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Sample records for acquired immune systems

  1. Plasmodesmata localizing proteins regulate transport and signaling during systemic acquired immunity in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Systemic acquired resistance (SAR) in plants is mediated by the signaling molecules azelaic acid (AzA),glycerol-3-phosphate (G3P), and salicylic acid (SA).Here, we show that AzA and G3P transport occurs via the symplastic route, which is regulated by channels known as plasmodesmata (PD). In contrast...

  2. A novel elicitor protein from Phytophthora parasitica induces plant basal immunity and systemic acquired resistance.

    PubMed

    Chang, Yi-Hsuan; Yan, Hao-Zhi; Liou, Ruey-Fen

    2015-02-01

    The interaction between Phytophthora pathogens and host plants involves the exchange of complex molecular signals from both sides. Recent studies of Phytophthora have led to the identification of various apoplastic elicitors known to trigger plant immunity. Here, we provide evidence that the protein encoded by OPEL of Phytophthora parasitica is a novel elicitor. Homologues of OPEL were identified only in oomycetes, but not in fungi and other organisms. Quantitative reverse transcription-polymerase chain reaction (RT-PCR) revealed that OPEL is expressed throughout the development of P. parasitica and is especially highly induced after plant infection. Infiltration of OPEL recombinant protein from Escherichia coli into leaves of Nicotiana tabacum (cv. Samsun NN) resulted in cell death, callose deposition, the production of reactive oxygen species and induced expression of pathogen-associated molecular pattern (PAMP)-triggered immunity markers and salicylic acid-responsive defence genes. Moreover, the infiltration conferred systemic resistance against a broad spectrum of pathogens, including Tobacco mosaic virus, the bacteria wilt pathogen Ralstonia solanacearum and P. parasitica. In addition to the signal peptide, OPEL contains three conserved domains: a thaumatin-like domain, a glycine-rich protein domain and a glycosyl hydrolase (GH) domain. Intriguingly, mutation of a putative laminarinase active site motif in the predicted GH domain abolished its elicitor activity, which suggests enzymatic activity of OPEL in triggering the defence response.

  3. Plasmodesmata Localizing Proteins Regulate Transport and Signaling during Systemic Acquired Immunity in Plants.

    PubMed

    Lim, Gah-Hyun; Shine, M B; de Lorenzo, Laura; Yu, Keshun; Cui, Weier; Navarre, Duroy; Hunt, Arthur G; Lee, Jung-Youn; Kachroo, Aardra; Kachroo, Pradeep

    2016-04-13

    Systemic acquired resistance (SAR) in plants is mediated by the signaling molecules azelaic acid (AzA), glycerol-3-phosphate (G3P), and salicylic acid (SA). Here, we show that AzA and G3P transport occurs via the symplastic route, which is regulated by channels known as plasmodesmata (PD). In contrast, SA moves via the extracytosolic apoplast compartment. We found that PD localizing proteins (PDLP) 1 and 5 were required for SAR even though PD permeability in pdlp1 and 5 mutants was comparable to or higher than wild-type plants, respectively. Furthermore, PDLP function was required in the recipient cell, suggesting regulatory function in SAR. Interestingly, overexpression of PDLP5 drastically reduced PD permeability, yet also impaired SAR. PDLP1 interacted with AZI1 (lipid transfer-like protein required for AzA- and G3P-induced SAR) and contributed to its intracellular partitioning. Together, these results reveal the transport routes of SAR chemical signals and highlight the regulatory role of PD-localizing proteins in SAR. PMID:27078071

  4. Immune System

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immune System KidsHealth > For Teens > Immune System Print A A ... could put us out of commission. What the Immune System Does The immune (pronounced: ih-MYOON) system, which ...

  5. Functions of innate and acquired immune system are reduced in domestic pigeons (Columba livia domestica) given a low protein diet

    PubMed Central

    Mabuchi, Yuko; Frankel, Theresa L.

    2016-01-01

    Racing pigeons are exposed to and act as carriers of diseases. Dietary protein requirement for their maintenance has not been determined experimentally despite their being domesticated for over 7000 years. A maintenance nitrogen (protein) requirement (MNR) for pigeons was determined in a balance study using diets containing 6, 10 and 14% crude protein (CP). Then, the effects of feeding the diets were investigated to determine whether they were adequate to sustain innate and acquired immune functions. Nitrogen intake from the 6% CP diet was sufficient to maintain nitrogen balance and body weight in pigeons. However, the immune functions of phagocytosis, oxidative burst and lymphocyte proliferation in pigeons fed this diet were reduced compared with those fed 10 and 14% CP diets. Pigeons given the 6 and 10% CP diets had lower antibody titres following inoculation against Newcastle disease (ND) than those on the 14% CP diet. A confounding factor found on autopsy was the presence of intestinal parasites in some of the pigeons given the 6 and 10% CP diets; however, none of the pigeons used to measure MNR or acquired immunity to ND were infested with parasites. In conclusion, neither the 6 nor 10% CP diets adequately sustained acquired immune function of pigeons. PMID:27069640

  6. Functions of innate and acquired immune system are reduced in domestic pigeons (Columba livia domestica) given a low protein diet.

    PubMed

    Mabuchi, Yuko; Frankel, Theresa L

    2016-03-01

    Racing pigeons are exposed to and act as carriers of diseases. Dietary protein requirement for their maintenance has not been determined experimentally despite their being domesticated for over 7000 years. A maintenance nitrogen (protein) requirement (MNR) for pigeons was determined in a balance study using diets containing 6, 10 and 14% crude protein (CP). Then, the effects of feeding the diets were investigated to determine whether they were adequate to sustain innate and acquired immune functions. Nitrogen intake from the 6% CP diet was sufficient to maintain nitrogen balance and body weight in pigeons. However, the immune functions of phagocytosis, oxidative burst and lymphocyte proliferation in pigeons fed this diet were reduced compared with those fed 10 and 14% CP diets. Pigeons given the 6 and 10% CP diets had lower antibody titres following inoculation against Newcastle disease (ND) than those on the 14% CP diet. A confounding factor found on autopsy was the presence of intestinal parasites in some of the pigeons given the 6 and 10% CP diets; however, none of the pigeons used to measure MNR or acquired immunity to ND were infested with parasites. In conclusion, neither the 6 nor 10% CP diets adequately sustained acquired immune function of pigeons.

  7. Acquired and innate immunity to polyaromatic hydrocarbons

    SciTech Connect

    Yusuf, Nabiha Timares, Laura; Seibert, Megan D.; Xu Hui; Elmets, Craig A.

    2007-11-01

    Polyaromatic hydrocarbons are ubiquitous environmental pollutants that are potent mutagens and carcinogens. Researchers have taken advantage of these properties to investigate the mechanisms by which chemicals cause cancer of the skin and other organs. When applied to the skin of mice, several carcinogenic polyaromatic hydrocarbons have also been shown to interact with the immune system, stimulating immune responses and resulting in the development of antigen-specific T-cell-mediated immunity. Development of cell-mediated immunity is strain-specific and is governed by Ah receptor genes and by genes located within the major histocompatibility complex. CD8{sup +} T cells are effector cells in the response, whereas CD4{sup +} T cells down-regulate immunity. Development of an immune response appears to have a protective effect since strains of mice that develop a cell-mediated immune response to carcinogenic polyaromatic hydrocarbons are less likely to develop tumors when subjected to a polyaromatic hydrocarbon skin carcinogenesis protocol than mice that fail to develop an immune response. With respect to innate immunity, TLR4-deficient C3H/HeJ mice are more susceptible to polyaromatic hydrogen skin tumorigenesis than C3H/HeN mice in which TLR4 is normal. These findings support the hypothesis that immune responses, through their interactions with chemical carcinogens, play an active role in the prevention of chemical skin carcinogenesis during the earliest stages. Efforts to augment immune responses to the chemicals that cause tumors may be a productive approach to the prevention of tumors caused by these agents.

  8. Heat shock proteins: stimulators of innate and acquired immunity.

    PubMed

    Colaco, Camilo A; Bailey, Christopher R; Walker, K Barry; Keeble, James

    2013-01-01

    Adjuvants were reintroduced into modern immunology as the dirty little secret of immunologists by Janeway and thus began the molecular definition of innate immunity. It is now clear that the binding of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors (PRRs) on antigen presenting cells (APCs) activates the innate immune response and provides the host with a rapid mechanism for detecting infection by pathogens and initiates adaptive immunity. Ironically, in addition to advancing the basic science of immunology, Janeway's revelation on induction of the adaptive system has also spurred an era of rational vaccine design that exploits PRRs. Thus, defined PAMPs that bind to known PRRs are being specifically coupled to antigens to improve their immunogenicity. However, while PAMPs efficiently activate the innate immune response, they do not mediate the capture of antigen that is required to elicit the specific responses of the acquired immune system. Heat shock proteins (HSPs) are molecular chaperones that are found complexed to client polypeptides and have been studied as potential cancer vaccines. In addition to binding PRRs and activating the innate immune response, HSPs have been shown to both induce the maturation of APCs and provide chaperoned polypeptides for specific triggering of the acquired immune response.

  9. Systemic Acquired Resistance

    PubMed Central

    2006-01-01

    Upon infection with necrotizing pathogens many plants develop an enhanced resistance to further pathogen attack also in the uninoculated organs. This type of enhanced resistance is referred to as systemic acquired resistance (SAR). In the SAR state, plants are primed (sensitized) to more quickly and more effectively activate defense responses the second time they encounter pathogen attack. Since SAR depends on the ability to access past experience, acquired disease resistance is a paradigm for the existence of a form of “plant memory”. Although the phenomenon has been known since the beginning of the 20th century, major progress in the understanding of SAR was made over the past sixteen years. This review covers the current knowledge of molecular, biochemical and physiological mechanisms that are associated with SAR. PMID:19521483

  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. DNA image cytometry in acquired immune deficiency syndrome (AIDS).

    PubMed

    Auffermann, W; Krueger, G R; Böcking, A

    1986-03-01

    In nine cases with the acquired immune deficiency syndrome (AIDS), including four stage I cases, three stage II cases and two stage III cases, DNA image cytometry was performed on Feulgen-stained lymph node imprint smears. Diploidy was found in three cases, tetraploidy in three cases and octoploidy in two cases. Aneuploid DNA distribution patterns were not seen. The lymphoid cells showed an enormously increased proliferation rate. Two cases in stage I revealed characteristic intranuclear DNA inclusions in lymphoid cells. These results indicate that DNA image cytometry may be useful as an adjunct to surgical pathology in certain cases to assist in the differential diagnosis between AIDS and benign conditions of the lymphoid system as well as between AIDS and malignant lymphomas, which usually have aneuploid DNA patterns.

  12. Progressive multifocal leukoencephalopathy occurring with the acquired immune deficiency syndrome.

    PubMed

    England, J D; Hsu, C Y; Garen, P D; Goust, J M; Biggs, P J

    1984-08-01

    A 33-year-old homosexual man with symptoms and signs of a focal brain process was subsequently found to have an acquired immune deficiency syndrome (AIDS) with biopsy-proven progressive multifocal leukoencephalopathy. This report reemphasizes the association of progressive multifocal leukoencephalopathy with AIDS and probably is best viewed as another example of an opportunistic CNS infection complicating deficient cell-mediated immunity. PMID:6540476

  13. Disentangling inborn and acquired immunity in human twins.

    PubMed

    Casanova, Jean-Laurent; Abel, Laurent

    2015-01-15

    The human geneticist Archibald Garrod noted in 1931 that, "It is, of necessity, no easy matter to distinguish between immunity which is inborn and that which has been acquired" (The Inborn Factors in Disease). In this issue of Cell, Brodin et al. show that the heritability of blood counts rapidly decreases with age for the lymphoid subsets responsible for adaptive immunity, unlike cells from other hematopoietic lineages.

  14. Acquired immune heterogeneity and its sources in human helminth infection

    PubMed Central

    BOURKE, C. D.; MAIZELS, R. M.; MUTAPI, F.

    2011-01-01

    SUMMARY Similarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recent in vitro and immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The ‘trade-off’ between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigens in utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations. PMID:20946693

  15. Autopsy pathology in the acquired immune deficiency syndrome.

    PubMed Central

    Reichert, C. M.; O'Leary, T. J.; Levens, D. L.; Simrell, C. R.; Macher, A. M.

    1983-01-01

    The acquired immune deficiency syndrome (AIDS) is a devastating new illness which appears to be sexually and parenterally transmissible. AIDS was first described in the male homosexual community; however, the disease has more recently been described among intravenous drug abusers, Haitians, hemophiliacs, and others. The etiologic agent is unknown. AIDS may represent an infection by a previously undescribed organism, a mutant of a known microorganism, or a multifactorial combination of environmental, immunologic, and genetic factors. As a consequence of the disease's seemingly irreversible ablation of the cell-mediated immune system, AIDS victims succumb to a variety of infections and/or unusual neoplasms. In its fully developed form, mortality approaches 100%. At autopsy the gross and microscopic pathology of the syndrome can be divided into three general categories: 1) morphologic manifestations of profound lymphoid depletion; 2) infections, usually with mixed opportunistic pathogens; and 3) unusual neoplasms, most frequently Kaposi's sarcoma or high-grade lymphomas. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 PMID:6311021

  16. Naturally acquired immunity to sexual stage P. falciparum parasites.

    PubMed

    Stone, Will J R; Dantzler, Kathleen W; Nilsson, Sandra K; Drakeley, Chris J; Marti, Matthias; Bousema, Teun; Rijpma, Sanna R

    2016-02-01

    Gametocytes are the specialized form of Plasmodium parasites that are responsible for human-to-mosquito transmission of malaria. Transmission of gametocytes is highly effective, but represents a biomass bottleneck for the parasite that has stimulated interest in strategies targeting the transmission stages separately from those responsible for clinical disease. Studying targets of naturally acquired immunity against transmission-stage parasites may reveal opportunities for novel transmission reducing interventions, particularly the development of a transmission blocking vaccine (TBV). In this review, we summarize the current knowledge on immunity against the transmission stages of Plasmodium. This includes immune responses against epitopes on the gametocyte-infected erythrocyte surface during gametocyte development, as well as epitopes present upon gametocyte activation in the mosquito midgut. We present an analysis of historical data on transmission reducing immunity (TRI), as analysed in mosquito feeding assays, and its correlation with natural recognition of sexual stage specific proteins Pfs48/45 and Pfs230. Although high antibody titres towards either one of these proteins is associated with TRI, the presence of additional, novel targets is anticipated. In conclusion, the identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocyte stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.

  17. Immune System Involvement

    MedlinePlus

    ... Tips" to find out more! Email * Zipcode The Immune System and Psoriatic Disease What is an autoimmune disease? ... swollen and painful joints and tendons. Treating the immune system The immune system is not only the key ...

  18. Toward immunogenetic studies of amphibian chytridiomycosis: Linking innate and acquired immunity

    USGS Publications Warehouse

    Richmond, J.Q.; Savage, Anna E.; Zamudio, Kelly R.; Rosenblum, E.B.

    2009-01-01

    Recent declines in amphibian diversity and abundance have contributed significantly to the global loss of biodiversity. The fungal disease chytridiomycosis is widely considered to be a primary cause of these declines, yet the critical question of why amphibian species differ in susceptibility remains unanswered. Considerable evidence links environmental conditions and interspecific variability of the innate immune system to differential infection responses, but other sources of individual, population, or species-typical variation may also be important. In this article we review the preliminary evidence supporting a role for acquired immune defenses against chytridiomycosis, and advocate for targeted investigation of genes controlling acquired responses, as well as those that functionally bridge the innate and acquired immune systems. Immunogenetic data promise to answer key questions about chytridiomycosis susceptibility and host-pathogen coevolution, and will draw much needed attention to the importance of considering evolutionary processes in amphibian conservation management and practice. ?? 2009 by American Institute of Biological Sciences.

  19. A cascade reaction network mimicking the basic functional steps of acquired immune response

    PubMed Central

    Han, Da; Wu, Cuichen; You, Mingxu; Zhang, Tao; Wan, Shuo; Chen, Tao; Qiu, Liping; Zheng, Zheng; Liang, Hao; Tan, Weihong

    2015-01-01

    Biological systems use complex ‘information processing cores’ composed of molecular networks to coordinate their external environment and internal states. An example of this is the acquired, or adaptive, immune system (AIS), which is composed of both humoral and cell-mediated components. Here we report the step-by-step construction of a prototype mimic of the AIS which we call Adaptive Immune Response Simulator (AIRS). DNA and enzymes are used as simple artificial analogues of the components of the AIS to create a system which responds to specific molecular stimuli in vitro. We show that this network of reactions can function in a manner which is superficially similar to the most basic responses of the vertebrate acquired immune system, including reaction sequences that mimic both humoral and cellular responses. As such, AIRS provides guidelines for the design and engineering of artificial reaction networks and molecular devices. PMID:26391084

  20. Immune response

    MedlinePlus

    Innate immunity; Humoral immunity; Cellular immunity; Immunity; Inflammatory response; Acquired (adaptive) immunity ... and usually does not react against them. INNATE IMMUNITY Innate, or nonspecific, immunity is the defense system ...

  1. Our Immune System

    MedlinePlus

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

  2. Effects of antibiotics on acquired immunity in vivo--current state of knowledge.

    PubMed

    Pomorska-Mól, M; Pejsak, Z

    2012-01-01

    Antibiotics are widely used in the therapy of infections. Besides the respective interactions between antibiotics and pathogens it seems that antibiotics also directly interact with the immune system. Some commonly used antibiotics are currently known to have effects on the innate immune response, as shown by in vitro, ex vivo and also in vivo animal experiments and clinical studies. Most of the experimental papers published to date, as well as most reviews, relate to how antibiotics affect the innate immune response or non-specific monocyte or lymphocyte proliferation. However the effects of antibiotics on the adaptive immune response are still not well characterized. This review of the literature considering different in vivo experiments indicate the real importance of interrelations existing between acquired immune responses and antibiotics, however, the mechanism of immunomodulatory effects of antibiotics are still poorly understood. Currently, data on the immunomodulating effects of antibiotics often remain heterogeneous, contradictory or insufficient, but most results published to date revealed the immunosuppressive effect of antibiotics on the antigen-specific immune response in vivo. In pigs as well as in poultry herds, it is not uncommon practice to add antibiotics to drinking water or feed at the time of vaccination. Information on the effects of such practices on the immune system of animals is restricted and more in vivo studies are needed to investigate the effects of antimicrobial drugs on the immune system, especially in the field conditions.

  3. 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 ...

  4. Monocyte function in the acquired immune deficiency syndrome. Defective chemotaxis.

    PubMed Central

    Smith, P D; Ohura, K; Masur, H; Lane, H C; Fauci, A S; Wahl, S M

    1984-01-01

    The ineffective immune response in patients with the acquired immune deficiency syndrome (AIDS) contributes to severe and widespread infections and unrestricted growth by certain tumors. To determine whether monocyte dysfunction contributes to this immunosuppressed condition, we investigated monocyte chemotaxis in patients with AIDS. Using three different chemotactic stimuli, N-formylmethionylleucylphenylalanine, lymphocyte-derived chemotactic factor, and C5a des Arg, we studied the chemotactic responses of monocytes from seven homosexual men with AIDS, three homosexuals with lymphadenopathy and an abnormal immunological profile, seven healthy homosexual men, and 23 heterosexual control individuals. Monocytes from each of the AIDS patients with Kaposi's sarcoma and/or opportunistic infection exhibited a marked reduction in chemotaxis to all stimuli compared with the healthy control subjects. The reduced chemotactic responses were observed over a wide range of concentrations for each stimulus. Monocytes from AIDS patients who had clinically apparent opportunistic infection(s) exhibited a greater reduction in monocyte migration to all three stimuli than monocytes from the AIDS patient with only Kaposi's sarcoma. Monocytes from each of three homosexuals with lymphadenopathy and an abnormal immunological profile exhibited decreased chemotactic responses that were intermediate between those of the AIDS patients and the healthy heterosexual control subjects. In contrast to these findings, monocytes from each of seven healthy homosexuals exhibited normal chemotactic responses to the same stimuli. In addition, monocytes from AIDS patients exhibited reduced chemotaxis to soluble products of Giardia lamblia, one of several protozoan parasites prevalent in AIDS patients. Thus the immune abnormality in AIDS, previously thought to involve only the T-, B-, and natural killer lymphocytes, extends to the monocyte-macrophage. Defective monocyte migratory function may contribute to

  5. Immune System Quiz

    MedlinePlus

    ... Homework? Here's Help White House Lunch Recipes Quiz: Immune System KidsHealth > For Kids > Quiz: Immune System Print A A A Text Size How much do you know about your immune system? Find out by taking this quiz! View Survey ...

  6. Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy.

    PubMed

    Drane, W E; Tipler, B M

    1987-06-01

    A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder.

  7. [The ageing immune system].

    PubMed

    Djukic, M; Nau, R; Sieber, C

    2014-10-01

    The aging of the immune system, also called immunosenescence, contributes to the increased morbidity and mortality from infections, autoimmune diseases and cancer as well as to the low efficacy of vaccination in elderly persons. Immunosenescence is characterized by a decrease in cell-mediated immune function and by reduced humoral immune responses caused by age-related changes in the innate immune system and age-dependent defects in T-and B-cell function. This paper gives an overview of the most important modifications in the different compartments of the immune system during the ageing process.

  8. [The ageing immune system].

    PubMed

    Djukic, M; Nau, R; Sieber, C

    2014-10-01

    The aging of the immune system, also called immunosenescence, contributes to the increased morbidity and mortality from infections, autoimmune diseases and cancer as well as to the low efficacy of vaccination in elderly persons. Immunosenescence is characterized by a decrease in cell-mediated immune function and by reduced humoral immune responses caused by age-related changes in the innate immune system and age-dependent defects in T-and B-cell function. This paper gives an overview of the most important modifications in the different compartments of the immune system during the ageing process. PMID:25254392

  9. 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…

  10. Trade-offs between acquired and innate immune defenses in humans

    PubMed Central

    McDade, Thomas W.; Georgiev, Alexander V.; Kuzawa, Christopher W.

    2016-01-01

    Immune defenses provide resistance against infectious disease that is critical to survival. But immune defenses are costly, and limited resources allocated to immunity are not available for other physiological or developmental processes. We propose a framework for explaining variation in patterns of investment in two important subsystems of anti-pathogen defense: innate (non-specific) and acquired (specific) immunity. The developmental costs of acquired immunity are high, but the costs of maintenance and activation are relatively low. Innate immunity imposes lower upfront developmental costs, but higher operating costs. Innate defenses are mobilized quickly and are effective against novel pathogens. Acquired responses are less effective against novel exposures, but more effective against secondary exposures due to immunological memory. Based on their distinct profiles of costs and effectiveness, we propose that the balance of investment in innate versus acquired immunity is variable, and that this balance is optimized in response to local ecological conditions early in development. Nutritional abundance, high pathogen exposure and low signals of extrinsic mortality risk during sensitive periods of immune development should all favor relatively higher levels of investment in acquired immunity. Undernutrition, low pathogen exposure, and high mortality risk should favor innate immune defenses. The hypothesis provides a framework for organizing prior empirical research on the impact of developmental environments on innate and acquired immunity, and suggests promising directions for future research in human ecological immunology. PMID:26739325

  11. The science base underlying research on acquired immune deficiency syndrome.

    PubMed

    Taube, S; Goldberg, M

    1983-01-01

    In order to define the clinical syndrome of AIDS and begin to deal with it effectively, scientists needed to understand how the immune system works. Fortunately, considerable knowledge was available: research in immunology over the last two decades had provided the technological advances and basic information about cell-mediated immunity that were necessary for identification of the syndrome. Without this knowledge base, immune suppression would not have been recognized as the common link among AIDS patients manifesting a variety of infections and unusual neoplasms. Similarly, research on infectious diseases, and in particular on the role of viruses as etiologic agents, has had an important bearing on understanding of AIDS. The epidemiologic data to date indicate that an infectious agent most likely is involved and that transmission of the disease requires intimate contact and perhaps some passage of blood. Among the candidates for viral agents are Epstein-Barr virus, cytomegalovirus, and human T-cell leukemia virus. All have been isolated from the cells of AIDS victims, but whether they are etiologic agents or opportunistic pathogens remains unresolved. Knowledge gained from the study of any of these viruses will contribute to understanding of AIDS, and vice versa. In this paper, we have attempted to show the integral relationship between specific research on AIDS and the ongoing research effort in related disciplines. It is important to recognize that effective research is the result of careful consideration of which questions can and should be addressed and the development of innovative approaches to gain answers to those questions. Research on AIDS is proceeding as rapidly as it is only because of the solid foundations that have been developed in the areas of immunology and virology. It is this base of research that ultimately will provide the rationale and the tools for solving new problems.

  12. Immune control strategies for vaccinia virus-related laboratory-acquired infections.

    PubMed

    Wei, Qiang; Jiang, Meng Nan; Han, Jun; Wang, Zi Jun

    2014-02-01

    While presenting biological characteristics of vaccinia virus and laboratory-acquired infections during related research processes, this paper focuses on benefits and risks of vaccinia virus immunization in relation to laboratory-acquired infections, describes characteristics and the adaptation of vaccinia virus vaccine, analyses the role vaccinia virus immunization plays in the prevention and control of laboratory-acquired infections, and finally proposes solutions and countermeasures to further promote and implement immune control strategies. The problem related to immune strategy and laboratory- acquired infections which is being raised, analyzed and explored plays an active and instructive role in vaccinia virus related researches and laboratory- acquired infections, and also helps to recommend and develop relevant immune strategy for future vaccine control of such infections.

  13. Antigen-Specific Acquired Immunity in Human Brucellosis: Implications for Diagnosis, Prognosis, and Vaccine Development

    PubMed Central

    Cannella, Anthony P.; Tsolis, Renee M.; Liang, Li; Felgner, Philip L.; Saito, Mayuko; Sette, Alessandro; Gotuzzo, Eduardo; Vinetz, Joseph M.

    2012-01-01

    Brucella spp., are Gram negative bacteria that cause disease by growing within monocyte/macrophage lineage cells. Clinical manifestations of brucellosis are immune mediated, not due to bacterial virulence factors. Acquired immunity to brucellosis has been studied through observations of naturally infected hosts (cattle, goats), mouse models (mice), and human infection. Even though Brucella spp. are known for producing mechanisms that evade the immune system, cell-mediated immune responses drive the clinical manifestations of human disease after exposure to Brucella species, as high antibody responses are not associated with protective immunity. The precise mechanisms by which cell-mediated immune responses confer protection or lead to disease manifestations remain undefined. Descriptive studies of immune responses in human brucellosis show that TH1 (interferon-γ-producing T cells) are associated with dominant immune responses, findings consistent with animal studies. Whether these T cell responses are protective, or determine the different clinical responses associated with brucellosis is unknown, especially with regard to undulant fever manifestations, relapsing disease, or are associated with responses to distinct sets of Brucella spp. antigens are unknown. Few data regarding T cell responses in terms of specific recognition of Brucella spp. protein antigens and peptidic epitopes, either by CD4+ or CD8+ T cells, have been identified in human brucellosis patients. Additionally because current attenuated Brucella vaccines used in animals cause human disease, there is a true need for a recombinant protein subunit vaccine for human brucellosis, as well as for improved diagnostics in terms of prognosis and identification of unusual forms of brucellosis. This review will focus on current understandings of antigen-specific immune responses induced Brucella peptidic epitopes that has promise for yielding new insights into vaccine and diagnostics development, and for

  14. 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...

  15. Feeding the immune system.

    PubMed

    Calder, Philip C

    2013-08-01

    A well-functioning immune system is key to providing good defence against pathogenic organisms and to providing tolerance to non-threatening organisms, to food components and to self. The immune system works by providing an exclusion barrier, by identifying and eliminating pathogens and by identifying and tolerating non-threatening sources of antigens, and by maintaining a memory of immunological encounters. The immune system is complex involving many different cell types distributed throughout the body and many different chemical mediators some of which are involved directly in defence while others have a regulatory role. Babies are born with an immature immune system that fully develops in the first few years of life. Immune competence can decline with ageing. The sub-optimal immune competence that occurs early and late in life increases susceptibility to infection. Undernutrition decreases immune defences, making an individual more susceptible to infection. However, the immune response to an infection can itself impair nutritional status and alter body composition. Practically all forms of immunity are affected by protein-energy malnutrition, but non-specific defences and cell-mediated immunity are most severely affected. Micronutrient deficiencies impair immune function. Here, vitamins A, D and E, and Zn, Fe and Se are discussed. The gut-associated lymphoid tissue is especially important in health and well-being because of its close proximity to a large and diverse population of organisms in the gastrointestinal tract and its exposure to food constituents. Certain probiotic bacteria which modify the gut microbiota enhance immune function in laboratory animals and may do so in human subjects.

  16. Immune System (For Parents)

    MedlinePlus

    ... lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has ... can't be prevented, you can help your child's immune system stay stronger and fight illnesses by ...

  17. The Unspecific Side of Acquired Immunity Against Infectious Disease: Causes and Consequences

    PubMed Central

    Muraille, Eric

    2016-01-01

    Acquired immunity against infectious disease (AIID) has long been considered as strictly dependent on the B and T lymphocytes of the adaptive immune system. Consequently, AIID has been viewed as highly specific to the antigens expressed by pathogens. However, a growing body of data motivates revision of this central paradigm of immunology. Unrelated past infection, vaccination, and chronic infection have been found to induce cross-protection against numerous pathogens. These observations can be partially explained by the poly-specificity of antigenic T and B receptors, the Mackaness effect and trained immunity. In addition, numerous studies highlight the importance of microbiota composition on resistance to infectious disease via direct competition or modulation of the immune response. All of these data support the idea that a non-negligible part of AIID in nature can be nonspecific to the pathogens encountered and even of the antigens expressed by pathogens. As this protection may be dependent on the private T and B repertoires produced by the random rearrangement of genes, past immune history, chronic infection, and microbiota composition, it is largely unpredictable at the individual level. However, we can reasonably expect that a better understanding of the underlying mechanisms will allow us to statistically predict cross-protection at the population level. From an evolutionary perspective, selection of immune mechanisms allowing for partially nonspecific AIID would appear to be advantageous against highly polymorphic and rapidly evolving pathogens. This new emerging paradigm may have several important consequences on our understanding of individual infectious disease susceptibility and our conception of tolerance, vaccination and therapeutic strategies against infection and cancer. It also underscores the importance of viewing the microbiota and persisting infectious agents as integral parts of the immune system. PMID:26793171

  18. Differences in acquired immune deficiency syndrome treatment and evaluation strategies between Chinese and Western Medicine.

    PubMed

    Liu, Zhibin; Li, Xia; Yang, Jiping; Xu, Liran; Guo, Huijun

    2015-12-01

    Complementary and alternative medicine, including Chinese medicine (CM), has been used to treat acquired immune deficiency syndrome (AIDS) foralmost 30 years. We aimed to compare the main differences between AIDS treatment and evaluation strategies between CM and Western Medicine (WM), and analyze advantages and disadvantages. The characteristics of integrative medicine (IM), based on CM and WM, include a patient-centered mode of medicine based on evidence. IM focuses on complex intervention and management with systemic and individual treatment. The evaluation indexes of IM might consist of objective indicators and subjective indexes. IM might be a more valuable method for treating AIDS in the future instead of WM or CM alone.

  19. Pneumonia - weakened immune system

    MedlinePlus

    If you have a weakened immune system, you may receive daily antibiotics to prevent some types of pneumonia. Ask your provider if you should receive the influenza (flu) and pneumococcal (pneumonia) vaccines. Practice ...

  20. Immune System 101

    MedlinePlus

    ... your healthy cells. How HIV Affects This Complex Process HIV disrupts this process by directly infecting the helper T-cells. Your ... T-cells are destroyed in the HIV replication process. For more information, see NIAID's The Immune System . ...

  1. Erythema elevatum diutinum in acquired immune deficiency syndrome: Can it be an immune reconstitution inflammatory syndrome?

    PubMed Central

    Jose, Sheethal K; Marfatia, Yogesh S.

    2016-01-01

    A 47-year-old male with acquired immune deficiency syndrome (AIDS) presented with multiple hyperpigmented papules and nodules on both ankles, dorsum of bilateral feet and soles. It was associated with mild itching and pain. The patient was diagnosed with human immunodeficiency virus (HIV) in 2007. First-line antiretroviral therapy (ART) was started in 2009 to which he responded initially. He was shifted to second-line ART 11 months ago in March 2015 due to treatment failure as suggested by CD4 count of 50 cells/mm3. The present skin lesions started 2 months after the initiation of second-line ART. Differential diagnoses considered were Kaposi's sarcoma and immune reconstitution inflammatory syndrome (IRIS) related infections, but biopsy was suggestive of erythema elevatum diutinum (EED). Patient was started on oral dapsone 100 mg/day and increased to 200 mg/day to which he is responding gradually. In the present case, appearance of the lesions after initiation of second-line ART coupled with increase in CD4 count and decrease of viral load below undetectable level suggest that EED could be an IRIS. PMID:27190420

  2. Proposed method for agglutinating antibody titer analysis and its use as indicator of acquired immunity in pacu, Piaractus mesopotamicus.

    PubMed

    Biller-Takahashi, J D; Montassier, H J; Takahashi, L S; Urbinati, E C

    2014-02-01

    Antibody can be assessed by agglutinating antibody titer which is a quantitative measure of circulating antibodies in serum from fish previously immunized. The antibody evaluation has been performed with different fish species, and is considered a reliable method that can be applied to confirm several hypothesis regarding acquired immunity, even in conjunction with precise methods to describe immune mechanisms. In order to provide appropriate analytical methods for future studies on the specific immune system of native fish, the present study standardized on assay to measure the serum agglutinating antibody titer produced after immunization with inactivated A. hydrophila and levamisole administration in pacu. It was possible to determine the agglutinating antibodies titer in a satisfactorily way in pacu immunized with inactive A. hydrophila, and the highest titers were observed on fish fed with levamisole.

  3. Early developmental exposures shape trade-offs between acquired and innate immunity in humans

    PubMed Central

    Georgiev, Alexander V.; Kuzawa, Christopher W.; McDade, Thomas W.

    2016-01-01

    Background and objectives Life history theory predicts resource allocation trade-offs between competing functions and processes. We test the hypothesis that relative investment towards innate versus acquired immunity in humans is subject to such trade-offs and that three types of early developmental exposures are particularly salient in shaping adult immunophenotype: (i) pathogen exposure, (ii) nutritional resources; and (iii) extrinsic mortality cues. Methodology We quantified one aspect each of innate and acquired immune function, via C-reactive protein and Epstein–Barr virus antibodies, respectively, in a sample of 1248 men and women from the Philippines (ca. 21.5 years old). Early developmental exposures were assessed via long-term data collected prospectively since participants’ birth (1983–4). We calculated a standardized ratio to assess relative bias towards acquired versus innate immune function and examined its relationship to a suite of predictors via multiple regression. Results In partial support of our predictions, some of the measures of higher pathogen exposure, greater availability of nutritional resources, and lower extrinsic mortality cues in early life were associated with a bias toward acquired immunity in both men and women. The immune profile of women, in particular, appeared to be more sensitive to early life pathogen exposures than those of men. Finally, contrary to prediction, women exhibited a greater relative investment toward innate, not acquired, immunity. Conclusions and implications Early environments can exert considerable influence on the development of immunity. They affect trade-offs between innate and acquired immunity, which show adaptive plasticity and may differ in their influence in men and women. PMID:27530543

  4. Protection against hepatitis E virus infection by naturally acquired and vaccine-induced immunity.

    PubMed

    Zhang, J; Zhang, X-F; Zhou, C; Wang, Z-Z; Huang, S-J; Yao, X; Liang, Z-L; Wu, T; Li, J-X; Yan, Q; Yang, C-L; Jiang, H-M; Huang, H-J; Xian, Y-L; Shih, J W-K; Ng, M-H; Li, Y-M; Wang, J-Z; Zhu, F-C; Xia, N-S

    2014-06-01

    Immunity acquired from infection or vaccination protects humans from symptomatic hepatitis E. However, whether the risk of hepatitis E virus (HEV) infection is reduced by the immunity remains unknown. To understand this issue, a cohort with 12 409 participants randomized to receive the hepatitis E vaccine Hecolin(®) or placebo were serologically followed up for 2 years after vaccination. About half (47%) of participants were initially seropositive. A total of 139 infection episodes, evidenced by four-fold or greater rise of anti-HEV level or positive seroconversion, occurred in participants who received three doses of treatment. Risk of infection was highest among the baseline seronegative placebo group participants (2.04%). Pre-existing immunity and vaccine-induced immunity lower the risk significantly, to 0.52% and 0.30%, respectively. In conclusion, both vaccine-induced and naturally acquired immunity can effectively protect against HEV infection. PMID:24118636

  5. Strong density-dependent competition and acquired immunity constrain parasite establishment: implications for parasite aggregation.

    PubMed

    Luong, Lien T; Vigliotti, Beth A; Hudson, Peter J

    2011-04-01

    The vast majority of parasites exhibit an aggregated frequency distribution within their host population, such that most hosts have few or no parasites while only a minority of hosts are heavily infected. One exception to this rule is the trophically transmitted parasite Pterygodermatites peromysci of the white-footed mouse (Peromyscus leucopus), which is randomly distributed within its host population. Here, we ask: what are the factors generating the random distribution of parasites in this system when the majority of macroparasites exhibit non-random patterns? We hypothesise that tight density-dependent processes constrain parasite establishment and survival, preventing the build-up of parasites within individual hosts, and preclude aggregation within the host population. We first conducted primary infections in a laboratory experiment using white-footed mice to test for density-dependent parasite establishment and survival of adult worms. Secondary or challenge infection experiments were then conducted to investigate underlying mechanisms, including intra-specific competition and host-mediated restrictions (i.e. acquired immunity). The results of our experimental infections show a dose-dependent constraint on within-host-parasite establishment, such that the proportion of mice infected rose initially with exposure, and then dropped off at the highest dose. Additional evidence of density-dependent competition comes from the decrease in worm length with increasing levels of exposure. In the challenge infection experiment, previous exposure to parasites resulted in a lower prevalence and intensity of infection compared with primary infection of naïve mice; the magnitude of this effect was also density-dependent. Host immune response (IgG levels) increased with the level of exposure, but decreased with the number of worms established. Our results suggest that strong intra-specific competition and acquired host immunity operate in a density-dependent manner to

  6. System Acquires Data On Reactivities Of Foams

    NASA Technical Reports Server (NTRS)

    Walls, Joe T.

    1994-01-01

    Data-acquisition and -plotting system, called DAPS(TM), developed enabling accurate and objective determination of physical properties related to reactivities of polyurethane and polyisocyanurate foams. Automated, computer-controlled test apparatus that acquires data on rates of rise, rise profiles, exothermic temperatures, and internal pressures of foams prepared from both manual and machine-mixed batches. Data used to determine minute differences between reaction kinetics and exothermic profiles of foam formulations, properties of end products which are statistically undifferentiated.

  7. How the codfish changed its immune system.

    PubMed

    Parham, Peter

    2016-09-28

    A common ancestor of the modern codfish acquired a set of mutations that eliminated a major arm of the adaptive immune system-the MHC II pathway of antigen presentation to CD4(+) T cells. Subsequent to this event, there was a radiation of these fish in which the number and diversity of MHC I genes increased in species-specific ways. PMID:27681288

  8. Feeding our immune system: impact on metabolism.

    PubMed

    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

  9. Technique Selectively Represses Immune System

    MedlinePlus

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

  10. Acquired immunity and asymptomatic reservoir impact on frontline and airport ebola outbreak syndromic surveillance and response.

    PubMed

    Tambo, Ernest; Xiao-Nong, Zhou

    2014-01-01

    The number of surveillance networks for infectious disease diagnosis and response has been growing. In 2000, the World Health Organization (WHO) established the Global Outbreak Alert and Response Network, which has been endorsed by each of the 46 WHO African members since then. Yet, taming the dynamics and plague of the vicious Ebola virus disease (EVD) in African countries has been patchy and erratic due to inadequate surveillance and contact tracing, community defiance and resistance, a lack of detection and response systems, meager/weak knowledge and information on the disease, inadequacies in protective materials protocols, contact tracing nightmare and differing priorities at various levels of the public health system. Despite the widespread acceptance of syndromic surveillance (SS) systems, their ability to provide early warning alerts and notifications of outbreaks is still unverified. Information is often too limited for any outbreak, or emerging or otherwise unexpected disease, to be recognized at either the community or the national level. Indeed, little is known about the role and the interactions between the Ebola infection and exposure to other syndemics and the development of acquired immunity, asymptomatic reservoir, and Ebola seroconversion. Can lessons be learnt from smallpox, polio, and influenza immunity, and can immunization against these serve as a guide? In most endemic countries, community health centers and disease control and prevention at airports solely relies on passive routine immunization control and reactive syndromic response. The frontline and airport Ebola SS systems in West Africa have shown deficiencies in terms of responding with an alarming number of case fatalities, and suggest that more detailed insights into Ebola, and proactive actions, are needed. The quest for effective early indicators (EEE) in shifting the public and global health paradigm requires the development and implementation of a comprehensive and effective

  11. Acquired Immune Deficiency Syndrome, AIDS: A Selected Bibliography of Federal Government Publications. Research Guide 90 104.

    ERIC Educational Resources Information Center

    Alexander, Margaret

    This research guide presents a selected bibliography of federal government publications about the Acquired Immune Deficiency Syndrome (AIDS). These documents are listed in five categories: (1) Bibliographies (7); (2) Congressional Publications (69 hearings and reports); (3) Executive Branch Publications (43 reports); (4) Federal Government…

  12. Semantic Differential Responses to Educational Posters on Acquired Immune Deficiency Syndrome (AIDS).

    ERIC Educational Resources Information Center

    Wilson, Christopher; Stewin, Leonard L.

    1992-01-01

    Undergraduate students (n=131) responded to eight educational posters dealing with the Acquired Immune Deficiency Syndrome (AIDS) using a nine-item semantic differential scale. Two posters were consistently rated as more informative, reassuring, effective, decent, and better than the others. The first utilized an objective and informative…

  13. Impact of acquired immunity and dose-dependent probability of illness on quantitative microbial risk assessment.

    PubMed

    Havelaar, A H; Swart, A N

    2014-10-01

    Dose-response models in microbial risk assessment consider two steps in the process ultimately leading to illness: from exposure to (asymptomatic) infection, and from infection to (symptomatic) illness. Most data and theoretical approaches are available for the exposure-infection step; the infection-illness step has received less attention. Furthermore, current microbial risk assessment models do not account for acquired immunity. These limitations may lead to biased risk estimates. We consider effects of both dose dependency of the conditional probability of illness given infection, and acquired immunity to risk estimates, and demonstrate their effects in a case study on exposure to Campylobacter jejuni. To account for acquired immunity in risk estimates, an inflation factor is proposed. The inflation factor depends on the relative rates of loss of protection over exposure. The conditional probability of illness given infection is based on a previously published model, accounting for the within-host dynamics of illness. We find that at low (average) doses, the infection-illness model has the greatest impact on risk estimates, whereas at higher (average) doses and/or increased exposure frequencies, the acquired immunity model has the greatest impact. The proposed models are strongly nonlinear, and reducing exposure is not expected to lead to a proportional decrease in risk and, under certain conditions, may even lead to an increase in risk. The impact of different dose-response models on risk estimates is particularly pronounced when introducing heterogeneity in the population exposure distribution.

  14. Teaching AIDS. A Resource Guide on Acquired Immune Deficiency Syndrome. Third Edition.

    ERIC Educational Resources Information Center

    Quackenbush, Marcia; Sargent, Pamela

    The first edition of this resource guide for educators on how to teach students about Acquired Immune Deficiency Syndrome (AIDS) was published in 1986. Since then, basic facts about the transmission and prevention of the AIDS virus have not changed substantially. The terminologies about the disease, however, have changed and the changing…

  15. Small intestinal lymphoma in three patients with acquired immune deficiency syndrome.

    PubMed

    Steinberg, J J; Bridges, N; Feiner, H D; Valensi, Q

    1985-01-01

    Three cases of small bowel lymphoma in young homosexual men are presented. All three had acquired immune deficiency syndrome as demonstrated by demography, sexual history, cachexia, opportunistic infections by Cytomegalovirus, Pneumocystis carinii, atypical Mycobacterium, Candida, and/or evidence of immune deficiency, such as skin test anergy, lymphopenia, inversion of T-helper/T-suppressor ratio, and diminished lymphocyte response to either phytohemmaglutinin or pokeweed mitogen. All had peripheral and/or abdominal lymphadenopathy, and gastrointestinal symptoms, e.g., diarrhea, spasms, constipation, and oral candidiasis. The diagnosis of lymphoma was made at laparotomy in all cases. All three had complete removal of localized tumor (stage Ie or IIe), yet died within 6 months of surgery and/or chemotherapy. Thus gastrointestinal complaints may not always be related to "gay bowel" syndrome, or other infectious diseases in patients with acquired immune deficiency syndrome. Small intestinal lymphoma should be added to the list of neoplasms to which this group is susceptible.

  16. Metronidazole and the immune system.

    PubMed

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

    2011-06-01

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

  17. Signal regulators of systemic acquired resistance

    PubMed Central

    Gao, Qing-Ming; Zhu, Shifeng; Kachroo, Pradeep; Kachroo, Aardra

    2015-01-01

    Salicylic acid (SA) is an important phytohormone that plays a vital role in a number of physiological responses, including plant defense. The last two decades have witnessed a number of breakthroughs related to biosynthesis, transport, perception and signaling mediated by SA. These findings demonstrate that SA plays a crictical role in both local and systemic defense responses. Systemic acquired resistance (SAR) is one such SA-dependent response. SAR is a long distance signaling mechanism that provides broad spectrum and long-lasting resistance to secondary infections throughout the plant. This unique feature makes SAR a highly desirable trait in crop production. This review summarizes the recent advances in the role of SA in SAR and discusses its relationship to other SAR inducers. PMID:25918514

  18. Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance.

    PubMed

    Hugo, Willy; Shi, Hubing; Sun, Lu; Piva, Marco; Song, Chunying; Kong, Xiangju; Moriceau, Gatien; Hong, Aayoung; Dahlman, Kimberly B; Johnson, Douglas B; Sosman, Jeffrey A; Ribas, Antoni; Lo, Roger S

    2015-09-10

    Clinically acquired resistance to MAPK inhibitor (MAPKi) therapies for melanoma cannot be fully explained by genomic mechanisms and may be accompanied by co-evolution of intra-tumoral immunity. We sought to discover non-genomic mechanisms of acquired resistance and dynamic immune compositions by a comparative, transcriptomic-methylomic analysis of patient-matched melanoma tumors biopsied before therapy and during disease progression. Transcriptomic alterations across resistant tumors were highly recurrent, in contrast to mutations, and were frequently correlated with differential methylation of tumor cell-intrinsic CpG sites. We identified in the tumor cell compartment supra-physiologic c-MET up-expression, infra-physiologic LEF1 down-expression and YAP1 signature enrichment as drivers of acquired resistance. Importantly, high intra-tumoral cytolytic T cell inflammation prior to MAPKi therapy preceded CD8 T cell deficiency/exhaustion and loss of antigen presentation in half of disease-progressive melanomas, suggesting cross-resistance to salvage anti-PD-1/PD-L1 immunotherapy. Thus, melanoma acquires MAPKi resistance with highly dynamic and recurrent non-genomic alterations and co-evolving intra-tumoral immunity.

  19. Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance

    PubMed Central

    Hugo, Willy; Shi, Hubing; Sun, Lu; Piva, Marco; Song, ChunYing; Kong, Xiangju; Moriceau, Gatien; Hong, Aayoung; Dahlman, Kimberly B.; Johnson, Douglas B.; Sosman, Jeffrey A.; Ribas, Antoni; Lo, Roger S.

    2015-01-01

    SUMMARY Clinically acquired resistance to MAPK inhibitor (MAPKi) therapies for melanoma cannot be fully explained by genomic mechanisms and may be accompanied by co-evolution of intra-tumoral immunity. We sought to discover non-genomic mechanisms of acquired resistance and dynamic immune compositions by a comparative, transcriptomic-methylomic analysis of patient-matched melanoma tumors biopsied before therapy and during disease progression. Transcriptomic alterations across resistant tumors were highly recurrent, in contrast to mutations, and were frequently correlated with differential methylation of tumor cell-intrinsic CpG sites. We identified in the tumor cell compartment supra-physiologic c-MET up-expression, infra-physiologic LEF1 down-expression, and YAP1 signature enrichment as drivers of acquired resistance. Importantly, high intra-tumoral cytolytic T-cell inflammation prior to MAPKi therapy preceded CD8 T-cell deficiency/exhaustion and loss of antigen-presentation in half of disease-progressive melanomas, suggesting cross-resistance to salvage anti-PD-1/PD-L1 immunotherapy. Thus, melanoma acquires MAPKi-resistance with highly dynamic and recurrent non-genomic alterations and co-evolving intra-tumoral immunity. PMID:26359985

  20. Primary cardiac lymphoma in a patient with acquired immune deficiency syndrome

    SciTech Connect

    Constantino, A.; West, T.E.; Gupta, M.; Loghmanee, F.

    1987-12-01

    A 34-year-old male prisoner with a history of intravenous drug abuse presented with fever, lymphadenopathy, weight loss, and recent onset of congestive heart failure. Serologic testing was positive for antibodies to human immune deficiency virus. There was intense myocardial uptake of gallium. Autopsy showed a primary immunoblastic lymphoma involving only the myocardium. While primary cardiac lymphoma is an extremely rare condition, the incidence may be higher in patients with acquired immune deficiency syndrome (AIDS) and should be suspected in cases with atypical cardiomyopathy.

  1. 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...

  2. Gut epithelial barrier dysfunction in human immunodeficiency virus-hepatitis C virus coinfected patients: Influence on innate and acquired immunity

    PubMed Central

    Márquez, Mercedes; Fernández Gutiérrez del Álamo, Clotilde; Girón-González, José Antonio

    2016-01-01

    Even in cases where viral replication has been controlled by antiretroviral therapy for long periods of time, human immunodeficiency virus (HIV)-infected patients have several non-acquired immunodeficiency syndrome (AIDS) related co-morbidities, including liver disease, cardiovascular disease and neurocognitive decline, which have a clear impact on survival. It has been considered that persistent innate and acquired immune activation contributes to the pathogenesis of these non-AIDS related diseases. Immune activation has been related with several conditions, remarkably with the bacterial translocation related with the intestinal barrier damage by the HIV or by hepatitis C virus (HCV)-related liver cirrhosis. Consequently, increased morbidity and mortality must be expected in HIV-HCV coinfected patients. Disrupted gut barrier lead to an increased passage of microbial products and to an activation of the mucosal immune system and secretion of inflammatory mediators, which in turn might increase barrier dysfunction. In the present review, the intestinal barrier structure, measures of intestinal barrier dysfunction and the modifications of them in HIV monoinfection and in HIV-HCV coinfection will be considered. Both pathogenesis and the consequences for the progression of liver disease secondary to gut microbial fragment leakage and immune activation will be assessed. PMID:26819512

  3. Potential Suppressive Effects of Two C60 Fullerene Derivatives on Acquired Immunity

    NASA Astrophysics Data System (ADS)

    Hirai, Toshiro; Yoshioka, Yasuo; Udaka, Asako; Uemura, Eiichiro; Ohe, Tomoyuki; Aoshima, Hisae; Gao, Jian-Qing; Kokubo, Ken; Oshima, Takumi; Nagano, Kazuya; Higashisaka, Kazuma; Mashino, Tadahiko; Tsutsumi, Yasuo

    2016-10-01

    The therapeutic effects of fullerene derivatives on many models of inflammatory disease have been demonstrated. The anti-inflammatory mechanisms of these nanoparticles remain to be elucidated, though their beneficial roles in allergy and autoimmune diseases suggest their suppressive potential in acquired immunity. Here, we evaluated the effects of C60 pyrrolidine tris-acid (C60-P) and polyhydroxylated fullerene (C60(OH)36) on the acquired immune response in vitro and in vivo. In vitro, both C60 derivatives had dose-dependent suppressive effects on T cell receptor-mediated activation of T cells and antibody production by B cells under anti-CD40/IL-4 stimulation, similar to the actions of the antioxidant N-acetylcysteine. In addition, C60-P suppressed ovalbumin-specific antibody production and ovalbumin-specific T cell responses in vivo, although T cell-independent antibodies responses were not affected by C60-P. Together, our data suggest that fullerene derivatives can suppress acquired immune responses that require T cells.

  4. The Role of Acquired Immunity in the Spread of Human Papillomavirus (HPV): Explorations with a Microsimulation Model

    PubMed Central

    Matthijsse, Suzette M.; van Rosmalen, Joost; Hontelez, Jan A. C.; Bakker, Roel; de Kok, Inge M. C. M.; van Ballegooijen, Marjolein; de Vlas, Sake J.

    2015-01-01

    Background Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already protect part of the risk population against new HPV infections. Methods We used STDSIM, an established stochastic microsimulation model, quantified to the Netherlands. We explored different assumptions regarding the natural history of HPV-16 and HPV-18, and estimated the transmission probabilities and durations of acquired immunity necessary to reproduce age-specific prevalence. Results A model without acquired immunity cannot reproduce the age-specific patterns of HPV. Also, it is necessary to assume a high degree of individual variation in the duration of infection and acquired immunity. According to the model estimates, on average 20% of women are immune for HPV-16 and 15% for HPV-18. After an HPV-16 infection, 50% are immune for less than 1 year, whereas 20% exceed 30 years. For HPV-18, up to 12% of the individuals are immune for less than 1 year, and about 50% over 30 years. Almost half of all women will never acquire HPV-16 or HPV-18. Conclusions Acquired immunity likely plays a major role in HPV epidemiology, but its duration shows substantial variation. Combined with the lifetime risk, this explains to a large extent why many women will never develop cervical cancer. PMID:25642941

  5. Ubiquitin in the immune system

    PubMed Central

    Zinngrebe, Julia; Montinaro, Antonella; Peltzer, Nieves; Walczak, Henning

    2014-01-01

    Ubiquitination is a post-translational modification process that has been implicated in the regulation of innate and adaptive immune responses. There is increasing evidence that both ubiquitination and its reversal, deubiquitination, play crucial roles not only during the development of the immune system but also in the orchestration of an immune response by ensuring the proper functioning of the different cell types that constitute the immune system. Here, we provide an overview of the latest discoveries in this field and discuss how they impact our understanding of the ubiquitin system in host defence mechanisms as well as self-tolerance. PMID:24375678

  6. Ubiquitin in the immune system.

    PubMed

    Zinngrebe, Julia; Montinaro, Antonella; Peltzer, Nieves; Walczak, Henning

    2014-01-01

    Ubiquitination is a post-translational modification process that has been implicated in the regulation of innate and adaptive immune responses. There is increasing evidence that both ubiquitination and its reversal, deubiquitination, play crucial roles not only during the development of the immune system but also in the orchestration of an immune response by ensuring the proper functioning of the different cell types that constitute the immune system. Here, we provide an overview of the latest discoveries in this field and discuss how they impact our understanding of the ubiquitin system in host defence mechanisms as well as self-tolerance.

  7. Comparative immune systems in animals.

    PubMed

    Yuan, Shaochun; Tao, Xin; Huang, Shengfeng; Chen, Shangwu; Xu, Anlong

    2014-02-01

    Animal immune systems can be classified into those of innate immunity and those of adaptive immunity. It is generally thought that the former are universal for all animals and depend on germline-encoded receptors that recognize highly conserved pathogen-associated molecular patterns (PAMPs), whereas the latter are vertebrate specific and are mediated primarily by lymphocytes bearing a unique antigen receptor. However, novel adaptive or adaptive-like immunities have been found in invertebrates and jawless vertebrates, and extraordinarily complex innate immunities, created through huge expansions of many innate gene families, have recently been found in the cephalochordate amphioxus and the echinoderm sea urchin. These studies not only inspire immunologists to seek novel immune mechanisms in invertebrates but also raise questions about the origin and evolution of vertebrate immunities.

  8. 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

  9. Cross-reactive acquired immunity influences transmission success of the Lyme disease pathogen, Borrelia afzelii.

    PubMed

    Jacquet, Maxime; Durand, Jonas; Rais, Olivier; Voordouw, Maarten J

    2015-12-01

    Cross-reactive acquired immunity in the vertebrate host induces indirect competition between strains of a given pathogen species and is critical for understanding the ecology of mixed infections. In vector-borne diseases, cross-reactive antibodies can reduce pathogen transmission at the vector-to-host and the host-to-vector lifecycle transition. The highly polymorphic, immunodominant, outer surface protein C (OspC) of the tick-borne spirochete bacterium Borrelia afzelii induces a strong antibody response in the vertebrate host. To test how cross-immunity in the vertebrate host influences tick-to-host and host-to-tick transmission, mice were immunized with one of two strain-specific recombinant OspC proteins (A3, A10), challenged via tick bite with one of the two B. afzelii ospC strains (A3, A10), and infested with xenodiagnostic ticks. Immunization with a given rOspC antigen protected mice against homologous strains carrying the same major ospC group allele but provided little or no cross-protection against heterologous strains carrying a different major ospC group allele. There were cross-immunity effects on the tick spirochete load but not on the probability of host-to-tick transmission. The spirochete load in ticks that had fed on mice with cross-immune experience was reduced by a factor of two compared to ticks that had fed on naive control mice. In addition, strain-specific differences in mouse spirochete load, host-to-tick transmission, tick spirochete load, and the OspC-specific IgG response revealed the mechanisms that determine variation in transmission success between strains of B. afzelii. This study shows that cross-immunity in infected vertebrate hosts can reduce pathogen load in the arthropod vector with potential consequences for vector-to-host pathogen transmission.

  10. Cross-reactive acquired immunity influences transmission success of the Lyme disease pathogen, Borrelia afzelii.

    PubMed

    Jacquet, Maxime; Durand, Jonas; Rais, Olivier; Voordouw, Maarten J

    2015-12-01

    Cross-reactive acquired immunity in the vertebrate host induces indirect competition between strains of a given pathogen species and is critical for understanding the ecology of mixed infections. In vector-borne diseases, cross-reactive antibodies can reduce pathogen transmission at the vector-to-host and the host-to-vector lifecycle transition. The highly polymorphic, immunodominant, outer surface protein C (OspC) of the tick-borne spirochete bacterium Borrelia afzelii induces a strong antibody response in the vertebrate host. To test how cross-immunity in the vertebrate host influences tick-to-host and host-to-tick transmission, mice were immunized with one of two strain-specific recombinant OspC proteins (A3, A10), challenged via tick bite with one of the two B. afzelii ospC strains (A3, A10), and infested with xenodiagnostic ticks. Immunization with a given rOspC antigen protected mice against homologous strains carrying the same major ospC group allele but provided little or no cross-protection against heterologous strains carrying a different major ospC group allele. There were cross-immunity effects on the tick spirochete load but not on the probability of host-to-tick transmission. The spirochete load in ticks that had fed on mice with cross-immune experience was reduced by a factor of two compared to ticks that had fed on naive control mice. In addition, strain-specific differences in mouse spirochete load, host-to-tick transmission, tick spirochete load, and the OspC-specific IgG response revealed the mechanisms that determine variation in transmission success between strains of B. afzelii. This study shows that cross-immunity in infected vertebrate hosts can reduce pathogen load in the arthropod vector with potential consequences for vector-to-host pathogen transmission. PMID:26384476

  11. 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.

  12. 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.

  13. 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

  14. Systems Biology and immune aging.

    PubMed

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

    2014-11-01

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

  15. Molecular characteristics of Illicium verum extractives to activate acquired immune response

    PubMed Central

    Peng, Wanxi; Lin, Zhi; Wang, Lansheng; Chang, Junbo; Gu, Fangliang; Zhu, Xiangwei

    2015-01-01

    Illicium verum, whose extractives can activate the demic acquired immune response, is an expensive medicinal plant. However, the rich extractives in I. verum biomass were seriously wasted for the inefficient extraction and separation processes. In order to further utilize the biomedical resources for the good acquired immune response, the four extractives were obtained by SJYB extraction, and then the immunology moleculars of SJYB extractives were identified and analyzed by GC–MS. The result showed that the first-stage extractives contained 108 components including anethole (40.27%), 4-methoxy-benzaldehyde (4.25%), etc.; the second-stage extractives had 5 components including anethole (84.82%), 2-hydroxy-2-(4-methoxy-phenyl)-n-methyl-acetamide (7.11%), etc.; the third-stage extractives contained one component namely anethole (100%); and the fourth-stage extractives contained 5 components including cyclohexyl-benzene (64.64%), 1-(1-methylethenyl)-3-(1-methylethyl)-benzene (17.17%), etc. The SJYB extractives of I. verum biomass had a main retention time between 10 and 20 min what’s more, the SJYB extractives contained many biomedical moleculars, such as anethole, eucalyptol, [1S-(1α,4aα,10aβ)]-1,2,3,4,4a,9,10,10a-octahydro-1,4a-dimethyl-7-(1-methylethyl)-1-phenanthrenecarboxylic acid, stigmast-4-en-3-one, γ-sitosterol, and so on. So the functional analytical results suggested that the SJYB extractives of I. verum had a function in activating the acquired immune response and a huge potential in biomedicine. PMID:27081359

  16. Length of survival of patients with acquired immune deficiency syndrome in the United Kingdom.

    PubMed Central

    Marasca, G; McEvoy, M

    1986-01-01

    An analysis of the lengths of survival of patients with the acquired immune deficiency syndrome presenting with different opportunistic diseases was performed using epidemiological data routinely collected at the PHLS Communicable Disease Surveillance Centre. The overall crude case fatality rate was 55.4% (93/168). The median survival times were: 21.2 months for Kaposi's sarcoma, 12.5 months for Pneumocystis carinii pneumonia, and 13.3 months for other opportunistic infections. The shortest median survival time (6.6 months) was found for those with both Kaposi's sarcoma and P carinii pneumonia. There were significant differences between durations of survival of patients with Kaposi's sarcoma and those with all other diseases, which indicated impaired cellular immunity apart from opportunistic infections. This analysis shows that those with Kaposi's sarcoma alone have the most favourable prognosis. PMID:3089373

  17. [Changes in the thoracic roentgen image in patients with acquired immune deficiency syndrome].

    PubMed

    Pölzleitner, D; Herold, C; Tscholakoff, D; Imhof, H

    1990-01-19

    Since the earliest reports of what was later termed the acquired immune deficiency syndrome (AIDS) appeared in 1980/81, with the recognition of opportunistic infections and Kaposi's sarcoma in homosexual men and i.v. drug abusers, more than 60% of AIDS patients develop pulmonary manifestations at some time in the course of their disease. Radiographic evaluation of the chest plays an important role in diagnosis. In fact, radiological changes are unspecific and either bacteriological proof or histological verification needs to be confirmed.

  18. Acquired immune response to oncogenic human papillomavirus associated with prophylactic cervical cancer vaccines.

    PubMed

    Einstein, Mark H

    2008-04-01

    Human papillomavirus (HPV) is a common infection among women and a necessary cause of cervical cancer. Oncogenic HPV types infecting the anogenital tract have the potential to induce natural immunity, but at present we do not clearly understand the natural history of infection in humans and the mechanisms by which the virus can evade the host immune response. Natural acquired immune responses against HPV may be involved in the clearance of infection, but persistent infection with oncogenic virus types leads to the development of precancerous lesions and cancer. B cell responses are important for viral neutralization, but antibody responses in patients with cervical cancer are poor. Prophylactic vaccines targeting oncogenic virus types associated with cervical cancer have the potential to prevent up to 80% of cervical cancers by targeting HPV types 16 and 18. Clinical data show that prophylactic vaccines are effective in inducing antibody responses and in preventing persistent infection with HPV, as well as the subsequent development of high-grade cervical intraepithelial neoplasia. This article reviews the known data regarding natural immune responses to HPV and those developed by prophylactic vaccination.

  19. 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.

  20. Antimicrobial synergism against Mycobacterium avium complex strains isolated from patients with acquired immune deficiency syndrome.

    PubMed Central

    Yajko, D M; Kirihara, J; Sanders, C; Nassos, P; Hadley, W K

    1988-01-01

    Pairs of 11 antimicrobial agents were tested in vitro for their ability to act synergistically against three strains of Mycobacterium avium complex isolated from patients with acquired immune deficiency syndrome. From the combinations tested, four drugs (ethambutol, rifampin, ciprofloxacin, and erythromycin) were selected for more extensive study against 20 strains of M. avium complex. The inhibitory and killing synergism obtained with combinations of two, three, or four drugs was assessed by determining the fractional inhibitory concentration index and fractional bactericidal concentration index. Inhibitory synergism occurred against 90 to 100% of the strains for all drug combinations in which ethambutol was included. Killing synergism occurred against 85 to 95% of the strains when ethambutol was used in combinations which included either rifampin or ciprofloxacin. However, killing synergism occurred against only 45% of the strains when drugs were tested at concentrations that can be obtained in patient serum. In other experiments, rifabutin (Ansamycin) gave results that were comparable to those obtained with rifampin. Clofazimine did not show synergistic killing activity at a concentration that is achievable in serum for any of the drugs tested. Our results indicate that there is considerable variability in the antimicrobial susceptibility of M. avium isolates obtained from patients with acquired immune deficiency syndrome. This variability could have significant impact on the clinical response to various therapies. PMID:3196000

  1. 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.

  2. 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.

  3. Cystatins in immune system.

    PubMed

    Magister, Spela; 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.

  4. 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

  5. Norovirus Infection and Acquired Immunity in 8 Countries: Results From the MAL-ED Study

    PubMed Central

    Rouhani, Saba; Peñataro Yori, Pablo; Paredes Olortegui, Maribel; Siguas Salas, Mery; Rengifo Trigoso, Dixner; Mondal, Dinesh; Bodhidatta, Ladaporn; Platts-Mills, James; Samie, Amidou; Kabir, Furqan; Lima, Aldo; Babji, Sudhir; Mason, Carl J.; Kalam, Adil; Bessong, Pascal; Ahmed, Tahmeed; Mduma, Estomih; Bhutta, Zulfiqar A.; Lima, Ila; Ramdass, Rakhi; Lang, Dennis; George, Ajila; Zaidi, Anita K. M.; Kang, Gagandeep; Houpt, Eric; Kosek, Margaret N.

    2016-01-01

    Background. Norovirus is an important cause of childhood diarrhea. We present data from a longitudinal, multicountry study describing norovirus epidemiology during the first 2 years of life. Methods. A birth cohort of 1457 children across 8 countries contributed 7077 diarrheal stools for norovirus testing. A subset of 199 children contributed additional asymptomatic samples (2307) and diarrheal stools (770), which were used to derive incidence rates and evaluate evidence for acquired immunity. Results. Across sites, 89% of children experienced at least 1 norovirus infection before 24 months, and 22.7% of all diarrheal stools were norovirus positive. Severity of norovirus-positive diarrhea was comparable to other enteropathogens, with the exception of rotavirus. Incidence of genogroup II (GII) infection was higher than genogroup I and peaked at 6–11 months across sites. Undernutrition was a risk factor for symptomatic norovirus infection, with an increase in 1 standard deviation of length-for-age z score associated with a 17% reduction (odds ratio, 0.83 [95% confidence interval, .72–.97]; P = .011) in the odds of experiencing diarrhea when norovirus was present, after accounting for genogroup, rotavirus vaccine, and age. Evidence of acquired immunity was observed among GII infections only: Children with prior GII infection were found to have a 27% reduction in the hazard of subsequent infection (hazard ratio, 0.727; P = .010). Conclusions. The high prevalence of norovirus across 8 sites in highly variable epidemiologic settings and demonstration of protective immunity for GII infections provide support for investment in vaccine development. PMID:27013692

  6. Outer Surface Protein A Protects Lyme Disease Spirochetes from Acquired Host Immunity in the Tick Vector▿

    PubMed Central

    Battisti, James M.; Bono, James L.; Rosa, Patricia A.; Schrumpf, Merry E.; Schwan, Tom G.; Policastro, Paul F.

    2008-01-01

    The Lyme disease spirochete Borrelia burgdorferi alters the expression of outer surface protein (osp) genes as the bacterium cycles between ticks and mammals. OspA is produced as borreliae enter the tick vector and remains a major surface antigen during midgut colonization. To elucidate the role of OspA in the vector, we created an insertional deletion of ospA in strain B31-A3. The ospA mutant infects mice when it is injected intradermally and is acquired by larval ticks fed on these mice, where it persists through the molt to the nymph stage. Bacterial survival rates in artificially infected tick larvae fed on naïve mice were compared with those in the vector fed on immune mice. The ospA mutant proliferates in larvae if it is exposed to blood from naïve mice, but it declines in density after larval feeding if the blood is from immune mice. When uninfected larvae are fed on B-cell-deficient mice infected with the ospA mutant, larvae show borrelial densities and persistence that are significantly greater than those fed on infected, immunocompetent mice. We conclude that OspA serves a critical antibody-shielding role during vector blood meal uptake from immune hosts and is not required for persistence in the tick vector. PMID:18779341

  7. 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.

  8. 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.

  9. TOR in the immune system.

    PubMed

    Araki, Koichi; Ellebedy, Ali H; Ahmed, Rafi

    2011-12-01

    The target of rapamycin (TOR) is a crucial intracellular regulator of the immune system. Recent studies have suggested that immunosuppression by TOR inhibition may be mediated by modulating differentiation of both effector and regulatory CD4 T cell subsets. However, it was paradoxically shown that inhibiting TOR signaling has immunostimulatory effects on the generation of long-lived memory CD8 T cells. Beneficial effects of TOR inhibition have also been observed with dendritic cells and hematopoietic stem cells. This immune modulation may contribute to lifespan extension seen in mice with mTOR inhibition. Here, we review recent findings on TOR modulation of innate and adaptive immune responses, and discuss potential applications of regulating TOR to provide longer and healthier immunity.

  10. Recent advances in systemic acquired resistance research--a review.

    PubMed

    Hunt, M D; Neuenschwander, U H; Delaney, T P; Weymann, K B; Friedrich, L B; Lawton, K A; Steiner, H Y; Ryals, J A

    1996-11-01

    Little is known about the signal transduction events that lead to the establishment of the broad-spectrum, inducible plant immunity called systemic acquired resistance (SAR). Salicylic acid (SA) accumulation has been shown to be essential for the expression of SAR and plays a key role in SAR signaling. Hydrogen peroxide has been proposed to serve as a second messenger of SA. However, our results do not support such a role in the establishment of SAR. Further elucidation of SAR signal transduction has been facilitated by the identification and characterization of mutants. The lesions simulating disease (lsd). resistance response mutant class exhibits spontaneous lesions similar to those that occur during the hypersensitive response. Interestingly, some lsd mutants lose their lesioned phenotype when SA accumulation is prevented by expression of the nahG gene (encoding salicylate hydroxylase), thereby providing evidence for a feedback loop in SAR signal transduction. Characterization of a mutant non-responsive to SAR activator treatments has provided additional evidence for common signaling components between SAR and gene-for-gene resistance.

  11. Social capital of Iranian patients living with acquired immune deficiency syndrome and associated factors.

    PubMed

    Ansari, S K; Nedjat, S; Jabbari, H; Saiepour, N; Heris, M J

    2015-12-13

    This study investigated the social capital of Iranian patients living with acquired immune deficiency syndrome (AIDS) and the associated factors. In a cross-sectional study the Integrated Social Capital Questionnaire was filled by a sequential sample of 300 patients visiting a referral counselling centre in Tehran. The patients' social capital scores were around 50% in the trust, social cohesion, collective action and cooperation and political empowerment domains. The groups and networks membership domain scored the lowest (27.1%). In regression analysis, employment status was significantly associated with groups and networks membership; age, marital status and financial status were associated with collective action and cooperation; period of disease awareness and marital status affected social cohesion and inclusion; and having risky behaviour affected empowerment and political action. Efforts are needed to enhance the social capital of those patients living with AIDS who are younger, unemployed, divorced/widowed, with risky behaviours and shorter disease awareness.

  12. In vivo treatment with interleukin 12 protects mice from immune abnormalities observed during murine acquired immunodeficiency syndrome (MAIDS)

    PubMed Central

    1994-01-01

    Lymphoproliferation, chronic B cell activation resulting in hypergammaglobulinemia, and profound immunodeficiency are prominent features of a retrovirus-induced syndrome designated murine acquired immunodeficiency syndrome (MAIDS). In vivo treatment of infected mice with recombinant interleukin 12 (IL-12) beginning at the time of infection or up to 9 wk after virus inoculation markedly inhibited the development of splenomegaly and lymphadenopathy, as well as B cell activation and Ig secretion. Treatment with IL-12 also had major effects in preventing induction of several immune defects including impaired production of interferon gamma (IFN-gamma) and IL-2 and depressed proliferative responses to various stimuli. The therapeutic effects of IL-12 on the immune system of mice with MAIDS were also associated with reduced expression of the retrovirus that causes this disease (BM5def), with lesser effects on expression of ecotropic MuLV. IL-12 treatment was not effective in IFN-gamma knockout mice or in infected mice treated simultaneously with IL-12 and anti-IFN-gamma. These results demonstrate that induction and progression of MAIDS are antagonized by IL-12 through high-level expression of IFN-gamma and may provide an experimental basis for developing treatments of retrovirus- induced immune disorders with similar immunopathogenic mechanisms. PMID:7964495

  13. 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…

  14. 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

  15. Herd immunity acquired indirectly from interactions between the ecology of infectious diseases, demography and economics.

    PubMed

    Bonds, Matthew H; Rohani, Pejman

    2010-03-01

    Patterns of morbidity and mortality around the globe are determined by interactions between infectious diseases and systematic human socioeconomic processes. The most obvious of these patterns is that the greatest burdens of infectious diseases are found among the poor, who lack the basic resources for disease prevention and treatment. Yet, it is becoming increasingly clear that many infectious diseases are themselves causes of poverty owing to their effects on labour productivity. A particularly subtle phenomenon that receives little attention in the epidemiology literature and is especially important for poor communities is the role of the birth rate as an important direct cause of high disease burdens. Because of their high rates of transmission and life-long immunity, the persistence of many child diseases such as measles relies on high rates of reproduction as their source of susceptible individuals. Thus, there are significant direct health benefits of lower fertility rates, which are further enhanced by interactions with economic processes. Indeed, fertility, poverty and disease all interact with each other in important and predictable ways that can be built into traditional disease ecology models. We present such a model here that provides insights into the long-term effect of policy interventions. For example, because of indirect income effects, herd immunity may be acquired with lower vaccine coverage than previously thought. Reductions in the disease burden can also occur through lower fertility. Our model thus provides a disease ecology framework that is useful for the analysis of demographic transitions.

  16. Effectiveness and safety of traditional Chinese medicine in treating acquired immune deficiency syndrome: 2004-2014.

    PubMed

    Liu, Zhi-Bin; Yang, Ji-Ping; Xu, Li-Ran

    2015-12-23

    Substantial progress has been made in China in using traditional Chinese medicine (TCM) to treat acquired immune deficiency syndrome (AIDS). Our objective was to review the latest developments in TCM treatment of AIDS in China between 2004 and 2014. We reviewed the content of original articles investigating the efficacy and safety of TCM for treating AIDS published in Chinese and English language journals. Relevant references from 2004 to 2014 were found using PubMed and the China National Knowledge Infrastructure Database. We found that TCM has been widely used for treating AIDS and its complications in China. The number of TCM studies has increased, which indicates efficacy and safety. Measures of efficacy in the reviewed articles included the alleviation of human immunodeficiency virus (HIV)-related signs and symptoms, improvements in quality of life, improvements in long-term survival, counteraction of the adverse side effects of antiviral drugs, promotion of immune reconstitution, and improvement of laboratory results. In sum, the literature indicates that TCM is safe. TCM plays an important role in the treatment of AIDS. Some studies have attempted to measure the efficacy and safety of TCM for treating AIDS, but more evidence is needed. Therefore, more research on this topic is required in the future.

  17. Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

    SciTech Connect

    Aitken, R.; Coulson, P.S.; Dixon, B.; Wilson, R.A.

    1987-11-01

    Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni.

  18. Optimal vaccination and bednet maintenance for the control of malaria in a region with naturally acquired immunity.

    PubMed

    Prosper, Olivia; Ruktanonchai, Nick; Martcheva, Maia

    2014-07-21

    Following over two decades of research, the malaria vaccine candidate RTS,S has reached the final stages of vaccine trials, demonstrating an efficacy of roughly 50% in young children. Regions with high malaria prevalence tend to have high levels of naturally acquired immunity (NAI) to severe malaria; NAI is caused by repeated exposure to infectious bites and results in large asymptomatic populations. To address concerns about how these vaccines will perform in regions with existing NAI, we developed a simple malaria model incorporating vaccination and NAI. Typically, if the basic reproduction number (R0) for malaria is greater than unity, the disease will persist; otherwise, the disease will become extinct. However, analysis of this model revealed that NAI, compounded by a subpopulation with only partial protection to malaria, may render vaccination efforts ineffective and potentially detrimental to malaria control, by increasing R0 and increasing the likelihood of malaria persistence even when R0<1. The likelihood of this scenario increases when non-immune infected individuals are treated disproportionately compared with partially immune individuals - a plausible scenario since partially immune individuals are more likely to be asymptomatically infected. Consequently, we argue that active case-detection of asymptomatic infections is a critical component of an effective malaria control program. We then investigated optimal vaccination and bednet control programs under two endemic settings with varying levels of naturally acquired immunity: a typical setting under which prevalence decays when R0<1, and a setting in which subthreshold endemic equilibria exist. A qualitative comparison of the optimal control results under the first setting revealed that the optimal policy differs depending on whether the goal is to reduce total morbidity, or to reduce clinical infections. Furthermore, this comparison dictates that control programs should place less effort in

  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. Making sense of scoring systems in community acquired pneumonia.

    PubMed

    Niederman, Michael S

    2009-04-01

    The site of care decision is one of the most important in the management of patients with community-acquired pneumonia (CAP). Several scoring systems have been developed to predict mortality risk in CAP, and these have been applied to guide physicians about whether patients should be admitted to the hospital or to the intensive care unit (ICU). However, these tools were initially developed to predict mortality risk, and studies have demonstrated that the risk for death does not always equate with need for hospitalization or ICU care. The most widely studied scoring systems are the Pneumonia Severity Index (PSI) and the CURB-65 (a modification of the British Thoracic Society rule). Each has advantages and limitations, with the more-complex PSI developed to identify low-mortality risk patients, and the CURB-65, which is simpler, being developed to easily identify more severely ill individuals. No scoring system can replace clinical judgement about the admission decision, and prospective studies have shown that physicians still admit at least 30-60% of low mortality risk patients when using the PSI to guide this decision. Limitations of these prognostic tools include their variable utility in the elderly, and their failure to include certain comorbidities (COPD, immune suppression) and social factors, in their calculations. The need for ICU care is also not well-defined by measuring the PSI or CURB-65, and other tools such as those developed by the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) guideline committee and the SMART-COP rule may have greater utility for this purpose. In the future, measurements of serum biomarkers, such as procalcitonin, may augment the information provided by prognostic scoring tools for patients with CAP.

  1. It's the immune system, stupid.

    PubMed

    1999-01-01

    A presentation by Dr. Franco Lori at the 6th CROI suggested that early implementation of HAART and strategic treatment interruptions may control HIV by bolstering the immune system. The case study of the "Berlin patient" inspired clinical tests of this theory. Another researcher, Bruce Walker, noted that HAART therapy administered within three months after the onset of HIV can preserve a dynamic immune response. Unfortunately, interrupting HAART can result in surges of HIV levels and an increased risk of developing resistant strains of HIV, regardless of when HAART is begun. The concept behind intermittent breaks in HAART is that the immune system needs to be exposed to small amounts of HIV to continue building a response. Other means of stimulating CD4 cell activity are discussed.

  2. Neurotrophins and the immune system

    PubMed Central

    Vega, José A; García-Suárez, Olivia; Hannestad, Jonas; Pérez-Pérez, Marta; Germanà, Antonino

    2003-01-01

    The neurotrophins are a family of polypeptide growth factors that are essential for the development and maintenance of the vertebrate nervous system. In recent years, data have emerged indicating that neurotrophins could have a broader role than their name might suggest. In particular, the putative role of NGF and its receptor TrkA in immune system homeostasis has become a much studied topic, whereas information on the other neurotrophins is scarce in this regard. This paper reviews what is known about the expression and possible functions of neurotrophins and their receptors in different immune tissues and cells, as well as recent data obtained from studies of transgenic mice in our laboratory. Results from studies to date support the idea that neurotrophins may regulate some immune functions. They also play an important role in the development of the thymus and in the survival of thymocytes. PMID:12892403

  3. Acquired enophthalmos with systemic lupus erythematosus.

    PubMed

    Park, K R; Seo, M R; Ryu, H J; Chi, M J; Baek, H J; Choi, H J

    2016-01-01

    Ocular involvement sometimes occurs with systemic lupus erythematosus (SLE) but enophthalmos with SLE is rare. We report a case of enophthalmos with SLE. A 25-year-old male was admitted for two weeks of fever, sore throat, arthralgia, chest pain and right arm weakness with pain. We diagnosed him with SLE with malar rash, arthritis, pleural effusion, proteinuria, leukopenia, positive antinuclear antibody, anti-dsDNA, and lupus anticoagulant. The patient was prescribed high-dose prednisolone and hydroxychloroquine 400 mg. One week after discharge, he complained about a sensation of a sunken right eye. CT showed right enophthalmos, a post-inflammatory change and chronic inflammation. Proteinuria increased to 3.8 g/day after the patient stopped taking prednisolone. Cyclophosphamide therapy was administered for three months without improvement. We decided to restart prednisolone and change cyclophosphamide to mycophenolate mofetil. Proteinuria decreased but enophthalmos remains as of this reporting.

  4. 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

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

    PubMed

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

    2013-09-01

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

  6. 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

  7. Bone and the immune system.

    PubMed

    Gruber, H E

    1991-07-01

    There are several lines of evidence which provide support for an important relationship between immune cells and bone. Clinical studies of immunodeficiency syndromes have shown that abnormalities in bone shape are evident on x-rays, and peculiarities in the structure of the growth plate have been identified by histopathology. Studies of bone histology, and quantitation of cellular abnormalities, are scarce. Abnormalities in bone turnover, have, however, been identified in the nude mouse model. Many lines of evidence derived from in vitro bone studies have shown that lymphokines and monokines can influence bone formation and bone resorption. Some clinical studies of postmenopausal osteoporosis have indicated the possible presence of immune cell changes in this condition. Although several hypotheses have been formed regarding the exact mechanisms of the effect of immune cytokine on bone, this is clearly a very large area of study and there is a need for additional carefully controlled experiments with special emphasis on bone cells and bone matrix, especially in the human. As knowledge progresses regarding immunology and hematology, a clearer understanding of the lineages of the osteoblast and osteoclast will emerge and we will better understand how specialized bone cells interact with and react to their immune cell neighbors in the bone marrow and to immune system signals. These findings will have especially important implications for the local bone loss seen in rheumatoid arthritis, periodontal disease, and chronic osteomyelitis. PMID:2068116

  8. Systems biology of innate immunity

    PubMed Central

    Zak, Daniel E.; Aderem, Alan

    2009-01-01

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

  9. 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.

  10. Vaccination and heterologous immunity: educating the immune system

    PubMed Central

    Gil, Anna; Kenney, Laurie L.; Mishra, Rabinarayan; Watkin, Levi B.; Aslan, Nuray; Selin, Liisa K.

    2015-01-01

    This review discusses three inter-related topics: (1) the immaturity of the neonatal and infant immune response; (2) heterologous immunity, where prior infection history with unrelated pathogens alters disease outcome resulting in either enhanced protective immunity or increased immunopathology to new infections, and (3) epidemiological human vaccine studies that demonstrate vaccines can have beneficial or detrimental effects on subsequent unrelated infections. The results from the epidemiological and heterologous immunity studies suggest that the immune system has tremendous plasticity and that each new infection or vaccine that an individual is exposed to during a lifetime will potentially alter the dynamics of their immune system. It also suggests that each new infection or vaccine that an infant receives is not only perturbing the immune system but is educating the immune system and laying down the foundation for all subsequent responses. This leads to the question, is there an optimum way to educate the immune system? Should this be taken into consideration in our vaccination protocols? PMID:25573110

  11. [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. PMID:18592962

  12. Changes in cytokine production associated with acquired immunity to Plasmodium falciparum malaria

    PubMed Central

    Rhee, M S M; Akanmori, B D; Waterfall, M; Riley, E M

    2001-01-01

    Individuals living in malaria-endemic areas eventually develop clinical immunity to Plasmodium falciparum. That is, they are able to limit blood parasite densities to extremely low levels and fail to show symptoms of infection. As the clinical symptoms of malaria infection are mediated in part by pro-inflammatory cytokines it is not clear whether the acquisition of clinical immunity is due simply to the development of antiparasitic mechanisms or whether the ability to regulate inflammatory cytokine production is also involved. We hypothesize that there is a correlation between risk of developing clinical malaria and the tendency to produce high levels of proinflammatory cytokines in response to malaria infection. In order to test this hypothesis, we have compared the ability of peripheral blood mononuclear cells from malaria-naive and malaria-exposed adult donors to proliferate and to secrete IFN-γ in response to P. falciparum schizont extract (PfSE). In order to determine how PfSE-induced IFN-γ production is regulated, we have also measured production of IL-12p40 and IL-10 from PfSE-stimulated PBMC and investigated the role of neutralizing antibody to IL-12 in modulating IFN-γ production. We find that cells from naive donors produce moderate amounts of IFN-γ in response to PfSE and that IFN-γ production is strongly IL-12 dependent. Cells from malaria-exposed donors living in an area of low malaria endemicity produce much higher levels of IFN-γ and this response is also at least partially IL-12 dependent. In complete contrast, cells from donors living in an area of very high endemicity produce minimal amounts of IFN-γ. No significant differences were detected between the groups in IL-10 production, suggesting that this cytokine does not play a major role in regulating malaria-induced IFN-γ production. The data from this study thus strongly support the hypothesis that down-regulation of inflammatory cytokine production may be a component of acquired clinical

  13. Predictive factors for the Nursing Diagnoses in people living with Acquired Immune Deficiency Syndrome 1

    PubMed Central

    da Silva, Richardson Augusto Rosendo; Costa, Romanniny Hévillyn Silva; Nelson, Ana Raquel Cortês; Duarte, Fernando Hiago da Silva; Prado, Nanete Caroline da Costa; Rodrigues, Eduardo Henrique Fagundes

    2016-01-01

    Abstract Objective: to identify the predictive factors for the nursing diagnoses in people living with Acquired Immune Deficiency Syndrome. Method: a cross-sectional study, undertaken with 113 people living with AIDS. The data were collected using an interview script and physical examination. Logistic regression was used for the data analysis, considering a level of significance of 10%. Results: the predictive factors identified were: for the nursing diagnosis of knowledge deficit-inadequate following of instructions and verbalization of the problem; for the nursing diagnosis of failure to adhere - years of study, behavior indicative of failure to adhere, participation in the treatment and forgetfulness; for the nursing diagnosis of sexual dysfunction - family income, reduced frequency of sexual practice, perceived deficit in sexual desire, perceived limitations imposed by the disease and altered body function. Conclusion: the predictive factors for these nursing diagnoses involved sociodemographic and clinical characteristics, defining characteristics, and related factors, which must be taken into consideration during the assistance provided by the nurse. PMID:27384466

  14. Schistosomiasis Coinfection in Children Influences Acquired Immune Response against Plasmodium falciparum Malaria Antigens

    PubMed Central

    Gaayeb, Lobna; Schacht, Anne-Marie; Charrier, Nicole; De Clerck, Dick; Dompnier, Jean-Pierre; Pillet, Sophie; Garraud, Olivier; N'Diaye, Abdoulaye A.; Riveau, Gilles

    2010-01-01

    Background Malaria and schistosomiasis coinfection frequently occurs in tropical countries. This study evaluates the influence of Schistosoma haematobium infection on specific antibody responses and cytokine production to recombinant merozoite surface protein-1-19 (MSP1-19) and schizont extract of Plasmodium falciparum in malaria-infected children. Methodology Specific IgG1 to MSP1-19, as well as IgG1 and IgG3 to schizont extract were significantly increased in coinfected children compared to P. falciparum mono-infected children. Stimulation with MSP1-19 lead to a specific production of both interleukin-10 (IL-10) and interferon-γ (IFN-γ), whereas the stimulation with schizont extract produced an IL-10 response only in the coinfected group. Conclusions Our study suggests that schistosomiasis coinfection favours anti-malarial protective antibody responses, which could be associated with the regulation of IL-10 and IFN-γ production and seems to be antigen-dependent. This study demonstrates the importance of infectious status of the population in the evaluation of acquired immunity against malaria and highlights the consequences of a multiple infection environment during clinical trials of anti-malaria vaccine candidates. PMID:20856680

  15. The role of spatial population structure on the evolution of parasites with acquired immunity and demography.

    PubMed

    Webb, Steven D; Keeling, Matt J; Boots, Mike

    2013-05-01

    It is clear that the evolution of infectious disease may be influenced by population spatial structure and transmission networks but we lack an understanding of the role of acquired immunity. Here we examine theoretically the role of spatial structure in the evolution of infectious disease described by the classic Susceptible, Infected, Recovered (SIR) model focusing on the impact of host demographics. We find that, for the classic assumption of a trade-off between transmission and virulence, localised transmission does favor, as predicted from other models, chronic pathogens with low transmission and virulence, but that this effect reduces as the recovery rate increases. However, under the assumption that pathogens reproduce rapidly within the host are harder to clear but result in higher virulence local interactions favor more virulent parasites and, depending on the nature of the disease interaction, can increase or decrease the chance of evolutionary bistabilities that may lead to sudden persistent changes in virulence. Therefore, our work further emphasizes the importance of spatial structure to parasite evolution. This spatial evolutionary theory is important because it predicts how different pathogens may respond to changes in patterns of mixing.

  16. The keys of oxidative stress in acquired immune deficiency syndrome apoptosis.

    PubMed

    Romero-Alvira, D; Roche, E

    1998-08-01

    Apoptosis is the main cause of CD4+ T-lymphocyte depletion in acquired immune deficiency syndrome (AIDS). Various agents appear to be able to trigger apoptosis in CD4+ T cells, including viral proteins (i.e. gp120, Tat), inappropriate secretion of inflammatory cytokines by activated macrophages (i.e. tumor necrosis factor alpha) and toxins produced by opportunistic micro-organisms. Since oxidative stress can also induce apoptosis, it can be hypothesized that such a mechanism could participate in CD4+ T-cell apoptosis observed in AIDS. This correlates strongly with the observation that AIDS patients present low levels of antioxidants (i.e. superoxide dismutase-Mn, vitamin E, selenium and glutathion) most likely due to inappropriate nutrition (i.e. diets poor in antioxidants), alcohol and drug consumption, and digestive problems associated with the disease. Furthermore, the coadministration of the antiviral drug zidovudine with antioxidants increases its therapeutic potential. Finally, the following additional observations support the hypothesis that oxidative stress is involved in cell apoptosis in AIDS: (1) The depletion of the anti-apoptotic/antioxidant protein Bcl-2 in human immunodeficiency virus (HIV)-infected CD4+ cells; (2) a decrease of apoptosis in HIV-infected cells treated with antioxidants and; (3) the presence of the pro-apoptotic/pro-oxidant cytokines secreted by activated macrophages in AIDS patients. Therefore, anti-apoptotic/antioxidant strategies should be considered, alongside antiviral strategies, in order to design a more efficient therapy for AIDS in the near future.

  17. Coping Strategies of Patients with Haemophilia as a Risk Group for AIDS (Acquired Immune Deficiency Syndrome). Brief Research Report.

    ERIC Educational Resources Information Center

    Naji, Simon; And Others

    1986-01-01

    Plans are described for a 2-year project whose major focus is the identification of ways in which patients with hemophilia and their families assimilate, interpret, and act on information about Acquired Immune Deficiency Syndrome (AIDS). Findings will be related to perceived risk, anxiety levels, and the development of coping strategies.…

  18. AIDS: Acquired Immune Deficiency Syndrome; Information and Procedural Guidelines for Providing Services to Persons with AIDS/HIV. Revised.

    ERIC Educational Resources Information Center

    Montana State Dept. of Health and Environmental Sciences, Helena. Health Education Bureau.

    This volume consists of updated information to be inserted into a Montana AIDS Project manual on providing services to persons with acquired immune deficiency syndrome/human immunodeficiency virus (AIDS/HIV), originally published in December 1985. The updates are mainly statistics and terminology, along with the addition of several new sections.…

  19. AIDS: Acquired Immune Deficiency Syndrome, Information and Procedural Guidelines for Providing Services to Persons with AIDS/HTLV-III.

    ERIC Educational Resources Information Center

    Montana State Dept. of Health and Environmental Sciences, Helena.

    This manual presents information about the disease, Acquired Immune Deficiency Syndrome (AIDS), and guidelines for service delivery to Montana residents who have been diagnosed with AIDS or related disorders. The first section describes the disease's causes, symptoms, and transmission; risk factors; high-risk populations; prevention suggestions;…

  20. Select Personality Characteristic Differences between Caregivers for Persons with Acquired Immune Deficiency Syndrome and Caregivers for Other Types of Illness.

    ERIC Educational Resources Information Center

    Angel, Daniel Scott; Heritage, Jeannette

    The purpose of this study was to analyze select personality characteristics of individuals working within the Acquired Immune Deficiency Syndrome (AIDS) population in comparison to non-AIDS caregivers by using two personality assessment instruments. Subjects were from two health care provider populations. Two hundred research packets were…

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

    ERIC Educational Resources Information Center

    Christensen, Damaris

    1999-01-01

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

  2. Synthetic immunology: modulating the human immune system.

    PubMed

    Geering, Barbara; Fussenegger, Martin

    2015-02-01

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

  3. Oscillations in the immune system.

    PubMed

    Stark, Jaroslav; Chan, Cliburn; George, Andrew J T

    2007-04-01

    Oscillations are surprisingly common in the immune system, both in its healthy state and in disease. The most famous example is that of periodic fevers caused by the malaria parasite. A number of hereditary disorders, which also cause periodic fevers, have also been known for a long time. Various reports of oscillations in cytokine concentrations following antigen challenge have been published over at least the past three decades. Oscillations can also occur at the intracellular level. Calcium oscillations following T-cell activation are familiar to all immunologists, and metabolic and reactive oxygen species oscillations in neutrophils have been well documented. More recently, oscillations in nuclear factor kappaB activity following stimulation by tumor necrosis factor alpha have received considerable publicity. However, despite all of these examples, oscillations in the immune system still tend to be considered mainly as pathological aberrations, and their causes and significance remained largely unknown. This is partly because of a lack of awareness within the immunological community of the appropriate theoretical frameworks for describing and analyzing such behavior. We provide an introduction to these frameworks and give a survey of the currently known oscillations that occur within the immune system. PMID:17367345

  4. Passive transfer of naturally acquired specific immunity against West Nile Virus to foals in a semi-feral pony herd.

    PubMed

    Wilkins, Pamela A; Glaser, Amy L; McDonnell, Sue M

    2006-01-01

    Horses naturally exposed to West Nile Virus (WNV) or vaccinated against WNV develop humoral immunity thought to be protective against development of clinical disease in exposed or infected animals. No reports evaluate the efficacy of passive transfer of naturally acquired specific WNV humoral immunity from dam to foal. The purpose of this study was to investigate passive transfer of naturally acquired immunity to WNV to foals born in a herd of semi-feral ponies, not vaccinated against WNV, in an endemic area, with many dams having seroconverted because of natural exposure. Microwell serum neutralization titers against WNV were determined in all mares and foals. Serum IgG concentration was determined in foals by serial radial immunodiffusion. Differences in IgG concentration between seropositive and seronegative foals were examined by means of the Mann-Whitney U-test. Linear regression was used to evaluate the association between mare and foal titers. Seventeen mare-foal pairs were studied; 1 foal had inadequate IgG concentration. IgG concentration was not different between seronegative and seropositive foals (P = .24). Mare and foal titers were significantly correlated in foals with adequate passive transfer of immunity (Spearman's rho = .84; P < .001); >90% of the foal's titer was explained by the mare's titer (R2 = 0.91; P < .001). Passive transfer of specific immunity to WNV is present in pony foals with adequate passive transfer of immunity born to seroconverted mares.

  5. Immune System Toxicity and Immunotoxicity Hazard Identification

    EPA Science Inventory

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

  6. Association between total immunoglobulin E and antibody responses to naturally acquired Ascaris lumbricoides infection and polymorphisms of immune system-related LIG4, TNFSF13B and IRS2 genes.

    PubMed

    Acevedo, N; Mercado, D; Vergara, C; Sánchez, J; Kennedy, M W; Jiménez, S; Fernández, A M; Gutiérrez, M; Puerta, L; Caraballo, L

    2009-08-01

    The 13q33-34 region harbours a susceptibility locus to Ascaris lumbricoides, although the underlying genes are unknown. Immunoglobulin (Ig)E and IgG confer protective immunity and here we sought to investigate in an endemic population whether LIG4, TNFSF13B and IRS2 genes influence IgE and IgG levels against Ascaris and the ABA-1 allergen as a putative resistance marker. Mite-allergic asthmatic patients were analysed for potential relationships between Ascaris predisposition and allergy. One thousand and sixty-four subjects from Cartagena, Colombia, were included. Single nucleotide polymorphisms (SNPs) were genotyped using TaqMan assays. Antibody levels were measured by enzyme-linked immunosorbent assay. Linear and logistic regressions were used to model effects of genotypes on antibody levels. The GG genotype of LIG4 (rs1805388) was associated with higher IgE levels to Ascaris compared with other genotypes. TNFSF13B (rs10508198) was associated positively with IgG levels against Ascaris extract and IgE levels against ABA-1. In asthmatics, IRS2 (rs2289046) was associated with high total IgE levels. Associations held up after correction by population stratification using a set of 52 ancestry markers, age, sex and disease status. There was no association with asthma or mite sensitization. In a tropical population, LIG4 and TNFSF13B polymorphisms are associated with specific IgE and IgG to Ascaris, supporting previous linkage studies implicating the 13q33 region. Our results suggest that genes protecting against parasite infections can be different to those predisposing to asthma and atopy.

  7. Association between total immunoglobulin E and antibody responses to naturally acquired Ascaris lumbricoides infection and polymorphisms of immune system-related LIG4, TNFSF13B and IRS2 genes

    PubMed Central

    Acevedo, N; Mercado, D; Vergara, C; Sánchez, J; Kennedy, M W; Jiménez, S; Fernández, A M; Gutiérrez, M; Puerta, L; Caraballo, L

    2009-01-01

    The 13q33–34 region harbours a susceptibility locus to Ascaris lumbricoides, although the underlying genes are unknown. Immunoglobulin (Ig)E and IgG confer protective immunity and here we sought to investigate in an endemic population whether LIG4, TNFSF13B and IRS2 genes influence IgE and IgG levels against Ascaris and the ABA-1 allergen as a putative resistance marker. Mite-allergic asthmatic patients were analysed for potential relationships between Ascaris predisposition and allergy. One thousand and sixty-four subjects from Cartagena, Colombia, were included. Single nucleotide polymorphisms (SNPs) were genotyped using TaqMan assays. Antibody levels were measured by enzyme-linked immunosorbent assay. Linear and logistic regressions were used to model effects of genotypes on antibody levels. The GG genotype of LIG4 (rs1805388) was associated with higher IgE levels to Ascaris compared with other genotypes. TNFSF13B (rs10508198) was associated positively with IgG levels against Ascaris extract and IgE levels against ABA-1. In asthmatics, IRS2 (rs2289046) was associated with high total IgE levels. Associations held up after correction by population stratification using a set of 52 ancestry markers, age, sex and disease status. There was no association with asthma or mite sensitization. In a tropical population, LIG4 and TNFSF13B polymorphisms are associated with specific IgE and IgG to Ascaris, supporting previous linkage studies implicating the 13q33 region. Our results suggest that genes protecting against parasite infections can be different to those predisposing to asthma and atopy. PMID:19604268

  8. Physicians' obligations to patients infected with Ebola: echoes of acquired immune deficiency syndrome.

    PubMed

    Minkoff, Howard; Ecker, Jeffrey

    2015-04-01

    Physicians across the United States are engaged in training in the identification, isolation, and initial care of patients with Ebola. Some will be asked to do more. The issue this viewpoint will address is the moral obligation of physicians to participate in these activities. In order to do so the implicit contract between society and its physicians will be considered, as will many of the arguments that are redolent of those that were litigated 30 years ago when acquired immune deficiency syndrome (AIDS) was raising public fears to similar levels, and some physicians were publically proclaiming their unwillingness to render care to those individuals. We will build the case that if steps are taken to reduce risks-optimal personal protective equipment and training-to what is essentially the lowest possible level then rendering care should be seen as obligatory. If not, as in the AIDS era there will be an unfair distribution of risk, with those who take their obligations seriously having to go beyond their fair measure of exposure. It would also potentially undermine patients' faith in the altruism of physicians and thereby degrade the esteem in which our profession is held and the trust that underpins the therapeutic relationship. Finally there is an implicit contract with society. Society gives tremendously to us; we encumber a debt from all society does and offers, a debt for which recompense is rarely sought. The mosaic of moral, historical, and professional imperatives to render care to the infected all echoes the words of medicine's moral leaders in the AIDS epidemic. Arnold Relman perhaps put it most succinctly, "the risk of contracting the patient's disease is one of the risks that is inherent in the profession of medicine. Physicians who are not willing to accept that risk…ought not be in the practice of medicine." PMID:25530596

  9. Innate versus acquired immune response in the pathogenesis of recurrent idiopathic pericarditis.

    PubMed

    Cantarini, Luca; Luca, Cantarini; Imazio, Massimo; Massimo, Imazio; Brucato, Antonio; Antonio, Brucato; Lucherini, Orso Maria; Maria, Lucherini Orso; Galeazzi, Mauro; Mauro, Galeazzi

    2010-04-01

    The pathogenesis of recurrent pericarditis is still poorly understood and may be related either to viral infections or autoimmune and autoinflammatory disorders. The immune system plays a major role in the pathogenesis of the disease, modulating individual responses to different noxa and explaining the variable reported recurrence rate (ranging from 20% to 50% of patients) following an attack of acute or recurrent pericarditis. Increasing interest is currently being devoted to autoinflammatory disorders, a group of conditions characterized by spontaneously relapsing and remitting bouts of systemic inflammation without apparent involvement of antigen-specific T cells or significant production of auto-antibodies. Ongoing basic and clinical research is needed to provide further evidence for the understanding of this common and troublesome disease, and to develop targeted and more efficacious therapies.

  10. Powering the Immune System: Mitochondria in Immune Function and Deficiency

    PubMed Central

    Walker, Melissa A.; Sims, Katherine B.; Walter, Jolan E.; Traggiai, Elisabetta

    2014-01-01

    Mitochondria are critical subcellular organelles that are required for several metabolic processes, including oxidative phosphorylation, as well as signaling and tissue-specific processes. Current understanding of the role of mitochondria in both the innate and adaptive immune systems is expanding. Concurrently, immunodeficiencies arising from perturbation of mitochondrial elements are increasingly recognized. Recent observations of immune dysfunction and increased incidence of infection in patients with primary mitochondrial disorders further support an important role for mitochondria in the proper function of the immune system. Here we review current findings. PMID:25309931

  11. Powering the immune system: mitochondria in immune function and deficiency.

    PubMed

    Walker, Melissa A; Volpi, Stefano; Sims, Katherine B; Walter, Jolan E; Traggiai, Elisabetta

    2014-01-01

    Mitochondria are critical subcellular organelles that are required for several metabolic processes, including oxidative phosphorylation, as well as signaling and tissue-specific processes. Current understanding of the role of mitochondria in both the innate and adaptive immune systems is expanding. Concurrently, immunodeficiencies arising from perturbation of mitochondrial elements are increasingly recognized. Recent observations of immune dysfunction and increased incidence of infection in patients with primary mitochondrial disorders further support an important role for mitochondria in the proper function of the immune system. Here we review current findings.

  12. 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.

  13. [Resistance to Naegleria fowleri infection passively acquired from immunized splenocyte, serum or milk].

    PubMed

    Ahn, M H; Min, D Y

    1989-06-01

    A pathogenic free-living amoeba, Naegleria fowleri, causes primary amoebic meningoencephalitis to human and experimental animals. This infection is rare, but the mortality is very high. Nowadays, drug treatment or active immunization of human or mice are being tried with partial effectiveness. This study shows passive immunization effect by transfer of immunized spleen cells, serum, or milk from immunized mother in mouse experimental model. Young BALB/c mice were immunized intraperitoneally with 2-3 X 10(6) trophozoites of N. fowleri, and spleen cells and sera were collected for injection to recipient mice. There were seven transfer groups, i.e., immunized mouse serum, spleen cells, serum and spleen cells, normal mouse serum, spleen cells, serum and spleen cells, and control group. Three days later, BALB/c mice were inoculated with 1 x 10(4) trophozoites of N. fowleri intranasally. After infection, decreased mortality and prolonged survival time of mice were noted in immunized groups compared with non-immunized control group. The groups injected with immunized spleen cells or normal serum showed lower mortality than that of controls but showed no changes of serum IgG level. The groups injected with immunized serum or normal spleen cells showed increased serum IgG level after immunization but hundred percent mortality was observed. Mother mice were immunized intraperitoneally with 2-3 X 10(6) trophozoites of N. fowleri at the end of pregnancy and weaning period. Soon after the delivery, litters born of non-immunized mother were matched with immunized mother for feeding immune milk. After three weeks, the litters were infected with 1 X 10(4) trophozoites of N. fowleri or sacrificed for serum collection to measure the IgG levels.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2486833

  14. [Resistance to Naegleria fowleri infection passively acquired from immunized splenocyte, serum or milk].

    PubMed

    Ahn, M H; Min, D Y

    1989-06-01

    A pathogenic free-living amoeba, Naegleria fowleri, causes primary amoebic meningoencephalitis to human and experimental animals. This infection is rare, but the mortality is very high. Nowadays, drug treatment or active immunization of human or mice are being tried with partial effectiveness. This study shows passive immunization effect by transfer of immunized spleen cells, serum, or milk from immunized mother in mouse experimental model. Young BALB/c mice were immunized intraperitoneally with 2-3 X 10(6) trophozoites of N. fowleri, and spleen cells and sera were collected for injection to recipient mice. There were seven transfer groups, i.e., immunized mouse serum, spleen cells, serum and spleen cells, normal mouse serum, spleen cells, serum and spleen cells, and control group. Three days later, BALB/c mice were inoculated with 1 x 10(4) trophozoites of N. fowleri intranasally. After infection, decreased mortality and prolonged survival time of mice were noted in immunized groups compared with non-immunized control group. The groups injected with immunized spleen cells or normal serum showed lower mortality than that of controls but showed no changes of serum IgG level. The groups injected with immunized serum or normal spleen cells showed increased serum IgG level after immunization but hundred percent mortality was observed. Mother mice were immunized intraperitoneally with 2-3 X 10(6) trophozoites of N. fowleri at the end of pregnancy and weaning period. Soon after the delivery, litters born of non-immunized mother were matched with immunized mother for feeding immune milk. After three weeks, the litters were infected with 1 X 10(4) trophozoites of N. fowleri or sacrificed for serum collection to measure the IgG levels.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. School Reentry for Children with Acquired Central Nervous Systems Injuries

    ERIC Educational Resources Information Center

    Carney, Joan; Porter, Patricia

    2009-01-01

    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special…

  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. Acquired hemophilia A in a patient with systemic lupus erythematosus.

    PubMed

    Ishikawa, T; Tsukamoto, N; Suto, M; Uchiumi, H; Mitsuhashi, H; Yokohama, A; Maesawa, A; Nojima, Y; Naruse, T

    2001-06-01

    A patient with systemic lupus erythematosus (SLE) developed acquired hemophilia A. The patient, a 24-year-old Japanese woman, was referred to our hospital because of uncontrollable bleeding following a tooth extraction. Laboratory examination revealed prolonged APTT (116 seconds), reduced factor VIII activity (2.8 %) and the presence of factor VIII inhibitor at a titer of 46.5 Bethesda units/ml. Transfusion of prothrombin complex concentrate and activated prothrombin complex concentrate followed by administration of prednisolone and cyclophosphamide successfully arrested bleeding and reduced the factor VIII inhibitor level. Acquired hemophilia A is a rare but lethal condition. Rapid diagnosis and introduction of adequate therapies are critical. PMID:11446683

  18. Schistosoma mansoni: is acquired immunity induced by highly x-irradiated cercariae dependent on the size of the challenging dose

    SciTech Connect

    Hsue, S.Y.; Hsue, H.F.; Osborne, J.W.; Johnson, S.C.

    1982-04-01

    A high degree of immunity, as shown by a 91% reduction of the number of worms recovered was found in five groups of mice that were immunized five times with highly X-irradiated cercariae and then challenged with 10, 20, 50, 100, or 500 normal Schistosoma mansoni cercariae. The results indicated that there were no significant differences in worm reduction in immunized mice challenged with different numbers of cercariae; consequently the immunity induced by this immunization method did not appear to be challenge-dose-dependent. However, the results also showed that when immunized mice were challenged with 500, 100, 50, 20, and 10 cercariae, 0, 13, 26, 56, and 68%, respectively, of the experimental animals were free of worms. Thus, the percentage of worm-negative cases increased as the number of challenge cercariae decreased. When viewed in this manner, the acquired immunity may be considered challenge-dose-dependent as well. If this method of vaccination is used for schistosomiasis control, we may anticipate that in both hypo- and hyperendemic areas, the intensity of infection and the severity of the disease will be reduced owing to a reduction in worms burdens, and in hypoendemic areas, there will be a number of worm-free cases.

  19. 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.

  20. Acquired immune response of white leghorn hens to populations of northern fowl mite, Ornithonyssus sylviarum (Canestrini and Fanzago).

    PubMed

    DeVaney, J A; Ziprin, R L

    1980-08-01

    Three levels (high, low and control) of northern fowl mite, Ornithonyssus sylviarum (Canestrini and Fanzago), were maintained on White Leghorn hens for 24 weeks. The hens were then treated with carbaryl to eradicate the mites, were induced to molt, and were reinfested with mites 9 weeks later. Subsequent levels of mites on the three groups showed that the degree of acquired immunity was related to the initial level of mite infestation. PMID:7413581

  1. Immune System and Its Link to Rheumatic Diseases

    MedlinePlus

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

  2. Effects of dietary fish meal and soybean meal on the ovine innate and acquired immune response during pregnancy and lactation.

    PubMed

    Stryker, J A; Fisher, R; You, Q; Or-Rashid, M M; Boermans, H J; Quinton, M; McBride, B W; Karrow, N A

    2013-01-01

    In recent years, livestock producers have been supplementing animal diets with fish meal (FM) to produce value-added products for health conscious consumers. As components of FM have unique neuroendocrine-immunomodulatory properties, we hypothesize that livestock producers may be influencing the overall health of their animals by supplementing diets with FM. In this study, 40 pregnant ewes were supplemented with rumen protected (RP) soybean meal (SBM: control diet) or RP FM, commencing gestation day 100 (gd100), in order to evaluate the impact of FM supplementation on the innate and acquired immune response and neuroendocrine response of sheep during pregnancy and lactation. On gd135, half the ewes from each diet (n = 10 FM, n = 10 SBM) were challenged iv with lipopolysaccharide (LPS) to simulate a systemic bacterial infection and the febrile, respiratory and neuroendocrine responses were monitored over time; the other half (n = 10 FM, n = 10 SBM) of the ewes received a saline injection as control. On lactation day 20 (ld20), all ewes (n = 20 FM, n = 20 SBM) were sensitized with hen egg white lysozyme (HEWL) and the serum haptoglobin (Hp) response was measured over time. The cutaneous hypersensitivity response (CHR) to HEWL challenge was measured on ld30 (n = 20 FM, n = 20 SBM), and blood samples were collected over time to measure the primary and secondary immunoglobulin G (IgG) response to HEWL. There was an attenuated trend in the LPS-induced febrile response by the FM treatment when compared with the SBM treatment (P = 0.06), as was also true for the respiratory response (P = 0.07), but significant differences in neuroendocrine function (serum cortisol and plasma ACTH) were not observed between treatments. Basal Hp levels were significantly lower in the FM supplemented ewes when compared with the SBM supplemented ewes (P < 0.01), and the Hp response to HEWL sensitization differed significantly over time between treatments (P < 0.01). The CHR to HEWL was also

  3. Acquire: an open-source comprehensive cancer biobanking system

    PubMed Central

    Dowst, Heidi; Pew, Benjamin; Watkins, Chris; McOwiti, Apollo; Barney, Jonathan; Qu, Shijing; Becnel, Lauren B.

    2015-01-01

    Motivation: The probability of effective treatment of cancer with a targeted therapeutic can be improved for patients with defined genotypes containing actionable mutations. To this end, many human cancer biobanks are integrating more tightly with genomic sequencing facilities and with those creating and maintaining patient-derived xenografts (PDX) and cell lines to provide renewable resources for translational research. Results: To support the complex data management needs and workflows of several such biobanks, we developed Acquire. It is a robust, secure, web-based, database-backed open-source system that supports all major needs of a modern cancer biobank. Its modules allow for i) up-to-the-minute ‘scoreboard’ and graphical reporting of collections; ii) end user roles and permissions; iii) specimen inventory through caTissue Suite; iv) shipping forms for distribution of specimens to pathology, genomic analysis and PDX/cell line creation facilities; v) robust ad hoc querying; vi) molecular and cellular quality control metrics to track specimens’ progress and quality; vii) public researcher request; viii) resource allocation committee distribution request review and oversight and ix) linkage to available derivatives of specimen. Availability and Implementation: Acquire implements standard controlled vocabularies, ontologies and objects from the NCI, CDISC and others. Here we describe the functionality of the system, its technological stack and the processes it supports. A test version Acquire is available at https://tcrbacquire-stg.research.bcm.edu; software is available in https://github.com/BCM-DLDCC/Acquire; and UML models, data and workflow diagrams, behavioral specifications and other documents are available at https://github.com/BCM-DLDCC/Acquire/tree/master/supplementaryMaterials. Contact: becnel@bcm.edu PMID:25573920

  4. I kappa B kinase alpha (IKKα) activity is required for functional maturation of dendritic cells and acquired immunity to infection.

    PubMed

    Mancino, Alessandra; Habbeddine, Mohamed; Johnson, Ella; Luron, Lionel; Bebien, Magali; Memet, Sylvie; Fong, Carol; Bajenoff, Marc; Wu, Xuefeng; Karin, Michael; Caamano, Jorge; Chi, Hongbo; Seed, Michael; Lawrence, Toby

    2013-03-20

    Dendritic cells (DC) are required for priming antigen-specific T cells and acquired immunity to many important human pathogens, including Mycobacteriuim tuberculosis (TB) and influenza. However, inappropriate priming of auto-reactive T cells is linked with autoimmune disease. Understanding the molecular mechanisms that regulate the priming and activation of naïve T cells is critical for development of new improved vaccines and understanding the pathogenesis of autoimmune diseases. The serine/threonine kinase IKKα (CHUK) has previously been shown to have anti-inflammatory activity and inhibit innate immunity. Here, we show that IKKα is required in DC for priming antigen-specific T cells and acquired immunity to the human pathogen Listeria monocytogenes. We describe a new role for IKKα in regulation of IRF3 activity and the functional maturation of DC. This presents a unique role for IKKα in dampening inflammation while simultaneously promoting adaptive immunity that could have important implications for the development of new vaccine adjuvants and treatment of autoimmune diseases.

  5. Testing the "toxin hypothesis of allergy": Mast cells, IgE, and innate and acquired immune responses to venoms*

    PubMed Central

    Tsai, Mindy; Starkl, Philipp; Marichal, Thomas; Galli, Stephen J.

    2015-01-01

    Summary Work in mice indicates that innate functions of mast cells, particularly degradation of venom toxins by mast cell-derived proteases, can enhance resistance to certain arthropod or reptile venoms. Recent reports indicate that acquired Th2 immune responses associated with the production of IgE antibodies, induced by Russell’s viper venom or honeybee venom, or by a component of honeybee venom, bee venom phospholipase 2 (bvPLA2), can increase the resistance of mice to challenge with potentially lethal doses of either of the venoms or bvPLA2. These findings support the conclusion that, in contrast to the detrimental effects associated with allergic Th2 immune responses, mast cells and IgE-dependent immune responses to venoms can contribute to innate and adaptive resistance to venom-induced pathology and mortality. PMID:26210895

  6. Production and function of cytokines in natural and acquired immunity to Candida albicans infection.

    PubMed Central

    Ashman, R B; Papadimitriou, J M

    1995-01-01

    Host resistance against infections caused by the yeast Candida albicans is mediated predominantly by polymorphonuclear leukocytes and macrophages. Antigens of Candida stimulate lymphocyte proliferation and cytokine synthesis, and in both humans and mice, these cytokines enhance the candidacidal functions of the phagocytic cells. In systemic candidiasis in mice, cytokine production has been found to be a function of the CD4+ T helper (Th) cells. The Th1 subset of these cells, characterized by the production of gamma interferon and interleukin-2, is associated with macrophage activation and enhanced resistance against reinfection, whereas the Th2 subset, which produces interleukins-4, -6, and -10, is linked to the development of chronic disease. However, other models have generated divergent data. Mucosal infection generally elicits Th1-type cytokine responses and protection from systemic challenge, and identification of cytokine mRNA present in infected tissues of mice that develop mild or severe lesions does not show pure Th1- or Th2-type responses. Furthermore, antigens of C. albicans, mannan in particular, can induce suppressor cells that modulate both specific and nonspecific cellular and humoral immune responses, and there is an emerging body of evidence that molecular mimicry may affect the efficiency of anti-Candida responses within defined genetic contexts. PMID:8531890

  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. School reentry for children with acquired central nervous systems injuries.

    PubMed

    Carney, Joan; Porter, Patricia

    2009-01-01

    Onset of acquired central nervous system (CNS) injury during the normal developmental process of childhood can have impact on cognitive, behavioral, and motor function. This alteration of function often necessitates special education programming, modifications, and accommodations in the education setting for successful school reentry. Special education is not necessarily a special classroom, but an individualized set of educational needs, determined by a multidisciplinary school team, to promote educational success. The purpose of this article is to inform those pediatricians and pediatric allied health professionals treating children with CNS injury of the systems in place to support successful school reentry and their role in contributing to developing an appropriate educational plan. PMID:19489086

  9. System Would Acquire Core and Powder Samples of Rocks

    NASA Technical Reports Server (NTRS)

    Bar-Cohen, Yoseph; Randolph, James; Bao, Xiaoqi; Sherrit, Stewart; Ritz, Chuck; Cook, Greg

    2006-01-01

    A system for automated sampling of rocks, ice, and similar hard materials at and immediately below the surface of the ground is undergoing development. The system, denoted a sample preparation, acquisition, handling, and delivery (SPAHD) device, would be mounted on a robotic exploratory vehicle that would traverse the terrain of interest on the Earth or on a remote planet. The SPAHD device would probe the ground to obtain data for optimization of sampling, prepare the surface, acquire samples in the form(s) of cores and/or powdered cuttings, and deliver the samples to a selected location for analysis and/or storage.

  10. Curcumin and tumor immune-editing: resurrecting the immune system.

    PubMed

    Bose, Sayantan; Panda, Abir Kumar; Mukherjee, Shravanti; Sa, Gaurisankar

    2015-01-01

    Curcumin has long been known to posses medicinal properties and recent scientific studies have shown its efficacy in treating cancer. Curcumin is now considered to be a promising anti-cancer agent and studies continue on its molecular mechanism of action. Curcumin has been shown to act in a multi-faceted manner by targeting the classical hallmarks of cancer like sustained proliferation, evasion of apoptosis, sustained angiogenesis, insensitivity to growth inhibitors, tissue invasion and metastasis etc. However, one of the emerging hallmarks of cancer is the avoidance of immune system by tumors. Growing tumors adopt several strategies to escape immune surveillance and successfully develop in the body. In this review we highlight the recent studies that show that curcumin also targets this process and helps restore the immune activity against cancer. Curcumin mediates several processes like restoration of CD4(+)/CD8(+) T cell populations, reversal of type-2 cytokine bias, reduction of Treg cell population and suppression of T cell apoptosis; all these help to resurrect tumor immune surveillance that leads to tumor regression. Thus interaction of curcumin with the immune system is also an important feature of its multi-faceted modes of action against cancer. Finally, we also point out the drawbacks of and difficulties in curcumin administration and indicate the use of nano-formulations of curcumin for better therapeutic efficacy. PMID:26464579

  11. 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.

  12. Systemic Therapy In Acquired Haemophilia – A Single Institute Experience

    PubMed Central

    Prantik, Das; Gary, Benson

    2016-01-01

    A cornerstone of the management of Acquired Haemophilia A (AHA) involves inhibitor eradication. First line immunosuppressive agents are usually steroids, either alone or in combination with cyclophosphamide. We present the use of Rituximab, cyclophosphamide, vincristine and prednisolone (RCVP) combination as immunosuppressant in AHA in a small cohort of patients in order to control their symptoms and eradicate inhibitors. This was a retrospective analysis of all AHA patients treated at the Northern Ireland Haemophilia centre over a six year period. During this time, a total of six patients were newly diagnosed with AHA. Four of these patients failed to respond conventional therapy of steroids and cyclophosphamide, they were however successfully treated with RCVP/ RCV. All patients achieved complete remission with this regimen after 1 to 2 cycles of treatment. Remission has been maintained for an extended time period (range 33-69 months). As AHA is related to immune modulation and, in some cases, underlying malignancy we decided to use this regime as it is effective in either condition. From our experience, we demonstrate that RCVP combination is a promising treatment in patients with AHA who fail to respond to steroids alone or who have been on pre-existing immunosuppression. PMID:27698522

  13. Systemic Therapy In Acquired Haemophilia – A Single Institute Experience

    PubMed Central

    Prantik, Das; Gary, Benson

    2016-01-01

    A cornerstone of the management of Acquired Haemophilia A (AHA) involves inhibitor eradication. First line immunosuppressive agents are usually steroids, either alone or in combination with cyclophosphamide. We present the use of Rituximab, cyclophosphamide, vincristine and prednisolone (RCVP) combination as immunosuppressant in AHA in a small cohort of patients in order to control their symptoms and eradicate inhibitors. This was a retrospective analysis of all AHA patients treated at the Northern Ireland Haemophilia centre over a six year period. During this time, a total of six patients were newly diagnosed with AHA. Four of these patients failed to respond conventional therapy of steroids and cyclophosphamide, they were however successfully treated with RCVP/ RCV. All patients achieved complete remission with this regimen after 1 to 2 cycles of treatment. Remission has been maintained for an extended time period (range 33-69 months). As AHA is related to immune modulation and, in some cases, underlying malignancy we decided to use this regime as it is effective in either condition. From our experience, we demonstrate that RCVP combination is a promising treatment in patients with AHA who fail to respond to steroids alone or who have been on pre-existing immunosuppression.

  14. The role of nurses in the human immunodeficiency virus/acquired immune deficiency syndrome policy process in Botswana.

    PubMed

    Phaladze, N A

    2003-03-01

    In Botswana, there is dearth of literature on the role of nursing in health-care policy and resource allocation and yet nurses constitute the majority (85%) of health manpower. The health-care delivery system depends mostly on nurses for service provision. There were two main purposes of this study: first, to gather descriptive data from major key players (with particular emphasis on nurses) concerning knowledge of the policy process and resource allocation for management and care of clients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) in Botswana; and, second, to identify nurse characteristics (e.g. position, education, experience, job category) associated with motivation to influence health-care policy in HIV/AIDS management and care in Botswana. A policy process conceptual framework was used to guide data collection and analysis. A case-study research method was used to conduct in-depth interviews from a purposive sample of 19 policy makers, and a survey questionnaire was used to collect data from a purposive sample of 95 registered nurses from six study sites in Botswana. The study findings indicate minimal participation of nurses in health-care policy process and resource allocation. The demographic variable of position was a predictor of the involvement of nurses in policy and in budgetary decisions. Both survey and interview data indicated that this minimal participation of nurses in the policy process resulted in implementation problems, thus compromising service provision. Implications of the findings for the nursing profession, nursing practice and policy, which address the importance of nurses' involvement, are discussed. PMID:12581124

  15. The immune system and cardiac repair

    PubMed Central

    Frangogiannis, Nikolaos G.

    2008-01-01

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

  16. The immune system, bone and RANKL.

    PubMed

    Guerrini, Matteo M; Takayanagi, Hiroshi

    2014-11-01

    Bone and immune systems are tightly linked. In the past years, many molecules originally believed to belong to the immune system were found to function in bone cells. It is now evident that the two systems are coregulated by many shared cytokines and signaling molecules. Here we exemplify the complex interaction between bone metabolism and immune response focusing on the multifaceted role of receptor activator of NF-κB ligand (RANKL). RANKL is expressed by cells of both systems, is an essential regulator of bone degradation and exerts either pro or anti-inflammatory effects on the immune response. In the present review, we summarize the multiple functions of RANKL in bone and in the immune systems, aiming to provide an overview of the field of osteoimmunology.

  17. The immune system, adaptation, and machine learning

    NASA Astrophysics Data System (ADS)

    Farmer, J. Doyne; Packard, Norman H.; Perelson, Alan S.

    1986-10-01

    The immune system is capable of learning, memory, and pattern recognition. By employing genetic operators on a time scale fast enough to observe experimentally, the immune system is able to recognize novel shapes without preprogramming. Here we describe a dynamical model for the immune system that is based on the network hypothesis of Jerne, and is simple enough to simulate on a computer. This model has a strong similarity to an approach to learning and artificial intelligence introduced by Holland, called the classifier system. We demonstrate that simple versions of the classifier system can be cast as a nonlinear dynamical system, and explore the analogy between the immune and classifier systems in detail. Through this comparison we hope to gain insight into the way they perform specific tasks, and to suggest new approaches that might be of value in learning systems.

  18. Malaria Transmission and Naturally Acquired Immunity to PfEMP-1

    PubMed Central

    Piper, Karen P.; Hayward, Rhian E.; Cox, Martin J.; Day, Karen P.

    1999-01-01

    Why there are so few gametocytes (the transmission stage of malaria) in the blood of humans infected with Plasmodium spp. is intriguing. This may be due either to reproductive restraint by the parasite or to unidentified gametocyte-specific immune-mediated clearance mechanisms. We propose another mechanism, a cross-stage immunity to Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1). This molecule is expressed on the surface of the erythrocyte infected with either trophozoite or early gametocyte parasites. Immunoglobulin G antibodies to PfEMP-1, expressed on both life cycle stages, were measured in residents from an area where malaria is endemic, Papua New Guinea. Anti-PfEMP-1 prevalence increased with age, mirroring the decline in both the prevalence and the density of asexual and transmission stages in erythrocytes. These data led us to propose that immunity to PfEMP-1 may influence malaria transmission by regulation of the production of gametocytes. This regulation may be achieved in two ways: (i) by controlling asexual proliferation and density and (ii) by affecting gametocyte maturation. PMID:10569752

  19. Development of Acquired Immunity following Repeated Respiratory Syncytial Virus Infections in Cotton Rats.

    PubMed

    Yamaji, Yoshiaki; Yasui, Yosuke; Nakayama, Tetsuo

    2016-01-01

    Respiratory syncytial virus (RSV) infections occur every year worldwide. Most infants are infected with RSV by one year of age and are reinfected because immune responses after the first infection are too weak to protect against subsequent infections. In the present study, immune responses against RSV were investigated in order to obtain a better understanding of repetitive RSV infections in cotton rats. No detectable neutralizing antibody (NT) was developed after the first infection, and the second infection was not prevented. The results of histological examinations revealed severe inflammation, viral antigens were detected around bronchial epithelial cells, and infectious viruses were recovered from lung homogenates. Following the second infection neutralizing antibodies were significantly elevated, and CD8+ cells were activated in response to RSV-F253-265. No viral antigens was detected thereafter in lung tissues and infectious viruses were not recovered. Similar results were obtained in the present study using the subgroups A and B. These results support the induction of humoral and cellular immune responses following repetitive infections with RSV; however, these responses were insufficient to eliminate viruses in the first and second infections. PMID:27224021

  20. Laparoscopic surgery and the systemic immune response.

    PubMed Central

    Vittimberga, F J; Foley, D P; Meyers, W C; Callery, M P

    1998-01-01

    OBJECTIVE: The authors review studies relating to the immune responses evoked by laparoscopic surgery. SUMMARY BACKGROUND DATA: Laparoscopic surgery has gained rapid acceptance based on clinical grounds. Patients benefit from faster recovery, decreased pain, and quicker return to normal activities. Only more recently have attempts been made to identify the metabolic and immune responses that may underlie this clinical success. The immune responses to laparoscopy are now being evaluated in relation to the present knowledge of immune responses to traditional laparotomy and surgery in general. METHODS: A review of the published literature of the immune and metabolic responses to laparoscopy was performed. Laparoscopic surgery is compared with the traditional laparotomy on the basis of local and systemic immune responses and patterns of tumor growth. The impact of pneumoperitoneum and insufflation gases on the immune response is also reviewed. CONCLUSIONS: The systemic immune responses for surgery in general may not apply to laparoscopic surgery. The body's response to laparoscopy is one of lesser immune activation as opposed to immunosuppression. PMID:9527054

  1. 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)

  2. 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.

  3. THE IMMUNE SYSTEM AND BONE

    PubMed Central

    Pacifici, Roberto

    2010-01-01

    T cells and B cells produce large amounts of cytokines which regulate bone resorption and bone formation. These factors play a critical role in the regulation of bone turnover in health and disease. In addition, immune cells of the bone marrow regulate bone homeostasis by cross-talking with bone marrow stromal cells and osteoblastic cells via cell surface molecules. These regulatory mechanisms are particularly relevant for postmenopausal osteoporosis and hyperparathyroidism, two common forms of bone loss caused primarily by an expansion of the osteoclastic pool only partially compensated by a stimulation of bone formation. This article describes the cytokines and immune factors that regulate bone cells, the immune cells relevant to bone, examines the connection between T cells and bone in health and disease, and reviews the evidence in favor of a link between T cells and the mechanism of action of estrogen and PTH in bone. PMID:20599675

  4. 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.

  5. Naturally-Acquired Immune Response against Plasmodium vivax Rhoptry-Associated Membrane Antigen

    PubMed Central

    Changrob, Siriruk; Wang, Bo; Han, Jin-Hee; Lee, Seong-Kyun; Nyunt, Myat Htut; Lim, Chae Seung; Tsuboi, Takafumi; Chootong, Patchanee; Han, Eun-Taek

    2016-01-01

    Rhoptry-associated membrane antigen (RAMA) is an abundant glycophosphatidylinositol (GPI)-anchored protein that is embedded within the lipid bilayer and is implicated in parasite invasion. Antibody responses against rhoptry proteins are produced by individuals living in a malaria-endemic area, suggesting the immunogenicity of Plasmodium vivax RAMA (PvRAMA) for induction of immune responses during P. vivax infection. To determine whether PvRAMA contributes to the acquisition of immunity to malaria and could be a rational candidate for a vaccine, the presence of memory T cells and the stability of the antibody response against PvRAMA were evaluated in P. vivax-exposed individuals. The immunogenicity of PvRAMA for the induction of T cell responses was evaluated by in vitro stimulation of peripheral blood mononuclear cells (PBMCs). High levels of interferon (IFN)-γ and interleukin (IL)-10 cytokines were detected in the culture supernatant of PBMCs, and the CD4+ T cells predominantly produced IL-10 cytokine. The levels of total anti-PvRAMA immunoglobulin G (IgG) antibody were significantly elevated, and these antibodies persisted over the 12 months of the study. Interestingly, IgG1, IgG2 and IgG3 were the major antibody subtypes in the response to PvRAMA. The frequency of IgG3 in specific to PvRAMA antigen maintained over 12 months. These data could explain the immunogenicity of PvRAMA antigen in induction of both cell-mediated and antibody-mediated immunity in natural P. vivax infection, in which IFN-γ helps antibody class switching toward the IgG1, IgG2 and IgG3 isotypes and IL-10 supports PvRAMA-specific antibody production. PMID:26886867

  6. Opportunistic infections in acquired immune deficiency syndrome result from synergistic defects of both the natural and adaptive components of cellular immunity.

    PubMed Central

    Siegal, F P; Lopez, C; Fitzgerald, P A; Shah, K; Baron, P; Leiderman, I Z; Imperato, D; Landesman, S

    1986-01-01

    We evaluated the cellular immunity of 408 clinically stratified subjects at risk for acquired immune deficiency syndrome (AIDS), to define the role of interferon-alpha production deficits in the pathogenesis of opportunistic infections (OI). We followed 115 prospectively for up to 45 mo. Onset of OI was associated with, and predicted by, deficiency both of interferon-alpha generation in vitro, and of circulating Leu-3a+ cells. Interferon-alpha production is an index of the function of certain non-T, non-B, large granular lymphocytes (LGL) that are independent of T cell help. Leu-3a+ cell counts are a marker of T cell function. OI did not usually develop until both of these mutually independent immune functions were simultaneously critically depressed, leading to a synergistic interaction. These data suggest that the AIDS virus affects a subset of LGL, and that cytokine production by these cells is an important component of the host defense against intracellular pathogens that becomes crucial in the presence of severe T cell immunodeficiency. PMID:3088039

  7. 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.

  8. Neural control of the immune system

    PubMed Central

    Sundman, Eva

    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 suggested that vagus nerve stimulation can improve symptoms in human rheumatoid arthritis. These discoveries have generated an increased interest in bioelectronic medicine, i.e., therapeutic delivery of electrical impulses that activate nerves to regulate immune system function. Here, we discuss the physiology and potential therapeutic implications of neural immune control. PMID:25039084

  9. [CRISPR adaptive immunity systems of procaryotes].

    PubMed

    2012-01-01

    CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a newly identified prokaryotic immunity system against foreign genetic elements. In contrast to other cellular defense mechanisms (e.g. restriction-modification) CRISPR-mediated immunity is adaptive and can be programmed to protect cells against a particular bacteriophage or conjugative plasmid. In this review we describe general principles of CRISPR systems action and summarize known details of CRISPR systems from different microorganisms.

  10. A brief journey through the immune system.

    PubMed

    Yatim, Karim M; Lakkis, Fadi G

    2015-07-01

    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.

  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. Toenail onychomycosis in patients with acquired immune deficiency syndrome: treatment with terbinafine.

    PubMed

    Herranz, P; García, J; De Lucas, R; González, J; Peña, J M; Díaz, R; Casado, M

    1997-10-01

    Skin infections caused by dermatophytes are one of the most frequent dermatological complications in patients with acquired immunodeficiency syndrome (AIDS) resulting from infection with human immunodeficiency virus (HIV). Tinea unguium associated with AIDS is characterized by being clinically more aggressive and therapeutically more difficult to treat than in the general population. Terbinafine is considered to be a first-choice option for the treatment of dermatophyte onychomycosis in immunocompetent individuals. This drug has been used in a series of 21 HIV-positive patients diagnosed with tinea unguium for 1 year in the University Hospital La Paz, Madrid. All patients underwent a subsequent clinical follow-up for 6 months. The results showed a high percentage of clinical and mycological cures, as well as maintenance of the response after follow-up; no drug interactions or significant adverse effects related to the drug under study were recorded.

  13. 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 ...

  14. Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate as first clinical manifestation of acquired immune deficiency syndrome

    PubMed Central

    Narwal, Anjali; Yadav, Achla Bharti; Prakash, Sant; Gupta, Shally

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is an uncommon disease, accounting for <5% of all cases of non-Hodgkin's lymphoma. We report a case of 48-year-old male who presented a clinically benign swelling in the right anterior palatal region since last 2 months. Radiographic evaluation showed no bone loss in palatal area. Histological and radiological examination was in favor of a peripheral reactive lesion like pyogenic granuloma or a benign salivary gland tumor. Immunohistochemistry confirmed the diagnosis of anaplastic lymphoma kinase-negative (ALK(−)) ALCL. Further laboratory tests ELISA for human immunodeficiency virus (HIV) and CD4 cell count was done which showed positivity for HIV. To the best of our knowledge, it is the first case of ALK(−) ALCL in the hard palate presenting as the first clinical manifestation of acquired immune deficiency syndrome. PMID:27041916

  15. Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate as first clinical manifestation of acquired immune deficiency syndrome.

    PubMed

    Narwal, Anjali; Yadav, Achla Bharti; Prakash, Sant; Gupta, Shally

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is an uncommon disease, accounting for <5% of all cases of non-Hodgkin's lymphoma. We report a case of 48-year-old male who presented a clinically benign swelling in the right anterior palatal region since last 2 months. Radiographic evaluation showed no bone loss in palatal area. Histological and radiological examination was in favor of a peripheral reactive lesion like pyogenic granuloma or a benign salivary gland tumor. Immunohistochemistry confirmed the diagnosis of anaplastic lymphoma kinase-negative (ALK(-)) ALCL. Further laboratory tests ELISA for human immunodeficiency virus (HIV) and CD4 cell count was done which showed positivity for HIV. To the best of our knowledge, it is the first case of ALK(-) ALCL in the hard palate presenting as the first clinical manifestation of acquired immune deficiency syndrome. PMID:27041916

  16. Anaplastic lymphoma kinase negative anaplastic large cell lymphoma of hard palate as first clinical manifestation of acquired immune deficiency syndrome.

    PubMed

    Narwal, Anjali; Yadav, Achla Bharti; Prakash, Sant; Gupta, Shally

    2016-01-01

    Anaplastic large cell lymphoma (ALCL) is an uncommon disease, accounting for <5% of all cases of non-Hodgkin's lymphoma. We report a case of 48-year-old male who presented a clinically benign swelling in the right anterior palatal region since last 2 months. Radiographic evaluation showed no bone loss in palatal area. Histological and radiological examination was in favor of a peripheral reactive lesion like pyogenic granuloma or a benign salivary gland tumor. Immunohistochemistry confirmed the diagnosis of anaplastic lymphoma kinase-negative (ALK(-)) ALCL. Further laboratory tests ELISA for human immunodeficiency virus (HIV) and CD4 cell count was done which showed positivity for HIV. To the best of our knowledge, it is the first case of ALK(-) ALCL in the hard palate presenting as the first clinical manifestation of acquired immune deficiency syndrome.

  17. Acquired resistance to innate immune clearance promotes Klebsiella pneumoniae ST258 pulmonary infection

    PubMed Central

    Ahn, Danielle; Peñaloza, Hernán; Wang, Zheng; Wickersham, Matthew; Parker, Dane; Patel, Purvi; Koller, Antonius; Chen, Emily I.; Bueno, Susan M.; Uhlemann, Anne-Catrin; Prince, Alice

    2016-01-01

    Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistant Klebsiella pneumoniae ST258 (KP35) were identified and help to explain the selection of this strain as a successful pulmonary pathogen. The acquisition of 4 new ortholog groups, including an arginine transporter, enabled KP35 to outcompete related ST258 strains lacking these genes. KP35 infection elicited a monocytic response, dominated by Ly6Chi monocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers. In comparison with other K. pneumoniae strains, KP35 induced global changes in the phagocytic response identified with proteomics, including evasion of Ca2+ and calpain activation necessary for phagocytic killing, confirmed in functional studies with neutrophils. This comprehensive analysis of an ST258 K. pneumoniae isolate reveals ongoing genetic adaptation to host microenvironments and innate immune clearance mechanisms that complements its repertoire of antimicrobial resistance genes and facilitates persistence in the lung. PMID:27777978

  18. Network representations of immune system complexity.

    PubMed

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

    2015-01-01

    The mammalian immune system is a dynamic multiscale 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 nonlinear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multiscale 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.

  19. Immune endocrinological evaluation in patients with severe vascular acquired brain injuries: therapeutical approaches.

    PubMed

    Amico, Angelo Paolo; Terlizzi, Annamaria; Annamaria, Terlizzi; Megna, Marisa; Marisa, Megna; Megna, Gianfranco; Gianfranco, Megna; Damiani, Sabino; Sabino, Damiani

    2013-06-01

    It is known that in severe acquired brain injuries there is process of neuroinflammation, with the activation of a local and general stress response. In our study we considered six patients with disorders of consciousness (five in vegetative state and one in minimal consciousness state) in subacute phase, which had both a clinical assessment and a functional imaging (fMRI): in all these patients we analised blood levels of osteopontin (OPN), a cytokin involved in neuroinflammation but also in neurorepair with a still discussed role. Besides we studied the lymphocyte subsets and blood levels of some hormones (ADH, ACTH, PRL, GH, TSH, fT3, fT4). We found a positive correlation between the levels of serum osteopontin (higher than normal in all subjects) and the severity of the brain injury, especially for prognosis: actually, the patient with the lowest level has emerged from minimal consciousness state, while the one with the highest level has died a few days after the evaluation. The lymphocyte subset was altered, with a general increase of CD4+/CD3+ ratio, but without a so strict correlation with clinical severity; the only hormone with a significant increase in the worse patients was prolactin. In fMRI we detected some responses to visual and acoustic stimuli also in vegetative states, which had no clinical response to this kind of stimulation but generally have had a better prognosis. So we conclude that osteopontin could be a good marker of neuroinflammation and relate to a worse prognosis of brain injuries; the lymphocyte alterations in these disorders are not clear, but we suspect an unbalance of CD4 towards Th2; PRL is the best endocrinological marker of brain injury severity; fMRI surely plays an important role in the detection of subclinical responses and in prognostic stratification, that is still to define with more studies and statistical analysis.

  20. Maternally acquired IgG immunity in neonates born to renal transplanted women.

    PubMed

    Viana, Patrícia Oliveira; Ono, Erika; Dinelli, Maria Isabel Saraiva; Costa-Carvalho, Beatriz Tavares; Santos, Amélia Miyashiro Nunes Dos; Sass, Nelson; Moraes-Pinto, Maria Isabel de

    2015-06-17

    Neonates born to renal transplanted women are exposed in utero to immunosuppressors and to antenatal conditions that may predispose the neonate to a high risk of prematurity and intrauterine growth retardation. These factors might interfere with the transfer of maternal IgG immunity. Total IgG levels and specific antibodies to measles, varicella, tetanus, Haemophilus influenzae type b (Hib) and Streptococcus pneumoniae (serotypes 4,6B,9V,14,18C,19F and 23F) were evaluated on maternal and cord blood samples of 23 sets of renal transplanted women and their newborns and 32 sets of healthy women-newborns at term. Total IgG levels were measured by nephelometry and specific antibodies, by ELISA. Renal transplanted mothers had lower median tetanus antibodies (0.67IU/mL) than controls (1.53IU/mL; p=0.017). Neonates from renal transplanted mothers had lower median tetanus antibodies (0.95IU/mL) than controls (1.97IU/mL, p=0.008). Antibodies to measles, varicella, Hib and the 7 serotypes of S. pneumoniae were similar between groups. Maternal antibodies were associated with an increase in neonatal antibodies for all antigens; gestational age was associated with an increase in Hib neonatal antibodies. Preeclampsia was associated with a decrease in neonatal total IgG and serotype 4 S. pneumoniae antibodies; chronic hypertension was associated with a decrease in neonatal serotype 6B S. pneumoniae antibodies. As neonates from transplanted women may be born with lower tetanus antibodies than controls, efforts should be made to keep maternal vaccines up-to-date. Clinical antenatal care with control of preeclampsia, chronic hypertension and prevention of premature delivery might also contribute to neonatal antibody levels to specific antigens at birth. PMID:25987539

  1. 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.

  2. Effect of traditional Chinese medicine for treating human immunodeficiency virus infections and acquired immune deficiency syndrome: Boosting immune and alleviating symptoms.

    PubMed

    Zou, Wen; Wang, Jian; Liu, Ying

    2016-01-01

    To respond to the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) epidemic in China, the integration of antiretroviral therapy (ART) and traditional Chinese medicine (TCM) has important implications in health outcomes, especially in China where the use of TCM is widespread. The National Free TCM Pilot Program for HIV Infected People began in 5 provinces (Henan, Hebei, Anhui, Hubei, and Guangdong) in 2004, and quickly scaled up to 19 provinces, autonomous regions, and municipalities in China including some places with high prevalence, 26,276 adults have been treated thus far. Usually, people with HIV infection seek TCM for four main reasons: to enhance immune function, to treat symptoms, to improve quality of life, and to reduce side effects related to medications. Evidences from randomized controlled clinical trials suggested some beneficial effects of use of traditional Chinese herbal medicine for HIV infections and AIDS. More proofs from large, well-designed, rigorous trials is needed to give firm support. Challenges include interaction between herbs and antiretroviral drugs, stigma and discrimination. The Free TCM Program has made considerable progress in providing the necessary alternative care and treatment for HIV-infected people in China, and has strong government support for continued improvement and expansion, establishing and improving a work mechanism integrating Chinese and Western medicines.

  3. Effect of traditional Chinese medicine for treating human immunodeficiency virus infections and acquired immune deficiency syndrome: Boosting immune and alleviating symptoms.

    PubMed

    Zou, Wen; Wang, Jian; Liu, Ying

    2016-01-01

    To respond to the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) epidemic in China, the integration of antiretroviral therapy (ART) and traditional Chinese medicine (TCM) has important implications in health outcomes, especially in China where the use of TCM is widespread. The National Free TCM Pilot Program for HIV Infected People began in 5 provinces (Henan, Hebei, Anhui, Hubei, and Guangdong) in 2004, and quickly scaled up to 19 provinces, autonomous regions, and municipalities in China including some places with high prevalence, 26,276 adults have been treated thus far. Usually, people with HIV infection seek TCM for four main reasons: to enhance immune function, to treat symptoms, to improve quality of life, and to reduce side effects related to medications. Evidences from randomized controlled clinical trials suggested some beneficial effects of use of traditional Chinese herbal medicine for HIV infections and AIDS. More proofs from large, well-designed, rigorous trials is needed to give firm support. Challenges include interaction between herbs and antiretroviral drugs, stigma and discrimination. The Free TCM Program has made considerable progress in providing the necessary alternative care and treatment for HIV-infected people in China, and has strong government support for continued improvement and expansion, establishing and improving a work mechanism integrating Chinese and Western medicines. PMID:26577109

  4. The Innate Immune System and Transplantation

    PubMed Central

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

    2013-01-01

    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. PMID:24086066

  5. Immune impairments and antibodies to HTLVIII/LAV in asymptomatic male homosexuals in Israel: relevance to the risk of acquired immune deficiency syndrome (AIDS).

    PubMed

    Bentwich, Z; Saxinger, C; Ben-Ishay, Z; Burstein, R; Berner, Y; Pecht, M; Trainin, N; Levin, S; Handzel, Z T

    1987-09-01

    We have studied 288 Israeli asymptomatic male homosexuals (MHS) to determine the prevalence of antibodies to HTLVI and HTLVIII and their correlation with impairments of the immune system and serum interferon (IFN). Seropositivity for HTLVI, HTLVIII, or both was found in 1.4, 8.3, and 0%, respectively. Significant decreases in the total peripheral T cells, TH cells, and TH/TS ratio as well as elevated alpha IFN serum levels were found in the MHS group in comparison with normal controls. Although no difference in the prevalence of either immune derangements or elevated serum IFN was observed between HTLVIII/LAV-seropositive and HTLVIII/LAV-seronegative MHS, the decreases in total T cells, TH cells, and TH/TS ratios were significantly greater in the seropositive MHS. These results indicate that (a) immune impairments and IFN system activation occur commonly in homosexuals, precede their exposure to HTLVIII/LAV, and probably reflect this group's increased risk for AIDS and (b) HTLVIII/LAV infection of MHS aggravates further their preexisting immune impairments.

  6. 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.

  7. 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.

  8. Systemic Induction of the Small Antibacterial Compound in the Leaf Exudate During Benzothiadiazole-elicited Systemic Acquired Resistance in Pepper.

    PubMed

    Lee, Boyoung; Park, Yong-Soon; Yi, Hwe-Su; Ryu, Choong-Min

    2013-09-01

    Plants protect themselves from diverse potential pathogens by induction of the immune systems such as systemic acquired resistance (SAR). Most bacterial plant pathogens thrive in the intercellular space (apoplast) of plant tissues and cause symptoms. The apoplastic leaf exudate (LE) is believed to contain nutrients to provide food resource for phytopathogenic bacteria to survive and to bring harmful phytocompounds to protect plants against bacterial pathogens. In this study, we employed the pepper-Xanthomonas axonopodis system to assess whether apoplastic fluid from LE in pepper affects the fitness of X. axonopodis during the induction of SAR. The LE was extracted from pepper leaves 7 days after soil drench-application of a chemical trigger, benzothiadiazole (BTH). Elicitation of plant immunity was confirmed by significant up-regulation of four genes, CaPR1, CaPR4, CaPR9, and CaCHI2, by BTH treatment. Bacterial fitness was evaluated by measuring growth rate during cultivation with LE from BTH- or water-treated leaves. LE from BTH-treatment significantly inhibited bacterial growth when compared to that from the water-treated control. The antibacterial activity of LE from BTH-treated samples was not affected by heating at 100°C for 30 min. Although the antibacterial molecules were not precisely identified, the data suggest that small (less than 5 kDa), heat-stable compound(s) that are present in BTH-induced LE directly attenuate bacterial growth during the elicitation of plant immunity. PMID:25288963

  9. Immune System to Brain Signaling: Neuropsychopharmacological Implications

    PubMed Central

    Capuron, Lucile; Miller, Andrew H.

    2011-01-01

    There has been an explosion in our knowledge of the pathways and mechanisms by which the immune system can influence the brain and behavior. In the context of inflammation, pro-inflammatory cytokines can access the central nervous system and interact with a cytokine network in the brain to influence virtually every aspect of brain function relevant to behavior including neurotransmitter metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits that regulate mood, motor activity, motivation, anxiety and alarm. Behavioral consequences of these effects of the immune system on the brain include depression, anxiety, fatigue, psychomotor slowing, anorexia, cognitive dysfunction and sleep impairment; symptoms that overlap with those which characterize neuropsychiatric disorders, especially depression. Pathways that appear to be especially important in immune system effects on the brain include the cytokine signaling molecules, p38 mitogen activated protein kinase and nuclear factor kappa B; indoleamine 2,3 dioxygenase and its down stream metabolites, kynurenine, quinolinic acid and kynurenic acid; the neurotransmitters, serotonin, dopamine and glutamate; and neurocircuits involving the basal ganglia and anterior cingulate cortex. A series of vulnerability factors including aging and obesity as well as chronic stress also appear to interact with immune to brain signaling to exacerbate immunologic contributions to neuropsychiatric disease. The elucidation of the mechanisms by which the immune system influences behavior yields a host of targets for potential therapeutic development as well as informing strategies for the prevention of neuropsychiatric disease in at risk populations. PMID:21334376

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

    PubMed

    Pulendran, Bali

    2014-08-26

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

  11. Colloidal carrier systems for transcutaneous immunization.

    PubMed

    Gupta, Prem N; Vyas, Suresh P

    2011-04-01

    Recently, the skin has emerged as a potential alternative route for non-invasive delivery of vaccine. It has been recognized as a highly immune-reactive tissue containing an abundance of antigen presenting cells, especially within the epidermis. Transcutaneous immunization, introduction of antigen through topical application onto the intact skin, has many practical merits compared to injectable routes of administration. It combines the advantages of needle-free delivery while targeting the immunologically rich milieu of the skin. This simple and non-invasive immunization procedure elicits systemic and cell mediated immune responses and therefore, it provides a viable and cost-effective strategy for disease prevention. Various strategies i.e physical, chemical and novel carrier systems can be explored for trancutaneous immunization. Specially designed vaccine carrier systems are attracting immense attention and these could be potential module for non-invasive antigen delivery. The review covers topical delivery consideration in brief followed by an insight into various novel delivery systems for transcutaneous vaccine delivery.

  12. 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…

  13. 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.

  14. Plasmodium vivax Reticulocyte Binding Proteins Are Key Targets of Naturally Acquired Immunity in Young Papua New Guinean Children

    PubMed Central

    França, Camila T.; He, Wen-Qiang; Gruszczyk, Jakub; Lim, Nicholas T. Y.; Lin, Enmoore; Kiniboro, Benson; Siba, Peter M.; Tham, Wai-Hong

    2016-01-01

    Background Major gaps in our understanding of Plasmodium vivax biology and the acquisition of immunity to this parasite hinder vaccine development. P. vivax merozoites exclusively invade reticulocytes, making parasite proteins that mediate reticulocyte binding and/or invasion potential key vaccine or drug targets. While protein interactions that mediate invasion are still poorly understood, the P. vivax Reticulocyte-Binding Protein family (PvRBP) is thought to be involved in P. vivax restricted host-cell selectivity. Methodology/Principal findings We assessed the binding specificity of five members of the PvRBP family (PvRBP1a, PvRBP1b, PvRBP2a, PvRBP2b, PvRBP2-P2 and a non-binding fragment of PvRBP2c) to normocytes or reticulocytes. PvRBP2b was identified as the only reticulocyte-specific binder (P<0.001), whereas the others preferentially bound to normocytes (PvRBP1a/b P≤0.034), or showed comparable binding to both (PvRBP2a/2-P2, P = 0.38). Furthermore, we measured levels of total and IgG subclasses 1, 2, 3 and 4 to the six PvRBPs in a cohort of young Papua New Guinean children, and assessed their relationship with prospective risk of P. vivax malaria. Children had substantial, highly correlated (rho = 0.49–0.82, P<0.001) antibody levels to all six PvRBPs, with dominant IgG1 and IgG3 subclasses. Both total IgG (Incidence Rate Ratio [IRR] 0.63–0.73, P = 0.008–0.041) and IgG1 (IRR 0.56–0.69, P = 0.001–0.035) to PvRBP2b and PvRBP1a were strongly associated with reduced risk of vivax-malaria, independently of age and exposure. Conclusion/Significance These results demonstrate a diversity of erythrocyte-binding phenotypes of PvRBPs, indicating binding to both reticulocyte-specific and normocyte-specific ligands. Our findings provide further insights into the naturally acquired immunity to P. vivax and highlight the importance of PvRBP proteins as targets of naturally acquired humoral immunity. In-depth studies of the role of PvRBPs in P. vivax invasion and

  15. 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

  16. Network representations of immune system complexity.

    PubMed

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

    2015-01-01

    The mammalian immune system is a dynamic multiscale 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 nonlinear behaviors arising from dynamic, feedback-regulated interactions among many components. One of the major goals of systems immunology is to quantitatively measure these complex multiscale 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

  17. 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

  18. Harnessing the immune system to improve cancer therapy.

    PubMed

    Papaioannou, Nikos E; Beniata, Ourania V; Vitsos, Panagiotis; Tsitsilonis, Ourania; Samara, Pinelopi

    2016-07-01

    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. Changes Related to Age in Natural and Acquired Systemic Self-IgG Responses in Malaria

    PubMed Central

    Dassé, Romuald; Lefranc, Didier; Dubucquoi, Sylvain; Dussart, Patricia; Dutoit-Lefevre, Virginie; Sendid, Boualem; Sombo Mambo, François; Vermersch, Patrick; Prin, Lionel

    2011-01-01

    Background. Absence of acquired protective immunity in endemic areas children leads to higher susceptibility to severe malaria. To investigate the involvement of regulatory process related to self-reactivity, we evaluated potent changes in auto-antibody reactivity profiles in children and older subjects living in malaria-endemic zones comparatively to none-exposed healthy controls. Methods. Analysis of IgG self-reactive footprints was performed using Western blotting against healthy brain antigens. Plasmas of 102 malaria exposed individuals (MEIs) from endemic zone, with or without cerebral malaria (CM) were compared to plasmas from non-endemic controls (NECs). Using linear discriminant and principal component analysis, immune footprints were compared by counting the number, the presence or absence of reactive bands. We identified the most discriminant bands with respect to age and clinical status. Results. A higher number of bands were recognized by IgG auto-antibodies in MEI than in NEC. Characteristic changes in systemic self-IgG-reactive repertoire were found with antigenic bands that discriminate Plasmodium falciparum infections with or without CM according to age. 8 antigenic bands distributed in MEI compared with NEC were identified while 6 other antigenic bands were distributed within MEI according to the age and clinical status. Such distortion might be due to evolutionary processes leading to pathogenic/protective events. PMID:22253622

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

    PubMed

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

    2016-10-01

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

  1. Prenatal cadmium exposure produces persistent changes to thymus and spleen cell phenotypic repertoire as well as the acquired immune response

    SciTech Connect

    Holásková, Ida; Elliott, Meenal; Hanson, Miranda L.; Schafer, Rosana; Barnett, John B.

    2012-12-01

    Cadmium (Cd) is a common environmental contaminant. Adult exposure to Cd alters the immune system, however, there are limited studies on the effects of prenatal exposure to Cd. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at 20 weeks of age. Prenatal Cd exposure caused an increase in the percent of CD4{sup −}CD8{sup −}CD44{sup +}CD25{sup −} (DN1) thymocytes in both sexes and a decrease in the percent of CD4{sup −}CD8{sup −}CD44{sup −}CD25{sup +} (DN3) thymocytes in females. Females had an increase in the percent of splenic CD4{sup +} T cells, CD8{sup +} T cells, and CD45R/B220{sup +} B cells and a decrease in the percent of NK cells and granulocytes (Gr-1{sup +}). Males had an increase in the percent of splenic CD4{sup +} T cells and CD45R/B220{sup +} B cells and a decrease in the percent of CD8{sup +} T cells, NK cells, and granulocytes. The percentage of neutrophils and myeloid-derived suppressor cells were reduced in both sexes. The percent of splenic nTreg cells was decreased in all Cd-exposed offspring. Cd-exposed offspring were immunized with a streptococcal vaccine and the antibody response was determined. PC-specific serum antibody titers were decreased in Cd exposed female offspring but increased in the males. PspA-specific serum IgG titers were increased in both females and males compared to control animals. Females had a decrease in PspA-specific serum IgM antibody titers. Females and males had a decrease in the number of splenic anti-PspA antibody-secreting cells when standardized to the number of B cells. These findings demonstrate that very low levels of Cd exposure during gestation can result in long term sex-specific alterations on the immune system of the offspring. -- Highlights: ► Prenatal exposure to cadmium alters the immune system of 20 week old offspring. ► The percentage of DN1 and DN3 thymocytes was changed

  2. Evolution of the immune system in humans from infancy to old age

    PubMed Central

    Hollander, Georg A.; McMichael, Andrew

    2015-01-01

    This article reviews the development of the immune response through neonatal, infant and adult life, including pregnancy, ending with the decline in old age. A picture emerges of a child born with an immature, innate and adaptive immune system, which matures and acquires memory as he or she grows. It then goes into decline in old age. These changes are considered alongside the risks of different types of infection, autoimmune disease and malignancy. PMID:26702035

  3. Health related quality of life: is it another comprehensive evaluation indicator of Chinese medicine on acquired immune deficiency syndrome treatment?

    PubMed

    Liu, Zhibin; Yang, Jiping

    2015-10-01

    Health related quality of life (HRQOL) can better reflect changes in acquired immune deficiency syndrome (AIDS) patients and inform economic evaluation of AIDS treatment services, and the assessment of HRQOL can help us to detect problems that may influence the progression of the disease, hence HRQOL has become a particularly important assessment indictor for HIV comprehensive interventions. Being a multi-angle, multi-level, and diversified complex intervention, roles of Chinese medicine (CM) in AIDS treatment have been recognized and accepted by more and more patients, and HRQOL has been widely used to evaluate the comprehensive management effects of CM on AIDS. In this article, the authors analyze the definition and measurement of HRQOL, measurement of HRQOL of HIV/AIDS patients and effects of CM on AIDS, and give some reasonable advices for the usage of the scale of HRQOL. The authors hold that some new HRQOL instruments specific for CM treatment of AIDS should be developed and further prospective studies should be carried out to demonstrate the practicality, reliability and validity of HRQOL as an evaluation indictor for CM treatment of AIDS.

  4. Reactions of immune system to physical exercises.

    PubMed

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

    2002-04-01

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

  5. Community acquired pneumonia: genetic variants influencing systemic inflammation.

    PubMed

    Ferrer Agüero, J M; Millán, S; Rodríguez de Castro, F; Martín-Loeches, I; Solé Violán, J

    2014-01-01

    The inflammatory response depends on several factors, including pathogenicity and duration of the stimulus, and also on the balance between inflammatory and antiinflammatory response. Several studies have presented evidence of the importance of genetic factors in severe infections. The innate immune response prevents the invasion and spread of pathogens during the first hours after infection. Each of the different processes involved in innate immunity may be affected by genetic polymorphisms, which can result in susceptibility or resistance to infection. The results obtained in the different studies do not irrefutably prove the role or function of a gene in the pathogenesis of respiratory infections. However, they can generate new hypotheses, suggest new candidate genes based on their role in the inflammatory response, and constitute a first step in understanding the underlying genetic factors.

  6. Community acquired pneumonia: genetic variants influencing systemic inflammation.

    PubMed

    Ferrer Agüero, J M; Millán, S; Rodríguez de Castro, F; Martín-Loeches, I; Solé Violán, J

    2014-01-01

    The inflammatory response depends on several factors, including pathogenicity and duration of the stimulus, and also on the balance between inflammatory and antiinflammatory response. Several studies have presented evidence of the importance of genetic factors in severe infections. The innate immune response prevents the invasion and spread of pathogens during the first hours after infection. Each of the different processes involved in innate immunity may be affected by genetic polymorphisms, which can result in susceptibility or resistance to infection. The results obtained in the different studies do not irrefutably prove the role or function of a gene in the pathogenesis of respiratory infections. However, they can generate new hypotheses, suggest new candidate genes based on their role in the inflammatory response, and constitute a first step in understanding the underlying genetic factors. PMID:24183496

  7. Systems integration of innate and adaptive immunity.

    PubMed

    Zak, Daniel E; Aderem, Alan

    2015-09-29

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

  8. [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

  9. CRISPR-Based Adaptive Immune Systems

    PubMed Central

    Terns, Michael P.; Terns, Rebecca M.

    2011-01-01

    CRISPR-Cas systems are recently discovered, RNA-based immune systems that control invasions of viruses and plasmids in archaea and bacteria. Prokaryotes with CRISPR-Cas immune systems capture short invader sequences within the CRISPR loci in their genomes, and small RNAs produced from the CRISPR loci (CRISPR (cr)RNAs) guide Cas proteins to recognize and degrade (or otherwise silence) the invading nucleic acids. There are multiple variations of the pathway found among prokaryotes, each mediated by largely distinct components and mechanisms that we are only beginning to delineate. Here we will review our current understanding of the remarkable CRISPR-Cas pathways with particular attention to studies relevant to systems found in the archaea. PMID:21531607

  10. 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

  11. Glycerol-3-phosphate is a critical mobile inducer of systemic immunity in plants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Glycerol-3-phosphate (G3P) is an important metabolite that contributes to the growth and disease-related physiologies of prokaryotes, plants, animals and humans alike. Here we show that G3P serves as the inducer of an important form of broad-spectrum immunity in plants, termed systemic acquired resi...

  12. 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.

  13. Development and Evaluation of a Complementary and Alternative Medicine Use Survey in African-Americans with Acquired Immune Deficiency Syndrome

    PubMed Central

    Sterk, Claire; McCarty, Frances; Hankerson-Dyson, Dana; DiClemente, Ralph

    2010-01-01

    Abstract Objectives The purpose of the current study was to develop and evaluate the psychometric properties of a culturally- and stage-of-disease-appropriate measure of complementary and alternative medicine (CAM) use among a population of African-American individuals with acquired immune deficiency syndrome (AIDS) using a mixed-method design. Design Data were collected in two phases. In phase 1, qualitative data were used to refine an existing CAM measure for the specific study population in the present study. In phase 2, this refined instrument was implemented in a larger sample. The resulting numeric data were analyzed to evaluate the psychometric properties of the revised CAM instrument. Setting Data were collected from patients who were receiving care from the infectious disease clinic of a large, public, urban hospital in the Southeastern United States. Subjects Patients were eligible to participate if they (1) were receiving their care from the clinic, (2) had an AIDS diagnosis, (3) were identified as African-American, (4) were ≥21 years of age, (5) spoke English, and (6) were not cognitively impaired. Measures Focus groups in phase 1 were conducted with a semistructured focus group guide. Participants also completed a basic sociodemographic survey. Phase 2 participants used programmed laptops to answer questions about their CAM use and several sociodemographic questions. Results Information from the focus groups prompted some substantive revisions in the already-existing CAM survey. The revised instrument had satisfactory face validity and adequate test–retest reliability (r = 0.79). Furthermore, the instrument factored in a manner that was interpretable and consistent with prior findings. Conclusions In order for human immunodeficiency virus health care providers to provide the best care to their patients, they need to be informed about the types and frequency of CAM use among their patients. This can be accomplished by methodologically developing

  14. Orchitis and human immunodeficiency virus type 1 infected cells in reproductive tissues from men with the acquired immune deficiency syndrome.

    PubMed Central

    Pudney, J.; Anderson, D.

    1991-01-01

    Mechanisms underlying human immunodeficiency virus type 1 (HIV-1) infection of the male reproductive tract and the sexual transmission of HIV-1 through semen are poorly understood. To address these issues, the authors performed morphologic and immunocytochemical analyses of reproductive tissues obtained at autopsy from 43 male acquired immune deficiency syndrome (AIDS) patients. Monoclonal antibodies recognizing different subpopulations of white blood cells were used to detect leukocyte infiltration and map the location of potential lymphocytic/monocytic HIV-1 host cells and immunocytochemistry and in situ hybridization techniques were used to detect HIV-1-infected cells in the testis, excurrent ducts, and prostate. Distinct pathologic changes were observed in a majority of testes of AIDS patients that included azoospermia, hyalinization of the boundary wall of seminiferous tubules, and lymphocytic infiltration of the interstitium. The reproductive excurrent ducts and prostate appeared morphologically normal except for the presence of focal accumulations of white blood cells in the connective tissue stroma. In the testis many white blood cells were shown to be CD4+, indicating the presence of abundant host cells (T-helper/inducer lymphocytes and macrophages) for HIV-1. Furthermore macrophages and cells of lymphocytic morphology were observed migrating across the boundary walls of hyalinized seminiferous in tubules to enter the lumen. In 9 of the 23 cases tested for HIV-1 protein expression by immunocytochemistry. HIV-1 + cells of lymphocytic/monocytic morphology were found in the seminiferous tubules and interstitium of the testis, epididymal epithelium, and connective tissue of the epididymis and prostate. One patient with epididymal blockage had accumulations of HIV-1-antigen-positive cells of macrophages morphology in the distended lumen of the efferent ducts. There was no evidence of active HIV-1 infection in germ cells or Sertoli cells of the seminiferous

  15. It takes two to tango: Understanding the interactions between engineered nanomaterials and the immune system.

    PubMed

    Farrera, Consol; Fadeel, Bengt

    2015-09-01

    The immune system represents our primary defense system against foreign intrusion, including pathogens as well as particles. In order to understand the potential toxicity of engineered nanomaterials of ever increasing sophistication, it is necessary to understand the sophistication of the immune system with its multiple, specialized cell types and soluble mediators. Moreover, it is important to consider not only material-intrinsic properties of the pristine nanomaterial, but also the acquired, context-dependent 'identity' of a nanomaterial in a living system resulting from the adsorption of biomolecules on its surface. The immune system has evolved to recognize a vast array of microbes through so-called pattern recognition; we discuss in the present review whether engineered nanomaterials with or without a corona of biomolecules could also be sensed as 'pathogens' by immune-competent cells.

  16. Community-, Healthcare- and Hospital-Acquired Severe Sepsis Hospitalizations in the University HealthSystem Consortium

    PubMed Central

    Page, David B.; Donnelly, John P.; Wang, Henry E.

    2015-01-01

    Objectives Severe sepsis poses a major burden on the U.S. healthcare system. Previous epidemiologic studies have not differentiated community-acquired severe sepsis from healthcare-associated severe sepsis or hospital-acquired severe sepsis hospitalizations. We sought to compare and contrast community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis hospitalizations in a national hospital sample. Setting United States Interventions None Measurements & Main Results Prevalence of community-acquired severe sepsis, healthcare-associated severe sepsis, and hospital-acquired severe sepsis, adjusted hospital mortality, length of hospitalization, length of stay in an ICU, and hospital costs. Among 3,355,753 hospital discharges, there were 307,491 with severe sepsis, including 193,081 (62.8%) community-acquired severe sepsis, 79,581 (25.9%) healthcare-associated severe sepsis, and 34,829 (11.3%) hospital-acquired severe sepsis. Hospital-acquired severe sepsis and healthcare-associated severe sepsis exhibited higher in-hospital mortality than community-acquired severe sepsis (hospital-acquired [19.2%] vs healthcare-associated [12.8%] vs community-acquired [8.6%]). Hospital-acquired severe sepsis had greater resource utilization than both healthcare-associated severe sepsis and community-acquired severe sepsis, with higher median length of hospital stay (hospital acquired [17 d] vs healthcare associated [7 d] vs community-acquired [6 d]), median length of ICU stay (hospital-acquired [8 d] vs healthcare-associated [3 d] vs community-acquired [3 d]), and median hospital costs (hospital-acquired [$38,369] vs healthcare-associated [$8,796] vs community-acquired [$7,024]). Conclusions In this series, severe sepsis hospitalizations included CA-SS (62.8%), HCA-SS (25.9%) and HA-SS (11.3%) cases. HA-SS was associated with both higher mortality and resource utilization than CA-SS and HCA-SS. PMID:26110490

  17. The porcine innate immune system: an update.

    PubMed

    Mair, K H; Sedlak, C; Käser, T; Pasternak, A; Levast, B; Gerner, W; Saalmüller, A; Summerfield, A; Gerdts, V; Wilson, H L; Meurens, F

    2014-08-01

    Over the last few years, we have seen an increasing interest and demand for pigs in biomedical research. Domestic pigs (Sus scrofa domesticus) are closely related to humans in terms of their anatomy, genetics, and physiology, and often are the model of choice for the assessment of novel vaccines and therapeutics in a preclinical stage. However, the pig as a model has much more to offer, and can serve as a model for many biomedical applications including aging research, medical imaging, and pharmaceutical studies to name a few. In this review, we will provide an overview of the innate immune system in pigs, describe its anatomical and physiological key features, and discuss the key players involved. In particular, we compare the porcine innate immune system to that of humans, and emphasize on the importance of the pig as model for human disease.

  18. Medications that Weaken Your Immune System and Fungal Infections

    MedlinePlus

    ... Diseases Mycotic Diseases Branch Medications that Weaken Your Immune System and Fungal Infections Recommend on Facebook Tweet Share ... They are most common among people with weak immune systems. People with certain health conditions may need to ...

  19. Interconnection between flowering time control and activation of systemic acquired resistance

    PubMed Central

    Banday, Zeeshan Z.; Nandi, Ashis K.

    2015-01-01

    The ability to avoid or neutralize pathogens is inherent to all higher organisms including plants. Plants recognize pathogens through receptors, and mount resistance against the intruders, with the help of well-elaborated defense arsenal. In response to some localinfections, plants develop systemic acquired resistance (SAR), which provides heightened resistance during subsequent infections. Infected tissues generate mobile signaling molecules that travel to the systemic tissues, where they epigenetically modify expression o a set of genes to initiate the manifestation of SAR in distant tissues. Immune responses are largely regulated at transcriptional level. Flowering is a developmental transition that occurs as a result of the coordinated action of large numbers of transcription factors that respond to intrinsic signals and environmental conditions. The plant hormone salicylic acid (SA) which is required for SAR activation positively regulates flowering. Certain components of chromatin remodeling complexes that are recruited for suppression of precocious flowering are also involved in suppression of SAR in healthy plants. FLOWERING LOCUS D, a putative histone demethylase positively regulates SAR manifestation and flowering transition in Arabidopsis. Similarly, incorporation of histone variant H2A.Z in nucleosomes mediated by PHOTOPERIOD-INDEPENDENT EARLY FLOWERING 1, an ortholog of yeast chromatin remodeling complex SWR1, concomitantly influences SAR and flowering time. SUMO conjugation and deconjugation mechanisms also similarly affect SAR and flowering in an SA-dependent manner. The evidences suggest a common underlying regulatory mechanism for activation of SAR and flowering in plants. PMID:25852723

  20. Interconnection between flowering time control and activation of systemic acquired resistance.

    PubMed

    Banday, Zeeshan Z; Nandi, Ashis K

    2015-01-01

    The ability to avoid or neutralize pathogens is inherent to all higher organisms including plants. Plants recognize pathogens through receptors, and mount resistance against the intruders, with the help of well-elaborated defense arsenal. In response to some localinfections, plants develop systemic acquired resistance (SAR), which provides heightened resistance during subsequent infections. Infected tissues generate mobile signaling molecules that travel to the systemic tissues, where they epigenetically modify expression o a set of genes to initiate the manifestation of SAR in distant tissues. Immune responses are largely regulated at transcriptional level. Flowering is a developmental transition that occurs as a result of the coordinated action of large numbers of transcription factors that respond to intrinsic signals and environmental conditions. The plant hormone salicylic acid (SA) which is required for SAR activation positively regulates flowering. Certain components of chromatin remodeling complexes that are recruited for suppression of precocious flowering are also involved in suppression of SAR in healthy plants. FLOWERING LOCUS D, a putative histone demethylase positively regulates SAR manifestation and flowering transition in Arabidopsis. Similarly, incorporation of histone variant H2A.Z in nucleosomes mediated by PHOTOPERIOD-INDEPENDENT EARLY FLOWERING 1, an ortholog of yeast chromatin remodeling complex SWR1, concomitantly influences SAR and flowering time. SUMO conjugation and deconjugation mechanisms also similarly affect SAR and flowering in an SA-dependent manner. The evidences suggest a common underlying regulatory mechanism for activation of SAR and flowering in plants.

  1. Arabidopsis Auxin Mutants Are Compromised in Systemic Acquired Resistance and Exhibit Aberrant Accumulation of Various Indolic Compounds1[W][OA

    PubMed Central

    Truman, William M.; Bennett, Mark H.; Turnbull, Colin G.N.; Grant, Murray R.

    2010-01-01

    Systemic acquired resistance is a widespread phenomenon in the plant kingdom that confers heightened and often enduring immunity to a range of diverse pathogens. Systemic immunity develops through activation of plant disease resistance protein signaling networks following local infection with an incompatible pathogen. The accumulation of the phytohormone salicylic acid in systemically responding tissues occurs within days after a local immunizing infection and is essential for systemic resistance. However, our knowledge of the signaling components underpinning signal perception and the establishment of systemic immunity are rudimentary. Previously, we showed that an early and transient increase in jasmonic acid in distal responding tissues was central to effective establishment of systemic immunity. Based upon predicted transcriptional networks induced in naive Arabidopsis (Arabidopsis thaliana) leaves following avirulent Pseudomonas syringae challenge, we show that a variety of auxin mutants compromise the establishment of systemic immunity. Linking together transcriptional and targeted metabolite studies, our data provide compelling evidence for a role of indole-derived compounds, but not auxin itself, in the establishment and maintenance of systemic immunity. PMID:20081042

  2. Impact detection using ultrasonic waves based on artificial immune system

    NASA Astrophysics Data System (ADS)

    Okamoto, Keisuke; Mita, Akira

    2009-03-01

    This paper presents a structural health monitoring system for judging structural condition of metallic plates by analyzing ultrasonic waves. Many critical accidents of structures like buildings and aircrafts are caused by small structural errors; cracks and loosened bolts etc. This is a reason why we need to detect little errors at an early stage. Moreover, to improve precision and to reduce cost for damage detection, it is necessary to build and update the database corresponding to environmental change. This study focuses our attention on the automatable structures, specifically, applying artificial immune system (AIS) algorithm to determine the structure safe or not. The AIS is a novelty computational detection algorithm inspired from biological defense system, which discriminates between self and non-self to reject nonself cells. Here, self is defined to be normal data patterns and non-self is abnormal data patterns. Furthermore, it is not only pattern recognition but also it has a storage function. In this study, a number of impact resistance experiments of duralumin plates, with normal structural condition and abnormal structural condition, are examined and ultrasonic waves are acquired by AE sensors on the surface of the aluminum plates. By accumulating several feature vectors of ultrasonic waves, a judging method, which can determine an abnormal wave as nonself, inspired from immune system is created. The results of the experiments show good performance of this method.

  3. Metabolomic analysis reveals the relationship between AZI1 and sugar signaling in systemic acquired resistance of Arabidopsis.

    PubMed

    Wang, Xiao-Yan; Li, Dian-Zhen; Li, Qi; Ma, Yan-Qin; Yao, Jing-Wen; Huang, Xuan; Xu, Zi-Qin

    2016-10-01

    The function of AZI1 in systemic acquired resistance of Arabidopsis was confirmed by investigation of the phenotypic features of wild-type Col-0, AZI1 T-DNA knockout and AZI1 overexpressing plants after infection with virulent and avirulent Pseudomonas syringae. Real-time quantitative PCR and Northern blotting analyses showed that the transcript abundances of PR genes increased significantly in local and systemic leaves of wild-type Col-0 and AZI1 overexpressing plants challenged with avirulent P. syringae, whereas the mRNA accumulation of PR genes was obviously attenuated in local and systemic leaves of AZI1 T-DNA knockout plants after localized infiltration with avirulent Psm avrRpm1. The changes of metabolomic profiles in distal leaves of three types of materials infected with avirulent P. syringae were determined by (1)H NMR spectrometry and data mining showed that the soluble carbonhydrates might function as signal substances in the systemic immunity of Arabidopsis. At the same time, the expression of the sugar signaling genes in local and distal leaves after infection of avirulent P. syringae was compared. As a result, it was found that the transcript abundances of sugar signaling genes, including SUS1, SUS2, SUS3, SUS6, SUT1, HXK1, HXK2, SNRK1.2, ERD6, TPS1, TOR, SNRK1.1, SNRK1.3 and bZIP11, were obviously changed in distal leaves of different materials with the modulated AZI1 activities, indicating sugar-related genes are involved in regulation of the systemic immunity mediated by AZI1. These results also illustrated that the immune system associated with sugar molecules probably was an important part of the systemic acquired resistance in Arabidopsis.

  4. 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.

  5. 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

  6. Interactions between the immune and nervous systems in pain

    PubMed Central

    Ren, Ke; Dubner, Ronald

    2010-01-01

    Immune cells and glia interact with neurons to alter pain sensitivity and to mediate the transition from acute to chronic pain. In response to injury, resident immune cells are activated and blood-borne immune cells are recruited to the site of injury. Immune cells not only contribute to immune protection but also initiate the sensitization of peripheral nociceptors. Through the synthesis and release of inflammatory mediators and interactions with neurotransmitters and their receptors, the immune cells, glia and neurons form an integrated network that coordinates immune responses and modulates the excitability of pain pathways. The immune system also reduces sensitization by producing immune-derived analgesic and anti-inflammatory or proresolution agents. A greater understanding of the role of the immune system in pain processing and modulation reveals potential targets for analgesic drug development and new therapeutic opportunities for managing chronic pain. PMID:20948535

  7. Transcutaneous immunization with Intercell's vaccine delivery system.

    PubMed

    Seid, Robert C; Look, Jee Loon; Ruiz, Christian; Frolov, Vladimir; Flyer, David; Schafer, Jason; Ellingsworth, Larry

    2012-06-19

    Transcutaneous immunization (TCI) has become an attractive alternate route of immunization due to increase understanding of the skin immune system and to recent technical innovations in skin patch delivery systems. Basic principles of TCI have been demonstrated in animal and human studies, covering a variety of bacterial, viral, and cancer diseases. At Intercell, we have advanced two major platforms of TCI: 1) a needle-free vaccine delivery patch (VDP) and 2) a vaccine enhancement patch (VEP). Simplified, the VDP contains an antigen with or without an adjuvant that is administered on the skin; while the VEP contains only the adjuvant and is used in combination with an injected vaccine. In many of our TCI studies, the VDP or VEP is routinely applied on pretreated skin, in which the stratum corneum has been partially removed by mild abrasion. Recently, we have achieved technical breakthroughs in formulating and stabilizing vaccines in a dry patch format. For instance, a microplate-based screening process has been implemented to rapidly identify excipients, singularly or in combination, to stabilize biological macromolecules in patch blend formulations. A second technical innovation is our nonwoven (patch) disc matrix-supported drying technology, which allows efficient drying of our patch formulation blend to produce dry stable dosage forms of VDP or VEP. The low cost and the facileness in the manufacturing of VDP (or VEP) combined with the development of thermostable dry patches should improve the supply chain efficiency and reduce the dependence on cold chain.

  8. How the innate immune system trains immunity: lessons from studying atopic dermatitis and cutaneous bacteria.

    PubMed

    Skabytska, Yuliya; Kaesler, Susanne; Volz, Thomas; Biedermann, Tilo

    2016-02-01

    The skin is the largest organ at the interface between environment and host. It plays a major protective role against pathogens as physical barrier, as site of first recognition, and as orchestrator of consecutive immune responses. In this process, immunological crosstalk between skin-resident and immune cells is required, and fixed innate immune responses were previously believed to orchestrate adaptive immunity of B and T lymphocytes. Today, we understand that diverse qualities of immune responses to different microbes need to be regulated by also varying responses at the level of first microbe recognition through receptors of the innate immune system. Only fine-tuning of the innate immune system allows for the orchestration of immune responses to the microbiota in the absence of inflammation as well as to pathogens in the context of protective responses including inflammation. Understanding how innate immunity precisely adapts is also important for diseases such as atopic dermatitis (AD) with chronic inflammation. In this review, we present data on how the innate immune system actually fine-tunes its responses with special focus on the immunological consequences of cutaneous innate immune sensing through TLR2. These new insights are highly relevant for understanding microbiota-associated state of health, immune defense, and the pathogenesis underlying chronic cutaneous inflammation as seen in AD.

  9. 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.

  10. [Comment on the intervention of Traditional Chinese Medicine on survival rates of patients living with human immunodeficiency virus and acquired immune deficiency syndrome].

    PubMed

    Li, Qiang; Liu, Zhibin; Yang, Jiping; Guo, Huijun; Xu, Liran

    2016-06-01

    Despite many differences between Traditional Chinese Medicine (TCM) and conventional medicine, the use of TCM in the treatment of human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is increasingly recognized and accepted by patients. Recent research findings on the benefits of Chinese herbal medicine on long-term survival in patients with HIV/AIDS are encouraging and hopeful, but inconclusive. More research is needed.

  11. Autonomously acquiring declarative and procedural knowledge for ICAT systems

    NASA Technical Reports Server (NTRS)

    Kovarik, Vincent J., Jr.

    1993-01-01

    The construction of Intelligent Computer Aided Training (ICAT) systems is critically dependent on the ability to define and encode knowledge. This knowledge engineering effort can be broadly divided into two categories: domain knowledge and expert or task knowledge. Domain knowledge refers to the physical environment or system with which the expert interacts. Expert knowledge consists of the set of procedures and heuristics employed by the expert in performing their task. Both these areas are a significant bottleneck in the acquisition of knowledge for ICAT systems. This paper presents a research project in the area of autonomous knowledge acquisition using a passive observation concept. The system observes an expert and then generalizes the observations into production rules representing the domain expert's knowledge.

  12. 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

  13. The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA): what is the future of pneumococcal conjugate vaccination in elderly?

    PubMed

    van Werkhoven, Cornelis H; Bonten, Marc J M

    2015-01-01

    Pneumococcal community-acquired pneumonia (PCAP) and invasive pneumococcal disease (IPD) are important causes of morbidity and mortality in elderly. In the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a randomized double-blind placebo-controlled trial of 84,496 community-dwelling immunocompetent adults over 65 years of age, the 13-valent pneumococcal conjugate vaccine (PCV13) reduced the incidence of first episode of vaccine-type (VT) PCAP with 38 and of VT-IPD with 76% in the modified intention-to-treat population. In The Netherlands, where PCV7 immunization of newborns was introduced in 2007 and replaced by PCV10 in 2011, introduction of PCV13 immunization of elderly--based on 2012 data--would be highly cost effective. However, this is probably different in countries where the VT disease burden has declined more, for instance due to herd effects following child immunization with PCV13. Apart from cost-effectiveness analyses, ethical aspects of PCAP prevention should be taken into account in policy making for pneumococcal vaccination in elderly.

  14. 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...

  15. 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.

  16. 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.

  17. HIV infection and the gastrointestinal immune system

    PubMed Central

    Brenchley, JM; Douek, DC

    2009-01-01

    There has recently been a resurgence of interest in the gastrointestinal pathology observed in patients infected with HIV. The gastrointestinal tract is a major site of HIV replication, which results in massive depletion of lamina propria CD4 T cells during acute infection. Highly active antiretroviral therapy leads to incomplete suppression of viral replication and substantially delayed and only partial restoration of gastrointestinal CD4 T cells. The gastrointestinal pathology associated with HIV infection comprises significant enteropathy with increased levels of inflammation and decreased levels of mucosal repair and regeneration. Assessment of gut mucosal immune system has provided novel directions for therapeutic interventions that modify the consequences of acute HIV infection. PMID:19079157

  18. 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

  19. 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.

  20. 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.

  1. Systemic and central immunity in Alzheimer's disease: therapeutic implications.

    PubMed

    Butchart, Joseph; Holmes, Clive

    2012-01-01

    Clinical pharmaceutical trials aimed at modulating the immune system in Alzheimer's Disease have largely focused on either dampening down central proinflammatory innate immunity or have manipulated adaptive immunity to facilitate the removal of centrally deposited beta amyloid. To date, these trials have had mixed clinical therapeutic effects. However, a number of clinical studies have demonstrated disturbances of both systemic and central innate immunity in Alzheimer's Disease and attention has been drawn to the close communication pathways between central and systemic immunity. This paper highlights the need to take into account the potential systemic effects of drugs aimed at modulating central immunity and the possibility of developing novel therapeutic approaches based on the manipulation of systemic immunity and its communication with the central nervous system.

  2. The intriguing mission of neuropeptide Y in the immune system.

    PubMed

    Dimitrijević, Mirjana; Stanojević, Stanislava

    2013-07-01

    For many years, the central nervous system and the immune system were considered two autonomous entities. However, extensive research in the field of neuroimmunomodulation during the past decades has demonstrated the presence of different neuropeptides and their respective receptors in the immune cells. More importantly, it has provided evidence for the direct effects of neuropeptides on the immune cell functions. Neuropeptide Y (NPY) is generally considered the most abundant peptide in the central and peripheral nervous system. However, it is also distinguished by exhibiting pleiotropic functions in many other physiological systems, including the immune system. NPY affects the functions of the cells of the adaptive and innate immunity. In this respect, NPY is known to modulate immune cell trafficking, T helper cell differentiation, cytokine secretion, natural killer cell activity, phagocytosis and the production of reactive oxygen species. The specific Y receptors have been found in immune cells, and their expression is amplified upon immune stimulation. Different Y receptor subtypes may mediate an opposite effect of NPY on the particular function, thus underlining its regulatory role. Since the immune cells are capable of producing NPY upon appropriate stimulation, this peptide can regulate immune cell functions in an autocrine/paracrine manner. NPY also has important implications in several immune-mediated disorders, which affirms the clear need for further investigation of its role in either the mechanisms of the disease development or its possible therapeutic capacity. This review summarises the key points of NPY's mission throughout the immune system.

  3. Prognostic score systems and community-acquired bacteraemic pneumococcal pneumonia.

    PubMed

    Spindler, C; Ortqvist, A

    2006-10-01

    The aim of this study was to evaluate the accuracy of three score systems: the pneumonia severity index (PSI); CURB-65 (confusion; urea >7 mM; respiratory rate > or =30 breaths x min(-1); blood pressure <90 mmHg systolic or < or =60 mmHg diastolic; aged > or =65 yrs old); and modified American Thoracic Society rule for predicting intensive care unit (ICU) need and mortality due to bacteraemic pneumococcal pneumonia. All adult patients (n = 114) with invasive pneumococcal pneumonia at the Karolinska University Hospital, Sweden, 1999-2000, were included in the study. Severity scores were calculated and the independent prognostic importance of different variables was analysed by multiple regression analyses. PSI > or = IV, CURB-65 > or = 2, and the presence of one major or more than one minor risk factor in mATS all had a high sensitivity, but somewhat lower specificity for predicting death and ICU need. The death rate was 12% (13 out of 114). Severity score and treatment in departments other than the Dept of Infectious Diseases were the only factors independently correlated to death. Patients treated in other departments more often had severe underlying illnesses and were more severely ill on admission. However, a significant difference in death rates remained after adjustment for severity between the two groups. In conclusion, all score systems were useful for predicting the need for intensive care unit treatment and death due to bacteremic pneumococcal pneumonia. The pneumonia severity index was the most sensitive, but CURB-65 was easier to use.

  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Effect of bacillus Calmette-Guérin vaccination on CD4+Foxp3+ T cells during acquired immune response to Mycobacterium tuberculosis infection.

    PubMed

    Henao-Tamayo, Marcela I; Obregón-Henao, Andres; Arnett, Kimberly; Shanley, Crystal A; Podell, Brendan; Orme, Ian M; Ordway, Diane J

    2016-04-01

    Increasing information has shown that many newly emerging strains of Mycobacterium tuberculosis, including the highly prevalent and troublesome Beijing family of strains, can potently induce the emergence of Foxp3(+)CD4 Tregs Although the significance of this is still not fully understood, we have previously provided evidence that the emergence of this population can significantly ablate the protective effect of BCG vaccination, causing progressive fatal disease in the mouse model. However, whether the purpose of this response is to control inflammation or to directly dampen the acquired immune response is still unclear. In the present study, we have shown, using both cell depletion and adoptive transfer strategies, that Tregs can have either properties. Cell depletion resulted in a rapid, but transient, decrease in the lung bacterial load, suggesting release or temporary re-expansion of effector immunity. Transfer of Tregs into Rag2(-/-)or marked congenic mice worsened the disease course and depressed cellular influx of effector T cells into the lungs. Tregs from infected donors seemed to preferentially depress the inflammatory response and granulocytic influx. In contrast, those from BCG-vaccinated and then challenged donors seemed more focused on depression of acquired immunity. These qualitative differences might be related to increasing knowledge reflecting the plasticity of the Treg response.

  9. 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.

  10. Immunizing digital systems against electromagnetic interference

    NASA Astrophysics Data System (ADS)

    Ewing, P. D.; Korsah, K.; Antonescu, C.

    This paper discusses the development of the technical basis for acceptance criteria applicable to the immunization of digital systems against electromagnetic interference (EMI). The work is sponsored by the US Nuclear Regulatory Commission and stems from the safety-related issues that need to be addressed as a result of the application of digital instrumentation and control systems in nuclear power plants. Designers of digital circuits are incorporating increasingly higher clock frequencies and lower logic level voltages, thereby leading to potentially greater susceptibility of spurious interference being misinterpreted as legitimate logic. Development of the technical basis for acceptance criteria to apply to these digital systems centers around establishing good engineering practices to ensure that sufficient levels of electromagnetic compatibility (EMC) are maintained between the nuclear power plant's electronic and electromechanical systems. First, good EMC design and installation practices are needed to control the emissions from interference sources and thereby their impact on other nearby circuits and systems. Secondly, a test and evaluation program is needed to outline the EMI tests to be performed, the associated test methods to be followed, and adequate test limits to ensure that the circuit or system under test meets the recommended guidelines. Test and evaluation should be followed by periodic maintenance to assess whether the recommended EMI control practices continue to be adhered to as part of the routine operation of the nuclear power plant. By following these steps, the probability of encountering safety-related instrumentation problems associated with EMI will be greatly reduced.

  11. 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.

  12. Evolution of adaptive immunity from transposable elements combined with innate immune systems.

    PubMed

    Koonin, Eugene V; Krupovic, Mart

    2015-03-01

    Adaptive immune systems in prokaryotes and animals give rise to long-term memory through modification of specific genomic loci, such as by insertion of foreign (viral or plasmid) DNA fragments into clustered regularly interspaced short palindromic repeat (CRISPR) loci in prokaryotes and by V(D)J recombination of immunoglobulin genes in vertebrates. Strikingly, recombinases derived from unrelated mobile genetic elements have essential roles in both prokaryotic and vertebrate adaptive immune systems. Mobile elements, which are ubiquitous in cellular life forms, provide the only known, naturally evolved tools for genome engineering that are successfully adopted by both innate immune systems and genome-editing technologies. In this Opinion article, we present a general scenario for the origin of adaptive immunity from mobile elements and innate immune systems.

  13. Chemical inducers of systemic immunity in plants.

    PubMed

    Gao, Qing-Ming; Kachroo, Aardra; Kachroo, Pradeep

    2014-04-01

    Systemic acquired resistance (SAR) is a highly desirable form of resistance that protects against a broad-spectrum of related or unrelated pathogens. SAR involves the generation of multiple signals at the site of primary infection, which arms distal portions against subsequent secondary infections. The last decade has witnessed considerable progress, and a number of chemical signals contributing to SAR have been isolated and characterized. The diverse chemical nature of these chemicals had led to the growing belief that SAR might involve interplay of multiple diverse and independent signals. However, recent results suggest that coordinated signalling from diverse signalling components facilitates SAR in plants. This review mainly discusses organized signalling by two such chemicals, glycerol-3-phoshphate and azelaic acid, and the role of basal salicylic acid levels in G3P-conferred SAR.

  14. Systemic acquired resistance (50 years after discovery): moving from the lab to the field.

    PubMed

    Gozzo, Franco; Faoro, Franco

    2013-12-26

    Induction of plant defense(s) against pathogen challenge(s) has been the object of progressively more intense research in the past two decades. Insights on mechanisms of systemic acquired resistance (SAR) and similar, alternative processes, as well as on problems encountered on moving to their practical application in open field, have been carefully pursued and, as far as possible, defined. In reviewing the number of research works published in metabolomic, genetic, biochemical, and crop protection correlated disciplines, the following outline has been adopted: 1, introduction to the processes currently considered as models of the innate immunity; 2, primary signals, such as salicylic acid (SA), jasmonic acid (JA), and abscisic acid (ABA), involved with different roles in the above-mentioned processes; 3, long-distance signals, identified from petiole exudates as mobile signaling metabolites during expressed resistance; 4, exogenous inducers, including the most significant chemicals known to stimulate the plant resistance induction and originated from both synthetic and natural sources; 5, fungicides shown to act as stimulators of SAR in addition to their biocidal action; 6, elusive mechanism of priming, reporting on the most recent working hypotheses on the pretranscriptional ways through which treated plants may express resistance upon pathogen attack and how this resistance can be transmitted to the next generation; 7, fitness costs and benefits of SAR so far reported from field application of induced resistance; 8, factors affecting efficacy of induced resistance in the open field, indicating that forces, unrevealed under controlled conditions, may be operative in the field; 9, concluding remarks address the efforts required to apply the strategy of crop resistance induction according to the rules of integrated pest management.

  15. Neuroendocrine and immune system responses with spaceflights.

    PubMed

    Tipton, C M; Greenleaf, J E; Jackson, C G

    1996-08-01

    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), aldosterone, 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-flights data indicates immunoglobulin concentrations are not significantly changed from pre-flight measurements. However, the numbers of T

  16. 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

  17. Severe Community-Acquired Pneumonia with Bacteremia Caused by Herbaspirillum aquaticum or Herbaspirillum huttiense in an Immune-Competent Adult

    PubMed Central

    Kimball, Joanna; Smith, L. Patrick; Salzer, William

    2015-01-01

    Herbaspirillum spp. are Gram-negative bacteria that inhabit soil and water. Infections caused by these organisms have been reported in immunocompromised hosts. We describe severe community-acquired pneumonia and bacteremia caused by Herbaspirillum aquaticum or H. huttiense in an immunocompetent adult male. PMID:26179298

  18. A Case of Mycobacterium riyadhense in an Acquired Immune Deficiency Syndrome (AIDS) Patient with a Suspected Paradoxical Response to Antituberculosis Therapy

    PubMed Central

    Badreddine, Samar Assem

    2016-01-01

    A 30-year-old male patient with acquired immune deficiency syndrome (AIDS) on highly active antiretroviral therapy (HAART) presented with clinical picture suggestive of pulmonary tuberculosis. He was commenced on antituberculosis therapy (ATT) with signs of improvement. Then he developed cervical lymph node abscess which was drained. Steroid was started for presumed paradoxical response to ATT which results in clinical regression. The culture result revealed Mycobacterium riyadhense. This report addresses the rarity of this bacteria in medical literature. It reviews clinical presentations and medical treatment particularly in the setting of coinfections. PMID:27703819

  19. Trauma equals danger—damage control by the immune system

    PubMed Central

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

    2012-01-01

    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. PMID:22654121

  20. CD4+ T cell-dependent acquired state of immunity that protects the brain against Cryptococcus neoformans.

    PubMed

    Hill, J O; Aguirre, K M

    1994-03-01

    In immunodeficient hosts, a failure in defense mechanisms allows Cryptococcus neoformans to establish foci of infection in the brain. Immune and nonspecific responses in the primary site of infection in the lung have been described, but those extrapulmonary defense mechanisms that can be mobilized against the yeast have received little attention. This paper describes a response expressed against yeast in the brain of immunocompetent hosts, a response that is weakened in hosts deficient in CD4+ T cells. When a small number of yeast gain access to the vasculature, for example through an i.v. injection, about 0.1% establish themselves in the brain. Normal mice but not SCID mice have the capacity to suppress the multiplication of these yeast cells. The host response is accelerated in mice that are recovering from a primary lung infection, resulting in long term survival without antibiotic chemotherapy. This response is ablated by anti-CD4 mAb treatment and CD4+ cells obtained from infected primed donors are needed to confer immunity on SCID recipients. The critical target for the anti-Cryptococcus immune response are yeast in the brain cortex. However, rather than preventing the colonization of the brain by blood-borne yeast, immunity apparently serves to restrict the growth of yeast in a small number of established foci.

  1. Influence of the home environment on the prevention of mother to child transmission of human immunodeficiency virus/acquired immune-deficiency syndrome in South Africa.

    PubMed

    Sewnunan, A; Modiba, L M

    2015-01-01

    The human immunodeficiency virus and acquired immune-deficiency syndrome (HIV/AIDS) is still a 'family crises' which marks the beginning of the deterioration of the family unit and the trauma in the emotional, psychological and material lives of both the mother and child. In South African context where the majority of HIV-positive mothers are young single women who live in extended families, disclosure to the sexual partner alone is not an adequate condition for the success of prevention of mother to child transmission (PMTCT). In South Africa, close to one in three women who attend antenatal clinics are HIV positive. KwaZulu-Natal is one of the worst affected provinces, where as many as 40-60% of pregnant women attending antenatal services are living with HIV infection. The study sought to investigate the link between the home environment and its contribution to the success of the programme on PMTCT of HIV/AIDS. A qualitative, explorative, descriptive and contextual study was used in this study to explore whether the home environment for the support system is available for the HIV-positive women on the PMTCT programme. The population of this study included all women who have undergone counselling and tested HIV positive and who have joined the programme on PMTCT of HIV/AIDS in a specific hospital in KwaZulu-Natal Province. Although 14 women agreed to participate in the study, only 10 women were interviewed as saturation was attained. Data were collected using semi-structured interview schedule. Interviews were audio-taped and field notes were taken. Content analysis was used and it was done manually. This study revealed that one of the major issues still surrounding HIV/AIDS and PMTCT is that of non-disclosure, selective disclosure and the stigma and discrimination that surrounds this disease. PMID:26694631

  2. Influence of the home environment on the prevention of mother to child transmission of human immunodeficiency virus/acquired immune-deficiency syndrome in South Africa.

    PubMed

    Sewnunan, A; Modiba, L M

    2015-01-01

    The human immunodeficiency virus and acquired immune-deficiency syndrome (HIV/AIDS) is still a 'family crises' which marks the beginning of the deterioration of the family unit and the trauma in the emotional, psychological and material lives of both the mother and child. In South African context where the majority of HIV-positive mothers are young single women who live in extended families, disclosure to the sexual partner alone is not an adequate condition for the success of prevention of mother to child transmission (PMTCT). In South Africa, close to one in three women who attend antenatal clinics are HIV positive. KwaZulu-Natal is one of the worst affected provinces, where as many as 40-60% of pregnant women attending antenatal services are living with HIV infection. The study sought to investigate the link between the home environment and its contribution to the success of the programme on PMTCT of HIV/AIDS. A qualitative, explorative, descriptive and contextual study was used in this study to explore whether the home environment for the support system is available for the HIV-positive women on the PMTCT programme. The population of this study included all women who have undergone counselling and tested HIV positive and who have joined the programme on PMTCT of HIV/AIDS in a specific hospital in KwaZulu-Natal Province. Although 14 women agreed to participate in the study, only 10 women were interviewed as saturation was attained. Data were collected using semi-structured interview schedule. Interviews were audio-taped and field notes were taken. Content analysis was used and it was done manually. This study revealed that one of the major issues still surrounding HIV/AIDS and PMTCT is that of non-disclosure, selective disclosure and the stigma and discrimination that surrounds this disease.

  3. 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.

  4. Arabidopsis TTR1 causes LRR-dependent lethal systemic necrosis, rather than systemic acquired resistance, to Tobacco ringspot virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most Arabidopsis ecotypes display tolerance to the Tobacco ringspot virus (TRSV), but a subset of Arabidopsis ecotypes, including Estland (Est), develop lethal systemic necrosis (LSN), which differs from the localized hypersensitive responses (HRs) or systemic acquired resistance (SAR) characteristi...

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

    PubMed

    Hato, Takashi; Dagher, Pierre C

    2015-08-01

    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.

  6. Effect of Recombination in the Evolutionary Dynamics of HIV under the Surveillance of Immune System

    NASA Astrophysics Data System (ADS)

    Peng, Weiqun; Yang, Wenjing; Wang, Guanyu

    2009-03-01

    Human immunodeficiency virus (HIV) is a retrovirus that causes acquired immunodeficiency syndrome (AIDS), which has become one of the most destructive pandemics in history. The fact that HIV virus evolves very fast plays a central role in AIDS immunopathogenesis and the difficulty we face in finding a cure or a vaccine for AIDS. A distinguishing feature of HIV is its high frequency of recombination. The effect of recombination in the HIV evolution is not clear. We establish a mathematical model of the evolutionary dynamics. This model incorporates both point mutation and recombination for genetic diversity, and employs a fitness function developed by Wang and Deem (PRL 97, 188106, 2006) that accounts for the effect of immune system. Using this model, we explore the role of recombination in the battle between the virus population and the immune system, with a special focus on the condition under which recombination helps the virus population to escape from the immune system.

  7. Acquired dyslexia in three writing systems: study of a Portuguese-Japanese bilingual aphasic patient.

    PubMed

    Senaha, Mirna Lie Hosogi; de Mattos Pimenta Parente, Maria Alice

    2012-01-01

    The Japanese language is represented by two different codes: syllabic and logographic while Portuguese employs an alphabetic writing system. Studies on bilingual Portuguese-Japanese individuals with acquired dyslexia therefore allow an investigation of the interaction between reading strategies and characteristics of three different writing codes. The aim of this study was to examine the differential impact of an acquired brain lesion on the reading of the logographic, syllabic and alphabetic writing systems of a bilingual Portuguese-Japanese aphasic patient (PF). Results showed impaired reading in the logographic system and when reading irregularly spelled Portuguese words but no effects on reading regular words and nonwords in syllabic and alphabetic writing systems. These dissociations are interpreted according to a multi-route cognitive model of reading assuming selective damage in the lexical route can result in acquired dyslexia across at least three different writing codes.

  8. When Unbiased Probabilistic Learning Is Not Enough: Acquiring a Parametric System of Metrical Phonology

    ERIC Educational Resources Information Center

    Pearl, Lisa S.

    2011-01-01

    Parametric systems have been proposed as models of how humans represent knowledge about language, motivated in part as a way to explain children's rapid acquisition of linguistic knowledge. Given this, it seems reasonable to examine if children with knowledge of parameters could in fact acquire the adult system from the data available to them.…

  9. Is central nervous system an immune-privileged site?

    PubMed

    Shrestha, R; Millington, O; Brewer, J; Bushell, T

    2013-01-01

    The central nervous system (CNS) was once considered to be an immune-privileged area. However, increasing evidence shows that the central nervous system is not an immune-privileged but is an active surveillance site. There is a bi-directional communication between the central nervous system and immune system. Normally, immune cells migrate into the central nervous system microenvironment through choroid plexus and interact with the central nervous system resident cells through either through neuromediators or immunomediators. This finding has led to a significant interest in neuroimmunological interactions and investigation onto the role of the immune system in the pathology of various neurological disorders and examine whether it can be targeted to produce novel therapeutic strategies. PMID:23774427

  10. 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. PMID:27664815

  11. 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.

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

    PubMed

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

    2014-05-01

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

  13. Bacteria-triggered systemic immunity in barley is associated with WRKY and ETHYLENE RESPONSIVE FACTORs but not with salicylic acid.

    PubMed

    Dey, Sanjukta; Wenig, Marion; Langen, Gregor; Sharma, Sapna; Kugler, Karl G; Knappe, Claudia; Hause, Bettina; Bichlmeier, Marlies; Babaeizad, Valiollah; Imani, Jafargholi; Janzik, Ingar; Stempfl, Thomas; Hückelhoven, Ralph; Kogel, Karl-Heinz; Mayer, Klaus F X; Vlot, A Corina

    2014-12-01

    Leaf-to-leaf systemic immune signaling known as systemic acquired resistance is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to systemic acquired resistance in Arabidopsis (Arabidopsis thaliana), systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid. Instead, we documented a moderate local but not systemic induction of abscisic acid after infection of leaves with Psj. In contrast to salicylic acid or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or abscisic acid triggered systemic immunity to Xtc. RNA sequencing analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest, and quantitative reverse transcription-polymerase chain reaction associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR (ERF)-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors, possibly facilitating transcriptional reprogramming to potentiate immunity.

  14. A national surveillance system for newly acquired HIV infection in Australia. National HIV Surveillance Committee.

    PubMed Central

    McDonald, A M; Gertig, D M; Crofts, N; Kaldor, J M

    1994-01-01

    OBJECTIVES. The purpose of this study was to describe the establishment of a national surveillance system for newly acquired human immunodeficiency virus (HIV) infection and present the first 3 years' results. METHODS. All new cases of diagnosed HIV infection were reported to the national HIV surveillance center through state and territory health authorities. Information sought on each case included evidence of whether the infection had been newly acquired, defined by the diagnosis of HIV seroconversion illness or by the report of a negative or indeterminate HIV antibody test result occurring within the 12 months prior to diagnosis of infection. RESULTS. Of 3602 reported cases of HIV infection in adults and adolescents newly diagnosed in Australia between 1991 and 1993, 11.4% were identified as newly acquired. The majority (85%) of cases of newly diagnosed HIV infection occurred among men who reported homosexual contact, and 15% of these cases were identified as newly acquired. Average age at diagnosis was 31 years for cases of newly acquired infection and 34 years for other cases. CONCLUSIONS. Surveillance for newly acquired HIV infection has been established at a national level in Australia and provides valuable information for planning primary HIV prevention programs. PMID:7998631

  15. 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

  16. 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. PMID:26619012

  17. 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.

  18. Impairment of the immune system in GH-overexpressing transgenic zebrafish (Danio rerio).

    PubMed

    Batista, Carolina R; Figueiredo, Márcio A; Almeida, Daniela V; Romano, Luis A; Marins, Luis F

    2014-02-01

    Growth hormone (GH) is an important regulator of immune functions in vertebrates, and it has been intensively reported a series of stimulatory actions of this hormone over on the immune system. Within aquaculture, overexpression of GH has been considered a promising alternative for promoting higher growth rates in organisms of commercial interest. Considering the various pleiotropic effects of GH, there are still few studies that aim to understand the consequences of the excess of GH on the physiological systems. In this context, our goal was to present the effects of the overexpression of GH on immune parameters using a model of zebrafish (Danio rerio) that overexpress this hormone. The results showed that GH transgenic zebrafish had 100% of mortality when immunosuppressed with dexamethasone, revealing a prior weakening of the immune system in this lineage. Morphometric analysis of thymus and head kidney revealed a reduction in the area of these structures in transgenic zebrafish. Moreover, the phenotypic expression of CD3 and CD4 thymocytes was also depreciated in transgenic zebrafish. Furthermore, a decrease was noted in the expression of genes RAG-1 (60%), IKAROS (50%), IL-1β (55%), CD4 (60%) and CD247 (40%), indicating that development parameters, of innate and acquired immunity, are being harmed. Based on these results, it can be concluded that the excess of GH impairs the immune functions in GH transgenic zebrafish, indicating that the maintenance of normal levels of this hormone is essential for the functioning of immunological activities.

  19. 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

  20. 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.

  1. Generation of Individual Diversity: A Too Neglected Fundamental Property of Adaptive Immune System

    PubMed Central

    Muraille, Eric

    2014-01-01

    The fitness gains resulting from development of the adaptive immune system (AIS) during evolution are still the subject of hot debate. A large random repertoire of antigenic receptors is costly to develop and could be the source of autoimmune reactions. And yet, despite their drawbacks, AIS-like systems seem to have been independently acquired in several phyla of metazoans with very different anatomies, longevities, and lifestyles. This article is a speculative attempt to explore the selective pressures, which favored this striking convergent evolution. It is well known that the AIS enables an organism to produce a specific immune response against all natural or artificial antigenic structures. However, it is frequently neglected that this response is highly variable among individuals. In practice, each individual possesses a “private” adaptive immune repertoire. This individualization of immune defenses implies that invasion and escape immune mechanisms developed by pathogens will certainly not always be successful as the specific targets and organization of the immune response are somewhat unpredictable. In a population, where individuals display heterogeneous immune responses to infection, the probability that a pathogen is able to infect all individuals could be reduced compared to a homogeneous population. This suggests that the individual diversity of the immune repertoire is not a by-product of the AIS but of its fundamental properties and could be in part responsible for repeated selection and conservation of the AIS during metazoan evolution. The capacity of the AIS to improve the management of cooperative or parasitic symbiotic relationships at the individual level could be a secondary development due to its progressive integration into the innate immune system. This hypothesis constitutes a new scenario for AIS emergence and explains the selection of MHC restriction and MHC diversification. PMID:24860570

  2. Leucocyte profiles and H/L ratios in chicks of Red-tailed Tropicbirds reflect the ontogeny of the immune system.

    PubMed

    Dehnhard, Nina; Quillfeldt, Petra; Hennicke, Janos C

    2011-07-01

    Immune defence is fundamentally important for the survival prospects of young animals. While innate immunity offers initial protection from a variety of pathogens, acquired immunity responds more specifically to pathogens, but is considered to be more costly and to respond slower. Moreover, the acquired immunity is not yet fully developed in neonatal chicks. Little is known about the ontogeny of the immune system of wild birds. Long-lived seabirds, with their slow chick development, are good models to investigate how young birds invest in both arms of their immune system. We determined leucocyte profiles and heterophil to lymphocyte (H/L) ratios of Red-tailed Tropicbirds (Phaeton rubricauda westralis) on Christmas Island, Indian Ocean. Young chicks (N = 10) had significantly higher H/L ratios than older chicks (N = 19), while adults (N = 47) showed intermediate values and did not differ from either chick age class. High H/L ratios in young chicks were caused by high initial numbers of heterophils per 10,000 erythrocytes that declined with age. In contrast, the number of lymphocytes per 10,000 erythrocytes was similar for young and older chicks. These data suggest that young chicks invested heavily in innate immunity to protect themselves from pathogens, while investment into acquired immunity became more important in older chicks with a functional acquired immune response. Body condition did not have a significant influence on any leucocyte parameter.

  3. Interactions between the gonadal steroids and the immune system.

    PubMed

    Grossman, C J

    1985-01-18

    The immune system is regulated by the gonadal steroids estrogen, androgen, and progesterone, but the circulating levels of these steroids can also be affected by immune system function. Such interactions appear to be mediated through the hypothalamic-pituitary-gonadal-thymic axis and depend on pituitary luteinizing hormone released by thymic factors under the control of the gonadal steroids.

  4. 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.

  5. 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

  6. Central Nervous System Immune Reconstitution Inflammatory Syndrome

    PubMed Central

    Boulware, David R.; Marais, Suzaan; Scriven, James; Wilkinson, Robert J.; Meintjes, Graeme

    2013-01-01

    Central nervous system immune reconstitution inflammatory syndrome (CNS-IRIS) develops in 9 %–47 % of persons with HIV infection and a CNS opportunistic infection who start antiretroviral therapy and is associated with a mortality rate of 13 %–75 %. These rates vary according to the causative pathogen. Common CNS-IRIS events occur in relation to Cryptococcus, tuberculosis (TB), and JC virus, but several other mycobacteria, fungi, and viruses have been associated with IRIS. IRIS symptoms often mimic the original infection, and diagnosis necessitates consideration of treatment failure, microbial resistance, and an additional neurological infection. These diagnostic challenges often delay IRIS diagnosis and treatment. Corticosteroids have been used to treat CNS-IRIS, with variable responses; the best supportive evidence exists for the treatment of TB-IRIS. Pathogenic mechanisms vary: Cryptococcal IRIS is characterized by a paucity of cerebrospinal inflammation prior to antiretroviral therapy, whereas higher levels of inflammatory markers at baseline predispose to TB meningitis IRIS. This review focuses on advances in the understanding of CNS-IRIS over the past 2 years. PMID:24173584

  7. Modulation of inflammatory pathways by the immune cholinergic system.

    PubMed

    Nizri, Eran; Brenner, Talma

    2013-07-01

    Research done in the past years pointed to a novel function of cholinergic transmission. It has been shown that cholinergic transmission can modulate various aspects of the immune function, whether innate or adaptive. Cholinergic transmission affects immune cell proliferation, cytokine production, T helper differentiation and antigen presentation. Theses effects are mediated by cholinergic muscarinic and nicotinic receptors and other cholinergic components present in immune cells, such as acetylcholinesterase (AChE) and cholineacetyltransferase. The α7 nicotinic acetylcholine receptor was designated anti-inflammatory activity and has shown promise in pre-clinical models of inflammatory disorders. We herein describe the various components of the immune cholinergic system, and specifically the immune suppressive effects of α7 activation. This activation can be accomplished either by direct stimulation or indirectly, by inhibition of AChE. Thus, the presence of the immune cholinergic system can pave the way for novel immunomodulatory agents, or to the broadening of use of known cholinergic agents.

  8. 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.

  9. CNS Remyelination and the Innate Immune System.

    PubMed

    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.

  10. Dust events, pulmonary diseases and immune system

    PubMed Central

    Esmaeil, Nafiseh; Gharagozloo, Marjan; Rezaei, Abbas; Grunig, Gabriele

    2014-01-01

    Incidences of sand storms have increased in recent years and there is evidence that these dusts can move across long distances. Sand dusts have different adverse effects on health, but one of the most important of them is pulmonary disease. After inhalation of dust, many dust particles are moved to the airways. Dust particles can be sensed by airways epithelial cells, activate macrophages, dendritic cells and innate immune cells and then initiate responses in various populations of specific immune cells such as T helper cells subsets (Th1, Th2, Th17), T cytotoxic cells and B cells. Initiation of inflammatory immune responses, activation of immune cells and releases of many cytokines, chemokines and other inflammatory molecules, have variable pathologic affects on lung in different respiratory diseases. Unfortunately control of desert dusts is more difficult than control of air pollution. For prevention and treatment of respiratory diseases that are caused by desert dusts, researchers need well-designed epidemiological studies, combined with analysis of the precise composition of sand dusts, and the precise mechanisms of the immune responses. Recognizing the exact cellular and molecular immune mechanisms would be very useful to find new approaches for treatment of desert dust associated pulmonary diseases. PMID:24660118

  11. 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.

  12. Multiple transport systems mediate virus-induced acquired resistance to oxidative stress

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this paper, we report the phenomenon of acquired cross-tolerance to oxidative (UV-C and H2O2) stress in Nicotiana benthamiana plants infected with Potato virus X (PVX) and investigate the functional expression of transport systems in mediating this phenomenon. By combining multiple approaches, we...

  13. Central nervous system infection due to Mycobacterium haemophilum in a patient with acquired immunodeficiency syndrome.

    PubMed

    Buppajarntham, Aubonphan; Apisarnthanarak, Anucha; Rutjanawech, Sasinuj; Khawcharoenporn, Thana

    2015-03-01

    Mycobacterium haemophilum is an environmental organism that rarely causes infections in humans. We report a patient with acquired immunodeficiency syndrome who had central nervous system infection due to M. haemophilum. The diagnosis required brain tissue procurement and molecular identification method while the treatment outcome was unfavourable.

  14. Immunization

    MedlinePlus

    ... a lot worse. Some are even life-threatening. Immunization shots, or vaccinations, are essential. They protect against things like measles, ... B, polio, tetanus, diphtheria, and pertussis (whooping cough). Immunizations are important for adults as well as children. ...

  15. Immunizations

    MedlinePlus

    ... How Can I Help a Friend Who Cuts? Immunizations KidsHealth > For Teens > Immunizations Print A A A ... That Shot? en español Las vacunas Why Are Vaccinations Important? Measles, mumps, and whooping cough may seem ...

  16. An Immunity-Based Anomaly Detection System with Sensor Agents

    PubMed Central

    Okamoto, Takeshi; Ishida, Yoshiteru

    2009-01-01

    This paper proposes an immunity-based anomaly detection system with sensor agents based on the specificity and diversity of the immune system. Each agent is specialized to react to the behavior of a specific user. Multiple diverse agents decide whether the behavior is normal or abnormal. Conventional systems have used only a single sensor to detect anomalies, while the immunity-based system makes use of multiple sensors, which leads to improvements in detection accuracy. In addition, we propose an evaluation framework for the anomaly detection system, which is capable of evaluating the differences in detection accuracy between internal and external anomalies. This paper focuses on anomaly detection in user's command sequences on UNIX-like systems. In experiments, the immunity-based system outperformed some of the best conventional systems. PMID:22291560

  17. 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.

  18. Method and system for calibrating acquired spectra for use in spectral analysis

    DOEpatents

    Reber, Edward L.; Rohde, Kenneth W.; Blackwood, Larry G.

    2010-09-14

    A method for calibrating acquired spectra for use in spectral analysis includes performing Gaussian peak fitting to spectra acquired by a plurality of NaI detectors to define peak regions. A Na and annihilation doublet may be located among the peak regions. A predetermined energy level may be applied to one of the peaks in the doublet and a location of a hydrogen peak may be predicted based on the location of at least one of the peaks of the doublet. Control systems for calibrating spectra are also disclosed.

  19. 12 CFR 617.7610 - What should the System institution do when it decides to sell acquired agricultural real estate?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... decides to sell acquired agricultural real estate? 617.7610 Section 617.7610 Banks and Banking FARM CREDIT... institution do when it decides to sell acquired agricultural real estate? (a) Notify the previous owner, (1) Within 15 days of the System institution's decision to sell acquired agricultural real estate, it...

  20. Genetic Regulation of Acquired Immune Responses to Antigens of Mycobacterium tuberculosis: a Study of Twins in West Africa

    PubMed Central

    Jepson, Annette; Fowler, Amanda; Banya, Winston; Singh, Mahavir; Bennett, Steve; Whittle, Hilton; Hill, Adrian V. S.

    2001-01-01

    The role of genetic factors in clinical tuberculosis is increasingly recognized; how such factors regulate the immune response to Mycobacterium tuberculosis in healthy individuals is unclear. In this study of 255 adult twin pairs residing in The Gambia, West Africa, it is apparent that memory T-cell responses to secreted mycobacterial antigens (85-kDa antigen complex, “short-term culture filtrate,” and peptides from the ESAT-6 protein), as well as to the 65-kDa heat shock protein, are subject to effective genetic regulation. The delayed hypersensitivity response to intradermal tuberculin also demonstrates significant genetic variance, while quantitative T-cell and antibody responses to the 38-kDa cell membrane protein appear to be determined largely by environmental factors. Such findings have implications for vaccine development. PMID:11349068

  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. Intensive care unit-acquired urinary tract infections in a regional critical care system

    PubMed Central

    Laupland, Kevin B; Bagshaw, Sean M; Gregson, Daniel B; Kirkpatrick, Andrew W; Ross, Terry; Church, Deirdre L

    2005-01-01

    Introduction Few studies have evaluated urinary tract infections (UTIs) specifically acquired within intensive care units (ICUs), and the effect of such infections on patient outcome is unclear. The objectives of this study were to describe the occurrence, microbiology, and risk factors for acquiring UTIs in the ICU and to determine whether these infections independently increase mortality. Methods A surveillance cohort study was conducted among all adults admitted to multi-system and cardiovascular surgery ICUs in the Calgary Health Region (CHR, population about 1 million) between 1 January 2000 and 31 December 2002. Results During the 3 years, 4465 patients were admitted 4915 times to a CHR ICU for 48 hours or more. A total of 356 ICU-acquired UTIs (defined as at least 105 colony-forming units/ml of one or two organisms 48 hours or more after ICU admission) occurred among 290 (6.5%) patients, yielding an overall incidence density of ICU-acquired UTIs of 9.6 per 1000 ICU days. Four bacteremic/fungemic ICU-acquired UTIs occurred (0.1 per 1000 ICU days). Development of an ICU-acquired UTI was more common in women (relative risk [RR] 1.58; 95% confidence interval [CI] 1.43–1.75; P < 0.0001) and in medical (9%) compared with non-cardiac surgical (6%), and cardiac surgical patients (2%). The most common organisms isolated were Escherichia coli (23%), Candida albicans (20%), and Enterococcus species (15%). Antibiotic-resistant organisms were identified among 14% isolates. Although development of an ICU-acquired UTI was associated with significantly higher crude in-hospital mortality (86/290 [30%] vs. 862/4167 [21%]; RR = 1.43; 95% CI 1.19–1.73; P < 0.001); an ICU-acquired UTI was not an independent predictor for death. Conclusions Development of an ICU-acquired UTI is common in critically ill patients. Although a marker of increased morbidity associated with critical illness, it is not a significant attributable cause of mortality. PMID:15774051

  3. Dynamic evolution of the innate immune system in Drosophila.

    PubMed

    Sackton, Timothy B; Lazzaro, Brian P; Schlenke, Todd A; Evans, Jay D; Hultmark, Dan; Clark, Andrew G

    2007-12-01

    The availability of complete genome sequence from 12 Drosophila species presents the opportunity to examine how natural selection has affected patterns of gene family evolution and sequence divergence among different components of the innate immune system. We have identified orthologs and paralogs of 245 Drosophila melanogaster immune-related genes in these recently sequenced genomes. Genes encoding effector proteins, and to a lesser extent genes encoding recognition proteins, are much more likely to vary in copy number across species than genes encoding signaling proteins. Furthermore, we can trace the apparent recent origination of several evolutionarily novel immune-related genes and gene families. Using codon-based likelihood methods, we show that immune-system genes, and especially those encoding recognition proteins, evolve under positive darwinian selection. Positively selected sites within recognition proteins cluster in domains involved in recognition of microorganisms, suggesting that molecular interactions between hosts and pathogens may drive adaptive evolution in the Drosophila immune system.

  4. 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.

  5. 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.

  6. Blowing on embers: commensal microbiota and our immune system.

    PubMed

    Spasova, Darina S; Surh, Charles D

    2014-01-01

    Vertebrates have co-evolved with microorganisms resulting in a symbiotic relationship, which plays an important role in health and disease. Skin and mucosal surfaces are colonized with a diverse population of commensal microbiota, over 1000 species, outnumbering the host cells by 10-fold. In the past 40 years, studies have built on the idea that commensal microbiota is in constant contact with the host immune system and thus influence immune function. Recent studies, focusing on mutualism in the gut, have shown that commensal microbiota seems to play a critical role in the development and homeostasis of the host immune system. In particular, the gut microbiota appears to direct the organization and maturation of lymphoid tissues and acts both locally and systemically to regulate the recruitment, differentiation, and function of innate and adaptive immune cells. While the pace of research in the area of the mucosal-immune interface has certainly intensified over the last 10 years, we are still in the early days of this field. Illuminating the mechanisms of how gut microbes shape host immunity will enhance our understanding of the causes of immune-mediated pathologies and improve the design of next-generation vaccines. This review discusses the recent advances in this field, focusing on the close relationship between the adaptive immune system and commensal microbiota, a constant and abundant source of foreign antigens.

  7. Natural selection on the Drosophila antimicrobial immune system.

    PubMed

    Lazzaro, Brian P

    2008-06-01

    The evolutionary dynamics of immune defenses have long attracted interest because of the special role the immune system plays in mediating the antagonistic interaction between hosts and pathogens. The antimicrobial immune system of the fruit fly Drosophila melanogaster is genetically well characterized and serves as a valuable model for studying insect and human innate immune defenses. I review here evolutionary and comparative genomic analyses of insect antimicrobial immune genes, with an emphasis on Drosophila. Core signal transduction pathways in the immune system are orthologously conserved across long evolutionary distances, but genes in these pathways evolve rapidly and adaptively at the amino acid sequence level. By contrast, families of genes encoding antimicrobial peptides are remarkably dynamic in genomic duplication and deletion, yet individual genes show little indication of adaptive sequence evolution. Pattern recognition receptors that trigger humoral immunity are evolutionarily rather static, but receptors required for phagocytosis show considerable genomic rearrangement and adaptive sequence divergence. The distinct evolutionary patterns exhibited by these various classes of immune system genes can be logically connected to the functions of the proteins they encode.

  8. 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.

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

    PubMed Central

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

    2014-01-01

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

  10. 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

  11. 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

  12. Unilateral acquired Brown's syndrome in systemic scleroderma: An unusual cause for diplopia

    PubMed Central

    Pawar, Neelam; Ravindran, Meenakshi; Ramakrishnan, Renagappa; Maheshwari, Devendra; Trivedi, Bhakti

    2015-01-01

    Brown's syndrome can be congenital or acquired with multiple causes. It has been described as a ocular complication in various rheumatic and nonrheumatic diseases. We describe a case of 27-year-old female patient with 5 years old history of systemic scleroderma who developed vertical diplopia, a left head tilt, and restriction of left eye on elevation in adduction. The patient responded to systemic steroids with resolution of diplopia. PMID:26669341

  13. Unilateral acquired Brown's syndrome in systemic scleroderma: An unusual cause for diplopia.

    PubMed

    Pawar, Neelam; Ravindran, Meenakshi; Ramakrishnan, Renagappa; Maheshwari, Devendra; Trivedi, Bhakti

    2015-11-01

    Brown's syndrome can be congenital or acquired with multiple causes. It has been described as a ocular complication in various rheumatic and nonrheumatic diseases. We describe a case of 27-year-old female patient with 5 years old history of systemic scleroderma who developed vertical diplopia, a left head tilt, and restriction of left eye on elevation in adduction. The patient responded to systemic steroids with resolution of diplopia. PMID:26669341

  14. Epidemiology of children with acquired immune deficiency syndrome (stage 3): A referral hospital-based study in Iran.

    PubMed

    Movahedi, Zahra; Mahmoudi, Shima; Pourakbari, Babak; Keshavarz Valian, Nasrin; Sabouni, Farah; Ramezani, Amitis; Bahador, Abbas; Mamishi, Setareh

    2016-01-01

    Lack of recognition of human immunodeficiency virus (HIV) infection especially in children and delayed implementation of effective control programs makes HIV infection as a major cause for concern. Information on HIV epidemiology in Iran as well as other Islamic countries is limited. The aim of our study was to describe the clinical manifestation and laboratory finding of HIV infected children who were admitted to a referral Children Medical Center (CMC) in Tehran, Iran, during 11 years from January 2002 to January 2013. This was a retrospective study carried out over a period of 11 years. The records of all patients attending to the CMC with confirmed acquired immunodeficiency syndrome (AIDS) were screened. The patients were evaluated for social circumstance, family history, age, gender, clinical, and laboratory features. Clinical data including fever, respiratory distress, diarrhea, rash, etc. as well as laboratory tests including complete blood count, serum glucose level, electrolytes, liver function test, cultures, CD4 lymphocyte count were evaluated. During the study period, 32 HIV positive children were enrolled. The majority of patients were presented with weight loss, prolonged fever, respiratory infection and chronic diarrhea. In this study, salmonella infections as well as streptococcal pneumonia and candida infections followed by, tuberculosis and Pseudomonas aeruginosa infections were the predominant opportunistic infections. Since the number of HIV-positive children has been alarmingly increasing in recent years and perinatal transmission is the most common route of HIV infection in children, essential recommendations for prenatal HIV testing as well as appropriate antiretroviral therapy by HIV infected mothers are needed.

  15. Refractory and/or Relapsing Cryptococcosis Associated with Acquired Immune Deficiency Syndrome: Clinical Features, Genotype, and Virulence Factors of Cryptococcus spp. Isolates.

    PubMed

    Nascimento, Erika; Vitali, Lucia H; Tonani, Ludmilla; Kress, Marcia R Von Zeska; Takayanagui, Osvaldo M; Martinez, Roberto

    2016-05-01

    Refractory and relapsing crytocococcosis in acquired immune deficiency syndrome (AIDS) patients have a poor prognosis. The risk factors for this complicated infection course were evaluated by comparing refractory and/or relapsing cryptococcosis in human immunodeficiency virus-coinfected patients (cohort 1) with another group of AIDS patients who adequately responded to antifungals (cohort 2). Except for one isolate of Cryptococcus gattii from a cohort 2 case, all other isolates were identified as Cryptococcus neoformans var. grubii, sex type α, genotype VNI, including Cryptococcus reisolated from the relapse or in the refractory state. No differences were observed with respect to Cryptococcus capsule size and in the melanin and phospholipase production. The cohort 1 patients presented higher prevalence of cryptococcemia, cerebral dissemination, chronic liver disease, and leucopenia, and have increased death rate. Apparently, the refractory and/or relapsing cryptococcosis in the AIDS patients were more related to the host and the extent of the infection than to the fungal characteristics. PMID:26928832

  16. Unified-planning, graded-administration, and centralized-controlling: a management modality for treating acquired immune deficiency syndrome with Chinese medicine in Henan Province of China.

    PubMed

    Xu, Li-Ran; Guo, Hui-jun; Liu, Zhi-bin; Li, Qiang; Yang, Ji-ping; He, Ying

    2015-04-01

    Henan Province in China has a major epidemic of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Chinese medicine (CM) has been used throughout the last decade, and a management modality was developed, which can be described by unified-planning, graded-administration, and centralized-controlling (UGC). The UGC modality has one primary concept (patient-centered medicine from CM theory), four basic foundations (classifying administrative region, characteristics of CM on disease treatment, health resource conditions, and distribution of patients living with HIV), six important relationships (the "three uniformities and three combinations," and the six relationships therein guide the treatment of AIDS with CM), and four key sections (management, operation, records, and evaluation). In this article, the authors introduce the UGC modality, which could be beneficial to developing countries or resource-limited areas for the management of chronic infectious disease. PMID:25877652

  17. Induction of antibody to asialo GM1 by spermatozoa and its occurrence in the sera of homosexual men with the acquired immune deficiency syndrome (AIDS).

    PubMed Central

    Witkin, S S; Sonnabend, J; Richards, J M; Purtilo, D T

    1983-01-01

    Compared to healthy homosexual and heterosexual men, homosexual men with acquired immune deficiency syndrome (AIDS) possessed significantly higher levels of IgG antibody to the neutral glycolipid asialo GM1 (ganglio-N-tetraosylceramide) (P less than 0.01). Of 31 homosexuals with AIDS, 36% possessed levels of this antibody that were at least two standard deviations above the mean of the healthy men. Furthermore, asialo GM1 antibody could be removed from serum by adsorption with spermatozoa. Weekly rectal insemination of male rabbits with rabbit semen also led to the appearance of antibody to asialo GM1 by 15 weeks. These results suggest that asialo GM1 is a component of ejaculated spermatozoa and demonstrate that rectal insemination by itself can lead to the production of antibodies to this glycolipid in the rabbit. In addition, asialo GM1 antibodies may be of value as a serological marker for the early detection of individuals with AIDS. PMID:6652964

  18. Unified-planning, graded-administration, and centralized-controlling: a management modality for treating acquired immune deficiency syndrome with Chinese medicine in Henan Province of China.

    PubMed

    Xu, Li-Ran; Guo, Hui-jun; Liu, Zhi-bin; Li, Qiang; Yang, Ji-ping; He, Ying

    2015-04-01

    Henan Province in China has a major epidemic of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Chinese medicine (CM) has been used throughout the last decade, and a management modality was developed, which can be described by unified-planning, graded-administration, and centralized-controlling (UGC). The UGC modality has one primary concept (patient-centered medicine from CM theory), four basic foundations (classifying administrative region, characteristics of CM on disease treatment, health resource conditions, and distribution of patients living with HIV), six important relationships (the "three uniformities and three combinations," and the six relationships therein guide the treatment of AIDS with CM), and four key sections (management, operation, records, and evaluation). In this article, the authors introduce the UGC modality, which could be beneficial to developing countries or resource-limited areas for the management of chronic infectious disease.

  19. Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni

    SciTech Connect

    Aitken, R.; Coulson, P.S.; Wilson, R.A.

    1988-05-15

    Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means.

  20. [Cellular immunotherapy: complexity of immune system and industrial development].

    PubMed

    Abastado, J-P

    2003-01-01

    Cell immunotherapy aims at treating patients by stimulating their own immune system using appropriate cells. This approach is one of the most promising therapeutic strategy against cancer. The use of cells, the mobilization of a system, the targeting of interactions between the immune system and the tumor constitute the hallmarks of complexity, an area of intense academic and industrial research during the past twenty years. The present article reviews some unique characteristics of the industrial development of these cell drugs.

  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. 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.

  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. Arabidopsis ENHANCED DISEASE SUSCEPTIBILITY1 promotes systemic acquired resistance via azelaic acid and its precursor 9-oxo nonanoic acid.

    PubMed

    Wittek, Finni; Hoffmann, Thomas; Kanawati, Basem; Bichlmeier, Marlies; Knappe, Claudia; Wenig, Marion; Schmitt-Kopplin, Philippe; Parker, Jane E; Schwab, Wilfried; Vlot, A Corina

    2014-11-01

    Systemic acquired resistance (SAR) is a form of inducible disease resistance that depends on salicylic acid and its upstream regulator ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Although local Arabidopsis thaliana defence responses activated by the Pseudomonas syringae effector protein AvrRpm1 are intact in eds1 mutant plants, SAR signal generation is abolished. Here, the SAR-specific phenotype of the eds1 mutant is utilized to identify metabolites that contribute to SAR. To this end, SAR bioassay-assisted fractionation of extracts from the wild type compared with eds1 mutant plants that conditionally express AvrRpm1 was performed. Using high-performance liquid chromatography followed by mass spectrometry, systemic immunity was associated with the accumulation of 60 metabolites, including the putative SAR signal azelaic acid (AzA) and its precursors 9-hydroperoxy octadecadienoic acid (9-HPOD) and 9-oxo nonanoic acid (ONA). Exogenous ONA induced SAR in systemic untreated leaves when applied at a 4-fold lower concentration than AzA. The data suggest that in planta oxidation of ONA to AzA might be partially responsible for this response and provide further evidence that AzA mobilizes Arabidopsis immunity in a concentration-dependent manner. The AzA fragmentation product pimelic acid did not induce SAR. The results link the C9 lipid peroxidation products ONA and AzA with systemic rather than local resistance and suggest that EDS1 directly or indirectly promotes the accumulation of ONA, AzA, or one or more of their common precursors possibly by activating one or more pathways that either result in the release of these compounds from galactolipids or promote lipid peroxidation.

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

    NASA Technical Reports Server (NTRS)

    Huntsberger, Terry

    2011-01-01

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

  6. 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.

  7. The echinoderm immune system. Characters shared with vertebrate immune systems and characters arising later in deuterostome phylogeny.

    PubMed

    Smith, L C; Davidson, E H

    1994-04-15

    In summary, the characters of the echinoderm immune system that we review here can be considered to illuminate the baseline nonadaptive immune systems that were our original deuterostome heritage. We still retain--and greatly rely upon--similarly functioning, nonadaptive cellular defense systems. It is worth stressing that sea urchins are long lived, normally healthy animals that display remarkable abilities to heal wounds and combat major infections. From an external point of view, their immune systems obviously work very well. Thus, their cellular defense systems are extremely sensitive, and they respond rapidly to minor perturbations, all without any specific adaptive capabilities. These systems probably function through the transduction of signals conveying information on injury and infection, just as do the equivalent systems that underlie and back up our own adaptive immune systems, and that provide the initial series of defenses against pathogenic invasions. Many extremely interesting questions remain regarding the evolution of the deuterostome immune response. Are the echinoderm and tunicate systems the same, or have the protochordates augmented the basic phagocyte system with an as yet unidentified chordate-like character? Do the jawless fishes produce Igs that would make them similar to the sharks, or are they vertebrates without an Ig system that essentially rely on an invertebrate-like, nonspecific, activated phagocyte type of immune system? How do sharks regulate their immune system without T cells and MHC class I? How do they avoid producing autoantibodies? Future research will not only answer these questions, but those answers will also be enlightening with regard to the origins of the mammalian immune system in which ancient functions and subsystems remain. PMID:8192333

  8. Short communication: Naturally sensitive Bacillus thuringiensis EG10368 produces thurincin H and acquires immunity after heterologous expression of the one-step-amplified thurincin H gene cluster.

    PubMed

    Wang, G; Manns, D C; Churey, J J; Worobo, R W

    2014-07-01

    Heterologous expression of bacteriocin genetic determinants (or operons) has long been a research interest for the functional analysis of genes involved in bacteriocin biosynthesis, regulation, modification, and immunity. Previously, construction of genomic libraries of the bacteriocin producer strains was usually required to identify new bacteriocin operons, a method that is tedious and time consuming. For the first time, we directly amplified an 8.14-kb bioinformatically identified thurincin H gene cluster using a one-step PCR method with 100% accuracy. This amplified gene cluster was cloned into plasmid pHT315, resulting in plasmid pGW139, and subsequently transformed to Bacillus thuringiensis EG10368, a strain naturally sensitive to thurincin H. Heterologous expression of the gene cluster makes the sensitive B. thuringiensis EG10368 produce thurincin H at a higher level compared with the wild-type producer, B. thuringiensis SF361. Moreover, B. thuringiensis EG10368pGW139 acquired complete immunity to thurincin H. The results indicated that one-step PCR is a promising tool to accurately amplify long bacteriocin gene clusters used in bacteriocin functional analysis studies and it is an effective way to produce bacteriocins at a higher level, without the need to clone large chromosomal fragments.

  9. Biomaterials-based modulation of the immune system.

    PubMed

    Gardner, Austin B; Lee, Simon K C; Woods, Elliot C; Acharya, Abhinav P

    2013-01-01

    The immune system is traditionally considered from the perspective of defending against bacterial or viral infections. However, foreign materials like implants can also illicit immune responses. These immune responses are mediated by a large number of molecular signals, including cytokines, antibodies and reactive radical species, and cell types, including macrophages, neutrophils, natural killer cells, T-cells, B-cells, and dendritic cells. Most often, these molecular signals lead to the generation of fibrous encapsulation of the biomaterials, thereby shielding the body from these biomaterials. In this review we will focus on two different types of biomaterials: those that actively modulate the immune response, as seen in antigen delivery vehicles for vaccines, and those that illicit relatively small immune response, which are important for implantable materials. The first serves to actively influence the immune response by co-opting certain immune pathways, while the second tries to mimic the properties of the host in an attempt to remain undetected by the immune system. As these are two very different end points, each type of biomaterial has been studied and developed separately and in recent years, many advances have been made in each respective area, which will be highlighted in this review. PMID:24171170

  10. 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

  11. Prenatal triclosan exposure and cord blood immune system biomarkers.

    PubMed

    Ashley-Martin, Jillian; Dodds, Linda; Arbuckle, Tye E; Marshall, Jean

    2016-07-01

    Triclosan is widely used as an antimicrobial agent and preservative that has been hypothesized to play a role in asthma and allergic disease. The limited body of literature regarding the allergenicity of triclosan has not evaluated prenatal exposure and subsequent potential effects on the developing immune system. The objective of the present study was to determine the association between prenatal urinary triclosan concentrations and cord blood immune system biomarker concentrations. Umbilical cord blood samples were obtained from the Maternal-Infant Research on Environmental Chemicals (MIREC) Biobank and were tested for three immune system biomarkers: immunoglobulin E (IgE), thymic stromal lymphopoietin (TSLP), and interleukin-33 (IL-33). Triclosan concentrations were measured in urine at 6-13 weeks gestation. No statistically significant associations were observed between prenatal triclosan concentrations and elevated concentrations of any immune system biomarker (n=1219 participants). Longitudinal studies are necessary to determine how the observed findings at birth translate into childhood.

  12. 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.

  13. 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....

  14. 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...

  15. The sense of place in the immune system

    PubMed Central

    Cahalan, Michael D; Gutman, George A

    2009-01-01

    This series of reviews examines the effect of differing tissue environments on the activity and functional capacity of cells in the immune system. From their origins as hematopoietic stem cells, throughout their development and as mature cells, cells of the immune system find themselves in distinct and highly specialized niches, and contact with antigen or inflammatory signals changes their phenotype, activity and trafficking. Two-photon microscopy has provided the first direct observations of living cells and their activation choreography in the tissue environment and will no doubt continue to provide greater understanding of cellular dynamics and immune function. PMID:16550194

  16. Generating compact classifier systems using a simple artificial immune system.

    PubMed

    Leung, Kevin; Cheong, France; Cheong, Christopher

    2007-10-01

    Current artificial immune system (AIS) classifiers have two major problems: 1) their populations of B-cells can grow to huge proportions, and 2) optimizing one B-cell (part of the classifier) at a time does not necessarily guarantee that the B-cell pool (the whole classifier) will be optimized. In this paper, the design of a new AIS algorithm and classifier system called simple AIS is described. It is different from traditional AIS classifiers in that it takes only one B-cell, instead of a B-cell pool, to represent the classifier. This approach ensures global optimization of the whole system, and in addition, no population control mechanism is needed. The classifier was tested on seven benchmark data sets using different classification techniques and was found to be very competitive when compared to other classifiers.

  17. 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.

  18. 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. PMID:26410104

  19. Precision Agriculture: Using Low-Cost Systems to Acquire Low-Altitude Images.

    PubMed

    Ponti, Moacir; Chaves, Arthur A; Jorge, Fabio R; Costa, Gabriel B P; Colturato, Adimara; Branco, Kalinka R L J C

    2016-01-01

    Low cost remote sensing imagery has the potential to make precision farming feasible in developing countries. In this article, the authors describe image acquisition from eucalyptus, bean, and sugarcane crops acquired by low-cost and low-altitude systems. They use different approaches to handle low-altitude images in both the RGB and NIR (near-infrared) bands to estimate and quantify plantation areas. PMID:27514030

  20. Precision Agriculture: Using Low-Cost Systems to Acquire Low-Altitude Images.

    PubMed

    Ponti, Moacir; Chaves, Arthur A; Jorge, Fabio R; Costa, Gabriel B P; Colturato, Adimara; Branco, Kalinka R L J C

    2016-01-01

    Low cost remote sensing imagery has the potential to make precision farming feasible in developing countries. In this article, the authors describe image acquisition from eucalyptus, bean, and sugarcane crops acquired by low-cost and low-altitude systems. They use different approaches to handle low-altitude images in both the RGB and NIR (near-infrared) bands to estimate and quantify plantation areas.

  1. Assessing the human immune system through blood transcriptomics

    PubMed Central

    2010-01-01

    Blood is the pipeline of the immune system. Assessing changes in transcript abundance in blood on a genome-wide scale affords a comprehensive view of the status of the immune system in health and disease. This review summarizes the work that has used this approach to identify therapeutic targets and biomarker signatures in the field of autoimmunity and infectious disease. Recent technological and methodological advances that will carry the blood transcriptome research field forward are also discussed. PMID:20619006

  2. Evasion of the human innate immune system by dengue virus

    PubMed Central

    Pagni, Sarah; Fernandez-Sesma, Ana

    2014-01-01

    Dengue virus is a worldwide health problem, with billions of people at risk annually. Dengue virus causes a spectrum of diseases, namely dengue fever, dengue hemorrhagic fever and dengue shock syndrome with the latter two being linked to death. Understanding how dengue is able to evade the immune system and cause enhanced severity of disease is the main topics of interest in the Fernandez-Sesma laboratory at Mount Sinai School of Medicine. Using primary human immune cells, our group investigates the contribution of dengue virus-specific proteins to the evasion of innate immunity by this virus and the host factors that the virus interacts with in order to evade immune recognition and to establish infection in humans. Here, we review recent findings from our group as well as published data from other groups regarding immune modulation by dengue virus. PMID:22569913

  3. 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.

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

    PubMed

    Singh, Gurinder; Pai, Roopa S

    2015-06-01

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

  5. Traumatic spinal cord injury in mice with human immune systems

    PubMed Central

    Carpenter, Randall S.; Kigerl, Kristina A.; Marbourg, Jessica M.; Gaudet, Andrew D.; Huey, Devra; Niewiesk, Stefan; Popovich, Phillip G.

    2015-01-01

    Mouse models have provided key insight into the cellular and molecular control of human immune system function. However, recent data indicate that extrapolating the functional capabilities of the murine immune system into humans can be misleading. Since immune cells significantly affect neuron survival and axon growth and also are required to defend the body against infection, it is important to determine the pathophysiological significance of spinal cord injury (SCI)-induced changes in human immune system function. Research projects using monkeys or humans would be ideal; however, logistical and ethical barriers preclude detailed mechanistic studies in either species. Humanized mice, i.e., immunocompromised mice reconstituted with human immune cells, can help overcome these barriers and can be applied in various experimental conditions that are of interest to the SCI community. Specifically, newborn NOD-SCID-IL2rgnull (NSG) mice engrafted with human CD34+ hematopoietic stem cells develop normally without neurological impairment. In this report, new data show that when mice with human immune systems receive a clinically-relevant spinal contusion injury, spontaneous functional recovery is indistinguishable from that achieved after SCI using conventional inbred mouse strains. Moreover, using routine immunohistochemical and flow cytometry techniques, one can easily phenotype circulating human immune cells and document the composition and distribution of these cells in the injured spinal cord. Lesion pathology in humanized mice is typical of mouse contusion injuries, producing a centralized lesion epicenter that becomes occupied by phagocytic macrophages and lymphocytes and enclosed by a dense astrocytic scar. Specific human immune cell types, including three distinct subsets of human monocytes, were readily detected in blood, spleen and liver. Future studies that aim to understand the functional consequences of manipulating the neuro-immune axis after SCI should

  6. Traumatic spinal cord injury in mice with human immune systems.

    PubMed

    Carpenter, Randall S; Kigerl, Kristina A; Marbourg, Jessica M; Gaudet, Andrew D; Huey, Devra; Niewiesk, Stefan; Popovich, Phillip G

    2015-09-01

    Mouse models have provided key insight into the cellular and molecular control of human immune system function. However, recent data indicate that extrapolating the functional capabilities of the murine immune system into humans can be misleading. Since immune cells significantly affect neuron survival and axon growth and also are required to defend the body against infection, it is important to determine the pathophysiological significance of spinal cord injury (SCI)-induced changes in human immune system function. Research projects using monkeys or humans would be ideal; however, logistical and ethical barriers preclude detailed mechanistic studies in either species. Humanized mice, i.e., immunocompromised mice reconstituted with human immune cells, can help overcome these barriers and can be applied in various experimental conditions that are of interest to the SCI community. Specifically, newborn NOD-SCID-IL2rg(null) (NSG) mice engrafted with human CD34(+) hematopoietic stem cells develop normally without neurological impairment. In this report, new data show that when mice with human immune systems receive a clinically-relevant spinal contusion injury, spontaneous functional recovery is indistinguishable from that achieved after SCI using conventional inbred mouse strains. Moreover, using routine immunohistochemical and flow cytometry techniques, one can easily phenotype circulating human immune cells and document the composition and distribution of these cells in the injured spinal cord. Lesion pathology in humanized mice is typical of mouse contusion injuries, producing a centralized lesion epicenter that becomes occupied by phagocytic macrophages and lymphocytes and enclosed by a dense astrocytic scar. Specific human immune cell types, including three distinct subsets of human monocytes, were readily detected in the blood, spleen and liver. Future studies that aim to understand the functional consequences of manipulating the neuro-immune axis after SCI

  7. Traumatic spinal cord injury in mice with human immune systems.

    PubMed

    Carpenter, Randall S; Kigerl, Kristina A; Marbourg, Jessica M; Gaudet, Andrew D; Huey, Devra; Niewiesk, Stefan; Popovich, Phillip G

    2015-09-01

    Mouse models have provided key insight into the cellular and molecular control of human immune system function. However, recent data indicate that extrapolating the functional capabilities of the murine immune system into humans can be misleading. Since immune cells significantly affect neuron survival and axon growth and also are required to defend the body against infection, it is important to determine the pathophysiological significance of spinal cord injury (SCI)-induced changes in human immune system function. Research projects using monkeys or humans would be ideal; however, logistical and ethical barriers preclude detailed mechanistic studies in either species. Humanized mice, i.e., immunocompromised mice reconstituted with human immune cells, can help overcome these barriers and can be applied in various experimental conditions that are of interest to the SCI community. Specifically, newborn NOD-SCID-IL2rg(null) (NSG) mice engrafted with human CD34(+) hematopoietic stem cells develop normally without neurological impairment. In this report, new data show that when mice with human immune systems receive a clinically-relevant spinal contusion injury, spontaneous functional recovery is indistinguishable from that achieved after SCI using conventional inbred mouse strains. Moreover, using routine immunohistochemical and flow cytometry techniques, one can easily phenotype circulating human immune cells and document the composition and distribution of these cells in the injured spinal cord. Lesion pathology in humanized mice is typical of mouse contusion injuries, producing a centralized lesion epicenter that becomes occupied by phagocytic macrophages and lymphocytes and enclosed by a dense astrocytic scar. Specific human immune cell types, including three distinct subsets of human monocytes, were readily detected in the blood, spleen and liver. Future studies that aim to understand the functional consequences of manipulating the neuro-immune axis after SCI

  8. 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

  9. The Mucosal Immune System and Its Regulation by Autophagy.

    PubMed

    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

  10. The Mucosal Immune System and Its Regulation by Autophagy.

    PubMed

    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.

  11. Multifaceted interactions between adaptive immunity and the central nervous system.

    PubMed

    Kipnis, Jonathan

    2016-08-19

    Neuroimmunologists seek to understand the interactions between the central nervous system (CNS) and the immune system, both under homeostatic conditions and in diseases. Unanswered questions include those relating to the diversity and specificity of the meningeal T cell repertoire; the routes taken by immune cells that patrol the meninges under healthy conditions and invade the parenchyma during pathology; the opposing effects (beneficial or detrimental) of these cells on CNS function; the role of immune cells after CNS injury; and the evolutionary link between the two systems, resulting in their tight interaction and interdependence. This Review summarizes the current standing of and challenging questions related to interactions between adaptive immunity and the CNS and considers the possible directions in which these aspects of neuroimmunology will be heading over the next decade. PMID:27540163

  12. Nanoparticle-Based Modulation of the Immune System.

    PubMed

    Fang, Ronnie H; Zhang, Liangfang

    2016-06-01

    The immune system is an incredibly complex biological network that plays a significant role in almost all disease pathogenesis. With an increased understanding of how this vital system operates, there has been a great emphasis on leveraging, manipulating, and/or supplementing endogenous immunity to better prevent or treat different disease states. More recently, the advent of nanotechnology has ushered in a plethora of new nanoparticle-based platforms that can be used to improve existing immunomodulation modalities. As the ability to engineer at the nanoscale becomes increasingly sophisticated, nanoparticles can be finely tuned to effect the desired immune responses, leading to exciting new avenues for addressing pressing issues in public health. In this review, we give an overview of the different areas in which nanoparticle technology has been applied toward modulating the immune system and highlight the recent advances within each.

  13. Current understanding of interactions between nanoparticles and the immune system.

    PubMed

    Dobrovolskaia, Marina A; Shurin, Michael; Shvedova, Anna A

    2016-05-15

    The delivery of drugs, antigens, and imaging agents benefits from using nanotechnology-based carriers. The successful translation of nanoformulations to the clinic involves thorough assessment of their safety profiles, which, among other end-points, includes evaluation of immunotoxicity. The past decade of research focusing on nanoparticle interaction with the immune system has been fruitful in terms of understanding the basics of nanoparticle immunocompatibility, developing a bioanalytical infrastructure to screen for nanoparticle-mediated immune reactions, beginning to uncover the mechanisms of nanoparticle immunotoxicity, and utilizing current knowledge about the structure-activity relationship between nanoparticles' physicochemical properties and their effects on the immune system to guide safe drug delivery. In the present review, we focus on the most prominent pieces of the nanoparticle-immune system puzzle and discuss the achievements, disappointments, and lessons learned over the past 15years of research on the immunotoxicity of engineered nanomaterials.

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

    PubMed

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

    2016-07-15

    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.

  15. Trauma: the role of the innate immune system

    PubMed Central

    Hietbrink, F; Koenderman, L; Rijkers, GT; Leenen, LPH

    2006-01-01

    Immune dysfunction can provoke (multiple) organ failure in severely injured patients. This dysfunction manifests in two forms, which follow a biphasic pattern. During the first phase, in addition to the injury by trauma, organ damage is caused by the immune system during a systemic inflammatory response. During the second phase the patient is more susceptible for sepsis due to host defence failure (immune paralysis). The pathophysiological model outlined in this review encompasses etiological factors and the contribution of the innate immune system in the end organ damage. The etiological factors can be divided into intrinsic (genetic predisposition and physiological status) and extrinsic components (type of injury or "traumaload" and surgery or "intervention load"). Of all the factors, the intervention load is the only one which, can be altered by the attending emergency physician. Adjustment of the therapeutic approach and choice of the most appropriate treatment strategy can minimize the damage caused by the immune response and prevent the development of immunological paralysis. This review provides a pathophysiological basis for the damage control concept, in which a staged approach of surgery and post-traumatic immunomonitoring have become important aspects of the treatment protocol. The innate immune system is the main objective of immunomonitoring as it has the most prominent role in organ failure after trauma. Polymorphonuclear phagocytes and monocytes are the main effector-cells of the innate immune system in the processes that lead to organ failure. These cells are controlled by cytokines, chemokines, complement factors and specific tissue signals. The contribution of tissue barrier integrity and its interaction with the innate immune system is further evaluated. PMID:16759367

  16. Systemic immune system alterations in early stages of Alzheimer's disease.

    PubMed

    Zhang, Rongzhen; Miller, Robert G; Madison, Catherine; Jin, Xia; Honrada, Ronald; Harris, Will; Katz, Jonathan; Forshew, Dallas A; McGrath, Michael S

    2013-03-15

    Immune activation and inflammation play significant roles in the pathogenesis of Alzheimer's disease (AD). To test whether AD patients showed systemic manifestations of inflammation, blood from 41 patients with early stages of AD and 31 aged-match elderly controls were evaluated. Cellular markers for monocyte/macrophage (MO) activation and CD8 T lymphocyte were increased in early AD patients. Expression of monocyte CCR2, the receptor for monocyte chemoattractant protein-1 (MCP-1), was decreased; however, plasma MCP-1 levels were significantly increased and were related to the degree of MO activation in AD. These findings suggest that AD pathogenesis may be influenced by systemic immunologic dysfunction and provides potential immunologic targets for therapeutic intervention.

  17. Postreplication targeting of transformants by bacterial immune systems?

    PubMed

    Johnston, Calum; Martin, Bernard; Polard, Patrice; Claverys, Jean-Pierre

    2013-10-01

    Bacteria are constantly challenged by foreign genetic elements such as bacteriophages and plasmids. Several defense systems provide immunity against such attackers, including restriction-modification (R-M) systems and clustered, regularly interspaced short palindromic repeats (CRISPRs). These systems target attacking DNA and thus antagonize natural transformation, which relies on uptake of exogenous DNA to promote acquisition of new genetic traits. It is unclear how this antagonization occurs, because transforming DNA is single stranded, and thus resistant to these immune systems. Here, we propose a simple model whereby these systems limit transformation by attack of transformed chromosomes once double strandedness is restored by chromosomal replication.

  18. 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

  19. Pediatric recurrent respiratory tract infections: when and how to explore the immune system? (About 53 cases)

    PubMed Central

    El-Azami-El-Idrissi, Mohammed; Lakhdar-Idrissi, Mounia; Chaouki, Sanae; Atmani, Samir; Bouharrou, Abdelhak; Hida, Moustapha

    2016-01-01

    Recurrent respiratory tract infections are one of the most frequent reasons for pediatric visits and hospitalization. Causes of this pathology are multiple ranging from congenital to acquired and local to general. Immune deficiencies are considered as underlying conditions predisposing to this pathology. Our work is about to determine when and how to explore the immune system when facing recurrent respiratory infections. This was based on the records of 53 children hospitalized at the pediatrics unit of Hassan II University Hospital, Fez Morocco. Thirty boys and 23 girls with age ranging from 5 months to 12 years with an average age of 2 years were involved in this study. Bronchial foreign body was the main etiology in children of 3 to 6 year old. Gastro-esophageal reflux, which in some cases is a consequence of chronic cough, as well as asthma were most frequent in infants (17 and 15% respectively). Immune deficiency was described in 7.5% of patients and the only death we deplored in our series belongs to this group. Recurrent respiratory tract infections have multiple causes. In our series they are dominated by foreign body inhalation and gastroesophageal reflux, which in some cases is a consequence of a chronic cough. Immune deficiency is not frequent but could influence the prognosis. Therefore immune explorations should be well codified. PMID:27642394

  20. Pediatric recurrent respiratory tract infections: when and how to explore the immune system? (About 53 cases).

    PubMed

    El-Azami-El-Idrissi, Mohammed; Lakhdar-Idrissi, Mounia; Chaouki, Sanae; Atmani, Samir; Bouharrou, Abdelhak; Hida, Moustapha

    2016-01-01

    Recurrent respiratory tract infections are one of the most frequent reasons for pediatric visits and hospitalization. Causes of this pathology are multiple ranging from congenital to acquired and local to general. Immune deficiencies are considered as underlying conditions predisposing to this pathology. Our work is about to determine when and how to explore the immune system when facing recurrent respiratory infections. This was based on the records of 53 children hospitalized at the pediatrics unit of Hassan II University Hospital, Fez Morocco. Thirty boys and 23 girls with age ranging from 5 months to 12 years with an average age of 2 years were involved in this study. Bronchial foreign body was the main etiology in children of 3 to 6 year old. Gastro-esophageal reflux, which in some cases is a consequence of chronic cough, as well as asthma were most frequent in infants (17 and 15% respectively). Immune deficiency was described in 7.5% of patients and the only death we deplored in our series belongs to this group. Recurrent respiratory tract infections have multiple causes. In our series they are dominated by foreign body inhalation and gastroesophageal reflux, which in some cases is a consequence of a chronic cough. Immune deficiency is not frequent but could influence the prognosis. Therefore immune explorations should be well codified. PMID:27642394

  1. Pediatric recurrent respiratory tract infections: when and how to explore the immune system? (About 53 cases).

    PubMed

    El-Azami-El-Idrissi, Mohammed; Lakhdar-Idrissi, Mounia; Chaouki, Sanae; Atmani, Samir; Bouharrou, Abdelhak; Hida, Moustapha

    2016-01-01

    Recurrent respiratory tract infections are one of the most frequent reasons for pediatric visits and hospitalization. Causes of this pathology are multiple ranging from congenital to acquired and local to general. Immune deficiencies are considered as underlying conditions predisposing to this pathology. Our work is about to determine when and how to explore the immune system when facing recurrent respiratory infections. This was based on the records of 53 children hospitalized at the pediatrics unit of Hassan II University Hospital, Fez Morocco. Thirty boys and 23 girls with age ranging from 5 months to 12 years with an average age of 2 years were involved in this study. Bronchial foreign body was the main etiology in children of 3 to 6 year old. Gastro-esophageal reflux, which in some cases is a consequence of chronic cough, as well as asthma were most frequent in infants (17 and 15% respectively). Immune deficiency was described in 7.5% of patients and the only death we deplored in our series belongs to this group. Recurrent respiratory tract infections have multiple causes. In our series they are dominated by foreign body inhalation and gastroesophageal reflux, which in some cases is a consequence of a chronic cough. Immune deficiency is not frequent but could influence the prognosis. Therefore immune explorations should be well codified.

  2. The shaping of modern human immune systems by multiregional admixture with archaic humans.

    PubMed

    Abi-Rached, Laurent; Jobin, Matthew J; Kulkarni, Subhash; McWhinnie, Alasdair; Dalva, Klara; Gragert, Loren; Babrzadeh, Farbod; Gharizadeh, Baback; Luo, Ma; Plummer, Francis A; Kimani, Joshua; Carrington, Mary; Middleton, Derek; Rajalingam, Raja; Beksac, Meral; Marsh, Steven G E; Maiers, Martin; Guethlein, Lisbeth A; Tavoularis, Sofia; Little, Ann-Margaret; Green, Richard E; Norman, Paul J; Parham, Peter

    2011-10-01

    Whole genome comparisons identified introgression from archaic to modern humans. Our analysis of highly polymorphic human leukocyte antigen (HLA) class I, vital immune system components subject to strong balancing selection, shows how modern humans acquired the HLA-B*73 allele in west Asia through admixture with archaic humans called Denisovans, a likely sister group to the Neandertals. Virtual genotyping of Denisovan and Neandertal genomes identified archaic HLA haplotypes carrying functionally distinctive alleles that have introgressed into modern Eurasian and Oceanian populations. These alleles, of which several encode unique or strong ligands for natural killer cell receptors, now represent more than half the HLA alleles of modern Eurasians and also appear to have been later introduced into Africans. Thus, adaptive introgression of archaic alleles has significantly shaped modern human immune systems.

  3. 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

  4. β-arrestins in the Immune System

    PubMed Central

    Xie, Ting; Liang, Jiurong

    2015-01-01

    Summary β-arrestins regulate G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) through receptor desensitization while also acting as signaling scaffolds to facilitate numerous effector pathways. Recent studies have provided evidence that β-arrestins play a key role in inflammatory responses. We here summarize these advances on the roles of β-arrestins in immune regulation and inflammatory responses under physiological and pathological conditions, with an emphasis on translational implications of β-arrestins on human diseases. PMID:23764061

  5. 12 CFR 617.7610 - What should the System institution do when it decides to sell acquired agricultural real estate?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 7 2012-01-01 2012-01-01 false What should the System institution do when it... institution do when it decides to sell acquired agricultural real estate? (a) Notify the previous owner, (1) Within 15 days of the System institution's decision to sell acquired agricultural real estate, it...

  6. 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

  7. Sex hormones and glucocorticoids: interactions with the immune system.

    PubMed

    Da Silva, J A

    1999-06-22

    Gender and sex hormones exert powerful effects in the susceptibility and progression of numerous human and experimental autoimmune diseases. This has been attributed to direct immunological effects of sex hormones that impact a clear gender dimorphism on the immune system. Globally, estrogens depress T cell-dependent immune function and diseases, but enhance antibody production and aggravate B cell-dependent diseases. Androgens suppress both T-cell and B-cell immune responses and virtually always result in the suppression of disease expression. Defects in the hypothalamic-pituitary-adrenal (HPA) axis have been proposed to play an important role in the pathogenesis of autoimmune diseases. Glucocorticoid response to stress, including immune challenge, is strongly inhibited by androgens and enhanced by estrogens. Complex three-way interactions between these systems appear to be involved in gender dimorphism of the immune system. This paper reviews the mechanisms involved in interactions between sex steroids and the HPA axis, addresses the possibility of similar interactions on immunocompetent cells, and explores an integrated perspective of the impact of these interplays on the immune system.

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

    PubMed Central

    2014-01-01

    Background Evaluating the features and performance of health information systems can serve to strengthen the systems themselves as well as to guide other organizations in the process of designing and implementing surveillance tools. We adapted an evaluation framework in order to assess electronic immunization data collection systems, and applied it in two Ontario public health units. Methods The Centers for Disease Control and Prevention’s Guidelines for Evaluating Public Health Surveillance Systems are broad in nature and serve as an organizational tool to guide the development of comprehensive evaluation materials. Based on these Guidelines, and informed by other evaluation resources and input from stakeholders in the public health community, we applied an evaluation framework to two examples of immunization data collection and examined several system attributes: simplicity, flexibility, data quality, timeliness, and acceptability. Data collection approaches included key informant interviews, logic and completeness assessments, client surveys, and on-site observations. Results Both evaluated systems allow high-quality immunization data to be collected, analyzed, and applied in a rapid fashion. However, neither system is currently able to link to other providers’ immunization data or provincial data sources, limiting the comprehensiveness of coverage assessments. We recommended that both organizations explore possibilities for external data linkage and collaborate with other jurisdictions to promote a provincial immunization repository or data sharing platform. Conclusions Electronic systems such as the ones described in this paper allow immunization data to be collected, analyzed, and applied in a rapid fashion, and represent the infostructure required to establish a population-based immunization registry, critical for comprehensively assessing vaccine coverage. PMID:24423014

  9. 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.

  10. 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.

  11. 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.

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

    PubMed Central

    Barrangou, Rodolphe; Marraffini, Luciano A.

    2014-01-01

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

  13. An Interactive Reference Framework for Modeling a Dynamic Immune System

    PubMed Central

    Spitzer, Matthew H.; Gherardini, Pier Federico; Fragiadakis, Gabriela K.; Bhattacharya, Nupur; Yuan, Robert T.; Hotson, Andrew N.; Finck, Rachel; Carmi, Yaron; Zunder, Eli R.; Fantl, Wendy J.; Bendall, Sean C.; Engleman, Edgar G.; Nolan, Garry P.

    2015-01-01

    Immune cells function in an interacting hierarchy that coordinates activities of various cell types according to genetic and environmental contexts. We developed graphical approaches to construct an extensible immune reference map from mass cytometry data of cells from different organs, incorporating landmark cell populations as flags on the map to compare cells from distinct samples. The maps recapitulated canonical cellular phenotypes and revealed reproducible, tissue-specific deviations. The approach revealed influences of genetic variation and circadian rhythms on immune system structure, enabled direct comparisons of murine and human blood cell phenotypes, and even enabled archival fluorescence-based flow cytometry data to be mapped onto the reference framework. This foundational reference map provides a working definition of systemic immune organization to which new data can be integrated to reveal deviations driven by genetics, environment, or pathology. PMID:26160952

  14. 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

  15. 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.

  16. Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) 'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance'.

    PubMed

    Simpson, Elizabeth

    2015-04-19

    'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance', published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603-606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

  17. Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) ‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’

    PubMed Central

    Simpson, Elizabeth

    2015-01-01

    ‘Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance’, published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603–606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society. PMID:25750245

  18. Salmonella abortusovis infection in susceptible BALB/cby mice: importance of Lyt-2+ and L3T4+ T cells in acquired immunity and granuloma formation.

    PubMed

    Guilloteau, L; Buzoni-Gatel, D; Bernard, F; Lantier, I; Lantier, F

    1993-01-01

    The role of T cells in granulomatous responses and in acquired immunity against Salmonella abortusovis (SAO) infection was studied in a murine model. Mice were subcutaneously (s.c.) vaccinated with a live attenuated strain of SAO. One month after vaccination, the transfer of primed spleen cells (1 x 10(8) cells per mouse) to syngeneic recipient mice conferred a significant protection of 3 log10, measured by spleen colonization on day 6 after s.c. challenge. In vitro treatment of spleen cells, before the transfer, with anti-Lyt-2 monoclonal antibody (IgG2b isotype MAb) and complement significantly impaired the protective activity. Treatment with anti-L3T4 MAb also diminished transferred protection, but to a lesser degree. Depletion of both L3T4+ and Lyt-2+ T cells completely abrogated protection. MAb treatment of spleen cells in vitro did not seem to have any effect on antibody response in recipient mice. Six days after the challenge protected recipient mice showed organized granulomas in the liver containing Mac-1+ macrophages and L3T4+ T cells. In non-protected mice at 6 days post-challenge, large infiltrates of T lymphocytes and macrophages were observed, but as numerous lesions with necrosis of hepatocytes; no granuloma were seen. In our experimental conditions, Lyt-2+ and L3T4+ T cells appeared to play, alone and in synergy, a role in vaccine-induced immunity against SAO and hepatic granulomas may contribute to the control of the infection.

  19. 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

  20. Space flight and the immune system.

    PubMed

    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.

  1. Space flight and the immune system.

    PubMed

    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. PMID:8488698

  2. 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.

  3. Acquired hyperpigmentations*

    PubMed Central

    Cestari, Tania Ferreira; Dantas, Lia Pinheiro; Boza, Juliana Catucci

    2014-01-01

    Cutaneous hyperpigmentations are frequent complaints, motivating around 8.5% of all dermatological consultations in our country. They can be congenital, with different patterns of inheritance, or acquired in consequence of skin problems, systemic diseases or secondary to environmental factors. The vast majority of them are linked to alterations on the pigment melanin, induced by different mechanisms. This review will focus on the major acquired hyperpigmentations associated with increased melanin, reviewing their mechanisms of action and possible preventive measures. Particularly prominent aspects of diagnosis and therapy will be emphasized, with focus on melasma, post-inflammatory hyperpigmentation, periorbital pigmentation, dermatosis papulosa nigra, phytophotodermatoses, flagellate dermatosis, erythema dyschromicum perstans, cervical poikiloderma (Poikiloderma of Civatte), acanthosis nigricans, cutaneous amyloidosis and reticulated confluent dermatitis PMID:24626644

  4. Nutritionally Mediated Programming of the Developing Immune System12

    PubMed Central

    Palmer, Amanda C.

    2011-01-01

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

  5. Automated system to acquire fluorescence, polarization and anisotropy maps within liquid flows

    PubMed Central

    Gonçalves, Cristiane C.; Pepe, Iuri; Lima, Angelo M. V.; Musse, Ana Paula S.

    2002-01-01

    Maps of polarization and anisotropy can be helpful for flow analysis systems (FIA, CFA, etc.) with reactions dependent on the intermolecular alignment as well as for dispersion control. Maps can be acquired manually, but when a scan over a sample area is required, the acquisition becomes tiresome and has low precision. The paper describes an automatic flexible system for high-precision sample positioning with closed loop self control, remote data acquisition and storage controlled by a BASIC program. The system was developed to acquire maps up to 850 mm2 of the sample (liquid flows, solids, interfaces, etc.), with up to 100 μm2 precision. To evaluate the equipment, performance is presented as the scan of a thin liquid film of monoethylene glycol (MEG) flowing on borosilicate. Tests were performed with and without surfactantes at submicellar concentrations: two concentrations of sodium dodecyl sulphate (SDS) and one of polyethylene oxide (PEO). For pure MEG, the intermolecular alignment initially increased, then decreased. When SDS was added, both polarization and anisotropy only increased progressively with the flow. This might be explained by the surfactant decrease of interfacial interaction. When PEO was added, both polarization and anisotropy decreased pronouncedly over the entire map, which might be due to macromolecular aggregates within the bulk generating misaligned molecular domains. The system presented as sample positioning repeatability of 0.1% and a high polarization reproducibility (error margin < 6 in 1000). PMID:18924741

  6. Peripheral education of the immune system by the colonic microbiota

    PubMed Central

    Kuhn, Kristine A.; Stappenbeck, Thaddeus S.

    2013-01-01

    There is growing interest in understanding the effects of host-microbial interactions on host physiologic processes. Much of the work in this arena is logically focused on the interaction at mucosal surfaces as this is a primary site of interaction. However, there is ample evidence to suggest that the effects of the microbiota have a much farther reach including the systemic immune system. While there are some similarities to effects at mucosal surfaces (i.e. reduced numbers of adaptive immune cells, diminished innate responses), there are some important differences that we highlight such as the response to immunogens and bacterial antigens. We propose that understanding the details of how specific components of the microbiota influence the systemic immune system likely will have significant impact on our understanding the pathophysiology of a variety of autoimmune diseases. PMID:24169518

  7. “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

  8. "Health system approach" for improving immunization program performance.

    PubMed

    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

  9. Programmed cell death in the plant immune system

    PubMed Central

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

    2011-01-01

    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. PMID:21475301

  10. 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

  11. Recognising promoter sequences using an artificial immune system

    SciTech Connect

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

    1995-12-31

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

  12. Strategies to discover regulatory circuits of the mammalian immune system.

    PubMed

    Amit, Ido; Regev, Aviv; Hacohen, Nir

    2011-12-01

    Recent advances in technologies for genome- and proteome-scale measurements and perturbations promise to accelerate discovery in every aspect of biology and medicine. Although such rapid technological progress provides a tremendous opportunity, it also demands that we learn how to use these tools effectively. One application with great potential to enhance our understanding of biological systems is the unbiased reconstruction of genetic and molecular networks. Cells of the immune system provide a particularly useful model for developing and applying such approaches. Here, we review approaches for the reconstruction of signalling and transcriptional networks, with a focus on applications in the mammalian innate immune system.

  13. Attitudes of Turkish midwives and nurses working at hospitals towards people living with human immunodeficiency virus/acquired immune deficiency syndrome.

    PubMed

    Akgun Kostak, Melahat; Unsar, Serap; Kurt, Seda; Erol, Ozgul

    2012-10-01

    Health professionals caring for people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) show poor or negative attitudes because of fear of contagion. Therefore, it is important to know the attitudes of midwives' and nurses' towards people living with HIV/AIDS. The aim of this descriptive and cross-sectional study is to assess the attitudes of Turkish midwives and nurses working at hospitals to people living with HIV/AIDS and to identify factors that affect these attitudes. A group of 46 midwives and 192 nurses working in hospitals were included in the study. Data were collected through AIDS Attitude Scale. Age, professional experience, number of children and marital status influenced the attitudes of the participants towards people living with HIV/AIDS. We concluded that higher level of education appear to positively influence the attitudes of the participants. Education programmes including evidence-based nursing implications might be planned to improve positive attitudes and to prevent stigmatization of people living with HIV/AIDS.

  14. The thymus in acquired immune deficiency syndrome. Comparison with other types of immunodeficiency diseases, and presence of components of human immunodeficiency virus type 1.

    PubMed Central

    Schuurman, H. J.; Krone, W. J.; Broekhuizen, R.; van Baarlen, J.; van Veen, P.; Golstein, A. L.; Huber, J.; Goudsmit, J.

    1989-01-01

    The authors studied thymus specimens taken at autopsy from eight acquired immune deficiency syndrome (AIDS) patients and compared these with those taken from four patients with congenital immunodeficiency (unrelated to an intrinsic thymus defect) and seven patients after allogeneic bone marrow transplantation. In all cases, histology showed a severely involuted architecture, compatible with a debilitating disease before death. There were no major differences between thymus tissue in AIDS patients and in the other patients studied. This argues against the claim expressed in the literature that the epithelial microenvironment incurs particular HIV-1-induced injury in AIDS. This conclusion is substantiated by immunohistochemistry for HIV-1 gag and env proteins, and by hybridohistochemistry for gag/pol and env mRNA of HIV-1. Positive cells were observed only in low numbers, both inside the epithelial parenchyma and in the (expanded) perivascular areas. An interesting finding was the labeling of subcapsular/medullary epithelium in normal uninvoluted thymus by a number of antibodies to HIV-1 gag p17 and p24 proteins. Compatible with this labeling was the staining of epithelial stalks in hyperinvoluted thymuses irrespective of disease category. The previously reported cross-reactivity between HIV-1 core protein and thymosin alpha 1 cannot fully explain this observation, because the epithelium in the hyperinvoluted state is negative for thymosin alpha 1. This study confirms and extends previous reports on the endogenous presence of epitopes of retroviral antigens in thymic epithelium. Images Figure 1 Figure 2 Figure 3 PMID:2474255

  15. Utility of /sup 67/Ga scintigraphy and bronchial washings in the diagnosis and treatment of Pneumocystis carinii pneumonia in patients with the acquired immune deficiency syndrome

    SciTech Connect

    Tuazon, C.U.; Delaney, M.D.; Simon, G.L.; Witorsch, P.; Varma, V.M.

    1985-11-01

    Twenty patients with the acquired immune deficiency syndrome (AIDS) and suspected Pneumocystis carinii pneumonia were evaluated by /sup 67/Ga scintigraphy and fiberoptic bronchoscopy for initial diagnosis and response to therapy. Lung uptake of /sup 67/Ga was demonstrated in 100% of AIDS patients with P. carinii pneumonia, including those with subclinical infection. Fiberoptic bronchoscopy identified P. carinii in the bronchial washings of 100% of cases (19 patients), whereas only 13 of 16 (81%) patients had P. carinii in lung tissue obtained by transbronchial biopsy. Repeat fiberoptic bronchoscopy was performed in 16 of 20 patients. After 2 to 4 wk of therapy, P. carinii was identified in bronchial washings in 8 of 16 (50%) patients and in transbronchial biopsy in 1 of 10 (10%) patients examined. Bronchial washing has a higher yield than transbronchial biopsy in demonstrating P. carinii in patients with AIDS and may evolve as the procedure of choice in such patients. Based on the clinical course and results of /sup 67/Ga scintigraphy and fiberoptic bronchoscopy in AIDS patients with P. carinii pneumonia, optimal therapy may require at least 3 wk of treatment.

  16. Acquired Immune Deficiency Syndrome (AIDS) and the Veterans' Administration. Hearing before the Subcommittee on Hospitals and Health Care of the Committee on Veterans' Affairs. House of Representatives, One Hundredth Congress, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Committee on Veterans' Affairs.

    This document presents witness testimony and prepared statements from the Congressional hearing called to examine the issue of acquired immune deficiency syndrome (AIDS) and the role of the Veterans' Administration (VA) in combating AIDS. Opening statements are included from Representatives G. V. Montgomery, J. Roy Rowland, Joseph P. Kennedy, II,…

  17. 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.

  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. 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.…

  20. The Neuro-Immune Pathophysiology of Central and Peripheral Fatigue in Systemic Immune-Inflammatory and Neuro-Immune Diseases.

    PubMed

    Morris, Gerwyn; Berk, Michael; Galecki, Piotr; Walder, Ken; Maes, Michael

    2016-03-01

    Many patients with systemic immune-inflammatory and neuro-inflammatory disorders, including depression, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's disease, cancer, cardiovascular disorder, Parkinson's disease, multiple sclerosis, stroke, and chronic fatigue syndrome/myalgic encephalomyelitis, endure pathological levels of fatigue. The aim of this narrative review is to delineate the wide array of pathways that may underpin the incapacitating fatigue occurring in systemic and neuro-inflammatory disorders. A wide array of immune, inflammatory, oxidative and nitrosative stress (O&NS), bioenergetic, and neurophysiological abnormalities are involved in the etiopathology of these disease states and may underpin the incapacitating fatigue that accompanies these disorders. This range of abnormalities comprises: increased levels of pro-inflammatory cytokines, e.g., interleukin-1 (IL-1), IL-6, tumor necrosis factor (TNF) α and interferon (IFN) α; O&NS-induced muscle fatigue; activation of the Toll-Like Receptor Cycle through pathogen-associated (PAMPs) and damage-associated (DAMPs) molecular patterns, including heat shock proteins; altered glutaminergic and dopaminergic neurotransmission; mitochondrial dysfunctions; and O&NS-induced defects in the sodium-potassium pump. Fatigue is also associated with altered activities in specific brain regions and muscle pathology, such as reductions in maximum voluntary muscle force, downregulation of the mitochondrial biogenesis master gene peroxisome proliferator-activated receptor gamma coactivator 1-alpha, a shift to glycolysis and buildup of toxic metabolites within myocytes. As such, both mental and physical fatigue, which frequently accompany immune-inflammatory and neuro-inflammatory disorders, are the consequence of interactions between multiple systemic and central pathways.

  1. [Immune system and rheumatic diseases in the elderly].

    PubMed

    Schirmer, Michael

    2016-06-01

    Impairments of the immune system play an important role in all immun-mediated rheumatic diseases. Recently, the following news were reported: · Early aging of the immune system with thymus insufficiency has now been reported for both patients with rheumatoid arthritis and axial spondyloarthritis, without prethymic lack of progenitors at least in rheumatoid arthritis.. · For giant cell arteritis, the most frequent vasculitis in the elderly, an increased expression of IL-17A in temporal artery biopsies coincides with good prognosis and reponse to glucocorticoids.. · Concerning immunosenescence in systemic lupus erythematosus, BAFF appears to have an important role for relapses after B-cell depletion.. For the future it can be anticipated that the use of unified classification criteria for rheumatic diseases (as with the new 2012 EULAR / ACR classification criteria for polymyalgia rheumatica) will ensure better comparability of immunological studies also in the elderly. PMID:27254630

  2. Opposing effects of alcohol on the immune system.

    PubMed

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

    2016-02-01

    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.

  3. AIDS Federal Policy Act of 1987. Hearings on S. 1575: To Amend the Public Health Service Act To Establish a Grant Program To Provide for Counseling and Testing Services Relating to Acquired Immune Deficiency Syndrome and To Establish Certain Prohibitions for the Purpose of Protecting Individuals with Acquired Immune Deficiency Syndrome or Related Conditions. Committee on Labor and Human Resources. United States Senate, One Hundredth Congress, First Session.

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. Senate Committee on Labor and Human Resources.

    This document presents the text from two Senate hearings on the AIDS Federal Policy Act of 1987 which concerns voluntary testing for AIDS virus, education and counseling to stop the spread of AIDS (Acquired Immune Deficiency Syndrome), and confidentiality and discrimination against AIDS victims. In the first hearing, opening statements are…

  4. 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. PMID:21824078

  5. 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.

  6. 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.

  7. Impact of the immune system and immunotherapy in colorectal cancer

    PubMed Central

    Markman, Janet L.

    2015-01-01

    The development of cancer is a multi-step process involving the gradual loss of regulation over the growth and functional capabilities of normal cells. Much research has been focused on the numerous cell intrinsic factors that govern this process; however, recent attention has turned to understanding the cell extrinsic factors in the tumor microenvironment that appear equally critical to the progression and treatment of cancer. One critical component of the tumor microenvironment is the immune system and it has become increasingly evident that the immune system plays an integral role in preventing and promoting the development of cancer. Understanding the immune cell types and pathways involved in this process has enabled the development of novel biomarkers for prognosis and accelerated the development of immune-based therapeutics, both of which have the potential to forever change the treatment paradigms for colorectal cancer (CRC). In this review, we discuss the impact of the immune system on the initiation, progression and treatment of cancer, specifically focusing on CRC. PMID:25830040

  8. Stress, opioid peptides, the immune system, and cancer.

    PubMed

    Shavit, Y; Terman, G W; Martin, F C; Lewis, J W; Liebeskind, J C; Gale, R P

    1985-08-01

    Our results indicate that a particular form of footshock stress can suppress immune function in rats and decrease their resistance to tumor challenge. These effects appear to be mediated by opioid peptides released by stress, and they can be mimicked by high doses of morphine given systemically or by a vastly smaller dose delivered intracerebroventricularly. Such findings fit well into the emerging field of behavioral neuroimmunology and reinforce continuing efforts to elucidate the neural and neurohumoral mechanisms by which the environment can affect the organism's immune system.

  9. [State of neuroendocrine systems and immunity in patients with burns].

    PubMed

    Nazarov, I P; Popov, A A; Mal'tseva, M A; Osetrov, I V; Kokaulina, G D; Popova, E A

    1994-01-01

    The study of hormonal shifts and immunity in 95 patients with burns has revealed hyperergic reaction of the neuroendocrine system in the early period after trauma, accompanied by a marked and prolonged inhibition of cellular and humoral immunity. The use of antistress agents (clofelin, pentamine) and intravenous laser blood irradiation leads to a more prompt arrest of hyperergic reaction of the neuroendocrine system and to the reduction of immunosuppressing effect of burn trauma, which decreases the number of pyoseptic complications from 26.4 to 16% and total lethality from 16 to 3.8%.

  10. 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.

  11. 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.

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

    SciTech Connect

    Hightower, R.; Forrest, S. . Dept. of Computer Science); Perelson, A.S. )

    1993-01-01

    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.

  13. 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…

  14. Taking advantage of the systemic immune system to cure brain diseases.

    PubMed

    Yong, V Wee; Rivest, Serge

    2009-10-15

    The systemic immune system has the ability to modulate multiple brain functions, including autonomic responses, glial reactivity following neural injuries, and neuronal excitability. Immune stimuli also influence microglia subpopulations originating from blood progenitors, and neuroprotective and reparative capacities of blood-derived microglia were recently described in mouse models of spinal cord injury and brain disorders. Furthermore, reparative roles for various immune subsets have been recognized, such as in inducing myelin repair. Nonetheless, uncontrolled and excessive activation of immune responses can be detrimental. The development of strategies to stimulate the systemic immune system safely to protect or repair brain disorders remains a major challenge ahead, but important inroads have been made. We discuss here some of the mechanisms underlying the neuroprotective and reparative effects of the systemic immune system and the most promising immunotherapies tested in mouse models of injuries and diseases, such as Alzheimer's disease, amyotrophic lateral sclerosis, and multiple sclerosis.

  15. Small and Long Regulatory RNAs in the Immune System and Immune Diseases

    PubMed Central

    Stachurska, Anna; Zorro, Maria M.; van der Sijde, Marijke R.; Withoff, Sebo

    2014-01-01

    Cellular differentiation is regulated on the level of gene expression, and it is known that dysregulation of gene expression can lead to deficiencies in differentiation that contribute to a variety of diseases, particularly of the immune system. Until recently, it was thought that the dysregulation was governed by changes in the binding or activity of a class of proteins called transcription factors. However, the discovery of micro-RNAs and recent descriptions of long non-coding RNAs (lncRNAs) have given enormous momentum to a whole new field of biology: the regulatory RNAs. In this review, we describe these two classes of regulatory RNAs and summarize what is known about how they regulate aspects of the adaptive and innate immune systems. Finally, we describe what is known about the involvement of micro-RNAs and lncRNAs in three different autoimmune diseases (celiac disease, inflammatory bowel disease, and multiple sclerosis). PMID:25368617

  16. 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

  17. The role of neutrophils in the immune system: an overview.

    PubMed

    Malech, Harry L; Deleo, Frank R; Quinn, Mark T

    2014-01-01

    Neutrophils, also known as polymorphonuclear leukocytes (PMNs), have long been considered as the short-lived, nonspecific white cells that form pus-and also happen to kill invading microbes. Indeed, neutrophils were often neglected (and largely not considered) as immune cells. This historic view of neutrophils has changed considerably over the past several decades, and we know now that, in addition to playing the predominant role in the clearance of bacteria and fungi, they play a major role in shaping the host response to infection and immune system homeostasis. The change in our view of the role of neutrophils in the immune system has been due in large part to the study of these cells in vitro. Such work has been made possible by new and/or improved methods and approaches used to investigate neutrophils. These methods are the focus of this volume.

  18. Overview of integrin signaling in the immune system.

    PubMed

    Kinashi, Tatsuo

    2012-01-01

    It has been well established that integrins mediate cell-cell and cell-matrix adhesion and play crucial roles in the immune system such as leukocyte-endothelium interactions, immune synapse formation, and effector functions. Since the discovery that integrins undergo dynamic changes of adhesive activities in response to external stimuli, intensive studies have been conducted to elucidate the signaling events that control the activation of integrins (inside-out signaling) and signaling events from the induced integrin-dependent adhesion (outside-in signaling). The molecular characterization of these signaling pathways highlights the importance of integrins as bidirectional signaling receptors. The characteristics of integrin signaling are best exemplified in the immune system. This chapter highlights the recent studies of intracellular signaling pathways that regulate integrins in immunological contexts.

  19. Complement - a key system for immune surveillance and homeostasis

    PubMed Central

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

    2010-01-01

    Nearly a century after the significance of the human complement system was recognized we have come to realize that its versatile functions extend far beyond the elimination of microbes. Indeed, 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 may 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 dual role in homeostasis and disease. PMID:20720586

  20. 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

  1. Effect of chemical systemic acquired resistance elicitors on avenanthramide biosynthesis in oat (Avena sativa).

    PubMed

    Wise, Mitchell L

    2011-07-13

    Oats produce a group of phenolic antioxidants termed avenanthramides. These metabolites are, among food crops, unique to oats and have shown, in experimental systems, certain desirable nutritional characteristics such as inhibiting atherosclerotic plaque formation and reducing inflammation. Avenanthramides occur in both the leaves and grain of oat. In the leaves they are expressed as phytoalexins in response to crown rust (Puccina coronata) infection. The experiments reported here demonstrate that avenanthramide levels in vegetative tissue can be enhanced by treatment with benzothiadiazole (BTH), an agrochemical formulated to elicit systemic acquired resistance (SAR). The response to BTH was dramatically stronger than those produced with salicylic acid treatment. The roots of BTH treated plants also showed a smaller but distinct increase in avenanthramides. The dynamics of the root avenanthramide increase was substantially slower than that observed in the leaves, suggesting that avenanthramides might be transported from the leaves.

  2. The Innate Immune System in Acute and Chronic Wounds

    PubMed Central

    MacLeod, Amanda S.; Mansbridge, Jonathan N.

    2016-01-01

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

  3. Contrasting Roles of the Apoplastic Aspartyl Protease APOPLASTIC, ENHANCED DISEASE SUSCEPTIBILITY1-DEPENDENT1 and LEGUME LECTIN-LIKE PROTEIN1 in Arabidopsis Systemic Acquired Resistance.

    PubMed

    Breitenbach, Heiko H; Wenig, Marion; Wittek, Finni; Jordá, Lucia; Maldonado-Alconada, Ana M; Sarioglu, Hakan; Colby, Thomas; Knappe, Claudia; Bichlmeier, Marlies; Pabst, Elisabeth; Mackey, David; Parker, Jane E; Vlot, A Corina

    2014-04-22

    Systemic acquired resistance (SAR) is an inducible immune response that depends on ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Here, we show that Arabidopsis (Arabidopsis thaliana) EDS1 is required for both SAR signal generation in primary infected leaves and SAR signal perception in systemic uninfected tissues. In contrast to SAR signal generation, local resistance remains intact in eds1 mutant plants in response to Pseudomonas syringae delivering the effector protein AvrRpm1. We utilized the SAR-specific phenotype of the eds1 mutant to identify new SAR regulatory proteins in plants conditionally expressing AvrRpm1. Comparative proteomic analysis of apoplast-enriched extracts from AvrRpm1-expressing wild-type and eds1 mutant plants led to the identification of 12 APOPLASTIC, EDS1-DEPENDENT (AED) proteins. The genes encoding AED1, a predicted aspartyl protease, and another AED, LEGUME LECTIN-LIKE PROTEIN1 (LLP1), were induced locally and systemically during SAR signaling and locally by salicylic acid (SA) or its functional analog, benzo 1,2,3-thiadiazole-7-carbothioic acid S-methyl ester. Because conditional overaccumulation of AED1-hemagglutinin inhibited SA-induced resistance and SAR but not local resistance, the data suggest that AED1 is part of a homeostatic feedback mechanism regulating systemic immunity. In llp1 mutant plants, SAR was compromised, whereas the local resistance that is normally associated with EDS1 and SA as well as responses to exogenous SA appeared largely unaffected. Together, these data indicate that LLP1 promotes systemic rather than local immunity, possibly in parallel with SA. Our analysis reveals new positive and negative components of SAR and reinforces the notion that SAR represents a distinct phase of plant immunity beyond local resistance.

  4. Do-Not-Resuscitate Orders and/or Hospice Care, Psychological Health, and Quality of Life among Children/Adolescents with Acquired Immune Deficiency Syndrome

    PubMed Central

    Lyon, Maureen E.; Williams, Paige L.; Woods, Elizabeth R.; Hutton, Nancy; Butler, Anne M.; Sibinga, Erica; Brady, Michael T.; Oleske, James M.

    2009-01-01

    Objective The frequency of do-not-resuscitate (DNR) orders and hospice enrollment in children/adolescents living with acquired immune deficiency syndrome (AIDS) and followed in Pediatric AIDS Clinical Trials Group (PACTG) Study 219C was examined, and evaluated for any association with racial disparities or enhanced quality of life (QOL), particularly psychological adjustment. Methods A cross-sectional analysis of children with AIDS enrolled in this prospective multicenter observational study between 2000 and 2005 was conducted to evaluate the incidence of DNR/hospice overall and by calendar time. Linear regression models were used to compare caregivers' reported QOL scores within 6 domains between those with and without DNR/hospice care, adjusting for confounders. Results Seven hundred twenty-six (726) children with AIDS had a mean age of 12.9 years (standard deviation [SD] = 4.5), 51% were male, 60% black, 25% Hispanic. Twenty-one (2.9%) had either a DNR order (n = 16), hospice enrollment (n = 7), or both (n = 2). Of 41 children who died, 80% had no DNR/hospice care. Increased odds of DNR/hospice were observed for those with CD4% less than 15%, no current antiretroviral use, and prior hospitalization. No differences by race were detected. Adjusted mean QOL scores were significantly lower for those with DNR/hospice enrollment than those without across all domains except for psychological status and health care utilization. Poorer psychological status correlated with higher symptom distress, but not with DNR/hospice enrollment after adjusting for symptoms. Conclusions Children who died of AIDS rarely had DNR/hospice enrollment. National guidelines recommend that quality palliative care be integrated routinely with HIV care. Further research is needed to explore the barriers to palliative care and advance care planning in this population. PMID:18363489

  5. 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.

  6. Bacteria-Triggered Systemic Immunity in Barley Is Associated with WRKY and ETHYLENE RESPONSIVE FACTORs But Not with Salicylic Acid1[C][W

    PubMed Central

    Dey, Sanjukta; Wenig, Marion; Langen, Gregor; Sharma, Sapna; Kugler, Karl G.; Knappe, Claudia; Hause, Bettina; Bichlmeier, Marlies; Babaeizad, Valiollah; Imani, Jafargholi; Janzik, Ingar; Stempfl, Thomas; Hückelhoven, Ralph; Kogel, Karl-Heinz; Mayer, Klaus F.X.

    2014-01-01

    Leaf-to-leaf systemic immune signaling known as systemic acquired resistance is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to systemic acquired resistance in Arabidopsis (Arabidopsis thaliana), systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid. Instead, we documented a moderate local but not systemic induction of abscisic acid after infection of leaves with Psj. In contrast to salicylic acid or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or abscisic acid triggered systemic immunity to Xtc. RNA sequencing analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest, and quantitative reverse transcription-polymerase chain reaction associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR (ERF)-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors, possibly facilitating transcriptional reprogramming to potentiate immunity. PMID:25332505

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

    PubMed

    Sotelo, Julio

    2015-02-01

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

  8. Ready-to-use colloidal adjuvant systems for intranasal immunization.

    PubMed

    Lee, Jeong-Jun; Shim, Aeri; Lee, Song Yi; Kwon, Bo-Eun; Kim, Seong Ryeol; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2016-04-01

    Adjuvant systems based on oil-in-water (o/w) microemulsions (MEs) for vaccination via intranasal administration were prepared and evaluated. A ready-to-use blank ME system composed of mineral oil (oil), Labrasol (surfactant), Tween 80 (cosurfactant), and water was prepared and blended with antigen (Ag) solution prior to use. The o/w ME system developed exhibited nano-size droplets within the tested range of Ag concentrations and dilution factors. The maintenance of primary, secondary, and tertiary structural stability of ovalbumin (OVA) in ME, compared with OVA in solution, was demonstrated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), and fluorescence intensity measurements, respectively. The uptake efficiency in RAW 264.7 cells, evaluated by flow cytometry, of OVA in the ME group was significantly higher than that of the OVA solution group (p<0.05). In an intranasal immunization study with OVA ME in mice, elevated adjuvant effects in terms of mucosal immunization and Th1-dominant cell-mediated immune responses were identified. Given the convenience of use (simply mixing with Ag solution prior to use) and the adjuvant effects after intranasal immunization, the new o/w ME may be a practical and efficient adjuvant system for intranasal vaccination. PMID:26775242

  9. 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.

  10. Diversity of CRISPR-Cas immune systems and molecular machines.

    PubMed

    Barrangou, Rodolphe

    2015-01-01

    Bacterial adaptive immunity hinges on CRISPR-Cas systems that provide DNA-encoded, RNA-mediated targeting of exogenous nucleic acids. A plethora of CRISPR molecular machines occur broadly in prokaryotic genomes, with a diversity of Cas nucleases that can be repurposed for various applications.

  11. 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.

  12. Control of commensal microbiota by the adaptive immune system.

    PubMed

    Zhang, Husen; Luo, Xin M

    2015-01-01

    The symbiotic relationship between the mammalian host and gut microbes has fascinated many researchers in recent years. Use of germ-free animals has contributed to our understanding of how commensal microbes affect the host. Immunodeficiency animals lacking specific components of the mammalian immune system, on the other hand, enable studying of the reciprocal function-how the host controls which microbes to allow for symbiosis. Here we review the recent advances and discuss our perspectives of how to better understand the latter, with an emphasis on the effects of adaptive immunity on the composition and diversity of gut commensal bacteria. PMID:25901893

  13. Systemic and Mucosal Immune Responses to Cryptosporidium—Vaccine Development

    PubMed Central

    Ludington, Jacob G.; Ward, Honorine D.

    2015-01-01

    Cryptosporidium spp is a major cause of diarrheal disease worldwide, particularly in malnourished children and untreated AIDS patients in developing countries in whom it can cause severe, chronic and debilitating disease. Unfortunately, there is no consistently effective drug for these vulnerable populations and no vaccine, partly due to a limited understanding of both the parasite and the host immune response. In this review, we will discuss our current understanding of the systemic and mucosal immune responses to Cryptosporidium infection, discuss the feasibility of developing a Cryptosporidium vaccine and evaluate recent advances in Cryptosporidium vaccine development strategies PMID:26279971

  14. [THE DEVELOPMENT OF IMMUNE ENZYME AND IMMUNE CHROMATOGRAPHIC MONOCLONAL TEST-SYSTEM FOR DETECTING TULAREMIA AGENT].

    PubMed

    Eremkin, A V; Elagin, G D; Petchenkin, D V; Fomenkov, O O; Bogatcheva, N V; Kitmanov, A A; Kuklina, G V; Tikhvinskaya, O V

    2016-03-01

    The immune enzyme and immunochromatographic test-systems for detecting tularemia agent were developed on the basis of selected set of monoclonal antibodies having immunochemical activity to antigens Francisella tularensis. The evaluation of sensitivity and specificity of developed test-systems demonstrated that samples provided detection of strains of F. tularensis in concentration from 5.0 x 105 mkxcm-3 to 1.0 x 106 mkxcm-3 and gave no false positive results in analysis of heterologous microorganisms in concentration of 1.0 x 108 mkxcm-3. PMID:27506111

  15. [THE DEVELOPMENT OF IMMUNE ENZYME AND IMMUNE CHROMATOGRAPHIC MONOCLONAL TEST-SYSTEM FOR DETECTING TULAREMIA AGENT].

    PubMed

    Eremkin, A V; Elagin, G D; Petchenkin, D V; Fomenkov, O O; Bogatcheva, N V; Kitmanov, A A; Kuklina, G V; Tikhvinskaya, O V

    2016-03-01

    The immune enzyme and immunochromatographic test-systems for detecting tularemia agent were developed on the basis of selected set of monoclonal antibodies having immunochemical activity to antigens Francisella tularensis. The evaluation of sensitivity and specificity of developed test-systems demonstrated that samples provided detection of strains of F. tularensis in concentration from 5.0 x 105 mkxcm-3 to 1.0 x 106 mkxcm-3 and gave no false positive results in analysis of heterologous microorganisms in concentration of 1.0 x 108 mkxcm-3.

  16. 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.

  17. Multifunctional antimicrobial proteins and peptides: natural activators of immune systems.

    PubMed

    Niyonsaba, François; Nagaoka, Isao; Ogawa, Hideoki; Okumura, Ko

    2009-01-01

    In addition to the physical barrier of the stratum corneum, cutaneous innate immunity also includes the release of various humoral mediators, such as cytokines and chemokines, recruitment and activation of phagocytes, and the production of antimicrobial proteins/peptides (AMPs). AMPs form an innate epithelial chemical shield, which provides a front-line component in innate immunity to inhibit microbial invasion; however, this might be an oversimplification of the diverse functions of these molecules. In fact, apart from exhibiting a broad spectrum of microbicidal properties, it is increasingly evident that AMPs display additional activities that are related to the stimulation and modulation of the cutaneous immune system. These diverse functions include chemoattraction and activation of immune and/or inflammatory cells, the production and release of cytokines and chemokines, acceleration of angiogenesis, promotion of wound healing, neutralization of harmful microbial products, and bridging of both innate and adaptive immunity. Thus, better understanding of the functions of AMPs in skin and identification of their signaling mechanisms may offer new strategies for the development of potential therapeutics for the treatment of infection- and/or inflammation-related skin diseases. Here, we briefly outline the structure, regulation of expression, and multifunctional roles of principal skin-derived AMPs.

  18. Endocannabinoids and the Immune System in Health and Disease.

    PubMed

    Cabral, Guy A; Ferreira, Gabriela A; Jamerson, Melissa J

    2015-01-01

    Endocannabinoids are bioactive lipids that have the potential to signal through cannabinoid receptors to modulate the functional activities of a variety of immune cells. Their activation of these seven-transmembranal, G protein-coupled receptors sets in motion a series of signal transductional events that converge at the transcriptional level to regulate cell migration and the production of cytokines and chemokines. There is a large body of data that supports a functional relevance for 2-arachidonoylglycerol (2-AG) as acting through the cannabinoid receptor type 2 (CB2R) to inhibit migratory activities for a diverse array of immune cell types. However, unequivocal data that supports a functional linkage of anandamide (AEA) to a cannabinoid receptor in immune modulation remains to be obtained. Endocannabinoids, as typical bioactive lipids, have a short half-life and appear to act in an autocrine and paracrine fashion. Their immediate effective action on immune function may be at localized sites in the periphery and within the central nervous system. It is speculated that endocannabinoids play an important role in maintaining the overall "fine-tuning" of the immune homeostatic balance within the host. PMID:26408161

  19. 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

  20. Links between the innate immune system and sleep.

    PubMed

    Majde, Jeannine A; Krueger, James M

    2005-12-01

    Sleep is a fundamental physiologic process with unknown functions. It is divided into 2 distinct states: non-rapid-eye-movement sleep and rapid-eye-movement sleep. After acute infection with nonneurotropic agents, there are stereotypic changes in non-rapid-eye-movement sleep, particularly increased time spent in slow-wave sleep, and often a reduction of time spent in rapid-eye-movement sleep. It is now recognized that both infection-associated sleep and spontaneous sleep are regulated, in part, by immune mediators called cytokines. This review provides brief tutorials on the elements of the innate immune system that detect infection, how sleep is characterized in the laboratory, issues regarding the interpretation of sleep effects on immune function, the interaction of sleep with circadian rhythms and stress, and some of the microbial products, cytokines, and neuropeptides associated with sleep regulation. We also summarize our current understanding of the role of sleep in host defense and asthma exacerbation.

  1. The interaction between cytomegalovirus and the human immune system.

    PubMed

    ten Berge, Ineke J M; van Lier, René A W

    2014-12-01

    Studies on antiviral immunity in man are hampered by the impossibility to standardize the infection as is done in experimental animal studies. An exception is the occurrence of cytomegalovirus infection transmitted by a donor organ into a transplant-recipient, where the time-point of infection is exactly known. Moreover, its strong interaction with the human immune system during evolution and the strong immunogenic properties of this persistent virus, as well as the need for intervention e.g. by vaccine development, all make studies towards the immune response against just this virus very attractive and relevant. In this work, we will present an overview of the studies on this topic that were performed in the departments of Experimental and Clinical Immunology in the AMC and Sanquin in Amsterdam.

  2. Discovery of functional genes for systemic acquired resistance in Arabidopsis thaliana through integrated data mining.

    PubMed

    Pan, Youlian; Pylatuik, Jeffrey D; Ouyang, Junjun; Famili, A Fazel; Fobert, Pierre R

    2004-12-01

    Various data mining techniques combined with sequence motif information in the promoter region of genes were applied to discover functional genes that are involved in the defense mechanism of systemic acquired resistance (SAR) in Arabidopsis thaliana. A series of K-Means clustering with difference-in-shape as distance measure was initially applied. A stability measure was used to validate this clustering process. A decision tree algorithm with the discover-and-mask technique was used to identify a group of most informative genes. Appearance and abundance of various transcription factor binding sites in the promoter region of the genes were studied. Through the combination of these techniques, we were able to identify 24 candidate genes involved in the SAR defense mechanism. The candidate genes fell into 2 highly resolved categories, each category showing significantly unique profiles of regulatory elements in their promoter regions. This study demonstrates the strength of such integration methods and suggests a broader application of this approach.

  3. Immunomodulatory and Antioxidant Effects of Purple Sweet Potato Extract in LP-BM5 Murine Leukemia Virus-Induced Murine Acquired Immune Deficiency Syndrome.

    PubMed

    Kim, Ok-Kyung; Nam, Da-Eun; Yoon, Ho-Geun; Baek, Sun Jung; Jun, Woojin; Lee, Jeongmin

    2015-08-01

    The immunomodulatory effects of a dietary supplement of purple sweet potato extract (PSPE) in LP-BM5 murine leukemia virus (MuLV)-induced immune-deficient mice were investigated. Mice were divided into six groups: normal control, infected control (LP-BM5 MuLV infection), positive control (LP-BM5 MuLV infection+dietary supplement of red ginseng 300 mg/kg), purple sweet potato water extract (PSPWE) (LP-BM5 MuLV infection+dietary supplement of PSPE 300 mg/kg), PSP10EE (LP-BM5 MuLV infection+dietary supplement of 10% ethanol PSPE 300 mg/kg), and PSP80EE (LP-BM5 MuLV infection+dietary supplement of 80% ethanol PSPE 300 mg/kg). Dietary supplementation began on the day of LP-BM5 MuLV infection and continued for 12 weeks. Dietary supplementation of PSPE inhibited LP-BM5 MuLV-induced splenomegaly and lymphadenopathy and attenuated the suppression of T- and B-cell proliferation and T helper 1/T helper 2 cytokine imbalance in LP-BM5 MuLV-infected mice. Dietary supplement of PSPE increased the activity of the antioxidant enzymes, superoxide dismutase and glutathione peroxidase. The data suggest that PSPE may ameliorate immune dysfunction due to LP-BM5 MuLV infection by modulating antioxidant defense systems. PMID:26076116

  4. [Cytokines. Transmittor substances of the immune system].

    PubMed

    Pisa, P; Söder, O

    1995-07-12

    Cytokines are hormone-like proteins and peptides whose principal function is that of signalling substances within the immunoinflammatory and haematopoietic systems. Since the first cytokines were characterised 15 years ago, over 50 cytokines have been strictly defined and characterised. Cytokines are classified mainly on the basis of functional criteria into families--e.g, interleukins, interferons, colony stimulating factors, and chemokines. The article provides a broad review of cytokine physiology and pathophysiology with an emphasis on recent findings of their involvement in various diseases such as infections, autoimmune and haematological disorders, and cancer. Different treatment modalities that affect cytokine activity are discussed.

  5. Platelets--an important element of the immune system.

    PubMed

    Trzeciak-Ryczek, A; Tokarz-Deptuła, B; Deptuła, W

    2013-01-01

    Platelets are anucleate cells derived from the megakaryocyte series, and have long been considered only as cells responsible for coagulation and the fibrinolysis process. However, recently more data shows that they are also effector cells in the inflammatory response and important elements of the immunological response. Platelets store and release many biologically active substances, including growth factors, cytokines and chemokines (tab. 1), which actively affect i.a. elements of the immune system, and thus become regulators of immunity and mediators of inflammatory response. Their impact on the immune system cells is also associated with the induction of leucocytes and progenitor cells to the site of pathogen permeation or vascular injury inflow, as well as endothelial cells. Interacting with neutrophils, monocytes and lymphocytes, they not only activate them, but also form platelet-leukocyte aggregates that immobilise pathogens and prevent their spreading. Furthermore, platelets are capable of absorbing pathogens, affecting anti-infection immunity of the system. It is also assumed that the presence of receptors on their surface, such as Toll-like receptors (TLRs), affects their initiation and activity of the immunological response.

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

    PubMed Central

    Ullrich, Oliver; Huber, Kathrin; Lang, Kerstin

    2008-01-01

    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. PMID:18957108

  7. 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. PMID:19704303

  8. 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. PMID:25123831

  9. The Microbiota, the Immune System and the Allograft

    PubMed Central

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

    2015-01-01

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

  10. 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.

  11. 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.

  12. Mucosal and systemic immunity in mice after intranasal immunization with recombinant Lactococcus lactis expressing ORF6 of PRRSV.

    PubMed

    Wang, Zhen-hua; Cao, Xiao-han; Du, Xiao-gang; Feng, Hai-bo; Di-Wang; He-Song; Zeng, Xian-yin

    2014-02-01

    The purpose of the study was to construct mucosal vaccine of a recombinant Lactococcus lactis expressing PRRSV ORF6 gene and evaluate mucosal and systemic immune response against PRRSV in mice after intranasal immunization. The result show that the vaccine can stimulate mice to produce specific IgG in serum and remarkable special s-IgA in lung lavage fluid, at the same time, the contents of cytokines IL-2 and IFN-γ of the experimental group were significant higher than those of the control group (P < 0.01), however, the contents of cytokines IL-4 was not different to the all groups. In summary, the constructed mucosal vaccine can significantly induce mucosal immune, humoral immunity and cellular immunity involved Th1 type cytokines, which will lay a theoretical foundation on immune mechanism and new efficient vaccines for PRRSV. PMID:24423464

  13. Mucosal and systemic immunity in mice after intranasal immunization with recombinant Lactococcus lactis expressing ORF6 of PRRSV.

    PubMed

    Wang, Zhen-hua; Cao, Xiao-han; Du, Xiao-gang; Feng, Hai-bo; Di-Wang; He-Song; Zeng, Xian-yin

    2014-02-01

    The purpose of the study was to construct mucosal vaccine of a recombinant Lactococcus lactis expressing PRRSV ORF6 gene and evaluate mucosal and systemic immune response against PRRSV in mice after intranasal immunization. The result show that the vaccine can stimulate mice to produce specific IgG in serum and remarkable special s-IgA in lung lavage fluid, at the same time, the contents of cytokines IL-2 and IFN-γ of the experimental group were significant higher than those of the control group (P < 0.01), however, the contents of cytokines IL-4 was not different to the all groups. In summary, the constructed mucosal vaccine can significantly induce mucosal immune, humoral immunity and cellular immunity involved Th1 type cytokines, which will lay a theoretical foundation on immune mechanism and new efficient vaccines for PRRSV.

  14. A PC-based telemetry system for acquiring and reducing data from multiple PCM streams

    NASA Astrophysics Data System (ADS)

    Simms, D. A.; Butterfield, C. P.

    1991-07-01

    The Solar Energy Research Institute's (SERI) Wind Research Program is using Pulse Code Modulation (PCM) Telemetry Data-Acquisition Systems to study horizontal-axis wind turbines. Many PCM systems are combined for use in test installations that require accurate measurements from a variety of different locations. SERI has found them ideal for data-acquisition from multiple wind turbines and meteorological towers in wind parks. A major problem has been in providing the capability to quickly combine and examine incoming data from multiple PCM sources in the field. To solve this problem, SERI has developed a low-cost PC-based PCM Telemetry Data-Reduction System (PC-PCM System) to facilitate quick, in-the-field multiple-channel data analysis. The PC-PCM System consists of two basic components. First, PC-compatible hardware boards are used to decode and combine multiple PCM data streams. Up to four hardware boards can be installed in a single PC, which provides the capability to combine data from four PCM streams directly to PC disk or memory. Each stream can have up to 62 data channels. Second, a software package written for use under DOS was developed to simplify data-acquisition control and management. The software, called the Quick-Look Data Management Program, provides a quick, easy-to-use interface between the PC and multiple PCM data streams. The Quick-Look Data Management Program is a comprehensive menu-driven package used to organize, acquire, process, and display information from incoming PCM data streams. The paper describes both hardware and software aspects of the SERI PC-PCM system, concentrating on features that make it useful in an experiment test environment to quickly examine and verify incoming data from multiple PCM streams. Also discussed are problems and techniques associated with PC-based telemetry data-acquisition, processing, and real-time display.

  15. Uncoupling High Light Responses from Singlet Oxygen Retrograde Signaling and Spatial-Temporal Systemic Acquired Acclimation.

    PubMed

    Carmody, Melanie; Crisp, Peter A; d'Alessandro, Stefano; Ganguly, Diep; Gordon, Matthew; Havaux, Michel; Albrecht-Borth, Verónica; Pogson, Barry J

    2016-07-01

    Distinct ROS signaling pathways initiated by singlet oxygen ((1)O2) or superoxide and hydrogen peroxide have been attributed to either cell death or acclimation, respectively. Recent studies have revealed that more complex antagonistic and synergistic relationships exist within and between these pathways. As specific chloroplastic ROS signals are difficult to study, rapid systemic signaling experiments using localized high light (HL) stress or ROS treatments were used in this study to uncouple signals required for direct HL and ROS perception and distal systemic acquired acclimation (SAA). A qPCR approach was chosen to determine local perception and distal signal reception. Analysis of a thylakoidal ascorbate peroxidase mutant (tapx), the (1)O2-retrograde signaling double mutant (ex1/ex2), and an apoplastic signaling double mutant (rbohD/F) revealed that tAPX and EXECUTER 1 are required for both HL and systemic acclimation stress perception. Apoplastic membrane-localized RBOHs were required for systemic spread of the signal but not for local signal induction in directly stressed tissues. Endogenous ROS treatments revealed a very strong systemic response induced by a localized 1 h induction of (1)O2 using the conditional flu mutant. A qPCR time course of (1)O2 induced systemic marker genes in directly and indirectly connected leaves revealed a direct vascular connection component of both immediate and longer term SAA signaling responses. These results reveal the importance of an EXECUTER-dependent (1)O2 retrograde signal for both local and long distance RBOH-dependent acclimation signaling that is distinct from other HL signaling pathways, and that direct vascular connections have a role in spatial-temporal SAA induction. PMID:27288360

  16. Designing neuroclassifier fusion system by immune genetic algorithm

    NASA Astrophysics Data System (ADS)

    Liang, Jimin; Zhao, Heng; Yang, Wanhai

    2001-09-01

    A multiple neural network classifier fusion system design method using immune genetic algorithm (IGA) is proposed. The IGA is modeled after the mechanics of human immunity. By using vaccination and immune selection in the evolution procedures, the IGA outperforms the traditional genetic algorithms in restraining the degenerate phenomenon and increasing the converging speed. The fusion system consists of N neural network classifiers that work independently and in parallel to classify a given input pattern. The classifiers' outputs are aggregated by a fusion scheme to decide the collective classification results. The goal of the system design is to obtain a fusion system with both good generalization and efficiency in space and time. Two kinds of measures, the accuracy of classification and the size of the neural networks, are used by IGA to evaluate the fusion system. The vaccines are abstracted by a self-adaptive scheme during the evolutionary process. A numerical experiment on the 'alternate labels' problem is implemented and the comparisons of IGA with traditional genetic algorithm are presented.

  17. 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.

  18. [Mechanisms of innate immunity].

    PubMed

    Sochocka, Marta; Błach-Olszewska, Zofia

    2005-01-01

    Innate (natural) immunity differs from acquired immunity with respect to the detection systems (receptors and structures detected on pathogens), the cells engaged, and the nature of the mechanisms. Innate immunity is an ancient system, with similar structures in plants, invertebrates, and vertebrates are involved in the development of defense against pathogens. Toll-like receptor (TLR) structures are present in all organisms, and some mechanisms (i.e. complement activation) were also discovered in invertebrates and vertebrates. During infection, innate reactions develop before acquired immune reactions do. Natural immunity involves such reactions as the production of different cytokines, chemokines, and interleukins; the innate, cytokines-dependent nonspecific immunity of leukocytes; HLA-independent pathogen-killing cells, and phagocytosis. Such cytokines as interferons, the TNF family, and interleukines 12 and 18 participate in antiviral, antibacterial, antiprotozoan and anticancer natural immunity. NK cells, cytokines of the TNF family, and the complement system activated by lectins are engaged in the non-specific killing of infected or tumor cells. As over-activation of the innate system can be dangerous, the system must be submitted the strict control. The exact mechanism of this control system is not yet known, but there are several indications of its presence.

  19. The Role of Age and Exposure to Plasmodium falciparum in the Rate of Acquisition of Naturally Acquired Immunity: A Randomized Controlled Trial

    PubMed Central

    Guinovart, Caterina; Dobaño, Carlota; Bassat, Quique; Nhabomba, Augusto; Quintó, Llorenç; Manaca, Maria Nélia; Aguilar, Ruth; Rodríguez, Mauricio H.; Barbosa, Arnoldo; Aponte, John J.; Mayor, Alfredo G.; Renom, Montse; Moraleda, Cinta; Roberts, David J.; Schwarzer, Evelin; Le Souëf, Peter N.; Schofield, Louis; Chitnis, Chetan E.; Doolan, Denise L.; Alonso, Pedro L.

    2012-01-01

    Background The rate of acquisition of naturally acquired immunity (NAI) against malaria predominantly depends on transmission intensity and age, although disentangling the effects of these is difficult. We used chemoprophylaxis to selectively control exposure to P. falciparum during different periods in infancy and explore the effect of age in the build-up of NAI, measured as risk of clinical malaria. Methods and Findings A three-arm double-blind randomized placebo-controlled trial was conducted in 349 infants born to Mozambican HIV-negative women. The late exposure group (LEG) received monthly Sulfadoxine-Pyrimethamine (SP) plus Artesunate (AS) from 2.5–4.5 months of age and monthly placebo from 5.5–9.5 months; the early exposure group (EEG) received placebo from 2.5–4.5 months and SP+AS from 5.5–9.5 months; and the control group (CG) received placebo from 2.5–9.5 months. Active and passive case detection (PCD) were conducted from birth to 10.5 and 24 months respectively. The primary endpoint was time to first or only episode of malaria in the second year detected by PCD. The incidence of malaria during the second year was of 0.50, 0.51 and 0.35 episodes/PYAR in the LEG, EEG and CG respectively (p = 0.379 for the adjusted comparison of the 3 groups). The hazard ratio of the adjusted comparison between the LEG and the CG was 1.38 (0.83–2.28, p = 0.642) and that between the EEG and the CG was 1.35 (0.81–2.24, p = 0.743). Conclusions After considerably interfering with exposure during the first year of life, there was a trend towards a higher risk of malaria in the second year in children who had received chemoprophylaxis, but there was no significant rebound. No evidence was found that the age of first exposure to malaria affects the rate of acquisition of NAI. Thus, the timing of administration of antimalarial interventions like malaria vaccines during infancy does not appear to be a critical determinant. Trial Registration Clinical

  20. 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.

  1. Predicting Hospital-Acquired Infections by Scoring System with Simple Parameters

    PubMed Central

    Chang, Ying-Jui; Yeh, Min-Li; Lin, Chao-Cheng; Hsu, Meng-Shiuan; Chiu, Wen-Ta

    2011-01-01

    Background Hospital-acquired infections (HAI) are associated with increased attributable morbidity, mortality, prolonged hospitalization, and economic costs. A simple, reliable prediction model for HAI has great clinical relevance. The objective of this study is to develop a scoring system to predict HAI that was derived from Logistic Regression (LR) and validated by Artificial Neural Networks (ANN) simultaneously. Methodology/Principal Findings A total of 476 patients from all the 806 HAI inpatients were included for the study between 2004 and 2005. A sample of 1,376 non-HAI inpatients was randomly drawn from all the admitted patients in the same period of time as the control group. External validation of 2,500 patients was abstracted from another academic teaching center. Sixteen variables were extracted from the Electronic Health Records (EHR) and fed into ANN and LR models. With stepwise selection, the following seven variables were identified by LR models as statistically significant: Foley catheterization, central venous catheterization, arterial line, nasogastric tube, hemodialysis, stress ulcer prophylaxes and systemic glucocorticosteroids. Both ANN and LR models displayed excellent discrimination (area under the receiver operating characteristic curve [AUC]: 0.964 versus 0.969, p = 0.507) to identify infection in internal validation. During external validation, high AUC was obtained from both models (AUC: 0.850 versus 0.870, p = 0.447). The scoring system also performed extremely well in the internal (AUC: 0.965) and external (AUC: 0.871) validations. Conclusions We developed a scoring system to predict HAI with simple parameters validated with ANN and LR models. Armed with this scoring system, infectious disease specialists can more efficiently identify patients at high risk for HAI during hospitalization. Further, using parameters either by observation of medical devices used or data obtained from EHR also provided good prediction outcome that

  2. 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

  3. Systemic PPARgamma ligation inhibits allergic immune response in the skin.

    PubMed

    Dahten, Anja; Koch, Christin; Ernst, Dennis; Schnöller, Corinna; Hartmann, Susanne; Worm, Margitta

    2008-09-01

    We have shown previously that specific ligands of the peroxisome proliferator-activated receptor-gamma (PPARgamma) inhibit the systemic allergic immune response. The objective of this study was to investigate the impact of PPARgamma-ligand treatment on the local allergic immune response. We established a murine model exhibiting clinical and histological features of AD-like skin lesions with high reproducibility. In this model, the PPARgamma ligand was applied in an either preventive or therapeutic manner via systemic and local routes. The affected skin areas were assessed by standardized skin score, histological analyses, and immunohistochemical examinations. Our data show that systemic application of PPARgamma ligand by a preventive protocol led to significantly reduced onset of eczematous skin lesions. This was confirmed by histology, showing decreased skin thickness accompanied by significantly reduced infiltrations of CD4+ and CD8+ lymphocytes but also mast cells. Additionally, early allergen-specific IgE and IgG1 responses were reduced (day 21/35), whereas IgG2a levels remained unchanged. In conclusion, our results demonstrate that PPARgamma-ligand treatment inhibits not only systemic allergic immune response, but also local allergen-mediated dermatitis. Our findings point to therapeutic strategies, including a PPARgamma-ligand-based treatment. PMID:18401424

  4. 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.

  5. 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

  6. Maternal Immune Activation Disrupts Dopamine System in the Offspring

    PubMed Central

    Luchicchi, Antonio; Lecca, Salvatore; Melis, Miriam; De Felice, Marta; Cadeddu, Francesca; Frau, Roberto; Muntoni, Anna Lisa; Fadda, Paola; Devoto, Paola

    2016-01-01

    Background: In utero exposure to maternal viral infections is associated with a higher incidence of psychiatric disorders with a supposed neurodevelopmental origin, including schizophrenia. Hence, immune response factors exert a negative impact on brain maturation that predisposes the offspring to the emergence of pathological phenotypes later in life. Although ventral tegmental area dopamine neurons and their target regions play essential roles in the pathophysiology of psychoses, it remains to be fully elucidated how dopamine activity and functionality are disrupted in maternal immune activation models of schizophrenia. Methods: Here, we used an immune-mediated neurodevelopmental disruption model based on prenatal administration of the polyriboinosinic-polyribocytidilic acid in rats, which mimics a viral infection and recapitulates behavioral abnormalities relevant to psychiatric disorders in the offspring. Extracellular dopamine levels were measured by brain microdialysis in both the nucleus accumbens shell and the medial prefrontal cortex, whereas dopamine neurons in ventral tegmental area were studied by in vivo electrophysiology. Results: Polyriboinosinic-polyribocytidilic acid-treated animals, at adulthood, displayed deficits in sensorimotor gating, memory, and social interaction and increased baseline extracellular dopamine levels in the nucleus accumbens, but not in the prefrontal cortex. In polyriboinosinic-polyribocytidilic acid rats, dopamine neurons showed reduced spontaneously firing rate and population activity. Conclusions: These results confirm that maternal immune activation severely impairs dopamine system and that the polyriboinosinic-polyribocytidilic acid model can be considered a proper animal model of a psychiatric condition that fulfills a multidimensional set of validity criteria predictive of a human pathology. PMID:26819283

  7. Regulation of metabolism by the innate immune system.

    PubMed

    Lackey, Denise E; Olefsky, Jerrold M

    2016-01-01

    Low-grade tissue inflammation induced by obesity can result in insulin resistance, which in turn is a key cause of type 2 diabetes mellitus. Cells of the innate immune system produce cytokines and other factors that impair insulin signalling, which contributes to the connection between obesity and the onset of type 2 diabetes mellitus. Here, we review the innate immune cells involved in secreting inflammatory factors in the obese state. In the adipose tissue, these cells include proinflammatory adipose tissue macrophages and natural killer cells. We also discuss the role of innate immune cells, such as anti-inflammatory adipose tissue macrophages, eosinophils, group 2 innate lymphoid cells and invariant natural killer T cells, in maintaining an anti-inflammatory and insulin-sensitive environment in the lean state. In the liver, both Kupffer cells and recruited hepatic macrophages can contribute to decreased hepatic insulin sensitivity. Proinflammatory macrophages might also adversely affect insulin sensitivity in the skeletal muscle and pancreatic β-cell function. Finally, this Review provides an overview of the mechanisms for regulating proinflammatory immune responses that could lead to future therapeutic opportunities to improve insulin sensitivity.

  8. 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.

  9. Systemic Acquired Resistance in Moss: Further Evidence for Conserved Defense Mechanisms in Plants

    PubMed Central

    Winter, Peter S.; Bowman, Collin E.; Villani, Philip J.; Dolan, Thomas E.; Hauck, Nathanael R.

    2014-01-01

    Vascular plants possess multiple mechanisms for defending themselves against pathogens. One well-characterized defense mechanism is systemic acquired resistance (SAR). In SAR, a plant detects the presence of a pathogen and transmits a signal throughout the plant, inducing changes in the expression of various pathogenesis-related (PR) genes. Once SAR is established, the plant is capable of mounting rapid responses to subsequent pathogen attacks. SAR has been characterized in numerous angiosperm and gymnosperm species; however, despite several pieces of evidence suggesting SAR may also exist in non-vascular plants6–8, its presence in non-vascular plants has not been conclusively demonstrated, in part due to the lack of an appropriate culture system. Here, we describe and use a novel culture system to demonstrate that the moss species Amblystegium serpens does initiate a SAR-like reaction upon inoculation with Pythium irregulare, a common soil-borne oomycete. Infection of A. serpens gametophores by P. irregulare is characterized by localized cytoplasmic shrinkage within 34 h and chlorosis and necrosis within 7 d of inoculation. Within 24 h of a primary inoculation (induction), moss gametophores grown in culture became highly resistant to infection following subsequent inoculation (challenge) by the same pathogen. This increased resistance was a response to the pathogen itself and not to physical wounding. Treatment with β-1,3 glucan, a structural component of oomycete cell walls, was equally effective at triggering SAR. Our results demonstrate, for the first time, that this important defense mechanism exists in a non-vascular plant, and, together with previous studies, suggest that SAR arose prior to the divergence of vascular and non-vascular plants. In addition, this novel moss – pathogen culture system will be valuable for future characterization of the mechanism of SAR in moss, which is necessary for a better understanding of the evolutionary history of SAR

  10. The effect of induced hyperthermia on the immune system.

    PubMed

    Dieing, Annette; Ahlers, Olaf; Hildebrandt, Bert; Kerner, Thoralf; Tamm, Ingo; Possinger, Kurt; Wust, Peter

    2007-01-01

    Therapeutical hyperthermia has been considered for cancer therapy since William Coley observed tumour remission after induction of fever by bacterial toxins at the end of the 19th century. Because fever is associated with a variety of immunological reactions, it has been suspected, that therapeutical hyperthermia might also activate the immune system in a reproducible manner and thereby positively influence the course of the disease. During the last decade, new insight has been gained regarding the immunological changes taking place during therapeutic hyperthermia. In this chapter, we review the most relevant data known about the effect of hyperthermia on the immune system with special focus on alterations induced by therapeutical whole-body hyperthermia (WBH) in cancer patients.

  11. 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.

  12. 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 ...

  13. 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 ...

  14. 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

    2011-06-16

    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.

  15. 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.

  16. 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).

  17. Caterpillar saliva interferes with induced Arabidopsis thaliana defence responses via the systemic acquired resistance pathway

    PubMed Central

    Weech, Marie-Hélène; Chapleau, Mélanie; Pan, Li; Ide, Christine; Bede, Jacqueline C.

    2008-01-01

    Arabidopsis thaliana (L.) Heynh. genotypes limited in their ability to mount either octadecanoid-dependent induced resistance (IR–) or systemic acquired resistance (SAR–) were used to characterize the roles of these pathways in plant–herbivore interactions. Molecular and biochemical markers of IR were analysed in plants subject to herbivory by caterpillars of the beet armyworm, Spodoptera exigua Hübner, which had either intact or impaired salivary secretions since salivary enzymes, such as glucose oxidase, have been implicated in the ability of caterpillars to circumvent induced plant defences. Transcript expression of genes encoding laccase-like multicopper oxidase [AtLMCO4 (polyphenol oxidase)] and defensin (AtPDF1.2) showed salivary-specific patterns which were disrupted in the SAR– mutant plants. The activity of octadecanoid-associated anti-nutritive proteins, such as LMCO and trypsin inhibitor, showed similar patterns. Gene and protein changes parallel plant hormone levels where elevated jasmonic acid was observed in wild-type plants fed upon by caterpillars with impaired salivary secretions compared with plants subject to herbivory by normal caterpillars. This salivary-specific difference in jasmonic acid levels was alleviated in SAR– mutants. These results support the model that caterpillar saliva interferes with jasmonate-dependent plant defences by activating the SAR pathway. PMID:18487634

  18. 12 CFR 617.7620 - What should the System institution do when it decides to sell acquired agricultural real estate...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false What should the System institution do when it decides to sell acquired agricultural real estate at a public auction? 617.7620 Section 617.7620 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM BORROWER RIGHTS Right of First Refusal §...

  19. 12 CFR 617.7615 - What should the System institution do when it decides to lease acquired agricultural real estate?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 7 2012-01-01 2012-01-01 false What should the System institution do when it... the System institution do when it decides to lease acquired agricultural real estate? (a) Notify the... estate, it must notify the previous owner, by certified mail, of the property's appraised rental...

  20. 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.

  1. Building a National Immunization System: A Guide to Immunization Services and Resources.

    ERIC Educational Resources Information Center

    Franklin, Paula; And Others

    Over the past several years, outbreaks of vaccine-preventable diseases have drawn greater attention to the problem of low immunization rates in the U.S. In response to this problem, the federal government created the Vaccines for Children program as a foundation for a new national immunization policy to ensure proper and timely immunizations for…

  2. 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. PMID:27039885

  3. Joint replacement surgery and the innate immune system.

    PubMed

    Goodman, Stuart B; Konttinen, Yrjo T; Takagi, Michiaki

    2014-01-01

    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

  4. 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.

  5. Extracellular RNAs: A Secret Arm of Immune System Regulation.

    PubMed

    de Candia, Paola; De Rosa, Veronica; Casiraghi, Maurizio; Matarese, Giuseppe

    2016-04-01

    The immune system has evolved to protect multicellular organisms from the attack of a variety of pathogens. To exert this function efficiently, the system has developed the capacity to coordinate the function of different cell types and the ability to down-modulate the response when the foreign attack is over. For decades, immunologists believed that these two characteristics were primarily related to cytokine/chemokine-based communication and cell-to-cell direct contact. More recently, it has been shown that immune cells also communicate by transferring regulatory RNAs, microRNAs in particular, from one cell to the other. Several studies have suggested a functional role of extracellular regulatory RNAs in cell-to-cell communication in different cellular contexts. This minireview focuses on the potential role of extracellular RNA transfer in the regulation of adaptive immune response, also contextualizing it in a broader field of what is known of cell-free RNAs in communication among different organisms in the evolutionary scale.

  6. Suppression of systemic autoimmunity by the innate immune adaptor STING

    PubMed Central

    Sharma, Shruti; Campbell, Allison M.; Chan, Jennie; Schattgen, Stefan A.; Orlowski, Gregory M.; Nayar, Ribhu; Huyler, Annie H.; Nündel, Kerstin; Mohan, Chandra; Berg, Leslie J.; Shlomchik, Mark J.; Marshak-Rothstein, Ann; Fitzgerald, Katherine A.

    2015-01-01

    Cytosolic DNA-sensing pathways that signal via Stimulator of interferon genes (STING) mediate immunity to pathogens and also promote autoimmune pathology in DNaseII- and DNaseIII-deficient mice. In contrast, we report here that STING potently suppresses inflammation in a model of systemic lupus erythematosus (SLE). Lymphoid hypertrophy, autoantibody production, serum cytokine levels, and other indicators of immune activation were markedly increased in STING-deficient autoimmune-prone mice compared with STING-sufficient littermates. As a result, STING-deficient autoimmune-prone mice had significantly shorter lifespans than controls. Importantly, Toll-like receptor (TLR)-dependent systemic inflammation during 2,6,10,14-tetramethylpentadecane (TMPD)-mediated peritonitis was similarly aggravated in STING-deficient mice. Mechanistically, STING-deficient macrophages failed to express negative regulators of immune activation and thus were hyperresponsive to TLR ligands, producing abnormally high levels of proinflammatory cytokines. This hyperreactivity corresponds to dramatically elevated numbers of inflammatory macrophages and granulocytes in vivo. Collectively these findings reveal an unexpected negative regulatory role for STING, having important implications for STING-directed therapies. PMID:25646421

  7. Comparative Proteomics Analysis of Phloem Exudates Collected during the Induction of Systemic Acquired Resistance1[OPEN

    PubMed Central

    Wilson, Daniel C.; Dey, Sanjukta; Hauck, Stefanie M.; Vlot, A. Corina; Cameron, Robin K.

    2016-01-01

    Systemic acquired resistance (SAR) is a plant defense response that provides long-lasting, broad-spectrum pathogen resistance to uninfected systemic leaves following an initial localized infection. In Arabidopsis (Arabidopsis thaliana), local infection with virulent or avirulent strains of Pseudomonas syringae pv tomato generates long-distance SAR signals that travel from locally infected to distant leaves through the phloem to establish SAR. In this study, a proteomics approach was used to identify proteins that accumulate in phloem exudates in response to the induction of SAR. To accomplish this, phloem exudates collected from mock-inoculated or SAR-induced leaves of wild-type Columbia-0 plants were subjected to label-free quantitative liquid chromatography-tandem mass spectrometry proteomics. Comparing mock- and SAR-induced phloem exudate proteomes, 16 proteins were enriched in phloem exudates collected from SAR-induced plants, while 46 proteins were suppressed. SAR-related proteins THIOREDOXIN h3, ACYL-COENZYME A-BINDING PROTEIN6, and PATHOGENESIS-RELATED1 were enriched in phloem exudates of SAR-induced plants, demonstrating the strength of this approach and suggesting a role for these proteins in the phloem during SAR. To identify novel components of SAR, transfer DNA mutants of differentially abundant phloem proteins were assayed for SAR competence. This analysis identified a number of new proteins (m-type thioredoxins, major latex protein-like protein, ULTRAVIOLET-B RESISTANCE8 photoreceptor) that contribute to the SAR response. The Arabidopsis SAR phloem proteome is a valuable resource for understanding SAR long-distance signaling and the dynamic nature of the phloem during plant-pathogen interactions. PMID:27208255

  8. Endosymbiotic bacteria in insects: guardians of the immune system?

    PubMed

    Eleftherianos, Ioannis; Atri, Jaishri; Accetta, Julia; Castillo, Julio C

    2013-01-01

    Insects have evolved obligate, mutualistic interactions with bacteria without further transmission to other eukaryotic organisms. Such long-term obligate partnerships between insects and bacteria have a profound effect on various physiological functions of the host. Here we provide an overview of the effects of endosymbiotic bacteria on the insect immune system as well as on the immune response of insects to pathogenic infections. Potential mechanisms through which endosymbionts can affect the ability of their host to resist an infection are discussed in the light of recent findings. We finally point out unresolved questions for future research and speculate how the current knowledge can be employed to design and implement measures for the effective control of agricultural insect pests and vectors of diseases.

  9. 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

  10. The behavioural immune system and the psychology of human sociality

    PubMed Central

    Schaller, Mark

    2011-01-01

    Because immunological defence against pathogens is costly and merely reactive, human anti-pathogen defence is also characterized by proactive behavioural mechanisms that inhibit contact with pathogens in the first place. This behavioural immune system comprises psychological processes that infer infection risk from perceptual cues, and that respond to these perceptual cues through the activation of aversive emotions, cognitions and behavioural impulses. These processes are engaged flexibly, producing context–contingent variation in the nature and magnitude of aversive responses. These processes have important implications for human social cognition and social behaviour—including implications for social gregariousness, person perception, intergroup prejudice, mate preferences, sexual behaviour and conformity. Empirical evidence bearing on these many implications is reviewed and discussed. This review also identifies important directions for future research on the human behavioural immune system—including the need for enquiry into underlying mechanisms, additional behavioural consequences and implications for human health and well-being. PMID:22042918

  11. Endosymbiotic bacteria in insects: guardians of the immune system?

    PubMed Central

    Eleftherianos, Ioannis; Atri, Jaishri; Accetta, Julia; Castillo, Julio C.

    2013-01-01

    Insects have evolved obligate, mutualistic interactions with bacteria without further transmission to other eukaryotic organisms. Such long-term obligate partnerships between insects and bacteria have a profound effect on various physiological functions of the host. Here we provide an overview of the effects of endosymbiotic bacteria on the insect immune system as well as on the immune response of insects to pathogenic infections. Potential mechanisms through which endosymbionts can affect the ability of their host to resist an infection are discussed in the light of recent findings. We finally point out unresolved questions for future research and speculate how the current knowledge can be employed to design and implement measures for the effective control of agricultural insect pests and vectors of diseases. PMID:23508299

  12. Single-cell technologies for monitoring immune systems

    PubMed Central

    Chattopadhyay, Pratip K; Gierahn, Todd M; Roederer, Mario; Love, J Christopher

    2014-01-01

    The complex heterogeneity of cells, and their interconnectedness with each other, are major challenges to identifying clinically relevant measurements that reflect the state and capability of the immune system. Highly multiplexed, single-cell technologies may be critical for identifying correlates of disease or immunological interventions as well as for elucidating the underlying mechanisms of immunity. Here we review limitations of bulk measurements and explore advances in single-cell technologies that overcome these problems by expanding the depth and breadth of functional and phenotypic analysis in space and time. The geometric increases in complexity of data make formidable hurdles for exploring, analyzing and presenting results. We summarize recent approaches to making such computations tractable and discuss challenges for integrating heterogeneous data obtained using these single-cell technologies. PMID:24448570

  13. Immune Restoration

    MedlinePlus

    ... marrow cells immune to HIV infection. Letting the immune system repair itself: CD4 counts have increased for many ... have taken ART. Some scientists believe that the immune system might be able to heal and repair itself ...

  14. The coagulation system and its function in early immune defense.

    PubMed

    van der Poll, Tom; Herwald, Heiko

    2014-10-01

    Blood coagulation has a Janus-faced role in infectious diseases. When systemically activated, it can cause serious complications associated with high morbidity and mortality. However, coagulation is also part of the innate immune system and its local activation has been found to play an important role in the early host response to infection. Though the latter aspect has been less investigated, phylogenetic studies have shown that many factors involved in coagulation have ancestral origins which are often combined with anti-microbial features. This review gives a general overview about the most recent advances in this area of research also referred to as immunothrombosis.

  15. Innate lymphoid cells and natural killer T cells in the gastrointestinal tract immune system.

    PubMed

    Montalvillo, Enrique; Garrote, José Antonio; Bernardo, David; Arranz, Eduardo

    2014-05-01

    The gastrointestinal tract is equipped with a highly specialized intrinsic immune system. However, the intestine is exposed to a high antigenic burden that requires a fast, nonspecific response -so-called innate immunity- to maintain homeostasis and protect the body from incoming pathogens. In the last decade multiple studies helped to unravel the particular developmental requirements and specific functions of the cells that play a role in innate immunity. In this review we shall focus on innate lymphoid cells, a newly discovered, heterogeneous set of cells that derive from an Id2-dependent lymphoid progenitor cell population. These cells have been categorized on the basis of the pattern of cytokines that they secrete, and the transcription factors that regulate their development and functions. Innate lymphoid cells play a role in the early response to pathogens, the anatomical contention of the commensal flora, and the maintenance of epithelial integrity.Amongst the various innate lymphoid cells we shall lay emphasis on a subpopulation with several peculiarities, namely that of natural killer T cells, a subset of T lymphocytes that express both T-cell and NK-cell receptors. The most numerous fraction of the NKT population are the so-called invariant NKT or iNKT cells. These iNKT cells have an invariant TCR and recognize the glycolipidic structures presented by the CD1d molecule, a homolog of class-I MHC molecules. Following activation they rapidly acquire cytotoxic activity and secrete both Th1 and Th2 cytokines, including IL-17. While their specific role is not yet established, iNKT cells take part in a great variety of intestinal immune responses ranging from oral tolerance to involvement in a number of gastrointestinal conditions.

  16. ANCA negative pauci-immune glomerulonephritis with systemic involvement.

    PubMed

    Sampathkumar, K; Ramakrishnan, M; Sah, A K; Gowtham, S; Ajeshkumar, R N

    2010-01-01

    Systemic vasculitides (SV) are a group of diseases with multi system involvement and varied clinical presentation. Anti-neutrophil cytoplasmic antibody (ANCA) testing has high sensitivity and specificity for SV. We describe the clinical course of four patients who had pauci-immune glomerulonephritis with systemic involvement without serological ANCA positivity; they were followed up for a cumulative 55 patient months. The mean Birmingham vasculitis score score was 23. All four had systemic symptoms with arthralgias and fever (100%). Neurological manifestations were seen in two patients (66%). Accelerated hypertension was seen in one. One patient had pulmonary renal syndrome. Renal manifestation was characterized by nephrotic range of proteinuria with glomerular hematuria in all (100%) and severe renal failure requiring dialysis in three (66%). At admission the mean blood urea was 146 +/- 19 mg% and mean serum creatinine was 5.6 +/- 1.9 mg%. Renal biopsy revealed focal proliferative glomerulonephritis with crescents only in 20-30% of glomeruli. There was significant chronic interstitial involvement in two patients (66%). Therapy with pulse steroids, cyclophosphamide, and mycophenolate mofetil (MMF) was effective in three patients while one died with lung hemorrhage. In conclusion, majority of patients with ANCA negative pauci-immune glomerulonephritis have multi-system involvement at admission. Renal biopsy is characterized by focal proliferative lesions with crescents and significant chronic interstitial fibrosis. Immunosuppressive drugs in the form of corticosteroids, MMF and cyclophosphamide bring about marked renal recovery in most patients. PMID:20535271

  17. NH4+ protects tomato plants against Pseudomonas syringae by activation of systemic acquired acclimation.

    PubMed

    Fernández-Crespo, Emma; Scalschi, Loredana; Llorens, Eugenio; García-Agustín, Pilar; Camañes, Gemma

    2015-11-01

    NH4 (+) nutrition provokes mild toxicity by enhancing H2O2 accumulation, which acts as a signal activating systemic acquired acclimation (SAA). Until now, induced resistance mechanisms in response to an abiotic stimulus and related to SAA were only reported for exposure to a subsequent abiotic stress. Herein, the first evidence is provided that this acclimation to an abiotic stimulus induces resistance to later pathogen infection, since NH4 (+) nutrition (N-NH4 (+))-induced resistance (NH4 (+)-IR) against Pseudomonas syringae pv tomato DC3000 (Pst) in tomato plants was demonstrated. N-NH4 (+) plants displayed basal H2O2, abscisic acid (ABA), and putrescine (Put) accumulation. H2O2 accumulation acted as a signal to induce ABA-dependent signalling pathways required to prevent NH4 (+) toxicity. This acclimatory event provoked an increase in resistance against later pathogen infection. N-NH4 (+) plants displayed basal stomatal closure produced by H2O2 derived from enhanced CuAO and rboh1 activity that may reduce the entry of bacteria into the mesophyll, diminishing the disease symptoms as well as strongly inducing the oxidative burst upon Pst infection, favouring NH4 (+)-IR. Experiments with inhibitors of Put accumulation and the ABA-deficient mutant flacca demonstrated that Put and ABA downstream signalling pathways are required to complete NH4 (+)-IR. The metabolic profile revealed that infected N-NH4 (+) plants showed greater ferulic acid accumulation compared with control plants. Although classical salicylic acid (SA)-dependent responses against biotrophic pathogens were not found, the important role of Put in the resistance of tomato against Pst was demonstrated. Moreover, this work revealed the cross-talk between abiotic stress acclimation (NH4 (+) nutrition) and resistance to subsequent Pst infection.

  18. NH4 + protects tomato plants against Pseudomonas syringae by activation of systemic acquired acclimation

    PubMed Central

    Fernández-Crespo, Emma; Scalschi, Loredana; Llorens, Eugenio; García-Agustín, Pilar; Camañes, Gemma

    2015-01-01

    NH4 + nutrition provokes mild toxicity by enhancing H2O2 accumulation, which acts as a signal activating systemic acquired acclimation (SAA). Until now, induced resistance mechanisms in response to an abiotic stimulus and related to SAA were only reported for exposure to a subsequent abiotic stress. Herein, the first evidence is provided that this acclimation to an abiotic stimulus induces resistance to later pathogen infection, since NH4 + nutrition (N-NH4 +)-induced resistance (NH4 +-IR) against Pseudomonas syringae pv tomato DC3000 (Pst) in tomato plants was demonstrated. N-NH4 + plants displayed basal H2O2, abscisic acid (ABA), and putrescine (Put) accumulation. H2O2 accumulation acted as a signal to induce ABA-dependent signalling pathways required to prevent NH4 + toxicity. This acclimatory event provoked an increase in resistance against later pathogen infection. N-NH4 + plants displayed basal stomatal closure produced by H2O2 derived from enhanced CuAO and rboh1 activity that may reduce the entry of bacteria into the mesophyll, diminishing the disease symptoms as well as strongly inducing the oxidative burst upon Pst infection, favouring NH4 +-IR. Experiments with inhibitors of Put accumulation and the ABA-deficient mutant flacca demonstrated that Put and ABA downstream signalling pathways are required to complete NH4 +-IR. The metabolic profile revealed that infected N-NH4 + plants showed greater ferulic acid accumulation compared with control plants. Although classical salicylic acid (SA)-dependent responses against biotrophic pathogens were not found, the important role of Put in the resistance of tomato against Pst was demonstrated. Moreover, this work revealed the cross-talk between abiotic stress acclimation (NH4 + nutrition) and resistance to subsequent Pst infection. PMID:26246613

  19. From rote learning to system building: acquiring verb morphology in children and connectionist nets.

    PubMed

    Plunkett, K; Marchman, V

    1993-07-01

    The traditional account of the acquisition of English verb morphology supposes that a dual architecture underlies the transition from early rote-learning processes (in which past tense forms of verbs are correctly produced) to the systematic treatment of verbs (in which irregular verbs are prone to error). A connectionist account supposes that this transition can occur in a single mechanism (in the form of a neural network) driven by gradual quantitative changes in the size of the training set to which the network is exposed. In this paper, a series of simulations is reported in which a multi-layered perceptron learns to map verb stems to past tense forms analogous to the mappings found in the English past tense system. By expanding the training set in a gradual, incremental fashion and evaluating network performance on both trained and novel verbs at successive points in learning, it is demonstrated that the network undergoes reorganizations that result in a shift from a mode of rote learning to a systematic treatment of verbs. Furthermore, we show that this reorganizational transition is dependent upon the number of regular and irregular verbs in the training set and is sensitive to the phonological sub-regularities characterizing the irregular verbs. The pattern of errors observed is compared to that of children acquiring the English past tense, as well as children's performance on experimental studies with nonsense verbs. It is concluded that a connectionist approach offers a viable alternative account of the acquisition of English verb morphology, given the current state of empirical evidence relating to processes of acquisition in young children.

  20. Systemic acquired resistance delays race shifts to major resistance genes in bell pepper.

    PubMed

    Romero, A M; Ritchie, D F

    2004-12-01

    ABSTRACT The lack of durability of host plant disease resistance is a major problem in disease control. Genotype-specific resistance that involves major resistance (R) genes is especially prone to failure. The compatible (i.e., disease) host-pathogen interaction with systemic acquired resistance (SAR) has been studied extensively, but the incompatible (i.e., resistant) interaction less so. Using the pepper-bacterial spot (causal agent, Xanthomonas axonopodis pv. vesicatoria) pathosystem, we examined the effect of SAR in reducing the occurrence of race-change mutants that defeat R genes in laboratory, greenhouse, and field experiments. Pepper plants carrying one or more R genes were sprayed with the plant defense activator acibenzolar-S-methyl (ASM) and challenged with incompatible strains of the pathogen. In the greenhouse, disease lesions first were observed 3 weeks after inoculation. ASM-treated plants carrying a major R gene had significantly fewer lesions caused by both the incompatible (i.e., hypersensitive) and compatible (i.e., disease) responses than occurred on nonsprayed plants. Bacteria isolated from the disease lesions were confirmed to be race-change mutants. In field experiments, there was a delay in the detection of race-change mutants and a reduction in disease severity. Decreased disease severity was associated with a reduction in the number of race-change mutants and the suppression of disease caused by the race-change mutants. This suggests a possible mechanism related to a decrease in the pathogen population size, which subsequently reduces the number of race-change mutants for the selection pressure of R genes. Thus, inducers of SAR are potentially useful for increasing the durability of genotype-specific resistance conferred by major R genes.