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Sample records for affect immune system

  1. 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.

  2. Rearing environment affects development of the immune system in neonates.

    PubMed

    Inman, C F; Haverson, K; Konstantinov, S R; Jones, P H; Harris, C; Smidt, H; Miller, B; Bailey, M; Stokes, C

    2010-06-01

    Early-life exposure to appropriate microbial flora drives expansion and development of an efficient immune system. Aberrant development results in increased likelihood of allergic disease or increased susceptibility to infection. Thus, factors affecting microbial colonization may also affect the direction of immune responses in later life. There is a need for a manipulable animal model of environmental influences on the development of microbiota and the immune system during early life. We assessed the effects of rearing under low- (farm, sow) and high-hygiene (isolator, milk formula) conditions on intestinal microbiota and immune development in neonatal piglets, because they can be removed from the mother in the first 24 h for rearing under controlled conditions and, due to placental structure, neither antibody nor antigen is transferred in utero. Microbiota in both groups was similar between 2 and 5 days. However, by 12-28 days, piglets reared on the mother had more diverse flora than siblings reared in isolators. Dendritic cells accumulated in the intestinal mucosa in both groups, but more rapidly in isolator piglets. Importantly, the minority of 2-5-day-old farm piglets whose microbiota resembled that of an older (12-28-day-old) pig also accumulated dendritic cells earlier than the other farm-reared piglets. Consistent with dendritic cell control of T cell function, the effects on T cells occurred at later time-points, and mucosal T cells from high-hygiene, isolator pigs made less interleukin (IL)-4 while systemic T cells made more IL-2. Neonatal piglets may be a valuable model for studies of the effects of interaction between microbiota and immune development on allergy.

  3. 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 ...

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

    PubMed

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

    2015-06-01

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

  5. Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis.

    PubMed

    López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

    2016-03-01

    Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen

  6. Comparative Proteomics Identifies Host Immune System Proteins Affected by Infection with Mycobacterium bovis

    PubMed Central

    López, Vladimir; Villar, Margarita; Queirós, João; Vicente, Joaquín; Mateos-Hernández, Lourdes; Díez-Delgado, Iratxe; Contreras, Marinela; Alves, Paulo C.; Alberdi, Pilar; Gortázar, Christian; de la Fuente, José

    2016-01-01

    Mycobacteria of the Mycobacterium tuberculosis complex (MTBC) greatly impact human and animal health worldwide. The mycobacterial life cycle is complex, and the mechanisms resulting in pathogen infection and survival in host cells are not fully understood. Eurasian wild boar (Sus scrofa) are natural reservoir hosts for MTBC and a model for mycobacterial infection and tuberculosis (TB). In the wild boar TB model, mycobacterial infection affects the expression of innate and adaptive immune response genes in mandibular lymph nodes and oropharyngeal tonsils, and biomarkers have been proposed as correlates with resistance to natural infection. However, the mechanisms used by mycobacteria to manipulate host immune response are not fully characterized. Our hypothesis is that the immune system proteins under-represented in infected animals, when compared to uninfected controls, are used by mycobacteria to guarantee pathogen infection and transmission. To address this hypothesis, a comparative proteomics approach was used to compare host response between uninfected (TB-) and M. bovis-infected young (TB+) and adult animals with different infection status [TB lesions localized in the head (TB+) or affecting multiple organs (TB++)]. The results identified host immune system proteins that play an important role in host response to mycobacteria. Calcium binding protein A9, Heme peroxidase, Lactotransferrin, Cathelicidin and Peptidoglycan-recognition protein were under-represented in TB+ animals when compared to uninfected TB- controls, but protein levels were higher as infection progressed in TB++ animals when compared to TB- and/or TB+ adult wild boar. MHCI was the only protein over-represented in TB+ adult wild boar when compared to uninfected TB- controls. The results reported here suggest that M. bovis manipulates host immune response by reducing the production of immune system proteins. However, as infection progresses, wild boar immune response recovers to limit pathogen

  7. Are fish immune systems really affected by parasites? an immunoecological study of common carp (Cyprinus carpio)

    PubMed Central

    2011-01-01

    Background The basic function of the immune system is to protect an organism against infection in order to minimize the fitness costs of being infected. According to life-history theory, energy resources are in a trade-off between the costly demands of immunity and other physiological demands. Concerning fish, both physiology and immunity are influenced by seasonal changes (i.e. temporal variation) associated to the changes of abiotic factors (such as primarily water temperature) and interactions with pathogens and parasites. In this study, we investigated the potential associations between the physiology and immunocompetence of common carp (Cyprinus carpio) collected during five different periods of a given year. Our sampling included the periods with temporal variability and thus, it presented a different level in exposure to parasites. We analyzed which of two factors, seasonality or parasitism, had the strongest impact on changes in fish physiology and immunity. Results We found that seasonal changes play a key role in affecting the analyzed measurements of physiology, immunity and parasitism. The correlation analysis revealed the relationships between the measures of overall host physiology, immunity and parasite load when temporal variability effect was removed. When analyzing separately parasite groups with different life-strategies, we found that fish with a worse condition status were infected more by monogeneans, representing the most abundant parasite group. The high infection by cestodes seems to activate the phagocytes. A weak relationship was found between spleen size and abundance of trematodes when taking into account seasonal changes. Conclusions Even if no direct trade-off between the measures of host immunity and physiology was confirmed when taking into account the seasonality, it seems that seasonal variability affects host immunity and physiology through energy allocation in a trade-off between life important functions, especially reproduction

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

    ERIC Educational Resources Information Center

    Littrell, Jill

    1996-01-01

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

  9. Prolonged weakening of the geomagnetic field (GMF) affects the immune system of rats.

    PubMed

    Roman, Adam; Tombarkiewicz, Barbara

    2009-01-01

    The aim of this study was to find out how a long-term shielding of the geomagnetic field (GMF) affected the immune system of rats. Male and female Wistar rats were kept up to an age of 2 months in a natural GMF (about 37 microT). Afterwards, the rats were divided into four groups (males and females separately): control rats were maintained in ambient GMF, while experimental animals were housed under conditions of a weakened GMF (below 12 microT) achieved with steel cages. After 6 months, the rats were sacrificed by decapitation. Spleens and thymuses were isolated and weighed. Peritoneal cells were eluted and cultured in vitro to study their ability to produce nitric oxide (NO) and to synthesize superoxide anion (O2(-)), important microbicidal molecules of macrophages. The number of macrophages was estimated by a crystal violet staining method. We found that the long-term shielding of the GMF could influence the functioning of the immune system in a sex-dependent manner. The deprivation of the GMF delayed physiological thymus involution, that effect being more strongly expressed in females. The weakening of the GMF resulted in an increased number of peritoneal macrophages, especially in males. The shielding of the GMF diminished the ability of macrophages to release NO and to synthesize O2(-), those effects being more powerfully expressed in males and females, respectively. It is proposed that the observed changes in the immune system occur as a consequence of the protective effect of GMF shielding on the circadian rhythm-dependent level of melatonin.

  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. Does the Agaricus blazei Murill mushroom have properties that affect the immune system? An integrative review.

    PubMed

    Lima, Cristiane Urcina Joanna Oliveira; Cordova, Cláudio Olavo de Almeida; Nóbrega, Otávio de Tolêdo; Funghetto, Silvana Schwerz; Karnikowski, Margô Gomes de Oliveira

    2011-01-01

    There has been a significant increase in the use of mushrooms for therapeutic and medicinal purposes, in particular, use of the species Agaricus blazei Murrill, a basidiomycota of Brazilian origin. The objective of this study was to identify scientific evidence regarding the influence of A. blazei Murrill on the immune system. We undertook an integrative review of indexed publications published between 2000 and 2009, using the following question as a guideline: "What evidence can be found in the literature regarding the influence of A. blazei Murrill on the immune system?" Fourteen studies verified that there is in vitro and in vivo research demonstrating this mushroom's influence on the immune system. All research was characterized as evidence level 7 (preclinical study [animals/in vitro]). The research shows that A. blazei Murrill functions through bioactive compounds via mechanisms that are not yet entirely clear, although it has been shown that they promote action on the innate and adaptive immunological response, activation of the complement system, and synthesis of pro- and anti-inflammatory cytokines and even aid in diapedesis. Despite broad scientific evidence demonstrating relevant immunomodulatory properties of A. blazei Murrill, randomized clinical trials with human subjects are still needed in order for the mushroom to be put into clinical practice.

  12. Target motifs affecting natural immunity by a constitutive CRISPR-Cas system in Escherichia coli.

    PubMed

    Almendros, Cristóbal; Guzmán, Noemí M; Díez-Villaseñor, César; García-Martínez, Jesús; Mojica, Francisco J M

    2012-01-01

    Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR associated (cas) genes conform the CRISPR-Cas systems of various bacteria and archaea and produce degradation of invading nucleic acids containing sequences (protospacers) that are complementary to repeat intervening spacers. It has been demonstrated that the base sequence identity of a protospacer with the cognate spacer and the presence of a protospacer adjacent motif (PAM) influence CRISPR-mediated interference efficiency. By using an original transformation assay with plasmids targeted by a resident spacer here we show that natural CRISPR-mediated immunity against invading DNA occurs in wild type Escherichia coli. Unexpectedly, the strongest activity is observed with protospacer adjoining nucleotides (interference motifs) that differ from the PAM both in sequence and location. Hence, our results document for the first time native CRISPR activity in E. coli and demonstrate that positions next to the PAM in invading DNA influence their recognition and degradation by these prokaryotic immune systems.

  13. 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 ...

  14. Sildenafil Can Affect Innate and Adaptive Immune System in Both Experimental Animals and Patients

    PubMed Central

    Boguska, Agnieszka

    2017-01-01

    Sildenafil, a type 5 phosphodiesterase inhibitor (PDE5-I), is primarily used for treating erectile dysfunction. Sildenafil inhibits the degradation of cyclic guanosine monophosphate (cGMP) by competing with cGMP for binding site of PDE5. cGMP is a secondary messenger activating protein kinases and a common regulator of ion channel conductance, glycogenolysis, and cellular apoptosis. PDE5 inhibitors (PDE-Is) found application in cardiology, nephrology, urology, dermatology, oncology, and gynecology. Positive result of sildenafil treatment is closely connected with its immunomodulatory effects. Sildenafil influences angiogenesis, platelet activation, proliferation of regulatory T cells, and production of proinflammatory cytokines and autoantibodies. Sildenafil action in humans and animals appears to be different. Surprisingly, it also acts differently in males and females organisms. Although the immunomodulatory effects of PDE5 inhibitors appear to be promising, none of them reached the point of being tested in clinical trials. Data on the influence of selective PDE5-Is on the human immune system are limited. The main objective of this review is to discuss the immunomodulatory effects of sildenafil in both patients and experimental animals. This is the first review of the current state of knowledge about the effects of sildenafil on the immune system. PMID:28316997

  15. 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 ...

  16. Administration routes affect the quality of immune responses: A cross-sectional evaluation of particulate antigen-delivery systems.

    PubMed

    Mohanan, Deepa; Slütter, Bram; Henriksen-Lacey, Malou; Jiskoot, Wim; Bouwstra, Joke A; Perrie, Yvonne; Kündig, Thomas M; Gander, Bruno; Johansen, Pål

    2010-11-01

    Particulate delivery systems such as liposomes and polymeric nano- and microparticles are attracting great interest for developing new vaccines. Materials and formulation properties essential for this purpose have been extensively studied, but relatively little is known about the influence of the administration route of such delivery systems on the type and strength of immune response elicited. Thus, the present study aimed at elucidating the influence on the immune response when of immunising mice by different routes, such as the subcutaneous, intradermal, intramuscular, and intralymphatic routes with ovalbumin-loaded liposomes, N-trimethyl chitosan (TMC) nanoparticles, and poly(lactide-co-glycolide) (PLGA) microparticles, all with and without specifically selected immune-response modifiers. The results showed that the route of administration caused only minor differences in inducing an antibody response of the IgG1 subclass, and any such differences were abolished upon booster immunisation with the various adjuvanted and non-adjuvanted delivery systems. In contrast, the administration route strongly affected both the kinetics and magnitude of the IgG2a response. A single intralymphatic administration of all evaluated delivery systems induced a robust IgG2a response, whereas subcutaneous administration failed to elicit a substantial IgG2a response even after boosting, except with the adjuvanted nanoparticles. The intradermal and intramuscular routes generated intermediate IgG2a titers. The benefit of the intralymphatic administration route for eliciting a Th1-type response was confirmed in terms of IFN-gamma production of isolated and re-stimulated splenocytes from animals previously immunised with adjuvanted and non-adjuvanted liposomes as well as with adjuvanted microparticles. Altogether the results show that the IgG2a associated with Th1-type immune responses are sensitive to the route of administration, whereas IgG1 response associated with Th2-type immune

  17. Pathogenesis of the immune reconstitution inflammatory syndrome affecting the central nervous system in patients infected with HIV.

    PubMed

    Martin-Blondel, Guillaume; Delobel, Pierre; Blancher, Antoine; Massip, Patrice; Marchou, Bruno; Liblau, Roland S; Mars, Lennart T

    2011-04-01

    Anti-retroviral therapy partially restores the immune function of patients infected with human immunodeficiency virus, thereby drastically reducing morbidity and mortality. However, the clinical condition of a subset of patients on anti-retroviral therapy secondarily deteriorates due to an inflammatory process termed immune reconstitution inflammatory syndrome. This condition results from the restoration of the immune system that upon activation can be detrimental to the host. Among the various clinical manifestations, central nervous system involvement is associated with greater morbidity and mortality. This review covers the pathogenesis of this novel neuroinflammatory disease, including the nature of the provoking pathogens and the composition and specificity of the evoked immune responses. Our current perception of this neuroinflammatory disease supports therapeutic strategies aimed at modulating immune aggression without dampening the life-saving restoration of the immune response.

  18. Colostrum quality affects immune system establishment and intestinal development of neonatal calves.

    PubMed

    Yang, M; Zou, Y; Wu, Z H; Li, S L; Cao, Z J

    2015-10-01

    The first meal of a neonatal calf after birth is crucial for survival and health. The present experiment was performed to assess the effects of colostrum quality on IgG passive transfer, immune and antioxidant status, and intestinal morphology and histology in neonatal calves. Twenty-eight Holstein neonatal male calves were used in the current study, 24 of which were assigned to 1 of 3 treatment groups: those that received colostrum (GrC), transitional milk (GrT, which was obtained after the first milking on 2-3 d after calving), and bulk tank milk (GrB) only at birth. The 4 extra neonatal calves who were not fed any milk were assigned to the control group and were killed immediately after birth to be a negative control to small intestinal morphology and histology detection. Calves in GrC gained more body weight than in GrT, whereas GrB calves lost 0.4 kg compared with the birth weight. Serum total protein, IgG, and superoxide dismutase concentrations were highest in GrC, GrT was intermediate, whereas GrB was the lowest on d 2, 3, and 7. Apparent efficiency of absorption at 48 h, serum complement 3 (C3), and complement 4 (C4) on d 2, 3, and 7 in GrB was low compared with GrC and GrT. On the contrary, malondialdehyde on d 7 increased in GrB. Calves in GrC had better villus length and width, crypt depth, villus height/crypt depth (V/C) value, and mucosal thickness in the duodenum, jejunum, and ileum, whereas GrT calves had lower villus length and width, crypt depth, and mucosal thickness than those fed colostrum. Villi of calves in GrB were nonuniform, sparse, severely atrophied, and apically abscised, and Peyer's patches and hydroncus were detected. Overall, colostrum is the best source for calves in IgG absorption, antioxidant activities, and serum growth metabolites, and promoting intestinal development. The higher quality of colostrum calves ingested, the faster immune defense mechanism and the more healthy intestinal circumstances they established.

  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. Immune System Quiz

    MedlinePlus

    ... los dientes Video: Getting an X-ray 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 ...

  1. [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.

  2. 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…

  3. 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

  4. 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 ...

  5. Swine immune system

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  6. Immune System 101

    MedlinePlus

    ... Infectious Diseases - The Immune System Related Topics on AIDS.gov CD4 Count Viral Load Cancer Opportunistic Infections ... Immune Response (video) Last revised: 08/22/2011 AIDS.gov HIV/AIDS Basics • Federal Resources • Using New ...

  7. Physalin B inhibits Trypanosoma cruzi infection in the gut of Rhodnius prolixus by affecting the immune system and microbiota.

    PubMed

    Castro, Daniele P; Moraes, Caroline S; Gonzalez, Marcelo S; Ribeiro, Ivone M; Tomassini, Therezinha C B; Azambuja, Patrícia; Garcia, Eloi S

    2012-12-01

    Physalin B is a natural secosteroidal, extracted from the Solanaceae plant, Physalis angulata, and it presents immune-modulator effects on the bloodsucking bug, Rhodnius prolixus. In this work, R. prolixus was treated with physalin B at a concentration of 1 mg/ml of blood meal (oral application), or 20 ng/insect (applied topically) or 57 ng/cm(2) of filter paper (contact treatment), and infected with Trypanosoma cruzi Dm28c clone (2×10(6) epimastigotes/insect). The three types of applications significantly decreased the number of T. cruzi Dm28c in the gut comparing with the non-treated infected insects (controls). All groups of infected insects treated with physalin B had higher numbers of bacterial microbiota in the gut than the non-treated controls infected with T. cruzi. We observed that the infected physalin B insects with topical and contact treatments had a lower antibacterial activity in the gut when compared with control infected insects. Furthermore, infected insects with the physalin B oral treatment produced higher levels of nitrite and nitrate in the gut than control infected insects. These results demonstrate that physalin B decreases the T. cruzi transmission by inhibiting the parasite development in the insect vector R. prolixus. Herein the importance of physalin B modulation on the immune system and microbiota population in terms of parasite development and transmission are discussed.

  8. The peptide semax affects the expression of genes related to the immune and vascular systems in rat brain focal ischemia: genome-wide transcriptional analysis

    PubMed Central

    2014-01-01

    Background The nootropic neuroprotective peptide Semax (Met-Glu-His-Phe-Pro-Gly-Pro) has proved efficient in the therapy of brain stroke; however, the molecular mechanisms underlying its action remain obscure. Our genome-wide study was designed to investigate the response of the transcriptome of ischemized rat brain cortex tissues to the action of Semax in vivo. Results The gene-expression alteration caused by the action of the peptide Semax was compared with the gene expression of the “ischemia” group animals at 3 and 24 h after permanent middle cerebral artery occlusion (pMCAO). The peptide predominantly enhanced the expression of genes related to the immune system. Three hours after pMCAO, Semax influenced the expression of some genes that affect the activity of immune cells, and, 24 h after pMCAO, the action of Semax on the immune response increased considerably. The genes implicated in this response represented over 50% of the total number of genes that exhibited Semax-induced altered expression. Among the immune-response genes, the expression of which was modulated by Semax, genes that encode immunoglobulins and chemokines formed the most notable groups. In response to Semax administration, 24 genes related to the vascular system exhibited altered expression 3 h after pMCAO, whereas 12 genes were changed 24 h after pMCAO. These genes are associated with such processes as the development and migration of endothelial tissue, the migration of smooth muscle cells, hematopoiesis, and vasculogenesis. Conclusions Semax affects several biological processes involved in the function of various systems. The immune response is the process most markedly affected by the drug. Semax altered the expression of genes that modulate the amount and mobility of immune cells and enhanced the expression of genes that encode chemokines and immunoglobulins. In conditions of rat brain focal ischemia, Semax influenced the expression of genes that promote the formation and

  9. Immune System (For Parents)

    MedlinePlus

    ... teens. Environmental allergies (to dust mites, for example), seasonal allergies (such as hay fever), drug allergies (reactions to ... For Parents MORE ON THIS TOPIC Definition: ... Allergies Activity: Immune System Word! Autoimmunity HIV and AIDS ...

  10. 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

  11. 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

  12. Dietary sodium selenite affects host intestinal and systemic immune response and disease susceptibility to necrotic enteritis in commercial broilers.

    PubMed

    Xu, S Z; Lee, S H; Lillehoj, H S; Bravo, D

    2015-01-01

    1. This study was to evaluate the effects of supplementary dietary selenium (Se) given as sodium selenite on host immune response against necrotic enteritis (NE) in commercial broiler chickens. 2. Chicks were fed from hatching on a non-supplemented diet or diets supplemented with different levels of Se (0.25, 0.50, and 1.00 Se mg/kg). To induce NE, broiler chickens were orally infected with Eimeria maxima at 14 d of age and then with Clostridium perfringens 4 d later using our previously established NE disease model. 3. NE-associated clinical signs and host protective immunity were determined by body weight changes, intestinal lesion scores, and serum antibodies against α-toxin and necrotic enteritis B (NetB) toxin. The effects of dietary Se on the gene expression of pro-inflammatory cytokines e.g., interleukin (IL)-1β, IL-6, IL-8LITAF (lipopolysaccharide-induced TNFα-factor), tumour necrosis factor (TNF) SF15, and inducible nitric oxide synthase (iNOS), glutathione peroxidase 7 (GPx7), and avian β-defensins (AvBD) 6, 8, and 13 (following NE infection) were analysed in the intestine and spleen. 4. The results showed that dietary supplementation of newly hatched broiler chicks with 0.25 Se mg/kg from hatch significantly reduced NE-induced gut lesions compared with infected birds given a non-supplemented diet. The levels of serum antibody against the NetB toxin in the chicks fed with 0.25 and 0.50 mg/kg Se were significantly higher than the non-supplemented control group. The transcripts for IL-1β, IL-6, IL-8, iNOS, LITAF, and GPx7, as well as AvBD6, 8, and 13 were increased in the intestine and spleen of Se-supplemented groups, whereas transcript for TNFSF15 was decreased in the intestine. 5. It was concluded that dietary supplementation with optimum levels of Se exerted beneficial effects on host immune response to NE and reduced negative consequence of NE-induced immunopathology.

  13. Immune system function, stress, exercise and nutrition profile can affect pregnancy outcome: Lessons from a Mediterranean cohort.

    PubMed

    Mparmpakas, D; Goumenou, A; Zachariades, E; Pados, G; Gidron, Y; Karteris, E

    2013-02-01

    Pregnancy is associated with major physiological and future psychosocial changes, and maternal adaptation to these changes is crucial for normal foetal development. Psychological stress in pregnancy predicts an earlier birth and lower birth weight. Pregnancy-specific stress contributes directly to preterm delivery. The importance of nutrition and exercise during pregnancy with regard to pregnancy outcome has long been acknowledged. This importance has only been further emphasized by the recent changes in food quality and availability, lifestyle changes and a new understanding of foetal programming's effects on adult outcomes. We hypothesised that for a successful pregnancy certain events at a nutritional, immune, psycho-emotional and genetic level should be tightly linked. Therefore, in this study we followed an 'integrative' approach to investigate how maternal stress, nutrition, pregnancy planning and exercise influence pregnancy outcome. A key finding of our study is that there was a significant reduction in the intake of alcohol, caffeine-containing and sugary drinks during pregnancy. However, passive smoking in the household remained unchanged. In terms of immune profile, a significant inverse correlation was noted between difficulty to 'fight' an infection and number of colds (r=-0.289, P=0.003) as well as the number of infections (r=-0.446, P<0.0001) during pregnancy. The vast majority of the pregnant women acquired a more sedentary lifestyle in the third trimester. In planned, but not in unplanned, pregnancies stress predicted infant weight, independent of age and body mass index (BMI). Notably, in mothers with negative attitudes towards the pregnancy, those with an unplanned pregnancy gave birth to infants with significantly higher weights than those with planned pregnancies. Collectively these data suggest that there is a higher order of complexity, possibly involving gene-environment interactions that work together to ensure a positive outcome for the

  14. Sublethal red tide toxin exposure in free-ranging manatees (Trichechus manatus) affects the immune system through reduced lymphocyte proliferation responses, inflammation, and oxidative stress.

    PubMed

    Walsh, Catherine J; Butawan, Matthew; Yordy, Jennifer; Ball, Ray; Flewelling, Leanne; de Wit, Martine; Bonde, Robert K

    2015-04-01

    The health of many Florida manatees (Trichechus manatus latirostris) is adversely affected by exposure to blooms of the toxic dinoflagellate, Karenia brevis. K. brevis blooms are common in manatee habitats of Florida's southwestern coast and produce a group of cyclic polyether toxins collectively referred to as red tide toxins, or brevetoxins. Although a large number of manatees exposed to significant levels of red tide toxins die, several manatees are rescued from sublethal exposure and are successfully treated and returned to the wild. Sublethal brevetoxin exposure may potentially impact the manatee immune system. Lymphocyte proliferative responses and a suite of immune function parameters in the plasma were used to evaluate effects of brevetoxin exposure on health of manatees rescued from natural exposure to red tide toxins in their habitat. Blood samples were collected from rescued manatees at Lowry Park Zoo in Tampa, FL and from healthy, unexposed manatees in Crystal River, FL. Peripheral blood leukocytes (PBL) isolated from whole blood were stimulated with T-cell mitogens, ConA and PHA. A suite of plasma parameters, including plasma protein electrophoresis profiles, lysozyme activity, superoxide dismutase (SOD) activity, and reactive oxygen/nitrogen (ROS/RNS) species, was also used to assess manatee health. Significant decreases (p<0.05) in lymphocyte proliferation were observed in ConA and PHA stimulated lymphocytes from rescued animals compared to non-exposed animals. Significant correlations were observed between oxidative stress markers (SOD, ROS/RNS) and plasma brevetoxin concentrations. Sublethal exposure to brevetoxins in the wild impacts some immune function components, and thus, overall health, in the Florida manatee.

  15. Skin rubdown with a dry towel, 'kanpu-masatsu' is an aerobic exercise affecting body temperature, energy production, and the immune and autonomic nervous systems.

    PubMed

    Watanabe, Mayumi; Takano, Osamu; Tomiyama, Chikako; Matsumoto, Hiroaki; Kobayashi, Takahiro; Urahigashi, Nobuatsu; Urahigashi, Nobuatsu; Abo, Toru

    2012-01-01

    Skin rubdown using a dry towel (SRDT) to scrub the whole body is a traditional therapy for health promotion. To investigate its mechanism, 24 healthy male volunteers were studied. Body temperature, pulse rate, red blood cells (RBCs), serum levels of catecholamines and cortisol, blood gases (PO(2), sO(2), PCO(2) and pH), lactate and glucose, and the ratio and number of white blood cells (WBCs) were assessed before and after SRDT. After SRDT, pulse rate and body temperature were increased. PO(2), sO(2) and pH were also increased and there was no Rouleaux formation by RBCs. Lactate level tended to increase, whereas that of glucose did not. Adrenaline and noradrenaline levels increased, indicating sympathetic nerve (SN) dominance with increase in granulocytes. WBC number and ratio were divided into two groups according to granulocyte ratio (≤ or < 60%) before SRDT: a normal group and a SN group. Only in the SN group did the granulocyte ratio decrease and the lymphocyte ratio and number increase after SRDT. It is suggested that SRDT is a mild aerobic, systemic exercise that might affect the immune system via the autonomic nervous system.

  16. 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.

  17. Pre-birth world and the development of the immune system: mum's diet affects our adult health: new insight on how the diet during pregnancy permanently influences offspring health and immune fitness.

    PubMed

    Ferreira, Manuela; Veiga-Fernandes, Henrique

    2014-12-01

    Secondary lymphoid organs form in utero through an inherited and well-established developmental program. However, maternal non-heritable features can have a major impact on the gene expression of the embryo, hence influencing the future health of the offspring. Recently, maternal retinoids were shown to regulate the formation of immune structures, shedding light on the role of maternal nutrition in the genetic signature of emergent immune cells. Here we highlight evidence showing how the maternal diet influences the establishment of the immune system, and we also discuss how unbalanced maternal diets may set the response to infection and vaccination in the progeny.

  18. Exposure to Melan-A/MART-126-35 tumor epitope specific CD8(+)T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS).

    PubMed

    Ebstein, Frédéric; Keller, Martin; Paschen, Annette; Walden, Peter; Seeger, Michael; Bürger, Elke; Krüger, Elke; Schadendorf, Dirk; Kloetzel, Peter-M; Seifert, Ulrike

    2016-05-04

    Efficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to altered expression of IFN-γ-inducible components of the antigen presentation machinery and consequent inefficient processing of HLA-dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that short-term co-culture of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-126-35-specific cytotoxic T lymphocytes (CTL) led to resistance against CTL-induced lysis because of impaired Melan-A/MART-126-35 epitope processing. Interestingly, deregulation of p97/VCP expression, which is an IFN-γ-independent component of the UPS and part of the ER-dependent protein degradation pathway (ERAD), was found to be essentially involved in the observed immune escape. In support, our data demonstrate that re-expression of p97/VCP in Melan-A/MART-126-35 CTL-resistant melanoma cells completely restored immune recognition by Melan-A/MART-126-35 CTL. In conclusion, our experiments show that impaired expression of IFN-γ-independent components of the UPS can exert rapid immune evasion of tumor cells and suggest that tumor antigens processed by distinct UPS degradation pathways should be simultaneously targeted in T cell therapies to restrict the likelihood of immune evasion due to impaired antigen processing.

  19. Exposure to Melan-A/MART-126-35 tumor epitope specific CD8+T cells reveals immune escape by affecting the ubiquitin-proteasome system (UPS)

    PubMed Central

    Ebstein, Frédéric; Keller, Martin; Paschen, Annette; Walden, Peter; Seeger, Michael; Bürger, Elke; Krüger, Elke; Schadendorf, Dirk; Kloetzel, Peter-M.; Seifert, Ulrike

    2016-01-01

    Efficient processing of target antigens by the ubiquitin-proteasome-system (UPS) is essential for treatment of cancers by T cell therapies. However, immune escape due to altered expression of IFN-γ-inducible components of the antigen presentation machinery and consequent inefficient processing of HLA-dependent tumor epitopes can be one important reason for failure of such therapies. Here, we show that short-term co-culture of Melan-A/MART-1 tumor antigen-expressing melanoma cells with Melan-A/MART-126-35-specific cytotoxic T lymphocytes (CTL) led to resistance against CTL-induced lysis because of impaired Melan-A/MART-126-35 epitope processing. Interestingly, deregulation of p97/VCP expression, which is an IFN-γ-independent component of the UPS and part of the ER-dependent protein degradation pathway (ERAD), was found to be essentially involved in the observed immune escape. In support, our data demonstrate that re-expression of p97/VCP in Melan-A/MART-126-35 CTL-resistant melanoma cells completely restored immune recognition by Melan-A/MART-126-35 CTL. In conclusion, our experiments show that impaired expression of IFN-γ-independent components of the UPS can exert rapid immune evasion of tumor cells and suggest that tumor antigens processed by distinct UPS degradation pathways should be simultaneously targeted in T cell therapies to restrict the likelihood of immune evasion due to impaired antigen processing. PMID:27143649

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

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

    PubMed

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

    2016-10-01

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

  7. Optimistic Expectancies and Cell-Mediated Immunity: The Role of Positive Affect

    PubMed Central

    Segerstrom, Suzanne C.; Sephton, Sandra E.

    2014-01-01

    Optimistic expectancies affect many psychosocial outcomes and may also predict immune system changes and health, but the nature and mechanisms of any such physiological effects have not been identified. The present study related law-school expectancies to cell-mediated immunity (CMI), examining the within- and between-person components of this relationship and affective mediators. First-year law students (N = 124) completed questionnaire measures of expectancies and affect and received delayed-type hypersensitivity skin tests at five time points. A positive relationship between optimistic expectancies and CMI occurred, in which that changes in optimism correlated with changes in CMI. Likewise, changes in optimism predicted changes in positive and, to a lesser degree, negative affect, but the relationship between optimism and immunity was partially accounted for only by positive affect. This dynamic relationship between expectancies and immunity has positive implications for psychological interventions to improve health, particularly those that increase positive affect. PMID:20424083

  8. 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.

  9. 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.

  10. Immune activation affects chemical sexual ornaments of male Iberian wall lizards

    NASA Astrophysics Data System (ADS)

    López, Pilar; Gabirot, Marianne; Martín, José

    2009-01-01

    Many animals use chemical signals in sexual selection, but it is not clear how these sexual traits might have evolved to signal honestly male condition. It is possible that there is a trade-off between maintaining the immune system and the elaboration of ornaments. We experimentally challenged the immune system of male Iberian wall lizards, Podarcis hispanica, with a bacterial antigen (lipopolysaccharide), without pathogenic effects, to explore whether the immune activation affected chemical ornaments. Immune activation resulted in decreased proportions of a major chemical in femoral secretions (cholesta-5,7-dien-3-ol = provitamin D3) known to be selected in scent of males by females and which active form (vitamin D) has a variety of important effects on immune system function. This result suggests the existence of a potential trade-off between physiological regulation of the immune system and the allocation of essential nutrients (vitamins) to sexual chemical ornaments in male lizards.

  11. 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

  12. Melatonin: Buffering the Immune System

    PubMed Central

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

    2013-01-01

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

  13. 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.

  14. 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.

  15. 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.

  16. 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…

  17. 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 ...

  18. 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

  19. 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.

  20. 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.

  1. Cross-talk between probiotic lactobacilli and host immune system.

    PubMed

    Kemgang, T S; Kapila, S; Shanmugam, V P; Kapila, R

    2014-08-01

    The mechanism by which probiotic lactobacilli affect the immune system is strain specific. As the immune system is a multicompartmental system, each strain has its way to interact with it and induce a visible and quantifiable effect. This review summarizes the interplay existing between the host immune system and probiotic lactobacilli, that is, with emphasis on lactobacilli as a prototype probiotic genus. Several aspects including the bacterial-host cross-talk with the mucosal and systemic immune system are presented, as well as short sections on the competing effect towards pathogenic bacteria and their uses as delivery vehicle for antigens.

  2. 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

  3. 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

  4. 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.

  5. 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

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

    PubMed

    Rachman, S J

    2016-12-01

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

  7. 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

  8. Immunological abnormalities in human immunodeficiency virus (HIV)-infected asymptomatic homosexual men. HIV affects the immune system before CD4+ T helper cell depletion occurs.

    PubMed Central

    Miedema, F; Petit, A J; Terpstra, F G; Schattenkerk, J K; de Wolf, F; Al, B J; Roos, M; Lange, J M; Danner, S A; Goudsmit, J

    1988-01-01

    To investigate the effect of persistent HIV infection on the immune system, we studied leukocyte functions in 14 asymptomatic homosexual men (CDC group II/III) who were at least two years seropositive, but who still had normal numbers of circulating CD4+ T cells. Compared with age-matched heterosexual men and HIV-negative homosexual men, the CD4+ and CD8+ T cells from seropositive men showed decreased proliferation to anti-CD3 monoclonal antibody and decreased CD4+ T-helper activity on PWM-driven differentiation of normal donor B cells. Monocytes of HIV-infected homosexual men showed decreased accessory function on normal T cell proliferation induced by CD3 monoclonal antibody. The most striking defect in leukocyte functional activities was observed in the B cells of HIV-infected men. B cells of 13 out of 14 seropositive men failed to produce Ig in response to PWM in the presence of adequate allogeneic T-helper activity. These findings suggest that HIV induces severe immunological abnormalities in T cells, B cells, and antigen-presenting cells early in infection before CD4+ T cell numbers start to decline. Impaired immunological function in subclinically HIV-infected patients may have clinical implications for vaccination strategies, in particular the use of live vaccines in groups with a high prevalence of HIV seropositivity. PMID:2974045

  9. 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.

  10. Trauma equals danger--damage control by the immune system.

    PubMed

    Stoecklein, Veit M; Osuka, Akinori; Lederer, James A

    2012-09-01

    Traumatic injuries induce a complex host response that disrupts immune system homeostasis and predisposes patients to opportunistic infections and inflammatory complications. The response to injuries varies considerably by type and severity, as well as by individual variables, such as age, sex, and genetics. These variables make studying the impact of trauma on the immune system challenging. Nevertheless, advances have been made in understanding how injuries influence immune system function as well as the immune cells and pathways involved in regulating the response to injuries. This review provides an overview of current knowledge about how traumatic injuries affect immune system phenotype and function. We discuss the current ideas that traumatic injuries induce a unique type of a response that may be triggered by a combination of endogenous danger signals, including alarmins, DAMPs, self-antigens, and cytokines. Additionally, we review and propose strategies for redirecting injury responses to help restore immune system homeostasis.

  11. 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

  12. [Psychoneuroimmunology--regulation of immunity at the systemic level].

    PubMed

    Boranić, Milivoj; Sabioncello, Ante; Gabrilovac, Jelka

    2008-01-01

    Innate and acquired immune reactions are controlled by their intrinsic regulatory mechanisms, ie. by an array of cytokines that mediate communication among cells of the immune system itself and with other cells and tissues, e. g. in areas of inflammation. In addition, the immune system is also subjected to systemic regulation by the vegetative and endocrine systems since immune cells express receptors for neurotransmitters and hormones. Neuroendocrine signals may enhance or suppress the immune reaction, accelerate or slow it, but do not affect specificity. Various stressful factors, including the psychosocial ones, affect immunity. In turn, cytokines generated by the immune system influence hormonal secretion and central nervous system, producing specific behavioral changes (the "sickness behavior") accompanying infectious and inflammatory diseases. That includes somnolence, loss of apetite, depression or anxiety and decrease of cognitive abilities, attention and memory. Local immune systems in skin and mucosa are also subjected to systemic neuroendocrine regulation and possess intrinsic neuroregulatory networks as well. These mechanisms render skin and respiratory and digestive tracts responsive to various forms of stress. Examples are neurodermitis, asthma and ulcerative colitis. In children, the immune and the neuroendocrine systems are still developing, particularly in fetal, neonatal and early infant periods, and exposure to stressful experiences at that time may result in late consequences in the form of deficient immunity or greater risks for allergic or autoimmune reactions. Recognition of the participation of neuroendocrine mechanisms in regulation of immunity helps us understand alterations and disturbances of immune reactions under the influence of stressful factors but so far has not produced reliable therapeutic implications. Psychosocial interventions involving the child and its family may be useful.

  13. The Skin Microbiome: Is It Affected by UV-induced Immune Suppression?

    PubMed Central

    Patra, VijayKumar; Byrne, Scott N.; Wolf, Peter

    2016-01-01

    Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. UV-R is well known to modulate the immune system, which can be both beneficial and deleterious. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides, affect the innate immune system and ultimately suppress the adaptive cellular immune response. This can contribute to skin carcinogenesis and the promotion of infectious agents such as herpes simplex virus and possibly others. On the other hand, a UV-established immunosuppressive environment may protect against the induction of immunologically mediated skin diseases including some of photodermatoses such as polymorphic light eruption. In this article, we share our perspective about the possibility that UV-induced immune suppression may alter the landscape of the skin’s microbiome and its components. Alternatively, or in concert with this, direct UV-induced DNA and membrane damage to the microbiome may result in pathogen associated molecular patterns (PAMPs) that interfere with UV-induced immune suppression. PMID:27559331

  14. 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.

  15. 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.

  16. 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

  17. Incubation temperature affects the immune function of hatchling soft-shelled turtles, Pelodiscus sinensis

    PubMed Central

    Dang, Wei; Zhang, Wen; Du, Wei-Guo

    2015-01-01

    Identifying how developmental temperature affects the immune system is critical for understanding how ectothermic animals defend against pathogens and their fitness in the changing world. However, reptiles have received little attention regarding this issue. We incubated eggs at three ecologically relevant temperatures to determine how incubation temperature affects the immune function of hatchling soft-shelled turtles, Pelodiscus sinensis. When exposed to bacterial infections, hatchlings from 24 °C had lower cumulative mortalities (55%, therefore, higher immunocompetence) than those from 28 °C (85%) or 32 °C (100%). Consistent with higher immunocompetence, hatchlings from low incubation temperature had higher IgM, IgD, and CD3γ expressions than their counterparts from the other two higher incubation temperatures. Conversely, the activity of immunity-related enzymes did not match the among-temperature difference in immune function. Specifically, enzyme activity was higher at intermediate temperatures (alkaline phosphatase) or was not affected by incubation temperature (acid phosphatase, lysozyme). Our study is the first to provide unequivocal evidence (at the molecular and organismal level) about the significant effect of incubation temperature on offspring immunity in reptiles. Our results also indicate that the reduced immunity induced by high developmental temperatures might increase the vulnerability of reptiles to the outbreak of diseases under global warming scenarios. PMID:26028216

  18. Incubation temperature affects the immune function of hatchling soft-shelled turtles, Pelodiscus sinensis.

    PubMed

    Dang, Wei; Zhang, Wen; Du, Wei-Guo

    2015-06-01

    Identifying how developmental temperature affects the immune system is critical for understanding how ectothermic animals defend against pathogens and their fitness in the changing world. However, reptiles have received little attention regarding this issue. We incubated eggs at three ecologically relevant temperatures to determine how incubation temperature affects the immune function of hatchling soft-shelled turtles, Pelodiscus sinensis. When exposed to bacterial infections, hatchlings from 24 °C had lower cumulative mortalities (55%, therefore, higher immunocompetence) than those from 28 °C (85%) or 32 °C (100%). Consistent with higher immunocompetence, hatchlings from low incubation temperature had higher IgM, IgD, and CD3γ expressions than their counterparts from the other two higher incubation temperatures. Conversely, the activity of immunity-related enzymes did not match the among-temperature difference in immune function. Specifically, enzyme activity was higher at intermediate temperatures (alkaline phosphatase) or was not affected by incubation temperature (acid phosphatase, lysozyme). Our study is the first to provide unequivocal evidence (at the molecular and organismal level) about the significant effect of incubation temperature on offspring immunity in reptiles. Our results also indicate that the reduced immunity induced by high developmental temperatures might increase the vulnerability of reptiles to the outbreak of diseases under global warming scenarios.

  19. 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.

  20. Mapping the effects of drugs on the immune system

    PubMed Central

    Kidd, Brian A; Wroblewska, Aleksandra; Boland, Mary R; Agudo, Judith; Merad, Miriam; Tatonetti, Nicholas P; Brown, Brian D; Dudley, Joel T

    2015-01-01

    Understanding how drugs affect the immune system has consequences for treating disease and minimizing unwanted side effects. Here we present an integrative computational approach for predicting interactions between drugs and immune cells in a system-wide manner. The approach matches gene sets between transcriptional signatures to determine their similarity. We apply the method to model the interactions between 1,309 drugs and 221 immune cell types and predict 69,995 known and novel interactions. The resulting immune-cell pharmacology map is used to predict how 5 drugs influence 4 immune cell types in humans and mice. To validate the predictions, we analyzed patient records and examined cell population changes from in vivo experiments. Our method offers a tool for screening thousands of interactions to identify relationships between drugs and the immune system. PMID:26619012

  1. Mapping the effects of drugs on the immune system.

    PubMed

    Kidd, Brian A; Wroblewska, Aleksandra; Boland, Mary R; Agudo, Judith; Merad, Miriam; Tatonetti, Nicholas P; Brown, Brian D; Dudley, Joel T

    2016-01-01

    Understanding how drugs affect the immune system has consequences for treating disease and minimizing unwanted side effects. Here we present an integrative computational approach for predicting interactions between drugs and immune cells in a system-wide manner. The approach matches gene sets between transcriptional signatures to determine their similarity. We apply the method to model the interactions between 1,309 drugs and 221 immune cell types and predict 69,995 interactions. The resulting immune-cell pharmacology map is used to predict how five drugs influence four immune cell types in humans and mice. To validate the predictions, we analyzed patient records and examined cell population changes from in vivo experiments. Our method offers a tool for screening thousands of interactions to identify relationships between drugs and the immune system.

  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. Alcohol consumption and antitumor immunity: dynamic changes from activation to accelerated deterioration of the immune system.

    PubMed

    Zhang, Hui; Zhu, Zhaohui; Zhang, Faya; Meadows, Gary G

    2015-01-01

    The molecular mechanisms of how alcohol and its metabolites induce cancer have been studied extensively. However, the mechanisms whereby chronic alcohol consumption affects antitumor immunity and host survival have largely been unexplored. We studied the effects of chronic alcohol consumption on the immune system and antitumor immunity in mice inoculated with B16BL6 melanoma and found that alcohol consumption activates the immune system leading to an increase in the proportion of IFN-γ-producing NK, NKT, and T cells in mice not injected with tumors. One outcome associated with enhanced IFN-γ activation is inhibition of melanoma lung metastasis. However, the anti-metastatic effects do not translate into increased survival of mice bearing subcutaneous tumors. Continued growth of the subcutaneous tumors and alcohol consumption accelerates the deterioration of the immune system, which is reflected in the following: (1) inhibition in the expansion of memory CD8+ T cells, (2) accelerated decay of Th1 cytokine-producing cells, (3) increased myeloid-derived suppressor cells, (4) compromised circulation of B cells and T cells, and (5) increased NKT cells that exhibit an IL-4 dominant cytokine profile, which is inhibitory to antitumor immunity. Taken together, the dynamic effects of alcohol consumption on antitumor immunity are in two opposing phases: the first phase associated with immune stimulation is tumor inhibitory and the second phase resulting from the interaction between the effects of alcohol and the tumor leads to immune inhibition and resultant tumor progression.

  4. 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.

  5. Overview of the Immune System

    MedlinePlus

    ... in the bone marrow is the precursor to innate immune cells—neutrophils, eosinophils, basophils, mast cells, monocytes, ... common lymphoid progenitor and share features of both innate and adaptive immune cells, as they provide immediate ...

  6. Mass Cytometry of the Human Mucosal Immune System Identifies Tissue- and Disease-Associated Immune Subsets.

    PubMed

    van Unen, Vincent; Li, Na; Molendijk, Ilse; Temurhan, Mine; Höllt, Thomas; van der Meulen-de Jong, Andrea E; Verspaget, Hein W; Mearin, M Luisa; Mulder, Chris J; van Bergen, Jeroen; Lelieveldt, Boudewijn P F; Koning, Frits

    2016-05-17

    Inflammatory intestinal diseases are characterized by abnormal immune responses and affect distinct locations of the gastrointestinal tract. Although the role of several immune subsets in driving intestinal pathology has been studied, a system-wide approach that simultaneously interrogates all major lineages on a single-cell basis is lacking. We used high-dimensional mass cytometry to generate a system-wide view of the human mucosal immune system in health and disease. We distinguished 142 immune subsets and through computational applications found distinct immune subsets in peripheral blood mononuclear cells and intestinal biopsies that distinguished patients from controls. In addition, mucosal lymphoid malignancies were readily detected as well as precursors from which these likely derived. These findings indicate that an integrated high-dimensional analysis of the entire immune system can identify immune subsets associated with the pathogenesis of complex intestinal disorders. This might have implications for diagnostic procedures, immune-monitoring, and treatment of intestinal diseases and mucosal malignancies.

  7. 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),…

  8. Juvenile immune status affects the expression of a sexually selected trait in field crickets.

    PubMed

    Jacot, A; Scheuber, H; Kurtz, J; Brinkhof, M W G

    2005-07-01

    Parasite-mediated sexual selection theory presumes that variation in sexual traits reliably reflects variation in parasite resistance among available mates. One mechanism that may warrant signal honesty involves costs of immune system activation in the case of a parasitic infection. We investigated this hypothesis in male field crickets Gryllus campestris, whose attractiveness to females depends on characteristics of the sound-producing harp that are essentially fixed following adult eclosion. During the nymphal stage, males subjected to one of two feeding regimes were challenged with bacterial lipopolysaccharides (LPS) to investigate condition-dependent effects on harp development as compared to other adult traits. Nymphal nutritional status positively affected adult body size, condition, and harp size. However, nymphal immune status affected harp size only, with LPS-males having smaller harps than control-injected males. In addition, the harps of LPS-males showed a lesser degree of melanization, indicating an enhanced substrate use by the melanin-producing enzyme cascade of the immune system. Thus, past immune status is specifically mirrored in sexual traits, suggesting a key role for deployment costs of immunity in parasite-mediated sexual selection.

  9. 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.

  10. The immune system and developmental programming of brain and behavior.

    PubMed

    Bilbo, Staci D; Schwarz, Jaclyn M

    2012-08-01

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

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

    PubMed Central

    Bilbo, Staci D.; Schwarz, Jaclyn M.

    2012-01-01

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

  12. 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.

  13. 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

  14. Larval nutritional stress affects vector immune traits in adult yellow fever mosquito Aedes aegypti (Stegomyia aegypti).

    PubMed

    Telang, A; Qayum, A A; Parker, A; Sacchetta, B R; Byrnes, G R

    2012-09-01

    We report key physiological traits that link larval nutritional experience to adult immune status in the yellow fever mosquito Aedes aegypti L. (Stegomyia aegypti) (Diptera: Culicidae). Many lines of defence make up the innate immune system of mosquitoes. Among defences, the epithelium-lined midgut is the first barrier, circulating haemocytes are cellular components of innate immunity and, when triggered, the Toll and Imd pathways signal production of antimicrobial peptides (AMP) as part of humoral defences. We quantified three lines of defence in Ae. aegypti in response to larval nutritional stress, and our data show that important female immune functions are modified by the larval rearing environment. Adult midgut basal lamina thickness was not affected by larval nutrient stress as has been observed in another Aedes sp. However, nutrient stresses experienced by larvae lead to a reduced number of haemocytes in females. Transcripts of Spaetzle (upstream regulator of Toll pathway that leads to induction of AMPs) and some immune-related genes were less abundant in stressed larvae but showed increased expression in females derived from stressed larvae. Results indicate a potential for compensation by the humoral branch for a reduced cellular branch of innate immunity in adults in response to larval nutrient stress.

  15. 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.

  16. 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

  17. [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.

  18. Scrapie Affects the Maturation Cycle and Immune Complex Trapping by Follicular Dendritic Cells in Mice

    PubMed Central

    McGovern, Gillian; Mabbott, Neil; Jeffrey, Martin

    2009-01-01

    Transmissible spongiform encephalopathies (TSEs) or prion diseases are infectious neurological disorders of man and animals, characterised by abnormal disease-associated prion protein (PrPd) accumulations in the brain and lymphoreticular system (LRS). Prior to neuroinvasion, TSE agents often accumulate to high levels within the LRS, apparently without affecting immune function. However, our analysis of scrapie-affected sheep shows that PrPd accumulations within the LRS are associated with morphological changes to follicular dendritic cells (FDCs) and tingible body macrophages (TBMs). Here we examined FDCs and TBMs in the mesenteric lymph nodes (MLNs) of scrapie-affected mice by light and electron microscopy. In MLNs from uninfected mice, FDCs could be morphologically categorised into immature, mature and regressing forms. However, in scrapie-affected MLNs this maturation cycle was adversely affected. FDCs characteristically trap and retain immune complexes on their surfaces, which they display to B-lymphocytes. In scrapie-affected MLNs, some FDCs were found where areas of normal and abnormal immune complex retention occurred side by side. The latter co-localised with PrPd plasmalemmal accumulations. Our data suggest this previously unrecognised morphology represents the initial stage of an abnormal FDC maturation cycle. Alterations to the FDCs included PrPd accumulation, abnormal cell membrane ubiquitin and excess immunoglobulin accumulation. Regressing FDCs, in contrast, appeared to lose their membrane-attached PrPd. Together, these data suggest that TSE infection adversely affects the maturation and regression cycle of FDCs, and that PrPd accumulation is causally linked to the abnormal pathology observed. We therefore support the hypothesis that TSEs cause an abnormality in immune function. PMID:19997557

  19. [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.

  20. 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

  1. The CRISPR-Cas immune system: biology, mechanisms and applications.

    PubMed

    Rath, Devashish; Amlinger, Lina; Rath, Archana; Lundgren, Magnus

    2015-10-01

    Viruses are a common threat to cellular life, not the least to bacteria and archaea who constitute the majority of life on Earth. Consequently, a variety of mechanisms to resist virus infection has evolved. A recent discovery is the adaptive immune system in prokaryotes, a type of system previously thought to be present only in vertebrates. The system, called CRISPR-Cas, provide sequence-specific adaptive immunity and fundamentally affect our understanding of virus-host interaction. CRISPR-based immunity acts by integrating short virus sequences in the cell's CRISPR locus, allowing the cell to remember, recognize and clear infections. There has been rapid advancement in our understanding of this immune system and its applications, but there are many aspects that await elucidation making the field an exciting area of research. This review provides an overview of the field and highlights unresolved issues.

  2. 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.

  3. Family Adversity and Autonomic Reactivity Association With Immune Changes in HIV-Affected School Children

    PubMed Central

    Thomas, Melanie; Wara, Diane; Saxton, Katherine; Truskier, Mary; Chesney, Margaret; Boyce, W. Thomas

    2013-01-01

    Objective To explore whether primary school entry is associated with changes in immune system parameters in HIV-affected children. HIV-affected children are vulnerable to psychosocial stressors, regardless of their own HIV serological status. Methods Data from 38 HIV+ and 29 HIV− children born to seropositive women were obtained before and after school entry. Measures included family adversity questionnaires, autonomic nervous system (ANS) reactivity (based on mean arterial responses to challenge tasks), and enumerative and functional changes in peripheral blood immune parameters. Results In comparison to children who were HIV−, children who were HIV+ at baseline had fewer CD4+ T lymphocytes (M = 916 vs. 1206 cells/mm3 × 103; F = 7.8, p = .007), more CD8+ cells (M = 1046 vs. 720 cells/mm3 ×103; F = 7.98, p = .006), and diminished NK cell cytotoxicity (M =−.29 vs. .41; F = 8.87, p = .004). School entry was associated with changes in immune parameters, but HIV status was not associated with the magnitude of changes. Changes in immune parameters following school entry were associated with family stress and pre school entry ANS reactivity. Highly ANS reactive children had either the greatest increase in CD8+ cells following school entry or the greatest decrease, depending upon reported levels of family adversity (B = 215.35; t = 3.74, p < .001). Changes in functional immune assays were significantly associated with the interactions between HIV status and ANS reactivity. Conclusions These results suggest that autonomic reactivity is associated with increased immunological sensitivity to adverse or challenging social contexts among children affected by HIV. PMID:23766380

  4. The role of the adaptive immune system in regulation of gut microbiota.

    PubMed

    Kato, Lucia M; Kawamoto, Shimpei; Maruya, Mikako; Fagarasan, Sidonia

    2014-07-01

    The gut nourishes rich bacterial communities that affect profoundly the functions of the immune system. The relationship between gut microbiota and the immune system is one of reciprocity. The microbiota contributes to nutrient processing and the development, maturation, and function of the immune system. Conversely, the immune system, particularly the adaptive immune system, plays a key role in shaping the repertoire of gut microbiota. The fitness of host immune system is reflected in the gut microbiota, and deficiencies in either innate or adaptive immunity impact on diversity and structures of bacterial communities in the gut. Here, we discuss the mechanisms that underlie this reciprocity and emphasize how the adaptive immune system via immunoglobulins (i.e. IgA) contributes to diversification and balance of gut microbiota required for immune homeostasis.

  5. 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.

  6. 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)

  7. [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.

  8. 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.

  9. [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.

  10. 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.

  11. 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

  12. 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

  13. The immune system and overtraining in athletes: clinical implications.

    PubMed

    Hackney, Anthony C; Koltun, Kristen J

    2012-12-01

    The primary objective of this review is to provide an overview of how overtraining and the overtraining syndrome (OTS) affect the immune system of athletes. A secondary objective is to provide sports medicine clinicians with guidance as to how best to prevent and/or treat some of the health consequences of overtraining and the OTS as related to the development of a compromised immune system associated with exercise training. The OTS is a physically debilitating condition that results in athletes being totally compromised in their capacity to perform and compete. Many physiological systems are affected by the process of overtraining and the OTS; but one system in particular, the immune, is highly susceptible to degradation resulting in a reduction in overall health and performance. Monitoring of an athlete's exercise training load and other life stresses is critical to the determination of when their training regimen may be excessive, thereby increasing the risk of OTS developing. Taking steps to mitigate prolonged exposure to extreme stress (training + life or otherwise) in athletes as well as promoting a healthy immune system can significantly aid in the advancement of an athlete's training regimen progression and ultimate physical performance and overall health. In this light, this review provides approaches to aid sports medicine clinicians in promoting a healthy immune system in athletes.

  14. 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.

  15. 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 ...

  16. Marine pharmacology in 2005–6: Marine Compounds with Anthelmintic, Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiprotozoal, Antituberculosis, and Antiviral Activities; affecting the Cardiovascular, Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

    PubMed Central

    Mayer, Alejandro M. S.; Rodriguez, Abimael D.; Berlinck, Roberto G. S.; Hamann, Mark T.

    2009-01-01

    BACKGROUND The review presents the 2005–2006 peer-reviewed marine pharmacology literature, and follows a similar format to the authors’ 1998–2004 reviews. The preclinical pharmacology of chemically characterized marine compounds isolated from marine animals, algae, fungi and bacteria is systematically presented. RESULTS Anthelminthic, antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 78 marine chemicals. Additionally 47 marine compounds were reported to affect the cardiovascular, immune and nervous system as well as possess anti-inflammatory effects. Finally, 58 marine compounds were shown to bind to a variety of molecular targets, and thus could potentially contribute to several pharmacological classes. CONCLUSIONS Marine pharmacology research during 2005–2006 was truly global in nature, involving investigators from 32 countries, and the United States, and contributed 183 marine chemical leads to the research pipeline aimed at the discovery of novel therapeutic agents. SIGNIFICANCE Continued preclinical and clinical research with marine natural products demonstrating a broad spectrum of pharmacological activity and will probably result in novel therapeutic agents for the treatment of multiple disease categories. PMID:19303911

  17. Marine pharmacology in 2007-8: Marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous system, and other miscellaneous mechanisms of action.

    PubMed

    Mayer, Alejandro M S; Rodríguez, Abimael D; Berlinck, Roberto G S; Fusetani, Nobuhiro

    2011-03-01

    The peer-reviewed marine pharmacology literature in 2007-8 is covered in this review, which follows a similar format to the previous 1998-2006 reviews of this series. The preclinical pharmacology of structurally characterized marine compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, anticoagulant, antifungal, antimalarial, antiprotozoal, antituberculosis and antiviral activities were reported for 74 marine natural products. Additionally, 59 marine compounds were reported to affect the cardiovascular, immune and nervous systems as well as to possess anti-inflammatory effects. Finally, 65 marine metabolites were shown to bind to a variety of receptors and miscellaneous molecular targets, and thus upon further completion of mechanism of action studies, will contribute to several pharmacological classes. Marine pharmacology research during 2007-8 remained a global enterprise, with researchers from 26 countries, and the United States, contributing to the preclinical pharmacology of 197 marine compounds which are part of the preclinical marine pharmaceuticals pipeline. Sustained preclinical research with marine natural products demonstrating novel pharmacological activities, will probably result in the expansion of the current marine pharmaceutical clinical pipeline, which currently consists of 13 marine natural products, analogs or derivatives targeting a limited number of disease categories.

  18. Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action †

    PubMed Central

    Mayer, Alejandro M. S.; Rodríguez, Abimael D.; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

    2013-01-01

    The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories. PMID:23880931

  19. Marine pharmacology in 2009-2011: marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action.

    PubMed

    Mayer, Alejandro M S; Rodríguez, Abimael D; Taglialatela-Scafati, Orazio; Fusetani, Nobuhiro

    2013-07-16

    The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998-2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009-2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories.

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

    PubMed

    Weyand, Cornelia M; Goronzy, Jörg J

    2016-12-01

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

  1. [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.

  2. Systemic affects of methamphetamine use.

    PubMed

    Hauer, Patrick

    2010-08-01

    Methamphetamine (meth) is the most widely used illegal stimulant in the United States and is especially prevalent in Midwestern states. The sense of euphoria caused by the drug, the ease of manufacturing and the relatively low cost make it a drug of choice for many. The broad range of systemic effects potentially caused by the use of this drug is wide reaching and can vary in degree and presentation from patient to patient. Abnormalities include cardiac and pulmonary disorders as well as observable integumentary problems, psychoses, CNS disturbances, problems associated with immunity and constitutional signs and symptoms. Health care providers need to be vigilant in their efforts to identify patients who may be users of meth and to identify any subtle abnormal findings that may be indicative of significant underlying systemic pathology. Questionnaires like the RAFFT (Relax, Alone, Forget, Friends, Trouble) and the MINI (Mini-International Neuropsychiatric Interview) can be helpful in identifying substance abuse disorders in patients.

  3. 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.

  4. Innate and adaptive immune traits are differentially affected by genetic and environmental factors

    PubMed Central

    Mangino, Massimo; Roederer, Mario; Beddall, Margaret H.; Nestle, Frank O.; Spector, Tim D.

    2017-01-01

    The diversity and activity of leukocytes is controlled by genetic and environmental influences to maintain balanced immune responses. However, the relative contribution of environmental compared with genetic factors that affect variations in immune traits is unknown. Here we analyse 23,394 immune phenotypes in 497 adult female twins. 76% of these traits show a predominantly heritable influence, whereas 24% are mostly influenced by environment. These data highlight the importance of shared childhood environmental influences such as diet, infections or microbes in shaping immune homeostasis for monocytes, B1 cells, γδ T cells and NKT cells, whereas dendritic cells, B2 cells, CD4+ T and CD8+ T cells are more influenced by genetics. Although leukocyte subsets are influenced by genetics and environment, adaptive immune traits are more affected by genetics, whereas innate immune traits are more affected by environment. PMID:28054551

  5. 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.

  6. 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.

  7. How Parents' Negative Experiences at Immunization Visits Affect Child Immunization Status in a Community in New York City

    PubMed Central

    Stockwell, Melissa S.; Irigoyen, Matilde; Martinez, Raquel Andres; Findley, Sally

    2011-01-01

    Objective Little is known about how families' experiences with immunization visits within the medical home may affect children's immunization status. We assessed the association between families' negative immunization experiences within the medical home and underimmunization. Methods We surveyed parents (n=392) of children aged 2–36 months about immunization experiences at community health centers, hospital-based clinics, private practices, and community-based organizations in New York City. We used Chi-square tests and odds ratios (ORs) to assess the relationship between medical home elements and parental immunization experience ratings. We used multivariable analysis to determine the association between negative experiences during immunization visits and underimmunization, controlling for insurance, maternal education, and receipt of benefits from the Special Supplemental Nutrition Program for Women, Infants, and Children. Results The majority of children were of Latino race/ethnicity and had Medicaid and a medical home. One-sixth (16.9%) of families reported a previous negative immunization experience, primarily related to the child's reaction, waiting time, and attitudes of medical and office staff. Parents' negative immunization experiences were associated with the absence of four components of the medical home: continuity of care, family-centered care, compassionate care, and comprehensive care. In addition, children in families who reported a negative experience were more likely to have been underimmunized (adjusted OR=2.00; 95% confidence interval 1.12, 3.58). Conclusions In a community in New York City, underimmunization of young children was associated with negative immunization experiences. Strategies to improve family experiences with immunization visits within the medical home (particularly around support for the family), medical and ancillary staff attitudes, and reduced waiting time may lead to improved immunization delivery. PMID:21812166

  8. 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.

  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. Aging of myelinating glial cells predominantly affects lipid metabolism and immune response pathways.

    PubMed

    Verdier, Valérie; Csárdi, Gábor; de Preux-Charles, Anne-Sophie; Médard, Jean-Jacques; Smit, August B; Verheijen, Mark H G; Bergmann, Sven; Chrast, Roman

    2012-05-01

    Both the central and the peripheral nervous systems are prone to multiple age-dependent neurological deficits, often attributed to still unknown alterations in the function of myelinating glia. To uncover the biological processes affected in glial cells by aging, we analyzed gene expression of the Schwann cell-rich mouse sciatic nerve at 17 time points throughout life, from day of birth until senescence. By combining these data with the gene expression data of myelin mouse mutants carrying deletions of either Pmp22, SCAP, or Lpin1, we found that the majority of age-related transcripts were also affected in myelin mutants (54.4%) and were regulated during PNS development (59.5%), indicating a high level of overlap in implicated molecular pathways. The expression profiles in aging copied the direction of transcriptional changes observed in neuropathy models; however, they had the opposite direction when compared with PNS development. The most significantly altered biological processes in aging involved the inflammatory/immune response and lipid metabolism. Interestingly, both these pathways were comparably changed in the aging optic nerve, suggesting that similar biological processes are affected in aging of glia-rich parts of the central and peripheral nervous systems. Our comprehensive comparison of gene expression in three distinct biological conditions including development, aging, and myelin disease thus revealed a previously unanticipated relationship among themselves and identified lipid metabolism and inflammatory/immune response pathways as potential therapeutical targets to prevent or delay so far incurable age-related and inherited forms of neuropathies.

  11. Metal-Based Nanoparticles and the Immune System: Activation, Inflammation, and Potential Applications

    PubMed Central

    Luo, Yueh-Hsia; Chang, Louis W.; Lin, Pinpin

    2015-01-01

    Nanomaterials, including metal-based nanoparticles, are used for various biological and medical applications. However, metals affect immune functions in many animal species including humans. Different physical and chemical properties induce different cellular responses, such as cellular uptake and intracellular biodistribution, leading to the different immune responses. The goals of this review are to summarize and discuss the innate and adaptive immune responses triggered by metal-based nanoparticles in a variety of immune system models. PMID:26125021

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

    PubMed

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

    2017-02-01

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

  13. 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…

  14. The Interplay between the Bone and the Immune System

    PubMed Central

    Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

    2013-01-01

    In the last two decades, numerous scientists have highlighted the interactions between bone and immune cells as well as their overlapping regulatory mechanisms. For example, osteoclasts, the bone-resorbing cells, are derived from the same myeloid precursor cells that give rise to macrophages and myeloid dendritic cells. On the other hand, osteoblasts, the bone-forming cells, regulate hematopoietic stem cell niches from which all blood and immune cells are derived. Furthermore, many of the soluble mediators of immune cells, including cytokines and growth factors, regulate the activities of osteoblasts and osteoclasts. This increased recognition of the complex interactions between the immune system and bone led to the development of the interdisciplinary osteoimmunology field. Research in this field has great potential to provide a better understanding of the pathogenesis of several diseases affecting both the bone and immune systems, thus providing the molecular basis for novel therapeutic strategies. In these review, we reported the latest findings about the reciprocal regulation of bone and immune cells. PMID:23935650

  15. The Interplay between the bone and the immune system.

    PubMed

    Mori, Giorgio; D'Amelio, Patrizia; Faccio, Roberta; Brunetti, Giacomina

    2013-01-01

    In the last two decades, numerous scientists have highlighted the interactions between bone and immune cells as well as their overlapping regulatory mechanisms. For example, osteoclasts, the bone-resorbing cells, are derived from the same myeloid precursor cells that give rise to macrophages and myeloid dendritic cells. On the other hand, osteoblasts, the bone-forming cells, regulate hematopoietic stem cell niches from which all blood and immune cells are derived. Furthermore, many of the soluble mediators of immune cells, including cytokines and growth factors, regulate the activities of osteoblasts and osteoclasts. This increased recognition of the complex interactions between the immune system and bone led to the development of the interdisciplinary osteoimmunology field. Research in this field has great potential to provide a better understanding of the pathogenesis of several diseases affecting both the bone and immune systems, thus providing the molecular basis for novel therapeutic strategies. In these review, we reported the latest findings about the reciprocal regulation of bone and immune cells.

  16. 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.

  17. Nutritionally mediated programming of the developing immune system.

    PubMed

    Palmer, Amanda C

    2011-09-01

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

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

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

  19. Environmentally related disorders of the hematologic and immune systems

    SciTech Connect

    Luster, M.I.; Wierda, D.; Rosenthal, G.J. )

    1990-03-01

    From observations in rodents and, to a lesser extent, in humans inadvertently or occupationally exposed, it appears that a number of xenobiotics adversely affect immune homeostatic systems, either through acting as a hapten and resulting in hypersensitivity reactions or through altering hematopoietic or immune functions. At present, however, there is no evidence that the immune or hematopoietic systems of the general population have been compromised by xenobiotics via environmental exposure. Nonetheless, these examples and our current knowledge about the pathogenesis of disease support the possibility that chemical-induced damage to the immune system may be associated with potential pathological conditions, some of which may become detectable only after a long latency. Likewise, exposure to immunotoxic xenobiotics might represent additional risk to individuals with already fragile immune systems (e.g., in malnutrition, infancy, old age). However, it is important to be cautious when attempting to extrapolate meaningful conclusions from experimental data or isolated epidemiologic studies to risk assessment for low-level human exposure.65 references.

  20. 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.

  1. 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

  2. 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.

  3. Job strain in different types of employment affects the immune response.

    PubMed

    Boscolo, Paolo; Forcella, Laura; Reale, Marcella; Vianale, Giovina; Battisti, Uliano; Bonfiglioli, Roberta; Cortini, Michela; Di Giampaolo, Luca; Di Donato, Angela; Salerno, Silvana

    2012-01-01

    The immune system, in cooperation with neuroendocrine functions, defends from cancer and infections mainly by the activity of blood natural killer (NK) cells. Blood NK activity may be influenced by the type of employment since work is the central part of life; moreover, job stress is a situation affecting both neuroendocrine and immune systems. This study examines anxiety (by STAI 1 and 2), job strain (by the Karasek's JCQ) and blood NK activity (by an in vitro radio-isotopic method) of 134 male workers. These men, over 38 years old with stable employment, were working in factories, in construction yards, in offices, as hospital attendants or as self-employed craftsmen. Workers in factories and in construction yards, with high job strain, showed lower NK activity, while office employees, with low job demand, and craftsmen with low anxiety and elevated decision latitude, showed higher NK activity; the level of NK activity of the hospital attendants was between the other groups. In conclusion, this study confirms that the type of employment, related to job stress, affects blood NK activity. Moreover, blood NK activity may be used in the bio-monitoring of workers at high risk.

  4. 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.

  5. Immunization

    MedlinePlus

    ... remembers" the germ and can fight it again. Vaccines contain germs that have been killed or weakened. When given to a healthy person, the vaccine triggers the immune system to respond and thus ...

  6. 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

  7. [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

  8. 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

  9. 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.

  10. 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.

  11. Human nutrition, the gut microbiome and the immune system.

    PubMed

    Kau, Andrew L; Ahern, Philip P; Griffin, Nicholas W; Goodman, Andrew L; Gordon, Jeffrey I

    2011-06-15

    Marked changes in socio-economic status, cultural traditions, population growth and agriculture are affecting diets worldwide. Understanding how our diet and nutritional status influence the composition and dynamic operations of our gut microbial communities, and the innate and adaptive arms of our immune system, represents an area of scientific need, opportunity and challenge. The insights gleaned should help to address several pressing global health problems.

  12. 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

  13. 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

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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.

  3. Yeast culture supplement during nursing and transport affects immunity and intestinal microbial ecology of weanling pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weaning and transport stress can have a negative impact on the piglet's immune system and intestinal microbiota. The objective of this study was to determine the influence of a yeast product on innate immunity and microbial ecology of the gastrointestinal tract following stress of weaning and trans...

  4. Central nervous system-immune system interactions: psychoneuroendocrinology of stress and its immune consequences.

    PubMed Central

    Black, P H

    1994-01-01

    Psychoneuroimmunology is a relatively new discipline which deals with CNS-immune system interactions. The evidence for such interactions was reviewed, as was the neuroendocrinologic response to stress. Recent evidence indicates that the behavioral, nervous system, and neuroendocrine responses to stress are mediated by hypothalamic CRF, which acts on both the sympathetic nervous system and the HPA axis, resulting in increased levels of corticosteroids, catecholamines, and certain opiates, substances which are generally immunosuppressive. Concentrations of growth hormone and prolactin, which are immunoenhancing, are elevated early during the response to stress but are later suppressed. Although several other neuromediators may also be released with stress, the net effect of a variety of acute stressors is down regulation of the immune system function. In the following minireview, I consider whether stress alters the resistance of the host to infection as well as the immunomodulatory effects of released immune system mediators on the brain. PMID:8141561

  5. 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.

  6. 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.

  7. Postmenopausal osteoporosis: the role of immune system cells.

    PubMed

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

    2013-01-01

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

  8. 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.

  9. B cells in the aging immune system: time to consider B-1 cells.

    PubMed

    Holodick, Nichol E; Rothstein, Thomas L

    2015-12-01

    The investigation of immune senescence has uncovered many changes in B cell development, maintenance, and function with increasing age. However, most of these studies have focused on conventional B cell subsets in the spleen. The B-1 cell subset is an essential arm of the innate immune system, which in general has been understudied in terms of immune senescence. Here, we review what is currently known about B cells during aging and go on to describe why B-1 cell biology is an important component of the aging immune system in the context of diseases that most affect the aged population.

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

    PubMed

    Usharauli, David

    2010-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Salamatova, T.; Zhukov, V.

    2017-02-01

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

  12. 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.

  13. Complement System Part II: Role in Immunity

    PubMed Central

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

    2015-01-01

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

  14. Mood Swings: An Affective Interactive Art System

    NASA Astrophysics Data System (ADS)

    Bialoskorski, Leticia S. S.; Westerink, Joyce H. D. M.; van den Broek, Egon L.

    The progress in the field of affective computing enables the realization of affective consumer products, affective games, and affective art. This paper describes the affective interactive art system Mood Swings, which interprets and visualizes affect expressed by a person. Mood Swings is founded on the integration of a framework for affective movements and a color model. This enables Mood Swings to recognize affective movement characteristics as expressed by a person and display a color that matches the expressed emotion. With that, a unique interactive system is introduced, which can be considered as art, a game, or a combination of both.

  15. The immune system: role in hypertension.

    PubMed

    Schiffrin, Ernesto L

    2013-05-01

    Over the past 20 years it has become recognized that low-grade inflammation plays a role in cardiovascular disease. More recently, participation of the innate and the adaptive immune response in mechanisms that contribute to inflammation in cardiovascular disease has been reported in atherosclerosis and hypertension. Different subsets of lymphocytes and their cytokines are involved in vascular remodelling and hypertensive renal disease as well as heart disease. Effector T cells including T-helper (Th) 1 (interferon-γ-producing) and Th2 lymphocytes (interleukin-4 producing), as well as Th17 (which produce interleukin-17), and T suppressor lymphocytes such as T regulatory cells, which express the transcription factor forkhead box P3, participate respectively as pro- and anti-inflammatory cells, and mediate effects of angiotensin II and mineralocorticoids. Involvement of immune mechanisms in cardiac, vascular, and renal changes in hypertension has been demonstrated in many experimental models, an example being the Dahl-salt sensitive rat and the spontaneously hypertensive rat. How activation of immunity is triggered remains unknown, but neoantigens could be generated by elevated blood pressure through damage-associated molecular pattern receptors or other mechanisms. When activated, Th1 may contribute to blood pressure elevation by affecting the kidney, vascular remodelling of blood vessels directly via effects of the cytokines produced, or through their effects on perivascular fat. T regulatory cells protect from blood pressure elevation acting on similar targets. These novel findings may open the way for new therapeutic approaches to improve outcomes in hypertension and cardiovascular disease in humans.

  16. Artificial Immune System for Recognizing Patterns

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terrance

    2005-01-01

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

  17. IMMUNE SYSTEM MATURITY AND SENSITIVITY TO CHEMICAL EXPOSURE

    EPA Science Inventory

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

  18. Hypo-gravity and immune system effects

    NASA Technical Reports Server (NTRS)

    Carter, Paul D.; Barnes, Frank

    1990-01-01

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

  19. Emerging Roles for the Immune System in Traumatic Brain Injury

    PubMed Central

    McKee, Celia A.; Lukens, John R.

    2016-01-01

    Traumatic brain injury (TBI) affects an ever-growing population of all ages with long-term consequences on health and cognition. Many of the issues that TBI patients face are thought to be mediated by the immune system. Primary brain damage that occurs at the time of injury can be exacerbated and prolonged for months or even years by chronic inflammatory processes, which can ultimately lead to secondary cell death, neurodegeneration, and long-lasting neurological impairment. Researchers have turned to rodent models of TBI in order to understand how inflammatory cells and immunological signaling regulate the post-injury response and recovery mechanisms. In addition, the development of numerous methods to manipulate genes involved in inflammation has recently expanded the possibilities of investigating the immune response in TBI models. As results from these studies accumulate, scientists have started to link cells and signaling pathways to pro- and anti-inflammatory processes that may contribute beneficial or detrimental effects to the injured brain. Moreover, emerging data suggest that targeting aspects of the immune response may offer promising strategies to treat TBI. This review will cover insights gained from studies that approach TBI research from an immunological perspective and will summarize our current understanding of the involvement of specific immune cell types and cytokines in TBI pathogenesis. PMID:27994591

  20. Immuno-epidemiology of a population structured by immune status: a mathematical study of waning immunity and immune system boosting.

    PubMed

    Barbarossa, M V; Röst, G

    2015-12-01

    When the body gets infected by a pathogen the immune system develops pathogen-specific immunity. Induced immunity decays in time and years after recovery the host might become susceptible again. Exposure to the pathogen in the environment boosts the immune system thus prolonging the time in which a recovered individual is immune. Such an interplay of within host processes and population dynamics poses significant challenges in rigorous mathematical modeling of immuno-epidemiology. We propose a framework to model SIRS dynamics, monitoring the immune status of individuals and including both waning immunity and immune system boosting. Our model is formulated as a system of two ordinary differential equations (ODEs) coupled with a PDE. After showing existence and uniqueness of a classical solution, we investigate the local and the global asymptotic stability of the unique disease-free stationary solution. Under particular assumptions on the general model, we can recover known examples such as large systems of ODEs for SIRWS dynamics, as well as SIRS with constant delay.

  1. Invader immunology: invasion history alters immune system function in cane toads (Rhinella marina) in tropical Australia.

    PubMed

    Brown, Gregory P; Phillips, Benjamin L; Dubey, Sylvain; Shine, Richard

    2015-01-01

    Because an individual's investment into the immune system may modify its dispersal rate, immune function may evolve rapidly in an invader. We collected cane toads (Rhinella marina) from sites spanning their 75-year invasion history in Australia, bred them, and raised their progeny in standard conditions. Evolved shifts in immune function should manifest as differences in immune responses among the progeny of parents collected in different locations. Parental location did not affect the offspring's cell-mediated immune response or stress response, but blood from the offspring of invasion-front toads had more neutrophils, and was more effective at phagocytosis and killing bacteria. These latter measures of immune function are negatively correlated with rate of dispersal in free-ranging toads. Our results suggest that the invasion of tropical Australia by cane toads has resulted in rapid genetically based compensatory shifts in the aspects of immune responses that are most compromised by the rigours of long-distance dispersal.

  2. The immune system in menopause: pros and cons of hormone therapy.

    PubMed

    Ghosh, Mimi; Rodriguez-Garcia, Marta; Wira, Charles R

    2014-07-01

    With aging, a general decline in immune function is observed leading to immune-senescence. Several of these changes are gender specific affecting postmenopausal women. Menopause is a normal part of a woman's lifecycle and consists of a series of body changes that can last from one to ten years. It is known that loss of sex hormones due to aging results in a reduction of immune functions. However, there remains a major gap in our understanding regarding the loss of immune functions particularly in the female reproductive tract (FRT) following menopause and the role of menopausal hormone therapy (MHT) in protecting against immune senescence. The current review presents an overview of changes in the immune system due to aging, focusing on genital tract immunity in menopausal women and the risks and benefits of using MHT. This article is part of a Special Issue entitled 'Menopause'.

  3. Space flight and the immune system

    NASA Technical Reports Server (NTRS)

    Cogoli, A.

    1993-01-01

    Depression of lymphocyte response to mitogens in cosmonauts after space flight was reported for the first time in the early 1970s by Soviet immunologists. Today we know that depression of lymphocyte function affects at least 50% of space crew members. Investigations on the ground on subjects undergoing physical and psychological stress indicate that stress is a major factor in immune depression of astronauts. This is despite the fact that weightlessness per se has a strong inhibitory effect on lymphocyte activation in vitro. Although the changes observed never harmed the health of astronauts, immunological changes must be seriously investigated and understood in view of long-duration flight on space stations in an Earth orbit, to other planets such as Mars and to the Moon.

  4. Prenatal Alcohol Exposure and the Developing Immune System.

    PubMed

    Gauthier, Theresa W

    2015-01-01

    Evidence from research in humans and animals suggest that ingesting alcohol during pregnancy can disrupt the fetal immune system and result in an increased risk of infections and disease in newborns that may persist throughout life. Alcohol may have indirect effects on the immune system by increasing the risk of premature birth, which itself is a risk factor for immune-related problems. Animal studies suggest that alcohol exposure directly disrupts the developing immune system. A comprehensive knowledge of the mechanisms underlying alcohol's effects on the developing immune system only will become clear once researchers establish improved methods for identifying newborns exposed to alcohol in utero.

  5. Ginseng, the 'Immunity Boost': The Effects of Panax ginseng on Immune System

    PubMed Central

    Kang, Soowon; Min, Hyeyoung

    2012-01-01

    Thousands of literatures have described the diverse role of ginseng in physiological processes such as cancer, neurodegenerative disorders, insulin resistance, and hypertension. In particular, ginseng has been extensively reported to maintain homeostasis of the immune system and to enhance resistance to illness or microbial attacks through the regulation of immune system. Immune system comprises of different types of cells fulfilling their own specialized functions, and each type of the immune cells is differentially influenced and may be simultaneously controlled by ginseng treatment. This review summarizes the current knowledge on the effects of ginseng on immune system. We discuss how ginseng regulates each type of immune cells including macrophages, natural killer cells, dendritic cells, T cells, and B cells. We also describe how ginseng exhibits beneficial effects on controlling inflammatory diseases and microbial infections. PMID:23717137

  6. Origins of immunity: transcription factors and homologues of effector genes of the vertebrate immune system expressed in sea urchin coelomocytes.

    PubMed

    Pancer, Z; Rast, J P; Davidson, E H

    1999-08-01

    Echinoderms share common ancestry with the chordates within the deuterostome clade. Molecular features that are shared between their immune systems and that of mammals thus illuminate the basal genetic framework on which these immune systems have been constructed during evolution. The immune effector cells of sea urchins are the coelomocytes, whose primary function is protection against invasive marine pathogens; here we identify six genes expressed in coelomocytes, homologues of which are also expressed in cells of the mammalian immune system. Three coelomocyte genes reported here encode transcription factors. These are an NFKB homologue (SpNFKB); a GATA-2/3 homologue (SpGATAc); and a runt domain factor (SpRunt-1). All three of these coelomocyte genes respond sharply to bacterial challenge: SpNFKB and SpRunt-1 genes are rapidly up-regulated, while transcripts of SpGATAc factor disappear within hours of injection of bacteria. Sham injection also activates SpNFKB and SpRunt, though with slower kinetics, but does not affect SpGATAc levels. Another gene, SpHS, encodes a protein related to the signal transduction intermediate HS1 of lymphoid cells. Two other newly discovered genes, SpSRCR1 and SpSRCR5, encode proteins featuring SRCR repeats. These genes are members of a complex family of SRCR genes all expressed specifically in coelomocytes. The SRCR repeats most closely resemble those of mammalian macrophage scavenger receptors. Remarkably, each individual sea urchin expresses a specific pattern of SRCR genes. Our results imply some shared immune functions and more generally, a shared regulatory architecture which underlies immune system gene expression in all deuterostomes. We conclude that the vertebrate immune system has evolved by inserting new genes into old gene regulatory networks dedicated to immunity.

  7. 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

  8. 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.

  9. 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.

  10. [The role of the innate immune system in atopic dermatitis].

    PubMed

    Volz, T; Kaesler, S; Skabytska, Y; Biedermann, T

    2015-02-01

    The mechanisms how the innate immune system detects microbes and mounts a rapid immune response have been more and more elucidated in the past years. Subsequently it has been shown that innate immunity also shapes adaptive immune responses and determines their quality that can be either inflammatory or tolerogenic. As atopic dermatitis is characterized by disturbances of innate and adaptive immune responses, colonization with pathogens and defects in skin barrier function, insight into mechanisms of innate immunity has helped to understand the vicious circle of ongoing skin inflammation seen in atopic dermatitis patients. Elucidating general mechanisms of the innate immune system and its functions in atopic dermatitis paves the way for developing new therapies. Especially the novel insights into the human microbiome and potential functional consequences make the innate immune system a very fundamental and promising target. As a result atopic dermatitis manifestations can be attenuated or even resolved. These currently developed strategies will be introduced in the current review.

  11. 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

  12. 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.

  13. Temperature stress affects the expression of immune response genes in the alfalfa leafcutting bee (Megachile rotundata)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The alfalfa leafcutting bee (Megachile rotundata) is affected by a fungal disease called chalkbrood. In several species of bees, chalkbrood is more likely to occur in larvae kept at 25-30 C than at 35 C. We found that both high and low temperature stress increased the expression of immune response g...

  14. Chasing the recipe for a pro-regenerative immune system.

    PubMed

    Godwin, James W; Pinto, Alexander R; Rosenthal, Nadia A

    2017-01-01

    Identification of the key ingredients and essential processes required to achieve perfect tissue regeneration in humans has so far remained elusive. Injury in vertebrates induces an obligatory wound response that will precede or overlap any regeneration specific program or scarring outcome. This process shapes the cellular and molecular landscape of the tissue, influencing the success of endogenous repair pathways or for potential clinical intervention. The involvement of immune cells is also required for aspects of development extending beyond the initial inflammatory phase of wounding. It has now become clear from amphibian, fish and mammalian models of tissue injury that the type of immune response and the profile of immune cells attending the site of injury can act as the gatekeepers that determine wound repair quality. The heterogeneity among innate and adaptive immune cell populations, along with the developmental origin of these cells, form key ingredients affecting the potential for downstream repair and the suppression of fibrosis. Cell-to-cell interactions between immune cells, such as macrophages and T cells, with stem cells and mesenchymal cells are critically important for shaping this process and these exchanges, are in turn influenced by the type of injury, tissue location and developmental stage of the organism. Developmentally, mouse cardiac regeneration is restricted to early stages of postnatal life where the balance of innate to adaptive immune cells may be poised towards regeneration. In the injured adult mouse liver, specific macrophage subsets improve repair while other bone marrow derived cells can exacerbate injury. Other studies using genetically diverse mice have shown enhanced regeneration in certain strains, restricted to specific tissues. This enhanced repair is linked with expression of genes such as Insulin-like Growth Factor- 1 (IGF-1) and activin (Act 1), that both play important roles in shaping the immune system. Immune cells are

  15. Chasing the recipe for a pro-regenerative immune system

    PubMed Central

    Pinto, Alexander R.; Rosenthal, Nadia A.

    2017-01-01

    Identification of the key ingredients and essential processes required to achieve perfect tissue regeneration in humans has so far remained elusive. Injury in vertebrates induces an obligatory wound response that will precede or overlap any regeneration specific program or scarring outcome. This process shapes the cellular and molecular landscape of the tissue, influencing the success of endogenous repair pathways or for potential clinical intervention. The involvement of immune cells is also required for aspects of development extending beyond the initial inflammatory phase of wounding. It has now become clear from amphibian, fish and mammalian models of tissue injury that the type of immune response and the profile of immune cells attending the site of injury can act as the gatekeepers that determine wound repair quality. The heterogeneity among innate and adaptive immune cell populations, along with the developmental origin of these cells, form key ingredients affecting the potential for downstream repair and the suppression of fibrosis. Cell-to-cell interactions between immune cells, such as macrophages and T cells, with stem cells and mesenchymal cells are critically important for shaping this process and these exchanges, are in turn influenced by the type of injury, tissue location and developmental stage of the organism. Developmentally, mouse cardiac regeneration is restricted to early stages of postnatal life where the balance of innate to adaptive immune cells may be poised towards regeneration. In the injured adult mouse liver, specific macrophage subsets improve repair while other bone marrow derived cells can exacerbate injury. Other studies using genetically diverse mice have shown enhanced regeneration in certain strains, restricted to specific tissues. This enhanced repair is linked with expression of genes such as Insulin-like Growth Factor- 1 (IGF-1) and activin (Act 1), that both play important roles in shaping the immune system. Immune cells are

  16. The Immune System in Cancer Prevention, Development and Therapy.

    PubMed

    Candeias, Serge M; Gaipl, Udo S

    2016-01-01

    The immune system plays a pivotal role in the maintenance of the integrity of an organism. Besides the protection against pathogens, it is strongly involved in cancer prevention, development and defense. This review focuses on how the immune system protects against infections and trauma and on its role in cancer development and disease. Focus is set on the interactions of the innate and adaptive immune system and tumors. The role of IFN-γ as a pleiotropic cytokine that plays a very important role at the interface of innate and adaptive immune systems in tumor development and induction of anti-tumor immune responses is outlined. Further, immune cells as prognostic and predictive markers of cancer will be discussed. Data are provided that even the brain as immune privileged organ is subjected to immune surveillance and consequently also brain tumors. Immune therapeutic approaches for glioblastoma multiforme, the most frequent and malignant brain tumor, based on vaccination with dendritic cells are outlined and application of hyperthermia in form of magnetic nanoparticles is discussed. We conclude that the immune system and developing tumors are intimately intertwined. Anti-tumor immune responses can be prominently boosted by multimodal therapies aiming on the one hand to induce immunogenic tumor cell death forms and on the other hand to actively counteract the immune suppressive microenvironment based on the tumor itself.

  17. Immune challenge but not dietary restriction affects spatial learning in the wild subterranean rodent Ctenomys talarum.

    PubMed

    Schleich, Cristian E; Zenuto, Roxana R; Cutrera, Ana P

    2015-02-01

    Several lines of evidence suggest that learning and triggering an immune response are both metabolically expensive and thus likely to be subject to nutritional trade-offs between them and other competing demands. Therefore, we evaluated if an immune challenge with a novel antigen affects spatial learning in the subterranean rodent Ctenomys talarum under two different dietary conditions. The results showed that immune-challenged animals were affected in their spatial learning capabilities, increasing the number of errors and marginally the time required to reach the goal of a complex labyrinth. No effect of the dietary restriction nor interaction between factors were observed. This work provides support for the existence of a trade-off between the costs of the immune defense and learning abilities, indicating that when investment is required to fight infection, fewer resources are available for learning. The absence of effect of nutritional condition on this trade-off suggests that other physiological processes, besides cognition, may be limited by the energetic resources necessary to the more immediately critical immune response.

  18. Trace Metals Affect Early Maternal Transfer of Immune Components in the Feral Pigeon.

    PubMed

    Chatelain, M; Gasparini, J; Haussy, C; Frantz, A

    2016-01-01

    Maternal early transfers of immune components influence eggs' hatching probability and nestlings' survival. They depend on females' own immunity and, because they are costly, on their physiological state. Therefore, trace metals, whether toxic and immunosuppressive (e.g., lead, cadmium, etc.) or necessary and immunostimulant (e.g., zinc, copper, iron, etc.), are likely to affect the amount of immune components transferred into the eggs. It may also vary with plumage eumelanin level, which is known to be linked to immunity, to transfer of antibodies, and to metal detoxification. In feral pigeons (Columba livia) injected with an antigen and experimentally exposed to lead and/or zinc (two highly abundant trace metals in urban areas), we measured specific antibody transfer and concentrations of two antimicrobial proteins (lysozyme and ovotransferrin) in eggs. As expected, lead had negative effects on specific antibody transfer, while zinc positively affected lysozyme egg concentrations. Moreover, eggs from lead-exposed females exhibited higher ovotransferrin concentrations; because it binds metal ions, ovotransferrin may enable egg detoxification and embryo protection. Finally, eggs' lysozyme concentrations increased with plumage darkness of females not exposed to zinc, while the relation was opposite among zinc-exposed females, suggesting that benefits and costs of plumage melanism depend on trace metal environmental levels. Overall, our study underlines the potential ecotoxicological effects of trace metals on maternal transfers of immune components and the role of plumage melanism in modulating these effects.

  19. [Plasticity of neuroendocrine and immune systems in early development].

    PubMed

    Zakharova, L A

    2014-01-01

    This article provides an analysis of our own and published data on the reciprocal morphogenetic influence of the neiuroendocriie and imnimune systems on their formation and function in mammals. It is substantiated that, in early ontogeny, neurohormones regulate the growth and differentiation of various tissues in the body, including the lymphoid tissue. Thymicpeptides, in turn, affect the development of the hypothalamic-pitiitary-adrenal and gonadal-systems. Various adverse factors and changes in the physiological concentrations of hormones in the critical periods of development of these systems change their functions, and the plasticity of physiological systems in early ontogeny allows the body to adapt to new conditions. Disturbances in the interaction of the neuroendocrineand immune systems in the perinatal period induce apredisposition to various diseases in progeny.

  20. Extracellular Adenosine Mediates a Systemic Metabolic Switch during Immune Response

    PubMed Central

    Bajgar, Adam; Kucerova, Katerina; Jonatova, Lucie; Tomcala, Ales; Schneedorferova, Ivana; Okrouhlik, Jan; Dolezal, Tomas

    2015-01-01

    Immune defense is energetically costly, and thus an effective response requires metabolic adaptation of the organism to reallocate energy from storage, growth, and development towards the immune system. We employ the natural infection of Drosophila with a parasitoid wasp to study energy regulation during immune response. To combat the invasion, the host must produce specialized immune cells (lamellocytes) that destroy the parasitoid egg. We show that a significant portion of nutrients are allocated to differentiating lamellocytes when they would otherwise be used for development. This systemic metabolic switch is mediated by extracellular adenosine released from immune cells. The switch is crucial for an effective immune response. Preventing adenosine transport from immune cells or blocking adenosine receptor precludes the metabolic switch and the deceleration of development, dramatically reducing host resistance. Adenosine thus serves as a signal that the “selfish” immune cells send during infection to secure more energy at the expense of other tissues. PMID:25915062

  1. 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

  2. Marine pharmacology in 2003-4: Marine Compounds with Anthelminthic, Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiplatelet, Antiprotozoal, Antituberculosis, and Antiviral Activities; affecting the Cardiovascular, Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

    PubMed Central

    Mayer, Alejandro M.S.; Rodriguez, Abimael D.; Berlinck, Roberto G.S.; Hamann, Mark T.

    2007-01-01

    The current marine pharmacology review that covers the peer-reviewed literature during 2003 and 2004 is a sequel to the authors' 1998-2002 reviews, and highlights the preclinical pharmacology of 166 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria. Anthelminthic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 67 marine chemicals. Additionally 45 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as possessing anti-inflammatory effects. Finally, 54 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2003-2004, research on the pharmacology of marine natural products which involved investigators from Argentina, Australia, Brazil, Belgium, Canada, China, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Morocco, the Netherlands, New Zealand, Norway, Panama, the Philippines, Portugal, Russia, Slovenia, South Korea, Spain, Thailand, Turkey, United Kingdom, and the United States, contributed numerous chemical leads for the continued global search for novel therapeutic agents with broad spectrum activity. PMID:17392033

  3. Marine pharmacology in 2001–2002: Marine compounds with anthelmintic, antibacterial, anticoagulant, antidiabetic, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems and other miscellaneous mechanisms of action

    PubMed Central

    Mayer, Alejandro M.S.; Hamann, Mark T.

    2016-01-01

    During 2001–2002, research on the pharmacology of marine chemicals continued to be global in nature involving investigators from Argentina, Australia, Brazil, Canada, China, Denmark, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Netherlands, New Zealand, Pakistan, the Philippines, Russia, Singapore, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Thailand, United Kingdom, and the United States. This current article, a sequel to the authors’ 1998, 1999 and 2000 marine pharmacology reviews, classifies 106 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria, on the basis of peer-reviewed preclinical pharmacology. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 56 marine chemicals. An additional 19 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as to possess anti-inflammatory and antidiabetic effects. Finally, 31 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2001–2002 pharmacological research with marine chemicals continued to contribute potentially novel chemical leads for the ongoing global search for therapeutic agents for the treatment of multiple disease categories. PMID:15919242

  4. Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence.

    PubMed

    Navarro-Arias, María J; Defosse, Tatiana A; Dementhon, Karine; Csonka, Katalin; Mellado-Mojica, Erika; Dias Valério, Aline; González-Hernández, Roberto J; Courdavault, Vincent; Clastre, Marc; Hernández, Nahúm V; Pérez-García, Luis A; Singh, Dhirendra K; Vizler, Csaba; Gácser, Attila; Almeida, Ricardo S; Noël, Thierry; López, Mercedes G; Papon, Nicolas; Mora-Montes, Héctor M

    2016-01-01

    The fungal cell wall contains glycoproteins that interact with the host immune system. In the prominent pathogenic yeast Candida albicans, Pmr1 acts as a Golgi-resident ion pump that provides cofactors to mannosyltransferases, regulating the synthesis of mannans attached to glycoproteins. To gain insight into a putative conservation of such a crucial process within opportunistic yeasts, we were particularly interested in studying the role of the PMR1 homolog in a low-virulent species that rarely causes candidiasis, Candida guilliermondii. We disrupted C. guilliermondii PMR1 and found that loss of Pmr1 affected cell growth and morphology, biofilm formation, susceptibility to cell wall perturbing agents, mannan levels, and the wall composition and organization. Despite the significant increment in the amount of β1,3-glucan exposed at the wall surface, this positively influenced only the ability of the mutant to stimulate IL-10 production by human monocytes, suggesting that recognition of both mannan and β1,3-glucan, is required to stimulate strong levels of pro-inflammatory cytokines. Accordingly, our results indicate C. guilliermondii sensing by monocytes was critically dependent on the recognition of N-linked mannans and β1,3-glucan, as reported in other Candida species. In addition, chemical remotion of cell wall O-linked mannans was found to positively influence the recognition of C. guilliermondii by human monocytes, suggesting that O-linked mannans mask other cell wall components from immune cells. This observation contrasts with that reported in C. albicans. Finally, mice infected with C. guilliermondii pmr1Δ null mutant cells had significantly lower fungal burdens compared to animals challenged with the parental strain. Accordingly, the null mutant showed inability to kill larvae in the Galleria mellonella infection model. This study thus demonstrates that mannans are relevant for the C. guilliermondii-host interaction, with an atypical role for O

  5. Disruption of Protein Mannosylation Affects Candida guilliermondii Cell Wall, Immune Sensing, and Virulence

    PubMed Central

    Navarro-Arias, María J.; Defosse, Tatiana A.; Dementhon, Karine; Csonka, Katalin; Mellado-Mojica, Erika; Dias Valério, Aline; González-Hernández, Roberto J.; Courdavault, Vincent; Clastre, Marc; Hernández, Nahúm V.; Pérez-García, Luis A.; Singh, Dhirendra K.; Vizler, Csaba; Gácser, Attila; Almeida, Ricardo S.; Noël, Thierry; López, Mercedes G.; Papon, Nicolas; Mora-Montes, Héctor M.

    2016-01-01

    The fungal cell wall contains glycoproteins that interact with the host immune system. In the prominent pathogenic yeast Candida albicans, Pmr1 acts as a Golgi-resident ion pump that provides cofactors to mannosyltransferases, regulating the synthesis of mannans attached to glycoproteins. To gain insight into a putative conservation of such a crucial process within opportunistic yeasts, we were particularly interested in studying the role of the PMR1 homolog in a low-virulent species that rarely causes candidiasis, Candida guilliermondii. We disrupted C. guilliermondii PMR1 and found that loss of Pmr1 affected cell growth and morphology, biofilm formation, susceptibility to cell wall perturbing agents, mannan levels, and the wall composition and organization. Despite the significant increment in the amount of β1,3-glucan exposed at the wall surface, this positively influenced only the ability of the mutant to stimulate IL-10 production by human monocytes, suggesting that recognition of both mannan and β1,3-glucan, is required to stimulate strong levels of pro-inflammatory cytokines. Accordingly, our results indicate C. guilliermondii sensing by monocytes was critically dependent on the recognition of N-linked mannans and β1,3-glucan, as reported in other Candida species. In addition, chemical remotion of cell wall O-linked mannans was found to positively influence the recognition of C. guilliermondii by human monocytes, suggesting that O-linked mannans mask other cell wall components from immune cells. This observation contrasts with that reported in C. albicans. Finally, mice infected with C. guilliermondii pmr1Δ null mutant cells had significantly lower fungal burdens compared to animals challenged with the parental strain. Accordingly, the null mutant showed inability to kill larvae in the Galleria mellonella infection model. This study thus demonstrates that mannans are relevant for the C. guilliermondii-host interaction, with an atypical role for O

  6. Multiple-Valued Immune Network with Apoptosis System

    NASA Astrophysics Data System (ADS)

    Yamaguchi, Takayuki; Tang, Zheng

    In this paper, we describe a new model of immune network based on biological immune response network. We propose an immunity like multiple-valued network with apoptosis mechanism. The model is based on the interaction between B cells and T cells and the biological apoptosis mechanism in human body. With the mechanism, a naturally immune system can be reproduced. The model is also applied to pattern recognition. It gets possible with a conventional model to restricting categories increase of memory patterns.

  7. Intercellular Communication in the Adaptive Immune System

    NASA Astrophysics Data System (ADS)

    Chakraborty, Arup

    2004-03-01

    Higher organisms, like humans, have an adaptive immune system that can respond to pathogens that have not been encountered before. T lymphocytes (T cells) are the orchestrators of the adaptive immune response. They interact with cells, called antigen presenting cells (APC), that display molecular signatures of pathogens. Recently, video microscopy experiments have revealed that when T cells detect antigen on APC surfaces, a spatially patterned supramolecular assembly of different types of molecules forms in the junction between cell membranes. This recognition motif is implicated in information transfer between APC and T cells, and so, is labeled the immunological synapse. The observation of synapse formation sparked two broad questions: How does the synapse form? Why does the synapse form? I will describe progress made in answering these fundamental questions in biology by synergistic use of statistical mechanical theory/computation, chemical engineering principles, and genetic and biochemical experiments. The talk will also touch upon mechanisms that may underlie the extreme sensitivity with which T cells discriminate between self and non-self.

  8. 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.

  9. [Mechanisms of immune system contribution to efficiency of antitumor cytostatic therapy].

    PubMed

    Stakheeva, M N; Kzhyshkowska, Yu G; Buldakov, M A; Cherdyntseva, N V

    2015-01-01

    Increasing the efficiency of antitumor therapy is one of major relevant tasks of oncology today. During recent years experimental evidence for active involvement of immune system in the regulation antitumor effects of cytostatic thereby has been obtained and theoretically justified. It was demonstrated that efficient cytostatic treatment is related to the cytotoxic activities of immune cells targeted against tumor cells. Such cytotoxic activities of immune cells are induced by radiotherapy or chemotherapy, where both innate and adaptive immune mechanisms are involved. However the disturbance in the functions of immune system can result in the impaired efficiency of cytostatic anti-tumor therapy. Cytotoxic agents can affect immune reactions by increasing the antigenic properties of tumor cells, facilitating their recognition of immune system, by stimulation of functional activation effector immune cells, elimination of immunosuppressive factors as well as systemic effects of antitumor therapy. A consideration of the crucial role of immune system in the providing of the efficiency of cytostatic antitumor therapy develops novel therapeutic approaches for treatment of malignant disorders based on balanced synergistic action of cytostatic agents and innovative immunomodulatory approaches.

  10. 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.

  11. Encapsulation of an EP67-Conjugated CTL Peptide Vaccine in Nanoscale Biodegradable Particles Increases the Efficacy of Respiratory Immunization and Affects the Magnitude and Memory Subsets of Vaccine-Generated Mucosal and Systemic CD8(+) T Cells in a Diameter-Dependent Manner.

    PubMed

    Karuturi, Bala V K; Tallapaka, Shailendra B; Yeapuri, Pravin; Curran, Stephen M; Sanderson, Sam D; Vetro, Joseph A

    2017-04-03

    The diameter of biodegradable particles used to coencapsulate immunostimulants and subunit vaccines affects the magnitude of memory CD8(+) T cells generated by systemic immunization. Possible effects on the magnitude of CD8(+) T cells generated by mucosal immunization or memory subsets that potentially correlate more strongly with protection against certain pathogens, however, are unknown. In this study, we conjugated our novel host-derived mucosal immunostimulant, EP67, to the protective MCMV CTL epitope, pp89, through a lysosomal protease-labile double arginine linker (pp89-RR-EP67) and encapsulated in PLGA 50:50 micro- or nanoparticles. We then compared total magnitude, effector/central memory (CD127/KRLG1/CD62L), and IFN-γ/TNF-α/IL-2 secreting subsets of pp89-specific CD8(+) T cells as well as protection of naive female BALB/c mice against primary respiratory infection with MCMV 21 days after respiratory immunization. We found that decreasing the diameter of encapsulating particle from ∼5.4 μm to ∼350 nm (i) increased the magnitude of pp89-specific CD8(+) T cells in the lungs and spleen; (ii) partially changed CD127/KLRG1 effector memory subsets in the lungs but not the spleen; (iii) changed CD127/KRLG1/CD62L effector/central memory subsets in the spleen; (iv) changed pp89-responsive IFN-γ/TNF-α/IL-2 secreting subsets in the lungs and spleen; (v) did not affect the extent to which encapsulation increased efficacy against primary MCMV respiratory infection over unencapsulated pp89-RR-EP67. Thus, although not observed under our current experimental conditions with MCMV, varying the diameter of nanoscale biodegradable particles may increase the efficacy of mucosal immunization with coencapsulated immunostimulant/subunit vaccines against certain pathogens by selectively increasing memory subset(s) of CD8(+) T cells that correlate the strongest with protection.

  12. Neuroendocrine and Immune System Responses with Spaceflights

    NASA Technical Reports Server (NTRS)

    Tipton, Charles M.; Greenleaf, John E.; Jackson, Catherine G. R.

    1996-01-01

    Despite the fact that the first human was in space during 1961 and individuals have existed in a microgravity environment for more than a year, there are limited spaceflight data available on the responses of the neuroendocrine and immune systems. Because of mutual interactions between these respective integrative systems, it is inappropriate to assume that the responses of one have no impact on functions of the other. Blood and plasma volume consistently decrease with spaceflight; hence, blood endocrine and immune constituents will be modified by both gravitational and measurement influences. The majority of the in-flight data relates to endocrine responses that influence fluids and electrolytes during the first month in space. Adrenocorticotropin (ACTH), aldo-sterone. and anti-diuretic hormone (ADH) appear to be elevated with little change in the atrial natriuretic peptides (ANP). Flight results longer than 60 d show increased ADH variability with elevations in angiotensin and cortisol. Although post-flight results are influenced by reentry and recovery events, ACTH and ADH appear to be consistently elevated with variable results being reported for the other hormones. Limited in-flight data on insulin and growth hormone levels suggest they are not elevated to counteract the loss in muscle mass. Post-flight results from short- and long-term flights indicate that thyroxine and insulin are increased while growth hormone exhibits minimal change. In-flight parathyroid hormone (PTH) levels are variable for several weeks after which they remain elevated. Post-flight PTH was increased on missions that lasted either 7 or 237 d, whereas calcitonin concentrations were increased after 1 wk but decreased after longer flights. Leukocytes are elevated in flights of various durations because of an increase in neutrophils. The majority of post-flight data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  13. [Understanding of immune system by visualization of spatiotemporal regulation of immune cells in the entire body].

    PubMed

    Tomura, Michio

    2013-01-01

    Immune system is high-dimensional integrated system distributed in the whole body. Many kinds of, total 10(11) of immune cells are regulated by receiving appropriate signals in appropriate places. We have been attempting to understand immune system by revealing spatiotemporal regulation of immune cells at the whole body level by "Visualization of immune response in vivo". Photoconvertible protein, "Kaede"-Tg mice allowed us to monitor cell-replacement and cell-movement in the whole body by marking cells with color of Kaede from green to red with exposure to violet light. It is applicable to small cell number populations in both lymphoid organs and also peripheral tissues under both normal and pathophysiological conditions. By using this system, we have demonstrated novel findings that "Naive CD4(+) T cell recirculation is an active process that they recirculate through lymphoid organs to seek limited niche for interacting with endogenous antigens and upregulate their function." and "Activated regulatory T cells emigrating from cutaneous immune response is responsible for termination of immune reponse." I will introduce these new tools of us and would like to discuss what is needed to understand immune system in the entire body.

  14. Reversal of hepatitis B virus-induced systemic immune tolerance by intrinsic innate immune stimulation.

    PubMed

    Han, Qiuju; Lan, Peixiang; Zhang, Jian; Zhang, Cai; Tian, Zhigang

    2013-08-01

    Systemic immune tolerance induced by chronic hepatitis B virus (HBV) infection is a significant question, but the mechanism of which remains unclear. In this mini-review, we summarize the impaired innate and adaptive immune responses involved in immune tolerance in chronic HBV infection. Furthermore, we delineate a novel dual functional small RNA to inhibit HBV replication and stimulate innate immunity against HBV, which proposed a promising immunotherapeutic intervention to interrupt HBV-induced immunotolerance. A mouse model of HBV persistence was established and used to observe the immune tolerant to HBV vaccination, the cell-intrinsic immune tolerance of which might be reversed by chemically synthesized dual functional small RNA (3p-hepatitis B Virus X gene [HBx]-small interfering RNA) in vitro experiments and by biologically constructed dual functional vector (single-stranded RNA-HBx- short hairpin RNA) in vivo experiment using HBV-carrier mice.

  15. [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.

  16. Reactive oxygen species in the immune system.

    PubMed

    Yang, Yuhui; Bazhin, Alexandr V; Werner, Jens; Karakhanova, Svetlana

    2013-06-01

    Reactive oxygen species (ROS) are a group of highly reactive chemicals containing oxygen produced either exogenously or endogenously. ROS are related to a wide variety of human disorders, such as chronic inflammation, age-related diseases and cancers. Besides, ROS are also essential for various biological functions, including cell survival, cell growth, proliferation and differentiation, and immune response. At present there are a number of excellent publications including some reviews about functions of these molecules either in normal cell biology or in pathophysiology. In this work, we reviewed available information and recent advances about ROS in the main immune cell types and gave summary about functions of these highly reactive molecules both in innate immunity as conservative defense mechanisms and in essential immune cells involved in adaptive immunity, and particularly in immune suppression.

  17. The potential impact of climate change and ultraviolet radiation on vaccine-preventable infectious diseases and immunization service delivery system.

    PubMed

    Guo, Biao; Naish, Suchithra; Hu, Wenbiao; Tong, Shilu

    2015-04-01

    Climate change and solar ultraviolet radiation may affect vaccine-preventable infectious diseases (VPID), the human immune response process and the immunization service delivery system. We systematically reviewed the scientific literature and identified 37 relevant publications. Our study shows that climate variability and ultraviolet radiation may potentially affect VPID and the immunization delivery system through modulating vector reproduction and vaccination effectiveness, possibly influencing human immune response systems to the vaccination, and disturbing immunization service delivery. Further research is needed to determine these affects on climate-sensitive VPID and on human immune response to common vaccines. Such research will facilitate the development and delivery of optimal vaccination programs for target populations, to meet the goal of disease control and elimination.

  18. How the Innate Immune System Senses Trouble and Causes Trouble.

    PubMed

    Hato, Takashi; Dagher, Pierre C

    2015-08-07

    The innate immune system is the first line of defense in response to nonself and danger signals from microbial invasion or tissue injury. It is increasingly recognized that each organ uses unique sets of cells and molecules that orchestrate regional innate immunity. The cells that execute the task of innate immunity are many and consist of not only "professional" immune cells but also nonimmune cells, such as renal epithelial cells. Despite a high level of sophistication, deregulated innate immunity is common and contributes to a wide range of renal diseases, such as sepsis-induced kidney injury, GN, and allograft dysfunction. This review discusses how the innate immune system recognizes and responds to nonself and danger signals. In particular, the roles of renal epithelial cells that make them an integral part of the innate immune apparatus of the kidney are highlighted.

  19. How sex and age affect immune responses, susceptibility to infections, and response to vaccination

    PubMed Central

    Giefing-Kröll, Carmen; Berger, Peter; Lepperdinger, Günter; Grubeck-Loebenstein, Beatrix

    2015-01-01

    Do men die young and sick, or do women live long and healthy? By trying to explain the sexual dimorphism in life expectancy, both biological and environmental aspects are presently being addressed. Besides age-related changes, both the immune and the endocrine system exhibit significant sex-specific differences. This review deals with the aging immune system and its interplay with sex steroid hormones. Together, they impact on the etiopathology of many infectious diseases, which are still the major causes of morbidity and mortality in people at old age. Among men, susceptibilities toward many infectious diseases and the corresponding mortality rates are higher. Responses to various types of vaccination are often higher among women thereby also mounting stronger humoral responses. Women appear immune-privileged. The major sex steroid hormones exhibit opposing effects on cells of both the adaptive and the innate immune system: estradiol being mainly enhancing, testosterone by and large suppressive. However, levels of sex hormones change with age. At menopause transition, dropping estradiol potentially enhances immunosenescence effects posing postmenopausal women at additional, yet specific risks. Conclusively during aging, interventions, which distinctively consider the changing level of individual hormones, shall provide potent options in maintaining optimal immune functions. PMID:25720438

  20. How sex and age affect immune responses, susceptibility to infections, and response to vaccination.

    PubMed

    Giefing-Kröll, Carmen; Berger, Peter; Lepperdinger, Günter; Grubeck-Loebenstein, Beatrix

    2015-06-01

    Do men die young and sick, or do women live long and healthy? By trying to explain the sexual dimorphism in life expectancy, both biological and environmental aspects are presently being addressed. Besides age-related changes, both the immune and the endocrine system exhibit significant sex-specific differences. This review deals with the aging immune system and its interplay with sex steroid hormones. Together, they impact on the etiopathology of many infectious diseases, which are still the major causes of morbidity and mortality in people at old age. Among men, susceptibilities toward many infectious diseases and the corresponding mortality rates are higher. Responses to various types of vaccination are often higher among women thereby also mounting stronger humoral responses. Women appear immune-privileged. The major sex steroid hormones exhibit opposing effects on cells of both the adaptive and the innate immune system: estradiol being mainly enhancing, testosterone by and large suppressive. However, levels of sex hormones change with age. At menopause transition, dropping estradiol potentially enhances immunosenescence effects posing postmenopausal women at additional, yet specific risks. Conclusively during aging, interventions, which distinctively consider the changing level of individual hormones, shall provide potent options in maintaining optimal immune functions.

  1. Burkholderia cenocepacia Lipopolysaccharide Modification and Flagellin Glycosylation Affect Virulence but Not Innate Immune Recognition in Plants

    PubMed Central

    Khodai-Kalaki, Maryam; Andrade, Angel; Fathy Mohamed, Yasmine

    2015-01-01

    ABSTRACT Burkholderia cenocepacia causes opportunistic infections in plants, insects, animals, and humans, suggesting that “virulence” depends on the host and its innate susceptibility to infection. We hypothesized that modifications in key bacterial molecules recognized by the innate immune system modulate host responses to B. cenocepacia. Indeed, modification of lipopolysaccharide (LPS) with 4-amino-4-deoxy-l-arabinose and flagellin glycosylation attenuates B. cenocepacia infection in Arabidopsis thaliana and Galleria mellonella insect larvae. However, B. cenocepacia LPS and flagellin triggered rapid bursts of nitric oxide and reactive oxygen species in A. thaliana leading to activation of the PR-1 defense gene. These responses were drastically reduced in plants with fls2 (flagellin FLS2 host receptor kinase), Atnoa1 (nitric oxide-associated protein 1), and dnd1-1 (reduced production of nitric oxide) null mutations. Together, our results indicate that LPS modification and flagellin glycosylation do not affect recognition by plant receptors but are required for bacteria to establish overt infection. PMID:26045541

  2. Imitating a stress response: a new hypothesis about the innate immune system's role in pregnancy.

    PubMed

    Schminkey, Donna L; Groer, Maureen

    2014-06-01

    Recent research challenges long-held hypotheses about mechanisms through which pregnancy induces maternal immune suppression or tolerance of the embryo/fetus. It is now understood that normal pregnancy engages the immune system and that the immune milieu changes with advancing gestation. We suggest that pregnancy mimics the innate immune system's response to stress, causing a sterile inflammatory response that is necessary for successful reproduction. The relationship between external stressors and immunomodulation in pregnancy has been acknowledged, but the specific mechanisms are still being explicated. Implantation and the first trimester are times of immune activation and intensive inflammation in the uterine environment. A period of immune quiescence during the second trimester allows for the growth and development of the maturing fetus. Labor is also an inflammatory event. The length of gestation and timing of parturition can be influenced by environmental stressors. These stressors affect pregnancy through neuroendocrine interaction with the immune system, specifically through the hypothalamic-pituitary-adrenal (HPA) axis and the hypothalamic-pituitary-ovarian axis. Trophoblastic cells that constitute the maternal-fetal interface appear to harness the maternal immune system to promote and maximize the reproductive success of the mother and fetus. Pregnancy is a time of upregulated innate immune responses and decreased adaptive, cell-mediated responses. The inflammatory processes of pregnancy resemble an immune response to brief naturalistic stressors: there is a shift from T helper (Th) 1 to T helper (Th) 2 dominant adaptive immunity with a concomitant shift in cytokine production, decreased proliferation of T cells, and decreased cytotoxicity of natural killer (NK) cells. Inclusion of both murine and human studies, allows an exploration of insights into how trophoblasts influence the activity of the maternal innate immune system during gestation.

  3. The immune system and cardiac repair

    PubMed Central

    Frangogiannis, Nikolaos G.

    2008-01-01

    role of the immune system in cardiac repair is necessary in order to design optimal strategies for cardiac regeneration. PMID:18620057

  4. Interactions between the host innate immune system and microbes in inflammatory bowel disease.

    PubMed

    Abraham, Clara; Medzhitov, Ruslan

    2011-05-01

    The intestinal immune system defends against pathogens and entry of excessive intestinal microbes; simultaneously, a state of immune tolerance to resident intestinal microbes must be maintained. Perturbation of this balance is associated with intestinal inflammation in various mouse models and is thought to predispose humans to inflammatory bowel disease (IBD). The innate immune system senses microbes; dendritic cells, macrophages, and epithelial cells produce an initial, rapid response. The immune system continuously monitors resident microbiota and utilizes constitutive antimicrobial mechanisms to maintain immune homeostasis. associations between IBD and genes that regulate microbial recognition and innate immune pathways, such as nucleotide oligomerization domain 2 (Nod2), genes that control autophagy (eg, ATG16L1, IRGM), and genes in the interleukin-23-T helper cell 17 pathway indicate the important roles of host-microbe interactions in regulating intestinal immune homeostasis. There is increasing evidence that intestinal microbes influence host immune development, immune responses, and susceptibility to human diseases such as IBD, diabetes mellitus, and obesity. Conversely, host factors can affect microbes, which in turn modulate disease susceptibility. We review the cell populations and mechanisms that mediate interactions between host defense and tolerance and how the dysregulation of host-microbe interactions leads to intestinal inflammation and IBD.

  5. Resident viruses and their interactions with the immune system.

    PubMed

    Duerkop, Breck A; Hooper, Lora V

    2013-07-01

    The human body is colonized with a diverse resident microflora that includes viruses. Recent studies of metagenomes have begun to characterize the composition of the human 'virobiota' and its associated genes (the 'virome'), and have fostered the emerging field of host-virobiota interactions. In this Perspective, we explore how resident viruses interact with the immune system. We review recent findings that highlight the role of the immune system in shaping the composition of the virobiota and consider how resident viruses may impact host immunity. Finally, we discuss the implications of virobiota-immune system interactions for human health.

  6. 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.

  7. Immune reconstitution and strategies for rebuilding the immune system after haploidentical stem cell transplantation.

    PubMed

    Oevermann, Lena; Lang, Peter; Feuchtinger, Tobias; Schumm, Michael; Teltschik, Heiko-Manuel; Schlegel, Patrick; Handgretinger, Rupert

    2012-08-01

    Haploidentical hematopoietic stem cell transplantation is a curative alternative option for patients without an otherwise suitable stem cell donor. In order to prevent graft-versus-host disease (GvHD), different in vitro and in vivo T cell-depletion strategies have been developed. A delayed immune reconstitution is common to all these strategies, and an impaired immune function after haploidentical transplantation with subsequent infections is a major cause of deaths in these patients. In addition to in vitro and in vivo T cell-depletion methods, posttransplant strategies to rapidly rebuild the immune system have been introduced in order to improve the outcome. Advances in in vitro and in vivo T cell-depletion methods, and adoptive transfer of immune cells of the innate and specific immune system, will contribute to reduce the risk of GvHD, lethal infections, and the risk of relapse of the underlying malignant disease.

  8. 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.

  9. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees.

    PubMed

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-11-12

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture.

  10. Neonicotinoid clothianidin adversely affects insect immunity and promotes replication of a viral pathogen in honey bees

    PubMed Central

    Di Prisco, Gennaro; Cavaliere, Valeria; Annoscia, Desiderato; Varricchio, Paola; Caprio, Emilio; Nazzi, Francesco; Gargiulo, Giuseppe; Pennacchio, Francesco

    2013-01-01

    Large-scale losses of honey bee colonies represent a poorly understood problem of global importance. Both biotic and abiotic factors are involved in this phenomenon that is often associated with high loads of parasites and pathogens. A stronger impact of pathogens in honey bees exposed to neonicotinoid insecticides has been reported, but the causal link between insecticide exposure and the possible immune alteration of honey bees remains elusive. Here, we demonstrate that the neonicotinoid insecticide clothianidin negatively modulates NF-κB immune signaling in insects and adversely affects honey bee antiviral defenses controlled by this transcription factor. We have identified in insects a negative modulator of NF-κB activation, which is a leucine-rich repeat protein. Exposure to clothianidin, by enhancing the transcription of the gene encoding this inhibitor, reduces immune defenses and promotes the replication of the deformed wing virus in honey bees bearing covert infections. This honey bee immunosuppression is similarly induced by a different neonicotinoid, imidacloprid, but not by the organophosphate chlorpyriphos, which does not affect NF-κB signaling. The occurrence at sublethal doses of this insecticide-induced viral proliferation suggests that the studied neonicotinoids might have a negative effect at the field level. Our experiments uncover a further level of regulation of the immune response in insects and set the stage for studies on neural modulation of immunity in animals. Furthermore, this study has implications for the conservation of bees, as it will contribute to the definition of more appropriate guidelines for testing chronic or sublethal effects of pesticides used in agriculture. PMID:24145453

  11. Impact of nest sanitation on the immune system of parents and nestlings in a passerine bird.

    PubMed

    Evans, Jessica K; Griffith, Simon C; Klasing, Kirk C; Buchanan, Katherine L

    2016-07-01

    Bacterial communities are thought to have fundamental effects on the growth and development of nestling birds. The antigen exposure hypothesis suggests that, for both nestlings and adult birds, exposure to a diverse range of bacteria would select for stronger immune defences. However, there are relatively few studies that have tested the immune/bacterial relationships outside of domestic poultry. We therefore sought to examine indices of immunity (microbial killing ability in naive birds, which is a measure of innate immunity, and the antibody response to sheep red blood cells, which measures adaptive immunity) in both adult and nestling zebra finches (Taeniopygia guttata). We did this throughout breeding and between reproductive attempts in nests that were experimentally manipulated to change the intensity of bacterial exposure. Our results suggest that nest sanitation and bacterial load affected measures of the adaptive immune system, but not the innate immune parameters tested. Adult finches breeding in clean nests had a lower primary antibody response to sheep red blood cells, particularly males, and a greater difference between primary and secondary responses. Adult microbial killing of Escherichia coli decreased as parents moved from incubation to nestling rearing for both nest treatments; however, killing of Candida albicans remained consistent throughout. In nestlings, both innate microbial killing and the adaptive antibody response did not differ between nest environments. Together, these results suggest that exposure to microorganisms in the environment affects the adaptive immune system in nesting birds, with exposure upregulating the antibody response in adult birds.

  12. Neutrophils: Cinderella of innate immune system.

    PubMed

    Kumar, V; Sharma, A

    2010-11-01

    Neutrophils are the first line of innate immune defense against infectious diseases. However, since their discovery by Elie Metchnikoff, they have always been considered tissue-destructive cells responsible for inflammatory tissue damage occurring during acute infections. Now, extensive research in the field of neutrophil cell biology and their role skewing the immune response in various infections or inflammatory disorders revealed their importance in the regulation of immune response. Along with releasing various antimicrobial molecules, neutrophils also release neutrophil extracellular traps (NETs) for the containment of infection and inflammation. Activated neutrophils provide signals for the activation and maturation of macrophages as well as dendritic cells. Neutrophils are also involved in the regulation of T-cell immune response against various pathogens and tumor antigens. Thus, the present review is intended to highlight the emerging role of neutrophils in the regulation of both innate and adaptive immunity during acute infectious or inflammatory conditions.

  13. 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.

  14. The Immune System in the Pathogenesis of Ovarian Cancer

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    2017-01-01

    Idiopathic chronic inflammatory conditions (ICIC) such as allergy, asthma, chronic obstructive pulmonary disease, and various autoimmune conditions are a worldwide health problem. Understanding the pathogenesis of ICIC is essential for their successful therapy and prevention. However, efforts are hindered by the lack of comprehensive understanding of the human immune system function. In line with those efforts, described here is a concept of stochastic continuous dual resetting (CDR) of the immune repertoire as a basic principle that governs the function of immunity. The CDR functions as a consequence of system's thermodynamically determined intrinsic tendency to acquire new states of inner equilibrium and equilibrium against the environment. Consequently, immune repertoire undergoes continuous dual (two-way) resetting: against the physiologic continuous changes of self and against the continuously changing environment. The CDR-based dynamic concept of immunity describes mechanisms of self-regulation, tolerance, and immunosenescence, and emphasizes the significance of immune system's compartmentalization in the pathogenesis of ICIC. The CDR concept's relative simplicity and concomitantly documented congruency with empirical, clinical, and experimental data suggest it may represent a plausible theoretical framework to better understand the human immune system function. PMID:28246613

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

    PubMed

    Balzar, Silvana

    2017-01-01

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

  17. Food availability and maternal immunization affect transfer and persistence of maternal antibodies in nestling pigeons.

    PubMed

    Ismail, Ahmad; Jacquin, Lisa; Haussy, Claudy; Legoupi, Julie; Perret, Samuel; Gasparini, Julien

    2013-01-01

    The ability of mothers to transfer antibodies (Abs) to their young and the temporal persistence of maternal Abs in offspring constitute important life-history traits that can impact the evolution of host-parasite interactions. Here, we examined the effects of food availability and parental immunization on the transfer and persistence of maternal antibodies in nestling pigeons (Columba livia). This species can transmit maternal Abs to offspring before hatching through the egg yolk and potentially after hatching through crop milk. However, the role of this postnatal substance in immunity remains elusive. We used a full cross-fostering design to disentangle the effects of food limitation and parental immunization both before and after hatching on the levels and persistence of maternal Abs in chicks. Parents were immunized via injection with keyhole limpet hemocyanin antigens. Using an immunoassay that specifically detected the IgY antibodies that are known to be transmitted via the yolk, we found that the levels of anti-KLH Abs in newly hatched chicks were positively correlated with the levels of anti-KLH Abs in the blood of their biological mothers. However, this correlation was not present between chicks and their foster parents, suggesting limited IgY transfer via crop milk to the chick's bloodstream. Interestingly, biological mothers subjected to food limitation during egg laying transferred significantly fewer specific maternal Abs, which suggests that the transfer of antibodies might be costly for them. In addition, the persistence of maternal Abs in a chick's bloodstream was not affected by food limitation or the foster parents' anti-KLH Ab levels; it was only affected by the initial level of maternal anti-KLH Abs that were present in newly hatched chicks. These results suggest that the maternal transfer of Abs could be costly but that their persistence in an offspring's bloodstream may not necessarily be affected by environmental conditions.

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

    NASA Astrophysics Data System (ADS)

    Deem, Michael

    2004-03-01

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

  19. The University Immune System: Overcoming Resistance to Change

    ERIC Educational Resources Information Center

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

    2009-01-01

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

  20. Overview of fish immune system and infectious diseases

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  1. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits.

    PubMed

    Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

    2015-01-01

    Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis.

  2. Phylogeny affects host's weight, immune response and parasitism in damselflies and dragonflies

    PubMed Central

    Suhonen, Jukka

    2016-01-01

    Host–parasite interactions are an intriguing part of ecology, and understanding how hosts are able to withstand parasitic attacks, e.g. by allocating resources to immune defence, is important. Damselflies and dragonflies show a variety of parasitism patterns, but large-scale comparative immune defence studies are rare, and it is difficult to say what the interplay is between their immune defence and parasitism. The aim of this study was to find whether there are differences in immune response between different damselfly and dragonfly species and whether these could explain their levels of gregarine and water mite parasitism. Using an artificial pathogen, a piece of nylon filament, we measured the encapsulation response of 22 different damselfly and dragonfly species and found that (i) there are significant encapsulation differences between species, (ii) body mass has a strong association with encapsulation and parasite prevalences, (iii) body mass shows a strong phylogenetic signal, whereas encapsulation response and gregarine and water mite prevalences show weak signals, and (iv) associations between the traits are affected by phylogeny. We do not know what the relationship is between these four traits, but it seems clear that phylogeny plays a role in determining parasitism levels of damselflies and dragonflies. PMID:28018621

  3. Phylogeny affects host's weight, immune response and parasitism in damselflies and dragonflies.

    PubMed

    Ilvonen, Jaakko J; Suhonen, Jukka

    2016-11-01

    Host-parasite interactions are an intriguing part of ecology, and understanding how hosts are able to withstand parasitic attacks, e.g. by allocating resources to immune defence, is important. Damselflies and dragonflies show a variety of parasitism patterns, but large-scale comparative immune defence studies are rare, and it is difficult to say what the interplay is between their immune defence and parasitism. The aim of this study was to find whether there are differences in immune response between different damselfly and dragonfly species and whether these could explain their levels of gregarine and water mite parasitism. Using an artificial pathogen, a piece of nylon filament, we measured the encapsulation response of 22 different damselfly and dragonfly species and found that (i) there are significant encapsulation differences between species, (ii) body mass has a strong association with encapsulation and parasite prevalences, (iii) body mass shows a strong phylogenetic signal, whereas encapsulation response and gregarine and water mite prevalences show weak signals, and (iv) associations between the traits are affected by phylogeny. We do not know what the relationship is between these four traits, but it seems clear that phylogeny plays a role in determining parasitism levels of damselflies and dragonflies.

  4. Hypothyroidism Affects Vascularization and Promotes Immune Cells Infiltration into Pancreatic Islets of Female Rabbits

    PubMed Central

    Rodríguez-Castelán, Julia; Martínez-Gómez, Margarita; Castelán, Francisco; Cuevas, Estela

    2015-01-01

    Thyroidectomy induces pancreatic edema and immune cells infiltration similarly to that observed in pancreatitis. In spite of the controverted effects of hypothyroidism on serum glucose and insulin concentrations, the number and proliferation of Langerhans islet cells as well as the presence of extracellular matrix are affected depending on the islet size. In this study, we evaluated the effect of methimazole-induced hypothyroidism on the vascularization and immune cells infiltration into islets. A general observation of pancreas was also done. Twelve Chinchilla-breed female adult rabbits were divided into control (n = 6) and hypothyroid groups (n = 6, methimazole, 0.02% in drinking water for 30 days). After the treatment, rabbits were sacrificed and their pancreas was excised, histologically processed, and stained with Periodic Acid-Schiff (PAS) or Masson's Trichrome techniques. Islets were arbitrarily classified into large, medium, and small ones. The external and internal portions of each islet were also identified. Student-t-test and Mann-Whitney-U test or two-way ANOVAs were used to compare variables between groups. In comparison with control rabbits, hypothyroidism induced a strong infiltration of immune cells and a major presence of collagen and proteoglycans in the interlobular septa. Large islets showed a high vascularization and immune cells infiltration. The present results show that hypothyroidism induces pancreatitis and insulitis. PMID:26175757

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

    PubMed Central

    Kitano, Hiroaki; Oda, Kanae

    2006-01-01

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

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

    PubMed Central

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

    2016-01-01

    Aging is a major risk factor for several conditions including neurodegenerative, cardiovascular diseases and cancer. Functional impairments in cellular pathways controlling genomic stability, and immune control have been identified. Biomarker of immune senescence is needed to improve vaccine response and to develop therapy to improve immune control. To identify phenotypic signature of circulating immune cells with aging, we enrolled 1068 Chinese healthy volunteers ranging from 18 to 80 years old. The decreased naïve CD4+ and CD8+ T cells, increased memory CD4+ or CD8+ T cells, loss of CD28 expression on T cells and reverse trend of CD38 and HLA-DR, were significant for aging of immune system. Conversely, the absolute counts and percentage of NK cells and CD19+B cells maintained stable in aging individuals. The Chinese reference ranges of absolute counts and percentage of peripheral lymphocyte in this study might be useful for future clinical evaluation. PMID:26886066

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

    PubMed

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

    2016-05-01

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

  8. Marine Toxin Okadaic Acid Affects the Immune Function of Bay Scallop (Argopecten irradians).

    PubMed

    Chi, Cheng; Giri, Sib Sankar; Jun, Jin Woo; Kim, Hyoun Joong; Yun, Saekil; Kim, Sang Guen; Park, Se Chang

    2016-08-24

    Okadaic acid (OA) is produced by dinoflagellates during harmful algal blooms and is a diarrhetic shellfish poisoning toxin. This toxin is particularly problematic for bivalves that are cultured for human consumption. This study aimed to reveal the effects of exposure to OA on the immune responses of bay scallop, Argopecten irradians. Various immunological parameters were assessed (total hemocyte counts (THC), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), lactate dehydrogenase (LDH), and nitric oxide (NO) in the hemolymph of scallops at 3, 6, 12, 24, and 48 h post-exposure (hpe) to different concentrations of OA (50, 100, and 500 nM). Moreover, the expression of immune-system-related genes (CLT-6, FREP, HSP90, MT, and Cu/ZnSOD) was also measured. Results showed that ROS, MDA, and NO levels and LDH activity were enhanced after exposure to different concentrations of OA; however, both THC and GSH decreased between 24-48 hpe. The expression of immune-system-related genes was also assessed at different time points during the exposure period. Overall, our results suggest that exposure to OA had negative effects on immune system function, increased oxygenic stress, and disrupted metabolism of bay scallops.

  9. Does cold activate the Drosophila melanogaster immune system?

    PubMed

    Salehipour-Shirazi, Golnaz; Ferguson, Laura V; Sinclair, Brent J

    2017-01-01

    Cold exposure appears to activate aspects of the insect immune system; however, the functional significance of the relationship between cold and immunity is unclear. Insect success at low temperatures is shaped in part by interactions with biotic stressors, such as pathogens, thus it is important to understand how and why immunity might be activated by cold. Here we explore which components of the immune system are activated, and whether those components differ among different kinds of cold exposure. We exposed Drosophila melanogaster to both acute (2h, -2°C) and sustained (10h, -0.5°C) cold, and measured potential (antimicrobial peptide expression, phenoloxidase activity, haemocyte counts) and realised (survival of fungal infection, wound-induced melanisation, bacterial clearance) immunity following recovery. Acute cold increased circulating haemocyte concentration and the expression of Turandot-A and diptericin, but elicited a short-term decrease in the clearance of gram-positive bacteria. Sustained cold increased the expression of Turandot-A, with no effect on other measures of potential or realised immunity. We show that measures of potential immunity were up-regulated by cold, whereas realised immunity was either unaffected or down-regulated. Thus, we hypothesize that cold-activation of potential immunity in Drosophila may be a compensatory mechanism to maintain stable immune function during or after low temperature exposure.

  10. Suppressive effects of androgens on the immune system.

    PubMed

    Trigunaite, Abhishek; Dimo, Joana; Jørgensen, Trine N

    2015-04-01

    Sex-based disparities in immune responses are well known phenomena. The two most important factors accounting for the sex-bias in immunity are genetics and sex hormones. Effects of female sex hormones, estrogen and progesterone are well established, however the role of testosterone is not completely understood. Evidence from unrelated studies points to an immunosuppressive role of testosterone on different components of the immune system, but the underlying molecular mechanisms remains unknown. In this review we evaluate the effect of testosterone on key cellular components of innate and adaptive immunity. Specifically, we highlight the importance of testosterone in down-regulating the systemic immune response by cell type specific effects in the context of immunological disorders. Further studies are required to elucidate the molecular mechanisms of testosterone-induced immunosuppression, leading the way to the identification of novel therapeutic targets for immune disorders.

  11. Evidence for a common mucosal immune system in the pig.

    PubMed

    Wilson, Heather L; Obradovic, Milan R

    2015-07-01

    The majority of lymphocytes activated at mucosal sites receive instructions to home back to the local mucosa, but a portion also seed distal mucosa sites. By seeding distal sites with antigen-specific effector or memory lymphocytes, the foundation is laid for the animal's mucosal immune system to respond with a secondary response should to this antigen be encountered at this site in the future. The common mucosal immune system has been studied quite extensively in rodent models but less so in large animal models such as the pig. Reasons for this paucity of reported induction of the common mucosal immune system in this species may be that distal mucosal sites were examined but no induction was observed and therefore it was not reported. However, we suspect that the majority of investigators simply did not sample distal mucosal sites and therefore there is little evidence of immune response induction in the literature. It is our hope that more pig immunologists and infectious disease experts who perform mucosal immunizations or inoculations on pigs will sample distal mucosal sites and report their findings, whether results are positive or negative. In this review, we highlight papers that show that immunization/inoculation using one route triggers mucosal immune system induction locally, systemically, and within at least one distal mucosal site. Only by understanding whether immunizations at one site triggers immunity throughout the common mucosal immune system can we rationally develop vaccines for the pig, and through these works we can gather evidence about the mucosal immune system that may be extrapolated to other livestock species or humans.

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

    PubMed

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

    2012-09-24

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

  13. Interactions between mesenchymal stem cells and the immune system.

    PubMed

    Li, Na; Hua, Jinlian

    2017-02-18

    In addition to being multi-potent, mesenchymal stem cells (MSCs) possess immunomodulatory functions that have been investigated as potential treatments in various immune disorders. MSCs can robustly interact with cells of the innate and adaptive immune systems, either through direct cell-cell contact or through their secretome. In this review, we discuss current findings regarding the interplay between MSCs and different immune cell subsets. We also draw attention to the mechanisms involved.

  14. 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.

  15. Effects of fenbendazole on the murine humoral immune system.

    PubMed

    Landin, Ana Marie; Frasca, Daniela; Zaias, Julia; Van der Put, Elaine; Riley, Richard L; Altman, Norman H; Blomberg, Bonnie B

    2009-05-01

    Pinworms are highly contagious parasites that have been effectively treated in laboratory rodents with fenbendazole (FBZ). Whether FBZ has any detrimental side effects that may compromise experimental results is unknown. Here we asked whether the immune systems from young and aged mice are altered under FBZ treatment. We compared control and FBZ-treated groups of young (age, 2 to 4 mo) and old (age, 22 to 24 mo) BALB/cN mice. The treated mice received a total of 4 wk (alternating-week treatment regimen) of FBZ-medicated feed. Spleen and bone marrow were collected for immunologic assays, and heart, stomach, intestines, kidneys, and liver were evaluated by histopathology. Our results indicate that FBZ treatment has significant effects on the immune systems of mice; these effects are greater in aged mice. FBZ treatment adversely affected mRNA and protein expression of E2A (a transcription factor crucial for B lymphocytes) in activated precursor B lymphocytes obtained from the bone marrow of young and old mice. These effects were reversed by 6 wk on regular feed after the end of treatment. Activated B lymphocytes from the spleens of young and old mice showed decreased function (cell proliferation, E2A mRNA and protein expression) through the last time point of FBZ treatment but recovered by 2 to 4 wk after treatment. Our findings suggest that FBZ treatment may alter sensitive immune and molecular measures as presented here, and postponing the experimental use of mice until at least 6 wk after treatment should be considered.

  16. Taenia solium: immune response against oral or systemic immunization with purified recombinant calreticulin in mice.

    PubMed

    Fonseca-Coronado, Salvador; Ruiz-Tovar, Karina; Pérez-Tapia, Mayra; Mendlovic, Fela; Flisser, Ana

    2011-01-01

    Recombinant functional Taenia solium calreticulin (rTsCRT) confers different degrees of protection in the experimental model of intestinal taeniosis in hamsters. The aim of this study was to evaluate the immune response induced after oral or systemic immunization with an electroeluted rTsCRT in BALB/c mice. Oral immunization elicited high fecal IgA and the production of IL-4 and IL-5 by mesenteric lymph node cells after in vitro stimulation with rTSCRT, indicating a Th2 response. Mice subcutaneously immunized produced high amounts of serum IgG, being IgG1 (Th2-related) the predominant isotype, while in vitro stimulated spleen cells synthesized IL-4, IL-5 and also IFN-γ, indicating a mixed Th1/Th2 cellular response after systemic immunization. Our data show that purified rTsCRT induces polarized Th2 responses after oral immunization of mice, a common characteristic of protective immunity against helminths and, consequently, a desirable hallmark in the search for a vaccine.

  17. Artificial Immune System for Flight Envelope Estimation and Protection

    DTIC Science & Technology

    2014-12-31

    consists of two equally important components: the innate system and the adaptive system1. The former is an inherited system that functions as the... innate immune system is always active and responds immediately to any class of pathogen without distinction. On the other hand, the adaptive immune...are macrophages (MΦs), dendritic cells (DCs), T-cells, and B-cells. The MΦ and DC populations form what is known as phagocytes (part of the innate

  18. Regulation of intestinal immune system by dendritic cells.

    PubMed

    Ko, Hyun-Jeong; Chang, Sun-Young

    2015-02-01

    Innate immune cells survey antigenic materials beneath our body surfaces and provide a front-line response to internal and external danger signals. Dendritic cells (DCs), a subset of innate immune cells, are critical sentinels that perform multiple roles in immune responses, from acting as principal modulators to priming an adaptive immune response through antigen-specific signaling. In the gut, DCs meet exogenous, non-harmful food antigens as well as vast commensal microbes under steady-state conditions. In other instances, they must combat pathogenic microbes to prevent infections. In this review, we focus on the function of intestinal DCs in maintaining intestinal immune homeostasis. Specifically, we describe how intestinal DCs affect IgA production from B cells and influence the generation of unique subsets of T cell.

  19. Possible roles of magnesium on the immune system.

    PubMed

    Tam, M; Gómez, S; González-Gross, M; Marcos, A

    2003-10-01

    During the last few years, magnesium (Mg) has been subject of research due to its functionality in the organism. It is one of the most important micronutrients, and therefore its role in biological systems has been extensively investigated. Particularly, Mg has a strong relation with the immune system, in both nonspecific and specific immune response, also known as innate and acquired immune response. The aim of this paper is to review the state of the art about the interactions between Mg and the immune system. We discuss the link between dietary Mg and inflammation, apoptosis and alterations in number and function of innate immune cell populations, described in animal models. Furthermore, the immune system can be compromised in human populations under certain circumstances, including athletes and elderly people. The importance of a balanced Mg homeostasis and its interaction with the immune system in these groups has also been reviewed. Although emerging data support the relevant role of Mg in the immune response, further research is needed; and special efforts should be made to establish the most adequate dose in nutritional supplements to reach beneficial effects on health.

  20. 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.

  1. New insights into innate immune control of systemic candidiasis.

    PubMed

    Lionakis, Michail S

    2014-08-01

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

  2. Heterogeneous hosts: how variation in host size, behaviour and immunity affects parasite aggregation.

    PubMed

    Johnson, Pieter T J; Hoverman, Jason T

    2014-09-01

    Infection heterogeneity is one of the most fundamental patterns in disease ecology, yet surprisingly few studies have experimentally explored its underlying drivers. Here, we used large-scale field assessments to evaluate the degree of parasite aggregation within amphibian host populations followed by a novel experimental approach to assess the potential influence of host size, behaviour and immunity in reproducing such heterogeneity. Among 227 wetlands, 2468 hosts and seven parasite species, infections were consistently aggregated among host individuals within populations of the Pacific chorus frog (Pseudacris regilla). For each parasite species, the relationship between the log-mean and log-variance of infection load was strongly linear (R(2): 0·91-0·98) with a slope between 1·37 and 1·67, indicative of aggregation relative to the expected Poisson slope of unity. In laboratory trials with P. regilla and the most virulent trematode (Ribeiroia ondatrae), experimental reductions in either host immunity (through corticosterone exposure) or antiparasite behaviours (through anaesthesia exposure) increased parasite infection loads in isolated hosts by 62-102% relative to unmanipulated individuals. In a second experiment designed to test how variation in host immunity, behaviour and body size affected variation in infection load within small groups (dyads), a reduction in immune function or behaviour of one host significantly amplified infection heterogeneity within the group, effectively doubling the variance-to-mean ratio. However, immunity affected aggregation only in the absence of behavioural manipulation, and changing the size distribution of hosts did not appreciably affect aggregation. Using Taylor's Power Law to integrate field and laboratory data, we found that only treatments involving behavioural reductions achieved aggregation levels comparable to natural host populations. Thus, despite their short duration, our treatments generated heterogeneity in

  3. Well-being and immune response: a multi-system perspective.

    PubMed

    Lasselin, Julie; Alvarez-Salas, Elena; Grigoleit, Jan-Sebastian

    2016-08-01

    Whereas it is well-established that inflammation and other immune responses can change how we feel, most people are still surprised to hear that, conversely, well-being and its violations also affect our immune system. Here we show that those effects are highly adaptive and bear potential for both research and therapeutic applications. The studies discussed in this review demonstrate that immunity is tuned by ones emotions, personality, and social status as well as by other life style variables like sleep, nutrition, obesity, or exercise. We further provide a short excursion on the effects of stress and depression on immunity and discuss acute experimental endotoxemia as a model to study the effects of well-being on the innate immune response in humans.

  4. 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.

  5. Immunizations

    MedlinePlus

    ... Get Weight Loss Surgery? A Week of Healthy Breakfasts Shyness Immunizations KidsHealth > For Teens > Immunizations Print A A A What's in this article? Why Are Vaccinations Important? Why Do I Need Shots? Which Vaccinations Do ...

  6. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine

    PubMed Central

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-01-01

    Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways. PMID:23453730

  7. Probiotics and colostrum/milk differentially affect neonatal humoral immune responses to oral rotavirus vaccine.

    PubMed

    Chattha, Kuldeep S; Vlasova, Anastasia N; Kandasamy, Sukumar; Esseili, Malak A; Siegismund, Christine; Rajashekara, Gireesh; Saif, Linda J

    2013-04-08

    Breast milk (colostrum [col]/milk) components and gut commensals play important roles in neonatal immune maturation, establishment of gut homeostasis and immune responses to enteric pathogens and oral vaccines. We investigated the impact of colonization by probiotics, Lactobacillus rhamnosus GG (LGG) and Bifidobacterium lactis Bb12 (Bb12) with/without col/milk (mimicking breast/formula fed infants) on B lymphocyte responses to an attenuated (Att) human rotavirus (HRV) Wa strain vaccine in a neonatal gnotobiotic pig model. Col/milk did not affect probiotic colonization in AttHRV vaccinated pigs. However, unvaccinated pigs fed col/milk shed higher numbers of probiotic bacteria in feces than non-col/milk fed colonized controls. In AttHRV vaccinated pigs, col/milk feeding with probiotic treatment resulted in higher mean serum IgA HRV antibody titers and intestinal IgA antibody secreting cell (ASC) numbers compared to col/milk fed, non-colonized vaccinated pigs. In vaccinated pigs without col/milk, probiotic colonization did not affect IgA HRV antibody titers, but serum IgG HRV antibody titers and gut IgG ASC numbers were lower, suggesting that certain probiotics differentially impact HRV vaccine responses. Our findings suggest that col/milk components (soluble mediators) affect initial probiotic colonization, and together, they modulate neonatal antibody responses to oral AttHRV vaccine in complex ways.

  8. Nociception and role of immune system in pain.

    PubMed

    Verma, Vivek; Sheikh, Zeeshan; Ahmed, Ahad S

    2015-09-01

    Both pain and inflammation are protective responses. However, these self-limiting conditions (with well-established negative feedback loops) become pathological if left uncontrolled. Both pain and inflammation can interact with each other in a multi-dimensional manner. These interactions are known to create an array of 'difficult to manage' pathologies. This review explains in detail the role of immune system and the related cells in peripheral sensitization and neurogenic inflammation. Various neuro-immune interactions are analyzed at peripheral, sensory and central nervous system levels. Innate immunity plays a critical role in central sensitization and in establishing acute pain as chronic condition. Moreover, inflammatory mediators also exhibit psychological effects, thus contributing towards the emotional elements associated with pain. However, there is also a considerable anti-inflammatory and analgesic role of immune system. This review also attempts to enlist various novel pharmacological approaches that exhibit their actions through modification of neuro-immune interface.

  9. The immune system and cancer evasion strategies: therapeutic concepts.

    PubMed

    Muenst, S; Läubli, H; Soysal, S D; Zippelius, A; Tzankov, A; Hoeller, S

    2016-06-01

    The complicated interplay between cancer and the host immune system has been studied for decades. New insights into the human immune system as well as the mechanisms by which tumours evade immune control have led to the new and innovative therapeutic strategies that are considered amongst the medical breakthroughs of the last few years. Here, we will review the current understanding of cancer immunology in general, including immune surveillance and immunoediting, with a detailed look at immune cells (T cells, B cells, natural killer cells, macrophages and dendritic cells), immune checkpoints and regulators, sialic acid-binding immunoglobulin-like lectins (Siglecs) and other mechanisms. We will also present examples of new immune therapies able to reverse immune evasion strategies of tumour cells. Finally, we will focus on therapies that are already used in daily oncological practice such as the blockade of immune checkpoints cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 (PD-1) in patients with metastatic melanoma or advanced lung cancer, or therapies currently being tested in clinical trials such as adoptive T-cell transfer.

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

    PubMed

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

    2014-01-01

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

  11. TANK-binding kinase-1 broadly affects oyster immune response to bacteria and viruses.

    PubMed

    Tang, Xueying; Huang, Baoyu; Zhang, Linlin; Li, Li; Zhang, Guofan

    2016-09-01

    As a benthic filter feeder of estuaries, the immune system of oysters provides one of the best models for studying the genetic and molecular basis of the innate immune pathway in marine invertebrates and examining the influence of environmental factors on the immune system. Here, the molecular function of molluscan TANK-binding kinase-1 (TBK1) (which we named CgTBK1) was studied in the Pacific oyster, Crassostrea gigas. Compared with known TBK1 proteins in other model organisms, CgTBK1 contains a conserved S-TKc domain and a coiled coil domain at the N- and C-terminals but lacks an important ubiquitin domain. Quantitative real-time PCR analysis revealed that the expression level of CgTBK1 was ubiquitous in all selected tissues, with highest expression in the gills. CgTBK1 expression was significantly upregulated in response to infections with Vibrio alginolyticus, ostreid herpesvirus 1 (OsHV-1 reference strain and μvar), and polyinosinic:polycytidylic acid sodium salt, suggesting its broad function in immune response. Subcellular localization showed the presence of CgTBK1 in the cytoplasm of HeLa cells, suggesting its potential function as the signal transducer between the receptor and transcription factor. We further demonstrated that CgTBK1 interacted with CgSTING in HEK293T cells, providing evidence that CgTBK1 could be activated by direct binding to CgSTING. In summary, we characterized the TBK1 gene in C. gigas and demonstrated its role in the innate immune response to pathogen infections.

  12. CNS Remyelination and the Innate Immune System

    PubMed Central

    McMurran, Christopher E.; Jones, Clare A.; Fitzgerald, Denise C.; Franklin, Robin J. M.

    2016-01-01

    A misguided inflammatory response is frequently implicated in myelin damage. Particularly prominent among myelin diseases, multiple sclerosis (MS) is an autoimmune condition, with immune–mediated damage central to its etiology. Nevertheless, a robust inflammatory response is also essential for the efficient regeneration of myelin sheaths after such injury. Here, we discuss the functions of inflammation that promote remyelination, and how these have been experimentally disentangled from the pathological facets of the immune response. We focus on the contributions that resident microglia and monocyte-derived macrophages make to remyelination and compare the roles of these two populations of innate immune cells. Finally, the current literature is framed in the context of developing therapies that manipulate the innate immune response to promote remyelination in clinical myelin disease. PMID:27200350

  13. Unbalanced Immune System: Immunodeficiencies and Autoimmunity

    PubMed Central

    Giardino, Giuliana; Gallo, Vera; Prencipe, Rosaria; Gaudino, Giovanni; Romano, Roberta; De Cataldis, Marco; Lorello, Paola; Palamaro, Loredana; Di Giacomo, Chiara; Capalbo, Donatella; Cirillo, Emilia; D’Assante, Roberta; Pignata, Claudio

    2016-01-01

    Increased risk of developing autoimmune manifestations has been identified in different primary immunodeficiencies (PIDs). In such conditions, autoimmunity and immune deficiency represent intertwined phenomena that reflect inadequate immune function. Autoimmunity in PIDs may be caused by different mechanisms, including defects of tolerance to self-antigens and persistent stimulation as a result of the inability to eradicate antigens. This general immune dysregulation leads to compensatory and exaggerated chronic inflammatory responses that lead to tissue damage and autoimmunity. Each PID may be characterized by distinct, peculiar autoimmune manifestations. Moreover, different pathogenetic mechanisms may underlie autoimmunity in PID. In this review, the main autoimmune manifestations observed in different PID, including humoral immunodeficiencies, combined immunodeficiencies, and syndromes with immunodeficiencies, are summarized. When possible, the pathogenetic mechanism underlying autoimmunity in a specific PID has been explained. PMID:27766253

  14. Systemic infection generates a local-like immune response of the bacteriome organ in insect symbiosis.

    PubMed

    Masson, Florent; Vallier, Agnès; Vigneron, Aurélien; Balmand, Séverine; Vincent-Monégat, Carole; Zaidman-Rémy, Anna; Heddi, Abdelaziz

    2015-01-01

    Endosymbiosis is common in insects thriving in nutritionally unbalanced habitats. The cereal weevil, Sitophilus oryzae, houses Sodalis pierantonius, a Gram-negative intracellular symbiotic bacterium (endosymbiont), within a dedicated organ called a bacteriome. Recent data have shown that the bacteriome expresses certain immune genes that result in local symbiont tolerance and control. Here, we address the question of whether and how the bacteriome responds to insect infections involving exogenous bacteria. We have established an infection model by challenging weevil larvae with the Gram-negative bacterium Dickeya dadantii. We showed that D. dadantii infects host tissues and triggers a systemic immune response. Gene transcript analysis indicated that the bacteriome is also immune responsive, but it expresses immune effector genes to a lesser extent than the systemic and intestinal responses. Most genes putatively involved in immune pathways remain weakly expressed in the bacteriome following D. dadantii infection. Moreover, quantitative PCR experiments showed that the endosymbiont load is not affected by insect infection or the resulting bacteriome immune activation. Thus, the contained immune effector gene expression in the bacteriome may prevent potentially harmful effects of the immune response on endosymbionts, whilst efficiently protecting them from bacterial intruders.

  15. The heterogeneous immune microenvironment in breast cancer is affected by hypoxia-related genes.

    PubMed

    Duechler, Markus; Peczek, Lukasz; Zuk, Karolina; Zalesna, Izabela; Jeziorski, Arkadiusz; Czyz, Malgorzata

    2014-02-01

    The immune system constitutes an important first-line defence against malignant transformation. However, cancer mediated immunosuppression inactivates the mechanisms of host immune surveillance. Cancer cells shut down anti-cancer immunity through direct cell-cell interactions with leukocytes and through soluble factors, establishing an immunosuppressive environment for unimpeded cancer growth. The composition of the immunosuppressive microenvironment in breast tumours is not well documented. To address this question, selected immunosuppressive factors were analyzed in tumour specimens from 33 breast cancer patients after surgery. The mRNA expression of selected genes was quantified in fresh tumour samples. Tumour infiltrating leukocytes were characterized by flow cytometry to identify regulatory T cells, myeloid derived suppressor cells, and type 2 macrophages. Statistical analysis revealed several interesting correlations between the studied parameters and clinical features. Overall, a surprisingly high degree of heterogeneity in the composition of the immunosuppressive environment was found across all breast cancer samples which adds to the complexity of this disease. The influence of the hypoxia inducible factors (HIFs) on the immune microenvironment was also addressed. The level of HIFs correlated with hormone receptor status and the expression of several immunosuppressive molecules. Targeting HIFs might not only sensitize breast tumours for radiation and chemotherapies but also interfere with cancer immunosuppression.

  16. Heavy oil fractions induce negative influences on mouse immune system.

    PubMed

    Nishimoto, Sogo; Kanda, Kota; Yamawaki, Manami; Okabe, Masaaki; Akiyama, Koichi; Kakinuma, Yoshimi; Sugahara, Takuya

    2009-10-01

    It is well known that heavy oil such as pollutant caused serious influences on the marine ecosystem. We may suffer from various disorders in our body via intake of marine foods polluted with heavy oil. However the influences of heavy oil on our immune system have not yet been clarified. Here we show the effects of heavy oil extracts, water-soluble fraction (WSF), methanol-soluble fraction (MSF) and ethanol-soluble fraction (ESF), on immunoglobulin production of mouse splenocytes. All extracts increased IgA productivity of splenocytes. In oral administration, shrinkage of the immune organs such as spleen or thymus was observed in only WSF-administrated mice at least during 7 days. The amount of IgG production level in splenocytes cultured medium and sera were reduced by each extract administration. A flowcytometry method, to monitor splenocytes of WSF-administrated mice, has been set up using double staining with B and T cell-specific surface antibody. The results from cell population analysis indicated that B cells, including plasma cells producing antibody were reduced. The decrease in IgG level in sera was caused by reduction of plasma cells in spleen. Hence, it is suggested that reduction of Ig production was affected by the chemical compounds contained in WSF possibly such as polycyclic aromatic hydrocarbons (PAHs) through the estrogen receptor expressed in lymphocytes.

  17. 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.

  18. Chronic stress and environmental enrichment as opposite factors affecting the immune response in Japanese quail (Coturnix coturnix japonica).

    PubMed

    Nazar, F N; Marin, R H

    2011-03-01

    Procedures in the commercial production of animals involve stressful situations which lessen the animal's welfare. This study on Japanese quail evaluated whether an environmental enrichment manipulation can affect avian immune responses and if combined with a chronic stressor exposure can help to counteract the negative effects of stress on the immune system. Potential gender effects were also considered. After hatch, half of the birds were housed in non-enriched boxes and half were housed in environmentally enriched boxes. From day 33 to 42 of age, all birds within half of the non-enriched and enriched boxes remained undisturbed while the other half were daily exposed to a 15 min restraint stressor (chronic stressor). The inflammatory response (lymphoproliferation after phytohemagglutinin-p), percentage of lymphocytes, heterophil/lymphocyte (H/L) ratio and primary antibody response against sheep red blood cells were assessed. The chronic stressor application and the enrichment procedure, respectively, either increased or reduced the four immunological parameters evaluated and always in opposite directions. Males consistently showed lower antibody titres than females and presented the highest H/L ratio in response to the stressor when reared in the non-enriched environment. The findings indicate that submitting these animals to an enriched environment can be effectively used to improve their immune response and to reduce the detrimental effects of a stressor exposure.

  19. [Defects in immune system response by our organisms].

    PubMed

    Español, Teresa

    2005-09-01

    When some of the mechanisms in our immune response system fail, this can be due to external problems such as infections or transplants or due to congenital errors, known as Primary Immunologic Deficiencies. Dr. Español briefly reviews the most important characteristics of our immune response system, and then continues with an analysis of the defects of this system, especially those defects which are classified as Primary Immunologic Deficiencies.

  20. A Systems Approach to Understand Antigen Presentation and the Immune Response.

    PubMed

    Dudek, Nadine L; Croft, Nathan P; Schittenhelm, Ralf B; Ramarathinam, Sri H; Purcell, Anthony W

    2016-01-01

    The mammalian immune system has evolved to respond to pathogenic, environmental, and cellular changes in order to maintain the health of the host. These responses include the comparatively primitive innate immune response, which represents a rapid and relatively nonspecific reaction to challenge by pathogens and the more complex cellular adaptive immune response. This adaptive response evolves with the pathogenic challenge, involves the cross talk of several cell types, and is highly specific to the pathogen due to the liberation of peptide antigens and their presentation on the surface of affected cells. Together these two forms of immunity provide a surveillance mechanism for the system-wide scrutiny of cellular function, environment, and health. As such the immune system is best understood at a systems biology level, and studies that combine gene expression, protein expression, and liberation of peptides for antigen presentation can be combined to provide a detailed understanding of immunity. This chapter details our experience in identifying peptide antigens and combining this information with more traditional proteomics approaches to understand the generation of immune responses on a holistic level.

  1. Autophagy as a Stress Response Pathway in the Immune System.

    PubMed

    Bhattacharya, Abhisek; Eissa, N Tony

    2015-01-01

    Macroautophagy, hereafter, referred to as autophagy, has long been regarded as a housekeeping pathway involved in intracellular degradation and energy recycling. These housekeeping and homeostatic functions are especially important during cellular stress, such as periods of nutrient deprivation. However, importance of autophagy extends far beyond its degradative functions. Recent evidence shows that autophagy plays an essential role in development, organization and functions of the immune system, and defects in autophagy lead to several diseases, including cancer and autoimmunity. In the immune system, autophagy is important in regulation of the innate and adaptive immune responses. This review focuses on the roles of autophagy in the adaptive immune system. We first introduce the autophagy pathway and provide a brief description of the major molecular players involved in autophagy. We then discuss the importance of autophagy as a stress integrator mechanism and provide relevant examples of this role of autophagy in adaptive immune cells. Then we proceed to describe how autophagy regulates development, activation and functions of different adaptive immune cells. In these contexts, we mention both degradative and non-degradative roles of autophagy, and illustrate their importance. We also discuss role of autophagy in antigen presenting cells, which play critical roles in the activation of adaptive immune cells. Further, we describe how autophagy regulates functions of different adaptive immune cells during infection, inflammation and autoimmunity.

  2. Recent developments in affective recommender systems

    NASA Astrophysics Data System (ADS)

    Katarya, Rahul; Verma, Om Prakash

    2016-11-01

    Recommender systems (RSs) are playing a significant role since 1990s as they provide relevant, personalized information to the users over the internet. Lots of work have been done in information filtering, utilization, and application related to RS. However, an important area recently draws our attention which is affective recommender system. Affective recommender system (ARS) is latest trending area of research, as publication in this domain are few and recently published. ARS is associated with human behaviour, human factors, mood, senses, emotions, facial expressions, body gesture and physiological with human-computer interaction (HCI). Due to this assortment and various interests, more explanation is required, as it is in premature phase and growing as compared to other fields. So we have done literature review (LR) in the affective recommender systems by doing classification, incorporate reputed articles published from the year 2003 to February 2016. We include articles which highlight, analyse, and perform a study on affective recommender systems. This article categorizes, synthesizes, and discusses the research and development in ARS. We have classified and managed ARS papers according to different perspectives: research gaps, nature, algorithm or method adopted, datasets, the platform on executed, types of information and evaluation techniques applied. The researchers and professionals will positively support this survey article for understanding the current position, research in affective recommender systems and will guide future trends, opportunity and research focus in ARS.

  3. Artificial immune system approach for air combat maneuvering

    NASA Astrophysics Data System (ADS)

    Kaneshige, John; Krishnakumar, Kalmanje

    2007-04-01

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

  4. Understanding the vertebrate immune system: insights from the reptilian perspective.

    PubMed

    Zimmerman, L M; Vogel, L A; Bowden, R M

    2010-03-01

    Reptiles are ectothermic amniotes, providing the key link between ectothermic anamniotic fishes and amphibians, and endothermic amniotic birds and mammals. A greater understanding of reptilian immunity will provide important insights into the evolutionary history of vertebrate immunity as well as the growing field of eco-immunology. Like mammals, reptile immunity is complex and involves innate, cell-mediated and humoral compartments but, overall, there is considerably less known about immune function in reptiles. We review the current literature on each branch of the reptilian immune system, placing this information in context to other vertebrates. Further, we identify key areas that are prime for research as well as areas that are lagging because of lack of reagents in non-model systems.

  5. Recognition of Streptococcus pneumoniae by the innate immune system.

    PubMed

    Koppe, Uwe; Suttorp, Norbert; Opitz, Bastian

    2012-04-01

    Streptococcus pneumoniae is both a frequent colonizer of the upper respiratory tract and a leading cause of life-threatening infections such as pneumonia, meningitis and sepsis. The innate immune system is critical for the control of colonization and for defence during invasive disease. Initially, pneumococci are recognized by different sensors of the innate immune system called pattern recognition receptors (PRRs), which control most subsequent host defence pathways. These PRRs include the transmembrane Toll-like receptors (TLRs) as well as the cytosolic NOD-like receptors (NLRs) and DNA sensors. Recognition of S. pneumoniae by members of these PRR families regulates the production of inflammatory mediators that orchestrate the following immune response of infected as well as neighbouring non-infected cells, stimulates the recruitment of immune cells such as neutrophils and macrophages, and shapes the adaptive immunity. This review summarizes the current knowledge of the function of different PRRs in S. pneumoniae infection.

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

    PubMed

    Proserpio, Valentina; Mahata, Bidesh

    2016-02-01

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

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

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terry

    2011-01-01

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

  8. Global control of hepatitis B virus: does treatment-induced antigenic change affect immunization?

    PubMed

    Clements, C John; Coghlan, Ben; Creati, Mick; Locarnini, Stephen; Tedder, Richard S; Torresi, Joseph

    2010-01-01

    Since its widespread introduction, the hepatitis B vaccine has become an essential part of infant immunization programmes globally. The vaccine has been particularly important for countries where the incidence of hepatitis B virus-related hepatocellular carcinoma is high. Effective treatment options for individuals with chronic hepatitis B infection were limited until 1998 when lamivudine, the first nucleoside analogue drug, was introduced. As a single treatment agent, however, lamivudine has a significant drawback: it induces lamivudine-resistant hepatitis B virus strains that may pose a risk to the global hepatitis B immunization programme. Mutations associated with drug treatment can cause changes to the surface antigen protein, the precise part of the virus that the hepatitis B vaccine mimics. However, the emergence of antiviral drug-associated potential vaccine escape mutants (ADAP-VEMs) in treated patients does not necessarily pose a significant, imminent threat to the global hepatitis B immunization programme. Nonetheless, there is already evidence that current treatment regimens have resulted in the selection of stable ADAP-VEMs. Treatment is currently intended to prevent the long-term complications of hepatitis B virus infection, with little consideration given to potential adverse public health impacts. To address individual and public health concerns, trials are urgently needed to find the optimal combination of existing drugs that are effective but do not induce the emergence of ADAP-VEMs. This paper examines the mechanism of antiviral drug-selected changes in the portion of the viral genome that also affects the surface antigen, and explores their potential impact on current hepatitis B immunization programmes.

  9. Document Retrieval Systems; Factors Affecting Search Time.

    ERIC Educational Resources Information Center

    Montgomery, K. Leon, Ed.

    An experiment was conducted to identify some of the important parameters affecting search time, a critical cost factor in retrieval systems. Using actual computer searches of Chemical Abstracts Condensate, a comparison was made between the effectiveness of linear and inverted filing systems. Since the results indicated that it was the type and…

  10. Modeling cancer evolution: evolutionary escape under immune system control

    NASA Astrophysics Data System (ADS)

    Korobeinikov, Andrei; Starkov, Konstantin E.; Valle, Paul A.

    2017-02-01

    It can be expected that adequate immune response should be able to annihilate cancer at a very early stage of its appearance. However, in some cases cancer is able to persist avoiding immune response. One can conject that cancer is able to avoid immune response control due to a succession of mutations leading to the development of immune-resistant cells. In order to illustrate this possibility, in this paper we present a 2n–dimensional mathematical model that describes interaction of n subtypes of tumor cells with corresponding genotype-specific immune response. The model postulates that there is a probability for tumor cells of each of n subtype to produce offsprings of other types. Each of the subtypes activates the genotype-specific immune response with a possibility of suppressing cancer cells of other genotypes (the cross-immunity). Numerical simulations show that if cancer cells are able to mutate comparatively fast and if immune response is not strong enough, then, despite immune system pressure, cancer is able to persist.

  11. Frank A. Beach award: programming of neuroendocrine function by early-life experience: a critical role for the immune system.

    PubMed

    Bilbo, Staci D

    2013-05-01

    Many neuropsychiatric disorders are associated with a strong dysregulation of the immune system, and several have a striking etiology in development as well. Our recent evidence using a rodent model of neonatal Escherichia coli infection has revealed novel insight into the mechanisms underlying cognitive deficits in adulthood, and suggests that the early-life immune history of an individual may be critical to understanding the relative risk of developing later-life mental health disorders in humans. A single neonatal infection programs the function of immune cells within the brain, called microglia, for the life of the rodent such that an adult immune challenge results in exaggerated cytokine production within the brain and associated cognitive deficits. I describe the important role of the immune system, notably microglia, during brain development, and discuss some of the many ways in which immune activation during early brain development can affect the later-life outcomes of neural function, immune function, and cognition.

  12. Ageing and the immune system: focus on macrophages

    PubMed Central

    Linehan, E.

    2015-01-01

    A fully functioning immune system is essential in order to maintain good health. However, the immune system deteriorates with advancing age, and this contributes to increased susceptibility to infection, autoimmunity, and cancer in the older population. Progress has been made in identifying age-related defects in the adaptive immune system. In contrast, relatively little research has been carried out on the impact of ageing on the innate immune response. This area requires further research as the innate immune system plays a crucial role in protection against infection and represents a first line of defence. Macrophages are central effector cells of the innate immune system and have many diverse functions. As a result, age-related impairments in macrophage function are likely to have important consequences for the health of the older population. It has been reported that ageing in macrophages impacts on many processes including toll-like receptor signalling, polarisation, phagocytosis, and wound repair. A detailed understanding of the impact of ageing on macrophages is required in order to develop therapeutics that will boost immune responses in the older population. PMID:25883791

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

    PubMed

    Linehan, E; Fitzgerald, D C

    2015-03-01

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

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

    PubMed

    Kradin, R L

    1995-01-01

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

  15. 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.

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

    PubMed

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

    2013-09-01

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

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

    PubMed

    Kiyono, Hiroshi; Azegami, Tatsuhiko

    2015-01-01

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

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

    PubMed Central

    KIYONO, Hiroshi; AZEGAMI, Tatsuhiko

    2015-01-01

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

  19. ALLERGIC ASTHMA AND THE DEVELOPING IMMUNE SYSTEM: A PILOT STUDY

    EPA Science Inventory

    Rationale: The predisposition towards atopic disease begins early in life, and that the risk of developing asthma is heightened following prenatal exposure to some compounds. Nonetheless, the effect of gestational aeroallergen exposure on the developing immune system is unclear....

  20. ISS Update: Space Flight and the Immune System

    NASA Video Gallery

    NASA Public Affairs Officer Kelly Humphries interviews Brian Crucian, NASA immunologist, about the issues with space flight and the immune system. Questions? Ask us on Twitter @NASA_Johnson and inc...

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

    PubMed

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

    2017-04-01

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

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

    PubMed Central

    Imeri, Luca; Opp, Mark R.

    2010-01-01

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

  3. Active immunization against leptin fails to affect reproduction and exerts only marginal effects on glucose metabolism in young female goats.

    PubMed

    Sauerwein, H; Heintges, U; Bruhns, S C; Hennies, M; Gertler, A

    2006-08-01

    Approximately 150 days before expected breeding time, 12 female goats (3 months of age) were actively immunized against ovine leptin. Booster injections were given throughout the following year. Control animals (n = 6) were sham-immunized. After the first observed oestrus, a buck was introduced and goats were mated. Blood samples were collected twice weekly and frequent blood sampling series were performed on days -15, 76, 153 and 286 relative to the first immunization. Nine of the immunized goats developed titres within 3 months and had elevated serum concentrations of leptin compared with controls (p < 0.0001). Hematological parameters and blood chemistry were not affected by the immunization. No differences were detectable in all reproductive parameters recorded. Serum insulin was higher in immunized goats during the frequent blood sampling series of day 287 after the first immunization. Glucose metabolism was investigated during pregnancy using hyperglycaemic and euglycaemic/hyperinsulinaemic clamps. None of the parameters derived from the clamp studies was different (p > 0.05) between the two groups. During the hyperglycaemic clamp there was a trend (p < 0.15) towards increased insulin concentrations in immunized animals whereas glucose infusion rates were not different between the groups. This indicates decreased insulin sensitivity in immunized goats. Our study describes the ontogenesis of serum concentrations of leptin during growth, puberty and first pregnancy and parturition for the caprine species. The effects of the immunization were not detectable or only marginal and the approach aimed at therefore not effective to investigate leptin action in detail.

  4. Prenatal fluoxetine exposure affects cytokine and behavioral response to an immune challenge.

    PubMed

    Avitsur, Ronit; Levy, Sigal; Grinshpahet, Rachel; Goren, Naama; Hirsh, Ofer; Zalko, Assaf

    2015-07-15

    Fluoxetine (FLX), a selective serotonin reuptake inhibitor (SSRI) is a commonly prescribed antidepressant drug in pregnant women. FLX readily crosses the placenta, consequently altering serotonergic neurotransmission in the fetus and causing physiological and behavioral disturbances in the newborn. Studies have shown that serotonin plays a role in modulating immune signaling. Thus, the goal of this study was to assess the effects of prenatal exposure to FLX on the response to an immune challenge in offspring mice. Male and female mice were prenatally exposed to FLX and later injected with lipopolysaccharide (LPS) at different stages of development. Results indicated that prenatal FLX modulated aspects of the response to the endotoxin challenge. Prenatal FLX diminished the secretion of interleukin (IL)-6 in adult male and female mice. Prenatal exposure to FLX further suppressed TNFα and augmented IL-1β secretion in adult males. Early effects of LPS (within 24h of administration) on body weight and food consumption were diminished by prenatal exposure to FLX in adult mice. Delayed effects of LPS (within 60h of administration) were modulated by prenatal FLX in young animals. These results provide an indication that prenatal modulations of the serotonergic system had lasting implications for host response to an immune challenge. These findings may contribute to the understanding of the effects of prenatal environment on the development of physiological systems that are important to coping with infectious challenges, and assist in understanding the limitations and precautions that should be taken in the use of SSRIs during pregnancy.

  5. Human immune system mice immunized with Plasmodium falciparum circumsporozoite protein induce protective human humoral immunity against malaria.

    PubMed

    Huang, Jing; Li, Xiangming; Coelho-dos-Reis, Jordana G A; Zhang, Min; Mitchell, Robert; Nogueira, Raquel Tayar; Tsao, Tiffany; Noe, Amy R; Ayala, Ramses; Sahi, Vincent; Gutierrez, Gabriel M; Nussenzweig, Victor; Wilson, James M; Nardin, Elizabeth H; Nussenzweig, Ruth S; Tsuji, Moriya

    2015-12-01

    In this study, we developed human immune system (HIS) mice that possess functional human CD4+ T cells and B cells, named HIS-CD4/B mice. HIS-CD4/B mice were generated by first introducing HLA class II genes, including DR1 and DR4, along with genes encoding various human cytokines and human B cell activation factor (BAFF) to NSG mice by adeno-associated virus serotype 9 (AAV9) vectors, followed by engrafting human hematopoietic stem cells (HSCs). HIS-CD4/B mice, in which the reconstitution of human CD4+ T and B cells resembles to that of humans, produced a significant level of human IgG against Plasmodium falciparum circumsporozoite (PfCS) protein upon immunization. CD4+ T cells in HIS-CD4/B mice, which possess central and effector memory phenotypes like those in humans, are functional, since PfCS protein-specific human CD4+ T cells secreting IFN-γ and IL-2 were detected in immunized HIS-CD4/B mice. Lastly, PfCS protein-immunized HIS-CD4/B mice were protected from in vivo challenge with transgenic P. berghei sporozoites expressing the PfCS protein. The immune sera collected from protected HIS-CD4/B mice reacted against transgenic P. berghei sporozoites expressing the PfCS protein and also inhibited the parasite invasion into hepatocytes in vitro. Taken together, these studies show that our HIS-CD4/B mice could mount protective human anti-malaria immunity, consisting of human IgG and human CD4+ T cell responses both specific for a human malaria antigen.

  6. Roles of Zinc Signaling in the Immune System.

    PubMed

    Hojyo, Shintaro; Fukada, Toshiyuki

    2016-01-01

    Zinc (Zn) is an essential micronutrient for basic cell activities such as cell growth, differentiation, and survival. Zn deficiency depresses both innate and adaptive immune responses. However, the precise physiological mechanisms of the Zn-mediated regulation of the immune system have been largely unclear. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the transport, distribution, and storage of Zn. There is growing evidence that Zn behaves like a signaling molecule, facilitating the transduction of a variety of signaling cascades in response to extracellular stimuli. In this review, we highlight the emerging functional roles of Zn and Zn transporters in immunity, focusing on how crosstalk between Zn and immune-related signaling guides the normal development and function of immune cells.

  7. Roles of Zinc Signaling in the Immune System

    PubMed Central

    2016-01-01

    Zinc (Zn) is an essential micronutrient for basic cell activities such as cell growth, differentiation, and survival. Zn deficiency depresses both innate and adaptive immune responses. However, the precise physiological mechanisms of the Zn-mediated regulation of the immune system have been largely unclear. Zn homeostasis is tightly controlled by the coordinated activity of Zn transporters and metallothioneins, which regulate the transport, distribution, and storage of Zn. There is growing evidence that Zn behaves like a signaling molecule, facilitating the transduction of a variety of signaling cascades in response to extracellular stimuli. In this review, we highlight the emerging functional roles of Zn and Zn transporters in immunity, focusing on how crosstalk between Zn and immune-related signaling guides the normal development and function of immune cells. PMID:27872866

  8. 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.

  9. Childhood infections, the developing immune system, and the origins of asthma.

    PubMed

    Openshaw, Peter J M; Yamaguchi, Yuko; Tregoning, John S

    2004-12-01

    Asthma is an immune-mediated inflammatory condition characterized by increased responsiveness to bronchoconstrictive stimuli. Viruses have been shown to play an important role in asthma, with viral infection being present during about 85% of exacerbations. However, the role they play in the onset of asthma is more controversial. Some respiratory viral infections might be protective, but there is a strong association between respiratory syncytial virus-induced bronchiolitis in infancy and recurrent wheeze up to 12 years of age. Both the respiratory tract and the immune system undergo rapid maturation during the first year of life, and it seems that postnatal development is affected by and affects responses to viral infections. Understanding postnatal developmental changes in the immune system might help to explain the origins and pathogenesis of asthma and thus the effectiveness or ineffectiveness of specific asthma therapies.

  10. 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

  11. The immune system in human milk and the developing infant.

    PubMed

    Goldman, Armond S

    2007-12-01

    The concept of the immune system in human milk emerged in the 1970s from clinical and laboratory observations made between the late 18th through the mid-20th centuries. The discovery of living leukocytes in human milk in 1970 was the final link to the chain of evidence that culminated in the concept. The concept was later expanded to include not only antimicrobial but also anti-inflammatory and immunoregulatory agents. These agents evolved to compensate for developmental delays in the immune system during infancy. Indeed, that explains the defense by human milk against common infectious diseases in infancy, necrotizing enterocolitis in preterm infants, and immune-mediated disorders such as Crohn's disease in later childhood. These diverse evolutionary outcomes underscore the superiority of human milk for the nutrition of human infants. Finally, other components of the immune system in human milk and their fate and functions in the developing infant may well be discovered in the near future.

  12. The Mucosal Immune System and Its Regulation by Autophagy

    PubMed Central

    Kabat, Agnieszka M.; Pott, Johanna; Maloy, Kevin J.

    2016-01-01

    The gastrointestinal tract presents a unique challenge to the mucosal immune system, which has to constantly monitor the vast surface for the presence of pathogens, while at the same time maintaining tolerance to beneficial or innocuous antigens. In the intestinal mucosa, specialized innate and adaptive immune components participate in directing appropriate immune responses toward these diverse challenges. Recent studies provide compelling evidence that the process of autophagy influences several aspects of mucosal immune responses. Initially described as a “self-eating” survival pathway that enables nutrient recycling during starvation, autophagy has now been connected to multiple cellular responses, including several aspects of immunity. Initial links between autophagy and host immunity came from the observations that autophagy can target intracellular bacteria for degradation. However, subsequent studies indicated that autophagy plays a much broader role in immune responses, as it can impact antigen processing, thymic selection, lymphocyte homeostasis, and the regulation of immunoglobulin and cytokine secretion. In this review, we provide a comprehensive overview of mucosal immune cells and discuss how autophagy influences many aspects of their physiology and function. We focus on cell type-specific roles of autophagy in the gut, with a particular emphasis on the effects of autophagy on the intestinal T cell compartment. We also provide a perspective on how manipulation of autophagy may potentially be used to treat mucosal inflammatory disorders. PMID:27446072

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

    PubMed Central

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

    2016-01-01

    Immunization information systems (IIS) are population-based and confidential computerized systems maintained by public health agencies containing individual data on immunizations from participating health care providers. IIS hold comprehensive vaccination histories given across providers and over time. An important aspect to IIS is the clinical decision support for immunizations (CDSi), consisting of vaccine forecasting algorithms to determine needed immunizations. The study objective was to analyze the CDSi presentation by IIS in Minnesota (Minnesota Immunization Information Connection [MIIC]) through direct access by IIS interface and by access through electronic health records (EHRs) to outline similarities and differences. The immunization data presented were similar across the three systems examined, but with varying ability to integrate data across MIIC and EHR, which impacts immunization data reconciliation. Study findings will lead to better understanding of immunization data display, clinical decision support, and user functionalities with the ultimate goal of promoting IIS CDSi to improve vaccination rates. PMID:28050128

  14. Dietary vitamin C and its derivatives affect immune responses in grass shrimp, Penaeus monodon.

    PubMed

    Lee, Min Hsien; Shiau, Shi Yen

    2002-02-01

    Effects of L-ascorbic acid (AA) and its four derivatives, namely L-ascorbyl-2-sulfate (C2S), L-ascorbyl-2-polyphosphate (C2PP), L-ascorbyl-2-monophosphate-Na (C2MP-Na) and L-ascorbyl-2-monophosphate-Mg (C2MP-Mg) on the immune responses of juvenile grass shrimp, Penaeus monodon, were studied. The vitamin C deprived diet together with diets supplemented with either adequate or high (five times adequate) levels of AA, C2S, C2PP, C2MP-Na and C2MP-Mg were each fed to triplicate groups of shrimp (mean initial weight: 0.37 +/- 0.01 g) for 8 weeks. Significantly (P<0.01) higher weight gain (WG), feed efficiency (FE), survival, total haemocyte count (THC), superoxide anion (O2) production ratio and phenoloxidase (PO) activity were observed in shrimp fed diets supplemented with adequate and high levels of ascorbate than shrimp fed the vitamin C deprived diet, regardless of the ascorbate source. Among the ascorbate sources, shrimp fed C2MP-Mg and C2PP containing diets had higher THC than shrimp fed AA, C2S and C2MP-Na containing diets, regardless of the supplementation level. Shrimp fed adequate levels of C2MP-Mg and C2PP and high levels of C2MP-Mg containing diets had higher O2 production ratios than shrimp fed AA and C2S containing diets. Shrimp fed adequate levels of C2MP-Mg and C2PP and high levels of C2PP containing diets had higher PO activity than shrimp fed AA, C2S and C2MP-Na containing diets. These data suggest that dietary ascorbate enhances immune responses in P. monodon and different ascorbate sources may affect the immune responses differently.

  15. Therapeutic electric stimulation does not affect immune status in healthy individuals – a preliminary report

    PubMed Central

    2012-01-01

    Background Neuromuscular electric stimulation is widely used for muscle strengthening in clinical practice and for preventative purposes. However, there are few reports on the effects of electric stimulation on the immune response of the organism, and even those mainly describe the changes observed immediately after the electrotherapeutic procedures. The objective of our study was to examine the possible immunological consequences of moderate low-frequency transcutaneous neuromuscular electric stimulation for quadriceps muscle strengthening in healthy individuals. Methods The study included 10 healthy volunteers (5 males, 5 females, mean age 37.5 years). At the beginning and after a two-week electric stimulation program, muscle strength was measured and peripheral blood was collected to analyse white blood cells by flow cytometry for the expression of cell surface antigens (CD3, CD19, CD4, CD8, CD4/8, DR/3, NK, Th reg, CD25 + CD3+, CD25 + CD4+, CD25 + CD8+, CD69 + CD3+, CD69 + CD4+, CD69 + CD8+) and phagocytosis/oxidative killing function. Results Muscle strength slightly increased after the program on the dominant and the nondominant side. No statistically or clinically significant difference was found in any of the measured blood and immune cells parameters as well as phagocytosis and oxidative burst function of neutrophil granulocytes and monocytes one day after the program. Conclusions The program of transcutaneous low-frequency electric stimulation slightly strengthened the quadriceps femoris muscle while producing no changes in measured immunological parameters. Hence, therapeutic low-frequency electric stimulation appears not to be affecting the immune response of healthy persons. PMID:22839574

  16. Modeling Systems-Level Regulation of Host Immune Responses

    PubMed Central

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

    2007-01-01

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

  17. Melanoma: oncogenic drivers and the immune system

    PubMed Central

    Karachaliou, Niki; Pilotto, Sara; Teixidó, Cristina; Viteri, Santiago; González-Cao, María; Riso, Aldo; Morales-Espinosa, Daniela; Molina, Miguel Angel; Chaib, Imane; Santarpia, Mariacarmela; Richardet, Eduardo; Bria, Emilio

    2015-01-01

    Advances and in-depth understanding of the biology of melanoma over the past 30 years have contributed to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. The finding that oncogenic BRAF mutations drive tumor growth in up to 50% of melanomas led to a molecular therapy revolution for unresectable and metastatic disease. Moving beyond BRAF, inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided targets for cancer immunotherapy. In this review, we discuss the molecular biology of melanoma and we focus on the recent advances of molecularly targeted and immunotherapeutic approaches. PMID:26605311

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

    PubMed Central

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

    2005-01-01

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

  19. 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

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

    PubMed

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

    2005-06-01

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

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

    PubMed

    Barrangou, Rodolphe; Marraffini, Luciano A

    2014-04-24

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

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

    NASA Technical Reports Server (NTRS)

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

    2005-01-01

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

  3. Comparative and Developmental Study of the Immune System in Xenopus

    PubMed Central

    Robert, Jacques; Ohta, Yuko

    2010-01-01

    Xenopus laevis is the model of choice for evolutionary, comparative, and developmental studies of immunity, and invaluable research tools including MHC-defined clones, inbred strains, cell lines, and monoclonal antibodies are available for these studies. Recent efforts to use Silurana (Xenopus) tropicalis for genetic analyses have led to the sequencing of the whole genome. Ongoing genome mapping and mutagenesis studies will provide a new dimension to the study of immunity. Here we review what is known about the immune system of X. laevis integrated with available genomic information from S. tropicalis. This review provides compelling evidence for the high degree of similarity and evolutionary conservation between Xenopus and mammalian immune systems. We propose to build a powerful and innovative comparative biomedical model based on modern genetic technologies that takes take advantage of X. laevis and S. tropicalis, as well as the whole Xenopus genus. PMID:19253402

  4. Conditioned effects of ethanol on the immune system.

    PubMed

    Gano, Anny; Pautassi, Ricardo Marcos; Doremus-Fitzwater, Tamara L; Deak, Terrence

    2017-04-01

    Several studies indicate that the immune system can be subjected to classical conditioning. Acute ethanol intoxication significantly modulates several pro-inflammatory cytokines (e.g. interleukins-1 and 6 [IL-1β and IL-6, respectively] and tumor necrosis factor alpha [TNFα])) in several brain areas, including amygdala (AMG), paraventricular nucleus (PVN), and hippocampus (HPC). It is unknown, however, whether cues associated with ethanol can elicit conditioned alterations in cytokine expression. The present study analyzed, in male Sprague-Dawley rats, whether ethanol-induced changes in the central cytokine response may be amenable to conditioning. In Experiments 1 and 2, the rats were given one or two pairings between a distinctive odor (conditional stimulus, CS) and the post-absorptive effects of a high (3.0 or 4.0 g/kg, Experiments 1 and 2, respectively) ethanol dose. Neither of these experiments revealed conditioning of IL-6, IL-1β, or TNFα, as measured via mRNA levels. Yet, re-exposure to the lemon-odor CS in Experiment 1 significantly increased C-Fos levels in the PVN. In Experiment 3, the rats were given four pairings between an odor CS and a moderate ethanol dose (2.0 g/kg), delivered intraperitoneally (i.p.) or intragastrically (i.g.). Re-exposure to the odor CS significantly increased IL-6 levels in HPC and AMG, an effect only evident in paired rats administered ethanol i.p. Overall, this study suggests that ethanol exposure can regulate the levels of IL-6 at HPC and AMG via classical conditioning mechanisms. These ethanol-induced, conditioned alterations in cytokine levels may ultimately affect the intake and motivational effects of ethanol. Impact statement This study examines, across three experiments, whether odor cues associated with ethanol exposure can condition changes in cytokine expression. The analysis of ethanol-induced conditioning of immune responses is a novel niche that can help understand the transition from social drinking to

  5. Effects of gastrointestinal nematode infection on the ruminant immune system.

    PubMed

    Gasbarre, L C

    1997-11-01

    Gastrointestinal (GI) nematodes of ruminants evoke a wide variety of immune responses in their hosts. In terms of specific immune responses directed against parasite antigens, the resulting immune responses may vary from those that give strong protection from reinfection after a relatively light exposure (e.g. Oesophagostomum radiatum) to responses that are very weak and delayed in their onset (e.g. Ostertagia ostertagi). The nature of these protective immune responses has been covered in another section of the workshop and the purpose of this section will be to explore the nature of changes that occur in the immune system of infected animals and to discuss the effect of GI nematode infections upon the overall immunoresponsiveness of the host. The discussion will focus primarily on Ostertagia ostertagi because this parasite has received the most attention in published studies. The interaction of Ostertagia and the host immune system presents what appears to be an interesting contradiction. Protective immunity directed against the parasite is slow to arise and when compared to some of the other GI nematodes, is relatively weak. Although responses that reduce egg output in the feces or increase the number of larvae undergoing inhibition may occur after a relatively brief exposure (3-4 months), immune responses which reduce the number of parasites that can establish in the host are not evident until the animal's second year. Additionally, even older animals that have spent several seasons on infected pastures will have low numbers of Ostertagia in their abomasa, indicating that sterilizing immune responses against the parasite are uncommon. In spite of this apparent lack of specific protective immune responses, infections with Ostertagia induce profound changes in the host immune system. These changes include a tremendous expansion of both the number of lymphocytes in the local lymph nodes and the number of lymphoid cells in the mucosa of the abomasum. This expansion

  6. In situ CUTANEOUS CELLULAR IMMUNE RESPONSE IN DOGS NATURALLY AFFECTED BY VISCERAL LEISHMANIASIS

    PubMed Central

    ROSSI, Claudio Nazaretian; TOMOKANE, Thaise Yumie; BATISTA, Luis Fábio da Silva; MARCONDES, Mary; LARSSON, Carlos Eduardo; LAURENTI, Márcia Dalastra

    2016-01-01

    SUMMARY Thirty-eight dogs naturally affected by visceral leishmaniasis were recruited in Araçatuba, São Paulo State, Brazil - an endemic area for visceral leishmaniasis. The animals were distributed into one of two groups, according to their clinical and laboratory features, as either symptomatic or asymptomatic dogs. Correlations between clinical features and inflammatory patterns, cellular immune responses, and parasitism in the macroscopically uninjured skin of the ear were investigated. Histological skin patterns were similar in both groups, and were generally characterized by a mild to intense inflammatory infiltrate in the dermis, mainly consisting of mononuclear cells. There was no difference in the number of parasites in the skin (amastigotes/mm²) between the two groups. Concerning the characterization of the cellular immune response, the number of positive inducible nitric oxide synthase (iNOS+) cells was higher in the dermis of symptomatic than in asymptomatic dogs (p = 0.0368). A positive correlation between parasite density and macrophages density (p = 0.031), CD4+ T-cells (p = 0.015), and CD8+ T-cells (p = 0.023) was observed. Furthermore, a positive correlation between density of iNOS+ cells and CD3+ T-cells (p = 0.005), CD4+ T-cells (p = 0.001), and CD8+ T-cells (p = 0.0001) was also found. The results showed the existence of a non-specific chronic inflammatory infiltrate in the dermis of dogs affected by visceral leishmaniasis, characterized by the presence of activated macrophages and T-lymphocytes, associated to cutaneous parasitism, independent of clinical status. PMID:27410908

  7. Trace elements, anxiety and immune parameters in patients affected by cancer.

    PubMed

    Bargellini, Annalisa; Piccinini, Lino; De Palma, Marisa; Giacobazzi, Pierluigi; Scaltriti, Stefania; Mariano, Maria; Roncaglia, Roberto; Borella, Paola

    2003-01-01

    The aim of this case-control study was to investigate the relationship between trace elements, immune parameters, and human cancer, taking into account some personality traits, such as anxiety, implicated in the modulation of both immune responses and pathology. Thirty patients affected by the most frequent cancer types were recruited at the onset of disease together with 30 healthy controls. Se, Zn and Cu were measured in plasma together with glutathione peroxidase (GSH-Px) activity, and lipid peroxidation (thiobarbituric acid-reactive substances--TBARS). Furthermore, Zn and GSH-Px activity were measured in red blood cells. A complete blood profile with the main lymphocytes subsets was obtained and the State-Trait Anxiety Inventory was applied to evaluate anxiety. The only differences found between trace element levels in cases and controls were significantly higher erythrocyte Zn in cancer patients and higher plasma Cu levels in male patients. In addition, subjects affected by cancer exhibited a significant reduction in TBARS levels, were more anxious, had lower total B cells percentage and T helper/T suppressor ratio, and had a higher percentage of natural killer cells. Interestingly, in patients only, GSH-Px in plasma was positively related to trait anxiety scores (p < 0.02) and Cu to state anxiety scores (p < 0.05). In conclusion, we could not confirm the existence of trace element deficiency in relation to cancer and no links between trace element levels and lymphocyte subsets were documented. However, interesting associations between state anxiety and Cu, and between trait anxiety and GSH-Px were observed thus deserving further investigations.

  8. Regulation of the Immune System by Hypothalamic Releasing Hormones.

    DTIC Science & Technology

    1986-07-14

    mechanisms of lymphokine induction. @• Depletion of macrophages from human peripheral blood mononuclear cells (PBMC) caused a marked decrease in...Harbour- McMenamin , D.V., E.M. Smith and J.E. Blalock. 1985. Endotoxin induction of leukocyte-derived proopiomelanocortin related peptides. Infect. immun...48:813-817. 3. Blalock, J.E., D.V. McMenamin , and E.M. Smith. 1985. Peptide hormones shared by the neuroendocrine and immune systems. J Immunol. 135

  9. Localization and Glassy Dynamics in the Immune System

    NASA Astrophysics Data System (ADS)

    Sun, Jun; Earl, David J.; Deem, Michael W.

    We discuss use of the generalized NK model to examine evolutionary dynamics within the immune system. We describe how randomness and diversity play key roles in the immune response and how their effects are captured by this hierarchical spin glass model. We discuss analytical aspects of the model as well as practical applications to design of the annual influenza vaccine. We discuss the subtle role that the glassy evolutionary dynamics plays in suppressing autoimmune disease.

  10. The Immune System of HIV-Exposed Uninfected Infants

    PubMed Central

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

    2016-01-01

    Infants born to human immunodeficiency virus (HIV) infected women are HIV-exposed but the majority remains uninfected [i.e., HIV-exposed uninfected (HEU)]. HEU infants suffer greater morbidity and mortality from infections compared to HIV-unexposed (HU) peers. The reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. This review comprehensively summarizes the current literature investigating the adaptive and innate immune system of HEU infants. HEU infants have altered cell-mediated immunity, including impaired T-cell maturation with documented hypo- as well as hyper-responsiveness to T-cell activation. And although prevaccination vaccine-specific antibody levels are often lower in HEU than HU, most HEU infants mount adequate humoral immune response following primary vaccination with diphtheria toxoid, haemophilus influenzae type b, whole cell pertussis, measles, hepatitis B, tetanus toxoid, and pneumococcal conjugate vaccines. However, HEU infants are often found to have lower absolute neutrophil counts as compared to HU infants. On the other hand, an increase of innate immune cytokine production and expression of co-stimulatory markers has been noted in HEU infants, but this increase appears to be restricted to the first few weeks of life. The immune system of HEU children beyond infancy remains largely unexplored. PMID:27733852

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

    PubMed

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

    2016-01-01

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

  12. 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

  13. The role of the neuroendocrine and immune systems in the pathogenesis of depression.

    PubMed

    Ogłodek, Ewa; Szota, Anna; Just, Marek; Moś, Danuta; Araszkiewicz, Aleksander

    2014-10-01

    Development of depression is associated with the body's response to prolonged stress, which adversely affects the functioning of the nervous, endocrine and immune systems. Prolonged stress can lead to the development of a so-called allostatic load and reduction of concentration of brain-derived neurotrophic factor. These changes result in impairment of neurogenesis and synaptic remodeling process. This article illustrates the involvement of key mediators of allostasis such as the neuroendocrine and immune systems, in the pathogenesis of depression. The literature concerning the contribution of the neuroendocrine and immune systems to depression incidence was reviewed. Development of depression is associated with disturbance of the body's allostasis and inflammatory activation of the immune system. It leads to a chronic increase in the concentration of cortisol and proinflammatory cytokines, which results in an allostatic load. This load leads to neurodegeneration, eventually causing irreversible cognitive impairment and permanent disability. Determination of the concentration of chemokines and their receptors is an important indicator of activation of the immune and neuroendocrine systems. The activity of these systems reflects the severity of the disease and provides important information for effective antidepressant treatment.

  14. The unresponsiveness of the immune system of the rat to hypergravity

    NASA Technical Reports Server (NTRS)

    Scibetta, S. M.; Caren, L. D.; Oyama, J.

    1984-01-01

    The immune response in rats exposed to simulated hypergravity (2.1 G and 3.1 G) by chronic centrifugation was assessed. Rats were immunized with sheep red blood cells (SRBC), either on the day of initial exposure to hypergravity (hyper-G), or after being centrifuged for 28 d and remaining on the centrifuge thereafter. Pair-fed and ad libitum fed noncentrifuged controls were used. Although there were some alterations in leukocyte counts, hyper-G did not systematically affect the primary or secondary anti-SRBC response, hematocrits, or the sizes of the liver, spleen, kidneys, thymus, or adrenal glands. The immune system is thus remarkably homeostatic under hypergravity conditions which do affect other physiologic parameters.

  15. Immune responses induced by oligogalacturonides are differentially affected by AvrPto and loss of BAK1/BKK1 and PEPR1/PEPR2.

    PubMed

    Gravino, Matteo; Locci, Federica; Tundo, Silvio; Cervone, Felice; Savatin, Daniel Valentin; De Lorenzo, Giulia

    2016-04-26

    Plants possess an innate immune system capable of restricting invasion by most potential pathogens. At the cell surface, the recognition of microbe-associated molecular patterns (MAMPs) and/or damage-associated molecular patterns (DAMPs) by pattern recognition receptors (PRRs) represents the first event for the prompt mounting of an effective immune response. Pathogens have evolved effectors that block MAMP-triggered immunity. The Pseudomonas syringae effector AvrPto abolishes immunity triggered by the peptide MAMPs flg22 and elf18, derived from the bacterial flagellin and elongation factor Tu, respectively, by inhibiting the kinase function of the corresponding receptors FLS2 and EFR, as well as their co-receptors BAK1 and BKK1. Oligogalacturonides (OGs), a well-known class of DAMPs, are oligomers of α-1,4-linked galacturonosyl residues, released on partial degradation of the plant cell wall homogalacturonan. We show here that AvrPto affects only a subset of the OG-triggered immune responses and that, among these responses, only a subset is affected by the concomitant loss of BAK1 and BKK1. However, the antagonistic effect on auxin-related responses is not affected by either AvrPto or the loss of BAK1/BKK1. These observations reveal an unprecedented complexity among the MAMP/DAMP response cascades. We also show that the signalling system mediated by Peps, another class of DAMPs, and their receptors PEPRs, contributes to OG-activated immunity. We hypothesize that OGs are sensed through multiple and partially redundant perception/transduction complexes, some targeted by AvrPto, but not necessarily comprising BAK1 and BKK1.

  16. Marine Pharmacology in 2000: Marine Compounds with Antibacterial, Anticoagulant, Antifungal, Anti-inflammatory, Antimalarial, Antiplatelet, Antituberculosis, and Antiviral Activities; Affecting the Cardiovascular, Immune, and Nervous Systems and Other Miscellaneous Mechanisms of Action

    PubMed Central

    Mayer, Alejandro M. S.; Hamann, Mark T.

    2016-01-01

    During 2000 research on the pharmacology of marine chemicals involved investigators from Australia, Brazil, Canada, Egypt, France, Germany, India, Indonesia, Israel, Italy, Japan, the Netherlands, New Zealand, Phillipines, Singapore, Slovenia, South Korea, Spain, Sweden, Switzerland, United Kingdom, and the United States. This current review, a sequel to the authors’ 1998 and 1999 reviews, classifies 68 peer-reviewed articles on the basis of the reported preclinical pharmacologic properties of marine chemicals derived from a diverse group of marine animals, algae, fungi, and bacteria. Antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis, or antiviral activity was reported for 35 marine chemicals. An additional 20 marine compounds were shown to have significant effects on the cardiovascular and nervous system, and to possess anti-inflammatory or immunosuppressant properties. Finally, 23 marine compounds were reported to act on a variety of molecular targets and thus could potentially contribute to several pharmacologic classes. Thus, as in 1998 and 1999, during 2000 pharmacologic research with marine chemicals continued to contribute potentially novel chemical leads to the ongoing global search for therapeutic agents in the treatment of multiple disease categories. PMID:14583811

  17. Book Review: Rediscovering the Immune System as an Integrated Organ.

    PubMed

    Corthay, A

    2016-07-01

    The immune system may seem incredibly complex. Researchers in immunology are amassing enormous amounts of detailed information without gaining proportional insights. Why might this be? So asks Peter Bretscher near the start of his book Rediscovering the Immune System as an Integrated Organ. He argues that contemporary immunology fails to provide understanding at the level of the system because it is dominated by molecular and cellular considerations. He reminds us of a famous quotation: Not everything that counts can be counted and not everything that can be counted counts, before stating the ambitious aim of his book: to make plausible an integrated and readily accessible view of how the immune system functions. By Peter Bretscher. FriesenPress, 2016. 288 pp. ISBN: 978-1-4602-7406-4.

  18. Strategies to improve the functions and redox state of the immune system in aged subjects.

    PubMed

    De la Fuente, Monica; Cruces, Julia; Hernandez, Oskarina; Ortega, Eduardo

    2011-12-01

    The aging process is accompanied by an impairment of the physiological systems including the immune system. This system is an excellent indicator of health. We have also observed that several functions of the immune cells are good markers of biological age and predictors of longevity. In agreement with the oxidation-inflammation theory that we have proposed, the chronic oxidative stress that appears with age affects all cells and especially those of the regulatory systems, such as the nervous, endocrine and immune systems and the communication between them. This fact prevents an adequate homeostasis and, therefore, the preservation of health. We have also proposed an involvement of the immune system in the aging process of the organism, concretely in the rate of aging, since there is a relation between the redox state and functional capacity of the immune cells and the longevity of individuals. A confirmation of the central role of the immune system in oxi-inflamm-aging is that several lifestyle strategies such as the administration of adequate amounts of antioxidants in the diet, physical exercise, physical and mental activity through environmental enrichment and hormetic interventions improve functions of immune cells, decreasing their oxidative stress, and consequently increasing the longevity of individuals. Recent results in mice of investigations on the effects of a new environmental enrichment (bathing in waters) as well as a hormetic intervention with slight infections (caused by injection of E.coli lipopolysaccharide, LPS), on several functions and redox parameters are shown. The advantages and possible problems of the use of those interventions to achieve a healthy aging and longevity are discussed.

  19. “Health system approach” for improving immunization program performance

    PubMed Central

    Lahariya, Chandrakant

    2015-01-01

    Immunization programs are one of the most well-recognized and successful public health programs across the world. The immunization programs have achieved significant successes in a number of countries; however, the coverage with available vaccines remains sub-optimal in many low- and middle-income countries (LMICs). This article, based upon extensive review of literature and using universal immunization program (UIP) in India as a case study, summarizes the latest developments and initiatives in the area of vaccination and immunization in the last few years. The article analyzes initiatives under UIP in India from the “health system approach” and argues that it is possible to increase coverage with available vaccines and overall program performance by focused attention on various functions of health systems. It also discusses the emerging evidence that health systems could be strengthened prior to the introduction of new interventions (vaccines included) and the introduction of new interventions (including vaccines) could be planned in a way to strengthen the health systems. It concludes that immunization programs could be one of the entry points for strengthening health systems in the countries and lessons from vaccine introduction could pave pathway for scaling up other health interventions and therefore, could contribute to advancing Universal Health Coverage (UHC). PMID:26985404

  20. Thermodynamics as the driving principle behind the immune system.

    PubMed

    Finger, Eduardo

    2012-01-01

    Over the last 120 years, few things contributed more to our understanding of immune system than the study of its behavior in the host/parasite relationship. Despite the advances though, a few questions remain, such as what drives the immune system? What are its guiding principles? If we ask these questions randomly, most will immediately answer "defend the body from external threats," but what exactly do we defend ourselves from? How do these threats harm us? What criteria define what constitutes a threat? On the other hand, if the immune system evolved to defend us against external threats, how does its action against "internal" processes, such as neoplasms, qualify? Why do we die from cancer? Or from infection? Or even, why do we die at all? These apparently obvious questions are nor simple neither trivial, and the difficulty answering them reveals the complex reality that the immune system handles. The objective of this article is to articulate for the reader something that he instinctively already knows: that the decisions of the immune system are thermodynamically driven. Additionally, we will discuss how this apparent change in paradigm alters concepts such as health, disease, and therapeutics.

  1. Selection based on indirect genetic effects for growth, environmental enrichment and coping style affect the immune status of pigs.

    PubMed

    Reimert, Inonge; Rodenburg, T Bas; Ursinus, Winanda W; Kemp, Bas; Bolhuis, J Elizabeth

    2014-01-01

    Pigs living in intensive husbandry systems may experience both acute and chronic stress through standard management procedures and limitations in their physical and social environment, which may have implications for their immune status. Here, the effect of a new breeding method where pigs were selected on their heritable influence on their pen mates' growth, and environmental enrichment on the immune status of pigs was investigated. Hereto, 240 pigs with a relatively positive genetic effect on the growth of their pen mates (+SBV) and 240 pigs with a relatively negative genetic effect on the growth of their pen mates (-SBV) were housed in barren or straw-enriched pens from 4 to 23 weeks of age (n  =  80 pens in total). A blood sample was taken from the pigs before, three days after a 24 h regrouping test, and at week 22. In addition, effects of coping style, as assessed in a backtest, and gender were also investigated. Mainly, +SBV were found to have lower leukocyte, lymphocyte and haptoglobin concentrations than -SBV pigs. Enriched housed pigs had a lower neutrophil to lymphocyte (N:L) ratio and lower haptoglobin concentrations, but had higher antibody titers specific for Keyhole Limpet Hemocyanin (KLH) than barren housed pigs. No interactions were found between SBV class and housing. Furthermore, pigs with a proactive coping style had higher alternative complement activity and, in the enriched pens, higher antibody titers specific for KLH than pigs with a reactive coping style. Lastly, females tended to have lower leukocyte, but higher haptoglobin concentrations than castrated males. Overall, these results suggest that +SBV pigs and enriched housed pigs were less affected by stress than -SBV and barren housed pigs, respectively. Moreover, immune activation might be differently organized in individuals with different coping styles and to a lesser extent in individuals of opposite genders.

  2. 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.

  3. Programmed cell death in the plant immune system.

    PubMed

    Coll, N S; Epple, P; Dangl, J L

    2011-08-01

    Cell death has a central role in innate immune responses in both plants and animals. Besides sharing striking convergences and similarities in the overall evolutionary organization of their innate immune systems, both plants and animals can respond to infection and pathogen recognition with programmed cell death. The fact that plant and animal pathogens have evolved strategies to subvert specific cell death modalities emphasizes the essential role of cell death during immune responses. The hypersensitive response (HR) cell death in plants displays morphological features, molecular architectures and mechanisms reminiscent of different inflammatory cell death types in animals (pyroptosis and necroptosis). In this review, we describe the molecular pathways leading to cell death during innate immune responses. Additionally, we present recently discovered caspase and caspase-like networks regulating cell death that have revealed fascinating analogies between cell death control across both kingdoms.

  4. Arginase: an emerging key player in the mammalian immune system

    PubMed Central

    Munder, Markus

    2009-01-01

    The enzyme arginase metabolizes L-arginine to L-ornithine and urea. Besides its fundamental role in the hepatic urea cycle, arginase is also expressed the immune system of mice and man. While significant interspecies differences exist regarding expression, subcellular localization and regulation of immune cell arginase, associated pathways of immunopathology are comparable between species. Arginase is induced in murine myeloid cells mainly by Th2 cytokines and inflammatory agents and participates in a variety of inflammatory diseases by down-regulation of nitric oxide synthesis, induction of fibrosis and tissue regeneration. In humans, arginase I is constitutively expressed in polymorphonuclear neutrophils and is liberated during inflammation. Myeloid cell arginase-mediated L-arginine depletion profoundly suppresses T cell immune responses and this has emerged as a fundamental mechanism of inflammation-associated immunosuppression. Pharmacological interference with L-arginine metabolism is a novel promising strategy in the treatment of cancer, autoimmunity or unwanted immune deviation. PMID:19764983

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

    PubMed

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

    2016-10-01

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

  6. Combination of prenatal immune challenge and restraint stress affects prepulse inhibition and dopaminergic/GABAergic markers.

    PubMed

    Deslauriers, Jessica; Larouche, Annie; Sarret, Philippe; Grignon, Sylvain

    2013-08-01

    Gestational immune challenge with the viral-like antigen poly I:C is a well-established neurodevelopmental model of schizophrenia. However, exposure to inflammation during early life may sensitize the developing brain to secondary insults and enhance the central nervous system vulnerability. To gain a better understanding of the pathophysiology of schizophrenia, we thus developed a two-hit animal model based on prenatal poly I:C immune challenge followed by restraint stress in juvenile mice. C57BL/6 gestational mice were intraperitoneally injected with poly I:C or saline at gestational day 12. Pups were then submitted or not, to restraint stress for 2h, for three consecutive days, from postnatal days 33 to 35. Prepulse inhibition (PPI) of acoustic startle response is commonly used to assess sensorimotor gating, a neural process severely disrupted in patients with schizophrenia. Our results revealed that the combination of prenatal immune challenge with poly I:C followed by a restraint stress period was able to induce a PPI disruption in 36-day-old pups, as opposed to each insult applied separately. PPI deficits were accompanied by dopaminergic and GABAergic abnormalities in the prefrontal cortex and striatum. Indeed, measurements of cortical and striatal dopamine D2 receptor (D2R) mRNA and protein levels revealed that the combination of gestational exposure to poly I:C and postnatal restraint stress induced an increase in D2R protein and mRNA levels. Likewise, the combination of both insults reduced the mRNA and protein expression levels of the 67 kDa form of glutamic acid decarboxylase (GAD67), in those two brain regions. To our knowledge, this two-hit animal model is the first in vivo model reporting PPI deficits at pubertal age. This two-hit animal model may also help in studying innovative therapies dedicated to the treatment of schizophrenia, especially in its early phase.

  7. Do androgen deprivation drugs affect the immune cross-talk between mononuclear and prostate cancer cells?

    PubMed

    Salman, Hertzel; Bergman, Michael; Blumberger, Naava; Djaldetti, Meir; Bessler, Hanna

    2014-02-01

    The aim of the study was to examine the effect of androgen deprivation drugs, i.e. leuprolide and bicalutamide on the immune cross-talk between human peripheral blood mononuclear cells (PBMC) and cells from PC-3 and LNCaP human prostate cancer lines. PBMC, PC-3 and LNCaP were separately incubated without and with two androgen-deprivation drugs, i.e. leuprolide and bicalutamide, and the secretion of IL-1β, IL-6, IL-1ra and IL-10 was examined. In addition, the effect of both drugs on the production of those cytokines was carried out after 24 hours incubation of PBMC with both types of cancer cells. Leuprolide or bicalutamide did not affect the production of the cytokines by PBMC or by the prostate cancer cells from the two lines. Incubation of PBMC with PC-3 or LNCaP cells caused increased production of IL-1β, IL-6 and IL-10 as compared with PBMC incubated without malignant cells. While 10(-7) M and 10(-8) M of leuprolide caused a decreased secretion of IL-1β by PBMC previously incubated with prostate cancer cells without the drug, bicalutamide did not affect this PBMC activity at any drug concentration. This observation suggests the existence of an additional mechanism explaining the effect of androgen deprivation therapy in prostate cancer patients.

  8. 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.

  9. ImmunoScenarios: A Game for the Immune System.

    ERIC Educational Resources Information Center

    Taylor, Mark F.; Jackson, Sally W.

    1996-01-01

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

  10. Multiple sclerosis immunology: The healthy immune system vs the MS immune system.

    PubMed

    Kasper, Lloyd H; Shoemaker, Jennifer

    2010-01-05

    Multiple sclerosis (MS) is a debilitating autoimmune disease characterized by both inflammation and axonal degeneration. The resulting demyelination and subsequent degeneration of axons account for the disability of patients with MS. Early investigations indicated that disease progression was driven by CD4(+) effector T cells. However, clinical therapies specifically targeting these cells have, for the most part, not been effective. Therefore, new areas of research in experimental autoimmune encephalomyelitis (the experimental model of MS) and human MS have identified previously unknown contributions to disease pathogenesis, including interleukin-17-producing T helper 17 cells, B cells, CD8(+) T cells, and both CD4(+) and CD8(+) T-regulatory cells. Research into the respective mechanisms of action of these cells has identified novel therapeutic targets to combat this devastating disease. This article reviews the autoimmune response in patients with MS compared with individuals without MS and summarizes the fundamental differences in the immunologic response between people with and without MS. Investigations into these autoimmune differences and the disruption of the homeostatic balance of the immune system will help guide future research into MS therapeutics, with particular attention to the long-term management of this disease.

  11. Opposing Effects of Alcohol on the Immune System

    PubMed Central

    Barr, Tasha; Helms, Christa; Grant, Kathleen; Messaoudi, Ilhem

    2016-01-01

    Several studies have described a dose-dependent effect of alcohol on human health with light to moderate drinkers having a lower risk of all-cause mortality than abstainers, while heavy drinkers are at the highest risk. In the case of the immune system, moderate alcohol consumption is associated with reduced inflammation and improved responses to vaccination, while chronic heavy drinking is associated with a decreased frequency of lymphocytes and increased risk of both bacterial and viral infections. However, the mechanisms by which alcohol exerts a dose-dependent effect on the immune system remain poorly understood due to a lack of systematic studies that examine the effect of multiple doses and different time courses. This review will summarize our current understanding of the impact of moderate versus excessive alcohol consumption on the innate and adaptive branches of the immune system derived from both in vitro as well as in vivo studies carried out in humans and animal model studies. PMID:26375241

  12. Immunization information systems--progress on integration of school nurses: a multi-state roundtable.

    PubMed

    Galemore, Cynthia A

    2011-03-01

    The following is an article and roundtable discussion on school nurse integration into immunization information systems. The discussion participants were April Bailey, Deputy Director, Immunization Division, Indiana State Department of Health; Thomas Maerz, Manager, Wisconsin Immunization Registry; Erin Seward, Immunization Program Manager, Nevada State Health Division; and Debra Warren, Project Manager, KSWebIZ, Kansas Immunization Program.

  13. Comparative analysis of the Monochamus alternatus immune system.

    PubMed

    Zhou, Jiao; Zhao, Li-Lin; Yu, Hai-Ying; Zhang, Wei; Ahmad, Faheem; Hu, Song-Nian; Zou, Zhen; Sun, Jiang-Hua

    2017-03-01

    The pine sawyer beetle, Monochamus alternatus, is regarded as a notorious forest pest in Asia, vectoring an invasive pathogenic nematode, Bursaphelenchus xylophilus, which is known to cause pine wilt disease. However, little sequence information is available for this vector beetle. This hampered the research on its immune system. Based on transcriptome of M. alternatus, we have identified and characterized 194 immunity-related genes in M. alternatus, and compared them with homologues molecules from other species known to exhibit immune responses against invading microbes. The lower number of putative immunity-related genes in M. alternatus were attributed to fewer C-type lectin, serine protease (SP) and anti-microbial peptide (AMP) genes. Phylogenetic analysis revealed that M. alternatus had a unique recognition gene, galectin3, orthologues of which was not identified in Tribolium castaneum, Drosophila melanogastor, Anopheles gambiae, and Apis mellifera. This suggested a lineage-specific gene evolution for coleopteran insects. Our study provides the comprehensive sequence resources of the immunity-related genes of M. alternatus, presenting valuable information for better understanding of the molecular mechanism of innate immunity processes in M. alternatus against B. xylophilus. This article is protected by copyright. All rights reserved.

  14. Primitive immune systems: are your ways my ways?

    PubMed

    Rinkevich, Baruch

    2004-04-01

    Although vertebrate immune systems have been commonly conceived as exquisitely developed to combat pervasiveness by pathogens, they are not infallible. The enigmatic expression of histocompatibility in vertebrates, the manifestation of natural chimerism, autoimmunity, malignancy, and other puzzling outcomes hint that immunity did not arise in evolution to fight infections and that this capacity is a late evolutionary appendage, owing its appearance to the redeployment of a system developed for other reasons. Allorecognition in the colonial tunicate Botryllus schlosseri serves here as a platform for a contending paradigm, advocating that immunity has developed as a surveillance machinery against and for purging of nascent selfish cells (stemmed from a kin organism or from transformed cells within the organism of origin). Defense against pathogens (always representing xenogeneic aliens) appeared later, revealing the multiplicity of newly developed phenomena. Allorecognition events characteristic of the Botryllus primitive immune system, such as fusion versus rejection, the morphological resorption with its expressed hierarchy, and the somatic/germ-cell parasitic outcomes, provide clues to the evolutionary basis of allorecognition. Recent work on Botryllus immunity that highlights the cost of littering individuality by somatic variants/allogeneic cells is discussed.

  15. A role of the adaptive immune system in glucose homeostasis

    PubMed Central

    Bronsart, Laura L; Contag, Christopher H

    2016-01-01

    Objective The immune system, including the adaptive immune response, has recently been recognized as having a significant role in diet-induced insulin resistance. In this study, we aimed to determine if the adaptive immune system also functions in maintaining physiological glucose homeostasis in the absence of diet-induced disease. Research design and methods SCID mice and immunocompetent control animals were phenotypically assessed for variations in metabolic parameters and cytokine profiles. Additionally, the glucose tolerance of SCID and immunocompetent control animals was assessed following introduction of a high-fat diet. Results SCID mice on a normal chow diet were significantly insulin resistant relative to control animals despite having less fat mass. This was associated with a significant increase in the innate immunity-stimulating cytokines granulocyte colony-stimulating factor, monocyte chemoattractant protein 1 (MCP1), and MCP3. Additionally, the SCID mouse phenotype was exacerbated in response to a high-fat diet as evidenced by the further significant progression of glucose intolerance. Conclusions These results support the notion that the adaptive immune system plays a fundamental biological role in glucose homeostasis, and that the absence of functional B and T cells results in disruption in the concentrations of various cytokines associated with macrophage proliferation and recruitment. Additionally, the absence of functional B and T cells is not protective against diet-induced pathology. PMID:27026807

  16. 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.

  17. Lymphatic system: an active pathway for immune protection.

    PubMed

    Liao, Shan; von der Weid, P Y

    2015-02-01

    Lymphatic vessels are well known to participate in the immune response by providing the structural and functional support for the delivery of antigens and antigen presenting cells to draining lymph nodes. Recent advances have improved our understanding of how the lymphatic system works and how it participates to the development of immune responses. New findings suggest that the lymphatic system may control the ultimate immune response through a number of ways which may include guiding antigen/dendritic cells (DC) entry into initial lymphatics at the periphery; promoting antigen/DC trafficking through afferent lymphatic vessels by actively facilitating lymph and cell movement; enabling antigen presentation in lymph nodes via a network of lymphatic endothelial cells and lymph node stroma cell and finally by direct lymphocytes exit from lymph nodes. The same mechanisms are likely also important to maintain peripheral tolerance. In this review we will discuss how the morphology and gene expression profile of the lymphatic endothelial cells in lymphatic vessels and lymph nodes provides a highly efficient pathway to initiate immune responses. The fundamental understanding of how lymphatic system participates in immune regulation will guide the research on lymphatic function in various diseases.

  18. The evolution of secondary organization in immune system gene libraries

    SciTech Connect

    Hightower, R.; Forrest, S.; Perelson, A.S.

    1993-02-01

    A binary model of the immune system is used to study the effects of evolution on the genetic encoding for antibody molecules. We report experiments which show that the evolution of immune system genes, simulated by the genetic algorithm, can induce a high degree of genetic organization even though that organization is not explicitly required by the fitness function. This secondary organization is related to the true fitness of an individual, in contrast to the sampled fitness which is the explicit fitness measure used to drive the process of evolution.

  19. Effect of simulated weightlessness on the immune system in rats

    NASA Technical Reports Server (NTRS)

    Caren, L. D.; Mandel, A. D.; Nunes, J. A.

    1980-01-01

    Rats suspended in a model system designed to simulate many aspects of weightlessness were immunized with sheep red blood cells. Parameters measured on these and control rats included titers of anti-sheep red blood cell antibodies, serum immunoglobulin levels, spleen and thymus weights, hematocrits, and leukocyte differential counts on peripheral blood. No significant differences were found between test and weight-bearing, harnessed controls; however, the thymuses of animals in both these groups were significantly smaller than untreated cage controls. The lack of an effect of simulated weightlessness on the immune system is an interesting result, and its significance is discussed.

  20. Effect of immunization route on mucosal and systemic immune response in Atlantic salmon (Salmo salar).

    PubMed

    Valdenegro-Vega, Victoria A; Crosbie, Philip; Vincent, Benita; Cain, Kenneth D; Nowak, Barbara F

    2013-01-15

    This study aimed to assess systemic and mucosal immune responses of Atlantic salmon (Salmo salar) exposed to two protein-hapten antigens - dinitrophenol (DNP) and fluorescein isothiocyanate (FITC) each conjugated with keyhole limpet haemocyanin (KLH) - administered using different delivery strategies. Fish were exposed to the antigens through different routes, and were given a booster 4 weeks post initial exposure. Both systemic and mucosal antibody responses were measured for a period of 12 weeks using an enzyme-linked immunosorbent assay (ELISA). Only fish exposed to both antigens via intraperitoneal (IP) injection showed increased systemic antibody response starting 6 weeks post immunization. No treatment was able to produce a mucosal antibody response; however there was an increase in antibody levels in the tissue supernatant from skin explants obtained 12 weeks post immunization from fish injected with FITC. Western blots probed with serum and culture supernatant from skin explants showed a specific response against the antigens. In conclusion, IP injection of hapten-antigen in Atlantic salmon was the best delivery route for inducing an antibody response against these antigens in this species. Even though IP injection did not induce an increase in antibody levels in the skin mucus, there was an increased systemic antibody response and an apparent increase of antibody production in mucosal tissues as demonstrated by the increased level of specific antibody levels in supernatants from the tissue explants.

  1. [Considerations about mechanisms of acupuncture therapy for improving hypertension by regulating immune system].

    PubMed

    Yu, Zheng; Wu, Qiao-Feng; Liang, Fan-Rong

    2014-08-01

    Essential hypertension (EH) is a very common clinical disorder affecting the patient's health. Accumulating evidence indicates that immunological factors play an important role in the pathogenesis of hypertension. In the present paper, the authors introduce 1) progress of researches on the pathogenesis of hypertension from cellular immune and body fluid immune (multiple immuno-humoral factors); 2) effects of acupuncture intervention on natural killer cell activity, exercise-induced immunosuppression, circulating inflammatory factor levels and balance of cytokines; 3) blood-pressure reduction effect of acupuncture intervention by lowering circulating TNF-alpha, IL-6, matrix metalloproteinases-9, angiotensin convertase and endothelin levels, and up-regulating serum opioid peptide content, etc. to decrease inflammatory injury of the cardiovascular system. Many researches have demonstrated that acupuncture may have a positive role in improving EH in clinical practice, which may be associated with its regulative effect on immune system, but its mechanism has not been fully elucidated.

  2. 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

  3. Complement: a key system for immune surveillance and homeostasis.

    PubMed

    Ricklin, Daniel; Hajishengallis, George; Yang, Kun; Lambris, John D

    2010-09-01

    Nearly a century after the significance of the human complement system was recognized, we have come to realize that its functions extend far beyond the elimination of microbes. Complement acts as a rapid and efficient immune surveillance system that has distinct effects on healthy and altered host cells and foreign intruders. By eliminating cellular debris and infectious microbes, orchestrating immune responses and sending 'danger' signals, complement contributes substantially to homeostasis, but it can also take action against healthy cells if not properly controlled. This review describes our updated view of the function, structure and dynamics of the complement network, highlights its interconnection with immunity at large and with other endogenous pathways, and illustrates its multiple roles in homeostasis and disease.

  4. 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

  5. Quantifying Adaptive Evolution in the Drosophila Immune System

    PubMed Central

    Obbard, Darren J.; Welch, John J.; Kim, Kang-Wook; Jiggins, Francis M.

    2009-01-01

    It is estimated that a large proportion of amino acid substitutions in Drosophila have been fixed by natural selection, and as organisms are faced with an ever-changing array of pathogens and parasites to which they must adapt, we have investigated the role of parasite-mediated selection as a likely cause. To quantify the effect, and to identify which genes and pathways are most likely to be involved in the host–parasite arms race, we have re-sequenced population samples of 136 immunity and 287 position-matched non-immunity genes in two species of Drosophila. Using these data, and a new extension of the McDonald-Kreitman approach, we estimate that natural selection fixes advantageous amino acid changes in immunity genes at nearly double the rate of other genes. We find the rate of adaptive evolution in immunity genes is also more variable than other genes, with a small subset of immune genes evolving under intense selection. These genes, which are likely to represent hotspots of host–parasite coevolution, tend to share similar functions or belong to the same pathways, such as the antiviral RNAi pathway and the IMD signalling pathway. These patterns appear to be general features of immune system evolution in both species, as rates of adaptive evolution are correlated between the D. melanogaster and D. simulans lineages. In summary, our data provide quantitative estimates of the elevated rate of adaptive evolution in immune system genes relative to the rest of the genome, and they suggest that adaptation to parasites is an important force driving molecular evolution. PMID:19851448

  6. The Adaptive Immune System of Haloferax volcanii.

    PubMed

    Maier, Lisa-Katharina; Dyall-Smith, Mike; Marchfelder, Anita

    2015-02-16

    To fight off invading genetic elements, prokaryotes have developed an elaborate defence system that is both adaptable and heritable-the CRISPR-Cas system (CRISPR is short for: clustered regularly interspaced short palindromic repeats and Cas: CRISPR associated). Comprised of proteins and multiple small RNAs, this prokaryotic defence system is present in 90% of archaeal and 40% of bacterial species, and enables foreign intruders to be eliminated in a sequence-specific manner. There are three major types (I-III) and at least 14 subtypes of this system, with only some of the subtypes having been analysed in detail, and many aspects of the defence reaction remaining to be elucidated. Few archaeal examples have so far been analysed. Here we summarize the characteristics of the CRISPR-Cas system of Haloferax volcanii, an extremely halophilic archaeon originally isolated from the Dead Sea. It carries a single CRISPR-Cas system of type I-B, with a Cascade like complex composed of Cas proteins Cas5, Cas6b and Cas7. Cas6b is essential for CRISPR RNA (crRNA) maturation but is otherwise not required for the defence reaction. A systematic search revealed that six protospacer adjacent motif (PAM) sequences are recognised by the Haloferax defence system. For successful invader recognition, a non-contiguous seed sequence of 10 base-pairs between the crRNA and the invader is required.

  7. Immunization.

    ERIC Educational Resources Information Center

    Guerin, Nicole; And Others

    1986-01-01

    Contents of this double journal issue concern immunization and primary health care of children. The issue decribes vaccine storage and sterilization techniques, giving particular emphasis to the role of the cold chain, i.e., the maintenance of a specific temperature range to assure potency of vaccines as they are moved from a national storage…

  8. Molecular insights on the cerebral innate immune system.

    PubMed

    Rivest, Serge

    2003-02-01

    All species need an immediate reply to the microbial pathogens that is part of an effective immune response and is essential for the survival of most organisms. This reply is known as the innate immune response and is characterized by the de novo production of mediators that either kill the microbes directly or activate phagocytic cells to ingest and kill them. The innate immune response can be driven through specific recognition systems, the best example being an interaction between the endotoxin lipopolysaccharide (LPS) and its receptors CD14 and Toll-like receptor 4 (TLR4). For a long time, the brain was considered to be a privileged organ from an immunological point of view, owing to its inability to mount an immune response and process antigens. Although this is partly true, the CNS shows a well-organized innate immune reaction in response to systemic bacterial infection and cerebral injury. The CD14 and TLR4 receptors are constitutively expressed in the circumventricular organs (CVOs), choroid plexus and leptomeninges. Circulating LPS is able to cause a rapid transcriptional activation of genes encoding CD14 and TLR2, as well as a wide variety of pro-inflammatory molecules in CVOs. A delayed response to LPS takes place in cells located at boundaries of the CVOs and in microglia across the CNS. Therefore, without having direct access to the brain parenchyma, pathogens have the ability to trigger an innate immune reaction throughout cerebral tissue. This review presents evidence supporting the existence of such a system in the brain, which is finely regulated at the transcription level. Transient activation of this system is not harmful toward neuronal elements.

  9. The Innate Immune System in Acute and Chronic Wounds

    PubMed Central

    MacLeod, Amanda S.; Mansbridge, Jonathan N.

    2016-01-01

    Significance: This review article provides an overview of the critical roles of the innate immune system to wound healing. It explores aspects of dysregulation of individual innate immune elements known to compromise wound repair and promote nonhealing wounds. Understanding the key mechanisms whereby wound healing fails will provide seed concepts for the development of new therapeutic approaches. Recent Advances: Our understanding of the complex interactions of the innate immune system in wound healing has significantly improved, particularly in our understanding of the role of antimicrobials and peptides and the nature of the switch from inflammatory to reparative processes. This takes place against an emerging understanding of the relationship between human cells and commensal bacteria in the skin. Critical Issues: It is well established and accepted that early local inflammatory mediators in the wound bed function as an immunological vehicle to facilitate immune cell infiltration and microbial clearance upon injury to the skin barrier. Both impaired and excessive innate immune responses can promote nonhealing wounds. It appears that the switch from the inflammatory to the proliferative phase is tightly regulated and mediated, at least in part, by a change in macrophages. Defining the factors that initiate the switch in such macrophage phenotypes and functions is the subject of multiple investigations. Future Directions: The review highlights processes that may be useful targets for further investigation, particularly the switch from M1 to M2 macrophages that appears to be critical as dysregulation of this switch occurs during defective wound healing. PMID:26862464

  10. Exploiting Gene-Expression Deconvolution to Probe the Genetics of the Immune System.

    PubMed

    Steuerman, Yael; Gat-Viks, Irit

    2016-04-01

    Sequence variation can affect the physiological state of the immune system. Major experimental efforts targeted at understanding the genetic control of the abundance of immune cell subpopulations. However, these studies are typically focused on a limited number of immune cell types, mainly due to the use of relatively low throughput cell-sorting technologies. Here we present an algorithm that can reveal the genetic basis of inter-individual variation in the abundance of immune cell types using only gene expression and genotyping measurements as input. Our algorithm predicts the abundance of immune cell subpopulations based on the RNA levels of informative marker genes within a complex tissue, and then provides the genetic control on these predicted immune traits as output. A key feature of the approach is the integration of predictions from various sets of marker genes and refinement of these sets to avoid spurious signals. Our evaluation of both synthetic and real biological data shows the significant benefits of the new approach. Our method, VoCAL, is implemented in the freely available R package ComICS.

  11. Exploiting Gene-Expression Deconvolution to Probe the Genetics of the Immune System

    PubMed Central

    Steuerman, Yael; Gat-Viks, Irit

    2016-01-01

    Sequence variation can affect the physiological state of the immune system. Major experimental efforts targeted at understanding the genetic control of the abundance of immune cell subpopulations. However, these studies are typically focused on a limited number of immune cell types, mainly due to the use of relatively low throughput cell-sorting technologies. Here we present an algorithm that can reveal the genetic basis of inter-individual variation in the abundance of immune cell types using only gene expression and genotyping measurements as input. Our algorithm predicts the abundance of immune cell subpopulations based on the RNA levels of informative marker genes within a complex tissue, and then provides the genetic control on these predicted immune traits as output. A key feature of the approach is the integration of predictions from various sets of marker genes and refinement of these sets to avoid spurious signals. Our evaluation of both synthetic and real biological data shows the significant benefits of the new approach. Our method, VoCAL, is implemented in the freely available R package ComICS. PMID:27035464

  12. Microbial Environment Affects Innate Immunity in Two Closely Related Earthworm Species Eisenia andrei and Eisenia fetida

    PubMed Central

    Dvořák, Jiří; Mančíková, Veronika; Pižl, Václav; Elhottová, Dana; Šilerová, Marcela; Roubalová, Radka; Škanta, František; Procházková, Petra; Bilej, Martin

    2013-01-01

    Survival of earthworms in the environment depends on their ability to recognize and eliminate potential pathogens. This work is aimed to compare the innate defense mechanisms of two closely related earthworm species, Eisenia andrei and Eisenia fetida, that inhabit substantially different ecological niches. While E. andrei lives in a compost and manure, E. fetida can be found in the litter layer in forests. Therefore, the influence of environment-specific microbiota on the immune response of both species was followed. Firstly, a reliable method to discern between E. andrei and E. fetida based on species-specific primers for cytochrome c oxidase I (COI) and stringent PCR conditions was developed. Secondly, to analyze the immunological profile in both earthworm species, the activity and expression of lysozyme, pattern recognition protein CCF, and antimicrobial proteins with hemolytic function, fetidin and lysenins, have been assessed. Whereas, CCF and lysozyme showed only slight differences in the expression and activity, fetidin/lysenins expression as well as the hemolytic activity was considerably higher in E. andrei as compared to E. fetida. The expression of fetidin/lysenins in E. fetida was not affected upon the challenge with compost microbiota, suggesting more substantial changes in the regulation of the gene expression. Genomic DNA analyses revealed significantly higher level of fetidin/lysenins (determined using universal primer pairs) in E. andrei compared to E. fetida. It can be hypothesized that E. andrei colonizing compost as a new habitat acquired an evolutionary selection advantage resulting in a higher expression of antimicrobial proteins. PMID:24223917

  13. Lead and cadmium at very low doses affect in vitro immune response of human lymphocytes

    SciTech Connect

    Borella, P.; Giardino, A. )

    1991-08-01

    The effect of lead chloride and cadmium chloride on in vitro immunoglobulin (Ig) production by human lymphocytes was investigated. After 7 days in culture, lead added in the range of human exposure (207-1035 {mu}g/liter) significantly enhanced Ig production either when cells were activated by pokeweed mitogen (PWM) or not. The effect was dose-dependent and was related to the Pb were measured in the extracellular medium and in the cells. Independently of the mitogen addition, about 2% of the Pb added was accumulated in the cells, most being associated with the nuclear fraction. Those findings suggest that the Pb effects could depend on its uptake and distribution in the cells. Cadmium added in the 50-500 nM range exhibited a dose-independent mitogenic activity in unstimulated cells, whereas the Ig secretion was not significantly affected by Cd when cells were PWM-activated. A considerable intraindividual variability, however, was observed when blood donors were separately examined, with both an increase, a decrease, or no variation on Ig production. Furthermore, higher percentages of Cd were accumulated in the nuclear fraction, and lower in the cytosol and precipitate, in PWM-activated compared to resting lymphocytes. Genetic factors could be of importance for the observed variability of the immune response to cadmium, and the authors support the hypothesis that differences in the metallothionein (MT) inducibility could play a role.

  14. Microbial environment affects innate immunity in two closely related earthworm species Eisenia andrei and Eisenia fetida.

    PubMed

    Dvořák, Jiří; Mančíková, Veronika; Pižl, Václav; Elhottová, Dana; Silerová, Marcela; Roubalová, Radka; Skanta, František; Procházková, Petra; Bilej, Martin

    2013-01-01

    Survival of earthworms in the environment depends on their ability to recognize and eliminate potential pathogens. This work is aimed to compare the innate defense mechanisms of two closely related earthworm species, Eisenia andrei and Eisenia fetida, that inhabit substantially different ecological niches. While E. andrei lives in a compost and manure, E. fetida can be found in the litter layer in forests. Therefore, the influence of environment-specific microbiota on the immune response of both species was followed. Firstly, a reliable method to discern between E. andrei and E. fetida based on species-specific primers for cytochrome c oxidase I (COI) and stringent PCR conditions was developed. Secondly, to analyze the immunological profile in both earthworm species, the activity and expression of lysozyme, pattern recognition protein CCF, and antimicrobial proteins with hemolytic function, fetidin and lysenins, have been assessed. Whereas, CCF and lysozyme showed only slight differences in the expression and activity, fetidin/lysenins expression as well as the hemolytic activity was considerably higher in E. andrei as compared to E. fetida. The expression of fetidin/lysenins in E. fetida was not affected upon the challenge with compost microbiota, suggesting more substantial changes in the regulation of the gene expression. Genomic DNA analyses revealed significantly higher level of fetidin/lysenins (determined using universal primer pairs) in E. andrei compared to E. fetida. It can be hypothesized that E. andrei colonizing compost as a new habitat acquired an evolutionary selection advantage resulting in a higher expression of antimicrobial proteins.

  15. Understanding the Role of the Immune System in the Development of Cancer: New Opportunities for Population-Based Research.

    PubMed

    Michaud, Dominique S; Houseman, E Andres; Marsit, Carmen J; Nelson, Heather H; Wiencke, John K; Kelsey, Karl T

    2015-12-01

    Understanding the precise role of the immune system in cancer has been hindered by the complexity of the immune response and challenges in measuring immune cell types in health and disease in the context of large epidemiologic studies. In this review, we present the rationale to study immunity in cancer and highlight newly available tools to further elucidate the epidemiologic factors driving individual variation in the immune response in cancer. Here, we summarize key studies that have evaluated the role of immunologic status on risk of cancer, discuss tools that have been used in epidemiologic studies to measure immune status, as well as new evolving methodologies where application to epidemiology is becoming more feasible. We also encourage further development of novel emerging technologies that will continue to enable prospective assessment of the dynamic and complex role played by the immune system in cancer susceptibility. Finally, we summarize characteristics and environmental factors that affect the immune response, as these will need to be considered in epidemiologic settings. Overall, we consider the application of a systems biologic approach and highlight new opportunities to understand the immune response in cancer risk.

  16. The genome sequence of Atlantic cod reveals a unique immune system.

    PubMed

    Star, Bastiaan; Nederbragt, Alexander J; Jentoft, Sissel; Grimholt, Unni; Malmstrøm, Martin; Gregers, Tone F; Rounge, Trine B; Paulsen, Jonas; Solbakken, Monica H; Sharma, Animesh; Wetten, Ola F; Lanzén, Anders; Winer, Roger; Knight, James; Vogel, Jan-Hinnerk; Aken, Bronwen; Andersen, Oivind; Lagesen, Karin; Tooming-Klunderud, Ave; Edvardsen, Rolf B; Tina, Kirubakaran G; Espelund, Mari; Nepal, Chirag; Previti, Christopher; Karlsen, Bård Ove; Moum, Truls; Skage, Morten; Berg, Paul R; Gjøen, Tor; Kuhl, Heiner; Thorsen, Jim; Malde, Ketil; Reinhardt, Richard; Du, Lei; Johansen, Steinar D; Searle, Steve; Lien, Sigbjørn; Nilsen, Frank; Jonassen, Inge; Omholt, Stig W; Stenseth, Nils Chr; Jakobsen, Kjetill S

    2011-08-10

    Atlantic cod (Gadus morhua) is a large, cold-adapted teleost that sustains long-standing commercial fisheries and incipient aquaculture. Here we present the genome sequence of Atlantic cod, showing evidence for complex thermal adaptations in its haemoglobin gene cluster and an unusual immune architecture compared to other sequenced vertebrates. The genome assembly was obtained exclusively by 454 sequencing of shotgun and paired-end libraries, and automated annotation identified 22,154 genes. The major histocompatibility complex (MHC) II is a conserved feature of the adaptive immune system of jawed vertebrates, but we show that Atlantic cod has lost the genes for MHC II, CD4 and invariant chain (Ii) that are essential for the function of this pathway. Nevertheless, Atlantic cod is not exceptionally susceptible to disease under natural conditions. We find a highly expanded number of MHC I genes and a unique composition of its Toll-like receptor (TLR) families. This indicates how the Atlantic cod immune system has evolved compensatory mechanisms in both adaptive and innate immunity in the absence of MHC II. These observations affect fundamental assumptions about the evolution of the adaptive immune system and its components in vertebrates.

  17. Molecular Players Involved in the Interaction Between Beneficial Bacteria and the Immune System

    PubMed Central

    Hevia, Arancha; Delgado, Susana; Sánchez, Borja; Margolles, Abelardo

    2015-01-01

    The human gastrointestinal tract is a very complex ecosystem, in which there is a continuous interaction between nutrients, host cells, and microorganisms. The gut microbiota comprises trillions of microbes that have been selected during evolution on the basis of their functionality and capacity to survive in, and adapt to, the intestinal environment. Host bacteria and our immune system constantly sense and react to one another. In this regard, commensal microbes contribute to gut homeostasis, whereas the necessary responses are triggered against enteropathogens. Some representatives of our gut microbiota have beneficial effects on human health. Some of the most important roles of these microbes are to help to maintain the integrity of the mucosal barrier, to provide nutrients such as vitamins, or to protect against pathogens. In addition, the interaction between commensal microbiota and the mucosal immune system is crucial for proper immune function. This process is mainly performed via the pattern recognition receptors of epithelial cells, such as Toll-like or Nod-like receptors, which are able to recognize the molecular effectors that are produced by intestinal microbes. These effectors mediate processes that can ameliorate certain inflammatory gut disorders, discriminate between beneficial and pathogenic bacteria, or increase the number of immune cells or their pattern recognition receptors (PRRs). This review intends to summarize the molecular players produced by probiotic bacteria, notably Lactobacillus and Bifidobacterium strains, but also other very promising potential probiotics, which affect the human immune system. PMID:26635753

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

    PubMed Central

    Pulendran, Bali

    2014-01-01

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

  19. A survey of children affected by ectomermal dysplasia syndromes shows an increased prevalence of atopic disorders and immune deficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ectodermal dysplasia (ED) syndromes are rare genetic disorders that affect the development of tissues derived from the embryonic ectoderm. Studies and anecdotal experience have indicated that atopic disorders (AD) and immune deficiencies (ID) may be associated with ED in children. Some ED genotypes ...

  20. Immunoendocrinology: faulty hormonal imprinting in the immune system.

    PubMed

    Csaba, György

    2014-06-01

    Hormonal imprinting is an epigenetic process which is taking place perinatally at the first encounter between the developing hormone receptors and their target hormones. The hormonal imprinting influences the binding capacity of receptors, the hormone synthesis of the cells, and other hormonally regulated functions, as sexual behavior, aggressivity, empathy, etc. However, during the critical period, when the window for imprinting is open, molecules similar to the physiological imprinters as synthetic hormone analogs, other members of the hormone families, environmental pollutants, etc. can cause faulty imprinting with life-long consequences. The developing immune system, the cells of which also have receptors for hormones, is very sensitive to faulty imprinting, which causes alterations in the antibody and cytokine production, in the ratio of immune cells, in the defense against bacterial and viral infections as well as against malignant tumors. Immune cells (lymphocytes, monocytes, granulocytes and mast cells) are also producing hormones which are secreted into the blood circulation as well as are transported locally (packed transport). This process is also disturbed by faulty imprinting. As immune cells are differentiating during the whole life, faulty imprinting could develop any time, however, the most decisive is the perinatal imprinting. The faulty imprinting is inherited to the progenies in general and especially in the case of immune system. In our modern world the number and amount of artificial imprinters (e.g. endocrine disruptors and drugs) are enormously increasing. The effects of the faulty imprinters most dangerous to the immune system are shown in the paper. The present and future consequences of the flood of faulty imprintings are unpredictable however, it is discussed.

  1. Materials to Engineer the Immune System

    DTIC Science & Technology

    2010-04-01

    tumor cell vac- cines in direct comparison and outperformed ex vivo DC vaccines re- ported in literature (1, 2, 4). This acellular biomaterial system...or Flt3-ligand. Cancer Res. 60, 3239–3246 (2000). 22. E. Daro, B. Pulendran, K. Brasel, M. Teepe, D. Pettit , D. H. Lynch, D. Vremec, L. Robb, K

  2. Psychosocial maternal stress during pregnancy affects serum corticosterone, blood immune parameters and anxiety behaviour in adult male rat offspring.

    PubMed

    Götz, Alexander A; Stefanski, Volker

    2007-01-30

    Exposure to prenatal stress can impair the behavioural and hormonal development in mammals. However, the consequences for the immune system are rarely investigated and there is only limited evidence that naturalistic prenatal stressors do also have the potential to affect the offspring. Thus, by using a social conflict model in female Long-Evans rats, we investigated the effects of prenatal social stress on several behavioural, hormonal and immunological parameters. Offspring from stressed and non-stressed pregnant females were housed in pairs after weaning, and tested at an age of 4-6 months. Prenatally stressed (PS) males were more active in the elevated plus-maze test as indicated by significantly more frequent entries into the open arms compared to prenatal control males (PC). In addition, PS males had significantly lower serum corticosterone concentrations under basal conditions as well as after ACTH-challenge. The basal number of total leukocytes was significantly lower in the PS group due to significantly lower lymphocyte counts. In particular, the CD4+ T-helper cell subset was affected. The lymphocyte proliferation to pokeweed mitogen was lower in PS males. Because some of the present findings do not correspond to previous studies using conventional stressors, we assume that the nature of the stressor plays an important role for pregnancy outcome and behaviour and physiology of the offspring in later life.

  3. Biology of longevity: role of the innate immune system.

    PubMed

    Candore, Giuseppina; Colonna-Romano, Giuseppina; Balistreri, Carmela Rita; Di Carlo, Daniele; Grimaldi, Maria Paola; Listì, Florinda; Nuzzo, Domenico; Vasto, Sonya; Lio, Domenico; Caruso, Calogero

    2006-01-01

    Genetic factors play a relevant role in the attainment of longevity because they are involved in cell maintenance systems, including the immune system. In fact, longevity may be correlated with optimal functioning of clonotypic and natural immunity. The aging of the immune system, known as immunosenescence, is the consequence of the continuous attrition caused by chronic antigenic overload. The antigenic load results in the progressive generation of inflammatory responses involved in age-related diseases. Most of the parameters influencing immunosenescence appear to be under genetic control, and immunosenescence fits with the basic assumptions of evolutionary theories of aging, such as antagonistic pleiotropy. In fact, by neutralizing infectious agents the immune system plays a beneficial role until reproduction and parenting. However, by determining chronic inflammation, it can be detrimental later in life, a period largely unforeseen by evolution. In particular, the data coming from the long-lived male population under study show that genetic polymorphisms responsible for a low inflammatory response might result in an increased chance of long lifespan in an environment with a reduced pathogen burden. Such a modern and healthy environment also permits a lower grade of survivable atherogenic inflammatory response.

  4. Progress in immunization information systems - United States, 2008.

    PubMed

    2010-02-12

    Immunization information systems (IISs) are confidential, computerized information systems that collect and consolidate vaccination data from multiple health-care providers, generate reminder and recall notifications, and assess vaccination coverage within a defined geographic area. A CDC program goal for 2010 is to achieve >or=95% participation in an IIS (defined as having two or more recorded vaccinations) among children aged <6 years. To monitor progress toward this goal, CDC annually surveys immunization grantees in 50 states, five cities, and the District of Columbia, using the Immunization Information Systems Annual Report (IISAR). All 56 grantees were asked to complete the IISAR; 52 did so for 2008. This report highlights results from the 2008 IISAR, which indicated that 75% of all U.S. children aged <6 years (approximately 18 million children) participated in an IIS in 2008, an increase from 65% in 2006. The majority of grantees (82%) reported that their IIS had the capacity to track vaccinations for persons of all ages, compared with 70% in 2006. Data-quality measures of timeliness and completeness indicated that in 2008, 67% of IIS data were received and processed within 30 days of vaccine administration, and data were reported for six of 17 core data elements in >or=90% of IIS records (both measures are similar to 2006 results). Increased provider use of electronic health record systems can benefit IISs and their users by producing immunization records that are more timely and complete.

  5. TV synchronization system features stability and noise immunity

    NASA Technical Reports Server (NTRS)

    Landauer, F. P.

    1967-01-01

    Horizontal jitter in the video presentation in television systems is prevented by using an additional sync level. This circuitry uses simultaneous signals at both sync and porch frequencies, providing a sync identification from which a coincidence circuit can generate pulses having the required stability and noise immunity.

  6. [Zinc- and tin-induced apoptotic mechanisms in immune system and cranial nerve system].

    PubMed

    Tomiyama, Kenichi; Arakawa, Yasuaki

    2016-07-01

    This review explains the mechanisms of apoptosis related to the impacts of zinc deficiency and organotin exposure on the immune and central nervous systems. In the immune systems, both zinc deficiency and trialkyltin exposure lead to severe thymic atrophy and affect T-lymphocyte development through apoptosis of double positive stage pre-T-cells(CD4+/CD8+) in the cortex region. Their apoptosis are caused mainly through decrease in Bcl-2 expression, activation of ROS production/release, oxidative stress, mitochondrial cytochrome c release and activation of caspase cascade, with increases in glucocorticoids in zinc deficiency, without the involvement of glucocorticoid in organotin exposure In the central nervous system, both zinc deficiency and trialkyltin exposure reduce learning, memory and sensory functions through neuronal apoptosis caused by activation of ROS production/release, release of pro-apoptotic factors such as cytochrome c or apoptosis-inducing factor(AIF), with Fe excessive accumulation leading to ROS production and with depletion of hippocampus Zn (mossy fiber Zn) causing various Ca2+ channel disorder of synapse in the hippocampus, and with excessive accumulation of Ca through cAMP-dependent Ca(2+)-channel disorder by excessive PTH and cAMP excessive production in the olfactory systems such as olfactory epithelium and olfactory bulb.

  7. Studies of Cell-Mediated Immunity Against Immune Disorders Using Synthetic Peptides and Rotating Bioreactor System

    NASA Technical Reports Server (NTRS)

    Sastry, Jagannadha K.

    1998-01-01

    We conducted a series of experiments using mouse immune-precursor cells, and observed that bioreactor culturing results in the loss of antigen-specific cytotoxic T lymphocyte (CTL) function. The reason for the abrogation of CTL function is microgravity conditions in the bioreactor, but not the antigen per se or its MHC restriction. Similarly, we observed that allostimulation of human PBMC in the bioreactor, but not in the T flask, resulted in the blunting of both allo-CTL function and the NK activity, indicating that the microgravity-associated functional defects are not unique to the mouse system. These results provide further confirmation to the microgravity-associated immune dysfunction, and constitute ground-based confirmatory data for those related to space-travel.

  8. Effects of activation of maternal immune system at early stages of pregnancy on antitumor immunity of the progeny.

    PubMed

    Obernikhin, S S

    2013-11-01

    The effects of maternal immune system on the formation and functioning of the fetus is an important problem. Single stimulation of immune system of female C57Bl/6 mice with concanavalin A at the early stages of pregnancy before the formation of fetal immune organs was followed by impairment of antitumor immunity in the progeny by the time of puberty. These changes manifested in the increased survival rate of B16 melanoma, high rate of death of tumor-bearing animals, and low cytotoxic activity of spleen cells on L-929 fibrosarcoma cells.

  9. Hospital For Special Surgery/Immune System REgulation In Musculoskeletal Disorders

    SciTech Connect

    Eric Meffre; Lionel Ivashkiv

    2007-08-20

    Inflammation on musculoskeletal disorders such as rheumatoid arthritis (RA) is the result of dysregulation of the immune system. When the immune system, which maintains the integrity of the organism in an environment rich in infectious microbes, becomes misdirected toward components of one’s own tissue, autoimmune disease can result with autoantibodies contributing to the inflammation and tissue damage. RA is a chronic autoimmune disease marked by severe inflammation that causes pain, swelling, stiffness and loss of function in the joints, which is estimated to affect 1 percent of the US adult population. Furthermore, autoimmune diseases, which affect women at a higher rate, are the fourth largest cause of disability among women in the US and among the top ten causes of death. The long range goal of this study is to elucidate the mechanisms that regulate the generation of autoantibodies by B cells in normal individuals and in patients with autoimmune diseases and provide insights into potential therapeutic interventions.

  10. Interactions between Artificial Gravity, the Affected Physiological Systems, and Nutrition

    NASA Technical Reports Server (NTRS)

    Heer, Martina; Baecker, Nathalie; Zwart, Sara; Smith, Scott

    2006-01-01

    Malnutrition, either by insufficient supply of some nutrients or by overfeeding, has a profound effect on the health of an organism. Therefore, optimal nutrition is a necessity in normal gravity on Earth, in microgravity, and when applying artificial gravity to the human system. Reduced physical activity, such as observed in microgravity or bed rest, has an effect on many physiological systems, such as the cardiovascular, musculoskeletal, immune, and body fluids regulation systems. There is currently no countermeasure that is effective to counteract both the cardiovascular and musculoskeletal deconditioning when applied for a short duration (see Chapter 1). Artificial gravity therefore seems the simplest physiological approach to keep these systems intact. The application of intermittent daily dose of artificial gravity by means of centrifugation has often been proposed as a potential countermeasure against the physiological deconditioning induced by spaceflight. However, neither the optimal gravity level, nor its optimal duration of exposure have been enough studied to recommend a validated, effective, and efficient artificial gravity application. As discussed in previous chapters, artificial gravity has a very high potential to counteract any changes caused by reduced physical activity. The nutrient supply, which ideally should match the actual needs, will interact with these changes and therefore has also to be taken into account. This chapter reviews the potential interactions between these nutrients (energy intake, vitamins, minerals) and the other physiological systems affected by artificial gravity generated by an on-board short-radius centrifuge.

  11. Effects of chalcone derivatives on players of the immune system.

    PubMed

    Lee, Jian Sian; Bukhari, Syed Nasir Abbas; Fauzi, Norsyahida Mohd

    2015-01-01

    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells.

  12. Effects of chalcone derivatives on players of the immune system

    PubMed Central

    Lee, Jian Sian; Bukhari, Syed Nasir Abbas; Fauzi, Norsyahida Mohd

    2015-01-01

    The immune system is the defense mechanism in living organisms that protects against the invasion of foreign materials, microorganisms, and pathogens. It involves multiple organs and tissues in human body, such as lymph nodes, spleen, and mucosa-associated lymphoid tissues. However, the execution of immune activities depends on a number of specific cell types, such as B cells, T cells, macrophages, and granulocytes, which provide various immune responses against pathogens. In addition to normal physiological functions, abnormal proliferation, migration, and differentiation of these cells (in response to various chemical stimuli produced by invading pathogens) have been associated with several pathological disorders. The unwanted conditions related to these cells have made them prominent targets in the development of new therapeutic interventions against various pathological implications, such as atherosclerosis and autoimmune diseases. Chalcone derivatives exhibit a broad spectrum of pharmacological activities, such as immunomodulation, as well as anti-inflammatory, anticancer, antiviral, and antimicrobial properties. Many studies have been conducted to determine their inhibitory or stimulatory activities in immune cells, and the findings are of significance to provide a new direction for subsequent research. This review highlights the effects of chalcone derivatives in different types of immune cells. PMID:26316713

  13. 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.

  14. Stochastic stage-structured modeling of the adaptive immune system

    SciTech Connect

    Chao, D. L.; Davenport, M. P.; Forrest, S.; Perelson, Alan S.,

    2003-01-01

    We have constructed a computer model of the cytotoxic T lymphocyte (CTL) response to antigen and the maintenance of immunological memory. Because immune responses often begin with small numbers of cells and there is great variation among individual immune systems, we have chosen to implement a stochastic model that captures the life cycle of T cells more faithfully than deterministic models. Past models of the immune response have been differential equation based, which do not capture stochastic effects, or agent-based, which are computationally expensive. We use a stochastic stage-structured approach that has many of the advantages of agent-based modeling but is more efficient. Our model can provide insights into the effect infections have on the CTL repertoire and the response to subsequent infections.

  15. Single nucleotide polymorphisms of human STING can affect innate immune response to cyclic dinucleotides.

    PubMed

    Yi, Guanghui; Brendel, Volker P; Shu, Chang; Li, Pingwei; Palanathan, Satheesh; Cheng Kao, C

    2013-01-01

    The STING (stimulator of interferon genes) protein can bind cyclic dinucleotides to activate the production of type I interferons and inflammatory cytokines. The cyclic dinucleotides can be bacterial second messengers c-di-GMP and c-di-AMP, 3'5'-3'5' cyclic GMP-AMP (3'3' cGAMP) produced by Vibrio cholerae and metazoan second messenger 2'5'-3'5' Cyclic GMP-AMP (2'3' cGAMP). Analysis of single nucleotide polymorphism (SNP) data from the 1000 Genome Project revealed that R71H-G230A-R293Q (HAQ) occurs in 20.4%, R232H in 13.7%, G230A-R293Q (AQ) in 5.2%, and R293Q in 1.5% of human population. In the absence of exogenous ligands, the R232H, R293Q and AQ SNPs had only modest effect on the stimulation of IFN-β and NF-κB promoter activities in HEK293T cells, while HAQ had significantly lower intrinsic activity. The decrease was primarily due to the R71H substitution. The SNPs also affected the response to the cyclic dinucleotides. In the presence of c-di-GMP, the R232H variant partially decreased the ability to activate IFN-βsignaling, while it was defective for the response to c-di-AMP and 3'3' cGAMP. The R293Q dramatically decreased the stimulatory response to all bacterial ligands. Surprisingly, the AQ and HAQ variants maintained partial abilities to activate the IFN-β signaling in the presence of ligands due primarily to the G230A substitution. Biochemical analysis revealed that the recombinant G230A protein could affect the conformation of the C-terminal domain of STING and the binding to c-di-GMP. Comparison of G230A structure with that of WT revealed that the conformation of the lid region that clamps onto the c-di-GMP was significantly altered. These results suggest that hSTING variation can affect innate immune signaling and that the common HAQ haplotype expresses a STING protein with reduced intrinsic signaling activity but retained the ability to response to bacterial cyclic dinucleotides.

  16. Progress in immunization information systems - United States, 2010.

    PubMed

    2012-06-29

    Immunization information systems (IIS) are confidential, computerized, population-based systems that collect and consolidate vaccination data from vaccination providers and provide important tools for designing and sustaining effective immunization strategies at the provider and immunization program levels. These tools include clinical decision support, vaccination coverage reports, interoperability with electronic health record systems, vaccine inventory management, and the ability to generate reminder and recall messages. In 2010, based on strong evidence of effectiveness, the Task Force on Community Preventive Services recommended IIS use as a means of increasing vaccination rates. A Healthy People 2020 target (IID-18) is to increase to 95% the proportion of children aged <6 years whose immunization records are in fully operational, population-based IIS. To monitor progress toward program goals, CDC annually surveys 56 immunization program grantees (50 states, five cities, and the District of Columbia) using the IIS Annual Report (IISAR). Results from the 2010 IISAR (completed by 54 grantees) indicate that 82% (18.8 million) of U.S. children aged <6 years participated in IIS, as defined by having at least two recorded vaccinations, an increase from 78% (18.0 million) in 2009. Among 52 grantees who responded to questions about the Vaccine Tracking System (VTrckS), CDC's new national vaccine ordering and inventory management system for publicly purchased vaccine, 38 (73%) indicated their intention to use the IIS in their state or city to interface with VTrckS. Use of IIS to interface with VTrckS might provide additional incentive for vaccination providers to participate in IIS and enhance IIS utility by supporting efficient and effective methods for providers to order vaccine and track inventory and by promoting greater accountability of publicly purchased vaccine.

  17. Bacillus cereus var. toyoi enhanced systemic immune response in piglets.

    PubMed

    Schierack, Peter; Wieler, Lothar H; Taras, David; Herwig, Volker; Tachu, Babila; Hlinak, Andreas; Schmidt, Michael F G; Scharek, Lydia

    2007-07-15

    Probiotic bacteria have been suggested to stimulate the host immune system. In this study we evaluated the immunomodulatory effects of probiotic Bacillus cereus var. toyoi on the systemic immunity of piglets. A pool of 70 piglets was divided into a probiotic or control group. We determined the ratios of peripheral blood mononuclear cell (PBMC) subsets and measured proliferative responses and cytokine production of PBMCs and effects on vaccination responses. Blood samples of probiotic-treated piglets showed a significantly lower frequency of CD8(high)/CD3+ T cells and CD8(low)/CD3+ T cells and a significant higher CD4+/CD8+ ratio. IL-4 and IFN-gamma production of polyclonally stimulated PBMCs was on average higher in the probiotic group. Specific proliferative responses of PBMCs to Influenza vaccination antigens were significantly higher and antibody titers against H3N2 Influenza and Mycoplasma vaccination antigens were on average higher in the probiotic group. In conclusion, B. cereus var. toyoi therefore alters the immune status of piglets as indicated by changes in the ratios as well as functionalities of systemic immune cell populations.

  18. Signal transduction in cells of the immune system in microgravity.

    PubMed

    Ullrich, Oliver; Huber, Kathrin; Lang, Kerstin

    2008-10-28

    Life on Earth developed in the presence and under the constant influence of gravity. Gravity has been present during the entire evolution, from the first organic molecule to mammals and humans. Modern research revealed clearly that gravity is important, probably indispensable for the function of living systems, from unicellular organisms to men. Thus, gravity research is no more or less a fundamental question about the conditions of life on Earth. Since the first space missions and supported thereafter by a multitude of space and ground-based experiments, it is well known that immune cell function is severely suppressed in microgravity, which renders the cells of the immune system an ideal model organism to investigate the influence of gravity on the cellular and molecular level. Here we review the current knowledge about the question, if and how cellular signal transduction depends on the existence of gravity, with special focus on cells of the immune system. Since immune cell function is fundamental to keep the organism under imnological surveillance during the defence against pathogens, to investigate the effects and possible molecular mechanisms of altered gravity is indispensable for long-term space flights to Earth Moon or Mars. Thus, understanding the impact of gravity on cellular functions on Earth will provide not only important informations about the development of life on Earth, but also for therapeutic and preventive strategies to cope successfully with medical problems during space exploration.

  19. Human nutrition, the gut microbiome, and immune system: envisioning the future

    PubMed Central

    Kau, Andrew L.; Ahern, Philip P.; Griffin, Nicholas W.; Goodman, Andrew L.; Gordon, Jeffrey I.

    2012-01-01

    Summary Paragraph Dramatic changes in socioeconomic status, cultural traditions, population growth, and agriculture are affecting diets worldwide. Understanding how our diet and nutritional status influence the composition and dynamic operations of our gut microbial communities, and the innate and adaptive arms of our immune system, represents an area of scientific need, opportunity and challenge. The insights gleaned should help address a number of pressing global health problems. PMID:21677749

  20. Immune system stimulation by the native gut microbiota of honey bees

    PubMed Central

    Mancenido, Amanda L.; Moran, Nancy A.

    2017-01-01

    Gut microbial communities can greatly affect host health by modulating the host's immune system. For many important insects, however, the relationship between the gut microbiota and immune function remains poorly understood. Here, we test whether the gut microbial symbionts of the honey bee can induce expression of antimicrobial peptides (AMPs), a crucial component of insect innate immunity. We find that bees up-regulate gene expression of the AMPs apidaecin and hymenoptaecin in gut tissue when the microbiota is present. Using targeted proteomics, we detected apidaecin in both the gut lumen and the haemolymph; higher apidaecin concentrations were found in bees harbouring the normal gut microbiota than in bees lacking gut microbiota. In in vitro assays, cultured strains of the microbiota showed variable susceptibility to honey bee AMPs, although many seem to possess elevated resistance compared to Escherichia coli. In some trials, colonization by normal gut symbionts resulted in improved survivorship following injection with E. coli. Our results show that the native, non-pathogenic gut flora induces immune responses in the bee host. Such responses might be a host mechanism to regulate the microbiota, and could potentially benefit host health by priming the immune system against future pathogenic infections. PMID:28386455

  1. Impact of Particle Irradiation on the Immune System: From the Clinic to Mars

    PubMed Central

    Fernandez-Gonzalo, Rodrigo; Baatout, Sarah; Moreels, Marjan

    2017-01-01

    Despite the generalized use of photon-based radiation (i.e., gamma rays and X-rays) to treat different cancer types, particle radiotherapy (i.e., protons and carbon ions) is becoming a popular, and more effective tool to treat specific tumors due to the improved physical properties and biological effectiveness. Current scientific evidence indicates that conventional radiation therapy affects the tumor immunological profile in a particular manner, which in turn, might induce beneficial effects both at local and systemic (i.e., abscopal effects) levels. The interaction between radiotherapy and the immune system is being explored to combine immune and radiation (including particles) treatments, which in many cases have a greater clinical effect than any of the therapies alone. Contrary to localized, clinical irradiation, astronauts are exposed to whole body, chronic cosmic radiation, where protons and heavy ions are an important component. The effects of this extreme environment during long periods of time, e.g., a potential mission to Mars, will have an impact on the immune system that could jeopardize the health of the astronauts, hence the success of the mission. To this background, the purpose of this mini review is to briefly present the current knowledge in local and systemic immune alterations triggered by particle irradiation and to propose new lines of future research. Immune effects induced by particle radiation relevant to clinical applications will be covered, together with examples of combined radiotherapy and immunotherapy. Then, the focus will move to outer space, where the immune system alterations induced by cosmic radiation during spaceflight will be discussed. PMID:28275377

  2. Impact of Particle Irradiation on the Immune System: From the Clinic to Mars.

    PubMed

    Fernandez-Gonzalo, Rodrigo; Baatout, Sarah; Moreels, Marjan

    2017-01-01

    Despite the generalized use of photon-based radiation (i.e., gamma rays and X-rays) to treat different cancer types, particle radiotherapy (i.e., protons and carbon ions) is becoming a popular, and more effective tool to treat specific tumors due to the improved physical properties and biological effectiveness. Current scientific evidence indicates that conventional radiation therapy affects the tumor immunological profile in a particular manner, which in turn, might induce beneficial effects both at local and systemic (i.e., abscopal effects) levels. The interaction between radiotherapy and the immune system is being explored to combine immune and radiation (including particles) treatments, which in many cases have a greater clinical effect than any of the therapies alone. Contrary to localized, clinical irradiation, astronauts are exposed to whole body, chronic cosmic radiation, where protons and heavy ions are an important component. The effects of this extreme environment during long periods of time, e.g., a potential mission to Mars, will have an impact on the immune system that could jeopardize the health of the astronauts, hence the success of the mission. To this background, the purpose of this mini review is to briefly present the current knowledge in local and systemic immune alterations triggered by particle irradiation and to propose new lines of future research. Immune effects induced by particle radiation relevant to clinical applications will be covered, together with examples of combined radiotherapy and immunotherapy. Then, the focus will move to outer space, where the immune system alterations induced by cosmic radiation during spaceflight will be discussed.

  3. Consumption of Oxidized Soybean Oil Increased Intestinal Oxidative Stress and Affected Intestinal Immune Variables in Yellow-feathered Broilers.

    PubMed

    Liang, Fangfang; Jiang, Shouqun; Mo, Yi; Zhou, Guilian; Yang, Lin

    2015-08-01

    This study investigated the effect of oxidized soybean oil in the diet of young chickens on growth performance and intestinal oxidative stress, and indices of intestinal immune function. Corn-soybean-based diets containing 2% mixtures of fresh and oxidized soybean oil provided 6 levels (0.15, 1.01, 3.14, 4.95, 7.05, and 8.97 meqO2/kg) of peroxide value (POV) in the diets. Each dietary treatment, fed for 22 d, had 6 replicates, each containing 30 birds (n = 1,080). Increasing POV levels reduced average daily feed intake (ADFI) of the broilers during d 1 to 10, body weight and average daily gain at d 22 but did not affect overall ADFI. Concentrations of malondialdehyde (MDA) increased in plasma and jejunum as POV increased but total antioxidative capacity (T-AOC) declined in plasma and jejunum. Catalase (CAT) activity declined in plasma and jejunum as did plasma glutathione S-transferase (GST). Effects were apparent at POV exceeding 3.14 meqO2/kg for early ADFI and MDA in jejunum, and POV exceeding 1.01 meqO2/kg for CAT in plasma and jejunum, GST in plasma and T-AOC in jejunum. Relative jejunal abundance of nuclear factor kappa B (NF-κB) P50 and NF-κB P65 increased as dietary POV increased. Increasing POV levels reduced the jejunal concentrations of secretory immunoglobulin A and cluster of differentiation (CD) 4 and CD8 molecules with differences from controls apparent at dietary POV of 3.14 to 4.95 meqO2/kg. These findings indicated that growth performance, feed intake, and the local immune system of the small intestine were compromised by oxidative stress when young broilers were fed moderately oxidized soybean oil.

  4. Nasal immunity is an ancient arm of the mucosal immune system of vertebrates

    PubMed Central

    Larragoite, Erin T.; Crossey, Kyle; Erhardt, Erik B.; Martin, Samuel A.M.; LaPatra, Scott E.; Salinas, Irene

    2015-01-01

    The mucosal surfaces of all vertebrates have been exposed to similar evolutionary pressures for millions of years. In terrestrial vertebrates such as birds and mammals, the nasopharynx-associated lymphoid tissue (NALT) represents a first line of immune defence. Here we propose that NALT is an ancient arm of the mucosal immune system not restricted to terrestrial vertebrates. We find that NALT is present in rainbow trout and that it resembles other teleost mucosa-associated lymphoid tissues. Trout NALT consists of diffuse lymphoid cells and lacks tonsils and adenoids. The predominant B-cell subset found in trout NALT are IgT + B cells, similar to skin and gut. The trout olfactory organ is colonized by abundant symbiotic bacteria, which are coated by trout secretory immunoglobulin. Trout NALT is capable of mounting strong anti-viral immune responses following nasal delivery of a live attenuated viral vaccine. Our results open up a new tool for the control of aquatic infectious diseases via nasal vaccination. PMID:25335508

  5. Cortisol and corticosterone in the songbird immune and nervous systems: local vs. systemic levels during development.

    PubMed

    Schmidt, Kim L; Soma, Kiran K

    2008-07-01

    Glucocorticoids (GCs) have profound effects on the immune and nervous systems during development. However, circulating GC levels are low neonatally and show little response to stressors. This paradox could be resolved if immune and neural tissues locally synthesize GCs. Here, we measured baseline corticosterone and cortisol levels in plasma, immune organs, and brain regions of developing zebra finches. Steroids were extracted using solid phase-extraction and quantified using specific immunoassays. As expected, corticosterone was the predominant GC in plasma and increased with age. In contrast, cortisol was the predominant GC in immune tissues (bursa of Fabricius, thymus, spleen) and decreased with age. Cortisol levels in immune tissues were higher than cortisol levels in plasma. In the brain, corticosterone and cortisol levels were similarly low, providing little evidence for local synthesis of GCs in the brain. This is the first study to measure 1) cortisol in the plasma of songbirds, 2) corticosterone or cortisol in the brain of songbirds, and 3) corticosterone or cortisol in the immune system of any species. Despite the prevailing dogma that corticosterone is the primary GC in birds, these results indicate that cortisol is the predominant GC in the immune system of developing zebra finches. These results raise the hypothesis that cortisol is synthesized de novo from cholesterol in the immune system as an "immunosteroid," analogous to neurosteroids synthesized in the brain. Local production of GCs in immune tissues may allow GCs to regulate lymphocyte selection while avoiding the costs of high systemic GCs during development.

  6. 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.

  7. Progress in immunization information systems--United States, 2011.

    PubMed

    2013-01-25

    Immunization information systems (IIS) are confidential, computerized, population-based systems that collect and consolidate vaccination data from vaccination providers and provide important tools for designing and sustaining effective immunization strategies. A Healthy People 2020 objective (IID-18) is to increase to 95% the proportion of children aged <6 years whose immunization records are in fully operational, population-based IIS. The National Vaccine Advisory Committee (NVAC) has published goals for IIS, including required and optional core data elements for which IIS should collect information. Two of the required core data elements are vaccine manufacturer and vaccine lot number. To monitor progress toward achieving these and other program goals, CDC annually surveys 56 immunization program grantees using the IIS Annual Report (IISAR). Results from the 2011 IISAR (completed by 54 grantees) indicate that 84% (19.2 million) of U.S. children aged <6 years participated in IIS, as defined by having at least two recorded vaccinations, an increase from 82% (18.8 million) in 2010. Grantees reported that an average of 63% of vaccination records for these children contained data in the field for vaccine manufacturer and 60% contained data in the field for lot number. A new project under way to capture vaccine product information, expiration date, and lot number on two-dimensional (2D) barcodes on vaccine vials might increase completeness, accuracy, and availability of these data elements in patient medical records and IIS, which in turn might enhance vaccine safety and support vaccine inventory management.

  8. HIV Immune Recovery Inflammatory Syndrome and Central Nervous System Paracoccidioidomycosis.

    PubMed

    de Almeida, Sérgio Monteiro; Roza, Thiago Henrique

    2017-04-01

    The immune reconstitution inflammatory syndrome (IRIS) is a deregulated inflammatory response to invading microorganisms. It is manifested when there is an abrupt change in host immunity from an anti-inflammatory and immunosuppressive state to a pro-inflammatory state as a result of rapid depletion or removal of factors that promote immune suppression or inhibition of inflammation. The aim of this paper is to discuss and re-interpret the possibility of association of paracoccidioidomycosis (PCM) with IRIS in the central nervous system (CNS) in a case from Brazil published by Silva-Vergara ML. et al. (Mycopathologia 177:137-141, 6). An AIDS patient who was not receiving medical care developed pulmonary PCM successfully treated with itraconazole. The patient developed central nervous system PCM (NPCM) after starting the ARV therapy with recovery of immunity and control of HIV viral load, although it was not interpreted as IRIS by the authors, it fulfills the criteria for CNS IRIS. This could be the first case of NPCM associated with IRIS described. Although not frequent, IRIS must be considered in PCM patients and HIV, from endemic areas or patients that traveled to endemic areas, receiving ARV treatment and with worsening symptoms.

  9. Controlling cytomegalovirus: helping the immune system take the lead.

    PubMed

    Hanley, Patrick J; Bollard, Catherine M

    2014-05-27

    Cytomegalovirus, of the Herpesviridae family, has evolved alongside humans for thousands of years with an intricate balance of latency, immune evasion, and transmission. While upwards of 70% of humans have evidence of CMV infection, the majority of healthy people show little to no clinical symptoms of primary infection and CMV disease is rarely observed during persistent infection in immunocompetent hosts. Despite the fact that the majority of infected individuals are asymptomatic, immunologically, CMV hijacks the immune system by infecting and remaining latent in antigen-presenting cells that occasionally reactivate subclinically and present antigen to T cells, eventually causing the inflation of CMV-specific T cells until they can compromise up to 10% of the entire T cell repertoire. Because of this impact on the immune system, as well as its importance in fields such as stem cell and organ transplant, the relationship between CMV and the immune response has been studied in depth. Here we provide a review of many of these studies and insights into how CMV-specific T cells are currently being used therapeutically.

  10. Toll-like Receptor 1 Polymorphisms Affect Innate Immune Responses and Outcomes in Sepsis

    PubMed Central

    Wurfel, Mark M.; Gordon, Anthony C.; Holden, Tarah D.; Radella, Frank; Strout, Jeanna; Kajikawa, Osamu; Ruzinski, John T.; Rona, Gail; Black, R. Anthony; Stratton, Seth; Jarvik, Gail P.; Hajjar, Adeline M.; Nickerson, Deborah A.; Rieder, Mark; Sevransky, Jonathan; Maloney, James P.; Moss, Marc; Martin, Greg; Shanholtz, Carl; Garcia, Joe G. N.; Gao, Li; Brower, Roy; Barnes, Kathleen C.; Walley, Keith R.; Russell, James A.; Martin, Thomas R.

    2008-01-01

    Rationale: Polymorphisms affecting Toll-like receptor (TLR)–mediated responses could predispose to excessive inflammation during an infection and contribute to an increased risk for poor outcomes in patients with sepsis. Objectives: To identify hypermorphic polymorphisms causing elevated TLR-mediated innate immune cytokine and chemokine responses and to test whether these polymorphisms are associated with increased susceptibility to death, organ dysfunction, and infections in patients with sepsis. Methods: We screened single-nucleotide polymorphisms (SNPs) in 43 TLR-related genes to identify variants affecting TLR-mediated inflammatory responses in blood from healthy volunteers ex vivo. The SNP associated most strongly with hypermorphic responses was tested for associations with death, organ dysfunction, and type of infection in two studies: a nested case–control study in a cohort of intensive care unit patients with sepsis, and a case–control study using patients with sepsis, patients with sepsis-related acute lung injury, and healthy control subjects. Measurements and Main Results: The SNP demonstrating the most hypermorphic effect was the G allele of TLR1−7202A/G (rs5743551), which associated with elevated TLR1-mediated cytokine production (P < 2 × 10−20). TLR1−7202G marked a coding SNP that causes higher TLR1-induced NF-κB activation and higher cell surface TLR1 expression. In the cohort of patients with sepsis TLR1−7202G predicted worse organ dysfunction and death (odds ratio, 1.82; 95% confidence interval, 1.07–3.09). In the case-control study TLR1−7202G was associated with sepsis-related acute lung injury (odds ratio, 3.40; 95% confidence interval, 1.59–7.27). TLR1−7202G also associated with a higher prevalence of gram-positive cultures in both clinical studies. Conclusions: Hypermorphic genetic variation in TLR1 is associated with increased susceptibility to organ dysfunction, death, and gram-positive infection in sepsis. PMID

  11. The use of an immunization information system to establish baseline childhood immunization rates and measure contract objectives.

    PubMed

    Schauer, Stephanie L; Maerz, Thomas R; Hurie, Marjorie B; Gabor, Gerald W; Flynn, John M; Davis, Jeffrey P

    2009-01-01

    Measuring progress toward national immunization objectives at the local level, although difficult, is becoming more feasible owing to statewide immunization information systems. This article describes how a state immunization program expanded the scope of immunization service contracts with local health departments (LHDs) to address the immunization rates among children living within their jurisdictions using the Wisconsin Immunization Registry (WIR) to measure achievement of population-based objectives. By contract year (CY) 2008, 99 percent of Wisconsin LHDs selected population-based contract objectives. In late 2008, the Wisconsin Immunization Program assessed all children at 24 months of age for completeness of the 4:3:1:3:3:1 (diphtheria, tetanus, pertussis/poliovirus/measles-containing vaccine/Haemophilus influenzae type b/hepatitis B/varicella) series by county for each of four CYs, using the WIR. From CY 2005 to CY 2008, LHDs in 61 (86%) of the 71 counties demonstrated increased series completeness rates for the series, and the overall statewide series completeness increased from 58 percent to 64 percent. However, the increases we observed cannot be attributed solely to LHDs' acceptance of population-based objectives because controlling for other factors known to influence immunization coverage levels was outside the scope of this case study. We found the WIR to be a powerful tool that can measure immunization coverage among local populations independent of the immunization provider, assess improvement toward contract objectives, and target resources toward pockets of need.

  12. Time of Initiating Enzyme Replacement Therapy Affects Immune Abnormalities and Disease Severity in Patients with Gaucher Disease

    PubMed Central

    Ioanou, Chidima; Plassmeyer, Matthew; Ryherd, Mark; Kozhaya, Lina; Austin, Lauren; Abidoglu, Cem; Unutmaz, Derya; Alpan, Oral; Goker-Alpan, Ozlem

    2016-01-01

    Gaucher disease (GD) patients often present with abnormalities in immune response that may be the result of alterations in cellular and/or humoral immunity. However, how the treatment and clinical features of patients impact the perturbation of their immunological status remains unclear. To address this, we assessed the immune profile of 26 GD patients who were part of an enzyme replacement therapy (ERT) study. Patients were evaluated clinically for onset of GD symptoms, duration of therapy and validated outcome measures for ERT. According to DS3 disease severity scoring system criteria, they were assigned to have mild, moderate or severe GD. Flow cytometry based immunophenotyping was performed to analyze subsets of T, B, NK, NKT and dendritic cells. GD patients showed multiple types of immune abnormalities associated to T and B lymphocytes with respect to their subpopulations as well as memory and activation markers. Skewing of CD4 and CD8 T cell numbers resulting in lower CD4/CD8 ratio and an increase in overall T cell activation were observed. A decrease in the overall B cells and an increase in NK and NKT cells were noted in the GD patients compared to controls. These immune alterations do not correlate with GD clinical type or level of biomarkers. However, subjects with persistent immune alterations, especially in B cells and DCs correlate with longer delay in initiation of ERT (ΔTX). Thus, while ERT may reverse some of these immune abnormalities, the immune cell alterations become persistent if therapy is further delayed. These findings have important implications in understanding the immune disruptions before and after treatment of GD patients. PMID:27942037

  13. Simulation of HIV infection in artificial immune systems

    NASA Astrophysics Data System (ADS)

    Sieburg, Hans B.; McCutchan, J. Allen; Clay, Oliver K.; Cabalerro, Lisa; Ostlund, James J.

    1990-09-01

    Infection by the human immunodeficiency virus (HIV) causes a multi-faceted disease process which ultimately leads to severe degenerative conditions in the immune and nervous systems. The complexity of the virus/host-system interaction has brought into sharp focus the need for alternative efforts by which to overcome the limitations of available animal models. This article reports on the dynamics of HIV infection in an artificial immune system (AIS), a novel in silico tool for bio-medical research. Using a method of graphical programming, the HIV/AIS interactions are described at the cellular level and then transferred into the setting of an asynchronous cellular automaton simulation. A specific problem in HIV pathogenesis is addressed: To determine the extent by which the physiological connectivity of a normal B-cell, T-cell, macrophage immune system supports persistence of infection and disease progression to AIDS. Several observations are discussed which will be presented in four categories: (a) the major known manifestations of HIV infection and AIDS; (b) the predictability of latency and sudden progression to disease; (c) the predictability of HIV-dependent alterations of cytokine secretion patterns, and (d) secondary infections, which are found to be a critical element in establishing and maintaining a progressive disease dynamics. The effects of exogenously applied cytokine Interleukin 2 are considered. All results are summarized in a phase-graph model of the global HIV/AIS dynamical system.

  14. Security framework for networked storage system based on artificial immune system

    NASA Astrophysics Data System (ADS)

    Huang, Jianzhong; Xie, Changsheng; Zhang, Chengfeng; Zhan, Ling

    2007-11-01

    This paper proposed a theoretical framework for the networked storage system addressing the storage security. The immune system is an adaptive learning system, which can recognize, classify and eliminate 'non-self' such as foreign pathogens. Thus, we introduced the artificial immune technique to the storage security research, and proposed a full theoretical framework for storage security system. Under this framework, it is possible to carry out the quantitative evaluation for the storage security system using modeling language of artificial immune system (AIS), and the evaluation can offer security consideration for the deployment of networked storage system. Meanwhile, it is potential to obtain the active defense technique suitable for networked storage system via exploring the principle of AIS and achieve a highly secure storage system with immune characteristic.

  15. Location of tumor affects local and distant immune cell type and number

    PubMed Central

    Hensel, Jonathan A.; Khattar, Vinayak; Ashton, Reading; Lee, Carnellia; Siegal, Gene P.

    2017-01-01

    Abstract Introduction Tumors comprise heterogeneous populations of cells, including immune infiltrates that polarize during growth and metastasis. Our preclinical studies on breast cancer (BCa) identified functional differences in myeloid‐derived suppressor cells based on tumor microenvironment (TME), prompting variations in host immune response to tumor growth, and dissemination based on tissue type. Methods In order to understand if such variations existed among other immune cells, and if such alteration occurs in response to tumor growth at the primary site or due to bone dissemination, we characterized immune cells, examining localized growth and in the tibia. In addition, immune cells from the spleen were examined from animals of both tumor locations by flow cytometry. Results The study demonstrates that location of tumor, and not simply the tumor itself, has a definitive role in regulating immune effectors. Among all immune cells characterized, macrophages were decreased and myeloid dendritic cell were increased in both tumor locations. This difference was more evident in subcutaneous tumors. Additionally, spleens from mice with subcutaneous tumors contained greater increases in both macrophages and myeloid dendritic cells than in mice with bone tumors. Furthermore, in subcutaneous tumors there was an increase in CD4+ and CD8+ T‐cell numbers, which was also observed in their spleens. Conclusions These data indicate that alterations in tumor‐reactive immune cells are more pronounced at the primary site, and exert a similar change at the major secondary lymphoid organ than in the bone TME. These findings could provide translational insight into designing therapeutic strategies that account for location of metastatic foci. PMID:28250928

  16. Dietary polyunsaturated fatty acids from flaxseed affect immune responses of dairy sheep around parturition.

    PubMed

    Caroprese, Mariangela; Ciliberti, Maria Giovanna; Albenzio, Marzia; Annicchiarico, Giovanni; Sevi, Agostino

    2015-11-15

    The objective of the study was to characterize the immune profile of dairy ewes fed flaxseed, rich in polyunsaturated fatty acids (PUFA), around parturition. The hypothesis to be verified was that a physiological stressor, such as parturition, could be overcome with a nutritional manipulation in the diet of the animal in order to guarantee welfare of animals and to sustain their immune responses. Twenty Comisana ewes were divided in two groups (10 ewes/group), and fed a supplementation of whole flaxseed in the diet (FS group) or no supplementation (CON group). Blood samples were collected at parturition and then 7, 14, 21, 28, and 42 day post partum. Plasma samples were used to assess the humoral immune response after ovalbumin (OVA) immunization. At parturition, at 14 day, and 42 day post partum the level of plasma cytokines was assessed. The sheep showed a reduced responsiveness to OVA immunization. In FS ewes the IL-6 level remained unchanged until 14 day post partum and then significantly decreased from 14 day to 42 day post partum. IL-10 level was significantly higher in FS ewes than in CON ewes at 14 day. At parturition IL-1β level was significantly lower in FS ewes than in CON ewes and significantly decreased in both groups from parturition to 42 day. In conclusion, PUFA from flaxseed, as supplement in the diet of ewes around parturition can modulate sheep immune reactivity by influencing cytokine production.

  17. Early-life Exposure to Widespread Environmental Toxicants and Health Risk: A Focus on the Immune and Respiratory Systems.

    PubMed

    Cao, Junjun; Xu, Xijin; Hylkema, Machteld N; Zeng, Eddy Y; Sly, Peter D; Suk, William A; Bergman, Åke; Huo, Xia

    2016-01-01

    Evidence has accumulated that exposure to widespread environmental toxicants, such as heavy metals, persistent organic pollutants, and tobacco smoke adversely affect fetal development and organ maturation, even after birth. The developing immune and respiratory systems are more sensitive to environmental toxicants due to their long-term physical development, starting from the early embryonic stage and persisting into early postnatal life, which requires complex signaling pathways that control proliferation and differentiation of highly heterogeneous cell types. In this review, we summarize the effect of early-life exposure to several widespread environmental toxicants on immune and lung development before and after birth, including the effects on immune cell counts, baseline characteristics of cell-mediated and humoral immunity, and alteration of lung structure and function in offspring. We also review evidence supporting the association between early-life exposure to environmental toxicants and risk for immune-related diseases and lung dysfunction in offspring in later life.

  18. Harnessing the immune system to improve cancer therapy

    PubMed Central

    Papaioannou, Nikos E.; Beniata, Ourania V.; Vitsos, Panagiotis

    2016-01-01

    Cancer immunotherapy uses the immune system and its components to mount an anti-tumor response. During the last decade, it has evolved from a promising therapy option to a robust clinical reality. Many immunotherapeutic modalities are already approved by the Food and Drug Administration (FDA) for treating cancer patients and many others are in the pipeline for approval as standalone or combinatorial therapeutic interventions, several also combined with standard treatments in clinical studies. The two main axes of cancer immunotherapeutics refer to passive and active treatments. Prominent examples of passive immunotherapy include administration of monoclonal antibodies and cytokines and adoptive cell transfer of ex vivo “educated” immune cells. Active immunotherapy refers, among others, to anti-cancer vaccines [peptide, dendritic cell (DC)-based and allogeneic whole cell vaccines], immune checkpoint inhibitors and oncolytic viruses, whereas new approaches that can further enhance anti-cancer immune responses are also widely explored. Herein, we present the most popular cancer immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials. To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure. PMID:27563648

  19. Terrestrial stress analogs for spaceflight associated immune system dysregulation.

    PubMed

    Crucian, Brian; Simpson, Richard J; Mehta, Satish; Stowe, Raymond; Chouker, Alexander; Hwang, Shen-An; Actor, Jeffrey K; Salam, Alex P; Pierson, Duane; Sams, Clarence

    2014-07-01

    Recent data indicates that dysregulation of the immune system occurs and persists during spaceflight. Impairment of immunity, especially in conjunction with elevated radiation exposure and limited clinical care, may increase certain health risks during exploration-class deep space missions (i.e. to an asteroid or Mars). Research must thoroughly characterize immune dysregulation in astronauts to enable development of a monitoring strategy and validate any necessary countermeasures. Although the International Space Station affords an excellent platform for on-orbit research, access may be constrained by technical, logistical vehicle or funding limitations. Therefore, terrestrial spaceflight analogs will continue to serve as lower cost, easier access platforms to enable basic human physiology studies. Analog work can triage potential in-flight experiments and thus result in more focused on-orbit studies, enhancing overall research efficiency. Terrestrial space analogs generally replicate some of the physiological or psychological stress responses associated with spaceflight. These include the use of human test subjects in a laboratory setting (i.e. exercise, bed rest, confinement, circadian misalignment) and human remote deployment analogs (Antarctica winterover, undersea, etc.) that incorporate confinement, isolation, extreme environment, physiological mission stress and disrupted circadian rhythms. While bed rest has been used to examine the effects of physical deconditioning, radiation and microgravity may only be simulated in animal or microgravity cell culture (clinorotation) analogs. This article will characterize the array of terrestrial analogs for spaceflight immune dysregulation, the current evidence base for each, and interpret the analog catalog in the context of acute and chronic stress.

  20. 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.

  1. 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

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

    PubMed

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

    2016-04-01

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

  3. Rheumatoid Arthritis When Your Immune System Attacks Your Body | NIH MedlinePlus the Magazine

    MedlinePlus

    ... Understanding Rheumatoid Arthritis (RA) Rheumatoid Arthritis When Your Immune System Attacks Your Body Past Issues / Summer 2014 Table ... disease, which means the arthritis results from your immune system attacking your body's own tissues. The course of ...

  4. Rheumatoid Arthritis When Your Immune System Attacks Your Body | NIH MedlinePlus the Magazine

    MedlinePlus

    ... In an autoimmune disease like rheumatoid arthritis, the immune system turns against parts of the body it is ... In an autoimmune disease like rheumatoid arthritis, the immune system turns against parts of the body it is ...

  5. Investigation of man's immune system (M112), part B

    NASA Technical Reports Server (NTRS)

    Ritzmann, S. E.; Levin, W. C.

    1973-01-01

    Fifty-six days of residence in a Skylab-type environment produce essentially no change in the reactivity of the human immune system, as typified by the rate of RNA or DNA synthesis in small lymphocytes. The one point of divergence between the Skylab simulation crew and previous Apollo crews, a marked depression in synthesis rates on the fourteenth day after the chamber study, may be due to some technical difficulty in the experiment. Lymphocyte morphology changes paralleled functional changes.

  6. Animal mdels for the study of the effects of spaceflight on the immune system

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, G.

    Animal models have been used extensively to study the effects of spaceflight on the immune system. The rat has been the animal used most extensively, but some studies have also been carried out utilizing mice and rhesus monkeys. Hindlimb unloading of rats and mice is a ground-based model that has been utilized to determine the effects of spaceflight-type conditions on the immune systems. The results using this model have shown that hindlimb unloading results in alterations of functional rodent immune responses, including cytokine production, blastogenesis of leukocytes, response of bone marrow cells to colony stimulating factors, neutrophil activity, and resistance to infection. Distribution of leukocyte subtypes was not affected by hindlimb unloading. Studies on rats flown in space have demonstrated that exposure to spaceflight results in alterations in cytokine production, alterations in the ability of bone marrow cells to respond to colony stimulating factors, alterations in leukocyte subset distribution, and alterations in natural killer cell function. When pregnant rats were flown in space, although the immune responses of the pregnant mothers were altered by exposure to spaceflight, no effects of spaceflight on the immune responses of the offspring were observed. In one study, rhesus monkeys were flown in space and their immune status was evaluated upon their return to earth. Results of that study showed alterations in the ability of monkey immune cells to produce cytokines, express cytokine receptors, and respond to colony stimulating factor. Therefore, it is clear that exposure to spaceflight results in alterations in immune responses of the test animals. These changes are similar to those observed for humans that have flown in space, and demonstrate that the animal models are appropriate for studying the effects of spaceflight on the immune system. Although use of the hindlimb unloading model on the ground has indicated that exposure to the model also

  7. Systemic Imidacloprid Affects Intraguild Parasitoids Differently.

    PubMed

    Taylor, Sally V; Burrack, Hannah J; Roe, R Michael; Bacheler, Jack S; Sorenson, Clyde E

    2015-01-01

    Toxoneuron nigriceps (Viereck) (Hymenoptera, Braconidae) and Campoletis sonorensis (Cameron) (Hymenoptera, Ichneumonidae) are solitary endoparasitoids of the tobacco budworm, Heliothis virescens (Fabricius) (Lepidoptera, Noctuidae). They provide biological control of H. virescens populations in Southeastern US agricultural production systems. Field and greenhouse experiments conducted from 2011-2014 compared parasitism rates of parasitoids that developed inside H. virescens larvae fed on tobacco plants treated with and without imidacloprid. The parasitoids in our study did not have a similar response. Toxoneuron nigriceps had reduced parasitism rates, but parasitism rates of C. sonorensis were unaffected. Preliminary data indicate that adult female lifespans of T. nigriceps are also reduced. ELISA was used to measure concentrations of neonicotinoids, imidacloprid and imidacloprid metabolites in H. virescens larvae that fed on imidacloprid-treated plants and in the parasitoids that fed on these larvae. Concentrations were detectable in the whole bodies of parasitized H. virescens larvae, T. nigriceps larvae and T. nigriceps adults, but not in C. sonorensis larvae and adults. These findings suggest that there are effects of imidacloprid on multiple trophic levels, and that insecticide use may differentially affect natural enemies with similar feeding niches.

  8. Systemic Imidacloprid Affects Intraguild Parasitoids Differently

    PubMed Central

    Roe, R. Michael; Bacheler, Jack S.

    2015-01-01

    Toxoneuron nigriceps (Viereck) (Hymenoptera, Braconidae) and Campoletis sonorensis (Cameron) (Hymenoptera, Ichneumonidae) are solitary endoparasitoids of the tobacco budworm, Heliothis virescens (Fabricius) (Lepidoptera, Noctuidae). They provide biological control of H. virescens populations in Southeastern US agricultural production systems. Field and greenhouse experiments conducted from 2011–2014 compared parasitism rates of parasitoids that developed inside H. virescens larvae fed on tobacco plants treated with and without imidacloprid. The parasitoids in our study did not have a similar response. Toxoneuron nigriceps had reduced parasitism rates, but parasitism rates of C. sonorensis were unaffected. Preliminary data indicate that adult female lifespans of T. nigriceps are also reduced. ELISA was used to measure concentrations of neonicotinoids, imidacloprid and imidacloprid metabolites in H. virescens larvae that fed on imidacloprid-treated plants and in the parasitoids that fed on these larvae. Concentrations were detectable in the whole bodies of parasitized H. virescens larvae, T. nigriceps larvae and T. nigriceps adults, but not in C. sonorensis larvae and adults. These findings suggest that there are effects of imidacloprid on multiple trophic levels, and that insecticide use may differentially affect natural enemies with similar feeding niches. PMID:26658677

  9. Dynamic immune intrusion detection system for IPv6

    NASA Astrophysics Data System (ADS)

    Yao, Li; Li, Zhi-tang; Hao, Tu

    2005-03-01

    We have set up a project aimed at developing a dynamical immune intrusion detection system for IPv6 and protecting the next generation Internet from intrusion. We focus on investigating immunelogical principles in designing a dynamic multi-agent system for intrusion detection in IPv6 environment, instead of attempting to describe all that is intrusion in the network try and describe what is normal use and define "non-self" as intrusion. The proposed intrusion detection system is designed as flexible, extendible, and adaptable in order to meet the needs and preferences of network administrators for IPv6 environment.

  10. Age and genetic selection affect auto-immune profiles of chickens.

    PubMed

    Parmentier, Henk K; Harms, Elmer; Lammers, Aart; Nieuwland, Mike G B

    2014-12-01

    Specificity, antibody isotype distribution and levels, of natural autoantibodies (NAAb) may be potential informative parameters for immune mediated natural disease resistance, immune modulation, and maintenance of physiological homeostasis. In a previous study we detected IgM and IgG antibodies to liver antigens in plasma from 1 year old chickens. Auto-immune profiles directed towards liver antigens differed between chicken lines divergently selected for specific antibody responses to sheep red blood cells. In the present study we measured the presence and typed levels and antibody isotypes (IgG and IgM) of NAAb binding the 'auto-antigen' complex chicken liver cell lysate (CLL) in plasma samples obtained from chickens at 5 weeks and at 1-year of age, respectively, by quantitative western blotting. Extensive staining patterns of plasma antibodies binding CLL were found for both isotypes and at both ages in all birds. At both ages, IgM and IgG bound similar numbers of CLL antigens, which remained almost constant for IgM, whereas the number of IgG stained bands in time was enhanced. Significant differences of binding patterns of NAAb (stained antigen fragments of CLL and staining intensity) were detected between the three different chicken lines at both ages and between both ages, and lines could be clustered on the basis of their auto-antibody profile. The present results indicate that analysis of the plasma NAAb repertoire of poultry like in mammals could provide a way of distinguishing differences of immune competence (as reflected by the selection criterion of antibody responses) between individuals and lines, and could provide tools to select individual birds for health and other traits. The age-dependency of the auto-immune profile suggest that such profiles may also reflect immune maturation, which should be taken into account when relating an auto-immune profile with other traits.

  11. Using systems biology to simplify complex disease: immune cartography.

    PubMed

    Polpitiya, Ashoka D; McDunn, Jonathan E; Burykin, Anton; Ghosh, Bijoy K; Cobb, J Perren

    2009-01-01

    What if there was a rapid, inexpensive, and accurate blood diagnostic that could determine which patients were infected, identify the organism(s) responsible, and identify patients who were not responding to therapy? We hypothesized that systems analysis of the transcriptional activity of circulating immune effector cells could be used to identify conserved elements in the host response to systemic inflammation, and furthermore, to discriminate between sterile and infectious etiologies. We review herein a validated, systems biology approach demonstrating that 1) abdominal and pulmonary sepsis diagnoses can be made in mouse models using microarray (RNA) data from circulating blood, 2) blood microarray data can be used to differentiate between the host response to Gram-negative and Gram-positive pneumonia, 3) the endotoxin response of normal human volunteers can be mapped at the level of gene expression, and 4) a similar strategy can be used in the critically ill to follow septic patients and quantitatively determine immune recovery. These findings provide the foundation of immune cartography and demonstrate the potential of this approach for rapidly diagnosing sepsis and identifying pathogens. Further, our data suggest a new approach to determine how specific pathogens perturb the physiology of circulating leukocytes in a cell-specific manner. Large, prospective clinical trails are needed to validate the clinical utility of leukocyte RNA diagnostics (e.g., the riboleukogram).

  12. Progress in immunization information systems - United States, 2012.

    PubMed

    2013-12-13

    Immunization information systems (IIS) are confidential, computerized, population-based systems that collect and consolidate vaccination data from vaccination providers that can be used in designing and sustaining effective immunization strategies. To monitor progress toward achieving IIS program goals, CDC annually surveys immunization program grantees using the IIS Annual Report (IISAR). Results from the 2012 IISAR, completed by 54 of 56 grantees, indicate that 86% (19.5 million) of U.S. children aged <6 years, and 25% (57.8 million) of U.S. adults participated in IIS. Eight of 12 minimum functional standards for IIS published by the National Vaccine Advisory Committee (NVAC) have been met by ≥90% of grantees. During 2011-2012, progress was also made in meeting three additional functional standards, including the presence of core data element fields, timeliness of vaccine records, and Health Level 7 (HL7) messaging, and will be monitored in new functional standards for IIS published in 2013. Several new and ongoing initiatives, including interoperability between IIS and electronic health records (i.e., ensuring systems can work together and exchange information), the use of IIS to support vaccine ordering and inventory management, the use of two-dimensional barcodes to record vaccination information, and collaboration with pharmacies, federal agencies, and other adult vaccination providers, will support further progress in meeting functional standards and enhance reporting of adult vaccinations to IIS.

  13. Temperature stress affects the expression of immune response genes in the alfalfa leafcutting bee, Megachile rotundata.

    PubMed

    Xu, J; James, Rosalind R

    2012-04-01

    Environmental stresses are thought to be associated with increases in disease suceptibility, attributable to evolutionary trade-offs between the energy demands required to deal with stress vs pathogens. We compared the effects of temperature stress and pathogen exposure on the immune response of a solitary bee, Megachile rotundata. Using an oligonucleotide microarray with 125 genes (375 probes), we determined that both high and low temperatures increased the expression of immune response genes in M. rotundata and reduced levels of a disease called chalkbrood. In the absence of the pathogen, trypsin-like serine and pathogen recognition proteases were most highly expressed at the lowest rearing temperature (20°C), while immune response signalling pathways and melanization were highly expressed at the warmest temperature tested (35°C). In pathogen-exposed bees, immune response genes tended to be most highly expressed at moderate temperatures, where we also saw the greatest infection levels. Temperature stress appears to have activated immunity before the pathogen elicited a response from the host, and this early activity prevented infection under stressful conditions. In this insect, the trade-off in energetic costs associated with stress and infection may be partially avoided by the use of conserved responses that reduce the effects of both.

  14. Light and immune systems: activation of immunological activities

    NASA Astrophysics Data System (ADS)

    Huang, Zheng; Liu, Hong; Chen, Wei R.

    2006-02-01

    Light has been used to treat diseases for hundreds of years. Convenient and powerful light sources such as lasers make photomedicine a major branch in diseases treatment and detection. Originally, light was often used for local treatment, using photomechanical, photochemical, photothermal reactions and photomodulation as the major mechanisms. More and more investigators have become interested in the systemic effects of light, particularly in its effects on immune systems. Much work has been done to activate and/or enhance the host immune system to combat cancer, either using light as a direct tool or as an adjuvant method. Light has long been used for assisting disease detection and diagnosis. Advances in light technology have made photo-diagnostics ever more precise spatially and temporally. Many techniques facilitate observation of bio-molecule interactions and other biological processes at the cellular level, hence providing opportunities to detect and monitor immune activities. This manuscript will review recent photo-immunological research in treatment of cancer. The recent development of combination therapies involving lasers will be presented. Specifically, the results of cancer treatment using laser photothermal interaction, either with or without additional immunological stimulation will be discussed. The immunological effects of photodynamic therapy (PDT), and of its combination with immunotherapy in cancer treatment will also be discussed. Much interest has been recently concentrated in the immunological responses after laser treatment. Such responses at cellular and molecular levels will be discussed. The effect of these treatment modalities on the distant metastases also showed promise of light induced antitumor immunity. The combination therapy and induced immunological responses appear to be the key for long-term control of tumors.

  15. Coordinate actions of innate immune responses oppose those of the adaptive immune system during Salmonella infection of mice.

    PubMed

    Hotson, Andrew N; Gopinath, Smita; Nicolau, Monica; Khasanova, Anna; Finck, Rachel; Monack, Denise; Nolan, Garry P

    2016-01-12

    The immune system enacts a coordinated response when faced with complex environmental and pathogenic perturbations. We used the heterogeneous responses of mice to persistent Salmonella infection to model system-wide coordination of the immune response to bacterial burden. We hypothesized that the variability in outcomes of bacterial growth and immune response across genetically identical mice could be used to identify immune elements that serve as integrators enabling co-regulation and interconnectedness of the innate and adaptive immune systems. Correlation analysis of immune response variation to Salmonella infection linked bacterial load with at least four discrete, interacting functional immune response "cassettes." One of these, the innate cassette, in the chronically infected mice included features of the innate immune system, systemic neutrophilia, and high serum concentrations of the proinflammatory cytokine interleukin-6. Compared with mice with a moderate bacterial load, mice with the highest bacterial burden exhibited high activity of this innate cassette, which was associated with a dampened activity of the adaptive T cell cassette-with fewer plasma cells and CD4(+) T helper 1 cells and increased numbers of regulatory T cells-and with a dampened activity of the cytokine signaling cassette. System-wide manipulation of neutrophil numbers revealed that neutrophils regulated signal transducer and activator of transcription (STAT) signaling in B cells during infection. Thus, a network-level approach demonstrated unappreciated interconnections that balanced innate and adaptive immune responses during the dynamic course of disease and identified signals associated with pathogen transmission status, as well as a regulatory role for neutrophils in cytokine signaling.

  16. Yeast culture supplement during nursing and transport affects immunity and intestinal microbial ecology of weanling pigs.

    PubMed

    Weedman, S M; Rostagno, M H; Patterson, J A; Yoon, I; Fitzner, G; Eicher, S D

    2011-06-01

    The objectives of this study were to determine the influence of a Saccharomyces cerevisiae fermentation product on innate immunity and intestinal microbial ecology after weaning and transport stress. In a randomized complete block design, before weaning and in a split-plot analysis of a 2 × 2 factorial arrangement of yeast culture (YY) and transport (TT) after weaning, 3-d-old pigs (n = 108) were randomly assigned within litter (block) to either a control (NY, milk only) or yeast culture diet (YY; delivered in milk to provide 0.1 g of yeast culture product/kg of BW) from d 4 to 21. At weaning (d 21), randomly, one-half of the NY and YY pigs were assigned to a 6-h transport (NY-TT and YY-TT) before being moved to nursery housing, and the other one-half were moved directly to nursery housing (NY-NT and YY-NT, where NT is no transport). The yeast treatment was a 0.2% S. cerevisiae fermentation product and the control treatment was a 0.2% grain blank in feed for 2 wk. On d 1 before transport and on d 1, 4, 7, and 14 after transport, blood was collected for leukocyte assays, and mesenteric lymph node, jejunal, and ileal tissue, and jejunal, ileal, and cecal contents were collected for Toll-like receptor expression (TLR); enumeration of Escherichia coli, total coliforms, and lactobacilli; detection of Salmonella; and microbial analysis. After weaning, a yeast × transport interaction for ADG was seen (P = 0.05). Transport affected (P = 0.09) ADFI after weaning. Yeast treatment decreased hematocrit (P = 0.04). A yeast × transport interaction was found for counts of white blood cells (P = 0.01) and neutrophils (P = 0.02) and for the neutrophil-to-lymphocyte ratio (P = 0.02). Monocyte counts revealed a transport (P = 0.01) effect. Interactions of yeast × transport (P = 0.001) and yeast × transport × day (P = 0.09) for TLR2 and yeast × transport (P = 0.08) for TLR4 expression in the mesenteric lymph node were detected. Day affected lactobacilli, total coliform, and E

  17. 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.

  18. Interaction of the tick immune system with transmitted pathogens

    PubMed Central

    Hajdušek, Ondřej; Šíma, Radek; Ayllón, Nieves; Jalovecká, Marie; Perner, Jan; de la Fuente, José; Kopáček, Petr

    2013-01-01

    Ticks are hematophagous arachnids transmitting a wide variety of pathogens including viruses, bacteria, and protozoans to their vertebrate hosts. The tick vector competence has to be intimately linked to the ability of transmitted pathogens to evade tick defense mechanisms encountered on their route through the tick body comprising midgut, hemolymph, salivary glands or ovaries. Tick innate immunity is, like in other invertebrates, based on an orchestrated action of humoral and cellular immune responses. The direct antimicrobial defense in ticks is accomplished by a variety of small molecules such as defensins, lysozymes or by tick-specific antimicrobial compounds such as microplusin/hebraein or 5.3-kDa family proteins. Phagocytosis of the invading microbes by tick hemocytes is likely mediated by the primordial complement-like system composed of thioester-containing proteins, fibrinogen-related lectins and convertase-like factors. Moreover, an important role in survival of the ingested microbes seems to be played by host proteins and redox balance maintenance in the tick midgut. Here, we summarize recent knowledge about the major components of tick immune system and focus on their interaction with the relevant tick-transmitted pathogens, represented by spirochetes (Borrelia), rickettsiae (Anaplasma), and protozoans (Babesia). Availability of the tick genomic database and feasibility of functional genomics based on RNA interference greatly contribute to the understanding of molecular and cellular interplay at the tick-pathogen interface and may provide new targets for blocking the transmission of tick pathogens. PMID:23875177

  19. The scope of the crustacean immune system for disease control.

    PubMed

    Hauton, Chris

    2012-06-01

    The culture or wild capture of marine and freshwater shellfish, including crustaceans, is without doubt a key source of protein for a burgeoning world population. Historically the expansion of aquaculture has, however, been accompanied by the increased incidence of economically significant diseases, most notably of viral and bacterial origin. Since the late 1970s great progress has been made in our understanding of the generalized protostome innate immune system. Distinct pathways, pathogen receptor proteins and effector molecules have since been identified that are not ancestral or homologous to those of the deuterostomes, including vertebrates. Within the past decade progress has accelerated with the rapid characterisation of new classes of recognition proteins, immune effectors and regulatory pathways. This paper provides a broad overview of our current understanding of invertebrate immunology, taking the crustacean decapod immune system as its focus. Recent developments in the field are described briefly and their implications and potential considered. These advances offer fundamental new insights in our efforts to understand disease in cultured populations and also to develop knowledge of environmental effects on host/pathogen interactions within a fishery context. Of course, challenges do remain, including the lack of an immortal cell line and the limited publically-available genomic resources. These are considered in this review as priorities for future research effort. With the continued application of more insightful technologies, coupled with associated investment, it is expected that the speed at which some of these issues are resolved will accelerate.

  20. 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

  1. Dysregulation of the immune system caused by silica and asbestos.

    PubMed

    Maeda, Megumi; Nishimura, Yasumitsu; Kumagai, Naoko; Hayashi, Hiroaki; Hatayama, Tamayo; Katoh, Minako; Miyahara, Naomi; Yamamoto, Shoko; Hirastuka, Junichi; Otsuki, Takemi

    2010-01-01

    Silica and asbestos cause pneumoconioses known as silicosis and asbestosis, respectively, that are each characterized by progressive pulmonary fibrosis. While local effects of inhaled silica particles alter the function of alveolar macrophages and sequential cellular and molecular biological events, general systemic immunological effects may also evolve. One well-known health outcome associated with silica exposure/silicosis is an increase in the incidence of autoimmune disorders. In addition, while exposure to silica--in the crystalline form--has also been seen to be associated with the development of lung cancers, it remains unclear as to whether or not silicosis is a necessary condition for the elevation of silica-associated lung cancer risks. Since asbestos is a mineral silicate, it would be expected to also possess generalized immunotoxicological effects similar to those associated with silica particles. However, asbestos-exposed patients are far better known than silicotic patients for development of malignant diseases such as lung cancer and mesothelioma, and less so for the development of autoimmune disorders. With both asbestos and crystalline silica, one important dysregulatory outcome that needs to be considered is an alteration in tumor immunity that allows for silica- or asbestos- (or asbestos-associated agent)-induced tumors to survive and thrive in situ. In this review, the immunotoxicological effects of both silica and asbestos are presented and contrasted in terms of their abilities to induce immune system dysregulation that then are manifest by the onset of autoimmunity or by alterations in host-tumor immunity.

  2. Compartmentalized and systemic control of tissue immunity by commensals

    PubMed Central

    Belkaid, Yasmine; Naik, Shruti

    2013-01-01

    The body is composed of various tissue microenvironments with finely tuned local immunosurveillance systems, many of which are in close apposition with distinct commensal niches. Mammals have formed an evolutionary partnership with the microbiota that is critical for metabolism, tissue development and host defense. Despite our growing understanding of the impact of this host-microbe alliance on immunity in the gastrointestinal tract, the extent to which individual microenvironments are controlled by resident microbiota remains unclear. In this Perspective we discuss how resident commensals outside the gastrointestinal tract can control unique physiological niches and the potential implications of the dialog between these commensals and the host for the establishment of immune homeostasis, protective responses and tissue pathology. PMID:23778791

  3. Identification of transcriptional regulators in the mouse immune system.

    PubMed

    Jojic, Vladimir; Shay, Tal; Sylvia, Katelyn; Zuk, Or; Sun, Xin; Kang, Joonsoo; Regev, Aviv; Koller, Daphne; Best, Adam J; Knell, Jamie; Goldrath, Ananda; Joic, Vladimir; Koller, Daphne; Shay, Tal; Regev, Aviv; Cohen, Nadia; Brennan, Patrick; Brenner, Michael; Kim, Francis; Rao, Tata Nageswara; Wagers, Amy; Heng, Tracy; Ericson, Jeffrey; Rothamel, Katherine; Ortiz-Lopez, Adriana; Mathis, Diane; Benoist, Christophe; Bezman, Natalie A; Sun, Joseph C; Min-Oo, Gundula; Kim, Charlie C; Lanier, Lewis L; Miller, Jennifer; Brown, Brian; Merad, Miriam; Gautier, Emmanuel L; Jakubzick, Claudia; Randolph, Gwendalyn J; Monach, Paul; Blair, David A; Dustin, Michael L; Shinton, Susan A; Hardy, Richard R; Laidlaw, David; Collins, Jim; Gazit, Roi; Rossi, Derrick J; Malhotra, Nidhi; Sylvia, Katelyn; Kang, Joonsoo; Kreslavsky, Taras; Fletcher, Anne; Elpek, Kutlu; Bellemarte-Pelletier, Angelique; Malhotra, Deepali; Turley, Shannon

    2013-06-01

    The differentiation of hematopoietic stem cells into cells of the immune system has been studied extensively in mammals, but the transcriptional circuitry that controls it is still only partially understood. Here, the Immunological Genome Project gene-expression profiles across mouse immune lineages allowed us to systematically analyze these circuits. To analyze this data set we developed Ontogenet, an algorithm for reconstructing lineage-specific regulation from gene-expression profiles across lineages. Using Ontogenet, we found differentiation stage-specific regulators of mouse hematopoiesis and identified many known hematopoietic regulators and 175 previously unknown candidate regulators, as well as their target genes and the cell types in which they act. Among the previously unknown regulators, we emphasize the role of ETV5 in the differentiation of γδ T cells. As the transcriptional programs of human and mouse cells are highly conserved, it is likely that many lessons learned from the mouse model apply to humans.

  4. The Drosophila immune system detects bacteria through specific peptidoglycan recognition.

    PubMed

    Leulier, François; Parquet, Claudine; Pili-Floury, Sebastien; Ryu, Ji-Hwan; Caroff, Martine; Lee, Won-Jae; Mengin-Lecreulx, Dominique; Lemaitre, Bruno

    2003-05-01

    The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions through selective activation of the Toll and the immune deficiency (Imd) signaling pathways. The Toll pathway mediates most defenses against Gram-positive bacteria and fungi, whereas the Imd pathway is required to resist infection by Gram-negative bacteria. The bacterial components recognized by these pathways remain to be defined. Here we report that Gram-negative diaminopimelic acid-type peptidoglycan is the most potent inducer of the Imd pathway and that the Toll pathway is predominantly activated by Gram-positive lysine-type peptidoglycan. Thus, the ability of Drosophila to discriminate between Gram-positive and Gram-negative bacteria relies on the recognition of specific forms of peptidoglycan.

  5. STRONG SELECTIVE SIGNAL AND HIGH GENETIC VARIABILITY AT AN IMMUNE SYSTEM LOCUS IN CONTAMINATED AND UNCONTAMINATED POPULATIONS OF AN ESTUARINE FISH

    EPA Science Inventory

    The major histocompatibility complex (MHC) is a group of linked genes that mediates the adaptive immune response in vertebrates. Studies using mammals and birds have shown that environmental stressors can produce genetic changes at MHC loci that can affect immune system function....

  6. Coverage and predictors of routine immunization among 12-23 months old children in disaster affected communities in Pakistan

    PubMed Central

    Rehman, Shafiq Ur; Siddiqui, Amna Rehana; Ahmed, Jamil; Fatmi, Zafar; Shah, Sayed Masoom; Rahman, Aisha; Yousafzai, Mohammad Tahir

    2017-01-01

    Objectives: We aimed this study to determine the relationship of various factors related to poor immunization in children in an earthquake affected community. Materials and Methods: We conducted this cross-sectional study during 2007-2008 in Muzaffarabad district of Pakistani side of Kashmir. We selected 43 villages as clusters and in the second, 860 children between 12 and 24 months were selected from households through systematic sampling. Mothers of the eligible children were interviewed with a questionnaire. Logistic regression analysis was run to measure the association of various factors with appropriate immunization status of the children. Results: We found that 74% of children had completed their required doses of routine immunization. There were greater odds of a child being unvaccinated if the family lived at a distance that was to be covered in more than 10 min by any transport (odds ratio [OR]: 1.12, confidence interval [CI]: 1.08-1.17), mother of the child was not educated (OR:2.4, 1.3-4.4), child belonged to a low socioeconomic status (OR:3.5, CI: 2.1-6.3), family had any challenge or situation that where they could not take the child to a health facility for vaccination (OR: 2.3, CI: 1.4-3.7) and for a female child that belonged to minority ethnic group (OR: 1.7, CI: 1.0-2.5). Conclusion: Improvement in access of communities, especially of minority and poor in disaster-stricken, to immunization services and female education and awareness about the need for immunization in children could play a role in improving immunization coverage in such settings. PMID:28293154

  7. Insights into immune system development and function from mouse T-cell repertoires

    PubMed Central

    Sethna, Zachary; Elhanati, Yuval; Dudgeon, Chrissy S.; Callan, Curtis G.; Levine, Arnold J.; Mora, Thierry; Walczak, Aleksandra M.

    2017-01-01

    The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors. This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gene each time a new immune cell is created from a stem cell. By analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and thymus of mice of different ages, we quantify the changes in the VDJ recombination process that occur from embryo to young adult. We find a rapid increase with age in the number of random insertions and a dramatic increase in diversity. Because the blood accumulates thymic output over time, blood repertoires are mixtures of different statistical recombination processes, and we unravel the mixture statistics to obtain a picture of the time evolution of the early immune system. Sequence repertoire analysis also allows us to detect the statistical impact of selection on the output of the VDJ recombination process. The effects we find are nearly identical between thymus and blood, suggesting that our analysis mainly detects selection for proper folding of the TCR receptor protein. We further find that selection is weaker in laboratory mice than in humans and it does not affect the diversity of the repertoire. PMID:28196891

  8. Polychlorinated biphenyl 126 affects expression of genes involved in stress-immune interaction in primary cultures of rainbow trout anterior kidney cells.

    PubMed

    Quabius, Elgar Susanne; Krupp, Guido; Secombes, Christopher J

    2005-12-01

    Stress and immune function are linked in all vertebrates, including teleost fish. Polychlorinated biphenyls (PCBs) are immunotoxic and impair the ability of fish to respond to additional stressors. In this study, we investigated the effects of PCB126 on stress and immune function and the interaction of these systems in fish using primary cultures of rainbow trout anterior kidney cells as a model. Gene expression levels of cytochrome P4501A (CYP1A), interleukin-1beta (IL-1beta), and glucocorticoid receptor (GR) were measured by real-time quantitative polymerase chain reaction. These genes play important roles in detoxification and immune and stress homeostasis, respectively. Incubation with PCB126 led to increased IL-1beta expression between 30 min and 2 h of exposure, with expression back to basal levels after 6 h. Lipopolysaccharide (LPS) incubation evoked normal IL-1beta responses after 2 and 24 h PCB incubation. Gene expression levels of GR and CYP1A increased in a time- and dose-dependent manner, reaching a plateau after 12 h of incubation. Preincubation with cortisol resulted in decreased IL-1beta expression, increased expression of CYP1A and GR, and was accompanied by an abolished PCB responsiveness after more than 4 h of cortisol incubation. We conclude that PCB126 exposure is not "stressful," as increased cortisol levels would result in depressed IL-1beta expression. Incubation with PCB126 evokes a transient stimulation rather than permanent damage of the immune system, as LPS stimulation resulted in increased IL-1beta expression after PCB incubation. Prolonged cortisol preincubation, resembling a chronic stress paradigm, negatively affects the immune responsiveness of the cells as well as their capacity for toxicant metabolization.

  9. Hide-and-seek: the interplay between cancer stem cells and the immune system.

    PubMed

    Sultan, Mohammad; Coyle, Krysta Mila; Vidovic, Dejan; Thomas, Margaret Lois; Gujar, Shashi; Marcato, Paola

    2016-11-19

    The enhanced ability of cancer stem cells (CSCs) to give rise to new tumors suggests that these cells may also have an advantage in evading immune detection and elimination. This tumor-forming ability, combined with the known plasticity of the immune system, which can play both protumorigenic and antitumorigenic roles, has motivated investigations into the interaction between CSCs and the immune system. Herein, we review the interplay between host immunity and CSCs by examining the immune-related mechanisms that favor CSCs and the CSC-mediated expansion of protumorigenic immune cells. Furthermore, we discuss immune cells, such as natural killer cells, that preferentially target CSCs and the strategies used by CSCs to evade immune detection and destruction. An increased understanding of these interactions and the pathways that regulate them may allow us to harness immune system components to create new adjuvant therapies that eradicate CSCs and improve patient survival.

  10. Dam heat load affects neonatal calves’ bacterial prevalence and innate immunity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heat stress is known to suppress animal’s immunity, making them more susceptible to bacterial infections. In Indiana, field observations showed that calves have greater morbidity and mortality when they are born after a heat event. Objectives of this study were to determine whether heat load increas...

  11. Pre-natal heat load affects bacterial levels and innate immunity in neonatal calves

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heat stress suppresses immunity, making animals more susceptible to bacterial infections. Additionally, field observations suggest that calves have greater morbidity and mortality when they are born after a heat event. However, scientific evidence is still lacking, limiting the development of target...

  12. Effects of 2-deoxy-D-glucose on the immune system of seabream (Sparus aurata L.).

    PubMed

    Guardiola, F A; Cerezuela, R; Meseguer, J; Esteban, M A

    2011-02-01

    Stressful situations are a major problem in aquaculture because they affect the immune system. 2-Deoxy-D-glucose (2-DG) is a derivative of a glucose analogue that reduces the availability of energy, thereby inhibiting cell metabolism so that it is unable to enter the glycolysis pathway. In this paper, 2-DG has been administered in order to study if the immune function is compromised during metabolic stress. Blood glucose level was measured as an indicator of the inhibition of glycolysis, and the effects of intraperitoneal administration of 2-DG on the main parameters of the humoral (complement, IgM levels and peroxidase activity in blood plasma) and cellular (respiratory burst, intracellular peroxidase level and phagocytosis activity) immune parameters of gilthead seabream (Sparus aurata, L) were evaluated. Furthermore, the expression levels of immune-associated genes (CSF-1R, NCCRP-1, Hep, TCR-β, IgM(H), MHC-IIα, C3 and IL-1β) were analyzed by real-time PCR in head-kidney. A total of 5 intraperitoneal injections were performed at 48 h intervals. Three experimental groups were established: a control group injected with phosphate buffer saline, group 2-DG 500 and group 2-DG 750 injected with 500 mg kg⁻¹ and 750 mg kg⁻¹ 2-DG, respectively (N=15). After the third and fourth injection, some specimens of both DG-treated groups died. Following the first and third injection, the blood glucose levels of both 2-DG treated groups increased to a statistically significant extent with respect to the control group. While the humoral immune parameters were not significantly affected as a consequence of 2-DG administration, the cellular activities of leucocytes were. The injection of 500 mg kg⁻¹ 2-DG provoked up- or down-regulation of the immune-relevant genes analyzed, while the injection of 750 mg kg⁻¹ always caused down-regulation of these genes. The results suggest that 2-DG provokes metabolic stress, which reduces the activities carried out by immune cells

  13. Human CD8+ T cells mediate protective immunity induced by a human malaria vaccine in human immune system mice.

    PubMed

    Li, Xiangming; Huang, Jing; Zhang, Min; Funakoshi, Ryota; Sheetij, Dutta; Spaccapelo, Roberta; Crisanti, Andrea; Nussenzweig, Victor; Nussenzweig, Ruth S; Tsuji, Moriya

    2016-08-31

    A number of studies have shown that CD8+ T cells mediate protective anti-malaria immunity in a mouse model. However, whether human CD8+ T cells play a role in protection against malaria remains unknown. We recently established human immune system (HIS) mice harboring functional human CD8+ T cells (HIS-CD8 mice) by transduction with HLA-A∗0201 and certain human cytokines using recombinant adeno-associated virus-based gene transfer technologies. These HIS-CD8 mice mount a potent, antigen-specific HLA-A∗0201-restricted human CD8+ T-cell response upon immunization with a recombinant adenovirus expressing a human malaria antigen, the Plasmodium falciparum circumsporozoite protein (PfCSP), termed AdPfCSP. In the present study, we challenged AdPfCSP-immunized HIS-CD8 mice with transgenic Plasmodium berghei sporozoites expressing full-length PfCSP and found that AdPfCSP-immunized (but not naïve) mice were protected against subsequent malaria challenge. The level of the HLA-A∗0201-restricted, PfCSP-specific human CD8+ T-cell response was closely correlated with the level of malaria protection. Furthermore, depletion of human CD8+ T cells from AdPfCSP-immunized HIS-CD8 mice almost completely abolished the anti-malaria immune response. Taken together, our data show that human CD8+ T cells mediate protective anti-malaria immunity in vivo.

  14. Maternal immune activation affects litter success, size and neuroendocrine responses related to behavior in adult offspring.

    PubMed

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

    2013-07-02

    It is increasingly evident that influences other than genetics can contribute to offspring phenotype. In particular, maternal influences are an important contributing factor to offspring survival, development, physiology and behavior. Common environmental pathogens such as viral or bacterial microorganisms can induce maternal immune responses, which have the potential to alter the prenatal environment via multiple independent pathways. The effects of maternal immune activation on endocrine responses and behavior are less well studied and provide the basis for the current study. Our approach in the current study was two-pronged: 1) quantify sickness responses during pregnancy in adult female hamsters experiencing varying severity of immune responsiveness (i.e., differing doses of lipopolysaccharide [LPS]), and 2) assess the effects of maternal immune activation on offspring development, immunocompetence, hormone profiles, and social behavior during adulthood. Pregnancy success decreased with increasing doses of LPS, and litter size was reduced in LPS dams that managed to successfully reproduce. Unexpectedly, pregnant females treated with LPS showed a hypothermic response in addition to the more typical anorexic and body mass changes associated with sickness. Significant endocrine changes related to behavior were observed in the offspring of LPS-treated dams; these effects were apparent in adulthood. Specifically, offspring from LPS treated dams showed significantly greater cortisol responses to stressful resident-intruder encounters compared with offspring from control dams. Post-behavior cortisol was elevated in male LPS offspring relative to the offspring of control dams, and was positively correlated with the frequency of bites during agonistic interactions, and cortisol levels in both sexes were related to defensive behaviors, suggesting that changes in hypothalamo-pituitary-adrenal axis responsiveness may play a regulatory role in the observed behavioral

  15. Methamphetamine: Effects on the brain, gut and immune system.

    PubMed

    Prakash, Monica D; Tangalakis, Kathy; Antonipillai, Juliana; Stojanovska, Lily; Nurgali, Kulmira; Apostolopoulos, Vasso

    2017-03-14

    Methamphetamine (METH) is a powerful central nervous system stimulant which elevates mood, alertness, energy levels and concentration in the short-term. However, chronic use and/or at higher doses METH use often results in psychosis, depression, delusions and violent behavior. METH was formerly used to treat conditions such as obesity and attention deficit hyperactivity disorder, but now is primarily used recreationally. Its addictive nature has led to METH abuse becoming a global problem. At a cellular level, METH exerts a myriad of effects on the central and peripheral nervous systems, immune system and the gastrointestinal system. Here we present how these effects might be linked and their potential contribution to the pathogenesis of neuropsychiatric disorders. In the long term, this pathway could be targeted therapeutically to protect people from the ill effects of METH use. This model of METH use may also provide insight into how gut, nervous and immune systems might break down in other conditions that may also benefit from therapeutic intervention.

  16. Cell mechanics and immune system link up to fight infections

    NASA Astrophysics Data System (ADS)

    Ekpenyong, Andrew; Man, Si Ming; Tourlomousis, Panagiotis; Achouri, Sarra; Cammarota, Eugenia; Hughes, Katherine; Rizzo, Alessandro; Ng, Gilbert; Guck, Jochen; Bryant, Clare

    2015-03-01

    Infectious diseases, in which pathogens invade and colonize host cells, are responsible for one third of all mortality worldwide. Host cells use special proteins (immunoproteins) and other molecules to fight viral and bacterial invaders. The mechanisms by which immunoproteins enable cells to reduce bacterial loads and survive infections remain unclear. Moreover, during infections, some immunoproteins are known to alter the cytoskeleton, the structure that largely determines cellular mechanical properties. We therefore used an optical stretcher to measure the mechanical properties of primary immune cells (bone marrow derived macrophages) during bacterial infection. We found that macrophages become stiffer upon infection. Remarkably, macrophages lacking the immunoprotein, NLR-C4, lost the stiffening response to infection. This in vitro result correlates with our in vivo data whereby mice lacking NLR-C4 have more lesions and hence increased bacterial distribution and spread. Thus, the immune-protein-dependent increase in cell stiffness in response to bacterial infection (in vitro result) seems to have a functional role in the system level fight against pathogens (in vivo result). We will discuss how this functional link between cell mechanical properties and innate immunity, effected by actin polymerization, reduces the spread of infection.

  17. Regulation of cytokine gene transcription in the immune system.

    PubMed

    Holloway, A F; Rao, S; Shannon, M F

    2002-01-01

    The controlled expression of cytokine genes is an essential component of an immune response. The specific types of cytokines as well as the time and place of their production is important in generating an appropriate immune response to an infectious agent. Aberrant expression is associated with pathological conditions of the immune system such as autoimmunity, atopy and chronic inflammation. Cytokine gene transcription is generally induced in a cell-specific manner. Over the last 15 years, a large amount of information has been generated describing the transcriptional controls that are exerted on cytokine genes. Recently, efforts have been directed at understanding how these genes are transcribed in a chromatin context. This review will discuss the mechanisms by which cytokine genes become available for transcription in a cell-restricted manner as well as the mechanisms by which these genes sense their environment and activate high level transcription in a transient manner. Particular attention will be paid to the role of chromatin in allowing transcription factor access to appropriate genes.

  18. Innate immune recognition of flagellin limits systemic persistence of Brucella.

    PubMed

    Terwagne, Matthieu; Ferooz, Jonathan; Rolán, Hortensia G; Sun, Yao-Hui; Atluri, Vidya; Xavier, Mariana N; Franchi, Luigi; Núñez, Gabriel; Legrand, Thomas; Flavell, Richard A; De Bolle, Xavier; Letesson, Jean-Jacques; Tsolis, Renée M

    2013-06-01

    Brucella are facultative intracellular bacteria that cause chronic infections by limiting innate immune recognition. It is currently unknown whether Brucella FliC flagellin, the monomeric subunit of flagellar filament, is sensed by the host during infection. Here, we used two mutants of Brucella melitensis, either lacking or overexpressing flagellin, to show that FliC hinders bacterial replication in vivo. The use of cells and mice genetically deficient for different components of inflammasomes suggested that FliC was a target of the cytosolic innate immune receptor NLRC4 in vivo but not in macrophages in vitro where the response to FliC was nevertheless dependent on the cytosolic adaptor ASC, therefore suggesting a new pathway of cytosolic flagellin sensing. However, our work also suggested that the lack of TLR5 activity of Brucella flagellin and the regulation of its synthesis and/or delivery into host cells are both part of the stealthy strategy of Brucella towards the innate immune system. Nevertheless, as a flagellin-deficient mutant of B. melitensis wasfound to cause histologically demonstrable injuries in the spleen of infected mice, we suggested that recognition of FliC plays a role in the immunological stand-off between Brucella and its host, which is characterized by a persistent infection with limited inflammatory pathology.

  19. Toxic effects of dietary methylmercury on immune system development in nestling American kestrels (Falco sparverius).

    PubMed

    Fallacara, Dawn M; Halbrook, Richard S; French, John B

    2011-06-01

    This study evaluated the effects of dietary methylmercury (MeHg) on immune system development in captive-reared nestling American kestrels (Falco sparverius) to determine whether T cell-mediated and antibody-mediated adaptive immunity are targets for MeHg toxicity at environmentally relevant concentrations. Nestlings received various diets, including 0 (control), 0.6, and 3.9 µg/g (dry wt) MeHg for up to 18 d posthatch. Immunotoxicity endpoints included cell-mediated immunity (CMI) using the phytohemagglutinin (PHA) skin-swelling assay and antibody-mediated immune response via the sheep red blood cell (SRBC) hemagglutination assay. T cell- and B cell-dependent histological parameters in the spleen, thymus, and bursa of Fabricius were correlated with the functional assays. For nestlings in the 0.6 and 3.9 µg/g MeHg groups, CMI was suppressed by 73 and 62%, respectively, at 11 d of age. Results of this functional assay were correlated with T cell-dependent components of the spleen and thymus. Dose-dependent lymphoid depletion in spleen tissue directly affected the proliferation of T-lymphocyte populations, insofar as lower stimulation indexes from the PHA assay occurred in nestlings with lower proportions of splenic white pulp and higher THg concentrations. Nestlings in the 3.9 µg/g group also exhibited lymphoid depletion and a lack of macrophage activity in the thymus. Methylmercury did not have a noticeable effect on antibody-mediated immune function or B cell-dependent histological correlates. We conclude that T cell-mediated immunosuppression is the primary target of MeHg toward adaptive immunity in developing kestrels. This study provides evidence that environmentally relevant concentrations of MeHg may compromise immunocompetence in a developing terrestrial predator and raises concern regarding the long-term health effects of kestrels that were exposed to dietary MeHg during early avian development.

  20. Toxic effects of dietary methylmercury on immune system development in nestling American kestrels (Falco sparverius)

    USGS Publications Warehouse

    Fallacara, Dawn M.; Halbrook, Richard S.; French, John B.

    2011-01-01

    This study evaluated the effects of dietary methylmercury (MeHg) on immune system development in captive-reared nestling American kestrels (Falco sparverius) to determine whether T cell–mediated and antibody-mediated adaptive immunity are targets for MeHg toxicity at environmentally relevant concentrations. Nestlings received various diets, including 0 (control), 0.6, and 3.9 μg/g (dry wt) MeHg for up to 18 d posthatch. Immunotoxicity endpoints included cell-mediated immunity (CMI) using the phytohemagglutinin (PHA) skin-swelling assay and antibody-mediated immune response via the sheep red blood cell (SRBC) hemagglutination assay. T cell– and B cell–dependent histological parameters in the spleen, thymus, and bursa of Fabricius were correlated with the functional assays. For nestlings in the 0.6 and 3.9 μg/g MeHg groups, CMI was suppressed by 73 and 62%, respectively, at 11 d of age. Results of this functional assay were correlated with T cell–dependent components of the spleen and thymus. Dose-dependent lymphoid depletion in spleen tissue directly affected the proliferation of T-lymphocyte populations, insofar as lower stimulation indexes from the PHA assay occurred in nestlings with lower proportions of splenic white pulp and higher THg concentrations. Nestlings in the 3.9 μg/g group also exhibited lymphoid depletion and a lack of macrophage activity in the thymus. Methylmercury did not have a noticeable effect on antibody-mediated immune function or B cell–dependent histological correlates. We conclude that T cell–mediated immunosuppression is the primary target of MeHg toward adaptive immunity in developing kestrels. This study provides evidence that environmentally relevant concentrations of MeHg may compromise immunocompetence in a developing terrestrial predator and raises concern regarding the long-term health effects of kestrels that were exposed to dietary MeHg during early avian development.

  1. Dynamics of immune system gene expression upon bacterial challenge and wounding in a social insect (Bombus terrestris).

    PubMed

    Erler, Silvio; Popp, Mario; Lattorff, H Michael G

    2011-03-29

    The innate immune system which helps individuals to combat pathogens comprises a set of genes representing four immune system pathways (Toll, Imd, JNK and JAK/STAT). There is a lack of immune genes in social insects (e.g. honeybees) when compared to Diptera. Potentially, this might be compensated by an advanced system of social immunity (synergistic action of several individuals). The bumble bee, Bombus terrestris, is a primitively eusocial species with an annual life cycle and colonies headed by a single queen. We used this key pollinator to study the temporal dynamics of immune system gene expression in response to wounding and bacterial challenge.Antimicrobial peptides (AMP) (abaecin, defensin 1, hymenoptaecin) were strongly up-regulated by wounding and bacterial challenge, the latter showing a higher impact on the gene expression level. Sterile wounding down-regulated TEP A, an effector gene of the JAK/STAT pathway, and bacterial infection influenced genes of the Imd (relish) and JNK pathway (basket). Relish was up-regulated within the first hour after bacterial challenge, but decreased strongly afterwards. AMP expression following wounding and bacterial challenge correlates with the expression pattern of relish whereas correlated expression with dorsal was absent. Although expression of AMPs was high, continuous bacterial growth was observed throughout the experiment.Here we demonstrate for the first time the temporal dynamics of immune system gene expression in a social insect. Wounding and bacterial challenge affected the innate immune system significantly. Induction of AMP expression due to wounding might comprise a pre-adaptation to accompanying bacterial infections. Compared with solitary species this social insect exhibits reduced immune system efficiency, as bacterial growth could not be inhibited. A negative feedback loop regulating the Imd-pathway is suggested. AMPs, the end product of the Imd-pathway, inhibited the up-regulation of the transcription

  2. Role of α7 nicotinic receptor in the immune system and intracellular signaling pathways

    PubMed Central

    Zdanowski, Robert; Ujazdowska, Dominika; Lewicka, Aneta; Lewicki, Sławomir

    2015-01-01

    Acetylcholine has been well known as one of the most exemplary neurotransmitters. In humans, this versatile molecule and its synthesizing enzyme, choline acetyltransferase, have been found in various non-neural tissues such as the epithelium, endothelium, mesothelium muscle, blood cells and immune cells. The non-neuronal acetylcholine is accompanied by the expression of acetylcholinesterase and nicotinic/muscarinic acetylcholine receptors. Increasing evidence of the non-neuronal acetylcholine system found throughout the last few years has indicated this neurotransmitter as one of the major cellular signaling molecules (associated e.g. with kinases and transcription factors activity). This system is responsible for maintenance and optimization of the cellular function, such as proliferation, differentiation, adhesion, migration, intercellular contact and apoptosis. Additionally, it controls proper activity of immune cells and affects differentiation, antigen presentation or cytokine production (both pro- and anti-inflammatory). The present article reviews recent findings about the non-neuronal cholinergic system in the field of immune system and intracellular signaling pathways. PMID:26648784

  3. Ammonia concentration and relative humidity in poultry houses affect the immune response of broilers.

    PubMed

    Wei, F X; Hu, X F; Xu, B; Zhang, M H; Li, S Y; Sun, Q Y; Lin, P

    2015-04-10

    To investigate the effect of ammonia (NH3) and humidity on the immune response of broilers, broilers were exposed to 30 or 70 mg/kg atmospheric NH3 for 21 days. Additionally, birds were exposed to 35, 60, and 85% relative humidity (RH). The relative weights of lymphoid organs, serum total protein, serum globulin, serum albumin, serum lysozyme, proliferation index of peripheral blood lymphocytes, and splenic cytokine gene expression were determined. Exposure to 70 mg/kg NH3 decreased the relative weight of the spleen during the experimental period, serum lysozyme concentration in the first and second weeks, and serum globulin concentration in the third week. The proliferation of peripheral blood lymphocytes was reduced. High levels of NH3 caused increase in IL-1β gene expression in the experimental period and IL-4 gene expression in the first week. Birds exposed to 85% RH had lower thymus and bursa of Fabricius weights in the third week and serum lysozyme concentration in the first week; IL-1β and IL-4 expressions were higher in the second and third weeks and first and second weeks, respectively, than in birds exposed to 60% RH. IL-4 expression was lower during the first week, and IL-1β expression was higher during the second week with 35% RH than with 60% RH. In conclusion, high NH3 level in the poultry house suppressed the immune response of broiler chickens. Neither high nor low RH benefited the immune response of broilers. Furthermore, there was an interactive effect between NH3 and RH on the immune response of broilers.

  4. Combined Oral and Intravenous Immunization Stimulates Strong IgA Responses in Both Systemic and Mucosal Compartments

    PubMed Central

    Yang, Zhe; Zhao, Qing; Gao, Yun-An; Zhang, Wei

    2016-01-01

    To investigate the influence of immunization routes onIgG, IgA and IgM production in systemic and mucosal compartments, we immunized mice with keyhole limpet hemocyanin (KLH) via oral, intranasal (i.n.) or subcutaneous (s.c.) routes alone or combined with the intravenous (i.v.) route. We found that administering antigen intravenously could affect antibody production and formation of antibody secreting cells (ASCs) depending on the immunization route previously used. Combined oral/i.v. immunization but not s.c./i.v. immunization caused a great increase of IgA ASCs in the spleen and enhanced IgA production in the small intestine and serum. Combined i.n./i.v. immunization could also increase IgA ASCs in the spleen and enhance IgA production in serum but had no effect on IgA production in the small intestine. Oral/i.v. immunization caused increase of IgG ASCs in both the spleen and bone marrow. In comparison, combined i.n./i.v. and s.c./i.v. immunization could increase IgG ASCs in the spleen but not in bone marrow. Intravenous administration of KLH in mice that had been immunized via oral, i.n. or s.c. routes caused some increase of IgM ASCs in the spleen but not in bone marrow. In conclusion, combined oral and i.v. administration of an antigen can induce fast and strong immune responses, especially for IgA, in both systemic and mucosal compartments. PMID:27936222

  5. Combined Oral and Intravenous Immunization Stimulates Strong IgA Responses in Both Systemic and Mucosal Compartments.

    PubMed

    Yang, Zhe; Zhao, Qing; Gao, Yun-An; Zhang, Wei

    2016-01-01

    To investigate the influence of immunization routes onIgG, IgA and IgM production in systemic and mucosal compartments, we immunized mice with keyhole limpet hemocyanin (KLH) via oral, intranasal (i.n.) or subcutaneous (s.c.) routes alone or combined with the intravenous (i.v.) route. We found that administering antigen intravenously could affect antibody production and formation of antibody secreting cells (ASCs) depending on the immunization route previously used. Combined oral/i.v. immunization but not s.c./i.v. immunization caused a great increase of IgA ASCs in the spleen and enhanced IgA production in the small intestine and serum. Combined i.n./i.v. immunization could also increase IgA ASCs in the spleen and enhance IgA production in serum but had no effect on IgA production in the small intestine. Oral/i.v. immunization caused increase of IgG ASCs in both the spleen and bone marrow. In comparison, combined i.n./i.v. and s.c./i.v. immunization could increase IgG ASCs in the spleen but not in bone marrow. Intravenous administration of KLH in mice that had been immunized via oral, i.n. or s.c. routes caused some increase of IgM ASCs in the spleen but not in bone marrow. In conclusion, combined oral and i.v. administration of an antigen can induce fast and strong immune responses, especially for IgA, in both systemic and mucosal compartments.

  6. The interaction between maternal stress and the ontogeny of the innate immune system during teleost embryogenesis: implications for aquaculture practice.

    PubMed

    Li, M; Leatherland, J F

    2012-11-01

    The barrier defences and acellular innate immune proteins play critical roles during the early-stage fish embryos prior to the development of functional organ systems. The innate immune proteins in the yolk of embryos are of maternal origin. Maternal stress affects the maternal-to-embryo transfer of these proteins and, therefore, environmental stressors may change the course of embryo development, including embryonic immunocompetency, via their deleterious effect on maternal physiology. This review focuses on the associations that exist between maternal stress, maternal endocrine disturbance and the responses of the acellular innate immune proteins of early-stage fish embryos. Early-stage teleostean embryos are dependent upon the adult female for the formation of the zona pellucida as an essential barrier defence, for their supply of nutrients, and for the innate immunity proteins and antibodies that are transferred from the maternal circulation to the oocytes; maternally derived hormones are also transferred, some of which (such as cortisol) are known to exert a suppressive action on some aspects of the immune defences. This review summarizes what is known about the effects of oocyte cortisol content on the immune system components in early embryos. The review also examines recent evidence that embryonic cells during early cleavage have the capacity to respond to increased maternal cortisol transfer; this emphasizes the importance of maternal and early immune competence on the later life of fishes, both in the wild and in intensive culture.

  7. Mechanisms of tumor escape from immune system: role of mesenchymal stromal cells.

    PubMed

    Poggi, Alessandro; Musso, Alessandra; Dapino, Irene; Zocchi, Maria Raffaella

    2014-01-01

    Tumor microenvironment represents the site where the tumor tries to survive and escape from immune system-mediated recognition. Indeed, to proliferate tumor cells can divert the immune response inducing the generation of myeloid derived suppressor cells and regulatory T cells which can limit the efficiency of effector antitumor lymphocytes in eliminating neoplastic cells. Many components of the tumor microenvironment can serve as a double sword for the tumor and the host. Several types of fibroblast-like cells, which herein we define mesenchymal stromal cells (MSC), secrete extracellular matrix components and surrounding the tumor mass can limit the expansion of the tumor. On the other hand, MSC can interfere with the immune recognition of tumor cells producing immunoregulatory cytokines as transforming growth factor (TGF)ß, releasing soluble ligands of the activating receptors expressed on cytolytic effector cells as decoy molecules, affecting the correct interaction among lymphocytes and tumor cells. MSC can also serve as target for the same anti-tumor effector lymphocytes or simply impede the interaction between these lymphocytes and neoplastic cells. Thus, several evidences point out the role of MSC, both in epithelial solid tumors and hematological malignancies, in regulating tumor cell growth and immune response. Herein, we review these evidences and suggest that MSC can be a suitable target for a more efficient anti-tumor therapy.

  8. Effects of 30-m nitrox saturation dive on the immune system in man.

    PubMed

    Shimamiya, T; Terada, N; Wakabayashi, S; Mohri, M

    2006-01-01

    Hyperbaria reportedly affects the immune system, but the role of psychological factors arising from confinement has not been taken into consideration. We investigated the immune changes in 4 subjects exposed to a 9-day simulated 30-m (400-kPa) nitrogen-oxygen (nitrox) saturation dive, and compared the results with those of our previous study that showed immune and mood changes in normobaric confinement. Blood samples were taken before, during, and after the dive or confinement, and activated with an anti-CD2 agonistic antibody. The percentages of granulocytes, natural killer (NK) cells, and cells positive for CD69, an early activation marker, were analyzed by flow cytometry. Reduction of CD69 expression percentage was observed under both hyperbaric and normobaric conditions. Percentages of innate immune cells, such as granulocytes and NK cells decreased or remained mostly unchanged, contrasting with our previous study, which demonstrated increases in both percentages coordinate with mood improvement. We conclude that these changes may have been triggered by suppression of sympathetic nerve activity that occurs in 30-m nitrox saturation hyperbaria.

  9. Tillage system affects microbiological properties of soil

    NASA Astrophysics Data System (ADS)

    Delgado, A.; de Santiago, A.; Avilés, M.; Perea, F.

    2012-04-01

    Soil tillage significantly affects organic carbon accumulation, microbial biomass, and subsequently enzymatic activity in surface soil. Microbial activity in soil is a crucial parameter contributing to soil functioning, and thus a basic quality factor for soil. Since enzymes remain soil after excretion by living or disintegrating cells, shifts in their activities reflect long-term fluctuations in microbial biomass. In order to study the effects of no-till on biochemical and microbiological properties in comparison to conventional tillage in a representative soil from South Spain, an experiment was conducted since 1982 on the experimental farm of the Institute of Agriculture and Fisheries Research of Andalusia (IFAPA) in Carmona, SW Spain (37o24'07''N, 5o35'10''W). The soil at the experimental site was a very fine, montomorillonitic, thermic Chromic Haploxerert (Soil Survey Staff, 2010). A randomized complete block design involving three replications and the following two tillage treatments was performed: (i) Conventional tillage, which involved mouldboard plowing to a depth of 50 cm in the summer (once every three years), followed by field cultivation to a depth of 15 cm before sowing; crop residues being burnt, (ii) No tillage, which involved controlling weeds before sowing by spraying glyphosate and sowing directly into the crop residue from the previous year by using a planter with double-disk openers. For all tillage treatments, the crop rotation (annual crops) consisted of winter wheat, sunflower, and legumes (pea, chickpea, or faba bean, depending on the year), which were grown under rainfed conditions. Enzymatic activities (ß-glucosidase, dehydrogenase, aryl-sulphatase, acid phosphatase, and urease), soil microbial biomass by total viable cells number by acridine orange direct count, the density of cultivable groups of bacteria and fungi by dilution plating on semi-selective media, the physiological profiles of the microbial communities by BiologR, and the

  10. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis.

    PubMed

    Hall, Jessica M F; Cruser, Desanges; Podawiltz, Alan; Mummert, Diana I; Jones, Harlan; Mummert, Mark E

    2012-01-01

    Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides) can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity) and alters antigen presentation by epidermal Langerhans cells (adaptive immunity). Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.

  11. Vaccine-enhanced artificial immune system for multimodal function optimization.

    PubMed

    Woldemariam, Kumlachew M; Yen, Gary G

    2010-02-01

    This paper emulates a biological notion in vaccines to promote exploration in the search space for solving multimodal function optimization problems using artificial immune systems (AISs). In this method, we first divide the decision space into equal subspaces. The vaccine is then randomly extracted from each subspace. A few of these vaccines, in the form of weakened antigens, are then injected into the algorithm to enhance the exploration of global and local optima. The goal of this process is to lead the antibodies to unexplored areas. Using this biologically motivated notion, we design the vaccine-enhanced AIS for multimodal function optimization, achieving promising performance.

  12. Toward an objective classification of cells in the immune system.

    PubMed Central

    Lefkovits, I; Kuhn, L; Valiron, O; Merle, A; Kettman, J

    1988-01-01

    The relative abundance of individual proteins shared among clones of lymphocytes provides a meaningful basis for cellular classification. Twelve clones of T cells (obtained by limiting dilution) were analyzed by two-dimensional gel electrophoresis for polypeptide content and then evaluated by the computational technique known as principal component analysis. As a result, relatedness of the clones was established and expressed in terms of taxonomic distances. The data show that a comprehensive and objective classification of the cells involved in the immune system can be approached. Images PMID:3259320

  13. Construction of Multi-Mode Affective Learning System: Taking Affective Design as an Example

    ERIC Educational Resources Information Center

    Lin, Hao-Chiang Koong; Su, Sheng-Hsiung; Chao, Ching-Ju; Hsieh, Cheng-Yen; Tsai, Shang-Chin

    2016-01-01

    This study aims to design a non-simultaneous distance instruction system with affective computing, which integrates interactive agent technology with the curricular instruction of affective design. The research subjects were 78 students, and prototype assessment and final assessment were adopted to assess the interface and usability of the system.…

  14. Tissue communication in a systemic immune response of Drosophila