develop rapidly progressing BMF due to accelerated bone marrow cell apoptosis associated with innate immune deviations in the bone marrow in response to Pneumocystis lung infection. However, the communication pathway between lung and bone marrow eliciting the induction of BMF in response to this strictly pulmonary infection has been unclear. Here we report that absence of an intact type-I-IFN-system during Pneumocystis lung infection not only causes BMF in lymphocyte-deficient mice but also transient bone marrow stress in lymphocyte-competent mice. This is associated with an exuberant systemic IFN-γ response. IFNγ neutralization prevented Pneumocystis lung infection-induced bone marrow depression in type-I-IFN-receptor-deficient (IFNAR−/−) mice, and prolonged neutrophil survival time in bone marrow from IFrag−/− mice. IL-1β and upstream regulators of IFNγ, IL-12 and IL-18, were also upregulated in lung and serum of IFrag−/− mice. In conjunction there was exuberant inflammasome-mediated caspase-1-activation in pulmonary innate immune cells required for processing of IL-18 and IL-1β. Thus, absence of type-I-IFN-signaling during Pneumocystis lung infection may result in deregulation of inflammasome-mediated pulmonary immune activation causing systemic immune deviations triggering BMF in this model. PMID:23975863

  11. Noise Immune Cavity Enhanced Optical Heterodyne Velocity Modulation Spectroscopy

    NASA Astrophysics Data System (ADS)

    Siller, Brian; Mills, Andrew; Porambo, Michael; McCall, Benjamin

    2011-06-01

    The technique of Cavity Enhanced Velocity Modulation Spectroscopy (CEVMS) has recently been developed. By demodulating the detector signal at twice the plasma modulation frequency (2f), the velocity-modulated ionic absorption signal can be extracted. Although the concentration-modulated excited neutral molecules are also observed at 2f, the ion and neutral signals can be distinguished and separated with phase-sensitive demodulation. The optical cavity provides two major benefits. It increases both the optical path length and the intracavity laser power by a factor of 2×Finesse/π. The multipass advantage allows for much longer path length than was previously possible with unidirectional multipass White cells. The power enhancement combined with perfectly overlapped counterpropagating beams within the cavity allows for sub-Doppler spectroscopy. Although CEVMS showed much potential, its sensitivity was ultimately limited by electronic noise from the plasma interfering with the cavity-locking electronics. We have further improved upon CEVMS by combining it with Noise Immune Cavity Enhanced Optical Heterodyne Molecular Spectroscopy (NICE-OHMS). The laser is frequency modulated at precisely an integer multiple of the free spectral range of the optical cavity; this allows the heterodyne sidebands to be coupled into the optical cavity. Heterodyne detection of the cavity leak-out is immune to noise in the laser-cavity lock, and 2f demodulation further decreases electronic noise in the system and retains ion-neutral discrimination. The additional level of modulation beyond ordinary CEVMS has the added advantage of enabling the observation of both absorption and dispersion signals simultaneously by using two RF mixers, each driving its own lock-in amplifier. In a single scan, four distinct signals can be obtained: absorption and dispersion for ions and excited neutrals. The technique has been demonstrated in the near-IR for N_2^+. B. M. Siller, A. A. Mills and B. J. Mc

  12. HSP90 and Immune Modulation in Cancer.

    PubMed

    Graner, Michael W

    2016-01-01

    Heat-shock protein 90 (HSP90) is a highly conserved molecular chaperone that plays prominent functional roles in nearly all aspects of cell biology. As a chaperone, it interacts with literally hundreds of "clients," many of which are important drivers, regulators, and promoters of cancer. Thus, HSP90 is a high-value target in the development of anticancer therapeutics. Despite its popularity, our overall knowledge of HSP90 in immune function has lagged behind its well-recognized tumor-supportive roles. The use of inhibitors of HSP90 as chemical biological probes has been invaluable in revealing important roles for the chaperone in multiple aspects of immune function. Given this critical link, we must now consider the question of how immune outcomes may be affected by the HSP90 inhibitors currently in clinical development for the treatment of cancer. This chapter will review some of the immunological aspects of HSP90 function in terms of its intracellular and extracellular roles in antigen presentation, immune effector cell tasks, and regulation of inflammatory processes. This review will further examine the value of HSP90 inhibitors within the context of cancer immunotherapy and will discuss how these drugs might be optimally utilized in combination with immune stimulatory approaches against cancer. © 2016 Elsevier Inc. All rights reserved.

  13. 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.

  14. The immune system and hypertension.

    PubMed

    Singh, Madhu V; Chapleau, Mark W; Harwani, Sailesh C; Abboud, Francois M

    2014-08-01

    A powerful interaction between the autonomic and the immune systems plays a prominent role in the initiation and maintenance of hypertension and significantly contributes to cardiovascular pathology, end-organ damage and mortality. Studies have shown consistent association between hypertension, proinflammatory cytokines and the cells of the innate and adaptive immune systems. The sympathetic nervous system, a major determinant of hypertension, innervates the bone marrow, spleen and peripheral lymphatic system and is proinflammatory, whereas the parasympathetic nerve activity dampens the inflammatory response through α7-nicotinic acetylcholine receptors. The neuro-immune synapse is bidirectional as cytokines may enhance the sympathetic activity through their central nervous system action that in turn increases the mobilization, migration and infiltration of immune cells in the end organs. Kidneys may be infiltrated by immune cells and mesangial cells that may originate in the bone marrow and release inflammatory cytokines that cause renal damage. Hypertension is also accompanied by infiltration of the adventitia and perivascular adipose tissue by inflammatory immune cells including macrophages. Increased cytokine production induces myogenic and structural changes in the resistance vessels, causing elevated blood pressure. Cardiac hypertrophy in hypertension may result from the mechanical afterload and the inflammatory response to resident or migratory immune cells. Toll-like receptors on innate immune cells function as sterile injury detectors and initiate the inflammatory pathway. Finally, abnormalities of innate immune cells and the molecular determinants of their activation that include toll-like receptor, adrenergic, cholinergic and AT1 receptors can define the severity of inflammation in hypertension. These receptors are putative therapeutic targets.

  15. Cystatins in Immune System

    PubMed Central

    Magister, Špela; Kos, Janko

    2013-01-01

    Cystatins comprise a large superfamily of related proteins with diverse biological activities. They were initially characterised as inhibitors of lysosomal cysteine proteases, however, in recent years some alternative functions for cystatins have been proposed. Cystatins possessing inhibitory function are members of three families, family I (stefins), family II (cystatins) and family III (kininogens). Stefin A is often linked to neoplastic changes in epithelium while another family I cystatin, stefin B is supposed to have a specific role in neuredegenerative diseases. Cystatin C, a typical type II cystatin, is expressed in a variety of human tissues and cells. On the other hand, expression of other type II cystatins is more specific. Cystatin F is an endo/lysosome targeted protease inhibitor, selectively expressed in immune cells, suggesting its role in processes related to immune response. Our recent work points on its role in regulation of dendritic cell maturation and in natural killer cells functional inactivation that may enhance tumor survival. Cystatin E/M expression is mainly restricted to the epithelia of the skin which emphasizes its prominent role in cutaneous biology. Here, we review the current knowledge on type I (stefins A and B) and type II cystatins (cystatins C, F and E/M) in pathologies, with particular emphasis on their suppressive vs. promotional function in the tumorigenesis and metastasis. We proposed that an imbalance between cathepsins and cystatins may attenuate immune cell functions and facilitate tumor cell invasion. PMID:23386904

  16. Cancer immune cycle: a video introduction to the interaction between cancer and the immune system.

    PubMed

    Preusser, Matthias; Berghoff, Anna S; Thallinger, Christiane; Zielinski, Christoph C

    2016-01-01

    This educational video discusses and visualises the key steps of the complex interaction between cancer and the immune system. Essential steps of the cancer immune cycle take place in the tumour itself and in regional lymph nodes, with immune cells travelling between these distinct sites. Antigen-presenting cells such as dendritic cells migrate into the tumour microenvironment and take up tumour antigens. Antigen-presenting cells travel to regional lymph nodes, where they present the tumour antigens to naïve T cells in order to initiate a tumour-specific T cell response. Activated tumour-specific T cells multiply by clonal expansion and enter the blood flow and travel from the regional lymph node to the tumour site. As soon as activated T cells arrive at the tumor site they start a tumour-specific immune response. Co-inhibitory receptors modulate the immune response and may be exploited by tumour cells to escape immunological destruction. In summary, the cancer immune cycle involves several pivotal steps that are essential for generation of a successful specific antitumour immune response. Importantly, dysfunction of a single step may interrupt the entire cycle, thus impairing the immune-mediated control of tumour growth. Immune modulatory therapies such as vaccines or immune checkpoint modulators target specific steps of the cancer immune cycle with the ultimate aim of facilitating an antitumour immune response.

  17. Psychoneuroimmunology--cross-talk between the immune and nervous systems.

    PubMed

    Ziemssen, Tjalf; Kern, Simone

    2007-05-01

    Psychoneuroimmunology is a relatively new field of study that investigates interactions between behaviour and the immune system, mediated by the endocrine and nervous systems. The immune and central nervous system (CNS) maintain extensive communication. On the one hand, the brain modulates the immune system by hardwiring sympathetic and parasympathetic nerves (autonomic nervous system) to lymphoid organs. On the other hand, neuroendocrine hormones such as corticotrophin-releasing hormone or substance P regulate cytokine balance. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and immune system-mediated disease.

  18. Validation of Immune Cell Modules in Multicellular Transcriptomic Data

    PubMed Central

    Heather, James M.; Byng-Maddick, Rachel; Guppy, Naomi; Ellis, Matthew; Turner, Carolin T.; Chain, Benjamin M.; Noursadeghi, Mahdad

    2017-01-01

    Numerous gene signatures, or modules have been described to evaluate the immune cell composition in transcriptomes of multicellular tissue samples. However, significant diversity in module gene content for specific cell types is associated with heterogeneity in their performance. In order to rank modules that best reflect their purported association, we have generated the modular discrimination index (MDI) score that assesses expression of each module in the target cell type relative to other cells. We demonstrate that MDI scores predict modules that best reflect independently validated differences in cellular composition, and correlate with the covariance between cell numbers and module expression in human blood and tissue samples. Our analyses demonstrate that MDI scores provide an ordinal summary statistic that reliably ranks the accuracy of gene expression modules for deconvolution of cell type abundance in transcriptional data. PMID:28045996

  19. Novel immune modulators used in hematology: impact on NK cells.

    PubMed

    Krieg, Stephanie; Ullrich, Evelyn

    2012-01-01

    There is a wide range of important pharmaceuticals used in treatment of cancer. Besides their known effects on tumor cells, there is growing evidence for modulation of the immune system. Immunomodulatory drugs (IMiDs(®)) play an important role in the treatment of patients with multiple myeloma or myelodysplastic syndrome and have already demonstrated antitumor, anti-angiogenic, and immunostimulating effects, in particular on natural killer (NK) cells. Tyrosine kinase inhibitors are directly targeting different kinases and are known to regulate effector NK cells and expression of NKG2D ligands (NKG2DLs) on tumor cells. Demethylating agents, histone deacetylases, and proteasome inhibitors interfere with the epigenetic regulation and protein degradation of malignant cells. There are first hints that these drugs also sensitize tumor cells to chemotherapy, radiation, and NK cell-mediated cytotoxicity by enhanced expression of TRAIL and NKG2DLs. However, these pharmaceuticals may also impair NK cell function in a dose- and time-dependent manner. In summary, this review provides an update on the effects of different novel molecules on the immune system focusing NK cells.

  20. 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

  1. Optical modulator system

    NASA Technical Reports Server (NTRS)

    Brand, J.

    1972-01-01

    The fabrication, test, and delivery of an optical modulator system which will operate with a mode-locked Nd:YAG laser indicating at either 1.06 or 0.53 micrometers is discussed. The delivered hardware operates at data rates up to 400 Mbps and includes a 0.53 micrometer electrooptic modulator, a 1.06 micrometer electrooptic modulator with power supply and signal processing electronics with power supply. The modulators contain solid state drivers which accept digital signals with MECL logic levels, temperature controllers to maintain a stable thermal environment for the modulator crystals, and automatic electronic compensation to maximize the extinction ratio. The modulators use two lithium tantalate crystals cascaded in a double pass configuration. The signal processing electronics include encoding electronics which are capable of digitizing analog signals between the limit of + or - 0.75 volts at a maximum rate of 80 megasamples per second with 5 bit resolution. The digital samples are serialized and made available as a 400 Mbps serial NRZ data source for the modulators. A pseudorandom (PN) generator is also included in the signal processing electronics. This data source generates PN sequences with lengths between 31 bits and 32,767 bits in a serial NRZ format at rates up to 400 Mbps.

  2. Reprogramming immune responses via microRNA modulation

    PubMed Central

    Cubillos-Ruiz, Juan R.; Rutkowski, Melanie R; Tchou, Julia; Conejo-Garcia, Jose R.

    2013-01-01

    It is becoming increasingly clear that there are unique sets of miRNAs that have distinct governing roles in several aspects of both innate and adaptive immune responses. In addition, new tools allow selective modulation of the expression of individual miRNAs, both in vitro and in vivo. Here, we summarize recent advances in our understanding of how miRNAs drive the activity of immune cells, and how their modulation in vivo opens new avenues for diagnostic and therapeutic interventions in multiple diseases, from immunodeficiency to cancer. PMID:25285232

  3. Brain Innate Immunity in the Regulation of Neuroinflammation: Therapeutic Strategies by Modulating CD200-CD200R Interaction Involve the Cannabinoid System

    PubMed Central

    Hernangómez, Miriam; Carrillo-Salinas, Francisco J; Mecha, Miriam; Correa, Fernando; Mestre, Leyre; Loría, Frida; Feliú, Ana; Docagne, Fabian; Guaza, Carmen

    2014-01-01

    The central nervous system (CNS) innate immune response includes an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons that is involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the CNS are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple sclerosis (MS) Alzheimer's disease (AD) being primary examples. Hence, it is important to identify the key regulatory mechanisms involved in the control of CNS innate immunity and which could be harnessed to explore novel therapeutic avenues. Neuroimmune regulatory proteins (NIReg) such as CD95L, CD200, CD47, sialic acid, complement regulatory proteins (CD55, CD46, fH, C3a), HMGB1, may control the adverse immune responses in health and diseases. In the absence of these regulators, when neurons die by apoptosis, become infected or damaged, microglia and infiltrating immune cells are free to cause injury as well as an adverse inflammatory response in acute and chronic settings. We will herein provide new emphasis on the role of the pair CD200-CD200R in MS and its experimental models: experimental autoimmune encephalomyelitis (EAE) and Theiler’s virus induced demyelinating disease (TMEV-IDD). The interest of the cannabinoid system as inhibitor of inflammation prompt us to introduce our findings about the role of endocannabinoids (eCBs) in promoting CD200-CD200 receptor (CD200R) interaction and the benefits caused in TMEV-IDD. Finally, we also review the current data on CD200-CD200R interaction in AD, as well as, in the aging brain. PMID:24588829

  4. Methylglyoxal modulates immune responses: relevance to diabetes.

    PubMed

    Price, Claire L; Hassi, Hafid O S Al; English, Nicholas R; Blakemore, Alexandra I F; Stagg, Andrew J; Knight, Stella C

    2010-06-01

    Increased methylglyoxal (MG) concentrations and formation of advanced glycation end-products (AGEs) are major pathways of glycaemic damage in diabetes, leading to vascular and neuronal complications. Diabetes patients also suffer increased susceptibility to many common infections, the underlying causes of which remain elusive. We hypothesized that immune glycation damage may account for this increased susceptibility. We previously showed that the reaction mixture (RM) for MG glycation of peptide blocks up regulation of CD83 in myeloid cells and inhibits primary stimulation of T cells. Here, we continue to investigate immune glycation damage, assessing surface and intracellular cytokine protein expression by flow cytometry, T-cell proliferation using a carboxyfluorescein succinimidyl ester assay, and mRNA levels by RT-PCR. We show that the immunomodulatory component of this RM was MG itself, with MG alone causing equivalent block of CD83 and loss of primary stimulation. Block of CD83 expression could be reversed by MG scavenger N-acetyl cysteine. Further, MG within RM inhibited stimulated production of interleukin (IL)-10 protein from myeloid cells plus interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha from T cells. Loss of IL-10 and IFN-gamma was confirmed by RT-PCR analysis of mRNA, while TNF-alpha message was raised. Loss of TNF-alpha protein was also shown by ELISA of culture supernatants. In addition, MG reduced major histocompatibility complex (MHC) class I expression on the surface of myeloid cells and increased their propensity to apoptose. We conclude that MG is a potent suppressor of myeloid and T-cell immune function and may be a major player in diabetes-associated susceptibility to infection.

  5. Innate immunity modulation in virus entry.

    PubMed

    Faure, Mathias; Rabourdin-Combe, Chantal

    2011-07-01

    Entry into a cell submits viruses to detection by pattern recognition receptors (PRRs) leading to an early innate anti-viral response. Several viruses evolved strategies to avoid or subvert PRR recognition at the step of virus entry to promote infection. Whereas viruses mostly escape from soluble PRR detection, endocytic/phagocytic PRRs, such as the mannose receptor or DC-SIGN, are commonly used for virus entry. Moreover, virion-incorporated proteins may also offer viruses a way to dampen anti-viral innate immunity upon virus entry, and entering viruses might usurp autophagy to improve their own infectivity. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Pneumonia - weakened immune system

    MedlinePlus

    ... treatments to remove fluid and mucus from the respiratory system are often needed. Outlook (Prognosis) Factors that may ... immunocompromised host Images Pneumococci organism Lungs The lungs Respiratory system References Donnelly JP, Blijlevens NMA, van der Velden ...

  7. Play the Immune System Defender Game

    MedlinePlus

    ... Nobel's Life and Work Teachers' Questionnaire The Immune System Play the Immune System Game About the game Granulocytes, macrophages and dendritic ... in the body. Read More » Readings The Immune System - Overview » The Immune System – in More Detail » The ...

  8. Cinobufagin Modulates Human Innate Immune Responses and Triggers Antibacterial Activity

    PubMed Central

    Xie, Shanshan; Spelmink, Laura; Codemo, Mario; Subramanian, Karthik; Pütsep, Katrin

    2016-01-01

    The traditional Chinese medicine Chan-Su is widely used for treatment of cancer and cardiovascular diseases, but also as a remedy for infections such as furunculosis, tonsillitis and acute pharyngitis. The clinical use of Chan-Su suggests that it has anti-infective effects, however, the mechanism of action is incompletely understood. In particular, the effect on the human immune system is poorly defined. Here, we describe previously unrecognized immunomodulatory activities of cinobufagin (CBG), a major bioactive component of Chan-Su. Using human monocyte-derived dendritic cells (DCs), we show that LPS-induced maturation and production of a number of cytokines was potently inhibited by CBG, which also had a pro-apoptotic effect, associated with activation of caspase-3. Interestingly, CBG triggered caspase-1 activation and significantly enhanced IL-1β production in LPS-stimulated cells. Finally, we demonstrate that CBG upregulates gene expression of the antimicrobial peptides (AMPs) hBD-2 and hBD-3 in DCs, and induces secretion of HNP1-3 and hCAP-18/LL-37 from neutrophils, potentiating neutrophil antibacterial activity. Taken together, our data indicate that CBG modulates the inflammatory phenotype of DCs in response to LPS, and triggers an antibacterial innate immune response, thus proposing possible mechanisms for the clinical effects of Chan-Su in anti-infective therapy. PMID:27529866

  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 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…

  11. Endothelin Receptors Expressed by Immune Cells Are Involved in Modulation of Inflammation and in Fibrosis: Relevance to the Pathogenesis of Systemic Sclerosis

    PubMed Central

    Elisa, Tinazzi; Antonio, Puccetti; Giuseppe, Patuzzo; Alessandro, Barbieri; Giuseppe, Argentino; Federico, Confente; Marzia, Dolcino; Ruggero, Beri; Giacomo, Marchi; Andrea, Ottria; Daniela, Righetti; Mariaelisa, Rampudda

    2015-01-01

    Endothelin-1 (ET-1) plays a pivotal role in vasoconstriction, fibrosis, and inflammation, the key features of systemic sclerosis (SSc). ET-1 receptors (ETA and ETB) are expressed on endothelial cells, smooth muscle cells, and fibroblasts, but their presence on immune cells has not been deeply investigated so far. Endothelin receptors antagonists such as bosentan have beneficial effects on vasoconstriction and fibrosis, but less is known about their potential anti-inflammatory effects. We studied the expression of ET-1 receptors on immune cells (T and B lymphocytes, monocytes, and neutrophils) and the link between ET-1 and inflammation in patients with SSc. We show here that ET-1 exerts a proinflammatory effect in CD4+ T cells, since it induces an increased IFN-γ production; preincubation with antagonists of both receptors reduces IFN-γ production. Moreover, following ET-1 stimulation, neutrophils produce proinflammatory mediators, thus amplifying the effects of activated CD4+ T cells. Our data indicate that ET-1 system is involved in the pathogenesis of inflammation and fibrosis typical of SSc, through the activation of T lymphocytes and neutrophils and the consequent release of proinflammatory and profibrotic cytokines. These findings suggest that dual ET-1 receptors antagonist therapy, besides its effect on vasculopathy, has a profound impact on the immune system favouring antiinflammatory and antifibrogenic effects. PMID:26090478

  12. Detection of innate immune response modulating impurities in therapeutic proteins.

    PubMed

    Haile, Lydia Asrat; Puig, Montserrat; Kelley-Baker, Logan; Verthelyi, Daniela

    2015-01-01

    Therapeutic proteins can contain multiple impurities, some of which are variants of the product, while others are derived from the cell substrate and the manufacturing process. Such impurities, even when present at trace levels, have the potential to activate innate immune cells in peripheral blood or embedded in tissues causing expression of cytokines and chemokines, increasing antigen uptake, facilitating processing and presentation by antigen presenting cells, and fostering product immunogenicity. Currently, while products are tested for host cell protein content, assays to control innate immune response modulating impurities (IIRMIs) in products are focused mainly on endotoxin and nucleic acids, however, depending on the cell substrate and the manufacturing process, numerous other IIRMI could be present. In these studies we assess two approaches that allow for the detection of a broader subset of IIRMIs. In the first, we use commercial cell lines transfected with Toll like receptors (TLR) to detect receptor-specific agonists. This method is sensitive to trace levels of IIRMI and provides information of the type of IIRMIs present but is limited by the availability of stably transfected cell lines and requires pre-existing knowledge of the IIRMIs likely to be present in the product. Alternatively, the use of a combination of macrophage cell lines of human and mouse origin allows for the detection of a broader spectrum of impurities, but does not identify the source of the activation. Importantly, for either system the lower limit of detection (LLOD) of impurities was similar to that of PBMC and it was not modified by the therapeutic protein tested, even in settings where the product had inherent immune modulatory properties. Together these data indicate that a cell-based assay approach could be used to screen products for the presence of IIRMIs and inform immunogenicity risk assessments, particularly in the context of comparability exercises.

  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. Approaches Mediating Oxytocin Regulation of the Immune System

    PubMed Central

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

    2017-01-01

    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

  15. Adaptation in the innate immune system and heterologous innate immunity.

    PubMed

    Martin, Stefan F

    2014-11-01

    The innate immune system recognizes deviation from homeostasis caused by infectious or non-infectious assaults. The threshold for its activation seems to be established by a calibration process that includes sensing of microbial molecular patterns from commensal bacteria and of endogenous signals. It is becoming increasingly clear that adaptive features, a hallmark of the adaptive immune system, can also be identified in the innate immune system. Such adaptations can result in the manifestation of a primed state of immune and tissue cells with a decreased activation threshold. This keeps the system poised to react quickly. Moreover, the fact that the innate immune system recognizes a wide variety of danger signals via pattern recognition receptors that often activate the same signaling pathways allows for heterologous innate immune stimulation. This implies that, for example, the innate immune response to an infection can be modified by co-infections or other innate stimuli. This "design feature" of the innate immune system has many implications for our understanding of individual susceptibility to diseases or responsiveness to therapies and vaccinations. In this article, adaptive features of the innate immune system as well as heterologous innate immunity and their implications are discussed.

  16. Dietary Bacillus subtilis FPTB13 and chitin, single or combined, modulate systemic and cutaneous mucosal immunity and resistance of catla, Catla catla (Hamilton) against edwardsiellosis.

    PubMed

    Sangma, Timothy; Kamilya, Dibyendu

    2015-12-01

    Effects of dietary administration of Bacillus subtilis FPTB13 and chitin, single or combined, on the systemic immunity, mucosal immunity and resistance of catla (Catla catla) against Edwardsiella tarda infection were investigated. The probiotic attributes of B. subtilis was tested by conducting antagonism study, safety in catla, in vitro immunomodulation and dietary immunomodulation. Results of these studies indicated the probiotic potential of the strain. From the preliminary dietary immunomodulation study, a dose of 10(9) B. subtilis cells g(-1) was selected for inclusion into diets for subsequent experiments. Experimental diets were prepared by adding B. subtilis (10(9) cells g(-1)), chitin (2%) and their combination to the basal diet. Different systemic and mucosal immunological parameters viz. oxygen radical production, myeloperoxidase content, lysozyme activity, total protein content and alkaline phosphatase activity showed significant enhancement (p<0.05) after 2 weeks of feeding with the combined diet. B. subtilis and chitin alone also significantly elevated most of the immune responses. All the diets significantly increased the resistance of catla against E. tarda challenge. The highest post-challenge survival was observed in combined group (i.e. 63.33%). In conclusion, B. subtilis and chitin, alone or combined, had a health ameliorating effect in catla. The results also collectively suggest the usefulness of applying a combined probiotic and immunostimulant supplemented diet to achieve greater benefits.

  17. big bang gene modulates gut immune tolerance in Drosophila.

    PubMed

    Bonnay, François; Cohen-Berros, Eva; Hoffmann, Martine; Kim, Sabrina Y; Boulianne, Gabrielle L; Hoffmann, Jules A; Matt, Nicolas; Reichhart, Jean-Marc

    2013-02-19

    Chronic inflammation of the intestine is detrimental to mammals. Similarly, constant activation of the immune response in the gut by the endogenous flora is suspected to be harmful to Drosophila. Therefore, the innate immune response in the gut of Drosophila melanogaster is tightly balanced to simultaneously prevent infections by pathogenic microorganisms and tolerate the endogenous flora. Here we describe the role of the big bang (bbg) gene, encoding multiple membrane-associated PDZ (PSD-95, Discs-large, ZO-1) domain-containing protein isoforms, in the modulation of the gut immune response. We show that in the adult Drosophila midgut, BBG is present at the level of the septate junctions, on the apical side of the enterocytes. In the absence of BBG, these junctions become loose, enabling the intestinal flora to trigger a constitutive activation of the anterior midgut immune response. This chronic epithelial inflammation leads to a reduced lifespan of bbg mutant flies. Clearing the commensal flora by antibiotics prevents the abnormal activation of the gut immune response and restores a normal lifespan. We now provide genetic evidence that Drosophila septate junctions are part of the gut immune barrier, a function that is evolutionarily conserved in mammals. Collectively, our data suggest that septate junctions are required to maintain the subtle balance between immune tolerance and immune response in the Drosophila gut, which represents a powerful model to study inflammatory bowel diseases.

  18. Immune Modulation in Primary Vaccinia virus Zoonotic Human Infections

    PubMed Central

    Gomes, Juliana Assis Silva; de Araújo, Fernanda Fortes; Trindade, Giliane de Souza; Quinan, Bárbara Resende; Drumond, Betânia Paiva; Ferreira, Jaqueline Maria Siqueira; Mota, Bruno Eduardo Fernandes; Nogueira, Maurício Lacerda; Kroon, Erna Geessien; Abrahão, Jônatas Santos; Côrrea-Oliveira, Rodrigo; da Fonseca, Flávio Guimarães

    2012-01-01

    In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+ cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans. PMID:22229039

  19. Modulation of Toll-like receptor signaling in innate immunity by natural products.

    PubMed

    Chen, Luxi; Yu, Jianhua

    2016-08-01

    For centuries, natural products and their derivatives have provided a rich source of compounds for the development of new immunotherapies in the treatment of human disease. Many of these compounds are currently undergoing clinical trials, particularly as anti-oxidative, anti-microbial, and anti-cancer agents. However, the function and mechanism of natural products in how they interact with our immune system has yet to be extensively explored. Natural immune modulators may provide the key to control and ultimately defeat disorders affecting the immune system. They can either up- or down-regulate the immune response with few undesired adverse effects. In this review, we summarize the recent advancements made in utilizing natural products for immunomodulation and their important molecular targets, members of the Toll-like receptor (TLR) family, in the innate immune system. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. 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.

  1. Control of adaptive immunity by the innate immune system

    PubMed Central

    Iwasaki, Akiko; Medzhitov, Ruslan

    2015-01-01

    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. PMID:25789684

  2. Modulation of immune response by organophosphorus pesticides: fishes as a potential model in immunotoxicology.

    PubMed

    Díaz-Resendiz, K J G; Toledo-Ibarra, G A; Girón-Pérez, M I

    2015-01-01

    Immune response is modulated by different substances that are present in the environment. Nevertheless, some of these may cause an immunotoxic effect. In this paper, the effect of organophosphorus pesticides (frequent substances spilled in aquatic ecosystems) on the immune system of fishes and in immunotoxicology is reviewed. Furthermore, some cellular and molecular mechanisms that might be involved in immunoregulation mechanisms of organophosphorus pesticides are discussed.

  3. Modulation of Immune Response by Organophosphorus Pesticides: Fishes as a Potential Model in Immunotoxicology

    PubMed Central

    Díaz-Resendiz, K. J. G.; Toledo-Ibarra, G. A.; Girón-Pérez, M. I.

    2015-01-01

    Immune response is modulated by different substances that are present in the environment. Nevertheless, some of these may cause an immunotoxic effect. In this paper, the effect of organophosphorus pesticides (frequent substances spilled in aquatic ecosystems) on the immune system of fishes and in immunotoxicology is reviewed. Furthermore, some cellular and molecular mechanisms that might be involved in immunoregulation mechanisms of organophosphorus pesticides are discussed. PMID:25973431

  4. Obesity, inflammation and the immune system.

    PubMed

    de Heredia, Fátima Pérez; Gómez-Martínez, Sonia; Marcos, Ascensión

    2012-05-01

    Obesity shares with most chronic diseases the presence of an inflammatory component, which accounts for the development of metabolic disease and other associated health alterations. This inflammatory state is reflected in increased circulating levels of pro-inflammatory proteins, and it occurs not only in adults but also in adolescents and children. The chronic inflammatory response has its origin in the links existing between the adipose tissue and the immune system. Obesity, like other states of malnutrition, is known to impair the immune function, altering leucocyte counts as well as cell-mediated immune responses. In addition, evidence has arisen that an altered immune function contributes to the pathogenesis of obesity. This review attempts to briefly comment on the various plausible explanations that have been proposed for the phenomenon: (1) the obesity-associated increase in the production of leptin (pro-inflammatory) and the reduction in adiponectin (anti-inflammatory) seem to affect the activation of immune cells; (2) NEFA can induce inflammation through various mechanisms (such as modulation of adipokine production or activation of Toll-like receptors); (3) nutrient excess and adipocyte expansion trigger endoplasmic reticulum stress; and (4) hypoxia occurring in hypertrophied adipose tissue stimulates the expression of inflammatory genes and activates immune cells. Interestingly, data suggest a greater impact of visceral adipose tissue and central obesity, rather than total body fat, on the inflammatory process. In summary, there is a positive feedback loop between local inflammation in adipose tissue and altered immune response in obesity, both contributing to the development of related metabolic complications.

  5. CRISPR adaptive immune systems of Archaea.

    PubMed

    Vestergaard, Gisle; Garrett, Roger A; Shah, Shiraz A

    2014-01-01

    CRISPR adaptive immune systems were analyzed for all available completed genomes of archaea, which included representatives of each of the main archaeal phyla. Initially, all proteins encoded within, and proximal to, CRISPR-cas loci were clustered and analyzed using a profile-profile approach. Then cas genes were assigned to gene cassettes and to functional modules for adaptation and interference. CRISPR systems were then classified primarily on the basis of their concatenated Cas protein sequences and gene synteny of the interference modules. With few exceptions, they could be assigned to the universal Type I or Type III systems. For Type I, subtypes I-A, I-B, and I-D dominate but the data support the division of subtype I-B into two subtypes, designated I-B and I-G. About 70% of the Type III systems fall into the universal subtypes III-A and III-B but the remainder, some of which are phyla-specific, diverge significantly in Cas protein sequences, and/or gene synteny, and they are classified separately. Furthermore, a few CRISPR systems that could not be assigned to Type I or Type III are categorized as variant systems. Criteria are presented for assigning newly sequenced archaeal CRISPR systems to the different subtypes. Several accessory proteins were identified that show a specific gene linkage, especially to Type III interference modules, and these may be cofunctional with the CRISPR systems. Evidence is presented for extensive exchange having occurred between adaptation and interference modules of different archaeal CRISPR systems, indicating the wide compatibility of the functionally diverse interference complexes with the relatively conserved adaptation modules.

  6. Systems biology of innate immunity

    PubMed Central

    Zak, Daniel E.; Aderem, Alan

    2009-01-01

    Summary Systems biology is the comprehensive and quantitative analysis of the interactions between all of the components of biological systems over time. Systems biology involves an iterative cycle, in which emerging biological problems drive the development of new technologies and computational tools. These technologies and tools then open new frontiers that revolutionize biology. Innate immunity is well suited for systems analysis, because the relevant cells can be isolated in various functional states and their interactions can be reconstituted in a biologically meaningful manner. Application of the tools of systems biology to the innate immune system will enable comprehensive analysis of the complex interactions that maintain the difficult balance between host defense and inflammatory disease. In this review, we discuss innate immunity in the context of the systems biology concepts, emergence, robustness, and modularity, and we describe emerging technologies we are applying in our systems-level analyses. These technologies include genomics, proteomics, computational analysis, forward genetics screens, and analyses that link human genetic polymorphisms to disease resistance. PMID:19120490

  7. 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.

  8. Tissue engineering tools for modulation of the immune response

    PubMed Central

    Boehler, Ryan M.; Graham, John G.; Shea, Lonnie D.

    2012-01-01

    Tissue engineering scaffolds have emerged as a powerful tool within regenerative medicine. These materials are being designed to create environments that promote regeneration through a combination of: (i) scaffold architecture, (ii) the use of scaffolds as vehicles for transplanting progenitor cells, and/or (iii) localized delivery of inductive factors or genes encoding for these inductive factors. This review describes the techniques associated with each of these components. Additionally, the immune response is increasingly recognized as a factor influencing regeneration. The immune reaction to an implant begins with an acute response to the injury and innate recognition of foreign materials, with the subsequent chronic immune response involving specific recognition of antigens (e.g., transplanted cells) by the adaptive immune response, which can eventually lead to rejection of the implant. Thus, we also describe the impact of each component on the immune response, and strategies (e.g., material design, anti-inflammatory cytokine delivery, and immune cell recruitment/transplantation) to modulate, yet not eliminate, the local immune response in order to promote regeneration, which represents another important tool for regenerative medicine. PMID:21988690

  9. Energetics and the immune system

    PubMed Central

    Reiches, Meredith W.; Prentice, Andrew M.; Moore, Sophie E.; Ellison, Peter T.

    2017-01-01

    Abstract Background and objectives: The human immune system is an ever-changing composition of innumerable cells and proteins, continually ready to respond to pathogens or insults. The cost of maintaining this state of immunological readiness is rarely considered. In this paper we aim to discern a cost to non-acute immune function by investigating how low levels of C-reactive protein (CRP) relate to other energetic demands and resources in adolescent Gambian girls. Methodology: Data from a longitudinal study of 66 adolescent girls was used to test hypotheses around investment in immune function. Non-acute (under 2 mg/L) CRP was used as an index of immune function. Predictor variables include linear height velocity, adiposity, leptin, and measures of energy balance. Results: Non-acute log CRP was positively associated with adiposity (β = 0.16, P < 0.001, R2 = 0.17) and levels of the adipokine leptin (β = 1.17, P = 0.006, R2 = 0.09). CRP was also negatively associated with increased investment in growth, as measured by height velocity (β = −0.58, P < 0.001, R2 = 0.13) and lean mass deposition β = −0.42, P = 0.005, R2 = 0.08). Relationships between adiposity and growth explained some, but not all, of this association. We do not find that CRP was related to energy balance. Conclusions and implications: These data support a hypothesis that investment in non-acute immune function is facultative, and sensitive to energetic resources and demands. We also find support for an adaptive association between the immune system and adipose tissue. PMID:28003312

  10. Priming in Systemic Plant Immunity

    SciTech Connect

    Jung, Ho Won; Tschaplinski, Timothy J; Wang, Lin; Glazebrook, Jane; Greenberg, Jean T.

    2009-01-01

    Upon local infection, plants possess inducible systemic defense responses against their natural enemies. Bacterial infection results in the accumulation to high levels of the mobile metabolite C9-dicarboxylic acid azelaic acid in the vascular sap of Arabidopsis. Azelaic acid confers local and systemic resistance against Pseudomonas syringae. The compound primes plants to strongly accumulate salicylic acid (SA), a known defense signal, upon infection. Mutation of a gene induced by azelaic acid (AZI1) results in the specific loss in plants of systemic immunity triggered by pathogen or azelaic acid and of the priming of SA induction. AZI1, a predicted secreted protein, is also important for generating vascular sap that confers disease resistance. Thus, azelaic acid and AZI1 comprise novel components of plant systemic immunity involved in priming defenses.

  11. Modulation of immune response in experimental Chagas disease.

    PubMed

    Basso, Beatriz

    2013-02-20

    Trypanosoma cruzi (T. cruzi), the etiological agent of Chagas disease, affects nearly 18 million people in Latin America and 90 million are at risk of infection. The parasite presents two stages of medical importance in the host, the amastigote, intracellular replicating form, and the extracellular trypomastigote, the infective form. Thus infection by T. cruzi induces a complex immune response that involves effectors and regulatory mechanisms. That is why control of the infection requires a strong humoral and cellular immune response; hence, the outcome of host-parasite interaction in the early stages of infection is extremely important. A critical event during this period of the infection is innate immune response, in which the macrophage's role is vital. Thus, after being phagocytized, the parasite is able to develop intracellularly; however, during later periods, these cells induce its elimination by means of toxic metabolites. In turn, as the infection progresses, adaptive immune response mechanisms are triggered through the TH1 and TH2 responses. Finally, T. cruzi, like other protozoa such as Leishmania and Toxoplasma, have numerous evasive mechanisms to the immune response that make it possible to spread around the host. In our Laboratory we have developed a vaccination model in mice with Trypanosoma rangeli, nonpathogenic to humans, which modulates the immune response to infection by T. cruzi, thus protecting them. Vaccinated animals showed an important innate response (modulation of NO and other metabolites, cytokines, activation of macrophages), a strong adaptive cellular response and significant increase in specific antibodies. The modulation caused early elimination of the parasites, low parasitaemia, the absence of histological lesions and high survival rates. Even though progress has been made in the knowledge of some of these mechanisms, new studies must be conducted which could target further prophylactic and therapeutic trials against T. cruzi

  12. Induction of mucosal immunity through systemic immunization: Phantom or reality?

    PubMed Central

    Su, Fei; Patel, Girishchandra B.; Hu, Songhua; Chen, Wangxue

    2016-01-01

    ABSTRACT Generation of protective immunity at mucosal surfaces can greatly assist the host defense against pathogens which either cause disease at the mucosal epithelial barriers or enter the host through these surfaces. Although mucosal routes of immunization, such as intranasal and oral, are being intensely explored and appear promising for eliciting protective mucosal immunity in mammals, their application in clinical practice has been limited due to technical and safety related challenges. Most of the currently approved human vaccines are administered via systemic (such as intramuscular and subcutaneous) routes. Whereas these routes are acknowledged as being capable to elicit antigen-specific systemic humoral and cell-mediated immune responses, they are generally perceived as incapable of generating IgA responses or protective mucosal immunity. Nevertheless, currently licensed systemic vaccines do provide effective protection against mucosal pathogens such as influenza viruses and Streptococcus pneumoniae. However, whether systemic immunization induces protective mucosal immunity remains a controversial topic. Here we reviewed the current literature and discussed the potential of systemic routes of immunization for the induction of mucosal immunity. PMID:26752023

  13. Neutrophils: Between Host Defence, Immune Modulation, and Tissue Injury

    PubMed Central

    Kruger, Philipp; Saffarzadeh, Mona; Weber, Alexander N. R.; Rieber, Nikolaus; Radsak, Markus; von Bernuth, Horst; Benarafa, Charaf; Roos, Dirk; Skokowa, Julia; Hartl, Dominik

    2015-01-01

    Neutrophils, the most abundant human immune cells, are rapidly recruited to sites of infection, where they fulfill their life-saving antimicrobial functions. While traditionally regarded as short-lived phagocytes, recent findings on long-term survival, neutrophil extracellular trap (NET) formation, heterogeneity and plasticity, suppressive functions, and tissue injury have expanded our understanding of their diverse role in infection and inflammation. This review summarises our current understanding of neutrophils in host-pathogen interactions and disease involvement, illustrating the versatility and plasticity of the neutrophil, moving between host defence, immune modulation, and tissue damage. PMID:25764063

  14. Bifidobacterium bifidum PRL2010 Modulates the Host Innate Immune Response

    PubMed Central

    Turroni, Francesca; Taverniti, Valentina; Ruas-Madiedo, Patricia; Duranti, Sabrina; Guglielmetti, Simone; Lugli, Gabriele Andrea; Gioiosa, Laura; Palanza, Paola; Margolles, Abelardo; van Sinderen, Douwe

    2014-01-01

    Here, we describe data obtained from transcriptome profiling of human cell lines and intestinal cells of a murine model upon exposure and colonization, respectively, with Bifidobacterium bifidum PRL2010. Significant changes were detected in the transcription of genes that are known to be involved in innate immunity. Furthermore, results from enzyme-linked immunosorbent assays (ELISAs) showed that exposure to B. bifidum PRL2010 causes enhanced production of interleukin 6 (IL-6) and IL-8 cytokines, presumably through NF-κB activation. The obtained global transcription profiles strongly suggest that Bifidobacterium bifidum PRL2010 modulates the innate immune response of the host. PMID:24242237

  15. Beta-glucan recognition by the innate immune system.

    PubMed

    Goodridge, Helen S; Wolf, Andrea J; Underhill, David M

    2009-07-01

    Beta-glucans are recognized by the innate immune system. This recognition plays important roles in host defense and presents specific opportunities for clinical modulation of the host immune response. Neutrophils, macrophages, and dendritic cells among others express several receptors capable of recognizing beta-glucan in its various forms. This review explores what is currently known about beta-glucan recognition and how this recognition stimulates immune responses. Special emphasis is placed on Dectin-1, as we know the most about how this key beta-glucan receptor translates recognition into intracellular signaling, stimulates cellular responses, and participates in orchestrating the adaptive immune response.

  16. 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

  17. Leptin as immune mediator: Interaction between neuroendocrine and immune system.

    PubMed

    Procaccini, Claudio; La Rocca, Claudia; Carbone, Fortunata; De Rosa, Veronica; Galgani, Mario; Matarese, Giuseppe

    2017-01-01

    Leptin is an adipocyte-derived hormone/cytokine that links nutritional status with neuroendocrine and immune functions. Initially described as an anti-obesity hormone, leptin has subsequently been shown to exert pleiotropic effects, being also able to influence haematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect both innate and adaptive immunity, by inducing a pro-inflammatory response and thus playing a key role in the regulation of the pathogenesis of several autoimmune/inflammatory diseases. In this review, we discuss the most recent advances on the role of leptin as immune-modulator in mammals and we also provide an overview on its main functions in non-mammalian vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. mTOR signaling, Tregs and immune modulation

    PubMed Central

    Chapman, Nicole M; Chi, Hongbo

    2015-01-01

    Foxp3+ Tregs are central regulators of immune tolerance. As dysregulated Treg responses contribute to disease pathogenesis, novel approaches to target the immunomodulatory functions of Tregs are currently under investigation. mTORC1 and mTORC2 are therapeutic targets of interest. Recent studies revealed that mTOR signaling impacts conventional T-cell homeostasis, activation and differentiation. Moreover, mTOR controls the differentiation and functions of Tregs, suggesting that its activity could be targeted to modulate Treg responses. Here, we summarize how Tregs suppress immune responses, their roles in disease development and methods used to alter their functions therapeutically. We also discuss the diverse effects exerted by mTOR inhibition on the development, homeostasis, and functions of conventional T cells and Tregs. We conclude with a discussion of how modulation of mTOR activity in Tregs may be therapeutically beneficial or detrimental in different disease settings. PMID:25524385

  19. Immune modulation using transdermal photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Levy, Julia G.; Chowdhary, R. K.; Ratkay, Leslie G.; Waterfield, Douglas; Obochi, Modestus; Leong, Simon; Hunt, David W. C.; Chan, Agnes H.

    1995-01-01

    The photosensitizer benzoporphyrin derivative monoacid ring A (VerteporfinR or BPD) has maximum absorption characteristics (690 nm) and biodistribution characteristics which permit activation of the drug in capillaries of the skin without causing skin photosensitivity (transdermal PDT). This permits targeting of cells in the circulation for selective ablation. Since BPD has been shown to accumulate preferentially in activated lymphocytes and monocytes, studies have been undertaken to determine the effect of transdermal PDT on murine models for rheumatoid arthritis (the MRL/lpr adjuvant enhanced model) and multiple sclerosis (the experimental allergic encephalomyelitis (EAE) model in PL mice). Localized transdermal PDT with BPD was found to be completely successful in preventing the development of adjuvant enhanced arthritis in the MRL/lpr mouse as well as improving the underlying arthritic condition of these animals. In the EAE model, in which an adoptive transfer system was used, it was found that transdermal PDT of recipients was effective in preventing EAE if treatments were implemented up to 24 hours after cell transfer but was not effective if given later, indicating the requirement for circulating T cells for effective treatment.

  20. Role of the mu opioid receptor in opioid modulation of immune function

    PubMed Central

    Ninković, Jana; Roy, Sabita

    2014-01-01

    SUMMARY Endogenous opioids are synthesized in vivo in order to modulate pain mechanisms and inflammatory pathways. Endogenous and exogenous opioids mediate analgesia in response to painful stimuli by binding to opioid receptors on neuronal cells. However, wide distribution of opioid receptors on tissues and organ systems outside the CNS, such as the cells of the immune system, indicate that opioids are capable of exerting additional effects in the periphery, such as immunomodulation. The increased prevalence of infections in opioid abusers based epidemiological studies further highlights the immunosuppressive effects of opioids. In spite of their many debilitating side effects, prescription opioids remain a gold standard for treatment of chronic pain. Therefore, given the prevalence of opioid use and abuse, opioid mediated immune suppression presents a serious concern in our society today. It is imperative to understand the mechanisms by which exogenous opioids modulate immune processes. In this review we will discuss the role of opioid receptors and their ligands in mediating immune suppressive functions. We will summarize recent studies on direct and indirect opioid modulation of the cells of the immune system as well as the role of opioids in exacerbation of certain disease states. PMID:22170499

  1. Enteral nutrition and immune modulation of acute pancreatitis.

    PubMed

    Hegazi, Refaat A; DeWitt, Tiffany

    2014-11-21

    Enteral nutrition has been strongly recommended by major scientific societies for the nutritional management of patients with acute pancreatitis. Providing severe acute pancreatitis patients with enteral nutrition within the first 24-48 h of hospital admission can help improve outcomes compared to parenteral nutrition and no feeding. New research is focusing in on when and what to feed to best improve outcomes for acute pancreatitis patients. Early enteral nutrition have the potential to modulate the immune responses. Despite this consistent evidence of early enteral nutrition in patients with acute pancreatitis, clinical practice continues to vary due to individual clinician preference. Achieving the immune modulating effects of enteral nutrition heavily depend on proper placement of the feeding tube and managing any tube feeding associated complications. The current article reviews the immune modulating effects of enteral nutrition and pro- and prebiotics and suggests some practical tools that help improve the patient adherence and tolerance to the tube feeding. Proper selection of the type of the tube, close monitoring of the tube for its placement, patency and securing its proper placement and routine checking the gastric residual volume could all help improve the outcome. Using peptide-based and high medium chain triglycerides feeding formulas help improving feeding tolerance.

  2. Retinoic Acid as a Modulator of T Cell Immunity

    PubMed Central

    Bono, Maria Rosa; Tejon, Gabriela; Flores-Santibañez, Felipe; Fernandez, Dominique; Rosemblatt, Mario; Sauma, Daniela

    2016-01-01

    Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, epithelial surface integrity, erythrocyte production, reproduction, and normal immune function. Vitamin A deficiency is one of the most common micronutrient deficiencies worldwide and is associated with defects in adaptive immunity. Reports from epidemiological studies, clinical trials and experimental studies have clearly demonstrated that vitamin A plays a central role in immunity and that its deficiency is the cause of broad immune alterations including decreased humoral and cellular responses, inadequate immune regulation, weak response to vaccines and poor lymphoid organ development. In this review, we will examine the role of vitamin A in immunity and focus on several aspects of T cell biology such as T helper cell differentiation, function and homing, as well as lymphoid organ development. Further, we will provide an overview of the effects of vitamin A deficiency in the adaptive immune responses and how retinoic acid, through its effect on T cells can fine-tune the balance between tolerance and immunity. PMID:27304965

  3. Retinoic Acid as a Modulator of T Cell Immunity.

    PubMed

    Bono, Maria Rosa; Tejon, Gabriela; Flores-Santibañez, Felipe; Fernandez, Dominique; Rosemblatt, Mario; Sauma, Daniela

    2016-06-13

    Vitamin A, a generic designation for an array of organic molecules that includes retinal, retinol and retinoic acid, is an essential nutrient needed in a wide array of aspects including the proper functioning of the visual system, maintenance of cell function and differentiation, epithelial surface integrity, erythrocyte production, reproduction, and normal immune function. Vitamin A deficiency is one of the most common micronutrient deficiencies worldwide and is associated with defects in adaptive immunity. Reports from epidemiological studies, clinical trials and experimental studies have clearly demonstrated that vitamin A plays a central role in immunity and that its deficiency is the cause of broad immune alterations including decreased humoral and cellular responses, inadequate immune regulation, weak response to vaccines and poor lymphoid organ development. In this review, we will examine the role of vitamin A in immunity and focus on several aspects of T cell biology such as T helper cell differentiation, function and homing, as well as lymphoid organ development. Further, we will provide an overview of the effects of vitamin A deficiency in the adaptive immune responses and how retinoic acid, through its effect on T cells can fine-tune the balance between tolerance and immunity.

  4. Intravaginal Lactic Acid Bacteria Modulated Local and Systemic Immune Responses and Lowered the Incidence of Uterine Infections in Periparturient Dairy Cows

    PubMed Central

    Deng, Qilan; Odhiambo, John F.; Farooq, Umar; Lam, Tran; Dunn, Suzanna M.; Ametaj, Burim N.

    2015-01-01

    The objective of this investigation was to evaluate whether intravaginal infusion of a lactic acid bacteria (LAB) cocktail around parturition could influence the immune response, incidence rate of uterine infections, and the overall health status of periparturient dairy cows. One hundred pregnant Holstein dairy cows were assigned to 1 of the 3 experimental groups as follows: 1) one dose of LAB on wk -2 and -1, and one dose of carrier (sterile skim milk) on wk +1 relative to the expected day of parturition (TRT1); 2) one dose of LAB on wk -2, -1, and +1 (TRT2), and 3) one dose of carrier on wk -2, -1, and +1 (CTR). The LAB were a lyophilized culture mixture composed of Lactobacillus sakei FUA3089, Pediococcus acidilactici FUA3138, and Pediococcus acidilactici FUA3140 with a cell count of 108-109 cfu/dose. Blood samples and vaginal mucus were collected once a week from wk -2 to +3 and analyzed for content of serum total immunoglobulin G (IgG), lipopolysaccharide-binding protein (LBP), serum amyloid A (SAA), haptoglobin (Hp), tumor necrosis factor (TNF), interleukin (IL)-1, IL-6, and vaginal mucus secretory IgA (sIgA). Clinical observations including rectal temperature, vaginal discharges, retained placenta, displaced abomasum, and laminitis were monitored from wk -2 to +8 relative to calving. Results showed that intravaginal LAB lowered the incidence of metritis and total uterine infections. Intravaginal LAB also were associated with lower concentrations of systemic LBP, an overall tendency for lower SAA, and greater vaginal mucus sIgA. No differences were observed for serum concentrations of Hp, TNF, IL-1, IL-6 and total IgG among the treatment groups. Administration with LAB had no effect on the incidence rates of other transition cow diseases. Overall intravaginal LAB lowered uterine infections and improved local and systemic immune responses in the treated transition dairy cows. PMID:25919010

  5. 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 ...

  6. 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 ...

  7. Modulation of host innate and adaptive immune defenses by cytomegalovirus: timing is everything

    PubMed Central

    Loewendorf, A.; Benedict, C. A.

    2010-01-01

    Loewendorf A, Benedict CA (La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA). Modulation of host innate and adaptive immune defenses by cytomegalovirus: timing is everything (Symposium). Human cytomegalovirus (HCMV) (HHV-5, a β-herpesvirus) causes the vast majority of infection-related congenital birth defects, and can trigger severe disease in immune suppressed individuals. The high prevalence of societal infection, the establishment of lifelong persistence and the growing number of immune-related diseases where HCMV is touted as a potential promoter is slowly heightening public awareness to this virus. The millions of years of co-evolution between CMV and the immune system of its host provides for a unique opportunity to study immune defense strategies, and pathogen counterstrategies. Dissecting the timing of the cellular and molecular processes that regulate innate and adaptive immunity to this persistent virus has revealed a complex defense network that is shaped by CMV immune modulation, resulting in a finely tuned host–pathogen relationship. PMID:20433576

  8. Immune Evasion, Immunopathology and the Regulation of the Immune System

    PubMed Central

    Sorci, Gabriele; Cornet, Stéphane; Faivre, Bruno

    2013-01-01

    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. PMID:25436882

  9. Preexisting antigen-specific immune responses are modulated by oral KLH feeding in humans.

    PubMed

    Hostmann, Arwed; Meyer, Tim; Maul, Jochen; Preiss, Jan; Boortz, Bertram; Thiel, Andreas; Duchmann, Rainer; Ullrich, Reiner

    2015-07-01

    Oral tolerance is the antigen-specific inhibition of a systemic immune response after oral antigen uptake and well established in animal models. We recently showed that keyhole limpet hemocyanin (KLH) feeding modulates subsequently induced systemic immune responses in humans as well. In the present study, we investigated whether oral KLH can also modulate preexisting antigen-specific systemic B- and T-cell responses. We induced delayed-type hypersensitivity (DTH) reactions as well as systemic KLH-specific B- and T-cell responses by subcutaneous KLH injections. Subsequent oral KLH administration decreased the small proportion of antigen-specific CD4(+) T cells positive for the cytokine IL-17 at the end of the feeding regimen even further. After reimmunization, there was no difference in DTH reactions and the KLH-specific B-cell responses, but KLH-fed volunteers had an increased proportion of antigen-specific CD4(+) T cells positive for IL-10 and a reduced proportion of antigen-specific CD4(+) T cells positive for the skin-homing receptor cutaneous lymphocyte antigen and IL-2 and IFN-γ. Taken together, oral KLH can modulate a preexisting systemic KLH-specific immune response. These results suggest that feeding antigen may offer therapeutic strategies for the suppression of unwanted immune reactions in humans.

  10. Pneumonia, Acute Respiratory Distress Syndrome, and Early Immune-Modulator Therapy

    PubMed Central

    Lee, Kyung-Yil

    2017-01-01

    Acute respiratory distress syndrome (ARDS) is caused by infectious insults, such as pneumonia from various pathogens or related to other noninfectious events. Clinical and histopathologic characteristics are similar across severely affected patients, suggesting that a common mode of immune reaction may be involved in the immunopathogenesis of ARDS. There may be etiologic substances that have an affinity for respiratory cells and induce lung cell injury in cases of ARDS. These substances originate not only from pathogens, but also from injured host cells. At the molecular level, these substances have various sizes and biochemical characteristics, classifying them as protein substances and non-protein substances. Immune cells and immune proteins may recognize and act on these substances, including pathogenic proteins and peptides, depending upon the size and biochemical properties of the substances (this theory is known as the protein-homeostasis-system hypothesis). The severity or chronicity of ARDS depends on the amount of etiologic substances with corresponding immune reactions, the duration of the appearance of specific immune cells, or the repertoire of specific immune cells that control the substances. Therefore, treatment with early systemic immune modulators (corticosteroids and/or intravenous immunoglobulin) as soon as possible may reduce aberrant immune responses in the potential stage of ARDS. PMID:28208675

  11. Modulation of Human Immune Response by Fungal Biocontrol Agents

    PubMed Central

    Konstantinovas, Cibele; de Oliveira Mendes, Tiago A.; Vannier-Santos, Marcos A.; Lima-Santos, Jane

    2017-01-01

    Although the vast majority of biological control agents is generally regarded as safe for humans and environment, the increased exposure of agriculture workers, and consumer population to fungal substances may affect the immune system. Those compounds may be associated with both intense stimulation, resulting in IgE-mediated allergy and immune downmodulation induced by molecules such as cyclosporin A and mycotoxins. This review discusses the potential effects of biocontrol fungal components on human immune responses, possibly associated to infectious, inflammatory diseases, and defective defenses. PMID:28217107

  12. Modulation of Human Immune Response by Fungal Biocontrol Agents.

    PubMed

    Konstantinovas, Cibele; de Oliveira Mendes, Tiago A; Vannier-Santos, Marcos A; Lima-Santos, Jane

    2017-01-01

    Although the vast majority of biological control agents is generally regarded as safe for humans and environment, the increased exposure of agriculture workers, and consumer population to fungal substances may affect the immune system. Those compounds may be associated with both intense stimulation, resulting in IgE-mediated allergy and immune downmodulation induced by molecules such as cyclosporin A and mycotoxins. This review discusses the potential effects of biocontrol fungal components on human immune responses, possibly associated to infectious, inflammatory diseases, and defective defenses.

  13. Modulation of immune responses in stress by Yoga.

    PubMed

    Arora, Sarika; Bhattacharjee, Jayashree

    2008-07-01

    Stress is a constant factor in today's fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS) and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress.

  14. Modulation of immune responses in stress by Yoga

    PubMed Central

    Arora, Sarika; Bhattacharjee, Jayashree

    2008-01-01

    Stress is a constant factor in today's fastpaced life that can jeopardize our health if left unchecked. It is only in the last half century that the role of stress in every ailment from the common cold to AIDS has been emphasized, and the mechanisms involved in this process have been studied. Stress influences the immune response presumably through the activation of the hypothalamic-pituitary adrenal axis, hypothalamic pituitary-gonadal axis, and the sympathetic-adrenal-medullary system. Various neurotransmitters, neuropeptides, hormones, and cytokines mediate these complex bidirectional interactions between the central nervous system (CNS) and the immune system. The effects of stress on the immune responses result in alterations in the number of immune cells and cytokine dysregulation. Various stress management strategies such as meditation, yoga, hypnosis, and muscle relaxation have been shown to reduce the psychological and physiological effects of stress in cancers and HIV infection. This review aims to discuss the effect of stress on the immune system and examine how relaxation techniques such as Yoga and meditation could regulate the cytokine levels and hence, the immune responses during stress. PMID:21829284

  15. Local not systemic modulation of dendritic cell S1P receptors in lung blunts virus-specific immune responses to influenza

    PubMed Central

    Marsolais, David; Hahm, Bumsuk; Edelmann, Kurt H.; Walsh, Kevin B.; Guerrero, Miguel; Hatta, Yasuko; Kawaoka, Yoshihiro; Roberts, Edward; Oldstone, Michael B. A.; Rosen, Hugh

    2008-01-01

    The mechanism by which locally delivered sphingosine analogs regulate host response to localized viral infection has never been addressed. In this report, we show that intra-tracheal (i.t.) delivery of chiral sphingosine analog AAL-R or its phosphate ester inhibits the T cell response to influenza-virus infection. In contrast, neither intra-peritoneal (i.p.) delivery of AAL-R nor i.t. instillation of the non-phosphorylable stereoisomer AAL-S suppressed virus-specific T cell response, indicating that in vivo phosphorylation of AAL-R and S1P receptor modulation in lungs are essential for immunomodulation. I.t. delivery of water soluble S1P1 receptor agonist at doses sufficient to induce systemic lymphopenia did not inhibit virus-specific T cell response indicating that S1P1 is not involved in the immunosuppressive activities of AAL-R and that immunosuppression acts independently of naïve lymphocyte recirculation. Accumulation of dendritic cells (DCs) in draining lymph nodes was inhibited by i.t. but not i.p. delivery of AAL-R. Direct modulation of DCs is demonstrated by the impaired ability of virus-infected bone-marrow derived DCs treated in vitro with AAL-R to trigger in vivo T cell response after adoptive transfer to the airways. Thus, our results suggest that locally delivered sphingosine analogs induce immunosuppression by modulating S1P receptors other than S1P1 or S1P2 on dendritic cells in the lungs after influenza virus infection. PMID:18577684

  16. Visual computing model for immune system and medical system.

    PubMed

    Gong, Tao; Cao, Xinxue; Xiong, Qin

    2015-01-01

    Natural immune system is an intelligent self-organizing and adaptive system, which has a variety of immune cells with different types of immune mechanisms. The mutual cooperation between the immune cells shows the intelligence of this immune system, and modeling this immune system has an important significance in medical science and engineering. In order to build a comprehensible model of this immune system for better understanding with the visualization method than the traditional mathematic model, a visual computing model of this immune system was proposed and also used to design a medical system with the immune system, in this paper. Some visual simulations of the immune system were made to test the visual effect. The experimental results of the simulations show that the visual modeling approach can provide a more effective way for analyzing this immune system than only the traditional mathematic equations.

  17. Photovoltaic module mounting system

    DOEpatents

    Miros, Robert H. J. [Fairfax, CA; Mittan, Margaret Birmingham [Oakland, CA; Seery, Martin N [San Rafael, CA; Holland, Rodney H [Novato, CA

    2012-04-17

    A solar array mounting system having unique installation, load distribution, and grounding features, and which is adaptable for mounting solar panels having no external frame. The solar array mounting system includes flexible, pedestal-style feet and structural links connected in a grid formation on the mounting surface. The photovoltaic modules are secured in place via the use of attachment clamps that grip the edge of the typically glass substrate. The panel mounting clamps are then held in place by tilt brackets and/or mid-link brackets that provide fixation for the clamps and align the solar panels at a tilt to the horizontal mounting surface. The tilt brackets are held in place atop the flexible feet and connected link members thus creating a complete mounting structure.

  18. Photovoltaic module mounting system

    DOEpatents

    Miros, Robert H. J.; Mittan, Margaret Birmingham; Seery, Martin N; Holland, Rodney H

    2012-09-18

    A solar array mounting system having unique installation, load distribution, and grounding features, and which is adaptable for mounting solar panels having no external frame. The solar array mounting system includes flexible, pedestal-style feet and structural links connected in a grid formation on the mounting surface. The photovoltaic modules are secured in place via the use of attachment clamps that grip the edge of the typically glass substrate. The panel mounting clamps are then held in place by tilt brackets and/or mid-link brackets that provide fixation for the clamps and align the solar panels at a tilt to the horizontal mounting surface. The tilt brackets are held in place atop the flexible feet and connected link members thus creating a complete mounting structure.

  19. Immunological memory within the innate immune system

    PubMed Central

    Sun, Joseph C; Ugolini, Sophie; Vivier, Eric

    2014-01-01

    Immune memory has traditionally been the domain of the adaptive immune system, present only in antigen-specific T and B cells. The purpose of this review is to summarize the evidence for immunological memory in lower organisms (which are not thought to possess adaptive immunity) and within specific cell subsets of the innate immune system. A special focus will be given to recent findings in both mouse and humans for specificity and memory in natural killer (NK) cells, which have resided under the umbrella of innate immunity for decades. The surprising longevity and enhanced responses of previously primed NK cells will be discussed in the context of several immunization settings. PMID:24674969

  20. Cellular immune activation in children with acute dengue virus infections is modulated by apoptosis.

    PubMed

    Myint, Khin S; Endy, Timothy P; Mongkolsirichaikul, Duangrat; Manomuth, Choompun; Kalayanarooj, Siripen; Vaughn, David W; Nisalak, Ananda; Green, Sharone; Rothman, Alan L; Ennis, Francis A; Libraty, Daniel H

    2006-09-01

    Apoptosis is an important modulator of cellular immune responses during systemic viral infections. Peripheral-blood mononuclear cell (PBMC) apoptosis and plasma soluble levels of CD95, a mediator of apoptosis, were determined in sequential samples from children participating in a prospective study of dengue virus (DV) infections. During the period of defervescence, levels of PBMC apoptosis were higher in children developing dengue hemorrhagic fever (DHF), the most severe form of illness, than in those with dengue fever (DF) and other, nondengue, febrile illnesses. CD8(+) T lymphocytes made up approximately half of the peak circulating apoptotic PBMCs in DHF and DF. Maximum plasma levels of soluble CD95 were also higher in children with DHF than in those with DF. The level of PBMC apoptosis correlated with dengue disease severity. Apoptosis appears to be involved in modulation of the innate and adaptive immune responses to DV infection and is likely involved in the evolution of immune responses in other viral hemorrhagic fevers.

  1. 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.

  2. Genomics and the immune system.

    PubMed

    Pipkin, Matthew E; Monticelli, Silvia

    2008-05-01

    While the hereditary information encoded in the Watson-Crick base pairing of genomes is largely static within a given individual, access to this information is controlled by dynamic mechanisms. The human genome is pervasively transcribed, but the roles played by the majority of the non-protein-coding genome sequences are still largely unknown. In this review we focus on insights to gene transcriptional regulation by placing special emphasis on genome-wide approaches, and on how non-coding RNAs, which derive from global transcription of the genome, in turn control gene expression. We review recent progress in the field with highlights on the immune system.

  3. Systems immune monitoring in cancer therapy.

    PubMed

    Greenplate, Allison R; Johnson, Douglas B; Ferrell, P Brent; Irish, Jonathan M

    2016-07-01

    Treatments that successfully modulate anti-cancer immunity have significantly improved outcomes for advanced stage malignancies and sparked intense study of the cellular mechanisms governing therapy response and resistance. These responses are governed by an evolving milieu of cancer and immune cell subpopulations that can be a rich source of biomarkers and biological insight, but it is only recently that research tools have developed to comprehensively characterize this level of cellular complexity. Mass cytometry is particularly well suited to tracking cells in complex tissues because >35 measurements can be made on each of hundreds of thousands of cells per sample, allowing all cells detected in a sample to be characterized for cell type, signalling activity, and functional outcome. This review focuses on mass cytometry as an example of systems level characterization of cancer and immune cells in human tissues, including blood, bone marrow, lymph nodes, and primary tumours. This review also discusses the state of the art in single cell tumour immunology, including tissue collection, technical and biological quality controls, computational analysis, and integration of different experimental and clinical data types. Ex vivo analysis of human tumour cells complements both in vivo monitoring, which generally measures far fewer features or lacks single cell resolution, and laboratory models, which incur cell type losses, signalling alterations, and genomic changes during establishment. Mass cytometry is on the leading edge of a new generation of cytomic tools that work with small tissue samples, such as a fine needle aspirates or blood draws, to monitor changes in rare or unexpected cell subsets during cancer therapy. This approach holds great promise for dissecting cellular microenvironments, monitoring how treatments affect tissues, revealing cellular biomarkers and effector mechanisms, and creating new treatments that productively engage the immune system to

  4. CNS leptin action modulates immune response and survival in sepsis

    PubMed Central

    Tschöp, Johannes; Nogueiras, Ruben; Haas-Lockie, Sarah; Kasten, Kevin; Castañeda, Tamara R.; Huber, Nadine; Guanciale, Kelsey; Perez-Tilve, Diego; Habegger, Kirk; Ottaway, Nickki; Woods, Stephen C.; Oldfield, Brian; Clarke, Iain; Chua, Streamson; Farooqi, I. Sadaf; O'Rahilly, Stephen; Caldwell, Charles C.; Tschöp, Matthias H.

    2010-01-01

    Sepsis describes a complex clinical syndrome that results from an infection, setting off a cascade of systemic inflammatory responses that can lead to multiple organ failure and death. Leptin is a 16 kDa adipokine that, among its multiple known effects, is involved in regulating immune function. Here we demonstrate that leptin deficiency in ob/ob mice leads to higher mortality and more severe organ damage in a standard model of sepsis in mice (cecal ligation and puncture, CLP). Moreover, systemic leptin replacement improved the immune response to CLP. Based on the molecular mechanisms of leptin regulation of energy metabolism and reproductive function, we hypothesized that leptin acts in the central nervous system (CNS) to efficiently coordinate peripheral immune defense in sepsis. We now report that leptin signaling in the brain increases survival during sepsis in leptin-deficient as well as in wild-type mice and that endogenous CNS leptin action is required for an adequate systemic immune response. These findings reveal the existence of a relevant neuroendocrine control of systemic immune defense, and suggest a possible therapeutic potential for leptin analogues in infectious disease. PMID:20427662

  5. Force Modulator System

    SciTech Connect

    Redmond Clark

    2009-04-30

    Many metal parts manufacturers use large metal presses to shape sheet metal into finished products like car body parts, jet wing and fuselage surfaces, etc. These metal presses take sheet metal and - with enormous force - reshape the metal into a fully formed part in a manner of seconds. Although highly efficient, the forces involved in forming metal parts also damage the press itself, limit the metals used in part production, slow press operations and, when not properly controlled, cause the manufacture of large volumes of defective metal parts. To date, the metal-forming industry has not been able to develop a metal-holding technology that allows full control of press forces during the part forming process. This is of particular importance in the automotive lightweighting efforts under way in the US automotive manufacturing marketplace. Metalforming Controls Technology Inc. (MC2) has developed a patented press control system called the Force Modulator that has the ability to control these press forces, allowing a breakthrough in stamping process control. The technology includes a series of hydraulic cylinders that provide controlled tonnage at all points in the forming process. At the same time, the unique cylinder design allows for the generation of very high levels of clamping forces (very high tonnages) in very small spaces; a requirement for forming medium and large panels out of HSS and AHSS. Successful production application of these systems testing at multiple stamping operations - including Ford and Chrysler - has validated the capabilities and economic benefits of the system. Although this technology has been adopted in a number of stamping operations, one of the primary barriers to faster adoption and application of this technology in HSS projects is system cost. The cost issue has surfaced because the systems currently in use are built for each individual die as a custom application, thus driving higher tooling costs. This project proposed to better

  6. Autopolyreactivity Confers a Holistic Role in the Immune System.

    PubMed

    Avrameas, S

    2016-04-01

    In this review, we summarize and discuss some key findings from the study of naturally occurring autoantibodies. The B-cell compartment of the immune system appears to recognize almost all endogenous and environmental antigens. This ability is accomplished principally through autopolyreactive humoral and cellular immune receptors. This extended autopolyreactivity (1) along immunoglobulin gene recombination contributes to the immune system's ability to recognize a very large number of self and non-self constituents; and (2) generates a vast immune network that creates communication channels between the organism's interior and exterior. Thus, the immune system continuously evolves depending on the internal and external stimuli it encounters. Furthermore, this far-reaching network's existence implies activities resembling those of classical biological factors or activities that modulate the function of other classical biological factors. A few such antibodies have already been found. Another important concept is that natural autoantibodies are highly dependent on the presence or absence of commensal microbes in the organism. These results are in line with past and recent findings showing the fundamental influence of the microbiota on proper immune system development, and necessitate the existence of a host-microbe homeostasis. This homeostasis requires that the participating humoral and cellular receptors are able to recognize self-antigens and commensal microbes without damaging them. Autopolyreactive immune receptors expressing low affinity for both types of antigens fulfil this role. The immune system appears to play a holistic role similar to that of the nervous system. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  7. Immune modulation in response to stress and relaxation.

    PubMed

    Mahbub-E-Sobhani; Haque, N; Salma, U; Ahmed, A

    2011-03-15

    Traditional medical science has kept the mind separate from the body. Recently people realize the effect of mind on health and psychoneuroimmunology is the new evolved science that describes the interactions between psyche and soma. In this review through a typical psycho-neuro-endocrino-immune network the effects of psychological stress (acute, brief naturalistic and chronic) and relaxation on immune modulation has been shown. From this network Corticotrophin Releasing Factor (CRF), Adrenocorticotrophic Hormone (ACTH), Glucocorticoids (GC), alpha-endorphin and Met-enkephalin are found as important endocrine components and T cells, B cells, monocytes/macrophages, Natural Killer (NK) cells and their cytokines that is Tumor Necrosis Factor-alpha (TNF-alpha), Interferon Gamma (IFN-alpha) and interleukins such as IL-1, IL-2, IL-4, IL-6, IL-10, IL-12 etc. are found as important immune components. Finally, it has been shown that, acute, brief naturalistic and chronic stress have different immune modulatory activities which are harmful to one's homeostasis and relaxation can help to maintain that homeostasis.

  8. A brief outline of the immune system.

    PubMed

    Tomar, Namrata; De, Rajat K

    2014-01-01

    The various cells and proteins responsible for immunity constitute the immune system, and their orchestrated response to defend foreign/non-self substances (antigen) is known as the immune response. When an antigen attacks the host system, two distinct, yet interrelated, branches of the immune system are active-the nonspecific/innate and specific/adaptive immune response. Both of these systems have certain physiological mechanisms, which enable the host to recognize foreign materials to itself and to neutralize, eliminate, or metabolize them. Innate immunity represents the earliest development of protection against antigens. Adaptive immunity has again two branches-humoral and cell mediated. It should be noted that both innate and adaptive immunities do not work independently. Moreover, most of the immune responses involve the activity and interplay of both the humoral and the cell-mediated immune branches of the immune system. We have described these branches in detail along with the mechanism of antigen recognition. This chapter also describes the disorders of immune system in brief.

  9. "Natural Regulators": NK Cells as Modulators of T Cell Immunity.

    PubMed

    Schuster, Iona S; Coudert, Jerome D; Andoniou, Christopher E; Degli-Esposti, Mariapia A

    2016-01-01

    Natural killer (NK) cells are known as frontline responders capable of rapidly mediating a response upon encountering transformed or infected cells. Recent findings indicate that NK cells, in addition to acting as innate effectors, can also regulate adaptive immune responses. Here, we review recent studies on the immunoregulatory function of NK cells with a specific focus on their ability to affect the generation of early, as well as long-term antiviral T cell responses, and their role in modulating immune pathology and disease. In addition, we summarize the current knowledge of the factors governing regulatory NK cell responses and discuss origin, tissue specificity, and open questions about the classification of regulatory NK cells as classical NK cells versus group 1 innate lymphoid cells.

  10. Plant LysM proteins: modules mediating symbiosis and immunity.

    PubMed

    Gust, Andrea A; Willmann, Roland; Desaki, Yoshitake; Grabherr, Heini M; Nürnberger, Thorsten

    2012-08-01

    Microbial glycans, such as bacterial peptidoglycans, fungal chitin or rhizobacterial Nod factors (NFs), are important signatures for plant immune activation or for the establishment of beneficial symbioses. Plant lysin motif (LysM) domain proteins serve as modules mediating recognition of these different N-acetylglucosamine (GlcNAc)-containing ligands, suggesting that this class of proteins evolved from an ancient sensor for GlcNAc. During early plant evolution, these glycans probably served as immunogenic patterns activating LysM protein receptor-mediated plant immunity and stopping microbial infection. The biochemical potential of plant LysM proteins for sensing microbial GlcNAc-containing glycans has probably since favored the evolution of receptors facilitating microbial infection and symbiosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Controlled release strategies for modulating immune responses to promote tissue regeneration.

    PubMed

    Dumont, Courtney M; Park, Jonghyuck; Shea, Lonnie D

    2015-12-10

    Advances in the field of tissue engineering have enhanced the potential of regenerative medicine, yet the efficacy of these strategies remains incomplete, and is limited by the innate and adaptive immune responses. The immune response associated with injury or disease combined with that mounted to biomaterials, transplanted cells, proteins, and gene therapies vectors can contribute to the inability to fully restore tissue function. Blocking immune responses such as with anti-inflammatory or immunosuppressive agents are either ineffective, as the immune response contributes significantly to regeneration, or have significant side effects. This review describes targeted strategies to modulate the immune response in order to limit tissue damage following injury, promote an anti-inflammatory environment that leads to regeneration, and induce antigen (Ag)-specific tolerance that can target degenerative diseases that destroy tissues and promote engraftment of transplanted cells. Focusing on targeted immuno-modulation, we describe local delivery techniques to sites of inflammation as well as systemic approaches that preferentially target subsets of immune populations.

  12. Influence of prebiotics on the human immune system (GALT).

    PubMed

    Bodera, Pawel

    2008-06-01

    Prebiotics have great potential to improve human health in specific intestinal disorders. The knowledge about the influence of prebiotics on the gut-associated lymphoid tissues (GALT) for the improvement of human health is still growing. This paper reviews the latest evidence for the immunity-enhancing effects of prebiotics. Prebiotics, include inulin, fructooligosaccharides, mannosoligosaccharides, and arabinogalactans, are a therapeutic nutritional preparation used for the gut function favoring growth of normal bacterial flora and impedes growth of pathogenic organisms. There is convincing preliminary data to suggest that the consumption of prebiotics can modulate immune parameters in GALT, secondary lymphoid tissues and peripheral circulation. There is increasing evidence that the newly described prebiotics and innovative means of administration can modulate various properties of the immune system, including those of the gut-associated lymphoid tissues (GALT). Authors of recently published patents showed new mechanisms for immuno-modulation, and the ultimate impact on immunological health of prebiotics.

  13. 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.

  14. Immune System and Its Link to Rheumatic Diseases

    MedlinePlus

    ... Immune System & Its Link to Rheumatic Disease The Immune System and Its Link to Rheumatic Disease Fast Facts ... of a vessel of the body). What’s the immune system? The immune system allows us to identify and ...

  15. Living Systems Energy Module

    SciTech Connect

    1995-09-26

    The Living Systems Energy Module, renamed Voyage from the Sun, is a twenty-lesson curriculum designed to introduce students to the major ways in which energy is important in living systems. Voyage from the Sun tells the story of energy, describing its solar origins, how it is incorporated into living terrestrial systems through photosynthesis, how it flows from plants to herbivorous animals, and from herbivores to carnivores. A significant part of the unit is devoted to examining how humans use energy, and how human impact on natural habitats affects ecosystems. As students proceed through the unit, they read chapters of Voyage from the Sun, a comic book that describes the flow of energy in story form (Appendix A). During the course of the unit, an ``Energy Pyramid`` is erected in the classroom. This three-dimensional structure serves as a classroom exhibit, reminding students daily of the importance of energy and of the fragile nature of our living planet. Interactive activities teach students about adaptations that allow plants and animals to acquire, to use and to conserve energy. A complete list of curricular materials and copies of all activity sheets appear in Appendix B.

  16. The immune system as a self-centered network of lymphocytes.

    PubMed

    Santori, Fabio R

    2015-08-01

    This essay makes a brief historical and comparative review of selective and network theories of the immune system which is presented as a chemical sensory system with immune and non-immune functions. The ontogeny of immune networks is the result of both positive and negative selection of lymphocytes to self-epitopes that serve as a "template" for the recognition of foreign antigens. The development of immune networks progresses from single individual clones in early ontogeny into complex "information processing networks" in which lymphocytes are linked to inhibitory and stimulatory immune cells. The results of these regulatory interactions modulate immune responses and tolerance.

  17. The immune system as a self-centered network of lymphocytes

    PubMed Central

    Santori, Fabio R.

    2015-01-01

    This essay makes a brief historical and comparative review of selective and network theories of the immune system which is presented as a chemical sensory system with immune and non-immune functions. The ontogeny of immune networks is the result of both positive and negative selection of lymphocytes to self-epitopes that serve as a “template” for the recognition of foreign antigens. The development of immune networks progresses from single individual clones in early ontogeny into complex “information processing networks” in which lymphocytes are linked to inhibitory and stimulatory immune cells. The results of these regulatory interactions modulate immune responses and tolerance. PMID:26092524

  18. 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.

  19. Bacterial toxins and the immune system

    PubMed Central

    Galán, Jorge E.

    2005-01-01

    Microorganisms that cause persistent infection often exhibit specific adaptations that allow them to avoid the adaptive immune response. Recently, several bacterial toxins have been shown in vitro to disrupt immune cell functions. However, it remains to be established whether these activities are relevant during infection and whether these toxins have specifically evolved to disrupt the adaptive immune system. PMID:15699067

  20. Immune system modifications and feto-maternal immune tolerance.

    PubMed

    Song, Dan; Shi, Yichao

    2014-01-01

    This review aimed at understanding pregnancy-induced changes in the maternal immune response and mechanisms for the establishment of feto-maternal tolerance. Articles cited in this review were obtained from PubMed in English from 2000 to 2014, and the search string included keywords such as feto-maternal tolerance, dendritic cells, macrophage, T regulatory cells, natural killer cells, cytokines and hormone. Articles regarding altered maternal immune response, including the proliferation and differentiation of the altered cells, and the production of cytokines and regulation of hormones in the feto-maternal interface were retrieved, reviewed and analyzed. The changes in immune cells and cytokines in the local uterine microenvironment and peripheral blood are correlated with the establishment of feto-maternal tolerance. The endocrine system regulates the maternal immune system, promoting modifications during pregnancy. In these regulatory networks, every factor is indispensible for others. The integration and balance of these immune factors during pregnancy give rise to an environment that enables the fetus to escape rejection by the maternal immune system. This progress is complicated, and needs more comprehensive exploration and explanation.

  1. Modulation of host adaptive immunity by hRSV proteins

    PubMed Central

    Espinoza, Janyra A; Bohmwald, Karen; Céspedes, Pablo F; Riedel, Claudia A; Bueno, Susan M; Kalergis, Alexis M

    2014-01-01

    Globally, the human respiratory syncytial virus (hRSV) is the major cause of lower respiratory tract infections (LRTIs) in infants and children younger than 2 years old. Furthermore, the number of hospitalizations due to LRTIs has shown a sustained increase every year due to the lack of effective vaccines against hRSV. Thus, this virus remains as a major public health and economic burden worldwide. The lung pathology developed in hRSV-infected humans is characterized by an exacerbated inflammatory and Th2 immune response. In order to rationally design new vaccines and therapies against this virus, several studies have focused in elucidating the interactions between hRSV virulence factors and the host immune system. Here, we discuss the main features of hRSV biology, the processes involved in virus recognition by the immune system and the most relevant mechanisms used by this pathogen to avoid the antiviral host response. PMID:25513775

  2. 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.

  3. 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),…

  4. 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),…

  5. Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation.

    PubMed

    Sánchez, Jon Andoni; Alfonso, Amparo; Rodriguez, Ines; Alonso, Eva; Cifuentes, José Manuel; Bermudez, Roberto; Rateb, Mostafa E; Jaspars, Marcel; Houssen, Wael E; Ebel, Rainer; Tabudravu, Jioji; Botana, Luís M

    2016-01-01

    The modulation of the immune system can have multiple applications such as cancer treatment, and a wide type of processes involving inflammation where the potent chemotactic agent cyclophilin A (Cyp A) is implicated. The Porifera phylum, in which Spongionella is encompassed, is the main producer of marine bioactive compounds. Four secondary metabolites obtained from Spongionella (Gracilin H, A, L, and Tetrahydroaplysulphurin-1) were described to hit Cyp A and to block the release of inflammation mediators. Based on these results, some role of Spongionella compounds on other steps of the signaling pathway mediated by this chemotactic agent can be hypothesized. In the present paper, we studied the effect of these four compounds on the surface membrane CD147 receptor expression, on the extracellular levels of Cyp A and on the ability to migrate of concanavalin (Con A)-activated T lymphocytes. Similar to a well-known immunosuppressive agent cyclosporine A (CsA), Gracilin H, A, L, and tetrahydroaplysulphurin-1 were able to reduce the CD147 membrane expression and to block the release of Cyp A to the medium. Besides, by using Cyp A as chemotactic agent, T cell migration was inhibited when cells were previously incubated with Gracilin A and Gracilin L. These positive results lead us to test the in vivo effect of Gracilin H and L in a mouse ear delayed hypersensitive reaction. Thus, both compounds efficiently reduce the ear swelling as well as the inflammatory cell infiltration. These results provide more evidences for their potential therapeutic application in immune-related diseases of Spongionella compounds.

  6. Spongionella Secondary Metabolites, Promising Modulators of Immune Response through CD147 Receptor Modulation

    PubMed Central

    Sánchez, Jon Andoni; Alfonso, Amparo; Rodriguez, Ines; Alonso, Eva; Cifuentes, José Manuel; Bermudez, Roberto; Rateb, Mostafa E.; Jaspars, Marcel; Houssen, Wael E.; Ebel, Rainer; Tabudravu, Jioji; Botana, Luís M.

    2016-01-01

    The modulation of the immune system can have multiple applications such as cancer treatment, and a wide type of processes involving inflammation where the potent chemotactic agent cyclophilin A (Cyp A) is implicated. The Porifera phylum, in which Spongionella is encompassed, is the main producer of marine bioactive compounds. Four secondary metabolites obtained from Spongionella (Gracilin H, A, L, and Tetrahydroaplysulphurin-1) were described to hit Cyp A and to block the release of inflammation mediators. Based on these results, some role of Spongionella compounds on other steps of the signaling pathway mediated by this chemotactic agent can be hypothesized. In the present paper, we studied the effect of these four compounds on the surface membrane CD147 receptor expression, on the extracellular levels of Cyp A and on the ability to migrate of concanavalin (Con A)-activated T lymphocytes. Similar to a well-known immunosuppressive agent cyclosporine A (CsA), Gracilin H, A, L, and tetrahydroaplysulphurin-1 were able to reduce the CD147 membrane expression and to block the release of Cyp A to the medium. Besides, by using Cyp A as chemotactic agent, T cell migration was inhibited when cells were previously incubated with Gracilin A and Gracilin L. These positive results lead us to test the in vivo effect of Gracilin H and L in a mouse ear delayed hypersensitive reaction. Thus, both compounds efficiently reduce the ear swelling as well as the inflammatory cell infiltration. These results provide more evidences for their potential therapeutic application in immune-related diseases of Spongionella compounds. PMID:27822214

  7. Evolution of innate and adaptive immune systems in jawless vertebrates.

    PubMed

    Kasamatsu, Jun

    2013-01-01

    Because jawless vertebrates are the most primitive vertebrates, they have been studied to gain understanding of the evolutionary processes that gave rise to the innate and adaptive immune systems in vertebrates. Jawless vertebrates have developed lymphocyte-like cells that morphologically resemble the T and B cells of jawed vertebrates, but they express variable lymphocyte receptors (VLRs) instead of the T and B cell receptors that specifically recognize antigens in jawed vertebrates. These VLRs act as antigen receptors, diversity being generated in their antigen-binding sites by assembly of highly diverse leucine-rich repeat modules. Therefore, jawless vertebrates have developed adaptive immune systems based on the VLRs. Although pattern recognition receptors, including Toll-like receptors (TLRs) and Rig-like receptors (RLRs), and their adaptor genes are conserved in jawless vertebrates, some transcription factor and inflammatory cytokine genes in the TLR and RLR pathways are not present. However, like jawed vertebrates, the initiation of adaptive immune responses in jawless vertebrates appears to require prior activation of the innate immune system. These observations imply that the innate immune systems of jawless vertebrates have a unique molecular basis that is distinct from that of jawed vertebrates. Altogether, although the molecular details of the innate and adaptive immune systems differ between jawless and jawed vertebrates, jawless vertebrates have developed versions of these immune systems that are similar to those of jawed vertebrates. © 2012 The Societies and Wiley Publishing Asia Pty Ltd.

  8. AINIDS: an immune-based network intrusion detection system

    NASA Astrophysics Data System (ADS)

    Yan, Qiao; Yu, Jianping

    2006-04-01

    Intrusion detection can be looked as a problem of pattern classification. Since intrusion detection has some intrinsic characteristic such as high dimensional feature spaces, linearity non-differentiation, severe unevenness of normal pattern and anomaly pattern, it is very difficult to detection intrusions directly by use of classical pattern recognition method. Nature immune system is a self-adaptive and self-learning classifier, which can accomplish recognition and classification by learning, remembrance and association. First we use four-tuple to define nature immune system and intrusion detection system, then we give the mathematic formalization description of performance index of intrusion detection system. Finally we design and develop an immune-based network intrusion detection system-- AINIDS, which includes a data collector component, a packet head parser and feature extraction component, antibody generation and antigen detection component, co-stimulation and report component and rule optimization component. The antibody generation and antigen detection component is the key module of AINIDS. In the component the passive immune antibodies and the automatic immune antibodies that include memory automatic immune antibodies and fuzzy automatic immune antibodies are proposed by analogy with natural immune system. The passive immune antibodies inherit available rules and can detect known intrusion rapidly. The automatic immune antibodies integrate statistic method with fuzzy reasoning system to improve the detection performance and can discover novel attacks. AINIDS is tested by the data that we collect from our LANs and by the data from 1999 DARPA intrusion detection evaluation data sets. Both experiments prove AINIDS has good detection rate for old and novel attacks.

  9. Metabolites: messengers between the microbiota and the immune system

    PubMed Central

    Levy, Maayan; Thaiss, Christoph A.; Elinav, Eran

    2016-01-01

    The mammalian intestine harbors one of the largest microbial densities on Earth, necessitating the implementation of control mechanisms by which the host evaluates the state of microbial colonization and reacts to deviations from homeostasis. While microbial recognition by the innate immune system has been firmly established as an efficient means by which the host evaluates microbial presence, recent work has uncovered a central role for bacterial metabolites in the orchestration of the host immune response. In this review, we highlight examples of how microbiota-modulated metabolites control the development, differentiation, and activity of the immune system and classify them into functional categories that illustrate the spectrum of ways by which microbial metabolites influence host physiology. A comprehensive understanding of how microbiota-derived metabolites shape the human immune system is critical for the rational design of therapies for microbiota-driven diseases. PMID:27474437

  10. Advances in targeting cell surface signalling molecules for immune modulation

    PubMed Central

    Yao, Sheng; Zhu, Yuwen; Chen, Lieping

    2013-01-01

    The past decade has witnessed a surge in the development of immunomodulatory approaches to combat a broad range of human diseases, including cancer, viral infections, autoimmunity and inflammation as well as in the prevention of transplant rejection. Immunomodulatory approaches mostly involve the use of monoclonal antibodies or recombinant fusion proteins that target cell surface signalling molecules on immune cells to drive immune responses towards the desired direction. Advances in our understanding of the human immune system, along with valuable lessons learned from the first generation of therapeutic biologics, are aiding the design of the next generation of immunomodulatory biologics with better therapeutic efficacy, minimized adverse effects and long-lasting clinical benefit. The recent encouraging results from antibodies targeting programmed cell death protein 1 (PD1) and B7 homolog 1 (B7H1; also known as PDL1) for the treatment of various advanced human cancers show that immunomodulatory therapy has come of age. PMID:23370250

  11. Participation of Leukotrienes in the Immune Modulation of Oral Tolerance

    PubMed Central

    de Oliveira, Sandra R. P.; Nomizo, Auro; Frantz, Fabiani G.; Faccioli, Lúcia H.; de Matos, Ana Paula Keller; Carrilho, Emanuel; Afonso, Ana; de Freitas Anibal, Fernanda

    2017-01-01

    Oral tolerance (OT) is characterized as a peripheral immune tolerance form, in which, mature lymphocytes in lymphoid tissues associated with mucosa, become non-functional or hypo responsive due to prior oral administration of antigen. OT is an important immunological phenomenon due to its therapeutic potential in inflammatory processes and others diseases. Here we evaluated leukotriene role in the induction of OT, as well as, the production of cytokines IL-5 and IFN-γ in leukotriene deficient animals (knock-out). Our results suggested that even in the presence of OT and leukotrienes absence, cytokine IFN-γ remains being secreted, which gives us an indication of immune system specificity and also that IFN-γ participates in various immune processes. PMID:28270799

  12. Learning and memory ... and the immune system.

    PubMed

    Marin, Ioana; Kipnis, Jonathan

    2013-09-19

    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), microglia constantly monitor synapses and participate in their pruning during development and possibly also throughout life. Classical inflammatory cytokines, such as interleukin (IL)-1β and tumor necrosis factor (TNF), are released during neuronal activity and play a crucial role in regulating the strength of synaptic transmission. Systemically, proper functioning of the immune system is critical for maintaining normal nervous system function. Disruption of the immune system functioning leads to impairments in cognition and in neurogenesis. In this review we provide examples of the communication between the nervous and the immune systems in the interest of normal CNS development and function.

  13. Label-free haemogram using wavelength modulated Raman spectroscopy for identifying immune-cell subset

    NASA Astrophysics Data System (ADS)

    Ashok, Praveen C.; Praveen, Bavishna B.; Campbell, Elaine C.; Dholakia, Kishan; Powis, Simon J.

    2014-03-01

    Leucocytes in the blood of mammals form a powerful protective system against a wide range of dangerous pathogens. There are several types of immune cells that has specific role in the whole immune system. The number and type of immune cells alter in the disease state and identifying the type of immune cell provides information about a person's state of health. There are several immune cell subsets that are essentially morphologically identical and require external labeling to enable discrimination. Here we demonstrate the feasibility of using Wavelength Modulated Raman Spectroscopy (WMRS) with suitable machine learning algorithms as a label-free method to distinguish between different closely lying immune cell subset. Principal Component Analysis (PCA) was performed on WMRS data from single cells, obtained using confocal Raman microscopy for feature reduction, followed by Support Vector Machine (SVM) for binary discrimination of various cell subset, which yielded an accuracy >85%. The method was successful in discriminating between untouched and unfixed purified populations of CD4+CD3+ and CD8+CD3+ T lymphocyte subsets, and CD56+CD3- natural killer cells with a high degree of specificity. It was also proved sensitive enough to identify unique Raman signatures that allow clear discrimination between dendritic cell subsets, comprising CD303+CD45+ plasmacytoid and CD1c+CD141+ myeloid dendritic cells. The results of this study clearly show that WMRS is highly sensitive and can distinguish between cell types that are morphologically identical.

  14. The Microbiome, Systemic Immune Function, and Allotransplantation.

    PubMed

    Nellore, Anoma; Fishman, Jay A

    2016-01-01

    Diverse effects of the microbiome on solid organ transplantation are beginning to be recognized. In allograft recipients, microbial networks are disrupted by immunosuppression, nosocomial and community-based infectious exposures, antimicrobial therapies, surgery, and immune processes. Shifting microbial patterns, including acute infectious exposures, have dynamic and reciprocal interactions with local and systemic immune systems. Both individual microbial species and microbial networks have central roles in the induction and control of innate and adaptive immune responses, in graft rejection, and in ischemia-reperfusion injury. Understanding the diverse interactions between the microbiome and the immune system of allograft recipients may facilitate clinical management in the future.

  15. The Microbiome, Systemic Immune Function, and Allotransplantation

    PubMed Central

    Nellore, Anoma

    2015-01-01

    SUMMARY Diverse effects of the microbiome on solid organ transplantation are beginning to be recognized. In allograft recipients, microbial networks are disrupted by immunosuppression, nosocomial and community-based infectious exposures, antimicrobial therapies, surgery, and immune processes. Shifting microbial patterns, including acute infectious exposures, have dynamic and reciprocal interactions with local and systemic immune systems. Both individual microbial species and microbial networks have central roles in the induction and control of innate and adaptive immune responses, in graft rejection, and in ischemia-reperfusion injury. Understanding the diverse interactions between the microbiome and the immune system of allograft recipients may facilitate clinical management in the future. PMID:26656674

  16. Immune modulation using mistletoe (Viscum album L.) extracts Iscador.

    PubMed

    Büssing, Arndt

    2006-06-01

    One repeatedly finds that mistletoe (Viscum album L.) extracts show immune-modulating effects. This is also true in many cases in the experimental setting. Many of the experimental trials cannot, however, be transferred to the clinical situation - or only in a limited way. The aim of this work was to pursue the question of the extent to which the function of immune-competent cells can be influenced by mistletoe extracts. To do this, 3 clinical studies were carried out. Results from the first two studies will be presented here. In a prospective observational study with defined inclusion and exclusion criteria, the impact of two different doses of Iscador M (Malus) or Iscador Qu (Quercus) on the function and number of T-lymphocytes from tumor patients was studied. The immunological tests took place monthly during the first six months. Thirty-one patients were included in the slow dose group and 36 patients in the group with swift dose escalation. It was postulated that too swift increase in dosage would lead to stronger local reactions and impairment of the stimulation capacity of T-cells taken ex vivo and incubated for 72 h. The evaluation showed that patients with stronger local reactions at the injection site have an impairment of mitogen-induced stimulation capacity of T-cells. However, patients with stronger local reaction showed a significant decrease of HLA-DR+ T cells as compared to patients In a GCP-conform, controlled bicentric phase II study the aim was to investigate the efficacy of a perioperative intravenous mistletoe extract application on the modulation of operation-induced immune suppression. For this purpose 105 patients with breast cancer were recruited. At the treatment centre the patients received an infusion of 1 mg Iscador M Spezial prior to the start of an operation, in addition to normal medication, while this was not practised at the control centre. The primary trial objective was the oxidative burst in granulocytes taken from patients ex

  17. 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

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

    PubMed

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

    2013-04-06

    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.

  19. The endogenous immune response modulates the course of IgA-immune complex mediated nephropathy.

    PubMed

    Chao, T-K; Rifai, A; Ka, S-M; Yang, S-M; Shui, H-A; Lin, Y-F; Sytwu, H-K; Lee, W-H; Kung, J T; Chen, A

    2006-07-01

    In animal models of IgA nephropathy, the inevitable endogenous immune response to passively administered antigens alone or in complex with specific IgA mask the exact role each might play in pathogenesis. To delineate the role the immune response might play, we have developed a passive model with exclusive IgA-immune complex-mediated nephropathy in B-cell-deficient (BCD) mice. Glomerular IgA immune deposits were induced by administration of purified IgA antiphosphorylcholine and the specific pneumococcal C-polysaccharide (PnC) antigen daily for 2 weeks into BCD and wild-type (WT) mice. In BCD mice IgA+PnC deposits induced severe glomerular injury and renal dysfunction. In contrast, WT mice developed intense glomerular IgG and IgM and C3 co-deposits of the IgA+PnC with significantly less renal injury. Cytofluorometric analysis revealed that PnC induced in BCD, but not in WT, a rapid and dramatic increase in number of activated CD3(+)/CD69(+) T-cell population. The nuclear factor-kappa B (NF-kappaB) transcription factor was activated early and progressively increased in response to glomerular IgA+PnC deposits. These results suggest that nephritogenic IgA+PnC immune deposits induce glomerular and renal dysfunction through activation of the NF-kappaB. This inflammatory pathway is modulated by the endogenous cellular and antibody response to the antigen affecting the course of IgA nephropathy progression.

  20. A corticoid-sensitive cytokine release assay for monitoring stress-mediated immune modulation.

    PubMed

    Feuerecker, M; Mayer, W; Kaufmann, I; Gruber, M; Muckenthaler, F; Yi, B; Salam, A P; Briegel, J; Schelling, G; Thiel, M; Choukèr, A

    2013-05-01

    The human immune system is orchestrated in a complex manner and protects the host against invading organisms and controls adequate immune responses to different antigen challenges in an endo-, auto- and paracrine-regulated fashion. The variety and intensity of immune responses are known to be dependent on stress-sensitive neural, humoral and metabolic pathways. The delayed-type hypersensitivity (DTH) skin test was a validated and standardized measure applied in clinical studies to monitor the integral function of cellular immune responses in vivo. The DTH skin test was, however, phased out in 2002. To obtain insight into the mechanisms of stress-sensitive immune reactions, we have developed an alternative in-vitro assay which allows the evaluation of antigen-dependent cellular immune responses triggered by T lymphocytes. The change in the concentration of proinflammatory cytokines in supernatant of the blood-antigen mixture is of particular interest to mirror the degree and adequacy of cellular immune responses. In this study we report that the proinflammatory cytokines interleukin (IL)-2, interferon (IFN)-γ and tumour necrosis factor (TNF)-α show a time-dependent increase upon ex-vivo bacterial, viral and fungal antigen stimulations. Furthermore, evidence is provided that this assay is sensitive to mirror stress hormone-mediated immune modulation in humans as shown either after hydrocortisone injection or after acute stress exposure during free fall in parabolic flight. This in-vitro test appears to be a suitable assay to sensitively mirror stress hormone-dependent inhibition of cellular immune responses in the human. Because of its standardization and relatively simple technical handling, it may also serve as an appropriate research tool in the field of psychoneuroendocrinology in clinical as in field studies. © 2012 British Society for Immunology.

  1. 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.

  2. Conceptual Spaces of the Immune System

    PubMed Central

    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. PMID:28018339

  3. Modulation of Caenorhabditis elegans immune response and modification of Shigella endotoxin upon interaction.

    PubMed

    Kesika, Periyanaina; Prasanth, Mani Iyer; Balamurugan, Krishnaswamy

    2015-04-01

    To analyze the pathogenesis at both physiological and molecular level using the model organism, Caenorhabditis elegans at different developmental stages in response to Shigella spp. and its pathogen associated molecular patterns such as lipopolysaccharide. The solid plate and liquid culture-based infection assays revealed that Shigella spp. infects C. elegans and had an impact on the brood size and pharyngeal pumping rate. LPS of Shigella spp. was toxic to C. elegans. qPCR analysis revealed that host innate immune genes have been modulated upon Shigella spp. infections and its LPS challenges. Non-destructive analysis was performed to kinetically assess the alterations in LPS during interaction of Shigella spp. with C. elegans. The modulation of innate immune genes attributed the surrendering of host immune system to Shigella spp. by favoring the infection. LPS appeared to have a major role in Shigella-mediated pathogenesis and Shigella employs a tactic behavior of modifying its LPS content to escape from the recognition of host immune system.

  4. [Immune System Reaction against Environmental Pollutants].

    PubMed

    Tanabe, Tsuyoshi; Yamaguchi, Natsu; Okuda, Masayuki; Ishimaru, Yasutaka; Takahashi, Hidekazu

    2015-01-01

    Environmental pollutants (such as diesel exhaust particles and silica) cause disorders ranging from bronchial asthma to malignant tumors. In recent years, it has been reported that some of the signaling pathways in which environmental contaminants act in vivo are associated with innate immunity. Innate immunity recognizes ligands and induces inflammation. Those ligands are pathogen-associated molecular patterns (PAMPs: e.g., lipopolysaccharide) and danger-associated molecular patterns (DAMPs: e.g., cholesterol crystallization or uric acid crystal). Activation of innate immunity stimulates the acquired immunity system. Therefore, innate immunity regulates the strength of the general immune system. Furthermore, crystal silica, which is an environmental pollutant, activates innate immunity as a ligand. Innate immunity involves the membrane-bound Toll-like receptors (TLR) and cytoplasm-localized nucleotide-binding oligomerization domain (NOD)-like receptors (NLR). We reported the innate immunity-system-related diseases such as Crohn's disease, Blau syndrome, myelogenous leukemia, and sarcoidosis. An inflammasome complex containing NLR has attracted attention owing to its correlation with the onset of several diseases. It is reported that the inflammasome activation is related to the development of lifestyle-related diseases such as myocardial infarction and fatty liver. It is also reported that the mechanism by which crystal silica and asbestos cause inflammation involves the inflammasome activation. Analyzing the genes of innate immunity contributes to the clarification of the mechanism of disease onset caused by environmental pollutants.

  5. Structural insights into the evolution of the adaptive immune system.

    PubMed

    Deng, Lu; Luo, Ming; Velikovsky, Alejandro; Mariuzza, Roy A

    2013-01-01

    The adaptive immune system, which is based on highly diverse antigen receptors that are generated by somatic recombination, arose approximately 500 Mya at the dawn of vertebrate evolution. In jawed vertebrates, adaptive immunity is mediated by antibodies and T cell receptors (TCRs), which are composed of immunoglobulin (Ig) domains containing hypervariable loops that bind antigen. In striking contrast, the adaptive immune receptors of jawless vertebrates, termed variable lymphocyte receptors (VLRs), are constructed from leucine-rich repeat (LRR) modules. Structural studies of VLRs have shown that these LRR-based receptors bind antigens though their concave surface, in addition to a unique hypervariable loop in the C-terminal LRR capping module. These studies have revealed a remarkable example of convergent evolution in which jawless vertebrates adopted the LRR scaffold to recognize as broad a spectrum of antigens as the Ig-based antibodies and TCRs of jawed vertebrates, with altogether comparable affinity and specificity.

  6. Dimethyl fumarate modulation of immune and antioxidant responses: application to HIV therapy

    PubMed Central

    Gill, Alexander J.; Kolson, Dennis L.

    2013-01-01

    The persistence of chronic immune activation and oxidative stress in human immunodeficiency virus (HIV)-infected, antiretroviral drug-treated individuals are major obstacles to fully preventing HIV disease progression. The immune modulator and antioxidant dimethyl fumarate (DMF) is effective in treating immune-mediated diseases and it also has potential applications to limiting HIV disease progression. Among the relevant effects of DMF and its active metabolite monomethyl fumarate (MMF) are induction of a Th1 → Th2 lymphocyte shift, inhibition of pro-inflammatory cytokine signaling, inhibition of NF-κB nuclear translocation, inhibition of dendritic cell maturation, suppression of lymphocyte and endothelial cell adhesion molecule expression, and induction of the Nrf2-dependent antioxidant response element (ARE) and effector genes. Associated with these effects are reduced lymphocyte and monocyte infiltration into psoriatic skin lesions in humans and immune-mediated demyelinating brain lesions in rodents, which confirms potent systemic and central nervous system (CNS) effects. In addition, DMF and MMF limit HIV infection in macrophages in vitro, albeit by unknown mechanisms. Finally, DMF and MMF also suppress neurotoxin production from HIV-infected macrophages, which drives CNS neurodegeneration. Thus, DMF might protect against systemic and CNS complications in HIV infection through its effective suppression of immune activation, oxidative stress, HIV replication, and macrophage-associated neuronal injury. PMID:23971529

  7. Dengue and soluble mediators of the innate immune system.

    PubMed

    Espada-Murao, Lyre Anni; Morita, Kouichi

    2011-12-01

    Huge emphasis has been placed on the role of the adaptive immune system in dengue pathogenesis. Yet there is increasing evidence for the importance of the innate immune system in regulating dengue infection and possibly influencing the disease. This review focuses on the interplay between the innate immune system and dengue and highlights the role of soluble immunological mediators. Type I and type II interferons of the innate immune system demonstrate non-overlapping roles in dengue infection. Furthermore, while some IFN responses to dengue are protective, others may exert disease-related effects on the host. But aside from interferons, a number of cytokines have also been implicated in dengue pathogenesis. Our expanding knowledge of cytokines indicates that these soluble mediators act upon a complicated network of events to provoke the disease. This cytokine storm is generally attributed to massive T cell activation as an outcome of secondary infection. However, there is reason to believe that innate immune response-derived cytokines also have contributory effects, especially in the context of severe cases of primary dengue infection. Another less popular but interesting perspective on dengue pathogenesis is the effect of mosquito feeding on host immune responses and viral infection. Various studies have shown that soluble factors from vector saliva have the capacity to alter immune reactions and thereby influence pathogen transmission and establishment. Hence, modulation of the innate immune system at various levels of infection is a critical component of dengue disease. In the absence of an approved drug or vaccine for dengue, soluble mediators of the innate immune system could be a strategic foothold for developing anti-viral therapeutics and improving clinical management.

  8. [Immune proteasomes in the development of rat immune system].

    PubMed

    Karpova, Ia D; Lyupina, Iu V; Astakhova, T M; Stepanova, A A; Erokhov, P A; Abramova, E B; Sharova, N P

    2013-01-01

    their plunge by P5 may be related to the loss of liver function of a primary lymphoid organ of the immune system by this stage and disappearance of B-lymphocytes enriched by immune proteasomes in it. In the spleen and liver, MHC class I molecules were revealed at the periods of the raise of proteasome immune subunits level. On E21 , the liver was enriched by neuronal NO-synthase, its level decreased after birth and enhanced to P18. This fact indicates the possibility of the induction of the immune subunits LMP7 [character: see text] LMP2 expression in hepatocytes in signal way with neuronal NO-synthase participation. The results obtained prove that T-cell immune response with spleen participation as regards rat liver cells is possible starting with P19-P21 stage. First, at this period, white pulp T-area is formed in the spleen. Second, enhanced immune proteasomes and MHC class I molecules levels in hepatocytes can procure antigenic epitopes formation from foreign proteins and their delivery to cell surface for their subsequent presentation for cytotoxic T-lymphocytes.

  9. Feeding Our Immune System: Impact on Metabolism

    PubMed Central

    Wolowczuk, Isabelle; Verwaerde, Claudie; Viltart, Odile; Delanoye, Anne; Delacre, Myriam; Pot, Bruno; Grangette, Corinne

    2008-01-01

    Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose) impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs) of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy. PMID:18350123

  10. Immunological memory within the innate immune system.

    PubMed

    Sun, Joseph C; Ugolini, Sophie; Vivier, Eric

    2014-06-17

    Immune memory has traditionally been the domain of the adaptive immune system, present only in antigen-specific T and B cells. The purpose of this review is to summarize the evidence for immunological memory in lower organisms (which are not thought to possess adaptive immunity) and within specific cell subsets of the innate immune system. A special focus will be given to recent findings in both mouse and humans for specificity and memory in natural killer (NK) cells, which have resided under the umbrella of innate immunity for decades. The surprising longevity and enhanced responses of previously primed NK cells will be discussed in the context of several immunization settings. © 2014 The Authors.

  11. Metronidazole and the immune system.

    PubMed

    Shakir, L; Javeed, A; Ashraf, M; Riaz, A

    2011-06-01

    Metronidazole (MTZ) is a nitroimidazole antibiotic used mainly for the treatment of infections caused by susceptible organisms, particularly anaerobic bacteria and protozoa. Distinct from its antibiotic, amoebicidal, and antiprotozoal effects, MTZ displays immunopharmacological behaviour. This review outlines multiple effects of MTZ on different aspects of immunity, including innate and acquired immunity, and also highlights the immunopharmacological behaviour of MTZ in terms of its relevance to inflammation, delayed type hypersensitivity (DTH) and graft versus host disease (GVHD).

  12. Hormetic Response to Low-Dose Radiation: Focus on the Immune System and Its Clinical Implications.

    PubMed

    Cui, Jiuwei; Yang, Guozi; Pan, Zhenyu; Zhao, Yuguang; Liang, Xinyue; Li, Wei; Cai, Lu

    2017-01-27

    The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications.

  13. Hormetic Response to Low-Dose Radiation: Focus on the Immune System and Its Clinical Implications

    PubMed Central

    Cui, Jiuwei; Yang, Guozi; Pan, Zhenyu; Zhao, Yuguang; Liang, Xinyue; Li, Wei; Cai, Lu

    2017-01-01

    The interrelationship between ionizing radiation and the immune system is complex, multifactorial, and dependent on radiation dose/quality and immune cell type. High-dose radiation usually results in immune suppression. On the contrary, low-dose radiation (LDR) modulates a variety of immune responses that have exhibited the properties of immune hormesis. Although the underlying molecular mechanism is not fully understood yet, LDR has been used clinically for the treatment of autoimmune diseases and malignant tumors. These advancements in preclinical and clinical studies suggest that LDR-mediated immune modulation is a well-orchestrated phenomenon with clinical potential. We summarize recent developments in the understanding of LDR-mediated immune modulation, with an emphasis on its potential clinical applications. PMID:28134809

  14. 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.

  15. 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.

  16. Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.

    PubMed

    Troutwine, B R; Ghezzi, A; Pietrzykowski, A Z; Atkinson, N S

    2016-04-01

    A growing body of evidence has shown that alcohol alters the activity of the innate immune system and that changes in innate immune system activity can influence alcohol-related behaviors. Here, we show that the Toll innate immune signaling pathway modulates the level of alcohol resistance in Drosophila. In humans, a low level of response to alcohol is correlated with increased risk of developing an alcohol use disorder. The Toll signaling pathway was originally discovered in, and has been extensively studied in Drosophila. The Toll pathway is a major regulator of innate immunity in Drosophila, and mammalian Toll-like receptor signaling has been implicated in alcohol responses. Here, we use Drosophila-specific genetic tools to test eight genes in the Toll signaling pathway for effects on the level of response to ethanol. We show that increasing the activity of the pathway increases ethanol resistance whereas decreasing the pathway activity reduces ethanol resistance. Furthermore, we show that gene products known to be outputs of innate immune signaling are rapidly induced following ethanol exposure. The interaction between the Toll signaling pathway and ethanol is rooted in the natural history of Drosophila melanogaster.

  17. Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway

    PubMed Central

    Troutwine, Benjamin R.; Ghezzi, Alfredo; Pietrzykowski, Andrzej Z.; Atkinson, Nigel S.

    2016-01-01

    A growing body of evidence has shown that alcohol alters the activity of the innate immune system and that changes in innate immune system activity can influence alcohol-related behaviors (Cui et al., 2014; Vetreno & Crews, 2014). Here we show that the Toll innate immune signaling pathway modulates the level of alcohol resistance in Drosophila. In humans, a low level of response to alcohol is correlated with increased risk of developing an alcohol use disorder (Schuckit, 1994). The Toll signaling pathway was originally discovered in, and has been extensively studied in Drosophila. The Toll pathway is a major regulator of innate immunity in Drosophila, and mammalian Toll-like receptor signaling has been implicated in alcohol responses. Here, we use Drosophila-specific genetic tools to test eight genes in the Toll signaling pathway for effects on the level of response to ethanol. We show that increasing the activity of the pathway increases ethanol resistance while decreasing pathway activity reduces ethanol resistance. Furthermore, we show that gene products known to be outputs of innate immune signaling are rapidly induced following ethanol exposure. The interaction between the Toll signaling pathway and ethanol is rooted in the natural history of Drosophila melanogaster. PMID:26916032

  18. 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

  19. Effect of age and maternal antibodies on the systemic and mucosal immune response after neonatal immunization in a porcine model

    PubMed Central

    Guzman-Bautista, Edgar R; Garcia-Ruiz, Carlos E; Gama-Espinosa, Alicia L; Ramirez-Estudillo, Carmen; Rojas-Gomez, Oscar I; Vega-Lopez, Marco A

    2014-01-01

    Newborn mammals are highly susceptible to respiratory infections. Although maternal antibodies (MatAb) offer them some protection, they may also interfere with their systemic immune response to vaccination. However, the impact of MatAb on the neonatal mucosal immune response remains incompletely described. This study was performed to determine the effect of ovalbumin (OVA)-specific MatAb on the anti-OVA antibody response in sera, nasal secretions and saliva from specific pathogen-free Vietnamese miniature piglets immunized at 7 or 14 days of age. Our results demonstrated that MatAb increased antigen-specific IgA and IgG responses in sera, and transiently enhanced an early secretory IgA response in nasal secretions of piglets immunized at 7 days of age. In contrast, we detected a lower mucosal (nasal secretion and saliva) anti-OVA IgG response in piglets with MatAb immunized at 14 days of age, compared with piglets with no MatAb, suggesting a modulatory effect of antigen-specific maternal factors on the isotype transfer to the mucosal immune exclusion system. In our porcine model, we demonstrated that passive maternal immunity positively modulated the systemic and nasal immune responses of animals immunized early in life. Our results, therefore, open the possibility of inducing systemic and respiratory mucosal immunity in the presence of MatAb through early vaccination. PMID:24754050

  20. Bone and the Innate Immune System

    PubMed Central

    Charles, Julia F.; Nakamura, Mary C.

    2014-01-01

    The immune system and bone are intimately linked with significant physical and functionally related interactions. The innate immune system functions as an immediate response system to initiate protections against local challenges such as pathogens and cellular damage. Bone is a very specific microenvironment in which infectious attack is less common but repair and regeneration are ongoing and important functions. Thus in the bone the primary goal of innate immune and bone interactions is to maintain tissue integrity. Innate immune signals are critical for removal of damaged and apoptotic cells and to stimulate normal tissue repair and regeneration. In this review we focus on these innate immune mechanisms that function to regulate bone homeostasis. PMID:24500569

  1. Worming Their Way into the Picture: Microbiota Help Helminths Modulate Host Immunity.

    PubMed

    Reynolds, Lisa A; Finlay, B Brett

    2015-11-17

    Parasitic helminths are potent regulators of host immunity, including inhibition of allergic inflammation. In this issue of Immunity, Zaiss et al. (2015) reveal that microbiota compositional shifts during helminth infection contribute to the multifaceted ways that helminths modulate host immunity. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Neuroimmune interactions: dendritic cell modulation by the sympathetic nervous system.

    PubMed

    Takenaka, Maisa C; Guereschi, Marcia G; Basso, Alexandre S

    2017-02-01

    Dendritic cells are of paramount importance bridging innate and adaptive immune responses. Depending on the context, after sensing environmental antigens, commensal microorganisms, pathogenic agents, or antigens from the diet, dendritic cells may drive either different effector adaptive immune responses or tolerance, avoiding tissue damage. Although the plasticity of the immune response and the capacity to regulate itself are considered essential to orchestrate appropriate physiological responses, it is known that the nervous system plays a relevant role controlling immune cell function. Dendritic cells present in the skin, the intestine, and lymphoid organs, besides expressing adrenergic receptors, can be reached by neurotransmitters released by sympathetic fibers innervating these tissues. These review focus on how neurotransmitters from the sympathetic nervous system can modulate dendritic cell function and how this may impact the immune response and immune-mediated disorders.

  3. 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)

  4. Physical Theory of the Immune System

    NASA Astrophysics Data System (ADS)

    Deem, Michael

    2012-10-01

    I will discuss to theories of the immune system and describe a theory of the immune response to vaccines. I will illustrate this theory by application to design of the annual influenza vaccine. I will use this theory to explain limitations in the vaccine for dengue fever and to suggest a transport-inspired amelioration of these limitations.

  5. 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)

  6. Systems biology of circadian-immune interactions.

    PubMed

    Mavroudis, P D; Scheff, J D; Calvano, S E; Androulakis, I P

    2013-01-01

    There is increasing evidence that the immune system is regulated by circadian rhythms. A wide range of immune parameters, such as the number of red blood cells and peripheral blood mononuclear cells as well as the level of critical immune mediators, such as cytokines, undergo daily fluctuations. Current experimental data indicate that circadian information reaches immune tissues mainly through diurnal patterns of autonomic and endocrine rhythms. In addition, immune factors such as cytokines can also influence the phase of the circadian clock, providing bidirectional flow of circadian information between the neuroendocrine and immune systems. This network of neuroendocrine-immune interactions consists of complexly integrated molecular feedback and feedforward loops that function in synchrony in order to optimize immune response. Chronic stress can disrupt this intrinsic orchestration, as several endocrine signals of chronically stressed patients present blunted rhythmic characteristics. Reprogramming of biological rhythms has recently gained much attention as a potent method to leverage homeostatic circadian controls to ultimately improve clinical outcomes. Elucidation of the intrinsic properties of such complex systems and optimization of intervention strategies require not only an accurate identification of the signaling pathways that mediate host responses, but also a system-level description and evaluation. Copyright © 2012 S. Karger AG, Basel.

  7. 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.

  8. How phototherapy affects the immune system

    NASA Astrophysics Data System (ADS)

    Dyson, Mary

    2008-03-01

    The immune system is a complex group of cells, tissues and organs that recognize and attack foreign substances, pathogenic organisms and cancer cells. It also responds to injury by producing inflammation. The immune system has peripheral components that include skin-associated lymphoid tissues (SALT) and mucosa-associated lymphoid tissues (MALT), located where pathogens and other harmful substances gain access to the body. Phototherapy, delivered at appropriate treatment parameters, exerts direct actions on the cellular elements of the peripheral part of the immune system since it is readily accessible to photons.

  9. Dying autologous cells as instructors of the immune system.

    PubMed

    Munoz, L E; Herrmann, M; Berens, C

    2015-01-01

    In an organism, cell death occurs at many different sites and in many different forms. It is frequently part of normal development or serves to maintain cell homeostasis. In other cases, cell death not only occurs due to injury, disease or infection, but also as a consequence of various therapeutic interventions. However, in all of these scenarios, the immune system has to react to the dying and dead cells and decide whether to mount an immune response, to remain quiet or to initiate healing and repopulation. This is essential for the organism, testified by many diseases that are associated with malfunctioning in the cell death process, the corpse removal, or the ensuing immune responsiveness. Therefore, dying cells generally have to be considered as instructors of the immune system. How this happens and which signals and pathways contribute to modulate or shape the immune response is still elusive in many conditions. The articles presented in this Special Issue address such open questions. They highlight that the context in which cell death occurs will not only influence the cell death process itself, but also affect the surrounding cellular milieu, how the generation and presence of 'eat me' signals can have an impact on cell clearance, and that the exact nature of the residual 'debris' and how it is processed are fundamental to determining the immunological consequences. Hopefully, these articles initiate new approaches and new experiments to complete our understanding of how cell death and the immune system interact with each other.

  10. Modulation of Innate Immune Mechanisms to Enhance Leishmania Vaccine-Induced Immunity: Role of Coinhibitory Molecules

    PubMed Central

    Gannavaram, Sreenivas; Bhattacharya, Parna; Ismail, Nevien; Kaul, Amit; Singh, Rakesh; Nakhasi, Hira L.

    2016-01-01

    No licensed human vaccines are currently available against any parasitic disease including leishmaniasis. Several antileishmanial vaccine formulations have been tested in various animal models, including genetically modified live-attenuated parasite vaccines. Experimental infection studies have shown that Leishmania parasites utilize a broad range of strategies to undermine effector properties of host phagocytic cells, i.e., dendritic cells (DCs) and macrophages (MΦ). Furthermore, Leishmania parasites have evolved strategies to actively inhibit TH1 polarizing functions of DCs and to condition the infected MΦ toward anti-inflammatory/alternative/M2 phenotype. The altered phenotype of phagocytic cells is characterized by decreased production of antimicrobial reactive oxygen, nitrogen molecules, and pro-inflammatory cytokines, such as IFN-γ, IL-12, and TNF-α. These early events limit the activation of TH1-effector cells and set the stage for pathogenesis. Furthermore, this early control of innate immunity by the virulent parasites results in substantial alteration in the adaptive immunity characterized by reduced proliferation of CD4+ and CD8+ T cells and TH2-biased immunity that results in production of anti-inflammatory cytokines, such as TGF-β, and IL-10. More recent studies have also documented the induction of coinhibitory ligands, such as CTLA-4, PD-L1, CD200, and Tim-3, that induce exhaustion and/or non-proliferation in antigen-experienced T cells. Most of these studies focus on viral infections in chronic phase, thus limiting the direct application of these results to parasitic infections and much less to parasitic vaccines. However, these studies suggest that vaccine-induced protective immunity can be modulated using strategies that enhance the costimulation that might reduce the threshold necessary for T cell activation and conversely by strategies that reduce or block inhibitory molecules, such as PD-L1 and CD200. In this review, we will focus on the

  11. Tamibarotene modulates the local immune response in experimental periodontitis.

    PubMed

    Jin, Ying; Wang, Linyuan; Liu, Dixin; Lin, Xiaoping

    2014-12-01

    Tamibarotene (Am80), a synthetic retinoic acid receptor (RAR), is an agonist with high specificity for RARα and RARβ. Retinoid agonists have been shown to inhibit Th17 cell polarization and to enhance forkhead box P3 (Foxp3) expression during the course of inflammatory diseases. The aim of this study was to evaluate the previously unrecognized role of Am80 in regulating the immune responses of periodontitis within the oral microenvironment. The experimental model of periodontitis in mice was induced by oral infection with Porphyromonas gingivalis (P. gingivalis) W83. Our results indicated that Am80 effectively suppressed alveolar bone resorption induced by P. gingivalis W83 and decreased the number of osteoclasts. We clarified that these effects were closely associated with the reduced percentage of CD4(+) retinoid-related orphan receptor (ROR)γt(+) cells and increased the percentage of CD4(+) Foxp3(+) cells in the gingival tissues, cervical lymph nodes (CLNs), and spleen. Furthermore, in P. gingivalis-infected mice, Am80 down-regulated mRNA expression levels of interleukin-17A (IL-17A), receptor activator of nuclear factor-kappa beta ligand (RANKL), monocyte chemotactic protein-1 (MCP-1), IL-6, and IL-1β. Simultaneously, Am80 up-regulated expression levels of IL-10 and transforming growth factor-β1 (TGF-β1) in gingival tissues and the CLNs. Our results suggest that Am80 could protect against periodontal bone resorption, primarily through the modulation of immune responses in the oral microenvironment, and demonstrate the potential of Am80 as a novel clinical strategy for preventing periodontitis.

  12. The immune system and cardiac repair.

    PubMed

    Frangogiannis, Nikolaos G

    2008-08-01

    Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll-like receptor-mediated pathways, the complement cascade and reactive oxygen generation induce nuclear factor (NF)-kappaB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming growth factor (TGF)-beta plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding

  13. The immune system and cardiac repair

    PubMed Central

    Frangogiannis, Nikolaos G.

    2008-01-01

    Myocardial infarction is the most common cause of cardiac injury and results in acute loss of a large number of myocardial cells. Because the heart has negligible regenerative capacity, cardiomyocyte death triggers a reparative response that ultimately results in formation of a scar and is associated with dilative remodeling of the ventricle. Cardiac injury activates innate immune mechanisms initiating an inflammatory reaction. Toll Like Receptor-mediated pathways, the complement cascade and reactive oxygen generation induce Nuclear Factor (NF)-κB activation and upregulate chemokine and cytokine synthesis in the infarcted heart. Chemokines stimulate the chemotactic recruitment of inflammatory leukocytes into the infarct, while cytokines promote adhesive interactions between leukocytes and endothelial cells, resulting in transmigration of inflammatory cells into the site of injury. Monocyte subsets play distinct roles in phagocytosis of dead cardiomyocytes and in granulation tissue formation through the release of growth factors. Clearance of dead cells and matrix debris may be essential for resolution of inflammation and transition into the reparative phase. Transforming Growth Factor (TGF)-β plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. Myofibroblast proliferation and angiogenesis result in formation of highly vascularized granulation tissue. As the healing infarct matures, fibroblasts become apoptotic and a collagen-based matrix is formed, while many infarct neovessels acquire a muscular coat and uncoated vessels regress. Timely resolution of the inflammatory infiltrate and spatial containment of the inflammatory and reparative response into the infarcted area are essential for optimal infarct healing. Targeting inflammatory pathways following infarction may reduce cardiomyocyte injury and attenuate adverse remodeling. In addition, understanding the

  14. Inhibitory Receptors of the Immune System: Functions and Therapeutic Implications

    PubMed Central

    Zhang, Jian; Xiao, Xiang; Liu, Wentao; Demirci, Gulcin; Li, Xian C

    2009-01-01

    The immune system has a remarkable ability to respond to seemingly endless antigens. In essence, a productive immune response takes place along a well defined but treacherous line, that is to effectively eradicate pathogens, and at the same time avoid causing damage to self organs. This type of response is fine-tuned, at least in part, by a complex array of pathways that either promote or inhibit the activation of innate and adaptive immune cells. Much effort has been focused on pathways that can support immune activation. In this article, we review specifically pathways that can inhibit immune responses and maintain immune homeostasis, highlighting our recent understanding on the role of inhibitory receptors that selectively engage the self MHC class I molecules and the B7 superfamily members, we also discuss the inhibitory Fc receptors and inhibitory cytokines and how such pathways, either individually or collectively, regulate innate and adaptive immune responses. Finally, we summarize new emerging approaches on how such negative pathways can be therapeutically modulated in various disease settings. PMID:20003816

  15. 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

  16. A brief journey through the immune system.

    PubMed

    Yatim, Karim M; Lakkis, Fadi G

    2015-07-07

    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.

  17. [Regulation of allergy by innate immune system].

    PubMed

    Kumagai, Yutaro; Akira, Shizuo

    2009-11-01

    Allergy is an immune disease including asthma. Activation of Th2 response, such as production of IL-4, IL-5 and IL-13 from CD4+ T cells and IgG1 or IgE from B cells is responsible for allergy. Activation of acquired immune system requires preceding activation of innate immunity, therefore innate immunity may control Th2 response and allergy. Recent studies revealed that dendritic cells, epithelial cells, and basophils play central roles in the initiation of Th2 response. In this review, we will summarize the current understanding on the control of Th2 and allergic responses by innate immune system, and discuss recent findings on house dust mite-induced allergic response based on these understandings.

  18. The Lymphatic System: Integral Roles in Immunity

    PubMed Central

    Randolph, Gwendalyn J.; Ivanov, Stoyan; Zinselmeyer, Bernd H.; Scallan, Joshua P.

    2017-01-01

    The lymphatic vasculature is not considered a formal part of the immune system, but it is critical to immunity. One of its major roles is in the coordination of the trafficking of antigen and immune cells. However, other roles in immunity are emerging. Lymphatic endothelial cells, for example, directly present antigen or express factors that greatly influence the local environment. We cover these topics herein and discuss how other properties of the lymphatic vasculature, such as mechanisms of lymphatic contraction (which immunologists traditionally do not take into account), are nonetheless integral in the immune system. Much is yet unknown, and this nascent subject is ripe for exploration. We argue that to consider the impact of lymphatic biology in any given immunological interaction is a key step toward integrating immunology with organ physiology and ultimately many complex pathologies. PMID:27860528

  19. Systemic tolerance and secretory immunity after oral immunization

    PubMed Central

    1980-01-01

    Diminished systemic immune reaction after ingestion of antigen has been reported in several animal models. Conversely, it has been reported recently that oral immunization may lead to the production of secretory antibodies. To determine whether these events could occur concurrently, CBA/J mice were immunized intragastrically with varying doses of ovalbumin (OVA) and Streptococcus mutans. After 7 d, the animals were challenged systemically with antigen in complete adjuvant and 8 d later serum and saliva taken, and the draining lymph nodes assayed for a proliferative response. Intragastric doses of 1 mg OVA or 10(9) S. mutans led to significant suppression of the proliferative response, and intragastric doses of 10 mg OVA or 2.5 X 10(9) S. mutans led to the production of detectable salivary antibodies using hemagglutination. Serum antibodies were not detected after intragastric administration of OVA or S. mutans. Suppression of the proliferative response could be detected from 2-60 d after intragastric administration of OVA, and 2-21 d after S. mutans. Prior intragastric immunization with heterologous antigens did not suppress the response to OVA or S. mutans. Transfer of 40 X 10(6) mesenteric lymph node cells from mice given 20 mg OVA or 10(9) S. mutans led to suppression of the proliferative response in syngeneic recipients. Salivary antibodies wer removed by absorption with anti-IgA, but not anti-IgG or IgM, indicating that they were of the IgA class. It appears that intragastric administration of soluble or particulate antigens in mice may lead to the concurrent induction of salivary antibodies and systemic suppression. PMID:7452148

  20. Immune Modulation in the Treatment of Amyotrophic Lateral Sclerosis: A Review of Clinical Trials

    PubMed Central

    Khalid, Syed I.; Ampie, Leonel; Kelly, Ryan; Ladha, Shafeeq S.; Dardis, Christopher

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the degeneration of motor neurons. Though many molecular and genetic causes are thought to serve as predisposing or disease propagating factors, the underlying pathogenesis of the disease is not known. Recent discoveries have demonstrated the presence of inflammation propagating substrates in the central nervous system of patients afflicted with ALS. Over the past decade, this hypothesis has incited an effort to better understand the role of the immune system in ALS and has led to the trial of several potential immune-modulating therapies. Here, we briefly review advances in the role of such therapies. The clinical trials discussed here are currently ongoing or have been concluded at the time of writing.

  1. The immune system as a sensor of the metabolic state

    PubMed Central

    Odegaard, Justin I.; Chawla, Ajay

    2013-01-01

    Mammals possess a remarkable ability to maintain and defend a constant internal milieu against diverse environmental threats. Unsurprisingly, the two systems tasked with these duties, metabolism and immunity, have evolved to share a common modular architecture that allows extensive bidirectional communication and coordination. Indeed, recent observations have highlighted numerous, functionally critical immune regulatory modules located within diverse metabolic circuits. In this Review, we discuss the architectural commonality between immunity and metabolism, and highlight how these two primordially disparate systems leverage shared regulatory axes to coordinate metabolic physiology under conditions of normality and chronic overnutrition. Such an integrated perspective both advances our understanding of basic physiology and highlights potential opportunities for therapeutic intervention in metabolic dysfunction. PMID:23601683

  2. BT cationic peptides: small peptides that modulate innate immune responses of chicken heterophils and monocytes.

    PubMed

    Kogut, Michael H; Genovese, Kenneth J; He, Haiqi; Swaggerty, Christina L; Jiang, Yi Wei

    2012-01-15

    Neonatal poultry exhibit a transient susceptibility to infectious diseases during the first week of life that stems from inefficient host defense mechanisms. Yet, the initial host immune response to pathogens is a critical determinant of disease resistance and susceptibility. With this context in mind, novel ways to stimulate or modulate the hosts' natural immune response is emerging as an important area of interest for food animal producers including the poultry industry. Specifically, we have been investigating new modulation strategies tailored around the selective stimulation of the host's immune system, and particularly rapid acting innate immunity, as an alternative to direct targeting of microbial pathogens. One such approach that we have been investigating is the use of a group of cationic peptides produced by a Gram-positive soil bacterium, Brevibacillus texasporus (BT peptides). We have previously shown that, provided as a feed additive, BT peptides significantly induced a concentration-dependent protection against cecal colonization and extraintestinal colonization by Salmonella enterica serovar Enteritidis (SE). This protection is not the result of direct antibacterial activity of the BT peptides on the SE since the concentrations used were below the minimum inhibitory concentration for SE. We also found that BT are not absorbed in the intestine, but still induce a significant up-regulation in the functional efficiency of peripheral blood heterophils and monocytes. The mechanisms of this immune modulation are unknown. Here, using in vitro models for measuring: (1) leukocyte oxidative burst, (2) changes in leukocyte cytokine and chemokines gene expression profiles, and (3) phosphorylation of the mitogen activated protein kinases (MAPKs) in leukocytes, we evaluated the role of BT peptides as priming mediators for heterophil and monocyte responses at the level of cell function, gene transcription/expression, and cell phosphorylation following stimulation

  3. Repeatedly administered antidepressant drugs modulate humoral and cellular immune response in mice through action on macrophages

    PubMed Central

    Kozlowski, Michael; Bryniarski, Pawel; Strobel, Spencer; Bryk, Agata; Myszka, Michal; Tyszka, Anna; Kuszmiersz, Piotr; Nowakowski, Jaroslaw; Filipczak-Bryniarska, Iwona

    2016-01-01

    Depression is associated with an altered immune response, which could be normalized by antidepressant drugs. However, little is known about the influence of antidepressants on the peripheral immune response and function of macrophages in individuals not suffering from depression. Our studies were aimed at determining the influence of antidepressant drugs on the humoral and cellular immune response in mice. Mice were treated intraperitoneally with imipramine, fluoxetine, venlafaxine, or moclobemide and contact immunized with trinitrophenyl hapten followed by elicitation and measurement of contact sensitivity by ear swelling response. Peritoneal macrophages from drug-treated mice were either pulsed with sheep erythrocytes or conjugated with trinitrophenyl and transferred into naive recipients to induce humoral or contact sensitivity response, respectively. Secretion of reactive oxygen intermediates, nitric oxide, and cytokines by macrophages from drug-treated mice was assessed, respectively, in chemiluminometry, Griess-based colorimetry and enzyme-linked immunosorbent assay, and the expression of macrophage surface markers was analyzed cytometrically. Treatment of mice with fluoxetine, venlafaxine, and moclobemide results in suppression of humoral and cell-mediated immunity with a reduction of the release of macrophage proinflammatory mediators and the expression of antigen-presentation markers. In contrast, treatment with imipramine enhanced the humoral immune response and macrophage secretory activity but slightly suppressed active contact sensitivity. Our studies demonstrated that systemically delivered antidepressant drugs modulate the peripheral humoral and cell-mediated immune responses, mostly through their action on macrophages. Imipramine was rather proinflammatory, whereas other tested drugs expressed immunosuppressive potential. Current observations may be applied to new therapeutic strategies dedicated to various disorders associated with excessive

  4. Selective estrogen receptor modulators differentially alter the immune response of gilthead seabream juveniles.

    PubMed

    Rodenas, M C; Cabas, I; García-Alcázar, A; Meseguer, J; Mulero, V; García-Ayala, A

    2016-05-01

    17α-ethynylestradiol (EE2), a synthetic estrogen used in oral contraceptives and hormone replacement therapy, tamoxifen (Tmx), a selective estrogen-receptor modulator used in hormone replacement therapy, and G1, a G protein-coupled estrogen receptor (GPER) selective agonist, differentially increased the hepatic vitellogenin (vtg) gene expression and altered the immune response in adult gilthead seabream (Sparus aurata L.) males. However, no information exists on the effects of these compounds on the immune response of juveniles. This study aims, for the first time, to investigate the effects of the dietary intake of EE2, Tmx or G1 on the immune response of gilthead seabream juveniles and the capacity of the immune system of the specimens to recover its functionality after ceasing exposures (recovery period). The specimens were immunized with hemocyanin in the presence of aluminium adjuvant 1 (group A) or 120 (group B) days after the treatments ceased (dpt). The results indicate that EE2 and Tmx, but not G1, differentially promoted a transient alteration in hepatic vtg gene expression. Although all three compounds did not affect the production of reactive oxygen intermediates, they inhibited the induction of interleukin-1β (il1b) gene expression after priming. Interestingly, although Tmx increased the percentage of IgM-positive cells in both head kidney and spleen during the recovery period, the antibody response of vaccinated fish varied depending on the compound used and when the immunization was administered. Taken together, our results suggest that these compounds differentially alter the capacity of fish to respond to infection during ontogeny and, more interestingly, that the adaptive immune response remained altered to an extent that depends on the compound.

  5. [Mucosal immune system and mucosal vaccine].

    PubMed

    Yanagita, M; Hiroi, T; Kiyono, H

    1997-02-01

    In the recent years, mucosal immune system is recognized as the new world in the area of immunology. The host is continuously exposed to the numerous numbers of environmental antigens via the mucosa and the skin. A total surface area of the mucosa is approximately 200 times larger than that of the skin, and the former surface area contains a large numbers of lymphoid cells (> 10(11)). In order to provide an effective defence for the host by vaccine, it is logical to consider the mucosal immune system. According to the new informations obtained by the modern cellular and molecular immunobiological knowledges and approaches, the concept of the mucosal immune system has been rapidly proceeded to apply for the development of mucosal vaccine. In this report, we have reviewed and discussed the recent progress in the characterization of mucosal immune system and the development of mucosal vaccine.

  6. The innate immune system in demyelinating disease.

    PubMed

    Mayo, Lior; Quintana, Francisco J; Weiner, Howard L

    2012-07-01

    Demyelinating diseases such as multiple sclerosis are chronic inflammatory autoimmune diseases with a heterogeneous clinical presentation and course. Both the adaptive and the innate immune systems have been suggested to contribute to their pathogenesis and recovery. In this review, we discuss the role of the innate immune system in mediating demyelinating diseases. In particular, we provide an overview of the anti-inflammatory or pro-inflammatory functions of dendritic cells, mast cells, natural killer (NK) cells, NK-T cells, γδ T cells, microglial cells, and astrocytes. We emphasize the interaction of astroctyes with the immune system and how this interaction relates to the demyelinating pathologies. Given the pivotal role of the innate immune system, it is possible that targeting these cells may provide an effective therapeutic approach for demyelinating diseases.

  7. Weakened Immune System and Adult Vaccination

    MedlinePlus

    ... for Healthcare Professionals Weakened Immune System and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... up to age 26 years Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  8. Symbiotic commensal bacteria direct maturation of the host immune system.

    PubMed

    Edelman, Sanna M; Kasper, Dennis L

    2008-11-01

    Although commensal bacteria are known to play an important role in the proper maturation of the immune system of their mammalian hosts, the molecular mechanisms underlying this immunomodulation are poorly characterized. The present review summarizes recent findings in the field and describes new knowledge on the interplay of the innate and adaptive arms of the immune response induced by symbiotic bacterial carbohydrate antigens. Commensal bacteria in the intestine not only interact directly with dendritic cells but also engage in cross-talk with epithelial cells. These interactions lead to the induction of tolerogenic antigen-presenting cells in the lamina propria and ultimately to the regulation of functional maturation of effector T cells. Upon recognition of capsular polysaccharide antigens of commensal bacteria by dendritic cells (through toll-like receptor 2), innate immune responses facilitate and act in conjunction with adaptive responses to promote optimal Th1 polarization. In contrast, adaptive immunoglobulin A responses to symbiotic bacteria regulate the magnitude of oxidative innate immune responses in the mucosa as well as bacterial epitope expression in the lumen. Accumulating evidence is elucidating surface carbohydrate structures of symbiotic bacteria that drive the modulation of the intestinal immune system, resulting in mature, balanced immune responses and oral tolerance.

  9. Innate immune system and tissue regeneration in Planarians: An area ripe for exploration

    PubMed Central

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

    2014-01-01

    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. PMID:25082737

  10. 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.

  11. Modulation of Antiviral Immunity by Heme Oxygenase-1.

    PubMed

    Espinoza, Janyra A; González, Pablo A; Kalergis, Alexis M

    2017-03-01

    Heme oxygenase-1 (HO-1) is a stress-inducible, anti-inflammatory, and cytoprotective enzyme expressed in most cell types in the organism. Under several stress stimuli, HO-1 expression and activity is up-regulated to catalyze the rate-limiting enzymatic step of heme degradation into carbon monoxide, free iron, and biliverdin. Besides its effects on cell metabolism, HO-1 is also capable of modulating host innate and adaptive immune responses in response to sepsis, transplantation, and autoimmunity, and preventing oxidative damage associated with inflammation. In addition, recent studies have reported that HO-1 can exert a significant antiviral activity against a wide variety of viruses, including HIV, hepatitis C virus, hepatitis B virus, enterovirus 71, influenza virus, respiratory syncytial virus, dengue virus, and Ebola virus, among others. Herein, we address the current understanding of the functional significance of HO-1 against a variety of viruses and its potential as a therapeutic strategy to prevent and control viral infections. Furthermore, we review the most important features of the immunoregulatory functions for this enzyme.

  12. Pathogen mimicry of host protein-protein interfaces modulates immunity.

    PubMed

    Guven-Maiorov, Emine; Tsai, Chung-Jung; Nussinov, Ruth

    2016-10-01

    Signaling pathways shape and transmit the cell's reaction to its changing environment; however, pathogens can circumvent this response by manipulating host signaling. To subvert host defense, they beat it at its own game: they hijack host pathways by mimicking the binding surfaces of host-encoded proteins. For this, it is not necessary to achieve global protein homology; imitating merely the interaction surface is sufficient. Different protein folds often interact via similar protein-protein interface architectures. This similarity in binding surfaces permits the pathogenic protein to compete with a host target protein. Thus, rather than binding a host-encoded partner, the host protein hub binds the pathogenic surrogate. The outcome can be dire: rewiring or repurposing the host pathways, shifting the cell signaling landscape and consequently the immune response. They can also cause persistent infections as well as cancer by modulating key signaling pathways, such as those involving Ras. Mapping the rewired host-pathogen 'superorganism' interaction network - along with its structural details - is critical for in-depth understanding of pathogenic mechanisms and developing efficient therapeutics. Here, we overview the role of molecular mimicry in pathogen host evasion as well as types of molecular mimicry mechanisms that emerged during evolution.

  13. Non-therapeutic administration of a model antimicrobial growth promoter modulates intestinal immune responses

    PubMed Central

    2011-01-01

    Background The development of efficacious alternatives to antimicrobial growth promoters (AGP) in livestock production is an urgent issue, but is hampered by a lack of knowledge regarding the mode of action of AGP. The belief that AGP modulate the intestinal microbiota has become prominent in the literature; however, there is a lack of experimental evidence to support this hypothesis. Using a chlortetracycline-murine-Citrobacter rodentium model, the ability of AGP to modulate the intestinal immune system in mammals was investigated. Results C. rodentium was transformed with the tetracycline resistance gene, tetO, and continuous oral administration of a non-therapeutic dose of chlortetracycline to mice did not affect densities of C. rodentium CFU in feces throughout the experiment or associated with mucosal surfaces in the colon (i.e. at peak and late infection). However, chlortetracycline regulated transcription levels of Th1 and Th17 inflammatory cytokines in a temporal manner in C. rodentium-inoculated mice, and ameliorated weight loss associated with infection. In mice inoculated with C. rodentium, those that received chlortetracycline had less pathologic changes in the distal colon than mice not administered CTC (i.e. relative to untreated mice). Furthermore, chlortetracycline administration at a non-therapeutic dose did not impart either prominent or consistent effects on the colonic microbiota. Conclusion Data support the hypothesis that AGP function by modulating the intestinal immune system in mammals. This finding may facilitate the development of biorationale-based and efficacious alternatives to AGP. PMID:21943280

  14. Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone

    PubMed Central

    Muñoz-Durango, N.; Vecchiola, A.; Gonzalez-Gomez, L. M.; Simon, F.; Riedel, C. A.; Fardella, C. E.; Kalergis, A. M.

    2015-01-01

    The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models. PMID:26448944

  15. Modulation of Immunity and Inflammation by the Mineralocorticoid Receptor and Aldosterone.

    PubMed

    Muñoz-Durango, N; Vecchiola, A; Gonzalez-Gomez, L M; Simon, F; Riedel, C A; Fardella, C E; Kalergis, A M

    2015-01-01

    The mineralocorticoid receptor (MR) is a ligand dependent transcription factor. MR has been traditionally associated with the control of water and electrolyte homeostasis in order to keep blood pressure through aldosterone activation. However, there is growing evidence indicating that MR expression is not restricted to vascular and renal tissues, as it can be also expressed by cells of the immune system, where it responds to stimulation or antagonism, controlling immune cell function. On the other hand, aldosterone also has been associated with proinflammatory immune effects, such as the release of proinflammatory cytokines, generating oxidative stress and inducing fibrosis. The inflammatory participation of MR and aldosterone in the cardiovascular disease suggests an association with alterations in the immune system. Hypertensive patients show higher levels of proinflammatory mediators that can be modulated by MR antagonism. Although these proinflammatory properties have been observed in other autoimmune and chronic inflammatory diseases, the cellular and molecular mechanisms that mediate these effects remain unknown. Here we review and discuss the scientific work aimed at determining the immunological role of MR and aldosterone in humans, as well as animal models.

  16. Role of the innate immune system in acute viral myocarditis.

    PubMed

    Huang, Chien-Hua; Vallejo, Jesus G; Kollias, George; Mann, Douglas L

    2009-05-01

    Although the adaptive immune system is thought to play an important role in the pathogenesis of viral myocarditis, the role of the innate immune system has not been well defined. To address this deficiency, we employed a unique line of mice that harbor a genomic "knock in" of a mutated TNF gene lacking the AU rich element (TNF(ARE/ARE)) that is critical for TNF mRNA stability and translation, in order to examine the contribution of the innate immune system in encephalomyocarditis-induced myocarditis (EMCV). Heterozygous mice (TNF(ARE/+)) were infected with 500 plaque-forming units of EMCV. TNF(ARE/+)mice had a significantly higher 14-day mortality and myocardial inflammation when compared to littermate control mice. Virologic studies showed that the viral load at 14 days was significantly lower in the hearts of TNF(ARE/+) mice. TNF(ARE/+) mice had an exaggerated proinflammatory cytokine and chemokine response in the heart following EMCV infection. Modulation of the innate immune response in TNF(ARE/+) mice by the late administration of prednisolone resulted in a significant improvement in survival and decreased cardiac inflammation, whereas early administration of prednisolone resulted in a blunted innate response and increased mortality in littermate control mice. Viewed together, these data suggest that the duration and degree of activation of the innate immune system plays a critical role in determining host outcomes in experimental viral myocarditis.

  17. In vitro effects of GSM modulated radiofrequency fields on human immune cells.

    PubMed

    Tuschl, Helga; Novak, Waltraud; Molla-Djafari, Hamid

    2006-04-01

    Despite the important role of the immune system in defending the body against infections and cancer, only few investigations on possible effects of radiofrequency (RF) radiation on function of human immune cells have been undertaken. Aim of the present investigation was therefore to assess whether GSM modulated RF fields have adverse effects on the functional competence of human immune cells. Within the frame of the multidisciplinary project "Biological effects of high frequency electromagnetic fields (EMF)" sponsored by the National Occupation Hazard Insurance Association (AUVA) in vitro investigations were carried out on human blood cells. Exposure was performed at GSM Basic 1950 MHz, an SAR of 1 mW/g in an intermittent mode (5 min "ON", 10 min "OFF") and a maximum Delta T of 0.06 degrees C for the duration of 8 h. The following immune parameters were evaluated: (1) the intracellular production of interleukin-2 (IL-2) and interferon (INF) gamma in lymphocytes, and IL-1 and tumor necrosis factor (TNF)-alpha in monocytes were evaluated with monoclonal antibodies. (2) The activity of immune-relevant genes (IL 1-alpha and beta, IL-2, IL-2-receptor, IL-4, macrophage colony stimulating factor (MCSF)-receptor, TNF-alpha, TNF-alpha-receptor) and housekeeping genes was analyzed with real time PCR. (3) The cytotoxicity of lymphokine activated killer cells (LAK cells) against a tumor cell line was determined in a flow cytometric test. For each parameter, blood samples of at least 15 donors were evaluated. No statistically significant effects of exposure were found and there is no indication that emissions from mobile phones are associated with adverse effects on the human immune system.

  18. Modulation of chicken intestinal immune gene expression by small cationic peptides as feed additives during the first week posthatch

    USDA-ARS?s Scientific Manuscript database

    We have been investigating modulation strategies tailored around the selective stimulation of the host’s immune system as an alternative to direct targeting of microbial pathogens by antibiotics. One such approach is the use of a group of small cationic peptides (BT) produced by a Gram-positive soi...

  19. 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.

  20. [Biotherapy targeting the immune system].

    PubMed

    Frenzel, Laurent

    2015-01-01

    The use of monoclonal antibody targeted therapy has changed the management of several diseases, including in hematology and immunology. The panel of the present available biotherapies allows a specific action at various stages of the immune response. Indeed, some of these molecules can target the naive T cell at the immunological synapse or the way of TH1, TH17 and regulatory T cell. Others may be more specific for the B cell and immunoglobulin. Some will even be active on both B and T cells.

  1. The immune system--multiple sites but one system.

    PubMed

    Harleman, Johannes H

    2006-07-01

    Recently several guidelines were published on immunotoxicity. Validation studies have shown that detailed extended examination of the immune system is able to flag immunotoxic compounds. Parameters of the examination are presented. In the final examination it is important that the whole immune system is evaluated as one functional system--multiple sites but one system.

  2. Fatty acids, lipid emulsions and the immune and inflammatory systems.

    PubMed

    Miles, Elizabeth A; Calder, Philip C

    2015-01-01

    Fatty acids modulate the responses of cells of the immune system. Inflammatory and immune responses in patients receiving parenteral nutrition may be modulated by the type of lipid used, which may influence clinical outcomes. Lipid emulsions based solely upon soybean oil may not be optimal because of the role of n-6 fatty acids in promoting inflammation and suppressing immune responses. Lipid emulsions with soybean oil in various combinations with medium-chain triglycerides (MCTs), olive oil and fish oil are available. Some early studies have suggested better immune function with MCT-soybean oil than with soybean oil alone, but the differences were small, and more recent studies suggested little difference between soybean oil, MCT-soybean oil and soybean oil-olive oil regarding markers of inflammation and immunity. The inclusion of fish oil in combination with one or more other oils (i.e. soybean, MCT, olive) in the parenteral regimen administered to patients following major gastrointestinal surgery reduces the post-surgery rise in inflammatory markers and the fall in cell-mediated immune markers. These changes are associated with improvements in clinical outcomes. Whether similar effects of intravenous fish oil occur in critically ill patients is not clear at present because of the small number, small size and variable findings of existing studies. The lipid component of parenteral nutrition may modify inflammatory and immune processes in ways that influence patient outcome. The inclusion of fish oil in parenteral nutrition for post-surgical patients is associated with benefits. The situation regarding critically ill patients is not clear. © 2015 S. Karger AG, Basel.

  3. 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.

  4. The immune system in space and microgravity.

    PubMed

    Sonnenfeld, Gerald

    2002-12-01

    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.

  5. Adrenal-Derived Hormones Differentially Modulate Intestinal Immunity in Experimental Colitis

    PubMed Central

    de Souza, Patrícia Reis; Basso, Paulo José; Nardini, Viviani; Silva, Angelica; Banquieri, Fernanda

    2016-01-01

    The adrenal glands are able to modulate immune responses through neuroimmunoendocrine interactions and cortisol secretion that could suppress exacerbated inflammation such as in inflammatory bowel disease (IBD). Therefore, here we evaluated the role of these glands in experimental colitis induced by 3% dextran sulfate sodium (DSS) in C57BL/6 mice subjected to adrenalectomy, with or without glucocorticoid (GC) replacement. Mice succumbed to colitis without adrenals with a higher clinical score and augmented systemic levels of IL-6 and lower LPS. Furthermore, adrenalectomy negatively modulated systemic regulatory markers. The absence of adrenals resulted in augmented tolerogenic lamina propria dendritic cells but no compensatory local production of corticosterone and decreased mucosal inflammation associated with increased IFN-γ and FasL in the intestine. To clarify the importance of GC in this scenario, GC replacement in adrenalectomized mice restored different markers to the same degree of that observed in DSS group. Finally, this is the first time that adrenal-derived hormones, especially GC, were associated with the differential local modulation of the gut infiltrate, also pointing to a relationship between adrenalectomy and the modulation of systemic regulatory markers. These findings may elucidate some neuroimmunoendocrine mechanisms that dictate colitis outcome. PMID:27403034

  6. The immune system and aging: a review.

    PubMed

    Castelo-Branco, Camil; Soveral, Iris

    2014-01-01

    Abstract The concept of immunosenescence reflects age-related changes in immune responses, both cellular and serological, affecting the process of generating specific responses to foreign and self-antigens. The decline of the immune system with age is reflected in the increased susceptibility to infectious diseases, poorer response to vaccination, increased prevalence of cancer, autoimmune and other chronic diseases. Both innate and adaptive immune responses are affected by the aging process; however, the adaptive response seems to be more affected by the age-related changes in the immune system. Additionally, aged individuals tend to present a chronic low-grade inflammatory state that has been implicated in the pathogenesis of many age-related diseases (atherosclerosis, Alzheimer's disease, osteoporosis and diabetes). However, some individuals arrive to advanced ages without any major health problems, referred to as healthy aging. The immune system dysfunction seems to be somehow mitigated in this population, probably due to genetic and environmental factors yet to be described. In this review, an attempt is made to summarize the current knowledge on how the immune system is affected by the aging process.

  7. Unraveling the Differences between Gram-Positive and Gram-Negative Probiotics in Modulating Protective Immunity to Enteric Infections

    PubMed Central

    Kandasamy, Sukumar; Vlasova, Anastasia N.; Fischer, David D.; Chattha, Kuldeep S.; Shao, Lulu; Kumar, Anand; Langel, Stephanie N.; Rauf, Abdul; Huang, Huang-Chi; Rajashekara, Gireesh; Saif, Linda J.

    2017-01-01

    The role of intestinal microbiota and probiotics in prevention and treatment of infectious diseases, including diarrheal diseases in children and animal models, is increasingly recognized. Intestinal commensals play a major role in development of the immune system in neonates and in shaping host immune responses to pathogens. Lactobacilli spp. and Escherichia coli Nissle 1917 are two probiotics that are commonly used in children to treat various medical conditions including human rotavirus diarrhea and inflammatory bowel disease. Although the health benefits of probiotics have been confirmed, the specific effects of these established Gram-positive (G+) and Gram-negative (G−) probiotics in modulating immunity against pathogens and disease are largely undefined. In this review, we discuss the differences between G+ and G− probiotics/commensals in modulating the dynamics of selected infectious diseases and host immunity. These probiotics modulate the pathogenesis of infectious diseases and protective immunity against pathogens in a species- and strain-specific manner. Collectively, it appears that the selected G− probiotic is more effective than the various tested G+ probiotics in enhancing protective immunity against rotavirus in the gnotobiotic piglet model. PMID:28396664

  8. Zinc transporter SLC39A10/ZIP10 controls humoral immunity by modulating B-cell receptor signal strength

    PubMed Central

    Hojyo, Shintaro; Miyai, Tomohiro; Fujishiro, Hitomi; Kawamura, Masami; Yasuda, Takuwa; Hijikata, Atsushi; Bin, Bum-Ho; Irié, Tarou; Tanaka, Junichi; Atsumi, Toru; Murakami, Masaaki; Nakayama, Manabu; Ohara, Osamu; Himeno, Seiichiro; Yoshida, Hisahiro; Koseki, Haruhiko; Ikawa, Tomokatsu; Mishima, Kenji; Fukada, Toshiyuki

    2014-01-01

    The humoral immune response, also called the antibody-mediated immune response, is one of the main adaptive immune systems. The essential micronutrient zinc (Zn) is known to modulate adaptive immune responses, and dysregulated Zn homeostasis leads to immunodeficiency. However, the molecular mechanisms underlying this Zn-mediated modulation are largely unknown. Here, we show that the Zn transporter SLC39A10/ZIP10 plays an important role in B-cell antigen receptor (BCR) signal transduction. Zip10-deficiency in mature B cells attenuated both T-cell–dependent and –independent immune responses in vivo. The Zip10-deficient mature B cells proliferated poorly in response to BCR cross-linking, as a result of dysregulated BCR signaling. The perturbed signaling was found to be triggered by a reduction in CD45R phosphatase activity and consequent hyperactivation of LYN, an essential protein kinase in BCR signaling. Our data suggest that ZIP10 functions as a positive regulator of CD45R to modulate the BCR signal strength, thereby setting a threshold for BCR signaling in humoral immune responses. PMID:25074919

  9. Adenovirus sensing by the immune system.

    PubMed

    Atasheva, Svetlana; Shayakhmetov, Dmitry M

    2016-12-01

    The host immune system developed multiple ways for recognition of viral pathogens. Upon disseminated adenovirus infection, the immune system senses adenovirus invasion from the moment it enters the bloodstream. The soluble blood factors, FX, antibodies, and complement, can bind and activate plethora of host-protective immune responses. Adenovirus binding to the cellular β3 integrin and endosomal membrane rupture trigger activation of IL-1α/IL-1R1 proinflammatory cascade leading to attraction of cytotoxic immune cells to the site of infection. Upon cell entry, adenovirus exposes its DNA genome in the cytoplasm and triggers DNA sensors signaling. Even when inside the nucleus, the specialized cellular machinery that recognizes the double-strand DNA breaks become activated and triggers viral DNA replication arrest. Thus, the host employs very diverse mechanisms to prevent viral dissemination.

  10. The innate immune system and transplantation.

    PubMed

    Farrar, Conrad A; Kupiec-Weglinski, Jerzy W; Sacks, Steven H

    2013-10-01

    The sensitive and broadly reactive character of the innate immune system makes it liable to activation by stress factors other than infection. Thermal and metabolic stresses experienced during the transplantation procedure are sufficient to trigger the innate immune response and also augment adaptive immunity in the presence of foreign antigen on the donor organ. The resulting inflammatory and immune reactions combine to form a potent effector response that can lead to graft rejection. Here we examine the evidence that the complement and toll-like receptor systems are central to these pathways of injury and present a formidable barrier to transplantation. We review extensive information about the effector mechanisms that are mediated by these pathways, and bring together what is known about the damage-associated molecular patterns that initiate this sequence of events. Finally, we refer to two ongoing therapeutic trials that are evaluating the validity of these concepts in man.

  11. 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

  12. Staphylococcus aureus Colonization: Modulation of Host Immune Response and Impact on Human Vaccine Design

    PubMed Central

    Brown, Aisling F.; Leech, John M.; Rogers, Thomas R.; McLoughlin, Rachel M.

    2014-01-01

    In apparent contrast to its invasive potential Staphylococcus aureus colonizes the anterior nares of 20–80% of the human population. The relationship between host and microbe appears particularly individualized and colonization status seems somehow predetermined. After decolonization, persistent carriers often become re-colonized with their prior S. aureus strain, whereas non-carriers resist experimental colonization. Efforts to identify factors facilitating colonization have thus far largely focused on the microorganism rather than on the human host. The host responds to S. aureus nasal colonization via local expression of anti-microbial peptides, lipids, and cytokines. Interplay with the co-existing microbiota also influences colonization and immune regulation. Transient or persistent S. aureus colonization induces specific systemic immune responses. Humoral responses are the most studied of these and little is known of cellular responses induced by colonization. Intriguingly, colonized patients who develop bacteremia may have a lower S. aureus-attributable mortality than their non-colonized counterparts. This could imply a staphylococcal-specific immune “priming” or immunomodulation occurring as a consequence of colonization and impacting on the outcome of infection. This has yet to be fully explored. An effective vaccine remains elusive. Anti-S. aureus vaccine strategies may need to drive both humoral and cellular immune responses to confer efficient protection. Understanding the influence of colonization on adaptive response is essential to intelligent vaccine design, and may determine the efficacy of vaccine-mediated immunity. Clinical trials should consider colonization status and the resulting impact of this on individual patient responses. We urgently need an increased appreciation of colonization and its modulation of host immunity. PMID:24409186

  13. Antimalarial Drugs as Immune Modulators: New Mechanisms for Old Drugs.

    PubMed

    An, Jie; Minie, Mark; Sasaki, Tomikazu; Woodward, Joshua J; Elkon, Keith B

    2017-01-14

    The best known of the naturally occurring antimalarial compounds are quinine, extracted from cinchona bark, and artemisinin (qinghao), extracted from Artemisia annua in China. These and other derivatives are now chemically synthesized and remain the mainstay of therapy to treat malaria. The beneficial effects of several of the antimalarial drugs (AMDs) on clinical features of autoimmune disorders were discovered by chance during World War II. In this review, we discuss the chemistry of AMDs and their mechanisms of action, emphasizing how they may impact multiple pathways of innate immunity. These pathways include Toll-like receptors and the recently described cGAS-STING pathway. Finally, we discuss the current and future impact of AMDs on systemic lupus erythematosus, rheumatoid arthritis, and devastating monogenic disorders (interferonopathies) characterized by expression of type I interferon in the brain.

  14. Endogenous μ-opioid peptides modulate immune response towards malignant melanoma.

    PubMed

    Boehncke, Sandra; Hardt, Katja; Schadendorf, Dirk; Henschler, Reinhard; Boehncke, Wolf-Henning; Duthey, Beatrice

    2011-01-01

    Opioids exert major effects not only in the central nervous system but also in immune responses. We investigated the effects of μ-opioid peptides, secreted by tumor cells, on anti-tumor immune responses. For this purpose, tumor growth was studied in wild-type and μ-opioid receptor-deficient (MOR-/-) mice injected with B16 melanoma cells. The ability of these cells to produce opioids was studied by Western blots in vitro. Finally, biopsy material from human melanomas was investigated by immunohistochemistry for ß endorphin expression. Injection of B16 melanoma cells, producing endogenous ß endorphin, in the flank of MOR-/- mice revealed a profound reduction in tumor growth, paralleled by a significantly higher infiltration of immune cells into the tumors, when compared to tumor growth after injection of B16 melanoma cells into wild-type mice. Opioids present in B16 cell supernatant significantly reduced the proliferation of normal but not MOR-/- leucocytes. Immunohistochemical analyses of biopsies from human melanoma tissues showed a positive correlation between expression of ß endorphin and tumor progression. Our data provide evidence that μ-opioid peptides may play a major role in cancer progression by modulating immune response. This finding may have implications for the future optimization of immunointerventions for cancer.

  15. Photochemistry-based immune modulation in the treatment of cutaneous leishmaniasis

    NASA Astrophysics Data System (ADS)

    Akilov, Oleg E.; Kosaka, Sachiko; Hasan, Tayyaba

    2009-06-01

    The destruction of infectious pathogens by photodynamic therapy (PDT) is an emerging modality. We demonstrated the efficacy of PDT for the management of cutaneous leishmaniasis in our previous studies. However, much remains to be done for the improvement of PDT regimens. The modulation of the immune response by photochemistry is an exciting but under-explored area of PDT research. The goal of this study is to understand the mechanisms of the augmentation of the host immune response after PDT of cutaneous leishmaniasis (CL). We found that PDT with phenoxiazine analogues was capable for induction of Th1 immune response due to stimulation of IL- 12 production by dendritic cells. Single PDT treatment facilitated fast healing of the CL lesions due to effective parasite eradication and augmentation of the immune system. Comparative study with different photosensitizers (PS) (porphyrins, pehnoxiazines) demonstrated different immunomodulating properties of PDT depending on chemical class of PS. Knowing the particular profiles and immunomodulating properties of the pertinent PSs allows us to select the optimal PS with regards to both the photodestructive and immunostimulating potential.

  16. Circadian Clocks in the Immune System.

    PubMed

    Labrecque, Nathalie; Cermakian, Nicolas

    2015-08-01

    The immune system is a complex set of physiological mechanisms whose general aim is to defend the organism against non-self-bodies, such as pathogens (bacteria, viruses, parasites), as well as cancer cells. Circadian rhythms are endogenous 24-h variations found in virtually all physiological processes. These circadian rhythms are generated by circadian clocks, located in most cell types, including cells of the immune system. This review presents an overview of the clocks in the immune system and of the circadian regulation of the function of immune cells. Most immune cells express circadian clock genes and present a wide array of genes expressed with a 24-h rhythm. This has profound impacts on cellular functions, including a daily rhythm in the synthesis and release of cytokines, chemokines and cytolytic factors, the daily gating of the response occurring through pattern recognition receptors, circadian rhythms of cellular functions such as phagocytosis, migration to inflamed or infected tissue, cytolytic activity, and proliferative response to antigens. Consequently, alterations of circadian rhythms (e.g., clock gene mutation in mice or environmental disruption similar to shift work) lead to disturbed immune responses. We discuss the implications of these data for human health and the areas that future research should aim to address. © 2015 The Author(s).

  17. Lung cancer: the immune system and radiation.

    PubMed

    Mendes, F; Antunes, C; Abrantes, A M; Gonçalves, A C; Nobre-Gois, I; Sarmento, A B; Botelho, M F; Rosa, M S

    2015-01-01

    Lung cancer has a known relationship with smoking and is one of the leading causes of cancer-related death worldwide. Although the number of studies discussing lung cancer is vast, treatment efficacy is still suboptimal due to the wide range of factors that affect patient outcome. This review aims to collect information on lung cancer treatment, specially focused on radiation therapy. It also compiles information regarding the influence of radiotherapy on the immune system and its response to tumour cells. It evaluates how immune cells react after radiation exposure and the influence of their cytokines in the tumour microenvironment. The literature analysis points out that the immune system is a very promising field of investigation regarding prognosis, mostly because the stromal microenvironment in the tumour can provide some information about what can succeed in the future concerning treatment choices and perspectives. T cells (CD4+ and CD8+), interleukin-8, vascular endothelial growth factor and transforming growth factor-β seem to have a key role in the immune response after radiation exposure. The lack of large scale studies means there is no common consensus in the scientific community about the role of the immune system in lung cancer patients treated with radiotherapy. Clarification of the mechanism behind the immune response after radiation can lead to better treatments and better quality life for patients.

  18. Immune system stimulation by probiotic microorganisms.

    PubMed

    Ashraf, Rabia; Shah, Nagendra P

    2014-01-01

    Probiotic organisms are claimed to offer several functional properties including stimulation of immune system. This review is presented to provide detailed informations about how probiotics stimulate our immune system. Lactobacillus rhamnosus GG, Lactobacillus casei Shirota, Bifidobacterium animalis Bb-12, Lactobacillus johnsonii La1, Bifidobacterium lactis DR10, and Saccharomyces cerevisiae boulardii are the most investigated probiotic cultures for their immunomodulation properties. Probiotics can enhance nonspecific cellular immune response characterized by activation of macrophages, natural killer (NK) cells, antigen-specific cytotoxic T-lymphocytes, and the release of various cytokines in strain-specific and dose-dependent manner. Mixture and type (gram-positive and gram-negative) of probiotic organisms may induce different cytokine responses. Supplementation of probiotic organisms in infancy could help prevent immune-mediated diseases in childhood, whereas their intervention in pregnancy could affect fetal immune parameters, such as cord blood interferon (IFN)-γ levels, transforming growth factor (TGF)-β1 levels, and breast milk immunoglobulin (Ig)A. Probiotics that can be delivered via fermented milk or yogurt could improve the gut mucosal immune system by increasing the number of IgA(+) cells and cytokine-producing cells in the effector site of the intestine.

  19. Metal ions affecting the immune system.

    PubMed

    Lehmann, Irina; Sack, Ulrich; Lehmann, Jörg

    2011-01-01

    Certain heavy metals have been reported to seriously affect the immune system potentially resulting in a broad range of harmful health effects. Reported alterations in immune cell function include a variety of affected mechanisms. Thereby, depending on the particular metal, its concentration, route and duration of exposure, and biologic availability, the net outcome may be either immunosuppression or stimulation of immune cell activity. Since the key importance of the immune system is protection of the host against pathogenic agents, an impaired immune competence inevitably increases the susceptibility to invading pathogens. However, being aware that the immune system represents a sensitively regulated network of different cells, tissues, and soluble mediators it has to be stated that any form of dys-regulation may result in adverse health effects with overstimulation being as harmful as inhibition of functional activity. Chronic-inflammatory reactions, cancer development, hypersensitivity, allergic and autoimmune diseases are known consequences of persisting overstimulation. All these manifestations were already found to be related with heavy metal exposure.

  20. 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.

  1. The contribution of the immune system to parturition

    PubMed Central

    Jorens, Ph.; Student, I.; Heylen, R.

    1996-01-01

    The immune system plays a central role before and during parturition, including the main physiological processes of parturition: uterine contractions and cervical ripening. The immune system comprises white blood cells and their secretions. Polymorphonuclear cells and macrophages invade the cervical tissue and release compounds, such as oxygen radicals and enzymes, which break down the cervical matrix to allow softening and dilatation. During this inflammatory process, white blood cells undergo chemotaxis, adherence to endothelial cells, diapedesis, migration and activation. Factors that regulate white blood cell invasion and secretion include cytokines such as tumour necrosis factor and interleukins. Glucocorticoids, sex hormones and prostaglandins, affect cytokine synthesis. They also modulate the target cells, resulting in altered responses to cytokines. On the other hand, the immune system has profound effects on the hormonal system and prostaglandin synthesis. In animals, nitric oxide has marked effects on uterine quiescence during gestation. At the same time, it plays an important role in regulating the vascular tone of uterine arteries and has anti-adhesive effects on leukocytes. Cytokines are found in amniotic fluid, and in maternal and foetal serum at term and preterm. Several intrauterine cells have been shown to produce these cytoldnes. Since neither white blood cells, cytokines nor nitric oxide seem to be the ultimate intermediate for human parturition, the immune system is an additional but obligatory and underestimated component in the physiology of delivery. Scientists, obstetricians and anaesthesiologists must thus be aware of these processes. PMID:18475712

  2. The Immune System in Irritable Bowel Syndrome

    PubMed Central

    Cremon, Cesare; Carini, Giovanni; Bellacosa, Lara; Zecchi, Lisa; De Giorgio, Roberto; Corinaldesi, Roberto; Stanghellini, Vincenzo

    2011-01-01

    The potential relevance of systemic and gastrointestinal immune activation in the pathophysiology and symptom generation in the irritable bowel syndrome (IBS) is supported by a number of observations. Infectious gastroenteritis is the strongest risk factor for the development of IBS and increased rates of IBS-like symptoms have been detected in patients with inflammatory bowel disease in remission or in celiac disease patients on a gluten free diet. The number of T cells and mast cells in the small and large intestine of patients with IBS is increased in a large proportion of patients with IBS over healthy controls. Mediators released by immune cells and likely from other non-immune competent cells impact on the function of enteric and sensory afferent nerves as well as on epithelial tight junctions controlling mucosal barrier of recipient animals, isolated human gut tissues or cell culture systems. Antibodies against microbiota antigens (bacterial flagellin), and increased levels of cytokines have been detected systemically in the peripheral blood advocating the existence of abnormal host-microbial interactions and systemic immune responses. Nonetheless, there is wide overlap of data obtained in healthy controls; in addition, the subsets of patients showing immune activation have yet to be clearly identified. Gender, age, geographic differences, genetic predisposition, diet and differences in the intestinal microbiota likely play a role and further research has to be done to clarify their relevance as potential mechanisms in the described immune system dysregulation. Immune activation has stimulated interest for the potential identification of biomarkers useful for clinical and research purposes and the development of novel therapeutic approaches. PMID:22148103

  3. Coastal Modeling System: Dredging Module

    DTIC Science & Technology

    2016-06-01

    spacing. Wave data from Wave Information Study (WIS) station 63401 (WIS 2014) were used for input to the wave model. a. b. Figure 1 . (a...ERDC/CHL CHETN-I-90 June 2016 Approved for public release; distribution is unlimited. Coastal Modeling System : Dredging Module by Chris Reed and...within the U.S. Army Corps of Engineers (USACE) Coastal Modeling System (CMS). The DM simulates one or more dredging operations during a CMS

  4. 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.

  5. 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.

  6. The nervous and the immune systems: conspicuous physiological analogies.

    PubMed

    Sotelo, Julio

    2015-02-01

    From all biological constituents of complex organisms, two are highly sophisticated: the nervous and the immune systems. Interestingly, their goals and processes appear to be distant from each other; however, their physiological mechanisms keep notorious similarities. Both construct intelligence, learn from experience, and keep memory. Their precise responses to innumerable stimuli are delicately modulated, and the exposure of the individual to thousands of potential challenges integrates their functionality; they use a large part of their constituents not in excitatory activities but in the maintenance of inhibitory mechanisms to keep silent vast intrinsic potentialities. The nervous and immune systems are integrated by a basic cell lineage (neurons and lymphocytes, respectively) but each embodies countless cell subgroups with different and specialized deeds which, in contrast with cells from other organs, labyrinthine molecular arrangements conduct to "one cell, one function". Also, nervous and immune actions confer identity that differentiates every individual from countless others in the same species. Both systems regulate and potentiate their responses aided by countless biological resources of variable intensity: hormones, peptides, cytokines, pro-inflammatory molecules, etc. How the immune and the nervous systems buildup memory, learning capability, and exquisite control of excitatory/inhibitory mechanisms constitute major intellectual challenges for contemporary research.

  7. 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

    2017-04-03

    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.

  8. 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.

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

    PubMed Central

    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. PMID:26635804

  10. 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

  11. The mucosal immune system for vaccine development.

    PubMed

    Lamichhane, Aayam; Azegamia, Tatsuhiko; Kiyonoa, Hiroshi

    2014-11-20

    Mucosal surfaces are continuously exposed to the external environment and therefore represent the largest lymphoid organ of the body. In the mucosal immune system, gut-associated lymphoid tissues (GALTs), including Peyer's patches and isolated lymphoid follicles, play an important role in the induction of antigen-specific immune responses in the gut. GALTs have unique organogenesis characteristics and interact with the network of dendritic cells and T cells for the simultaneous induction and regulation of IgA responses and oral tolerance. In these lymphoid tissues, antigens are up taken by M cells in the epithelial layer, and antigen-specific immune responses are subsequently initiated by GALT cells. Nasopharynx- and tear-duct-associated lymphoid tissues (NALTs and TALTs) are key organized lymphoid structures in the respiratory tract and ocular cavities, respectively, and have been shown to interact with each other. Mucosal surfaces are also characterized by host-microbe interactions that affect the genesis and maturation of mucosa-associated lymphoid tissues and the induction and regulation of innate and acquired mucosal immune responses. Because most harmful pathogens enter the body through mucosal surfaces by ingestion, inhalation, or sexual contact, the mucosa is a candidate site for vaccination. Mucosal vaccination has some physiological and practical advantages, such as decreased costs and reduced risk of needle-stick injuries and transmission of bloodborne diseases, and it is painless. Recently, the application of modern bioengineering and biochemical engineering technologies, including gene transformation and manipulation systems, resulted in the development of systems to express vaccine antigens in transgenic plants and nanogels, which will usher in a new era of delivery systems for mucosal vaccine antigens. In this review, based on some of our research group's thirty seven years of progress and effort, we highlight the unique features of mucosal immune

  12. Environmental exposure to lead induces oxidative stress and modulates the function of the antioxidant defense system and the immune system in the semen of males with normal semen profile

    SciTech Connect

    Kasperczyk, Aleksandra; Dobrakowski, Michał; Czuba, Zenon P.; Horak, Stanisław; Kasperczyk, Sławomir

    2015-05-01

    We investigated the associations between environmental exposure to lead and a repertoire of cytokines in seminal plasma of males with normal semen profile according to the WHO criteria. Based on the median lead concentration in seminal plasma, 65 samples were divided into two groups: low (LE) and high exposure to lead (HE). Differences in semen volume and the pH, count, motility and morphology of sperm cells were not observed between the examined groups. The total oxidant status value and the level of protein sulfhydryl groups as well as the activities of manganese superoxide dismutase and catalase were significantly higher in the HE group, whereas the total antioxidant capacity value and the activities of glutathione reductase and glutathione-S-transferase were depressed. IL-7, IL-10, IL-12, and TNF-α levels were significantly higher in the HE group compared with the LE group. Environmental exposure to lead is sufficient to induce oxidative stress in seminal plasma and to modulate antioxidant defense system. - Highlights: • Lead induces oxidative stress in seminal plasma in human. • Lead modulates antioxidant defense system in seminal plasma in human. • Lead does not change a Th1/Th2 imbalance in seminal plasma in human.

  13. Innate immune response during Yersinia infection: critical modulation of cell death mechanisms through phagocyte activation.

    PubMed

    Bergsbaken, Tessa; Cookson, Brad T

    2009-11-01

    Yersinia pestis, the etiological agent of plague, is one of the most deadly pathogens on our planet. This organism shares important attributes with its ancestral progenitor, Yersinia pseudotuberculosis, including a 70-kb virulence plasmid, lymphotropism during growth in the mammalian host, and killing of host macrophages. Infections with both organisms are biphasic, where bacterial replication occurs initially with little inflammation, followed by phagocyte influx, inflammatory cytokine production, and tissue necrosis. During infection, plasmid-encoded attributes facilitate bacterial-induced macrophage death, which results from two distinct processes and corresponds to the inflammatory crescendo observed in vivo: Naïve cells die by apoptosis (noninflammatory), and later in infection, activated macrophages die by pyroptosis (inflammatory). The significance of this redirected cell death for the host is underscored by the importance of phagocyte activation for immunity to Yersinia and the protective role of pyroptosis during host responses to anthrax lethal toxin and infections with Francisella, Legionella, Pseudomonas, and Salmonella. The similarities of Y. pestis and Y. pseudotuberculosis, including conserved, plasmid-encoded functions inducing at least two distinct mechanisms of cell death, indicate that comparative studies are revealing about their critical pathogenic mechanism(s) and host innate immune responses during infection. Validation of this idea and evidence of similar interactions with the host immune system are provided by Y. pseudotuberculosis-priming, cross-protective immunity against Y. pestis. Despite these insights, additional studies indicate much remains to be understood concerning effective host responses against Yersinia, including chromosomally encoded attributes that also contribute to bacterial evasion and modulation of innate and adaptive immune responses.

  14. Quantum systems under frequency modulation

    NASA Astrophysics Data System (ADS)

    Silveri, M. P.; Tuorila, J. A.; Thuneberg, E. V.; Paraoanu, G. S.

    2017-05-01

    We review the physical phenomena that arise when quantum mechanical energy levels are modulated in time. The dynamics resulting from changes in the transition frequency is a problem studied since the early days of quantum mechanics. It has been of constant interest both experimentally and theoretically since, with the simple two-state model providing an inexhaustible source of novel concepts. When the transition frequency of a quantum system is modulated, several phenomena can be observed, such as Landau-Zener-Stückelberg-Majorana interference, motional averaging and narrowing, and the formation of dressed states with the appearance of sidebands in the spectrum. Adiabatic changes result in the accumulation of geometric phases, which can be used to create topological states. In recent years, an exquisite experimental control in the time domain was gained through the parameters entering the Hamiltonian, and high-fidelity readout schemes allowed the state of the system to be monitored non-destructively. These developments were made in the field of quantum devices, especially in superconducting qubits, as a well as in atomic physics, in particular in ultracold gases. As a result of these advances, it became possible to demonstrate many of the fundamental effects that arise in a quantum system when its transition frequencies are modulated. The purpose of this review is to present some of these developments, from two-state atoms and harmonic oscillators to multilevel and many-particle systems.

  15. Quantum systems under frequency modulation.

    PubMed

    Silveri, M P; Tuorila, J A; Thuneberg, E V; Paraoanu, G S

    2017-05-01

    We review the physical phenomena that arise when quantum mechanical energy levels are modulated in time. The dynamics resulting from changes in the transition frequency is a problem studied since the early days of quantum mechanics. It has been of constant interest both experimentally and theoretically since, with the simple two-state model providing an inexhaustible source of novel concepts. When the transition frequency of a quantum system is modulated, several phenomena can be observed, such as Landau-Zener-Stückelberg-Majorana interference, motional averaging and narrowing, and the formation of dressed states with the appearance of sidebands in the spectrum. Adiabatic changes result in the accumulation of geometric phases, which can be used to create topological states. In recent years, an exquisite experimental control in the time domain was gained through the parameters entering the Hamiltonian, and high-fidelity readout schemes allowed the state of the system to be monitored non-destructively. These developments were made in the field of quantum devices, especially in superconducting qubits, as a well as in atomic physics, in particular in ultracold gases. As a result of these advances, it became possible to demonstrate many of the fundamental effects that arise in a quantum system when its transition frequencies are modulated. The purpose of this review is to present some of these developments, from two-state atoms and harmonic oscillators to multilevel and many-particle systems.

  16. Innate immune system cells in atherosclerosis.

    PubMed

    Chávez-Sánchez, Luis; Espinosa-Luna, Jose E; Chávez-Rueda, Karina; Legorreta-Haquet, María V; Montoya-Díaz, Eduardo; Blanco-Favela, Francisco

    2014-01-01

    Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by innate and adaptive immune system involvement. A key component of atherosclerotic plaque inflammation is the persistence of different innate immune cell types including mast cells, neutrophils, natural killer cells, monocytes, macrophages and dendritic cells. Several endogenous signals such as oxidized low-density lipoproteins, and exogenous signals such as lipopolysaccharides, trigger the activation of these cells. In particular, these signals orchestrate the early and late inflammatory responses through the secretion of pro-inflammatory cytokines and contribute to plaque evolution through the formation of foam cells, among other events. In this review we discuss how innate immune system cells affect atherosclerosis pathogenesis.

  17. Nutritional components regulate the gut immune system and its association with intestinal immune disease development.

    PubMed

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases.

  18. 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.

  19. THE PROPERDIN SYSTEM AND IMMUNITY

    PubMed Central

    Wardlaw, Alastair C.; Pillemer, Louis

    1956-01-01

    Methods for the preparation and standardization of reagents suitable for studies on the bactericidal action of the properdin system are described. The preparation and properties of serum free of properdin (RPb) are presented in detail because of the necessity for a suitable RPb in these studies. The properdin system is responsible for the bactericidal action of normal human serum against a variety of microorganisms. The present work shows that the removal of properdin from serum also removes bactericidal activity. Addition of properdin to properdin-deficient serum restores bactericidal activity. A quantitative relationship exists between the final properdin concentration and bactericidal activity against sensitive organisms. The possibilities of a bactericidal assay for properdin are discussed. It is demonstrated that, in addition to properdin, the four components of complement (present in RPb) are necessary for the destruction of properdinsensitive bacteria. If any component is missing, bactericidal activity is lost; when the component is replaced, bactericidal activity is restored. Magnesium is also necessary for the bactericidal activity of the properdin system. Maximal bactericidal activity is obtained with magnesium concentrations similar to that of normal human serum (10–3 to 10–4 M). The bactericidal activity of the properdin system occurs only at temperatures above 15°. Resistant strains have been encountered in species of bacteria sensitive to the properdin system. Resistance or sensitivity is a characteristic of the individual strain and not of the species. The widespread occurrence of the properdin system in normal mammalian serum and the variety of bacteria destroyed by it suggest that the properdin system is a factor in natural resistance. PMID:13319578

  20. Outsmarting the host: bacteria modulating the immune response.

    PubMed

    Woolard, Matthew D; Frelinger, Jeffrey A

    2008-01-01

    Pathogenic bacteria and their hosts have had a two-way conversation for millions of years. This interaction has led to many measure/counter-measure responses by the host and bacteria. The host immune response has developed many mechanisms to neutralize and remove pathogen bacteria. In turn pathogenic bacteria have developed mechanisms to alter and evade the host immune response. We will review some of the mechanisms utilized by bacteria to accomplish this goal. We will also examine the current state of understanding of Francisella tularensis mediated immune evasion.

  1. Modulation of immune cell proliferation by glycerol monolaurate.

    PubMed Central

    Witcher, K J; Novick, R P; Schlievert, P M

    1996-01-01

    Previous studies have shown that glycerol monolaurate (GML), a surfactant commonly used in a wide variety of food and cosmetic products, inhibits the production of a variety of exotoxins by group A streptococci and staphylococci. Given the highly lipophilic nature of the structure of GML, it is suspected that the surfactant exerts its toxin inhibition effects via interaction with the cell membrane. The present study attempted to characterize some of the potential targets of GML action using the model system of lymphocyte activation. Results from murine splenocytes show that GML stimulates proliferation at concentrations between 10(-5) and 5 micrograms/ml/5 x 10(5) splenocytes. At concentrations greater than 5 micrograms/ml, GML inhibited lymphocyte proliferation and blocked the proliferative effects of the lymphocyte mitogens phorbol myristate acetate and concanavalin A and the potent T-cell mitogen toxic shock syndrome toxin-1. Studies using purified immune cell subsets indicated that GML at a concentration of 0.1 microgram/ml optimally induced proliferation of T cells but did not affect B cells. At higher concentrations, GML inhibited the toxic shock syndrome toxin-1 mitogenic effects on T cells, but did not inhibit the lipopolysaccharide-induced stimulation of B cells, suggesting that GML preferentially affects the T-cell population. GML-induced proliferation was blocked by the immunosuppressive drug cyclosporin A, suggesting that GML may be exerting its T-cell-proliferative effects along the calcium-dependent inositol phospholipid signal transduction pathway. PMID:8770497

  2. 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.

  3. Crosstalk between the nociceptive and immune systems in host defence and disease.

    PubMed

    McMahon, Stephen B; La Russa, Federica; Bennett, David L H

    2015-07-01

    Nociceptors and immune cells both protect the host from potential threats to homeostasis. There is growing evidence for bidirectional signalling between these two systems, and the underlying mechanisms are beginning to be elucidated. An understanding is emerging of how both the adaptive and innate immune systems can activate and sensitize nociceptors, and, reciprocally, how nociceptors modulate immune cells. In this Review, we discuss how these interactions can be adaptive and useful to the organism but also consider when such signalling might be maladaptive and pathophysiological, contributing to immune-mediated diseases and persistent pain states.

  4. Nutritional modulation of the immune response in poultry

    USDA-ARS?s Scientific Manuscript database

    Economic efficiency demanded by the poultry industry has pushed selection towards high production with improved feed conversion ratios (FCR) and high yield; however, selection based heavily on growth characteristics and other phenotypic traits has adversely affected immune competence. Despite incre...

  5. Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function

    PubMed Central

    Reunanen, Justus; Meijerink, Marjolein; Pietilä, Taija E.; Kainulainen, Veera; Klievink, Judith; Huuskonen, Laura; Aalvink, Steven; Skurnik, Mikael; Boeren, Sjef; Satokari, Reetta; Mercenier, Annick; Palva, Airi; Smidt, Hauke; de Vos, Willem M.; Belzer, Clara

    2017-01-01

    Gut barrier function is key in maintaining a balanced response between the host and its microbiome. The microbiota can modulate changes in gut barrier as well as metabolic and inflammatory responses. This highly complex system involves numerous microbiota-derived factors. The gut symbiont Akkermansia muciniphila is positively correlated with a lean phenotype, reduced body weight gain, amelioration of metabolic responses and restoration of gut barrier function by modulation of mucus layer thickness. However, the molecular mechanisms behind its metabolic and immunological regulatory properties are unexplored. Herein, we identify a highly abundant outer membrane pili-like protein of A. muciniphila MucT that is directly involved in immune regulation and enhancement of trans-epithelial resistance. The purified Amuc_1100 protein and enrichments containing all its associated proteins induced production of specific cytokines through activation of Toll-like receptor (TLR) 2 and TLR4. This mainly leads to high levels of IL-10 similar to those induced by the other beneficial immune suppressive microorganisms such as Faecalibacterium prausnitzii A2-165 and Lactobacillus plantarum WCFS1. Together these results indicate that outer membrane protein composition and particularly the newly identified highly abundant pili-like protein Amuc_1100 of A. muciniphila are involved in host immunological homeostasis at the gut mucosa, and improvement of gut barrier function. PMID:28249045

  6. Mesenchymal stromal cells; role in tissue repair, drug discovery and immune modulation.

    PubMed

    English, Karen; Mahon, Bernard P; Wood, Kathryn J

    2014-01-01

    Mesenchymal stromal cells (MSCs) participate in repair of damaged tissues, possess the potential to serve as a useful tool in the drug discovery field and exert immunosuppressive effects as demonstrated by their ability to modulate the immune response. Herein, the roles played by MSC differentiation and/or production of trophic factors involved in tissue repair are discussed. MSCs offer the opportunity to probe targets that conventional or differentiated cell lines do not express; thus providing a more refined system that allows identification of novel therapeutics. However, there are difficulties associated with drug discovery assays to which MSCs are not exempt. The immunosuppressive potential of MSCs has already been utilised in clinical trials where MSCs have been used to treat patients with graft- versus- host disease (GvHD) and autoimmune diseases. Another possible therapeutic application of MSCs lies in the field of transplantation tolerance. Although the capacity of MSCs to modulate immune responses has received much attention, the role of MSCs in transplantation tolerance is as yet unclear. In this review, we discuss the evidence for MSC induction of a state of tolerance in the transplantation setting.

  7. Earth System Science Education Modules

    NASA Astrophysics Data System (ADS)

    Hall, C.; Kaufman, C.; Humphreys, R. R.; Colgan, M. W.

    2009-12-01

    The College of Charleston is developing several new geoscience-based education modules for integration into the Earth System Science Education Alliance (ESSEA). These three new modules provide opportunities for science and pre-service education students to participate in inquiry-based, data-driven experiences. The three new modules will be discussed in this session. Coastal Crisis is a module that analyzes rapidly changing coastlines and uses technology - remotely sensed data and geographic information systems (GIS) to delineate, understand and monitor changes in coastal environments. The beaches near Charleston, SC are undergoing erosion and therefore are used as examples of rapidly changing coastlines. Students will use real data from NASA, NOAA and other federal agencies in the classroom to study coastal change. Through this case study, learners will acquire remotely sensed images and GIS data sets from online sources, utilize those data sets within Google Earth or other visualization programs, and understand what the data is telling them. Analyzing the data will allow learners to contemplate and make predictions on the impact associated with changing environmental conditions, within the context of a coastal setting. To Drill or Not To Drill is a multidisciplinary problem based module to increase students’ knowledge of problems associated with nonrenewable resource extraction. The controversial topic of drilling in the Arctic National Wildlife Refuge (ANWR) examines whether the economic benefit of the oil extracted from ANWR is worth the social cost of the environmental damage that such extraction may inflict. By attempting to answer this question, learners must balance the interests of preservation with the economic need for oil. The learners are exposed to the difficulties associated with a real world problem that requires trade-off between environmental trust and economic well-being. The Citizen Science module challenges students to translate scientific

  8. Altered miRNAs expression profiles and modulation of immune response genes and proteins during neonatal sepsis.

    PubMed

    Chen, Jiande; Jiang, Siyuan; Cao, Yun; Yang, Yi

    2014-04-01

    The dysregulated expression of miRNAs in the immune system may be critical for immune responses to pathogens and evolve into the inflammation seen in sepsis. The aim of this study is to explore the important role of miRNAs in the regulation of the immune response during neonatal sepsis. Using a microarray we performed the miRNA expression profiling of peripheral blood leukocytes from neonates with sepsis and uninfected neonates. Based on the predicted target genes of these miRNAs we selected 26 immune-related miRNAs out of the differentially expressed miRNAs for further testing by quantitative PCR. We simultaneously detected the immune response genes by PCR array and plasma cytokine levels using a protein chip to investigate the effect of the altered miRNAs on the immune response in neonatal sepsis. There were 10 immune regulatory miRNAs whose expression was significantly changed more than two fold in the neonates with sepsis compared with the uninfected neonates. The expression levels of 11 immune response genes and the plasma levels of 15 cytokines or receptors were significantly up- or down-regulated in the neonates with sepsis compared to the uninfected neonates. This comprehensive analysis suggests that the altered miRNAs modulate the immune response during neonatal sepsis in a way that represses the inflammatory response. Our investigation demonstrated some miRNAs with altered expression levels and their probable association with the regulation of immune response during neonatal sepsis. The characteristics of the neonatal inflammatory response could be attributed to immature immune function of neonates.

  9. Prion Disease and the Innate Immune System

    PubMed Central

    Bradford, Barry M.; Mabbott, Neil A.

    2012-01-01

    Prion diseases or transmissible spongiform encephalopathies are a unique category of infectious protein-misfolding neurodegenerative disorders. Hypothesized to be caused by misfolding of the cellular prion protein these disorders possess an infectious quality that thrives in immune-competent hosts. While much has been discovered about the routing and critical components involved in the peripheral pathogenesis of these agents there are still many aspects to be discovered. Research into this area has been extensive as it represents a major target for therapeutic intervention within this group of diseases. The main focus of pathological damage in these diseases occurs within the central nervous system. Cells of the innate immune system have been proven to be critical players in the initial pathogenesis of prion disease, and may have a role in the pathological progression of disease. Understanding how prions interact with the host innate immune system may provide us with natural pathways and mechanisms to combat these diseases prior to their neuroinvasive stage. We present here a review of the current knowledge regarding the role of the innate immune system in prion pathogenesis. PMID:23342365

  10. The Chemical Characteristics and Immune-Modulating Activity of Polysaccharides Isolated from Cold-Brew Coffee

    PubMed Central

    Shin, Kwang-Soon

    2017-01-01

    To elucidate new biological ingredients in cold-brew coffee extracted with cold water, crude polysaccharide (CCP-0) was isolated by ethanol precipitation, and its immune-stimulating activities were assayed. CCP-0 mainly comprised galactose (53.6%), mannose (15.7%), arabinose (11.9%), and uronic acid (12.4%), suggesting that it might exist as a mixture of galactomannan and arabinogalactan. CCP-0 significantly increased cell proliferation on both murine peritoneal macrophages and splenocytes in a dose dependent manner. CCP-0 also significantly augmented nitric oxide and reactive oxygen species production by murine peritoneal macrophages. In addition, macrophages stimulated by CCP-0 enhanced production of various cytokines such as tumor necrosis factor-α, interleukin (IL)-6, and IL-12. In an in vitro assay for intestinal immune-modulating activity, CCP-0 showed higher bone-marrow cell-proliferation activity through Peyer’s patch cells at 100 μg/mL than the negative control. These results suggest that CCP-0 may potentially enhance macrophage functions and the intestinal immune system. PMID:28702426

  11. Neutrophils are dispensable in the modulation of T cell immunity against cutaneous HSV-1 infection

    PubMed Central

    Hor, Jyh Liang; Heath, William R.; Mueller, Scott N.

    2017-01-01

    Neutrophils rapidly infiltrate sites of inflammation during peripheral infection or tissue injury. In addition to their well described roles as pro-inflammatory phagocytes responsible for pathogen clearance, recent studies have demonstrated a broader functional repertoire including mediating crosstalk between innate and adaptive arms of the immune system. Specifically, neutrophils have been proposed to mediate antigen transport to lymph nodes (LN) to modulate T cell priming and to influence T cell migration to infected tissues. Using a mouse model of cutaneous herpes simplex virus type 1 (HSV-1) infection we explored potential contributions of neutrophils toward anti-viral immunity. While a transient, early influx of neutrophils was triggered by dermal scarification, we did not detect migration of neutrophils from the skin to LN. Furthermore, despite recruitment of neutrophils into LN from the blood, priming and expansion of CD4+ and CD8+ T cells was unaffected following neutrophil depletion. Finally, we found that neutrophils were dispensable for the migration of effector T cells into infected skin. Our study suggests that the immunomodulatory roles of neutrophils toward adaptive immunity may be context-dependent, and are likely determined by the type of pathogen and anatomical site of infection. PMID:28112242

  12. The cell surface receptor Slamf6 modulates innate immune responses during Citrobacter rodentium-induced colitis.

    PubMed

    van Driel, Boaz; Wang, Guoxing; Liao, Gongxian; Halibozek, Peter J; Keszei, Marton; O'Keeffe, Michael S; Bhan, Atul K; Wang, Ninghai; Terhorst, Cox

    2015-09-01

    The homophilic cell surface receptors CD150 (Slamf1) and CD352 (Slamf6) are known to modulate adaptive immune responses. Although the Th17 response was enhanced in Slamf6(-/-) C57BL/6 mice upon oral infection with Citrobacter rodentium, the pathologic consequences are indistinguishable from an infection of wild-type C57BL/6 mice. Using a reporter-based binding assay, we show that Slamf6 can engage structures on the outer cell membrane of several Gram(-) bacteria. Therefore, we examined whether Slamf6, like Slamf1, is also involved in innate responses to bacteria and regulates peripheral inflammation by assessing the outcome of C. rodentium infections in Rag(-/-) mice. Surprisingly, the pathology and immune responses in the lamina propria of C. rodentium-infected Slamf6(-/-) Rag(-/-) mice were markedly reduced as compared with those of Rag(-/-) mice. Infiltration of inflammatory phagocytes into the lamina propria was consistently lower in Slamf6(-/-) Rag(-/-) mice than in Rag(-/-) animals. Concomitant with the reduced systemic translocation of the bacteria was an enhanced production of IL-22, suggesting that Slamf6 suppresses a mucosal protective program. Furthermore, administering a mAb (330) that inhibits bacterial interactions with Slamf6 to Rag(-/-) mice ameliorated the infection compared with a control antibody. We conclude that Slamf6-mediated interactions of colonic innate immune cells with specific Gram(-) bacteria reduce mucosal protection and enhance inflammation, contributing to lethal colitis that is caused by C. rodentium infections in Rag(-/-) mice.

  13. Modulation of neuroinflammation: Role and therapeutic potential of TRPV1 in the neuro-immune axis.

    PubMed

    Kong, Wei-Lin; Peng, Yuan-Yuan; Peng, Bi-Wen

    2017-08-01

    Transient receptor potential vanilloid type 1 channel (TRPV1), as a ligand-gated non-selective cation channel, has recently been demonstrated to have wide expression in the neuro-immune axis, where its multiple functions occur through regulation of both neuronal and non-neuronal activities. Growing evidence has suggested that TRPV1 is functionally expressed in glial cells, especially in the microglia and astrocytes. Glial cells perform immunological functions in response to pathophysiological challenges through pro-inflammatory or anti-inflammatory cytokines and chemokines in which TRPV1 is involved. Sustaining inflammation might mediate a positive feedback loop of neuroinflammation and exacerbate neurological disorders. Accumulating evidence has suggested that TRPV1 is closely related to immune responses and might be recognized as a molecular switch in the neuroinflammation of a majority of seizures and neurodegenerative diseases. In this review, we evidenced that inflammation modulates the expression and activity of TRPV1 in the central nervous system (CNS) and TRPV1 exerts reciprocal actions over neuroinflammatory processes. Together, the literature supports the hypothesis that TRPV1 may represent potential therapeutic targets in the neuro-immune axis. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. The Chemical Characteristics and Immune-Modulating Activity of Polysaccharides Isolated from Cold-Brew Coffee.

    PubMed

    Shin, Kwang-Soon

    2017-06-01

    To elucidate new biological ingredients in cold-brew coffee extracted with cold water, crude polysaccharide (CCP-0) was isolated by ethanol precipitation, and its immune-stimulating activities were assayed. CCP-0 mainly comprised galactose (53.6%), mannose (15.7%), arabinose (11.9%), and uronic acid (12.4%), suggesting that it might exist as a mixture of galactomannan and arabinogalactan. CCP-0 significantly increased cell proliferation on both murine peritoneal macrophages and splenocytes in a dose dependent manner. CCP-0 also significantly augmented nitric oxide and reactive oxygen species production by murine peritoneal macrophages. In addition, macrophages stimulated by CCP-0 enhanced production of various cytokines such as tumor necrosis factor-α, interleukin (IL)-6, and IL-12. In an in vitro assay for intestinal immune-modulating activity, CCP-0 showed higher bone-marrow cell-proliferation activity through Peyer's patch cells at 100 μg/mL than the negative control. These results suggest that CCP-0 may potentially enhance macrophage functions and the intestinal immune system.

  15. [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

  16. 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.

  17. Antifouling biocides: Impairment of bivalve immune system by chlorothalonil.

    PubMed

    Guerreiro, Amanda da Silveira; Rola, Regina Coimbra; Rovani, Monique Tomazele; Costa, Simone Rutz da; Sandrini, Juliana Zomer

    2017-08-01

    Marine ecosystems are subjected to a variety of contaminants. Antifouling paints, for example, have been extensively used to protect ship surfaces from marine biofouling, but their toxicity has generated great concern. Thus, we evaluated the effect of the biocide chlorothalonil on the immune system of Perna perna mussels. The mussels were exposed to 0 (control), 0.1μg/L and 10μg/L of chlorothalonil for up to 96h. After 24h and 96h of exposure, the following immune-related parameters were analyzed in the hemolymph of mussels: total hemocyte count, cell adhesion, phagocytic activity, level of reactive oxygen species, cell viability and comet assay. After 24h and 96h of chlorothalonil exposure, cellular adhesion increased and the hemocyte viability reduced. Moreover, an increase in phagocytic activity was also observed after 96h of exposure to cholorothalonil. The exposure to 10μg/L of chlorothalonil for 96h reduced the air survival capacity of mussels. Total hemocyte count, ROS generation and DNA damage were not affected by the contaminant exposure. Our results indicate that chlorothalonil affected important immune responses of the bivalves, demonstrating that this biocide has effects on non-target species. This modulation of immune system reduced the health status of mussels, which could compromise their ability to survive in the environment. Copyright © 2017. Published by Elsevier B.V.

  18. Reactions of the immune system in epilepsy

    PubMed Central

    COJOCARU, Inimioara Mihaela; COJOCARU, Manole

    2010-01-01

    ABSTRACT Epilepsy may present as a symptom of many neurological disorders and often an etiological explanation cannot be identified. There is growing evidence that autoimmune mechanisms might have a role in some patients. The evidence for immunological mechanisms in epilepsy can be examined within the following three main areas: the childhood epilepsy syndromes, epilepsy associated with other immunologically mediated diseases, and the more common unselected groups of patients with epilepsy. Autoimmunity was recently suspected to be involved in the pathology of certain human epilepsies. This includes numerous reports of the detection of theoretically relevant serum autoantibodies, experimental data showing that antibodies can be epileptogenic, and a response of some epilepsy syndromes to immunomodulation. The high prevalence of epilepsies in specific immune diseases suggests that immune system may play a role in the pathogenesis of epilepsy or might be associated with it. There is some evidence that immune mechanisms play a role in the pathogenesis of some epilepsy syndromes. PMID:21977153

  19. The humoral immune system of anadromous fish.

    PubMed

    Zwollo, Patty

    2017-01-03

    The immune system of anadromous fish is extremely complex, a direct consequence of their diadromous nature. Hormone levels fluctuate widely throughout their life cycle, as fish move between fresh and salt water. This poses major challenges to the physiology of anadromous fish, including adaptation to very different saline environments, distinct pathogen fingerprints, and different environmental stressors. Elevated cortisol and sex hormone levels inhibit B lymphopoiesis and IgM(+) antibody responses, while catecholamines, growth hormones and thyroid hormones are generally stimulatory and enhance the humoral immune response. Immunological memory in the form of long-lived plasma cells likely plays important roles in health and survival during the life cycle of anadromous fishes. This review discusses some of the complex immune-endocrine pathways in anadromous fish, focusing on essential roles for B lineage cells in the successful completion of their life cycle. A discussion is included on potential differences in immuno-competence between wild and hatchery-raised fish.

  20. Airborne pollutants and the immune system.

    PubMed

    Albright, J F; Goldstein, R A

    1996-02-01

    The effects of airborne pollutants on the immune system have been most widely studied in the respiratory tract. Entry may occur as a volatile gas (ozone, benzene), as liquid droplets (sulfuric acid, nitrogen dioxide), or as particulate matter (diesel exhaust, aromatic hydrocarbons). The subsequent interaction with the immune system may result in local and systemic responses, and studies have shown examples of disease occurring from both overactive immune responses and immunosuppression. For the most part, airborne pollutants (small molecular weight chemicals) have to be coupled with other substances (proteins or conjugates) before they can be recognized by the immune system and exert their effects. Fortunately, this encounter rarely causes immunologically mediated human disorders. The following briefly reviews some of the disorders that may occur. Immunologically nonspecific inflammation of the lung can occur after inhalation of ozone in anyone given sufficient dose and time of exposure. Immunologically specific cell-mediated (T lymphocyte) reactions appear to predominate in chronic beryllium disease, which results in a granulomatous form of lung disease. Beryllium alone does not appear to be antigenic but requires chemical linkage with a larger molecule. Mercury-induced autoimmune disease (immune system attacks self-antigens) affecting kidneys and lungs has been demonstrated in animal models (changes similar to those seen in people with Goodpasture's syndrome). Immunosuppression can be demonstrated after exposure to polycyclic aromatic hydrocarbons (2,3,7,8-tetrachlorodibenzo-p-dioxin). Hypersensitivity (or allergic) reactions can occur after exposure to toluene diisocyanate (occupational asthma). In summary, airborne pollutants may cause a wide spectrum of immunologically mediated disorders. There is clearly an underlying genetic basis for the susceptibility to immunologic disease resulting from exposure to pollutants, but knowledge in this area is rudimentary at

  1. Effects of triterpenes on the immune system.

    PubMed

    Ríos, José-Luis

    2010-03-02

    Triterpenes, which comprise a broad chemical group of active principles, are implicated in the mechanisms of action and pharmacological effects of many medicinal plants used in folk medicine against diseases in which the immune system is implicated. They have been described as anti-inflammatory, antiviral, antimicrobial, and antitumoral agents, as well as being immunomodulator compounds. Several of them are implicated in the resolution of immune diseases, although their effects have not always been clearly correlated. The aim of this review is to compile relevant data on the mechanisms of action of triterpenes isolated from active ethnomedicinal plants and their role in the resolution of diseases in which the immune system is implicated to examine the mechanism by which they are useful as ethnopharmacological medicines. The selection of papers was made using the most relevant databases for the biomedical sciences on the basis of their ethnopharmacological use. We principally chose those studies that examined the resolution of allergic responses in vivo and those that studied the effects of the more relevant mediators implicated in the immune response in vitro. The number of compounds actually studied is limited compared with the high number of principles that have been isolated and identified. Many studies focus on specific pathologies such cancer or inflammation, but in many cases they are clearly correlated with the immune response. Lanostanes, cucurbitanes, and oleananes are probably the most interesting groups; however, other compounds are also of potential importance. Studies of specific mechanisms against mediators or transcription factors could be the objective for future research on ethnomedicinal plants used to combat immune diseases since the results obtained with cucurbitacins or derivatives of oleanolic acid support the use of different medicinal plants, thereby opening up a new frontier for future studies. Copyright (c) 2010 Elsevier Ireland Ltd. All

  2. 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.

  3. Lactobacilli and Bifidobacteria Promote Immune Homeostasis by Modulating Innate Immune Responses to Human Rotavirus in Neonatal Gnotobiotic Pigs

    PubMed Central

    Vlasova, Anastasia N.; Chattha, Kuldeep S.; Kandasamy, Sukumar; Liu, Zhe; Esseili, Malak; Shao, Lulu; Rajashekara, Gireesh; Saif, Linda J.

    2013-01-01

    The effects of co-colonization with Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) on 3-dose vaccination with attenuated HRV and challenge with virulent human rotavirus (VirHRV) were assessed in 4 groups of gnotobiotic (Gn) pigs: Pro+Vac (probiotic-colonized/vaccinated), Vac (vaccinated), Pro (probiotic-colonized, non-vaccinated) and Control (non-colonized, non-vaccinated). Subsets of pigs were euthanized pre- [post-challenge day (PCD) 0] and post (PCD7)-VirHRV challenge to assess diarrhea, fecal HRV shedding and dendritic cell/innate immune responses. Post-challenge, Pro+Vac and Vac groups were completely protected from diarrhea; protection rates against HRV shedding were 100% and 83%, respectively. Diarrhea and HRV shedding were reduced in Pro compared to Control pigs following VirHRV challenge. Diarrhea scores and virus shedding were significantly higher in Controls, compared to all other groups, coincident with significantly higher serum interferon-alpha levels post-challenge. LGG+Bb12 colonization ±vaccine promoted immunomaturation as reflected by increased frequencies of CD4, SWC3a, CD11R1, MHCII expressing mononuclear cells (MNCs) and conventional dendritic cells in intestinal tissues and blood post-challenge. Colonization decreased frequencies of toll-like receptors (TLR) 2 and TLR4 expressing MNCs from vaccinated pigs (Pro+Vac) pre-challenge and increased frequencies of TLR3 expressing MNCs from Pro pigs post-challenge, suggesting that probiotics likely exert anti-inflammatory (TLR2 and 4 down-regulation) and antiviral (TLR3 up-regulation by HRV dsRNA) actions via TLR signaling. Probiotic colonization alone (Pro) increased frequencies of intestinal and systemic apoptotic MNCs pre-challenge, thereby regulating immune hyperreactivity and tolerance. However, these frequencies were decreased in intestinal and systemic tissues post-challenge, moderating HRV-induced apoptosis. Additionally, post-challenge, Pro+Vac and Pro groups had

  4. Lactobacilli and bifidobacteria promote immune homeostasis by modulating innate immune responses to human rotavirus in neonatal gnotobiotic pigs.

    PubMed

    Vlasova, Anastasia N; Chattha, Kuldeep S; Kandasamy, Sukumar; Liu, Zhe; Esseili, Malak; Shao, Lulu; Rajashekara, Gireesh; Saif, Linda J

    2013-01-01

    The effects of co-colonization with Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) on 3-dose vaccination with attenuated HRV and challenge with virulent human rotavirus (VirHRV) were assessed in 4 groups of gnotobiotic (Gn) pigs: Pro+Vac (probiotic-colonized/vaccinated), Vac (vaccinated), Pro (probiotic-colonized, non-vaccinated) and Control (non-colonized, non-vaccinated). Subsets of pigs were euthanized pre- [post-challenge day (PCD) 0] and post (PCD7)-VirHRV challenge to assess diarrhea, fecal HRV shedding and dendritic cell/innate immune responses. Post-challenge, Pro+Vac and Vac groups were completely protected from diarrhea; protection rates against HRV shedding were 100% and 83%, respectively. Diarrhea and HRV shedding were reduced in Pro compared to Control pigs following VirHRV challenge. Diarrhea scores and virus shedding were significantly higher in Controls, compared to all other groups, coincident with significantly higher serum interferon-alpha levels post-challenge. LGG+Bb12 colonization ±vaccine promoted immunomaturation as reflected by increased frequencies of CD4, SWC3a, CD11R1, MHCII expressing mononuclear cells (MNCs) and conventional dendritic cells in intestinal tissues and blood post-challenge. Colonization decreased frequencies of toll-like receptors (TLR) 2 and TLR4 expressing MNCs from vaccinated pigs (Pro+Vac) pre-challenge and increased frequencies of TLR3 expressing MNCs from Pro pigs post-challenge, suggesting that probiotics likely exert anti-inflammatory (TLR2 and 4 down-regulation) and antiviral (TLR3 up-regulation by HRV dsRNA) actions via TLR signaling. Probiotic colonization alone (Pro) increased frequencies of intestinal and systemic apoptotic MNCs pre-challenge, thereby regulating immune hyperreactivity and tolerance. However, these frequencies were decreased in intestinal and systemic tissues post-challenge, moderating HRV-induced apoptosis. Additionally, post-challenge, Pro+Vac and Pro groups had

  5. ODIN system technology module library, 1972 - 1973

    NASA Technical Reports Server (NTRS)

    Hague, D. S.; Watson, D. A.; Glatt, C. R.; Jones, R. T.; Galipeau, J.; Phoa, Y. T.; White, R. J.

    1978-01-01

    ODIN/RLV is a digital computing system for the synthesis and optimization of reusable launch vehicle preliminary designs. The system consists of a library of technology modules in the form of independent computer programs and an executive program, ODINEX, which operates on the technology modules. The technology module library contains programs for estimating all major military flight vehicle system characteristics, for example, geometry, aerodynamics, economics, propulsion, inertia and volumetric properties, trajectories and missions, steady state aeroelasticity and flutter, and stability and control. A general system optimization module, a computer graphics module, and a program precompiler are available as user aids in the ODIN/RLV program technology module library.

  6. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    NASA Astrophysics Data System (ADS)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  7. Health Occupations Module. The Integumentary System.

    ERIC Educational Resources Information Center

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the integumentary system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, objectives (e.g., list and describe the types of glands formed in the skin, and explain the…

  8. Health Occupations Module. The Integumentary System.

    ERIC Educational Resources Information Center

    Temple Univ., Philadelphia, PA. Div. of Vocational Education.

    This module on the integumentary system is one of eight modules designed for individualized instruction in health occupations education programs at both the secondary and postsecondary levels. This module contains an introduction to the module topic, objectives (e.g., list and describe the types of glands formed in the skin, and explain the…

  9. Autonomous cotton module forming system

    USDA-ARS?s Scientific Manuscript database

    Cotton producers often have difficulty finding adequate labor during harvest. Module builder operators are often inexperienced and may build poorly shaped modules. Equipment manufacturers have recently introduced harvesters with on-board module building capabilities to reduce labor requirements; h...

  10. [Linoleic acid and the immune system. Controversies about lipid emulsions].

    PubMed

    García de Lorenzo, A; Culebras, J M

    1992-01-01

    The selection of a given lipidic function for nutritional backup requires not only knowledge of the metabolism of the different existing lipidic emulsions and of their specific therapeutic indications, but also of their contraindications and controversies because, apart from their calorific value, the contribution of liposoluble vitamins and their function in preventing essential fatty acid deficiencies, we know that they are powerful metabolic modulators. This in associated with the fact that manipulation of dietary lipids (enteral or parenteral) can affect and modulate the response to the disease, attack or infection by improving or impairing the different immune functions. This review is focused on the scientific publications which have examined the varying effects of lipidic emulsions, in quantity and in quality (particularly linoleic acid) on the immune system, on the fatty acid composition of the cellular membranes and on the production of and prostaglandins and leukotrienes. An update is given of the known interrelation between lipids and immunity, with appraisal of triglycerides and long-medium -- and short-chain fatty acids, mixtures of medium -- and long-chain triglycerides, the proportions between infinity-3/infinity-6, and structured lipids.

  11. Cellular factors targeting APCs to modulate adaptive T cell immunity.

    PubMed

    Visperas, Anabelle; Do, Jeongsu; Min, Booki

    2014-01-01

    The fate of adaptive T cell immunity is determined by multiple cellular and molecular factors, among which the cytokine milieu plays the most important role in this process. Depending on the cytokines present during the initial T cell activation, T cells become effector cells that produce different effector molecules and execute adaptive immune functions. Studies thus far have primarily focused on defining how these factors control T cell differentiation by targeting T cells themselves. However, other non-T cells, particularly APCs, also express receptors for the factors and are capable of responding to them. In this review, we will discuss how APCs, by responding to those cytokines, influence T cell differentiation and adaptive immunity.

  12. Modulation of macrophage activation and programming in immunity.

    PubMed

    Liu, Guangwei; Yang, Hui

    2013-03-01

    Macrophages are central mediators of the immune, contributing both to the initiation and the resolution of inflammation. The concept of macrophage activation and program has stimulated interest in its definition, and functional significance in homeostasis and diseases. It has been known that macrophages could be differently activated and programmed into different functional subtypes in response to different types of antigen stumuli or different kinds of cytokines present in the microenvironment and could thus profoundly influence immune responses, but little is known about the state and exact regulatory mechanism of macrophage activation and program from cell or molecular signaling level in immunity. In this review, we summarize the recent finding regarding the regulatory mechanism of macrophage activation and program toward M1 and M2, especially on M2 macrophages.

  13. Interactions between the microbiota, immune and nervous systems in health and disease.

    PubMed

    Fung, Thomas C; Olson, Christine A; Hsiao, Elaine Y

    2017-02-01

    The diverse collection of microorganisms that inhabit the gastrointestinal tract, collectively called the gut microbiota, profoundly influences many aspects of host physiology, including nutrient metabolism, resistance to infection and immune system development. Studies investigating the gut-brain axis demonstrate a critical role for the gut microbiota in orchestrating brain development and behavior, and the immune system is emerging as an important regulator of these interactions. Intestinal microbes modulate the maturation and function of tissue-resident immune cells in the CNS. Microbes also influence the activation of peripheral immune cells, which regulate responses to neuroinflammation, brain injury, autoimmunity and neurogenesis. Accordingly, both the gut microbiota and immune system are implicated in the etiopathogenesis or manifestation of neurodevelopmental, psychiatric and neurodegenerative diseases, such as autism spectrum disorder, depression and Alzheimer's disease. In this review, we discuss the role of CNS-resident and peripheral immune pathways in microbiota-gut-brain communication during health and neurological disease.

  14. Acute exercise modulates BDNF and pro-BDNF protein content in immune cells.

    PubMed

    Brunelli, Andrea; Dimauro, Ivan; Sgrò, Paolo; Emerenziani, Gian Pietro; Magi, Fiorenza; Baldari, Carlo; Guidetti, Laura; Di Luigi, Luigi; Parisi, Paolo; Caporossi, Daniela

    2012-10-01

    Although several studies have shown that immune cells stimulated by in vitro stress are capable to produce neurotrophins, there is still no evidence whether physiological stress, such as exercise, can modulate the in vivo levels of brain-derived neurotrophic factor (BDNF) in peripheral blood mononuclear cells (PBMCs). This work investigated whether acute exercise modulates the expression of BDNF, pro-BDNF, and p75(NTR) in the PBMCs of 10 healthy young men who performed a cycling incremental test to exhaustion (MAX) or exercised at individual anaerobic threshold (IAT). The PBMC expression of stress response proteins and the level of circulating BDNF, vascular endothelial growth growth factor, platelet-derived growth factor subunit B, basic fibroblast growth factor pro-inflammatory, and anti-inflammatory cytokines were analyzed as well. A major finding is that both sessions of acute exercise regulated the content of BDNF isoforms within PBMCs in a manner related to the physiological stress exerted. Although the pro-BDNF increased after both MAX and IAT protocols, BDNF showed a kinetics dependent on exercise type: MAX induced a 54% protein increase immediately after exercise, followed by a significant drop 60 min after its conclusion (38% lower than the baseline). Differently, in the IAT, BDNF increased significantly up to 75% from the baseline throughout the recovery phase. All physiological parameters, as well as the p75(NTR) receptor and the stress-inducible proteins, were also differently regulated by the two exercise conditions. These data supported the hypothesis that PBMCs might produce and secrete BDNF isoforms, as well as modulate the proteins p75(NTR) , Bcl-xL, hsp90, hsp27, and αB-crystallin, as part of the physiological stress response induced by acute exercise, offering a novel example of bidirectional interaction between nervous and immune systems.

  15. The Mucosal Immune System of Teleost Fish

    PubMed Central

    Salinas, Irene

    2015-01-01

    Teleost fish possess an adaptive immune system associated with each of their mucosal body surfaces. Evidence obtained from mucosal vaccination and mucosal infection studies reveal that adaptive immune responses take place at the different mucosal surfaces of teleost. The main mucosa-associated lymphoid tissues (MALT) of teleosts are the gut-associated lymphoid tissue (GALT), skin-associated lymphoid tissue (SALT), the gill-associated lymphoid tissue (GIALT) and the recently discovered nasopharynx-associated lymphoid tissue (NALT). Teleost MALT includes diffuse B cells and T cells with specific phenotypes different from their systemic counterparts that have co-evolved to defend the microbe-rich mucosal environment. Both B and T cells respond to mucosal infection or vaccination. Specific antibody responses can be measured in the gills, gut and skin mucosal secretions of teleost fish following mucosal infection or vaccination. Rainbow trout studies have shown that IgT antibodies and IgT+ B cells are the predominant B cell subset in all MALT and respond in a compartmentalized manner to mucosal infection. Our current knowledge on adaptive immunity in teleosts is limited compared to the mammalian literature. New research tools and in vivo models are currently being developed in order to help reveal the great intricacy of teleost mucosal adaptive immunity and help improve mucosal vaccination protocols for use in aquaculture. PMID:26274978

  16. Fishing for mammalian paradigms in the teleost immune system.

    PubMed

    Sunyer, J Oriol

    2013-04-01

    Recent years have witnessed a renaissance in the study of fish immune systems. Such studies have greatly expanded the knowledge of the evolution and diversification of vertebrate immune systems. Several findings in those studies have overturned old paradigms about the immune system and led to the discovery of novel aspects of mammalian immunity. Here I focus on how findings pertaining to immunity in teleost (bony) fish have led to major new insights about mammalian B cell function in innate and adaptive immunity. Additionally, I illustrate how the discovery of the most ancient mucosal immunoglobulin described thus far will help resolve unsettled paradigms of mammalian mucosal immunity.

  17. Fishing for mammalian paradigms in the teleost immune system

    PubMed Central

    Sunyer, J Oriol

    2013-01-01

    Recent years have witnessed a renaissance in the study of fish immune systems. Such studies have greatly expanded the knowledge of the evolution and diversification of vertebrate immune systems. Several findings in those studies have overturned old paradigms about the immune system and led to the discovery of novel aspects of mammalian immunity. Here I focus on how findings pertaining to immunity in teleost (bony) fish have led to major new insights about mammalian B cell function in innate and adaptive immunity. Additionally, I illustrate how the discovery of the most ancient mucosal immunoglobulin described thus far will help resolve unsettled paradigms of mammalian mucosal immunity. PMID:23507645

  18. The Role of Environmental Factors in Modulating Immune Responses in Early Life

    PubMed Central

    MacGillivray, Duncan M.; Kollmann, Tobias R.

    2014-01-01

    The concept of immunological memory stipulates that past exposures shape present immune function. These exposures include not only specific antigens impacting adaptive immune memory but also conserved pathogen or danger associated molecular patterns that mold innate immune responses for prolonged periods of time. It should thus not come as a surprise that there is a vast range of external or environmental factors that impact immunity. The importance of environmental factors modulating immunity is most readily recognized in early life, a period of rapidly changing environments. We here summarize available data on the role of environment shaping immune development and from it derive an overarching hypothesis relating the underlying molecular mechanisms and evolutionary principles involved. PMID:25309535

  19. 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.

  20. Radiation-Induced Immune Modulation in Prostate Cancer

    DTIC Science & Technology

    2007-01-01

    postulate that radiation-induced TNFR I probably acts as a “ brake ” on immunity. Because of the high risk of the proposed experiment and high...the rest of body shielded. Tumor diameters were measured in three mutually orthogonal dimensions at 2–3 day intervals with a vernier caliper and the

  1. Immune checkpoint modulation for non-small cell lung cancer.

    PubMed

    Soria, Jean-Charles; Marabelle, Aurélien; Brahmer, Julie R; Gettinger, Scott

    2015-05-15

    Therapies targeting immune checkpoints have recently shown encouraging activity in patients with heavily pretreated advanced non-small cell lung cancer (NSCLC), independently of NSCLC histology or mutational status, with low toxicity profiles when used as monotherapy. Objective response rates of approximately 20% have been reported in patients with advanced NSCLC treated with antagonist antibodies targeting the immune checkpoint, programmed death 1 (PD-1) on activated T cells, or its primary ligand, programmed death ligand 1 (PD-L1) expressed within the tumor microenvironment. Response rates appear to be higher in patients with tumor PD-L1 expression documented by immunohistochemistry, although responses have been appreciated in patients with reportedly PD-L1-negative tumor specimens. Antibodies directed against cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), another immunosuppressive T-cell signaling molecule, are also being evaluated in clinical trials, with one randomized phase II trial demonstrating improved immune-related progression-free survival in lung cancer patients when added to standard chemotherapy. Additional clinical trials are combining anti-CTLA-4 antibodies with either anti-PD-1 or anti-PD-L1 antibodies. Combinations of other immune checkpoint antagonists or agonist antibodies with anti-PD-1 or anti-PD-L1 antibodies are also being pursued.

  2. From network-to-antibody robustness in a bio-inspired immune system.

    PubMed

    Fernandez-Leon, Jose A; Acosta, Gerardo G; Mayosky, Miguel A

    2011-01-01

    Behavioural robustness at antibody and immune network level is discussed. The robustness of the immune response that drives an autonomous mobile robot is examined with two computational experiments in the autonomous mobile robots trajectory generation context in unknown environments. The immune response is met based on the immune network metaphor for different low-level behaviours coordination. These behaviours are activated when a robot sense the appropriate conditions in the environment in relation to the network current state. Results are obtained over a case study in computer simulation as well as in laboratory experiments with a Khepera II microrobot. In this work, we develop a set of tests where such an immune response is externally perturbed at network or low-level behavioural modules to analyse the robust capacity of the system to unexpected perturbations. Emergence of robust behaviour and high-level immune response relates to the coupling between behavioural modules that are selectively engaged with the environment based on immune response. Experimental evidence leads discussions on a dynamical systems perspective of behavioural robustness in artificial immune systems that goes beyond the isolated immune network response.

  3. Dissecting Phaseolus vulgaris Innate Immune System against Colletotrichum lindemuthianum Infection

    PubMed Central

    Chowdhury, Bablu; Caldas, Danielle Gregório Gomes; Tsai, Siu Mui; Camargo, Luis Eduardo Aranha; Melotto, Maeli

    2012-01-01

    Background The genus Colletotrichum is one of the most economically important plant pathogens, causing anthracnose on a wide range of crops including common beans (Phaseolus vulgaris L.). Crop yield can be dramatically decreased depending on the plant cultivar used and the environmental conditions. This study aimed to identify potential genetic components of the bean immune system to provide environmentally friendly control measures against this fungus. Methodology and Principal Findings As the common bean is not amenable to reverse genetics to explore functionality and its genome is not fully curated, we used putative Arabidopsis orthologs of bean expressed sequence tag (EST) to perform bioinformatic analysis and experimental validation of gene expression to identify common bean genes regulated during the incompatible interaction with C. lindemuthianum. Similar to model pathosystems, Gene Ontology (GO) analysis indicated that hormone biosynthesis and signaling in common beans seem to be modulated by fungus infection. For instance, cytokinin and ethylene responses were up-regulated and jasmonic acid, gibberellin, and abscisic acid responses were down-regulated, indicating that these hormones may play a central role in this pathosystem. Importantly, we have identified putative bean gene orthologs of Arabidopsis genes involved in the plant immune system. Based on experimental validation of gene expression, we propose that hypersensitive reaction as part of effector-triggered immunity may operate, at least in part, by down-regulating genes, such as FLS2-like and MKK5-like, putative orthologs of the Arabidopsis genes involved in pathogen perception and downstream signaling. Conclusions/Significance We have identified specific bean genes and uncovered metabolic processes and pathways that may be involved in the immune response against pathogens. Our transcriptome database is a rich resource for mining novel defense-related genes, which enabled us to develop a model of

  4. Dissecting Phaseolus vulgaris innate immune system against Colletotrichum lindemuthianum infection.

    PubMed

    Oblessuc, Paula Rodrigues; Borges, Aline; Chowdhury, Bablu; Caldas, Danielle Gregório Gomes; Tsai, Siu Mui; Camargo, Luis Eduardo Aranha; Melotto, Maeli

    2012-01-01

    The genus Colletotrichum is one of the most economically important plant pathogens, causing anthracnose on a wide range of crops including common beans (Phaseolus vulgaris L.). Crop yield can be dramatically decreased depending on the plant cultivar used and the environmental conditions. This study aimed to identify potential genetic components of the bean immune system to provide environmentally friendly control measures against this fungus. As the common bean is not amenable to reverse genetics to explore functionality and its genome is not fully curated, we used putative Arabidopsis orthologs of bean expressed sequence tag (EST) to perform bioinformatic analysis and experimental validation of gene expression to identify common bean genes regulated during the incompatible interaction with C. lindemuthianum. Similar to model pathosystems, Gene Ontology (GO) analysis indicated that hormone biosynthesis and signaling in common beans seem to be modulated by fungus infection. For instance, cytokinin and ethylene responses were up-regulated and jasmonic acid, gibberellin, and abscisic acid responses were down-regulated, indicating that these hormones may play a central role in this pathosystem. Importantly, we have identified putative bean gene orthologs of Arabidopsis genes involved in the plant immune system. Based on experimental validation of gene expression, we propose that hypersensitive reaction as part of effector-triggered immunity may operate, at least in part, by down-regulating genes, such as FLS2-like and MKK5-like, putative orthologs of the Arabidopsis genes involved in pathogen perception and downstream signaling. We have identified specific bean genes and uncovered metabolic processes and pathways that may be involved in the immune response against pathogens. Our transcriptome database is a rich resource for mining novel defense-related genes, which enabled us to develop a model of the molecular components of the bean innate immune system regulated upon

  5. 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.

  6. Immune inflammation indicators and implication for immune modulation strategies in advanced hepatocellular carcinoma patients receiving sorafenib

    PubMed Central

    Gardini, Andrea Casadei; Scarpi, Emanuela; Faloppi, Luca; Scartozzi, Mario; Silvestris, Nicola; Santini, Daniele; de Stefano, Giorgio; Marisi, Giorgia; Negri, Francesca V.; Foschi, Francesco Giuseppe; Valgiusti, Martina; Ercolani, Giorgio; Frassineti, Giovanni Luca

    2016-01-01

    We evalueted a systemic immune-inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) with the aim to explored their prognostic value in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. 56 advanced HCC patients receiving sorafenib were available for our analysis. Lymphocyte, neutrophil and platelet were measured before beginning of treatment and after one month. Patient with SII ≥ 360 showed lower median PFS (2.6 vs. 3.9 months, P < 0.026) and OS (5.6 vs. 13.9 months, P = 0.027) with respect to patients with SII < 360. NLR ≥ 3 had a lower median PFS (2.6 vs. 3.3 months, P < 0.049) but not OS (5.6 vs. 13.9 months, P = 0.062) than those with NLR < 3. After adjusting for clinical covariates SII and NLR remained an independent prognostic factor for OS. The SII and NLR represent potential prognostic indicator in patients with advanced HCC treated with sorafenib. PMID:27613839

  7. Interaction between the skeletal and immune systems in cancer: mechanisms and clinical implications.

    PubMed

    Terpos, Evangelos; Dimopoulos, Meletios A

    2011-03-01

    The skeletal and immune systems have a complex relationship. Both systems are intimately coupled, with osteoclastogenesis and hematopoiesis occurring in the bone marrow. Bone and immune cells also share common hematopoietic precursors. Furthermore, the skeletal and immune systems share various cytokines, receptors, and transcription factors that regulate signal transduction pathways involved in osteoclastogenesis and immune system activation, including the receptor activator of nuclear factor-κΒ ligand/receptor activator of nuclear factor-κΒ/osteoprotegerin (RANKL-RANK-OPG) pathway. Cancer cells can disrupt both the skeletal and immune systems. Interaction between cancer and bone cells results in a vicious cycle of bone destruction and cancer growth. Bone remodeling generates a growth-factor-rich environment that attracts cancer cells and promotes their proliferation. In turn, cancer cells stimulate osteoclast formation and activity, resulting in additional bone resorption that further stimulates cancer cell growth. Currently available bone-targeted therapies may also modulate the immune system. Bisphosphonates such as zoledronic acid exert stimulating effects on the immune system, resulting in possible anticancer activity against malignant cells. Denosumab, an anti-RANKL monoclonal antibody with proven antiosteoclast activity, may suppress immune responses. This may result in the reported association with an increased risk of neoplasms, as well as serious skin and other infections as reported in some studies, mainly in the postmenopausal setting. When assessing bone-targeted therapies, it is important to consider the shared signaling pathways between bone and the immune system, as well as the clinical risk:benefit ratio.

  8. Regulatory T Cells, a Potent Immunoregulatory Target for CAM Researchers: Modulating Tumor Immunity, Autoimmunity and Alloreactive Immunity (III)

    PubMed Central

    Vojdani, Aristo; Erde, Jonathan

    2006-01-01

    Regulatory T (Treg) cells are the major arbiter of immune responses, mediating actions through the suppression of inflammatory and destructive immune reactions. Inappropriate Treg cell frequency or functionality potentiates the pathogenesis of myriad diseases with ranging magnitudes of severity. Lack of suppressive capability hinders restraint on immune responses involved in autoimmunity and alloreactivity, while excessive suppressive capacity effectively blocks processes necessary for tumor destruction. Although the etiology of dysfunctional Treg cell populations is under debate, the ramifications, and their mechanisms, are increasingly brought to light in the medical community. Methods that compensate for aberrant immune regulation may not address the underlying complications; however, they hold promise for the alleviation of debilitating immune system-related disorders. The dominant immunoregulatory nature of Treg cells, coupled with recent mechanistic knowledge of natural immunomodulatory compounds, highlights the importance of Treg cells to practitioners and researchers of complementary and alternative medicine (CAM). PMID:16951715

  9. [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.

  10. Reciprocity in microbiome and immune system interactions and its implications in disease and health.

    PubMed

    Nikoopour, Enayat; Singh, Bhagirath

    2014-01-01

    Adaptation of the whole microbial normal flora residing in a host to its natural habitat over an evolutionary peroid has resulted in peaceful coexistence with mutual benefits for both microbiota and host in steady state. This symbiotic relationship between host and microbiota has a significant impact on shaping the immune response in the host to achieve an immune tolerance to microbiota but retaining the ability to respond to invading pathogens. Perturbation of this balance by manipulation of microbial communities in the host can lead to immune dysregulation and susceptibility to diseases. By studying the host in the absence of microbiota or with alteration of microbiota the complexity of microbial impact on the immune system can be resolved. Conversely, the study of microbiota in the absence of immune system factors can show how the immune system contributes to preservation of the host-microbiota balance. The absence of molecules involved in innate or adaptive immunity in knockout models can perturb the balance between host and microbiota further adding to more immune dysregulation. A better understanding of Microbiome-immune system interaction provides a new opportunity to identify biomarkers and drug targets. This will allow the development of new therapeutic agents for modulating the immune system to improve health with little or no toxicity. The study of interplay between host and microbiota has a promising role in the design of therapeutic interventions for immunopathological diseases arising from imbalanced host and microbiota interactions.

  11. Effect of laparoscopy on the immune system.

    PubMed

    Kuhry, E; Jeekel, J; Bonjer, H J

    2004-03-01

    Surgery induces alterations in local and systemic immune responses. These changes appear to be associated with an increase in postoperative morbidity. Minimally invasive techniques are considered to improve the preservation of immune function compared with open surgery and may therefore be beneficial for patient recovery. As laparoscopic techniques are increasingly used in abdominal surgery, more research has focussed on the immunologic consequences of these techniques. Nevertheless, the changes that occur in response to trauma are still not completely understood. The immunologic benefits of laparoscopic surgery are the most obvious for minor surgical procedures such as cholecystectomy and antireflux surgery. For more complex procedures such as colorectal surgery for cancer, the benefits are not immediately obvious. Although laparoscopic surgery for colorectal malignancies may be associated with higher survival rates and lower recurrence rates because of improved immune function, it has also been related to high incidences of port-site metastases. Reviews in the literature have now shown that incidences of port-site metastases are comparable to incidences of wound metastases after open surgery. However, it will be necessary to wait for the long-term results of randomized, clinical trials to provide further clarification of how immune function is altered after laparoscopic and open surgery for colorectal cancer.

  12. Expression-based network biology identifies immune-related functional modules involved in plant defense.

    PubMed

    Tully, Joel P; Hill, Aubrey E; Ahmed, Hadia M R; Whitley, Ryan; Skjellum, Anthony; Mukhtar, M Shahid

    2014-06-03

    Plants respond to diverse environmental cues including microbial perturbations by coordinated regulation of thousands of genes. These intricate transcriptional regulatory interactions depend on the recognition of specific promoter sequences by regulatory transcription factors. The combinatorial and cooperative action of multiple transcription factors defines a regulatory network that enables plant cells to respond to distinct biological signals. The identification of immune-related modules in large-scale transcriptional regulatory networks can reveal the mechanisms by which exposure to a pathogen elicits a precise phenotypic immune response. We have generated a large-scale immune co-expression network using a comprehensive set of Arabidopsis thaliana (hereafter Arabidopsis) transcriptomic data, which consists of a wide spectrum of immune responses to pathogens or pathogen-mimicking stimuli treatments. We employed both linear and non-linear models to generate Arabidopsis immune co-expression regulatory (AICR) network. We computed network topological properties and ascertained that this newly constructed immune network is densely connected, possesses hubs, exhibits high modularity, and displays hallmarks of a "real" biological network. We partitioned the network and identified 156 novel modules related to immune functions. Gene Ontology (GO) enrichment analyses provided insight into the key biological processes involved in determining finely tuned immune responses. We also developed novel software called OCCEAN (One Click Cis-regulatory Elements ANalysis) to discover statistically enriched promoter elements in the upstream regulatory regions of Arabidopsis at a whole genome level. We demonstrated that OCCEAN exhibits higher precision than the existing promoter element discovery tools. In light of known and newly discovered cis-regulatory elements, we evaluated biological significance of two key immune-related functional modules and proposed mechanism(s) to explain

  13. Environmental and genetic activation of hypothalamic BDNF modulates T-cell immunity to exert an anticancer phenotype

    PubMed Central

    Huang, Wei; Slater, Andrew M.; Liu, Xianglan; Judd, Ryan T; Lin, En-Ju D.; Widstrom, Kyle J.; Scoville, Steven D; Yu, Jianhua; Caligiuri, Michael A.; Cao, Lei

    2016-01-01

    Macro-environmental factors, including a patient’s physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) providing complex stimuli confers an anticancer phenotype in mice mediated in part by a specific neuroendocrine axis, with brain-derived neurotrophic factor (BDNF) as the key brain mediator. Here we investigated how an EE modulated T-cell immunity and its role in the EE-induced anticancer effects. Our data demonstrated that CD8 T cells were required to mediate the anticancer effects of an EE in an orthotropic model of melanoma. In secondary lymphoid tissue (SLT), an EE induced early changes in the phenotype of T-cell populations, characterized by a decrease in the ratio of CD4 T helper to CD8 cytotoxic T lymphocytes (CTLs). Overexpression of hypothalamic BDNF reproduced EE-induced T-cell phenotypes in SLT whereas knockdown of hypothalamic BDNF inhibited EE-induced immune modulation in SLT. Both propranolol and mifepristone blocked the EE-associated modulation of CTLs in SLT suggesting both the sympathetic nervous system and hypothalamic-pituitary-adrenal axis were involved. Our results demonstrated that enhanced anticancer effect of an EE was mediated at least in part through modulation of T-cell immunity and provided support to the emerging concept of manipulating a single gene in the brain to improve cancer immunotherapy. PMID:27045020

  14. 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.

  15. Vitamin effects on the immune system: vitamins A and D take centre stage

    PubMed Central

    Mora, J. Rodrigo; Iwata, Makoto; von Andrian, Ulrich H.

    2010-01-01

    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. PMID:19172691

  16. Modulation of innate and adaptive immunity by biodegradable nanoparticles.

    PubMed

    Uto, Tomofumi; Akagi, Takami; Hamasaki, Takayuki; Akashi, Mitsuru; Baba, Masanori

    2009-06-30

    Vaccine strategy needs efficient adjuvants to induce potent antigen-specific immune responses by targeting antigens to antigen presenting cells followed by their functional maturation. In this study, biodegradable poly(gamma-glutamic acid) (gamma-PGA) nanoparticles (NPs) were examined for their immunological activities in mice. Like lipopolysaccharide, gamma-PGA NPs strongly activated spleen dendritic cells (DCs) and induced their cytokine production and costimulatory molecule expression through the nuclear factor-kappaB and mitogen-activated protein kinase signaling pathways. The immunization of mice with ovalbumin-carrying gamma-PGA NPs could induce the antigen-specific and long-lived effector and central memory CD8(+) T cells as well as antibody responses. Thus, gamma-PGA NPs have great potential as an efficient antigen carrier and strong adjuvant to DCs.

  17. CD147: a novel modulator of inflammatory and immune disorders.

    PubMed

    Zhu, X; Song, Z; Zhang, S; Nanda, A; Li, G

    2014-01-01

    CD147, a transmembrane glycoprotein, is expressed on all leukocytes, platelets, and endothelial cells. It has been implicated in a variety of physiological and pathological activities through interacting with multiple partners, including cyclophilins, monocarboxylate transporters, Caveolin-1, and integrins. While CD147 is best known as a potent inducer of extracellular matrix metalloproteinases (hence also called EMMPRIN), it can also function as a key mediator of inflammatory and immune responses. Increased expression of CD147 has been implicated in the pathogenesis of a number of diseases, such as asthma-mediated lung inflammation, rheumatoid arthritis, multiple sclerosis, myocardial infarction and ischemic stroke. Therapeutic targeting of CD147 has yielded encouraging effects in a number of experimental models of human diseases, suggesting CD147 as an attractive target for treatment of inflammation-related diseases. Here we review the current understanding of CD147 expression and functions in inflammatory and immune responses and potential implications for treatment of inflammatory disorders.

  18. Modulation of host immunity and reproduction by horizontally acquired Wolbachia.

    PubMed

    Pigeault, Romain; Braquart-Varnier, Christine; Marcadé, Isabelle; Mappa, Gaëtan; Mottin, Elmina; Sicard, Mathieu

    2014-11-01

    The Wolbachia are symbiotic bacteria vertically transmitted from one host generation to another. However, a growing amount of data shows that horizontal transfers of Wolbachia also frequently occur within and between host species. The consequences of the arrival of new symbionts on host physiology can be studied by their experimental introduction in asymbiotic hosts. After experimental transfers of the eight major isopod Wolbachia strains in the isopod Porcellio dilatatus only two of them (wCon and wDil) were found to (1) have no pathogenic effect on the host and (2) be able to pass vertically to the host offspring. In the present work, we studied the influence of these two strains, able to complete an horizontal transfer, on immunity and reproduction of P. dilatatus at two stages of the transfer: (1) in recipient hosts that encounter the symbionts: to test the influence of symbiont when acquired during host life and (2) in vertically infected offspring: to test the influence of a symbiotic interaction occurring all lifelong. The impact of Wolbachia varied depending on the stage: there were clearer effects in vertically infected individuals than in those that acquired the symbionts during their lives. Moreover, the two Wolbachia strains showed contrasted effects: the strain wCon tended to reduce the reproductive investment but to maintain or increase immune parameters whilst wDil had positive effects on reproductive investment but decreased the investment in some immune parameters. These results suggest that horizontally acquisition of Wolbachia can influence the balance between host immune and reproductive traits. Copyright © 2014. Published by Elsevier Ltd.

  19. CB2 and GPR55 Receptors as Therapeutic Targets for Systemic Immune Dysregulation

    PubMed Central

    Zhou, Juan; Burkovskiy, Ian; Yang, Hyewon; Sardinha, Joel; Lehmann, Christian

    2016-01-01

    The endocannabinoid system (ECS) is involved in many physiological processes and has been suggested to play a critical role in the immune response and the central nervous system (CNS). Therefore, ECS modulation has potential therapeutic effects on immune dysfunctional disorders, such as sepsis and CNS injury-induced immunodeficiency syndrome (CIDS). In sepsis, excessive release of pro- and anti-inflammatory mediators results in multi-organ dysfunction, failure, and death. In CIDS, an acute CNS injury dysregulates a normally well-balanced interplay between CNS and the immune system, leading to increased patients’ susceptibility to infections. In this review, we will discuss potential therapeutic modulation of the immune response in sepsis and CNS injury by manipulation of the ECS representing a novel target for immunotherapy. PMID:27597829

  20. Mast cells: new therapeutic target in helminth immune modulation.

    PubMed

    Vukman, K V; Lalor, R; Aldridge, A; O'Neill, S M

    2016-01-01

    Helminth infection and their secreted antigens have a protective role in many immune-mediated inflammatory disorders such as inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. However, studies have focused primarily on identifying immune protective mechanisms of helminth infection and their secreted molecules on dendritic cells and macrophages. Given that mast cells have been shown to be implicated in the pathogenesis and progression of many inflammatory disorders, their role should also be examined and considered as cellular target for helminth-based therapies. As there is a dearth of studies examining the interaction of helminth-derived antigens and mast cells, this review will focus on the role of mast cells during helminth infection and examine our current understanding of the involvement of mast cells in TH 1/TH 17-mediated immune disorders. In this context, potential mechanisms by which helminths could target the TH 1/TH 17 promoting properties of mast cells can be identified to unveil novel therapeutic mast cell driven targets in combating these inflammatory disorders.

  1. 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

  2. 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

  3. Targeting microRNAs as key modulators of tumor immune response.

    PubMed

    Paladini, Laura; Fabris, Linda; Bottai, Giulia; Raschioni, Carlotta; Calin, George A; Santarpia, Libero

    2016-06-27

    The role of immune response is emerging as a key factor in the complex multistep process of cancer. Tumor microenvironment contains different types of immune cells, which contribute to regulate the fine balance between anti and protumor signals. In this context, mechanisms of crosstalk between cancer and immune cells remain to be extensively elucidated. Interestingly, microRNAs (miRNAs) have been demonstrated to function as crucial regulators of immune response in both physiological and pathological conditions. Specifically, different miRNAs have been reported to have a role in controlling the development and the functions of tumor-associated immune cells. This review aims to describe the most important miRNAs acting as critical modulators of immune response in the context of different solid tumors. In particular, we discuss recent studies that have demonstrated the existence of miRNA-mediated mechanisms regulating the recruitment and the activation status of specific tumor-associated immune cells in the tumor microenvironment. Moreover, various miRNAs have been found to target key cancer-related immune pathways, which concur to mediate the secretion of immunosuppressive or immunostimulating factors by cancer or immune cells. Modalities of miRNA exchange and miRNA-based delivery strategies are also discussed. Based on these findings, the modulation of individual or multiple miRNAs has the potential to enhance or inhibit specific immune subpopulations supporting antitumor immune responses, thus contributing to negatively affect tumorigenesis. New miRNA-based strategies can be developed for more effective immunotherapeutic interventions in cancer.

  4. 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.

  5. Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

    PubMed Central

    Kornberg, Arno

    2015-01-01

    Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liver disease (MELD) score helped to reduce waiting list mortality in liver transplantation (LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients’ infectious and immunologic risk profiles. The administration of intravenous immunoglobulins (IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in

  6. Did the molecules of adaptive immunity evolve from the innate immune system?

    PubMed

    Bartl, Simona; Baish, Meredith; Weissman, Irving L; Diaz, Marilyn

    2003-04-01

    The antigen receptors on cells of innate immune systems recognize broadly expressed markers on non-host cells while the receptors on lymphocytes of the adaptive immune system display a higher level of specificity. Adaptive immunity, with its exquisite specificity and immunological memory, has only been found in the jawed vertebrates, which also display innate immunity. Jawless fishes and invertebrates only have innate immunity. In the adaptive immune response, T and B-lymphocytes detect foreign agents or antigens using T cell receptors (TCR) or immunoglobulins (Ig), respectively. While Ig can bind free intact antigens, TCR only binds processed antigenic fragments that are presented on molecules encoded in the major histocompatibility complex (MHC). MHC molecules display variation through allelic polymorphism. A diverse repertoire of Ig and TCR molecules is generated by gene rearrangement and junctional diversity, processes carried out by the recombinase activating gene (RAG) products and terminal deoxynucleotidyl transferase (TdT). Thus, the molecules that define adaptive immunity are TCR, Ig, MHC molecules, RAG products and TdT. No direct predecessors of these molecules have been found in the jawless fishes or invertebrates. In contrast, the complement cascade can be activated by either adaptive or innate immune systems and contains examples of molecules that gradually evolved from non-immune functions to being part of the innate and then adaptive immune system. In this paper we examine the molecules of the adaptive immune system and speculate on the existence of direct predecessors that were part of innate immunity.

  7. 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.

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

    PubMed Central

    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. PMID:27065209

  9. A national survey of immunization programs regarding immunization information systems data sharing and use.

    PubMed

    Curran, Eileen A; Seib, Katherine G; Wells, Katelyn; Hannan, Claire; Bednarczyk, Robert A; Hinman, Alan R; Omer, Saad B

    2014-01-01

    To determine and characterize practices regarding data sharing and usage (particularly for research) in immunization information systems (IISs), as well as barriers to using such data for research. We surveyed immunization program managers (IPMs) associated with all 64 Centers for Disease Control and Prevention grantee immunization programs (IPs) between July and September 2012. More than 95% of IPMs (61/64) responded. The top 2 barriers reported by IPMs to using IIS data for research were insufficient time and too few employees, irrespective of whether or not the jurisdiction reported using data for research purposes. Those IPMs who agreed with the statement "Research is part of the mission of an immunization program" were more likely to report using data for research (P = .045). Among those who responded, the most common kind of IIS research conducted involved determinants of vaccination coverage (n = 24/26; 92%). A greater percentage of IPMs in jurisdictions that reported using IIS data for research reported having data-sharing agreements in place. Those IPs that have used IIS data for research were more likely to report online IIS provider enrollment, integration with insurance company records, and integration with hospital records. Alternatively, IPs that did not report using IIS data for research were more likely to have IISs with modules addressing topics such as adverse event reporting, smallpox, and first-responder vaccination. Staff size and time were the 2 most cited barriers to conducting research with IIS data. Therefore, focus should also be placed on providing IPs with the resources needed to conduct such research.

  10. Does khat chewing increases the risk of Mycobacterium tuberculosis infection by macrophage immune modulation?

    PubMed

    Alvi, Ayesha; Rizwan, Mohammed; Sunosi, Rashad A L; Bin Ali Jerah, Ahmed

    2014-06-01

    Drug abuse is a serious problem associated with different pathological outcomes including modulating the immune system. Drug abuse is rising in Saudi Arabia and so as TB, a disease of worldwide significance, caused by immunological modulation in the host system. Khat chewing is a common practice in Arabian Peninsula which is now gaining momentum in other parts of the world. It is considered as an addiction. It has been associated with different adverse outcomes such as periodontitis, oral leukoplakia and oral cancer and also has shown to promote apoptotic cell death through cysteine proteases. The active ingredient of khat, cathinone is shown to have immunomodulatory effect. In principle, this leads to enhanced susceptibility to various infections. The present study is designed to delineate the mechanism of immunomodulation produced by khat/cathinone in human/mouse macrophage. Further, this activity will be evaluated both in vivo and in vitro in response to infection with Mycobacterium smegmatis to get an insight if there exists a co relation between the Mycobacterium tuberculosis infection and khat chewing. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. 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

  12. A dialogue between the immune system and brain, spoken in the language of serotonin.

    PubMed

    Baganz, Nicole L; Blakely, Randy D

    2013-01-16

    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

  13. Integration of the immune system: a complex adaptive supersystem

    NASA Astrophysics Data System (ADS)

    Crisman, Mark V.

    2001-10-01

    Immunity to pathogenic organisms is a complex process involving interacting factors within the immune system including circulating cells, tissues and soluble chemical mediators. Both the efficiency and adaptive responses of the immune system in a dynamic, often hostile, environment are essential for maintaining our health and homeostasis. This paper will present a brief review of one of nature's most elegant, complex adaptive systems.

  14. Systemic activation of the immune system in HIV infection: The role of the immune complexes (hypothesis).

    PubMed

    Korolevskaya, Larisa B; Shmagel, Konstantin V; Shmagel, Nadezhda G; Saidakova, Evgeniya V

    2016-03-01

    Currently, immune activation is proven to be the basis for the HIV infection pathogenesis and a strong predictor of the disease progression. Among the causes of systemic immune activation the virus and its products, related infectious agents, pro-inflammatory cytokines, and regulatory CD4+ T cells' decrease are considered. Recently microbial translocation (bacterial products yield into the bloodstream as a result of the gastrointestinal tract mucosal barrier integrity damage) became the most popular hypothesis. Previously, we have found an association between immune complexes present in the bloodstream of HIV infected patients and the T cell activation. On this basis, we propose a significantly modified hypothesis of immune activation in HIV infection. It is based on the immune complexes' participation in the immunocompetent cells' activation. Immune complexes are continuously formed in the chronic phase of the infection. Together with TLR-ligands (viral antigens, bacterial products coming from the damaged gut) present in the bloodstream they interact with macrophages. As a result macrophages are transformed into the type II activated forms. These macrophages block IL-12 production and start synthesizing IL-10. High level of this cytokine slows down the development of the full-scale Th1-response. The anti-viral reactions are shifted towards the serogenesis. Newly synthesized antibodies' binding to viral antigens leads to continuous formation of the immune complexes capable of interacting with antigen-presenting cells.

  15. Joint Replacement Surgery and the Innate Immune System

    PubMed Central

    Goodman, Stuart; Konttinen, Yrjö T.; Takagi, Michiaki

    2015-01-01

    Total joint replacement is a highly successful, cost-effective surgical procedure that relieves pain and improves function for patients with end-stage arthritis. The most commonly used materials for modern joint replacements include metal alloys such as cobalt chrome and titanium alloys, polymers including polymethylmethacrylate and polyethylene, and ceramics. Implantation of a joint prosthesis incites an acute inflammatory reaction that is regulated by the innate immune system, a preprogrammed non-antigen specific biological response composed of cells, proteins, and other factors. This “frontline” immune mechanism was originally designed to combat invading microorganisms, but now responds to both pathogen-associated molecular patterns or PAMPS (by-products from microorganisms), and damage associated molecular patterns or DAMPS (molecular by-products from cells), via pattern recognition receptors (PRRs). In this way, potentially injurious stimuli that might disrupt the normal homeostatic regulatory mechanisms of the organism are efficiently dealt with, ensuring the survival of the host. Initial surgical implantation of the joint replacement, as well as ongoing generation of wear debris and byproducts during usage of the joint, activates the innate immune system. Understanding and potentially modulating these events may lead to improved function and increased longevity of joint replacements in the future. PMID:25747028

  16. Immune modulation by MANF promotes tissue repair and regenerative success in the retina.

    PubMed

    Neves, Joana; Zhu, Jie; Sousa-Victor, Pedro; Konjikusic, Mia; Riley, Rebeccah; Chew, Shereen; Qi, Yanyan; Jasper, Heinrich; Lamba, Deepak A

    2016-07-01

    Regenerative therapies are limited by unfavorable environments in aging and diseased tissues. A promising strategy to improve success is to balance inflammatory and anti-inflammatory signals and enhance endogenous tissue repair mechanisms. Here, we identified a conserved immune modulatory mechanism that governs the interaction between damaged retinal cells and immune cells to promote tissue repair. In damaged retina of flies and mice, platelet-derived growth factor (PDGF)-like signaling induced mesencephalic astrocyte-derived neurotrophic factor (MANF) in innate immune cells. MANF promoted alternative activation of innate immune cells, enhanced neuroprotection and tissue repair, and improved the success of photoreceptor replacement therapies. Thus, immune modulation is required during tissue repair and regeneration. This approach may improve the efficacy of stem-cell-based regenerative therapies.

  17. The Influence of Modulated Signal Risetime in Flight Electronics Radiated Immunity Testing with a Mode-Stirred Chamber

    NASA Technical Reports Server (NTRS)

    Ely, Jay J.; Nguyen, Truong X.; Scearce, Stephen A.

    2000-01-01

    For electromagnetic immunity testing of an electronic system, it is desirable to demonstrate its functional integrity when exposed to the full range and intensity of environmental electromagnetic threats that may be encountered over its operational life. As part of this, it is necessary to show proper system operation when exposed to representative threat signal modulations. Modulated signal transition time is easily overlooked, but can be highly significant to system susceptibility. Radiated electromagnetic field immunity testing is increasingly being performed in Mode Stirred Chambers. Because the peak field vs. time relationship is affected by the operation of a reverberating room, it is important to understand how the room may influence any input signal modulation characteristics. This paper will provide insight into the field intensity vs. time relationship within the test environment of a mode stirred chamber. An understanding of this relationship is important to EMC engineers in determining what input signal modulation characteristics will be transferred to the equipment under test. References will be given for the development of this topic, and experimental data will be presented

  18. Immune modulation following aerobic exercise in children with cystic fibrosis.

    PubMed

    Boas, S R; Danduran, M J; McColley, S A; Beaman, K; O'Gorman, M R

    2000-05-01

    Previous studies have demonstrated altered immune response following exercise in healthy adults and children. As data are lacking in children with cystic fibrosis, we evaluated the immune response following acute exercise and hypothesized that acute increases in cellular changes would be seen but would be blunted in subjects with CF. Leukocytes, lymphocytes, and their subsets as well as natural killer cell number and activity were determined before, immediately after, and one hour post exhaustive exercise in 15 children with cystic fibrosis (8-21 yrs, FEV1 69.5+/-18.0%, colonized with P aeruginosa) and 15 healthy controls (8-18 yrs, FEV1 107.5+/-10.7%). At baseline the cystic fibrosis group had greater leukocytes (9.25+/-2.83 vs. 5.17+/-0.96 x 10(9) cells/liter). Immediately post exercise, the cystic fibrosis group demonstrated increases in cell counts for leukocytes (32.4%), lymphocytes (61.8%), granulocytes (36.4%), monocytes (76.2%), and natural killer cells (315%). Similar percentage increases were seen in cell counts for the controls (leukocytes: 39.5%, lymphocytes: 78.5%, granulocytes: 32.0%, monocytes: 75.9%, and NK cells: 442%). Natural killer cell activity also increased by 57.9% in the group with cystic fibrosis and by 43.6% in the healthy controls. Except for elevated leukocyte and granulocyte counts, values returned to baseline at one hour post-exercise. In conclusion, the cellular immune response to acute exercise in children with mild to moderate cystic fibrosis appears normal.

  19. A gastrointestinal rotavirus infection mouse model for immune modulation studies

    PubMed Central

    2011-01-01

    Background Rotaviruses are the single most important cause of severe diarrhea in young children worldwide. The current study was conducted to assess whether colostrum containing rotavirus-specific antibodies (Gastrogard-R®) could protect against rotavirus infection. In addition, this illness model was used to study modulatory effects of intervention on several immune parameters after re-infection. Methods BALB/c mice were treated by gavage once daily with Gastrogard-R® from the age of 4 to 10 days, and were inoculated with rhesus rotavirus (RRV) at 7 days of age. A secondary inoculation with epizootic-diarrhea infant-mouse (EDIM) virus was administered at 17 days of age. Disease symptoms were scored daily and viral shedding was measured in fecal samples during the post-inoculation periods. Rotavirus-specific IgM, IgG and IgG subclasses in serum, T cell proliferation and rotavirus-specific delayed-type hypersensitivity (DTH) responses were also measured. Results Primary inoculation with RRV induced a mild but consistent level of diarrhea during 3-4 days post-inoculation. All mice receiving Gastrogard-R® were 100% protected against rotavirus-induced diarrhea. Mice receiving both RRV and EDIM inoculation had a lower faecal-viral load following EDIM inoculation then mice receiving EDIM alone or Gastrogard-R®. Mice receiving Gastrogard-R® however displayed an enhanced rotavirus-specific T-cell proliferation whereas rotavirus-specific antibody subtypes were not affected. Conclusions Preventing RRV-induced diarrhea by Gastrogard-R® early in life showed a diminished protection against EDIM re-infection, but a rotavirus-specific immune response was developed including both B cell and T cell responses. In general, this intervention model can be used for studying clinical symptoms as well as the immune responses required for protection against viral re-infection. PMID:21385425

  20. Immunization with Culex tarsalis mosquito salivary gland extract modulates West Nile virus infection and disease in mice.

    PubMed

    Machain-Williams, Carlos; Reagan, Krystle; Wang, Tian; Zeidner, Nordin S; Blair, Carol D

    2013-02-01

    Mosquito salivary proteins inoculated during blood feeding modulate the host immune response, which can contribute to the pathogenesis of viruses transmitted by mosquito bites. Previous studies with mosquito bite-naïve mice indicated that exposure to arthropod salivary proteins resulted in a shift toward a Th2-type immune response in flavivirus-susceptible mice but not flavivirus-resistant animals. In the study presented here, we tested the hypothesis that immunization with high doses of Culex tarsalis salivary gland extracts (SGE) with an adjuvant would prevent Th2 polarization after mosquito bite and enhance resistance to mosquito-transmitted West Nile virus (WNV). Our results indicate that mice immunized with Cx. tarsalis SGE produced increased levels of Th1-type cytokines (IFNγ and TNFα) after challenge with mosquito-transmitted WNV and exhibited both a delay in infection of the central nervous system (CNS) and significantly lower WNV brain titers compared to mock-immunized mice. Moreover, mortality was significantly reduced in the SGE-immunized mice, as none of these mice died, compared to mortality of 37.5% of mock-vaccinated mice by 8 days after infected mosquito bite. These results suggest that development of a mosquito salivary protein vaccine might be a strategy to control arthropod-borne viral pathogens such as WNV.

  1. Radiation-Induced Immune Modulation in Prostate Cancer

    DTIC Science & Technology

    2006-01-01

    Research Society, Denver, CO, 2004. Dörthe Schaue, Yu-Pei Liao, Begonya Comin-Anduix, Antoni Ribas , Annelies Debucquoy, Karin Haustermans, and William H...Submitted, 2006. Schaue, D., Y. Liao, B. Comin-Anduix, A. Ribas , D.C. Altieri, A. Debucquoy, K. Haustermans and W.H. McBride: The Effect of Radiation...Comin-Anduix, A. Ribas , D.C. Altieri, A. Debucquoy, K. Haustermans and W.H. McBride: The Effect of Radiation Therapy on Tumor-Specific Immune Responses

  2. 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.

  3. Peptidylarginine Deiminase Inhibition Reduces Vascular Damage and Modulates Innate Immune Responses in Murine Models of Atherosclerosis

    PubMed Central

    Knight, Jason S.; Luo, Wei; O’Dell, Alexander A.; Yalavarthi, Srilakshmi; Zhao, Wenpu; Subramanian, Venkataraman; Guo, Chiao; Grenn, Robert C.; Thompson, Paul R.; Eitzman, Daniel T.; Kaplan, Mariana J.

    2014-01-01

    Rationale Neutrophil extracellular trap (NET) formation promotes vascular damage, thrombosis, and activation of interferon-α-producing plasmacytoid dendritic cells in diseased arteries. Peptidylarginine deiminase inhibition is a strategy that can decrease in vivo NET formation. Objective To test whether peptidylarginine deiminase inhibition, a novel approach to targeting arterial disease, can reduce vascular damage and inhibit innate immune responses in murine models of atherosclerosis. Methods and Results Apolipoprotein-E (Apoe)−/− mice demonstrated enhanced NET formation, developed autoantibodies to NETs, and expressed high levels of interferon-α in diseased arteries. Apoe−/− mice were treated for 11 weeks with daily injections of Cl-amidine, a peptidylarginine deiminase inhibitor. Peptidylarginine deiminase inhibition blocked NET formation, reduced atherosclerotic lesion area, and delayed time to carotid artery thrombosis in a photochemical injury model. Decreases in atherosclerosis burden were accompanied by reduced recruitment of netting neutrophils and macrophages to arteries, as well as by reduced arterial interferon-α expression. Conclusions Pharmacological interventions that block NET formation can reduce atherosclerosis burden and arterial thrombosis in murine systems. These results support a role for aberrant NET formation in the pathogenesis of atherosclerosis through modulation of innate immune responses. PMID:24425713

  4. Radiation-Induce Immune Modulation in Prostate Cancer

    DTIC Science & Technology

    2005-01-01

    Riverside, CA Invited Seminar: "The Proteasome as a Senor of Stress " 3/17/04 UCLA Department of Dentistry Monthly Seminar, Los Angeles, CA Invited...affects protective antitutnor imnmunity induced by Chymotrypsin-like activity was measured using 100 pM SucLLVY-7- AdVMARTI/DC vaccination amido -4...adjuvant activity was heightened if the cells were first stressed by radiation, indicating that injury can modulate this effect. In situ induction of

  5. Mechanism of action and effect of immune-modulating agents in the treatment of psoriasis.

    PubMed

    El-Gharabawy, Rehab M; Ahmed, Amira S; Al-Najjar, Amal H

    2017-01-01

    The aim of this work is to study the possible mechanisms through which different immune-modulating agents can produce their beneficial effects on treatment of psoriasis and to determine whether the supplementation of these agents for psoriasis patients induces regression of psoriasis. One hundred fifty participants were included in this study. The participants were divided into five groups: 1. Normal control group, 2. Psoriasis patients not taking any treatment, 3. Psoriasis patients treated with anti-psoriatic treatment (including coal tar, vitamin D3 analogues and corticosteroids). 4. Psoriasis patients treated with anti-psoriatic treatment and oral metformin (850mg twice daily) and 5. Psoriasis patients treated with anti-psoriatic treatment and oral pioglitazone (15mg once a day). Demographic characteristics, diabetic index, lipid profile and liver function tests were monitored. The CD4+ Tcells, CD8+ Tcells, CD4+/CD8+ ratio, interleukin-2 (IL-2), C-reactive protein (CRP) and ceruloplasmin (CP) were assayed. After treatment of psoriasis patients with a traditional anti-psoriatic drug in combination with metformin and peroxisome proliferator-activated receptor gamma (PPARɤ) agonist (pioglitazone), the CD4+ T cells, IL-2, CRP, CP, ALT and AST levels were statistically significantly decreased compared to psoriasis patients without treatment. Positive and significant correlations between CD4+ % and IL-2, CRP, CP, ALT and AST in psoriasis patients were recorded. The activation of PPAR-γ receptors by pioglitazone results in reduced formation of the proinflammatory cytokines and infiltration by inflammatory cells. Additionally, metformin acts as a modulator of the immune system in psoriasis patients and has a remarkable effect on the early stages of psoriasis. Therefore, either pioglitazone or metformin in combination with traditional anti-psoriatic drugs provides better results in the treatment of psoriasis than does each alone. Copyright © 2016 Elsevier Masson SAS

  6. Evolution of immune systems: specificity and autoreactivity.

    PubMed

    Bailey, Mick; Christoforidou, Zoe; Lewis, Marie

    2013-04-01

    Multicellularity evolved well before 600 million years ago, and all multicellular animals have evolved since then with the need to protect against pathogens. There is no reason to expect their immune systems to be any less sophisticated than ours. The vertebrate system, based on rearranging immunoglobulin-superfamily domains, appears to have evolved partly as a result of chance insertion of RAG genes by horizontal transfer. Remarkably sophisticated systems for expansion of immunological repertoire have evolved in parallel in many groups of organisms. Vaccination of invertebrates against commercially important pathogens has been empirically successful, and suggests that the definition of an adaptive and innate immune system should no longer depend on the presence of memory and specificity, since these terms are hard to define in themselves. The evolution of randomly-created immunological repertoire also carries with it the potential for generating autoreactive specificities and consequent autoimmune damage. While invertebrates may use systems analogous to ours to control autoreactive specificities, they may have evolved alternative mechanisms which operate either at the level of individuals-within-populations rather than cells-within-individuals, by linking self-reactive specificities to regulatory pathways and non-self-reactive to effector pathways. Copyright © 2012. Published by Elsevier B.V.

  7. PERINATAL MALNUTRITION AND THE PROTECTIVE ROLE OF THE PHYSICAL TRAINING ON THE IMMUNE SYSTEM.

    PubMed

    Moreno Senna, Sueli; Ferraz, José Cândido; Leandro, Carol Góis

    2015-09-01

    Developing organisms have the ability to cope with environmental demands through physiologic and morphologic adaptations. Early life malnutrition has been recognized as an environmental stimulus that is related with down-regulation of immune responses. Some of these effects are explained by the epigenetics and the programming of hormones and cytokines impairing the modulation of the immune cells in response to environmental stimuli. Recently, it has been demonstrated that these effects are not deterministic and current environment, such as physical activity, can positively influence the immune system. Here, we discuss the effects of perinatal malnutrition on the immune system and how it can be modulated by physical training. The mechanism includes the normalization of some hormones concentrations related to growth and metabolism such as leptin, IGF-1 and glucocorticoids.

  8. Construction of an integrated gene regulatory network link to stress-related immune system in cattle.

    PubMed

    Behdani, Elham; Bakhtiarizade