WorldWideScience

Sample records for immune system signaling

  1. Roles of Zinc Signaling in the Immune System.

    Science.gov (United States)

    Hojyo, Shintaro; Fukada, Toshiyuki

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Huber Kathrin

    2008-10-01

    Full Text Available Abstract 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.

  3. Zinc Signals and Immunity.

    Science.gov (United States)

    Maywald, Martina; Wessels, Inga; Rink, Lothar

    2017-10-24

    Zinc homeostasis is crucial for an adequate function of the immune system. Zinc deficiency as well as zinc excess result in severe disturbances in immune cell numbers and activities, which can result in increased susceptibility to infections and development of especially inflammatory diseases. This review focuses on the role of zinc in regulating intracellular signaling pathways in innate as well as adaptive immune cells. Main underlying molecular mechanisms and targets affected by altered zinc homeostasis, including kinases, caspases, phosphatases, and phosphodiesterases, will be highlighted in this article. In addition, the interplay of zinc homeostasis and the redox metabolism in affecting intracellular signaling will be emphasized. Key signaling pathways will be described in detail for the different cell types of the immune system. In this, effects of fast zinc flux, taking place within a few seconds to minutes will be distinguish from slower types of zinc signals, also designated as "zinc waves", and late homeostatic zinc signals regarding prolonged changes in intracellular zinc.

  4. Design principles of paradoxical signaling in the immune system

    Science.gov (United States)

    Hart, Yuval

    A widespread feature of cell-cell signaling systems is paradoxical pleiotropy: the same secreted signaling molecule can induce opposite effects in the responding cells. For example, the cytokine IL-2 can promote proliferation and death of T-cells. The role of such paradoxical signaling remains unclear. We suggest that this mechanism provides homeostatic concentration of cells, independent of initial conditions. The crux of the paradoxical mechanism is the combination of a positive and a negative feedback loops creating two stable states - an OFF state and an ON state. Experimentally, we found that CD4 + cells grown in culture with a 30-fold difference in initial concentrations reached a homeostatic concentration nearly independent of initial cell levels (ON-state). Below an initial threshold, cell density decayed to extinction (OFF-state). Mathematical modeling explained the observed cell and cytokine dynamics and predicted conditions that shifted cell fate from homeostasis to the OFF-state. We suggest that paradoxical signaling provides cell circuits with specific dynamical features that are robust to environmental perturbations.

  5. Cholinergic signalling in gut immunity

    NARCIS (Netherlands)

    Dhawan, Shobhit; Cailotto, Cathy; Harthoorn, Lucien F.; de Jonge, Wouter J.

    2012-01-01

    The gut immune system shares many signalling molecules and receptors with the autonomic nervous system. A good example is the vagal neurotransmitter acetylcholine (ACh), for which many immune cell types express cholinergic receptors (AChR). In the last decade the vagal nerve has emerged as an

  6. DMPD: Glucocorticoids and the innate immune system: crosstalk with the toll-likereceptor signaling network. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17576036 Glucocorticoids and the innate immune system: crosstalk with the toll-like...07 May 13. (.png) (.svg) (.html) (.csml) Show Glucocorticoids and the innate immune system: crosstalk with t...nd the innate immune system: crosstalk with the toll-likereceptor signaling network. Authors Chinenov Y, Rog

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

    Science.gov (United States)

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

    2015-01-01

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

  8. Immune System

    Science.gov (United States)

    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...

  9. Modular and coordinated expression of immune system regulatory and signaling components in the developing and adult nervous system.

    Science.gov (United States)

    Monzón-Sandoval, Jimena; Castillo-Morales, Atahualpa; Crampton, Sean; McKelvey, Laura; Nolan, Aoife; O'Keeffe, Gerard; Gutierrez, Humberto

    2015-01-01

    During development, the nervous system (NS) is assembled and sculpted through a concerted series of neurodevelopmental events orchestrated by a complex genetic programme. While neural-specific gene expression plays a critical part in this process, in recent years, a number of immune-related signaling and regulatory components have also been shown to play key physiological roles in the developing and adult NS. While the involvement of individual immune-related signaling components in neural functions may reflect their ubiquitous character, it may also reflect a much wider, as yet undescribed, genetic network of immune-related molecules acting as an intrinsic component of the neural-specific regulatory machinery that ultimately shapes the NS. In order to gain insights into the scale and wider functional organization of immune-related genetic networks in the NS, we examined the large scale pattern of expression of these genes in the brain. Our results show a highly significant correlated expression and transcriptional clustering among immune-related genes in the developing and adult brain, and this correlation was the highest in the brain when compared to muscle, liver, kidney and endothelial cells. We experimentally tested the regulatory clustering of immune system (IS) genes by using microarray expression profiling in cultures of dissociated neurons stimulated with the pro-inflammatory cytokine TNF-alpha, and found a highly significant enrichment of immune system-related genes among the resulting differentially expressed genes. Our findings strongly suggest a coherent recruitment of entire immune-related genetic regulatory modules by the neural-specific genetic programme that shapes the NS.

  10. Targeting Cannabinoid Signaling in the Immune System: “High”-ly Exciting Questions, Possibilities, and Challenges

    Directory of Open Access Journals (Sweden)

    Attila Oláh

    2017-11-01

    Full Text Available It is well known that certain active ingredients of the plants of Cannabis genus, i.e., the “phytocannabinoids” [pCBs; e.g., (−-trans-Δ9-tetrahydrocannabinol (THC, (−-cannabidiol, etc.] can influence a wide array of biological processes, and the human body is able to produce endogenous analogs of these substances [“endocannabinoids” (eCB, e.g., arachidonoylethanolamine (anandamide, AEA, 2-arachidonoylglycerol (2-AG, etc.]. These ligands, together with multiple receptors (e.g., CB1 and CB2 cannabinoid receptors, etc., and a complex enzyme and transporter apparatus involved in the synthesis and degradation of the ligands constitute the endocannabinoid system (ECS, a recently emerging regulator of several physiological processes. The ECS is widely expressed in the human body, including several members of the innate and adaptive immune system, where eCBs, as well as several pCBs were shown to deeply influence immune functions thereby regulating inflammation, autoimmunity, antitumor, as well as antipathogen immune responses, etc. Based on this knowledge, many in vitro and in vivo studies aimed at exploiting the putative therapeutic potential of cannabinoid signaling in inflammation-accompanied diseases (e.g., multiple sclerosis or in organ transplantation, and to dissect the complex immunological effects of medical and “recreational” marijuana consumption. Thus, the objective of the current article is (i to summarize the most recent findings of the field; (ii to highlight the putative therapeutic potential of targeting cannabinoid signaling; (iii to identify open questions and key challenges; and (iv to suggest promising future directions for cannabinoid-based drug development.

  11. High-dimensional analysis of the aging immune system: verification of age-associated differences in immune signaling responses in healthy donors.

    Science.gov (United States)

    Longo, Diane M; Louie, Brent; Ptacek, Jason; Friedland, Greg; Evensen, Erik; Putta, Santosh; Atallah, Michelle; Spellmeyer, David; Wang, Ena; Pos, Zoltan; Marincola, Francesco M; Schaeffer, Andrea; Lukac, Suzanne; Railkar, Radha; Beals, Chan R; Cesano, Alessandra; Carayannopoulos, Leonidas N; Hawtin, Rachael E

    2014-06-21

    Single-cell network profiling (SCNP) is a multiparametric flow cytometry-based approach that simultaneously measures evoked signaling in multiple cell subsets. Previously, using the SCNP approach, age-associated immune signaling responses were identified in a cohort of 60 healthy donors. In the current study, a high-dimensional analysis of intracellular signaling was performed by measuring 24 signaling nodes in 7 distinct immune cell subsets within PBMCs in an independent cohort of 174 healthy donors [144 elderly (>65 yrs); 30 young (25-40 yrs)]. Associations between age and 9 immune signaling responses identified in the previously published 60 donor cohort were confirmed in the current study. Furthermore, within the current study cohort, 48 additional immune signaling responses differed significantly between young and elderly donors. These associations spanned all profiled modulators and immune cell subsets. These results demonstrate that SCNP, a systems-based approach, can capture the complexity of the cellular mechanisms underlying immunological aging. Further, the confirmation of age associations in an independent donor cohort supports the use of SCNP as a tool for identifying reproducible predictive biomarkers in areas such as vaccine response and response to cancer immunotherapies.

  12. Crosstalk between bone niche and immune system: osteoimmunology signaling as a potential target for cancer treatment.

    Science.gov (United States)

    Criscitiello, Carmen; Viale, Giulia; Gelao, Lucia; Esposito, Angela; De Laurentiis, Michele; De Placido, Sabino; Santangelo, Michele; Goldhirsch, Aron; Curigliano, Giuseppe

    2015-02-01

    There is a well recognized link between the bone and the immune system and in recent years there has been a major effort to elucidate the multiple functions of the molecules expressed in both bone and immune cells. Several molecules that were initially identified and studied in the immune system have been shown to have essential functions also in the bone. An interdisciplinary field embracing immune and bone biology has been brought together and called "osteoimmunology". The co-regulation of the skeletal and immune systems strikingly exemplifies the extreme complexity of such an interaction. Their interdependency must be considered in designing therapeutic approaches for either of the two systems. In other words, it is necessary to think of the osteoimmune system as a complex physiological unit. Denosumab was originally introduced to specifically target bone resorption, but it is now under evaluation for its effect on the long term immune response. Similarly, our current and still growing knowledge of the intimate link between the immune system and bone will be beneficial for the safety of drugs targeting either of these integrated systems. Given the large number of molecules exerting functions on both the skeletal and immune systems, osteoimmunological understanding is becoming increasingly important. Both bone and immune systems are frequently disrupted in cancer; and they may be crucial in regulating tumor growth and progression. Some therapies - such as bisphosphonates and receptor activator of NF-κB ligand (RANKL) targeted drugs - that aim at reducing pathologic osteolysis in cancer may interact with the immune system, thus providing potential favorable effects on survival. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Immune System

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario Whether you're stomping through the showers ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on TeensHealth® is for ...

  14. [Zinc signaling : a novel regulatory system on bone homeostasis, and immune and allergic responses].

    Science.gov (United States)

    Fukada, Toshiyuki; Nishida, Keigo; Yamasaki, Satoru; Hojyo, Shintaro

    2012-11-01

    Zinc (Zn) is an essential trace element that is required for proliferation, differentiation, and variety of cellular functions, and unbalanced homeostasis of Zn ion (Zn(2 + )) results in health problems such as abnormal bone formation and immunodeficiency. Recent studies have shed light on important roles of Zn(2 + )as a signaling mediator, called Zn signal. Zn(2 + )homeostasis is regulated through Zn transporters and cation channels. Advances of genetic and molecular approaches have revealed that Zn signal regulates mammalian physiology and pathogenesis. We will address that Zn signal undoubtedly contributes to our health, by highlighting it in bone homeostasis and immune regulation, and discuss that the "Zn signal axis" selectively controls intracellular signal transduction to fine-tune cellular functions.

  15. Necroptotic signaling in adaptive and innate immunity.

    Science.gov (United States)

    Lu, Jennifer V; Chen, Helen C; Walsh, Craig M

    2014-11-01

    The vertebrate immune system is highly dependent on cell death for efficient responsiveness to microbial pathogens and oncogenically transformed cells. Cell death pathways are vital to the function of many immune cell types during innate, humoral and cellular immune responses. In addition, cell death regulation is imperative for proper adaptive immune self-tolerance and homeostasis. While apoptosis has been found to be involved in several of these roles in immunity, recent data demonstrate that alternative cell death pathways are required. Here, we describe the involvement of a programmed form of cellular necrosis called "necroptosis" in immunity. We consider the signaling pathways that promote necroptosis downstream of death receptors, type I transmembrane proteins of the tumor necrosis factor (TNF) receptor family. The involvement of necroptotic signaling through a "RIPoptosome" assembled in response to innate immune stimuli or genotoxic stress is described. We also characterize the induction of necroptosis following antigenic stimulation in T cells lacking caspase-8 or FADD function. While necroptotic signaling remains poorly understood, it is clear that this pathway is an essential component to effective vertebrate immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Weakened Immune Systems

    Science.gov (United States)

    ... Issues Health Issues Health Issues Conditions Injuries & Emergencies Vaccine Preventable Diseases ... Children > Safety & Prevention > Immunizations > Weakened Immune Systems Safety & Prevention ...

  17. Immune System Quiz

    Science.gov (United States)

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

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

    Science.gov (United States)

    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.

  19. Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection

    Directory of Open Access Journals (Sweden)

    Vidlak Debbie

    2012-06-01

    Full Text Available Abstract Although IL-17A (commonly referred to as IL-17 has been implicated in the pathogenesis of central nervous system (CNS autoimmune disease, its role during CNS bacterial infections remains unclear. To evaluate the broader impact of IL-17 family members in the context of CNS infection, we utilized IL-17 receptor (IL-17R knockout (KO mice that lack the ability to respond to IL-17, IL-17F and IL-17E (IL-25. In this article, we demonstrate that IL-17R signaling regulates bacterial clearance as well as natural killer T (NKT cell and gamma-delta (γδ T cell infiltrates during Staphylococcus aureus-induced brain abscess formation. Specifically, when compared with wild-type (WT animals, IL-17R KO mice exhibited elevated bacterial burdens at days 7 and 14 following S. aureus infection. Additionally, IL-17R KO animals displayed elevated neutrophil chemokine production, revealing the ability to compensate for the lack of IL-17R activity. Despite these differences, innate immune cell recruitment into brain abscesses was similar in IL-17R KO and WT mice, whereas IL-17R signaling exerted a greater influence on adaptive immune cell recruitment. In particular, γδ T cell influx was increased in IL-17R KO mice at day 7 post-infection. In addition, NK1.1high infiltrates were absent in brain abscesses of IL-17R KO animals and, surprisingly, were rarely detected in the livers of uninfected IL-17R KO mice. Although IL-17 is a key regulator of neutrophils in other infection models, our data implicate an important role for IL-17R signaling in regulating adaptive immunity during CNS bacterial infection.

  20. Our Immune System

    Science.gov (United States)

    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, ” ...

  1. Immune System (For Parents)

    Science.gov (United States)

    ... of the Immune System Print en español El sistema inmunitario The immune system, which is made up ... of Use Notice of Nondiscrimination Visit the Nemours Web site. Note: All information on KidsHealth® is for ...

  2. Immune System and Disorders

    Science.gov (United States)

    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 ...

  3. Skin innate immune system

    Directory of Open Access Journals (Sweden)

    Berna Aksoy

    2013-06-01

    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  4. [Immune system and tumors].

    Science.gov (United States)

    Terme, Magali; Tanchot, Corinne

    2017-02-01

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

  5. Immune system simulation online

    DEFF Research Database (Denmark)

    Rapin, Nicolas; Lund, Ole; Castiglione, Filippo

    2011-01-01

    MOTIVATION: The recognition of antigenic peptides is a major event of an immune response. In current mesoscopic-scale simulators of the immune system, this crucial step has been modeled in a very approximated way. RESULTS: We have equipped an agent-based model of the immune system with immuno...

  6. Trichomoniasis immunity and the involvement of the purinergic signaling

    Directory of Open Access Journals (Sweden)

    Camila Braz Menezes

    2016-08-01

    Full Text Available Innate and adaptive immunity play a significant role in trichomoniasis, the most common non-viral sexually transmitted disease worldwide. In the urogenital tract, innate immunity is accomplished by a defense physical barrier constituted by epithelial cells, mucus, and acidic pH. During infection, immune cells, antimicrobial peptides, cytokines, chemokines, and adaptive immunity evolve in the reproductive tract, and a proinflammatory response is generated to eliminate the invading extracellular pathogen Trichomonas vaginalis. However, the parasite has developed complex evolutionary mechanisms to evade the host immune response through cysteine proteases, phenotypic variation, and molecular mimicry. The purinergic system constitutes a signaling cellular net where nucleotides and nucleosides, enzymes, purinoceptors and transporters are involved in almost all cells and tissues signaling pathways, especially in central and autonomic nervous systems, endocrine, respiratory, cardiac, reproductive, and immune systems, during physiological as well as pathological processes. The involvement of the purinergic system in T. vaginalis biology and infection has been demonstrated and this review highlights the participation of this signaling pathway in the parasite immune evasion strategies. Keywords: Trichomoniasis, Innate immune response, Adaptive immune response, Evasion mechanisms, Purinergic signaling

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

    Science.gov (United States)

    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.

  8. Signaling through IL-17C/IL-17RE is dispensable for immunity to systemic, oral and cutaneous candidiasis.

    Science.gov (United States)

    Conti, Heather R; Whibley, Natasha; Coleman, Bianca M; Garg, Abhishek V; Jaycox, Jillian R; Gaffen, Sarah L

    2015-01-01

    Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C. albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the best-characterized member of the IL-17 family to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C. albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates similar to WT littermate controls. Moreover, these mice demonstrated similar gene transcription profiles and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and illustrate a surprisingly limited specificity of the IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida infections.

  9. Signaling through IL-17C/IL-17RE is dispensable for immunity to systemic, oral and cutaneous candidiasis.

    Directory of Open Access Journals (Sweden)

    Heather R Conti

    Full Text Available Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C. albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations or IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the best-characterized member of the IL-17 family to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C. albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates similar to WT littermate controls. Moreover, these mice demonstrated similar gene transcription profiles and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and illustrate a surprisingly limited specificity of the IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida infections.

  10. Signaling through IL-17C/IL-17RE Is Dispensable for Immunity to Systemic, Oral and Cutaneous Candidiasis

    Science.gov (United States)

    Conti, Heather R.; Whibley, Natasha; Coleman, Bianca M.; Garg, Abhishek V.; Jaycox, Jillian R.; Gaffen, Sarah L.

    2015-01-01

    Candida albicans is a commensal fungal microbe of the human orogastrointestinal tract and skin. C. albicans causes multiple forms of disease in immunocompromised patients, including oral, vaginal, dermal and disseminated candidiasis. The cytokine IL-17 (IL-17A) and its receptor subunits, IL-17RA and IL-17RC, are required for protection to most forms of candidiasis. The importance of the IL-17R pathway has been observed not only in knockout mouse models, but also in humans with rare genetic mutations that impact generation of Th17 cells or the IL-17 signaling pathway, including Hyper-IgE Syndrome (STAT3 or TYK2 mutations) or IL17RA or ACT1 gene deficiency. The IL-17 family of cytokines is a distinct subclass of cytokines with unique structural and signaling properties. IL-17A is the best-characterized member of the IL-17 family to date, but far less is known about other IL-17-related cytokines. In this study, we sought to determine the role of a related IL-17 cytokine, IL-17C, in protection against oral, dermal and disseminated forms of C. albicans infection. IL-17C signals through a heterodimeric receptor composed of the IL-17RA and IL-17RE subunits. We observed that IL-17C mRNA was induced following oral C. albicans infection. However, mice lacking IL-17C or IL-17RE cleared C. albicans infections in the oral mucosa, skin and bloodstream at rates similar to WT littermate controls. Moreover, these mice demonstrated similar gene transcription profiles and recovery kinetics as WT animals. These findings indicate that IL-17C and IL-17RE are dispensable for immunity to the forms of candidiasis evaluated, and illustrate a surprisingly limited specificity of the IL-17 family of cytokines with respect to systemic, oral and cutaneous Candida infections. PMID:25849644

  11. The Immune System Game

    Science.gov (United States)

    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…

  12. Hormonal signaling in plant immunity

    NARCIS (Netherlands)

    Caarls, L.

    2016-01-01

    Insect hervivores and pathogens are a major problem in agriculture and therefore, control of these pests and diseases is essential. For this, understanding the plant immune response can be instrumental. The plant hormones salicylic acid (SA) and jasmonic acid (JA) play an essential role in defense

  13. Systems biology integration of proteomic data in rodent models of depression reveals involvement of the immune response and glutamatergic signaling.

    Science.gov (United States)

    Carboni, Lucia; Nguyen, Thanh-Phuong; Caberlotto, Laura

    2016-12-01

    The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. Network analysis is performed integrating preexisting proteomic data from rodent models of depression. The IntAct mouse and the HRPD are used as reference protein-protein interaction databases. The functionality analyses of the networks are then performed by testing overrepresented GO biological process terms and pathways. Functional enrichment analyses of the networks revealed an association with molecular processes related to depression in humans, such as those involved in the immune response. Pathways impacted by clinically effective antidepressants are modulated, including glutamatergic signaling and neurotrophic responses. Moreover, dysregulations of proteins regulating energy metabolism and circadian rhythms are implicated. The comparison with protein pathways modulated in depressive patients revealed significant overlapping. This systems biology study supports the notion that animal models can contribute to the research into the biology and therapeutics of depression. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Alternative Immune Systems

    Directory of Open Access Journals (Sweden)

    Luis Fernando Cadavid Gutierrez

    2011-09-01

    Full Text Available The immune system in animals is a complex network of molecules, cells and tissues that coordinately maintain the physiological and genetic integrity of the organism. Traditionally, two classes of immunity have been considered, the innate immunity and the adaptive immunity. The former is ancestral, with limited variability and low discrimination. The latter is highly variable, specific and limited to jawed vertebrates. Adaptive immunity is based on antigen receptors that rearrange somatically to generate a nearly unlimited diversity of molecules. Likely, this mechanism of somatic recombination arose as a consequence of a horizontal transfer of transposons and transposases from bacterial genomes in the ancestor of jawed vertebrates. The recent discovery in jawless vertebrates and invertebrates of alternative adaptive immune mechanisms, suggests during evolution different animal groups have found alternative solutions to the problem of immune recognition.

  15. TAM Receptor Signaling in Immune Homeostasis

    Science.gov (United States)

    Rothlin, Carla V.; Carrera-Silva, Eugenio A.; Bosurgi, Lidia; Ghosh, Sourav

    2015-01-01

    The TAM receptor tyrosine kinases (RTKs)—TYRO3, AXL, and MERTK—together with their cognate agonists GAS6 and PROS1 play an essential role in the resolution of inflammation. Deficiencies in TAM signaling have been associated with chronic inflammatory and autoimmune diseases. Three processes regulated by TAM signaling may contribute, either independently or collectively, to immune homeostasis: the negative regulation of the innate immune response, the phagocytosis of apoptotic cells, and the restoration of vascular integrity. Recent studies have also revealed the function of TAMs in infectious diseases and cancer. Here, we review the important milestones in the discovery of these RTKs and their ligands and the studies that underscore the functional importance of this signaling pathway in physiological immune settings and disease. PMID:25594431

  16. Are innate immune signaling pathways in plants and animals conserved?

    Science.gov (United States)

    Ausubel, Frederick M

    2005-10-01

    Although adaptive immunity is unique to vertebrates, the innate immune response seems to have ancient origins. Common features of innate immunity in vertebrates, invertebrate animals and plants include defined receptors for microbe-associated molecules, conserved mitogen-associated protein kinase signaling cascades and the production of antimicrobial peptides. It is commonly reported that these similarities in innate immunity represent a process of divergent evolution from an ancient unicellular eukaryote that pre-dated the divergence of the plant and animal kingdoms. However, at present, data suggest that the seemingly analogous regulatory modules used in plant and animal innate immunity are a consequence of convergent evolution and reflect inherent constraints on how an innate immune system can be constructed.

  17. On Modelling an Immune System

    OpenAIRE

    Monroy, Raúl; Saab, Rosa; Godínez, Fernando

    2004-01-01

    Immune systems of live forms have been an abundant source of inspiration to contemporary computer scientists. Problem solving strategies, stemming from known immune system phenomena, have been successfully applied to challenging problems of modern computing. However, research in artificial immune systems has overlooked establishing a coherent model of known immune system behaviour. This paper aims reports on an preliminary computer model of an immune system, where each immune system component...

  18. Signaling Mechanisms in Pattern-Triggered Immunity (PTI)

    KAUST Repository

    Bigeard, Jean; Colcombet, Jean; Hirt, Heribert

    2015-01-01

    In nature, plants constantly have to face pathogen attacks. However, plant disease rarely occurs due to efficient immune systems possessed by the host plants. Pathogens are perceived by two different recognition systems that initiate the so-called pattern-triggered immunity (PTI) and effector-triggered immunity (ETI), both of which are accompanied by a set of induced defenses that usually repel pathogen attacks. Here we discuss the complex network of signaling pathways occurring during PTI, focusing on the involvement of mitogen-activated protein kinases. © 2015 The Author.

  19. Met1-linked Ubiquitination in Immune Signalling

    DEFF Research Database (Denmark)

    Fiil, Berthe Katrine; Gyrd-Hansen, Mads

    2014-01-01

    Methionine 1-linked ubiquitin chains (Met1-Ub), or linear ubiquitin, has emerged as a central post-translational modification in innate immune signalling. Molecular machinery that assembles, senses and, more recently, disassembles Met1-Ub has been identified, and technical advances have enabled...... identification of physiological substrates for Met1-Ub in response to activation of innate immune receptors. These discoveries have significantly advanced our understanding of how non-degradative ubiquitin modifications control pro-inflammatory responses mediated by nuclear factor κB and mitogen...

  20. Innate immune signalling of the zebrafish embryo

    NARCIS (Netherlands)

    Stockhammer, Oliver W.

    2010-01-01

    In the last decade the study of the innate immune system has gained renewed scientific momentum as a result of the discovery of essential receptor families, such as the Toll-like receptor (TLR) family, that are required for pathogen recognition. These receptors detect specific molecular structures

  1. Technique Selectively Represses Immune System

    Science.gov (United States)

    ... 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 ...

  2. Regulation of vitamin D homeostasis: implications for the immune system.

    Science.gov (United States)

    van Etten, Evelyne; Stoffels, Katinka; Gysemans, Conny; Mathieu, Chantal; Overbergh, Lut

    2008-10-01

    Vitamin D homeostasis in the immune system is the focus of this review. The production of both the activating (25- and 1alpha-hydroxylase) and the metabolizing (24-hydroxylase) enzymes by cells of the immune system itself, indicates that 1,25(OH)(2)D(3) can be produced locally in immune reaction sites. Moreover, the strict regulation of these enzymes by immune signals is highly suggestive for an autocrine/paracrine role in the immune system, and opens new treatment possibilities.

  3. Linear ubiquitination signals in adaptive immune responses.

    Science.gov (United States)

    Ikeda, Fumiyo

    2015-07-01

    Ubiquitin can form eight different linkage types of chains using the intrinsic Met 1 residue or one of the seven intrinsic Lys residues. Each linkage type of ubiquitin chain has a distinct three-dimensional topology, functioning as a tag to attract specific signaling molecules, which are so-called ubiquitin readers, and regulates various biological functions. Ubiquitin chains linked via Met 1 in a head-to-tail manner are called linear ubiquitin chains. Linear ubiquitination plays an important role in the regulation of cellular signaling, including the best-characterized tumor necrosis factor (TNF)-induced canonical nuclear factor-κB (NF-κB) pathway. Linear ubiquitin chains are specifically generated by an E3 ligase complex called the linear ubiquitin chain assembly complex (LUBAC) and hydrolyzed by a deubiquitinase (DUB) called ovarian tumor (OTU) DUB with linear linkage specificity (OTULIN). LUBAC linearly ubiquitinates critical molecules in the TNF pathway, such as NEMO and RIPK1. The linear ubiquitin chains are then recognized by the ubiquitin readers, including NEMO, which control the TNF pathway. Accumulating evidence indicates an importance of the LUBAC complex in the regulation of apoptosis, development, and inflammation in mice. In this article, I focus on the role of linear ubiquitin chains in adaptive immune responses with an emphasis on the TNF-induced signaling pathways. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Immune System and Kidney Transplantation.

    Science.gov (United States)

    Shrestha, Badri Man

    2017-01-01

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

  5. Metabolic signals and innate immune activation in obesity and exercise.

    Science.gov (United States)

    Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

    2015-01-01

    The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

  6. Danger Signals Activating the Immune Response after Trauma

    Directory of Open Access Journals (Sweden)

    Stefanie Hirsiger

    2012-01-01

    Full Text Available Sterile injury can cause a systemic inflammatory response syndrome (SIRS that resembles the host response during sepsis. The inflammatory response following trauma comprises various systems of the human body which are cross-linked with each other within a highly complex network of inflammation. Endogenous danger signals (danger-associated molecular patterns; DAMPs; alarmins as well as exogenous pathogen-associated molecular patterns (PAMPs play a crucial role in the initiation of the immune response. With popularization of the “danger theory,” numerous DAMPs and PAMPs and their corresponding pathogen-recognition receptors have been identified. In this paper, we highlight the role of the DAMPs high-mobility group box protein 1 (HMGB1, interleukin-1α (IL-1α, and interleukin-33 (IL-33 as unique dual-function mediators as well as mitochondrial danger signals released upon cellular trauma and necrosis.

  7. Dynamics of immune system vulnerabilities

    Science.gov (United States)

    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.

  8. Viral subversion of the immune system

    International Nuclear Information System (INIS)

    Gillet, L.; Vanderplasschen, A.

    2005-01-01

    The continuous interactions between host and viruses during their co-evolution have shaped not only the immune system but also the countermeasures used by viruses. Studies in the last decade have described the diverse arrays of pathways and molecular targets that are used by viruses to elude immune detection or destruction, or both. These include targeting of pathways for major histocompatibility complex class I and class II antigen presentation, natural killer cell recognition, apoptosis, cytokine signalling, and complement activation. This paper provides an overview of the viral immune-evasion mechanisms described to date. It highlights the contribution of this field to our understanding of the immune system, and the importance of understanding this aspect of the biology of viral infection to develop efficacious and safe vaccines. (author)

  9. The innate immune signaling in cancer and cardiometabolic diseases: Friends or foes?

    Science.gov (United States)

    Wang, Weijun; Zhang, Yaxing; Yang, Ling; Li, Hongliang

    2017-02-28

    The innate immune system is responsible for sensing pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) by several types of germline-encoded pattern-recognition receptors (PRRs). It has the capacity to help the human body maintain homeostasis under normal conditions. However, in pathological conditions, PAMPs or DAMPs trigger aberrant innate immune and inflammatory responses and thus negatively or positively influence the progression of cancer and cardiometabolic diseases. Interestingly, we found that some elements of innate immune signaling are involved in these diseases partially via immune-independent manners, indicating a deeper understanding of the function of innate immune signaling in these diseases is urgent. In this review, we summarize the primary innate immune signaling pathways and their association with cancer and cardiometabolic diseases, with the aim of providing effective therapies for these diseases. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Biomedical signals and systems

    CERN Document Server

    Tranquillo, Joseph V

    2013-01-01

    Biomedical Signals and Systems is meant to accompany a one-semester undergraduate signals and systems course. It may also serve as a quick-start for graduate students or faculty interested in how signals and systems techniques can be applied to living systems. The biological nature of the examples allows for systems thinking to be applied to electrical, mechanical, fluid, chemical, thermal and even optical systems. Each chapter focuses on a topic from classic signals and systems theory: System block diagrams, mathematical models, transforms, stability, feedback, system response, control, time

  11. Inter-donor variation in cell subset specific immune signaling responses in healthy individuals.

    Science.gov (United States)

    Longo, Diane M; Louie, Brent; Wang, Ena; Pos, Zoltan; Marincola, Francesco M; Hawtin, Rachael E; Cesano, Alessandra

    2012-01-01

    Single cell network profiling (SCNP) is a multi-parameter flow cytometry based approach that allows for the simultaneous interrogation of intracellular signaling pathways in multiple cell subpopulations within heterogeneous tissues, without the need for individual cell subset isolation. Thus, the technology is extremely well-suited for characterizing the multitude of interconnected signaling pathways and immune cell subpopulations that regulate the function of the immune system. Recently, SCNP was applied to generate a functional map of the healthy human immune cell signaling network by profiling immune signaling pathways downstream of 12 immunomodulators in 7 distinct immune cell subsets within peripheral blood mononuclear cells (PBMCs) from 60 healthy donors. In the study reported here, the degree of inter-donor variation in the magnitude of the immune signaling responses was analyzed. The highest inter-donor differences in immune signaling pathway activity occurred following perturbation of the immune signaling network, rather than in basal signaling. When examining the full panel of immune signaling responses, as one may expect, the overall degree of inter-donor variation was positively correlated (r = 0.727) with the magnitude of node response (i.e. a larger median signaling response was associated with greater inter-donor variation). However, when examining the degree of heterogeneity across cell subpopulations for individual signaling nodes, cell subset specificity in the degree of inter-donor variation was observed for several nodes. For such nodes, relatively weak correlations between inter-donor variation and the magnitude of the response were observed. Further, within the phenotypically distinct subpopulations, a fraction of the immune signaling responses had bimodal response profiles in which (a) only a portion of the cells had elevated phospho-protein levels following modulation and (b) the proportion of responsive cells varied by donor. These data

  12. Ebola and Immune System

    OpenAIRE

    KOMENAN, Alexis

    2016-01-01

    Ebola hemorrhagic fever is a formidable disease whose surges always result in a high number of victims in sub-Saharan Africa. There is no official treatment against the virus, which makes the task of containment extremely delicate. However, the existence of survivors to the virus demonstrates curable nature of the disease and suggests the existence of favorable factors of immunity. The author examines these factors and their challenges and perspectives in the cure of the disease.

  13. Melatonin: Buffering the Immune System

    Directory of Open Access Journals (Sweden)

    Juan M. Guerrero

    2013-04-01

    Full Text Available 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.

  14. Melatonin: Buffering the Immune System

    Science.gov (United States)

    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

  15. Play the Immune System Defender Game

    Science.gov (United States)

    ... Questionnaire The Immune System Play the Immune System Game About the game Granulocytes, macrophages and dendritic cells are immune cells ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...

  16. Serotonergic Chemosensory Neurons Modify the C. elegans Immune Response by Regulating G-Protein Signaling in Epithelial Cells

    Science.gov (United States)

    Anderson, Alexandra; Laurenson-Schafer, Henry; Partridge, Frederick A.; Hodgkin, Jonathan; McMullan, Rachel

    2013-01-01

    The nervous and immune systems influence each other, allowing animals to rapidly protect themselves from changes in their internal and external environment. However, the complex nature of these systems in mammals makes it difficult to determine how neuronal signaling influences the immune response. Here we show that serotonin, synthesized in Caenorhabditis elegans chemosensory neurons, modulates the immune response. Serotonin released from these cells acts, directly or indirectly, to regulate G-protein signaling in epithelial cells. Signaling in these cells is required for the immune response to infection by the natural pathogen Microbacterium nematophilum. Here we show that serotonin signaling suppresses the innate immune response and limits the rate of pathogen clearance. We show that C. elegans uses classical neurotransmitters to alter the immune response. Serotonin released from sensory neurons may function to modify the immune system in response to changes in the animal's external environment such as the availability, or quality, of food. PMID:24348250

  17. The Immune System in Hypertension

    Science.gov (United States)

    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…

  18. Bioelectric Signal Measuring System

    Science.gov (United States)

    Guadarrama-Santana, A.; Pólo-Parada, L.; García-Valenzuela, A.

    2015-01-01

    We describe a low noise measuring system based on interdigitated electrodes for sensing bioelectrical signals. The system registers differential voltage measurements in order of microvolts. The base noise during measurements was in nanovolts and thus, the sensing signals presented a very good signal to noise ratio. An excitation voltage of 1Vrms with 10 KHz frequency was applied to an interdigitated capacitive sensor without a material under test and to a mirror device simultaneously. The output signals of both devices was then subtracted in order to obtain an initial reference value near cero volts and reduce parasitic capacitances due to the electronics, wiring and system hardware as well. The response of the measuring system was characterized by monitoring temporal bioelectrical signals in real time of biological materials such as embryo chicken heart cells and bovine suprarenal gland cells.

  19. Functional comparison of innate immune signaling pathways in primates.

    Directory of Open Access Journals (Sweden)

    Luis B Barreiro

    2010-12-01

    Full Text Available Humans respond differently than other primates to a large number of infections. Differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. Consistent with that notion, genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates, suggesting that immune responses evolve rapidly, yet providing only indirect evidence for possible inter-species functional differences. To directly compare immune responses among primates, we stimulated primary monocytes from humans, chimpanzees, and rhesus macaques with lipopolysaccharide (LPS and studied the ensuing time-course regulatory responses. We find that, while the universal Toll-like receptor response is mostly conserved across primates, the regulatory response associated with viral infections is often lineage-specific, probably reflecting rapid host-virus mutual adaptation cycles. Additionally, human-specific immune responses are enriched for genes involved in apoptosis, as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. Finally, we find that chimpanzee-specific immune signaling pathways are enriched for HIV-interacting genes. Put together, our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases.

  20. Vitamin D signaling in intestinal innate immunity and homeostasis.

    Science.gov (United States)

    Dimitrov, Vassil; White, John H

    2017-09-15

    The lumen of the gut hosts a plethora of microorganisms that participate in food assimilation, inactivation of harmful particles and in vitamin synthesis. On the other hand, enteric flora, a number of food antigens, and toxins are capable of triggering immune responses causing inflammation, which, when unresolved, may lead to chronic conditions such as inflammatory bowel disease (IBD). It is important, therefore, to contain the gut bacteria within the lumen, control microbial load and composition, as well as ensure adequate innate and adaptive immune responses to pathogenic threats. There is growing evidence that vitamin D signaling has impacts on all these aspects of intestinal physiology, contributing to healthy enteric homeostasis. VD was first discovered as the curative agent for nutritional rickets, and its classical actions are associated with calcium absorption and bone health. However, vitamin D exhibits a number of extra-skeletal effects, particularly in innate immunity. Notably, it stimulates production of pattern recognition receptors, anti-microbial peptides, and cytokines, which are at the forefront of innate immune responses. They play a role in sensing the microbiota, in preventing excessive bacterial overgrowth, and complement the actions of vitamin D signaling in enhancing intestinal barrier function. Vitamin D also favours tolerogenic rather than inflammogenic T cell differentiation and function. Compromised innate immune function and overactive adaptive immunity, as well as defective intestinal barrier function, have been associated with IBD. Importantly, observational and intervention studies support a beneficial role of vitamin D supplementation in patients with Crohn's disease, a form of IBD. This review summarizes the effects of vitamin D signaling on barrier integrity and innate and adaptive immunity in the gut, as well as on microbial load and composition. Collectively, studies to date reveal that vitamin D signaling has widespread effects

  1. Convergent and Divergent Signaling in PAMP-Triggered Immunity and Effector-Triggered Immunity.

    Science.gov (United States)

    Peng, Yujun; van Wersch, Rowan; Zhang, Yuelin

    2018-04-01

    Plants use diverse immune receptors to sense pathogen attacks. Recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors localized on the plasma membrane leads to PAMP-triggered immunity (PTI). Detection of pathogen effectors by intracellular or plasma membrane-localized immune receptors results in effector-triggered immunity (ETI). Despite the large variations in the magnitude and duration of immune responses triggered by different PAMPs or pathogen effectors during PTI and ETI, plasma membrane-localized immune receptors activate similar downstream molecular events such as mitogen-activated protein kinase activation, oxidative burst, ion influx, and increased biosynthesis of plant defense hormones, indicating that defense signals initiated at the plasma membrane converge at later points. On the other hand, activation of ETI by immune receptors localized to the nucleus appears to be more directly associated with transcriptional regulation of defense gene expression. Here, we review recent progress in signal transductions downstream of different groups of plant immune receptors, highlighting the converging and diverging molecular events.

  2. DMPD: IRAK1: a critical signaling mediator of innate immunity. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17890055 IRAK1: a critical signaling mediator of innate immunity. Gottipati S, Rao ...IRAK1: a critical signaling mediator of innate immunity. PubmedID 17890055 Title IRAK1: a critical signaling mediator

  3. Signals and systems

    CERN Document Server

    Rao, K Deergha

    2018-01-01

    This textbook covers the fundamental theories of signals and systems analysis, while incorporating recent developments from integrated circuits technology into its examples. Starting with basic definitions in signal theory, the text explains the properties of continuous-time and discrete-time systems and their representation by differential equations and state space. From those tools, explanations for the processes of Fourier analysis, the Laplace transform, and the z-Transform provide new ways of experimenting with different kinds of time systems. The text also covers the separate classes of analog filters and their uses in signal processing applications. Intended for undergraduate electrical engineering students, chapter sections include exercise for review and practice for the systems concepts of each chapter. Along with exercises, the text includes MATLAB-based examples to allow readers to experiment with signals and systems code on their own. An online repository of the MATLAB code from this textbook can...

  4. Radiation signal processing system

    International Nuclear Information System (INIS)

    Bennett, M.; Knoll, G.; Strange, D.

    1980-01-01

    An improved signal processing system for radiation imaging apparatus comprises: a radiation transducer producing transducer signals proportional to apparent spatial coordinates of detected radiation events; means for storing true spatial coordinates corresponding to a plurality of predetermined apparent spatial coordinates relative to selected detected radiation events said means for storing responsive to said transducer signal and producing an output signal representative of said true spatial coordinates; and means for interpolating the true spatial coordinates of the detected radiation events located intermediate the stored true spatial coordinates, said means for interpolating communicating with said means for storing

  5. Signalling through C-type lectin receptors: shaping immune responses

    NARCIS (Netherlands)

    Geijtenbeek, Teunis B. H.; Gringhuis, Sonja I.

    2009-01-01

    C-type lectin receptors (CLRs) expressed by dendritic cells are crucial for tailoring immune responses to pathogens. Following pathogen binding, CLRs trigger distinct signalling pathways that induce the expression of specific cytokines which determine T cell polarization fates. Some CLRs can induce

  6. Cyclic Dinucleotides in the Scope of the Mammalian Immune System.

    Science.gov (United States)

    Mankan, Arun K; Müller, Martina; Witte, Gregor; Hornung, Veit

    2017-01-01

    First discovered in prokaryotes and more recently in eukaryotes, cyclic dinucleotides (CDNs) constitute a unique branch of second messenger signaling systems. Within prokaryotes CDNs regulate a wide array of different biological processes, whereas in the vertebrate system CDN signaling is largely dedicated to activation of the innate immune system. In this book chapter we summarize the occurrence and signaling pathways of these small-molecule second messengers, most importantly in the scope of the mammalian immune system. In this regard, our main focus is the role of the cGAS-STING axis in the context of microbial infection and sterile inflammation and its implications for therapeutic applications.

  7. The essential role of G protein-coupled receptor (GPCR) signaling in regulating T cell immunity.

    Science.gov (United States)

    Wang, Dashan

    2018-06-01

    The aim of this paper is to clarify the critical role of GPCR signaling in T cell immunity. The G protein-coupled receptors (GPCRs) are the most common targets in current pharmaceutical industry, and represent the largest and most versatile family of cell surface communicating molecules. GPCRs can be activated by a diverse array of ligands including neurotransmitters, chemokines as well as sensory stimuli. Therefore, GPCRs are involved in many key cellular and physiological processes, such as sense of light, taste and smell, neurotransmission, metabolism, endocrine and exocrine secretion. In recent years, GPCRs have been found to play an important role in immune system. T cell is an important type of immune cell, which plays a central role in cell-mediated immunity. A variety of GPCRs and their signaling mediators (RGS proteins, GRKs and β-arrestin) have been found to express in T cells and involved T cell-mediated immunity. We will summarize the role of GPCR signaling and their regulatory molecules in T cell activation, homeostasis and function in this article. GPCR signaling plays an important role in T cell activation, homeostasis and function. GPCR signaling is critical in regulating T cell immunity.

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

    Science.gov (United States)

    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

  9. Systems biology of host-mycobiota interactions: dissecting Dectin-1 and Dectin-2 signalling in immune cells with DC-ATLAS.

    Science.gov (United States)

    Rizzetto, Lisa; De Filippo, Carlotta; Rivero, Damariz; Riccadonna, Samantha; Beltrame, Luca; Cavalieri, Duccio

    2013-11-01

    Modelling the networks sustaining the fruitful coexistence between fungi and their mammalian hosts is becoming increasingly important to control emerging fungal pathogens. The C-type lectins Dectin-1 and Dectin-2 are involved in host defense mechanisms against fungal infection driving inflammatory and adaptive immune responses and complement in containing fungal burdens. Recognizing carbohydrate structures in pathogens, their engagement induces maturation of dendritic cells (DCs) into potent immuno-stimulatory cells endowed with the capacity to efficiently prime T cells. Owing to these properties, Dectin-1 and Dectin-2 agonists are currently under investigation as promising adjuvants in vaccination procedures for the treatment of fungal infection. Thus, a detailed understanding of events' cascade specifically triggered in DCs upon engagement is of great interest in translational research. Here, we summarize the current knowledge on Dectin-1 and Dectin-2 signalling in DCs highlighting similarities and differences. Detailed maps are annotated, using the Biological Connection Markup Language (BCML) data model, and stored in DC-ATLAS, a versatile resource for the interpretation of high-throughput data generated perturbing the signalling network of DCs. Copyright © 2013 Elsevier GmbH. All rights reserved.

  10. Signaling pathways and immune evasion mechanisms in classical Hodgkin lymphoma.

    Science.gov (United States)

    Liu, W Robert; Shipp, Margaret A

    2017-11-23

    Classical Hodgkin lymphoma (cHL) is an unusual B-cell-derived malignancy in which rare malignant Hodgkin and Reed-Sternberg (HRS) cells are surrounded by an extensive but ineffective inflammatory/immune cell infiltrate. This striking feature suggests that malignant HRS cells escape immunosurveillance and interact with immune cells in the cancer microenvironment for survival and growth. We previously found that cHLs have a genetic basis for immune evasion: near-uniform copy number alterations of chromosome 9p24.1 and the associated PD-1 ligand loci, CD274/PD-L1 and PDCD1LG2/PD-L2, and copy number-dependent increased expression of these ligands. HRS cells expressing PD-1 ligands are thought to engage PD-1 receptor-positive immune effectors in the tumor microenvironment and induce PD-1 signaling and associated immune evasion. The genetic bases of enhanced PD-1 signaling in cHL make these tumors uniquely sensitive to PD-1 blockade. © 2017 by The American Society of Hematology.

  11. IL-4/5 signalling plays an important role during Litomosoides sigmodontis infection, influencing both immune system regulation and tissue pathology in the thoracic cavity.

    Science.gov (United States)

    Ritter, Manuel; Tamadaho, Ruth S; Feid, Judith; Vogel, Wenzel; Wiszniewsky, Katharina; Perner, Sven; Hoerauf, Achim; Layland, Laura E

    2017-12-01

    -/- mice. In summary, this study unravels the essential role of IL-4/IL-5 signalling in controlling immunity against filarial infections and demonstrates the requirement of this pathway for the host to control ensuing pathology and inflammation. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  12. Ebola Virus Altered Innate and Adaptive Immune Response Signalling Pathways: Implications for Novel Therapeutic Approaches.

    Science.gov (United States)

    Kumar, Anoop

    2016-01-01

    Ebola virus (EBOV) arise attention for their impressive lethality by the poor immune response and high inflammatory reaction in the patients. It causes a severe hemorrhagic fever with case fatality rates of up to 90%. The mechanism underlying this lethal outcome is poorly understood. In 2014, a major outbreak of Ebola virus spread amongst several African countries, including Leone, Sierra, and Guinea. Although infections only occur frequently in Central Africa, but the virus has the potential to spread globally. Presently, there is no vaccine or treatment is available to counteract Ebola virus infections due to poor understanding of its interaction with the immune system. Accumulating evidence indicates that the virus actively alters both innate and adaptive immune responses and triggers harmful inflammatory responses. In the literature, some reports have shown that alteration of immune signaling pathways could be due to the ability of EBOV to interfere with dendritic cells (DCs), which link innate and adaptive immune responses. On the other hand, some reports have demonstrated that EBOV, VP35 proteins act as interferon antagonists. So, how the Ebola virus altered the innate and adaptive immune response signaling pathways is still an open question for the researcher to be explored. Thus, in this review, I try to summarize the mechanisms of the alteration of innate and adaptive immune response signaling pathways by Ebola virus which will be helpful for designing effective drugs or vaccines against this lethal infection. Further, potential targets, current treatment and novel therapeutic approaches have also been discussed.

  13. Weakened Immune System and Adult Vaccination

    Science.gov (United States)

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

  14. Network modeling reveals prevalent negative regulatory relationships between signaling sectors in Arabidopsis immune signaling.

    Directory of Open Access Journals (Sweden)

    Masanao Sato

    Full Text Available Biological signaling processes may be mediated by complex networks in which network components and network sectors interact with each other in complex ways. Studies of complex networks benefit from approaches in which the roles of individual components are considered in the context of the network. The plant immune signaling network, which controls inducible responses to pathogen attack, is such a complex network. We studied the Arabidopsis immune signaling network upon challenge with a strain of the bacterial pathogen Pseudomonas syringae expressing the effector protein AvrRpt2 (Pto DC3000 AvrRpt2. This bacterial strain feeds multiple inputs into the signaling network, allowing many parts of the network to be activated at once. mRNA profiles for 571 immune response genes of 22 Arabidopsis immunity mutants and wild type were collected 6 hours after inoculation with Pto DC3000 AvrRpt2. The mRNA profiles were analyzed as detailed descriptions of changes in the network state resulting from the genetic perturbations. Regulatory relationships among the genes corresponding to the mutations were inferred by recursively applying a non-linear dimensionality reduction procedure to the mRNA profile data. The resulting static network model accurately predicted 23 of 25 regulatory relationships reported in the literature, suggesting that predictions of novel regulatory relationships are also accurate. The network model revealed two striking features: (i the components of the network are highly interconnected; and (ii negative regulatory relationships are common between signaling sectors. Complex regulatory relationships, including a novel negative regulatory relationship between the early microbe-associated molecular pattern-triggered signaling sectors and the salicylic acid sector, were further validated. We propose that prevalent negative regulatory relationships among the signaling sectors make the plant immune signaling network a "sector

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

    Directory of Open Access Journals (Sweden)

    Bruno Faivre

    2013-02-01

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

  16. Immune System Toxicity and Immunotoxicity Hazard Identification

    Science.gov (United States)

    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 ...

  17. Innate immune system and preeclampsia

    Directory of Open Access Journals (Sweden)

    Alejandra ePerez-Sepulveda

    2014-05-01

    Full Text Available Normal pregnancy is considered as a Th2 type immunological state that favors an immune-tolerance environment in order to prevent fetal rejection. PE has been classically described as a Th1/Th2 imbalance; however, the Th1/Th2 paradigm has proven insufficient to fully explain the functional and molecular changes observed during normal/pathological pregnancies. Recent studies have expanded the Th1/Th2 into a Th1⁄Th2⁄Th17 and regulatory T (Treg cells paradigm and where dendritic cells could have a crucial role. Recently, some evidence has emerged supporting the idea that mesenchymal stem cells might be part of the feto-maternal tolerance environment. This review will discuss the involvement of the innate immune system in the establishment of a physiological environment that favors pregnancy and possible alterations related to the development of preeclampsia.

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

    Science.gov (United States)

    Imeri, Luca; Opp, Mark R

    2009-03-01

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

  19. Immune System Dysfunction in the Elderly.

    Science.gov (United States)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2015-06-23

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

  1. The role of innate signaling in the homeostasis of tolerance and immunity in the intestine.

    Science.gov (United States)

    Wells, Jerry M; Loonen, Linda M P; Karczewski, Jurgen M

    2010-01-01

    In the intestine innate recognition of microbes is achieved through pattern recognition receptor (PRR) families expressed in immune cells and different cell lineages of the intestinal epithelium. Toll-like receptor (TLR) and nucleotide-binding and oligomerization domain-like receptor (NLR) families are emerging as key mediators of immunity through their role as maturation factors of immune cells and triggers for the production of cytokines and chemokines and antimicrobial factors. At the mucosal surface chronic activation of the immune system is avoided through the epithelial production of a glycocalyx, steady-state production of antimicrobial factors as well as the selective expression and localization of PRRs. Additionally, the polarization of epithelial TLR signaling and suppression of NF-kappaB activation by luminal commensals appears to contribute to the homeostasis of tolerance and immunity. Several studies have demonstrated that TLR signaling in epithelial cells contributes to a range of homeostatic mechanisms including proliferation, wound healing, epithelial integrity, and regulation of mucosal immune functions. The intestinal epithelium appears to have uniquely evolved to maintain mucosal tolerance and immunity, and future efforts to further understand the molecular mechanisms of intestinal homeostasis may have a major impact on human health. Copyright 2009 Elsevier GmbH. All rights reserved.

  2. DMPD: Innate immune responses: crosstalk of signaling and regulation of genetranscription. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 16753195 Innate immune responses: crosstalk of signaling and regulation of genetran...l) (.csml) Show Innate immune responses: crosstalk of signaling and regulation of genetranscription. PubmedI...D 16753195 Title Innate immune responses: crosstalk of signaling and regulation o

  3. Unique aspects of the perinatal immune system.

    Science.gov (United States)

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

    2017-08-01

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

  4. Inside the mucosal immune system.

    Directory of Open Access Journals (Sweden)

    Jerry R McGhee

    Full Text Available An intricate network of innate and immune cells and their derived mediators function in unison to protect us from toxic elements and infectious microbial diseases that are encountered in our environment. This vast network operates efficiently by use of a single cell epithelium in, for example, the gastrointestinal (GI and upper respiratory (UR tracts, fortified by adjoining cells and lymphoid tissues that protect its integrity. Perturbations certainly occur, sometimes resulting in inflammatory diseases or infections that can be debilitating and life threatening. For example, allergies in the eyes, skin, nose, and the UR or digestive tracts are common. Likewise, genetic background and environmental microbial encounters can lead to inflammatory bowel diseases (IBDs. This mucosal immune system (MIS in both health and disease is currently under intense investigation worldwide by scientists with diverse expertise and interests. Despite this activity, there are numerous questions remaining that will require detailed answers in order to use the MIS to our advantage. In this issue of PLOS Biology, a research article describes a multi-scale in vivo systems approach to determine precisely how the gut epithelium responds to an inflammatory cytokine, tumor necrosis factor-alpha (TNF-α, given by the intravenous route. This article reveals a previously unknown pathway in which several cell types and their secreted mediators work in unison to prevent epithelial cell death in the mouse small intestine. The results of this interesting study illustrate how in vivo systems biology approaches can be used to unravel the complex mechanisms used to protect the host from its environment.

  5. Learning and Memory... and the Immune System

    Science.gov (United States)

    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),…

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

    Science.gov (United States)

    Muscoplat, Miriam Halstead; Rajamani, Sripriya

    2017-01-01

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

  7. Local and systemic tumor immune dynamics

    Science.gov (United States)

    Enderling, Heiko

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2017-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  10. GDSL LIPASE1 Modulates Plant Immunity through Feedback Regulation of Ethylene Signaling1[W

    Science.gov (United States)

    Kim, Hye Gi; Kwon, Sun Jae; Jang, Young Jin; Nam, Myung Hee; Chung, Joo Hee; Na, Yun-Cheol; Guo, Hongwei; Park, Ohkmae K.

    2013-01-01

    Ethylene is a key signal in the regulation of plant defense responses. It is required for the expression and function of GDSL LIPASE1 (GLIP1) in Arabidopsis (Arabidopsis thaliana), which plays an important role in plant immunity. Here, we explore molecular mechanisms underlying the relationship between GLIP1 and ethylene signaling by an epistatic analysis of ethylene response mutants and GLIP1-overexpressing (35S:GLIP1) plants. We show that GLIP1 expression is regulated by ethylene signaling components and, further, that GLIP1 expression or application of petiole exudates from 35S:GLIP1 plants affects ethylene signaling both positively and negatively, leading to ETHYLENE RESPONSE FACTOR1 activation and ETHYLENE INSENSITIVE3 (EIN3) down-regulation, respectively. Additionally, 35S:GLIP1 plants or their exudates increase the expression of the salicylic acid biosynthesis gene SALICYLIC ACID INDUCTION-DEFICIENT2, known to be inhibited by EIN3 and EIN3-LIKE1. These results suggest that GLIP1 regulates plant immunity through positive and negative feedback regulation of ethylene signaling, and this is mediated by its activity to accumulate a systemic signal(s) in the phloem. We propose a model explaining how GLIP1 regulates the fine-tuning of ethylene signaling and ethylene-salicylic acid cross talk. PMID:24170202

  11. Immune Homeostasis in Epithelial Cells: Evidence and Role of Inflammasome Signaling Reviewed.

    Science.gov (United States)

    Peeters, Paul M; Wouters, Emiel F; Reynaert, Niki L

    2015-01-01

    The epithelium regulates the interaction between the noxious xenogenous, as well as the microbial environment and the immune system, not only by providing a barrier but also by expressing a number of immunoregulatory membrane receptors, and intracellular danger sensors and their downstream effectors. Amongst these are a number of inflammasome sensor subtypes, which have been initially characterized in myeloid cells and described to be activated upon assembly into multiprotein complexes by microbial and environmental triggers. This review compiles a vast amount of literature that supports a pivotal role for inflammasomes in the various epithelial barriers of the human body as essential factors maintaining immune signaling and homeostasis.

  12. Immune Signaling and Antimicrobial Peptide Expression in Lepidoptera

    Directory of Open Access Journals (Sweden)

    Heidi Goodrich-Blair

    2013-07-01

    Full Text Available Many lepidopteran insects are agricultural pests that affect stored grains, food and fiber crops. These insects have negative ecological and economic impacts since they lower crop yield, and pesticides are expensive and can have off-target effects on beneficial arthropods. A better understanding of lepidopteran immunity will aid in identifying new targets for the development of specific insect pest management compounds. A fundamental aspect of immunity, and therefore a logical target for control, is the induction of antimicrobial peptide (AMP expression. These peptides insert into and disrupt microbial membranes, thereby promoting pathogen clearance and insect survival. Pathways leading to AMP expression have been extensively studied in the dipteran Drosophila melanogaster. However, Diptera are an important group of pollinators and pest management strategies that target their immune systems is not recommended. Recent advances have facilitated investigation of lepidopteran immunity, revealing both conserved and derived characteristics. Although the general pathways leading to AMP expression are conserved, specific components of these pathways, such as recognition proteins have diverged. In this review we highlight how such comparative immunology could aid in developing pest management strategies that are specific to agricultural insect pests.

  13. Conceptual Spaces of the Immune System.

    Science.gov (United States)

    Fierz, Walter

    2016-01-01

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

  14. Transport modeling: An artificial immune system approach

    Directory of Open Access Journals (Sweden)

    Teodorović Dušan

    2006-01-01

    Full Text Available This paper describes an artificial immune system approach (AIS to modeling time-dependent (dynamic, real time transportation phenomenon characterized by uncertainty. The basic idea behind this research is to develop the Artificial Immune System, which generates a set of antibodies (decisions, control actions that altogether can successfully cover a wide range of potential situations. The proposed artificial immune system develops antibodies (the best control strategies for different antigens (different traffic "scenarios". This task is performed using some of the optimization or heuristics techniques. Then a set of antibodies is combined to create Artificial Immune System. The developed Artificial Immune transportation systems are able to generalize, adapt, and learn based on new knowledge and new information. Applications of the systems are considered for airline yield management, the stochastic vehicle routing, and real-time traffic control at the isolated intersection. The preliminary research results are very promising.

  15. High-resolution mass spectrometry driven discovery of peptidic danger signals in insect immunity.

    Directory of Open Access Journals (Sweden)

    Arton Berisha

    Full Text Available The 'danger model' is an alternative concept for immune response postulating that the immune system reacts to entities that do damage (danger associated molecular patterns, DAMP and not only to entities that are foreign (pathogen-associated molecular patterns, PAMP as proposed by classical immunology concepts. In this study we used Galleria mellonella to validate the danger model in insects. Hemolymph of G. mellonella was digested with thermolysin (as a representative for virulence-associated metalloproteinases produced by humanpathogens followed by chromatographic fractionation. Immune-stimulatory activity was tested by measuring lysozyme activity with the lytic zone assays against Micrococcus luteus cell wall components. Peptides were analyzed by nano-scale liquid chromatography coupled to high-resolution Fourier transform mass spectrometers. Addressing the lack of a genome sequence we complemented the rudimentary NCBI protein database with a recently established transcriptome and de novo sequencing methods for peptide identification. This approach led to identification of 127 peptides, 9 of which were identified in bioactive fractions. Detailed MS/MS experiments in comparison with synthetic analogues confirmed the amino acid sequence of all 9 peptides. To test the potential of these putative danger signals to induce immune responses we injected the synthetic analogues into G. mellonella and monitored the anti-bacterial activity against living Micrococcus luteus. Six out of 9 peptides identified in the bioactive fractions exhibited immune-stimulatory activity when injected. Hence, we provide evidence that small peptides resulting from thermolysin-mediated digestion of hemolymph proteins function as endogenous danger signals which can set the immune system into alarm. Consequently, our study indicates that the danger model also plays a role in insect immunity.

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

    Science.gov (United States)

    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.

  17. Nutritional support for the infant's immune system

    NARCIS (Netherlands)

    Niers, L.; Stasse-Wolthuis, M.; Rombouts, F.M.; Rijkers, G.T.

    2007-01-01

    Newborn babies possess a functional but immature immune system as a defense against a world teeming with microorganisms. Breast milk contains a number of biological, active compounds that support the infant's immune system. These include secretory immunoglobulin A (IgA), which confers specific

  18. The Immune System and Bodily Defence

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 2. The Immune System and Bodily Defence How Do Parasites and the Immune System Choose their Dances? Vineeta Bal Satyajit Rath. Series Article Volume 2 Issue 2 February 1997 pp 17-24 ...

  19. The Immune System and Bodily Defence

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 6. The Immune System and Bodily Defence How Does the Immune System Organize Itself so as to Connect Target Recognition to Expected Functions? Vineeta Bal Satyajit Rath. Series Article Volume 2 Issue 6 June 1997 pp 25-38 ...

  20. The Immune System and Bodily Defence

    Indian Academy of Sciences (India)

    Home; Journals; Resonance – Journal of Science Education; Volume 2; Issue 9. The Immune System and Bodily Defence How Does the Immune System Recognize Everything Under the Sun? Vineeta Bal Satyajit Rath. Series Article Volume 2 Issue 9 September 1997 pp 6-10 ...

  1. Feeding Our Immune System: Impact on Metabolism

    Directory of Open Access Journals (Sweden)

    Isabelle Wolowczuk

    2008-01-01

    Full Text Available 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.

  2. MenTORing Immunity: mTOR Signaling in the Development and Function of Tissue-Resident Immune Cells.

    Science.gov (United States)

    Jones, Russell G; Pearce, Edward J

    2017-05-16

    Tissue-resident immune cells must balance survival in peripheral tissues with the capacity to respond rapidly upon infection or tissue damage, and in turn couple these responses with intrinsic metabolic control and conditions in the tissue microenvironment. The serine/threonine kinase mammalian/mechanistic target of rapamycin (mTOR) is a central integrator of extracellular and intracellular growth signals and cellular metabolism and plays important roles in both innate and adaptive immune responses. This review discusses the function of mTOR signaling in the differentiation and function of tissue-resident immune cells, with focus on the role of mTOR as a metabolic sensor and its impact on metabolic regulation in innate and adaptive immune cells. We also discuss the impact of metabolic constraints in tissues on immune homeostasis and disease, and how manipulating mTOR activity with drugs such as rapamycin can modulate immunity in these contexts. Copyright © 2017. Published by Elsevier Inc.

  3. Promoting tissue regeneration by modulating the immune system.

    Science.gov (United States)

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

    2017-04-15

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

  4. Apoptotic Cells Induced Signaling for Immune Homeostasis in Macrophages and Dendritic Cells

    Directory of Open Access Journals (Sweden)

    Uriel Trahtemberg

    2017-10-01

    Full Text Available Inefficient and abnormal clearance of apoptotic cells (efferocytosis contributes to systemic autoimmune disease in humans and mice, and inefficient chromosomal DNA degradation by DNAse II leads to systemic polyarthritis and a cytokine storm. By contrast, efficient clearance allows immune homeostasis, generally leads to a non-inflammatory state for both macrophages and dendritic cells (DCs, and contributes to maintenance of peripheral tolerance. As many as 3 × 108 cells undergo apoptosis every hour in our bodies, and one of the primary “eat me” signals expressed by apoptotic cells is phosphatidylserine (PtdSer. Apoptotic cells themselves are major contributors to the “anti-inflammatory” nature of the engulfment process, some by secreting thrombospondin-1 (TSP-1 or adenosine monophosphate and possibly other immune modulating “calm-down” signals that interact with macrophages and DCs. Apoptotic cells also produce “find me” and “tolerate me” signals to attract and immune modulate macrophages and DCs that express specific receptors for some of these signals. Neither macrophages nor DCs are uniform, and each cell type may variably express membrane proteins that function as receptors for PtdSer or for opsonins like complement or opsonins that bind to PtdSer, such as protein S and growth arrest-specific 6. Macrophages and DCs also express scavenger receptors, CD36, and integrins that function via bridging molecules such as TSP-1 or milk fat globule-EGF factor 8 protein and that differentially engage in various multi-ligand interactions between apoptotic cells and phagocytes. In this review, we describe the anti-inflammatory and pro-homeostatic nature of apoptotic cell interaction with the immune system. We do not review some forms of immunogenic cell death. We summarize the known apoptotic cell signaling events in macrophages and DCs that are related to toll-like receptors, nuclear factor kappa B, inflammasome, the lipid

  5. Quantitative Evaluation of Stomatal Cytoskeletal Patterns during the Activation of Immune Signaling in Arabidopsis thaliana.

    Directory of Open Access Journals (Sweden)

    Masaki Shimono

    Full Text Available Historically viewed as primarily functioning in the regulation of gas and water vapor exchange, it is now evident that stomata serve an important role in plant immunity. Indeed, in addition to classically defined functions related to cell architecture and movement, the actin cytoskeleton has emerged as a central component of the plant immune system, underpinning not only processes related to cell shape and movement, but also receptor activation and signaling. Using high resolution quantitative imaging techniques, the temporal and spatial changes in the actin microfilament array during diurnal cycling of stomatal guard cells has revealed a highly orchestrated transition from random arrays to ordered bundled filaments. While recent studies have demonstrated that plant stomata close in response to pathogen infection, an evaluation of stimulus-induced changes in actin cytoskeletal dynamics during immune activation in the guard cell, as well as the relationship of these changes to the function of the actin cytoskeleton and stomatal aperture, remains undefined. In the current study, we employed quantitative cell imaging and hierarchical clustering analyses to define the response of the guard cell actin cytoskeleton to pathogen infection and the elicitation of immune signaling. Using this approach, we demonstrate that stomatal-localized actin filaments respond rapidly, and specifically, to both bacterial phytopathogens and purified pathogen elicitors. Notably, we demonstrate that higher order temporal and spatial changes in the filament array show distinct patterns of organization during immune activation, and that changes in the naïve diurnal oscillations of guard cell actin filaments are perturbed by pathogens, and that these changes parallel pathogen-induced stomatal gating. The data presented herein demonstrate the application of a highly tractable and quantifiable method to assign transitions in actin filament organization to the activation of

  6. Recent Advances in Aptamers Targeting Immune System.

    Science.gov (United States)

    Hu, Piao-Ping

    2017-02-01

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

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

    Science.gov (United States)

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

    2017-05-17

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

  8. The immune system, adaptation, and machine learning

    Science.gov (United States)

    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.

  9. Role of neuropilin-2 in the immune system.

    Science.gov (United States)

    Schellenburg, S; Schulz, A; Poitz, D M; Muders, M H

    2017-10-01

    Neuropilins (NRPs) are single transmembrane receptors with short cytoplasmic tails and are dependent on receptors like VEGF receptors or Plexins for signal transduction. NRPs are known to be important in angiogenesis, lymphangiogenesis, and axon guidance. The Neuropilin-family consists of two members, Neuropilin-1 (NRP1) and Neuropilin-2 (NRP2). They are up to 44 % homologous and conserved in all vertebrates. High levels of NRP2 are found on immune cells. Current research is very limited regarding the functions of NRP2 on these cells. Recent evidence suggests that NRP2 is important for migration, antigen presentation, phagocytosis and cell-cell contact within the immune system. Additionally, posttranslational NRP2 modifications like polysialylation are crucial for the function of some immune cells. This review is an overview about expression and functions of NRP2 in the immune system. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Signals and systems for dummies

    CERN Document Server

    Wickert, Mark

    2013-01-01

    Getting mixed signals in your signals and systems course? The concepts covered in a typical signals and systems course are often considered by engineering students to be some of the most difficult to master. Thankfully, Signals & Systems For Dummies is your intuitive guide to this tricky course, walking you step-by-step through some of the more complex theories and mathematical formulas in a way that is easy to understand. From Laplace Transforms to Fourier Analyses, Signals & Systems For Dummies explains in plain English the difficult concepts that can trip you up

  11. Wireless data signal transmission system

    DEFF Research Database (Denmark)

    2014-01-01

    The present invention relates to a method for providing a radio frequency signal for transmission, a system for providing a radio frequency signal for transmission and a method for wireless data transmission between a transmitter and a receiver.......The present invention relates to a method for providing a radio frequency signal for transmission, a system for providing a radio frequency signal for transmission and a method for wireless data transmission between a transmitter and a receiver....

  12. The molecular mechanisms of signaling by cooperative assembly formation in innate immunity pathways.

    Science.gov (United States)

    Vajjhala, Parimala R; Ve, Thomas; Bentham, Adam; Stacey, Katryn J; Kobe, Bostjan

    2017-06-01

    The innate immune system is the first line of defense against infection and responses are initiated by pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs). PRRs also detect endogenous danger-associated molecular patterns (DAMPs) that are released by damaged or dying cells. The major PRRs include the Toll-like receptor (TLR) family members, the nucleotide binding and oligomerization domain, leucine-rich repeat containing (NLR) family, the PYHIN (ALR) family, the RIG-1-like receptors (RLRs), C-type lectin receptors (CLRs) and the oligoadenylate synthase (OAS)-like receptors and the related protein cyclic GMP-AMP synthase (cGAS). The different PRRs activate specific signaling pathways to collectively elicit responses including the induction of cytokine expression, processing of pro-inflammatory cytokines and cell-death responses. These responses control a pathogenic infection, initiate tissue repair and stimulate the adaptive immune system. A central theme of many innate immune signaling pathways is the clustering of activated PRRs followed by sequential recruitment and oligomerization of adaptors and downstream effector enzymes, to form higher-order arrangements that amplify the response and provide a scaffold for proximity-induced activation of the effector enzymes. Underlying the formation of these complexes are co-operative assembly mechanisms, whereby association of preceding components increases the affinity for downstream components. This ensures a rapid immune response to a low-level stimulus. Structural and biochemical studies have given key insights into the assembly of these complexes. Here we review the current understanding of assembly of immune signaling complexes, including inflammasomes initiated by NLR and PYHIN receptors, the myddosomes initiated by TLRs, and the MAVS CARD filament initiated by RIG-1. We highlight the co-operative assembly mechanisms during assembly of each of these complexes. Copyright

  13. Acoustic Signals and Systems

    DEFF Research Database (Denmark)

    2008-01-01

    The Handbook of Signal Processing in Acoustics will compile the techniques and applications of signal processing as they are used in the many varied areas of Acoustics. The Handbook will emphasize the interdisciplinary nature of signal processing in acoustics. Each Section of the Handbook...... will present topics on signal processing which are important in a specific area of acoustics. These will be of interest to specialists in these areas because they will be presented from their technical perspective, rather than a generic engineering approach to signal processing. Non-specialists, or specialists...... from different areas, will find the self-contained chapters accessible and will be interested in the similarities and differences between the approaches and techniques used in different areas of acoustics....

  14. Adrenergic Signaling: A Targetable Checkpoint Limiting Development of the Antitumor Immune Response

    Science.gov (United States)

    Qiao, Guanxi; Chen, Minhui; Bucsek, Mark J.; Repasky, Elizabeth A.; Hylander, Bonnie L.

    2018-01-01

    An immune response must be tightly controlled so that it will be commensurate with the level of response needed to protect the organism without damaging normal tissue. The roles of cytokines and chemokines in orchestrating these processes are well known, but although stress has long been thought to also affect immune responses, the underlying mechanisms were not as well understood. Recently, the role of nerves and, specifically, the sympathetic nervous system, in regulating immune responses is being revealed. Generally, an acute stress response is beneficial but chronic stress is detrimental because it suppresses the activities of effector immune cells while increasing the activities of immunosuppressive cells. In this review, we first discuss the underlying biology of adrenergic signaling in cells of both the innate and adaptive immune system. We then focus on the effects of chronic adrenergic stress in promoting tumor growth, giving examples of effects on tumor cells and immune cells, explaining the methods commonly used to induce stress in preclinical mouse models. We highlight how this relates to our observations that mandated housing conditions impose baseline chronic stress on mouse models, which is sufficient to cause chronic immunosuppression. This problem is not commonly recognized, but it has been shown to impact conclusions of several studies of mouse physiology and mouse models of disease. Moreover, the fact that preclinical mouse models are chronically immunosuppressed has critical ramifications for analysis of any experiments with an immune component. Our group has found that reducing adrenergic stress by housing mice at thermoneutrality or treating mice housed at cooler temperatures with β-blockers reverses immunosuppression and significantly improves responses to checkpoint inhibitor immunotherapy. These observations are clinically relevant because there are numerous retrospective epidemiological studies concluding that cancer patients who were

  15. SUMO-, MAPK- and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    Burg, van den H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

  16. SUMO-, MAPK-, and resistance protein-signaling converge at transcription complexes that regulate plant innate immunity

    NARCIS (Netherlands)

    van den Burg, H.A.; Takken, F.L.W.

    2010-01-01

    Upon pathogen perception plant innate immune receptors activate various signaling pathways that trigger host defenses. PAMP-triggered defense signaling requires mitogen-activated protein kinase (MAPK) pathways, which modulate the activity of transcription factors through phosphorylation. Here, we

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

    Science.gov (United States)

    Eleftherianos, Ioannis; Castillo, Julio Cesar

    2012-01-01

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

  18. METHODS OF PROVIDING NOISE IMMUNITY IN AUTOMOBILE ANTI-THEFT SYSTEM CONTROL

    Directory of Open Access Journals (Sweden)

    Frolov, V.

    2013-06-01

    Full Text Available In modern ani-theft systems they use frequency and phase modulation. Since the width of the signal is limited, it is possible to intercept the signal and then switch off the alarm at the right time.To ensure the noise immunity and secrecy manufacturers use more sophisticated codes using the methods of cryptography. Significant increase in noise immunity in modern ani-theft systems is possible using broadband signals.

  19. Trauma: the role of the innate immune system

    Directory of Open Access Journals (Sweden)

    Rijkers GT

    2006-05-01

    Full Text Available Abstract 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.

  20. Cyclic GMP-AMP as an Endogenous Second Messenger in Innate Immune Signaling by Cytosolic DNA.

    Science.gov (United States)

    Kato, Kazuki; Omura, Hiroki; Ishitani, Ryuichiro; Nureki, Osamu

    2017-06-20

    The innate immune system functions as the first line of defense against invading bacteria and viruses. In this context, the cGAS/STING [cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase/STING] signaling axis perceives the nonself DNA associated with bacterial and viral infections, as well as the leakage of self DNA by cellular dysfunction and stresses, to elicit the host's immune responses. In this pathway, the noncanonical cyclic dinucleotide 2',3'-cyclic GMP-AMP (2',3'-cGAMP) functions as a second messenger for signal transduction: 2',3'-cGAMP is produced by the enzyme cGAS upon its recognition of double-stranded DNA, and then the 2',3'-cGAMP is recognized by the receptor STING to induce the phosphorylation of downstream factors, including TBK1 (TANK binding kinase 1) and IRF3 (interferon regulatory factor 3). Numerous crystal structures of the components of this cGAS/STING signaling axis have been reported and these clarify the structural basis for their signal transduction mechanisms. In this review, we summarize recent progress made in the structural dissection of this signaling pathway and indicate possible directions of forthcoming research.

  1. Regional specialization within the intestinal immune system

    DEFF Research Database (Denmark)

    Mowat, Allan M.; Agace, William Winston

    2014-01-01

    The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly...... implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout...... the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease...

  2. DMPD: Peptidoglycan signaling in innate immunity and inflammatory disease. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 15802263 Peptidoglycan signaling in innate immunity and inflammatory disease. McDon...ald C, Inohara N, Nunez G. J Biol Chem. 2005 May 27;280(21):20177-80. Epub 2005 Mar 31. (.png) (.svg) (.html) (.csml) Show Peptidog...lycan signaling in innate immunity and inflammatory disease. PubmedID 15802263 Title Peptidog

  3. Interleukin-21 receptor signalling is important for innate immune protection against HSV-2 infections.

    Directory of Open Access Journals (Sweden)

    Sine K Kratholm

    Full Text Available Interleukin (IL -21 is produced by Natural Killer T (NKT cells and CD4(+ T cells and is produced in response to virus infections, where IL-21 has been shown to be essential in adaptive immune responses. Cells from the innate immune system such as Natural Killer (NK cells and macrophages are also important in immune protection against virus. These cells express the IL-21 receptor (IL-21R and respond to IL-21 with increased cytotoxicity and cytokine production. Currently, however it is not known whether IL-21 plays a significant role in innate immune responses to virus infections. The purpose of this study was to investigate the role of IL-21 and IL-21R in the innate immune response to a virus infection. We used C57BL/6 wild type (WT and IL-21R knock out (KO mice in a murine vaginal Herpes Simplex Virus type 2 (HSV-2 infection model to show that IL-21 - IL-21R signalling is indeed important in innate immune responses against HSV-2. We found that the IL-21R was expressed in the vaginal epithelium in uninfected (u.i WT mice, and expression increased early after HSV-2 infection. IL-21R KO mice exhibited increased vaginal viral titers on day 2 and 3 post infection (p.i. and subsequently developed significantly higher disease scores and a lower survival rate compared to WT mice. In addition, WT mice infected with HSV-2 receiving intra-vaginal pre-treatment with murine recombinant IL-21 (mIL-21 had decreased vaginal viral titers on day 2 p.i., significantly lower disease scores, and a higher survival rate compared to infected untreated WT controls. Collectively our data demonstrate the novel finding that the IL-21R plays a critical role in regulating innate immune responses against HSV-2 infection.

  4. Keeping the immune system in check: a role for mitophagy.

    Science.gov (United States)

    Lazarou, Michael

    2015-01-01

    Mitochondria play a central role in many facets of cellular function including energy production, control of cell death and immune signaling. Breakdown of any of these pathways because of mitochondrial deficits or excessive reactive oxygen species production has detrimental consequences for immune system function and cell viability. Maintaining the functional integrity of mitochondria is therefore a critical challenge for the cell. Surveillance systems that monitor mitochondrial status enable the cell to identify and either repair or eliminate dysfunctional mitochondria. Mitophagy is a selective form of autophagy that eliminates dysfunctional mitochondria from the population to maintain overall mitochondrial health. This review covers the major players involved in mitophagy and explores the role mitophagy plays to support the immune system.

  5. Modulating the immune system through nanotechnology.

    Science.gov (United States)

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

    2017-12-01

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

  6. The influence of pregnancy on systemic immunity.

    Science.gov (United States)

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

    2012-12-01

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

  7. The ontogeny of the porcine immune system

    Czech Academy of Sciences Publication Activity Database

    Šinkora, Marek; Butler, J. E.

    2009-01-01

    Roč. 33, č. 3 (2009), s. 273-283 ISSN 0145-305X R&D Projects: GA ČR GA524/07/0087; GA ČR GA523/07/0088 Institutional research plan: CEZ:AV0Z50200510 Keywords : ontogeny of the porcine immune system * swine adaptive immunity * development of alpha beta and gamma delta T cells Subject RIV: EC - Immunology Impact factor: 3.290, year: 2009

  8. Immune regulation in gut and cord : opportunities for directing the immune system

    NARCIS (Netherlands)

    de Roock, S.

    2012-01-01

    The gut is an important organ for the immune system. Microbes and immune cells interact directly or via epithelial cells. Both TH17 and Treg cells mature in this environment. The composition of the microbiota has an important influence on the immune homeostasis. Influencing the immune system via the

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

    Science.gov (United States)

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

    2010-09-01

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

  10. Signaling by myeloid C-type lectin receptors in immunity and homeostasis.

    Science.gov (United States)

    Sancho, David; Reis e Sousa, Caetano

    2012-01-01

    Myeloid cells are key drivers of physiological responses to pathogen invasion or tissue damage. Members of the C-type lectin receptor (CLR) family stand out among the specialized receptors utilized by myeloid cells to orchestrate these responses. CLR ligands include carbohydrate, protein, and lipid components of both pathogens and self, which variably trigger endocytic, phagocytic, proinflammatory, or anti-inflammatory reactions. These varied outcomes rely on a versatile system for CLR signaling that includes tyrosine-based motifs that recruit kinases, phosphatases, or endocytic adaptors as well as nontyrosine-based signals that modulate the activation of other pathways or couple to the uptake machinery. Here, we review the signaling properties of myeloid CLRs and how they impact the role of myeloid cells in innate and adaptive immunity.

  11. Physical Activities, Exercises, and Their Effects to the Immune System

    OpenAIRE

    Nurmasitoh, Titis

    2015-01-01

    Every systems in human body correlate to maintain homeostasis. One of those systems which contribute to maintain homeostasis is the immune system. The immune system defends physiological functions against foreign substances and cancer cells through a complex and multilayered mechanism. The ability to defend against foreign substances and abnormal cells is done by two types of immune system, which are Innate immune system and adaptive/acquired immune system. There are also certain factors that...

  12. The Immune System in Irritable Bowel Syndrome

    Science.gov (United States)

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

    2011-01-01

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

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

    Science.gov (United States)

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

    2017-04-01

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

  14. Immune system alterations in amyotrophic lateral sclerosis

    DEFF Research Database (Denmark)

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

    2013-01-01

    Amyotrophic lateral sclerosis is a disease of which the underlying cause and pathogenesis are unknown. Cumulatative data clearly indicates an active participation by the immune system in the disease. An increasingly recognized theory suggests a non-cell autonomous mechanism, meaning that multiple...... cells working together are necessary for the pathogenesis of the disease. Observed immune system alterations could indicate an active participation in this mechanism. Damaged motor neurons are able to activate microglia, astrocytes and the complement system, which further can influence each other...... and contribute to neurodegeneration. Infiltrating peripheral immune cells appears to correlate with disease progression, but their significance and composition is unclear. The deleterious effects of this collaborating system of cells appear to outweigh the protective aspects, and revealing this interplay might...

  15. The neonicotinoid insecticide Clothianidin adversely affects immune signaling in a human cell line.

    Science.gov (United States)

    Di Prisco, Gennaro; Iannaccone, Marco; Ianniello, Flora; Ferrara, Rosalba; Caprio, Emilio; Pennacchio, Francesco; Capparelli, Rosanna

    2017-10-18

    Clothianidin is a widely used neonicotinoid insecticide, which is a potent agonist of the nicotinic acetylcholine receptor in insects. This neurotoxic compound has a negative impact on insect immunity, as it down-regulates the activation of the transcription factor NF-κB. Given the evolutionary conserved role of NF-κB in the modulation of the immune response in the animal kingdom, here we want to assess any effect of Clothianidin on vertebrate defense barriers. In presence of this neonicotinoid insecticide, a pro-inflammatory challenge with LPS on the human monocytic cell line THP-1 results both in a reduced production of the cytokine TNF-α and in a down-regulation of a reporter gene under control of NF-κB promoter. This finding is corroborated by a significant impact of Clothianidin on the transcription levels of different immune genes, characterized by a core disruption of TRAF4 and TRAF6 that negatively influences NF-κB signaling. Moreover, exposure to Clothianidin concurrently induces a remarkable up-regulation of NGFR, which supports the occurrence of functional ties between the immune and nervous systems. These results suggest a potential risk of immunotoxicity that neonicotinoids may have on vertebrates, which needs to be carefully assessed at the organism level.

  16. Signals and systems with MATLAB

    CERN Document Server

    Yang, Won Young; Song, Ik H; Cho, Yong S

    2009-01-01

    Covers some of the theoretical foundations and mathematical derivations that can be used in higher-level related subjects such as signal processing, communication, and control, minimizing the mathematical difficulty and computational burden. This book illustrates the usage of MATLAB and Simulink for signal and system analysis and design.

  17. Dengue vaccine safety signal: Immune enhancement, waning immunity, or chance occurrence?

    Science.gov (United States)

    Gessner, Bradford D; Halsey, Neal

    2017-06-14

    A new dengue vaccine was associated with increased risk of hospitalized virologically-confirmed disease during year 3 of follow-up among children age 2-5years. Among hypotheses to explain this finding, we could not distinguish definitively between antibody dependent enhancement, waning immunity, or chance occurrence. However, any theory must account for the following: (a) the signal occurred mainly because of decreased dengue among controls rather than increased dengue among vaccinees; (b) among 48 data points, a statistically significant increase in hospitalization among vaccinated children occurred for only one age group, during one year, and in one region; (c) cumulative risk was similar for vaccinated vs. control children age 2-5years at the end of year 5 and lower for vaccinated vs. control children among older age groups; (d) the protective effect of vaccine against hospitalization decreased from years 1-2 to years 3-5 of follow-up for all age groups and regions. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. Neural Control of the Immune System

    Science.gov (United States)

    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…

  19. Artificial immune system applications in computer security

    CERN Document Server

    Tan, Ying

    2016-01-01

    This book provides state-of-the-art information on the use, design, and development of the Artificial Immune System (AIS) and AIS-based solutions to computer security issues. Artificial Immune System: Applications in Computer Security focuses on the technologies and applications of AIS in malware detection proposed in recent years by the Computational Intelligence Laboratory of Peking University (CIL@PKU). It offers a theoretical perspective as well as practical solutions for readers interested in AIS, machine learning, pattern recognition and computer security. The book begins by introducing the basic concepts, typical algorithms, important features, and some applications of AIS. The second chapter introduces malware and its detection methods, especially for immune-based malware detection approaches. Successive chapters present a variety of advanced detection approaches for malware, including Virus Detection System, K-Nearest Neighbour (KNN), RBF networ s, and Support Vector Machines (SVM), Danger theory, ...

  20. Protein Kinase C Enzymes in the Hematopoietic and Immune Systems.

    Science.gov (United States)

    Altman, Amnon; Kong, Kok-Fai

    2016-05-20

    The protein kinase C (PKC) family, discovered in the late 1970s, is composed of at least 10 serine/threonine kinases, divided into three groups based on their molecular architecture and cofactor requirements. PKC enzymes have been conserved throughout evolution and are expressed in virtually all cell types; they represent critical signal transducers regulating cell activation, differentiation, proliferation, death, and effector functions. PKC family members play important roles in a diverse array of hematopoietic and immune responses. This review covers the discovery and history of this enzyme family, discusses the roles of PKC enzymes in the development and effector functions of major hematopoietic and immune cell types, and points out gaps in our knowledge, which should ignite interest and further exploration, ultimately leading to better understanding of this enzyme family and, above all, its role in the many facets of the immune system.

  1. Signal system data mining

    Science.gov (United States)

    2000-09-01

    Intelligent transportation systems (ITS) include large numbers of traffic sensors that collect enormous quantities of data. The data provided by ITS is necessary for advanced forms of control, however basic forms of control, primarily time-of-day (TO...

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

    Science.gov (United States)

    Lamichhane, Aayam; Kiyono, Hiroshi; Kunisawa, Jun

    2013-12-01

    The gut is equipped with a unique immune system for maintaining immunological homeostasis, and its functional immune disruption can result in the development of immune diseases such as food allergy and intestinal inflammation. Accumulating evidence has demonstrated that nutritional components play an important role in the regulation of gut immune responses and also in the development of intestinal immune diseases. In this review, we focus on the immunological functions of lipids, vitamins, and nucleotides in the regulation of the intestinal immune system and as potential targets for the control of intestinal immune diseases. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  3. Role of the Immune System in Hypertension.

    Science.gov (United States)

    Rodriguez-Iturbe, Bernardo; Pons, Hector; Johnson, Richard J

    2017-07-01

    High blood pressure is present in more than one billion adults worldwide and is the most important modifiable risk factor of death resulting from cardiovascular disease. While many factors contribute to the pathogenesis of hypertension, a role of the immune system has been firmly established by a large number of investigations from many laboratories around the world. Immunosuppressive drugs and inhibition of individual cytokines prevent or ameliorate experimental hypertension, and studies in genetically-modified mouse strains have demonstrated that lymphocytes are necessary participants in the development of hypertension and in hypertensive organ injury. Furthermore, immune reactivity may be the driving force of hypertension in autoimmune diseases. Infiltration of immune cells, oxidative stress, and stimulation of the intrarenal angiotensin system are induced by activation of the innate and adaptive immunity. High blood pressure results from the combined effects of inflammation-induced impairment in the pressure natriuresis relationship, dysfunctional vascular relaxation, and overactivity of the sympathetic nervous system. Imbalances between proinflammatory effector responses and anti-inflammatory responses of regulatory T cells to a large extent determine the severity of inflammation. Experimental and human studies have uncovered autoantigens (isoketal-modified proteins and heat shock protein 70) of potential clinical relevance. Further investigations on the immune reactivity in hypertension may result in the identification of new strategies for the treatment of the disease. Copyright © 2017 the American Physiological Society.

  4. Role of Osmolytes in Regulating Immune System.

    Science.gov (United States)

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

    2016-01-01

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

  5. Handbook of signal processing systems

    CERN Document Server

    Deprettere, Ed; Leupers, Rainer; Takala, Jarmo

    2013-01-01

    Handbook of Signal Processing Systems is organized in three parts. The first part motivates representative applications that drive and apply state-of-the art methods for design and implementation of signal processing systems; the second part discusses architectures for implementing these applications; the third part focuses on compilers and simulation tools, describes models of computation and their associated design tools and methodologies. This handbook is an essential tool for professionals in many fields and researchers of all levels.

  6. The role of the immune system in the generation of neuropathic pain.

    Science.gov (United States)

    Calvo, Margarita; Dawes, John M; Bennett, David L H

    2012-07-01

    Persistent pain is a sequela of several neurological conditions with a primary immune basis, such as Guillain-Barré syndrome and multiple sclerosis. Additionally, diverse forms of injury to the peripheral or the central nervous systems--whether traumatic, metabolic, or toxic--result in substantial recruitment and activation of immune cells. This response involves the innate immune system, but evidence also exists of T-lymphocyte recruitment, and in some patient cohorts antibodies to neuronal antigens have been reported. Mediators released by immune cells, such as cytokines, sensitise nociceptive signalling in the peripheral and central nervous systems. Preclinical data suggest an immune pathogenesis of neuropathic pain, but clinical evidence of a central role of the immune system is less clear. An important challenge for the future is to establish to what extent this immune response initiates or maintains neuropathic pain in patients and thus whether it is amenable to therapy. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. DMPD: Regulation of innate immunity by suppressor of cytokine signaling (SOCS)proteins. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18406369 Regulation of innate immunity by suppressor of cytokine signaling (SOCS)proteins...svg) (.html) (.csml) Show Regulation of innate immunity by suppressor of cytokine signaling (SOCS)proteins. ...PubmedID 18406369 Title Regulation of innate immunity by suppressor of cytokine signaling (SOCS)proteins

  8. DMPD: Innate immune sensing of pathogens and danger signals by cell surface Toll-likereceptors. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 17275324 Innate immune sensing of pathogens and danger signals by cell surface Toll... Show Innate immune sensing of pathogens and danger signals by cell surface Toll-likereceptors. PubmedID 172...75324 Title Innate immune sensing of pathogens and danger signals by cell surface

  9. Molecular signaling networks in regulation of immunity and disease

    DEFF Research Database (Denmark)

    Laursen, Janne Marie; Jensen, Stina Rikke; Sørensen, Morten

    and dynamic microbial communities with the immune cell compartment in the gut, and therefore the interaction between components from different gut bacteria can efficiently shape the phenotype of the immune response. A specialized antigenpresenting cell present at mucosal surfaces, the dendritic cell (DC......), plays a crucial role in shaping the nature of the adaptive/memorybased immune response after encountering inflammatory compounds. In the gut, the DC is continuously exposed to microbial and dietary components that are recognized by its innate pattern recognition receptors, and the phenotype developed...... in the DC during activation is of profound importance for the state of immune response and thereby also affects the inflammatory and metabolic status in tissues. We have shown that specific fermentation products from gut bacteria have distinct immunoregulatory effects that effectively inhibit...

  10. SIGNALING MECHANISMS IN SEPSIS-INDUCED IMMUNE DYSFUNCTION

    OpenAIRE

    Hasan, Zirak

    2013-01-01

    Sepsis and subsequent organ failure remain the major cause of mortality in intensive care units in spite of significant research efforts. The lung is the most vulnerable organ affected by early hyper-inflammatory immune response in septic patients. On the other hand, the septic insult induces immune dysfunction in later phases of sepsis which in turn increases susceptibility to infections. The aim of this thesis was to investigate early and late inflammatory mechanisms in abdominal sepsis ind...

  11. TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke

    Directory of Open Access Journals (Sweden)

    Buckwalter Marion S

    2010-10-01

    Full Text Available Abstract Background TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging. Methods We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia. Results TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes. Conclusions We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial

  12. TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke.

    Science.gov (United States)

    Doyle, Kristian P; Cekanaviciute, Egle; Mamer, Lauren E; Buckwalter, Marion S

    2010-10-11

    TGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging. We performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia. TGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes. We found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.

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

    Science.gov (United States)

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

    2016-12-01

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

  14. Quantifying adaptive evolution in the Drosophila immune system.

    Directory of Open Access Journals (Sweden)

    Darren J Obbard

    2009-10-01

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

  15. Hibernation : the immune system at rest?

    NARCIS (Netherlands)

    Bouma, Hjalmar R.; Carey, Hannah V.; Kroese, Frans G. M.

    2010-01-01

    Mammalian hibernation consists of torpor phases when metabolism is severely depressed, and T can reach as low as approximately -2 degrees C, interrupted by euthermic arousal phases. Hibernation affects the function of the innate and the adaptive immune systems. Torpor drastically reduces numbers of

  16. [The liver and the immune system].

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    Paula Rodrigues Oblessuc

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

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Immune system investigations for radiation workers

    International Nuclear Information System (INIS)

    Obreja, Doina; Tulbure, Rodica; Marinescu, Irina

    2001-01-01

    During the last decade a great deal of attention has been paid to the research in the field of the immune system. Some important steps forward have been achieved in understanding the mechanisms of action and control of the immunologic responses. At the same time the concern for the possible health effects of exposure to ionizing radiation has considerably increased. On the purpose of the evaluation of the modifications induced by the ionizing radiation for radiation workers, we have applied the method of lymphocytic subpopulations, a method that evinces the proportions for the various subtypes of lymphocytes having different roles within the immune system. A number of 62 persons, employees of the Institute of Physics and Nuclear Engineering at Bucharest - Magurele were involved in this study. All radiation workers from 2 departments characterized by a high exposure to ionizing radiation were included, as follows: Group no. 1, consisting of 20 persons working at RWTS (Radioactive Waste Treating Station), thus presenting both external and internal irradiation; Group no. 2, consisting of 18 persons working at RPC (Radioactive Isotopes Preparing Center), a place where besides the radioactive contamination, the chemical risk was also present. The control group (consisting of 24 persons) was formed of employees from the same institute, with the difference that they were not radiation workers. For the statistical processing of the results the programs EPI INFO 6 and CIA were used. Significantly, when analyzing globally the lymphocytic modifications for TT and/or B lymphocytes (either increments or decrements when compared to the normal values), a noticeable statistical difference among the groups in terms of the frequency of the immune system modifications (Hi square test p=0.001) occurs. The results are in accordance to those in special literature mentioning age as a factor having a role in the appearance of the immune modifications. The obtained results indicate a

  20. The conservative physiology of the immune system

    Directory of Open Access Journals (Sweden)

    N.M. Vaz

    2003-01-01

    Full Text Available Current immunological opinion disdains the necessity to define global interconnections between lymphocytes and regards natural autoantibodies and autoreactive T cells as intrinsically pathogenic. Immunological theories address the recognition of foreignness by independent clones of lymphocytes, not the relations among lymphocytes or between lymphocytes and the organism. However, although extremely variable in cellular/molecular composition, the immune system preserves as invariant a set of essential relations among its components and constantly enacts contacts with the organism of which it is a component. These invariant relations are reflected, for example, in the life-long stability of profiles of reactivity of immunoglobulins formed by normal organisms (natural antibodies. Oral contacts with dietary proteins and the intestinal microbiota also result in steady states that lack the progressive quality of secondary-type reactivity. Autoreactivity (natural autoantibody and autoreactive T cell formation is also stable and lacks the progressive quality of clonal expansion. Specific immune responses, currently regarded as the fundament of the operation of the immune system, may actually result from transient interruptions in this stable connectivity among lymphocytes. More permanent deficits in interconnectivity result in oligoclonal expansions of T lymphocytes, as seen in Omenn's syndrome and in the experimental transplantation of a suboptimal diversity of syngeneic T cells to immunodeficient hosts, which also have pathogenic consequences. Contrary to theories that forbid autoreactivity as potentially pathogenic, the physiology of the immune system is conservative and autoreactive. Pathology derives from failures of these conservative mechanisms.

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

    Science.gov (United States)

    Nikolich-Žugich, Janko

    2018-01-01

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

  2. Deletion of the innate immune NLRP3 receptor abolishes cardiac ischemic preconditioning and is associated with decreased Il-6/STAT3 signaling

    NARCIS (Netherlands)

    Zuurbier, C.J.; Jong, W.M.; Eerbeek, O.; Koeman, A.; Pulskens, W.P.C.; Butter, L.M.; Leemans, J.C.; Hollmann, M.W.

    2012-01-01

    OBJECTIVE: Recent studies indicate that the innate immune system is not only triggered by exogenous pathogens and pollutants, but also by endogenous danger signals released during ischemia and necrosis. As triggers for the innate immune NLRP3 inflammasome protein complex appear to overlap with those

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

    Science.gov (United States)

    Rubinow, Katya B; Rubinow, David R

    2017-03-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

    Vaccines for protection against respiratory infections should optimally induce a mucosal immune response in the respiratory tract in addition to a systemic immune response. However, current parenteral immunization modalities generally fail to induce mucosal immunity, while mucosal vaccine delivery

  5. Sympathetic neural modulation of the immune system

    International Nuclear Information System (INIS)

    Madden, K.S.

    1989-01-01

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

  6. The Mucosal Immune System of Teleost Fish

    Directory of Open Access Journals (Sweden)

    Irene Salinas

    2015-08-01

    Full Text Available 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.

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

    Science.gov (United States)

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

    2017-01-01

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

  8. Archaeal CRISPR-based immune systems

    DEFF Research Database (Denmark)

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

    2011-01-01

    CRISPR (clustered regularly interspaced short palindromic repeats)-based immune systems are essentially modular with three primary functions: the excision and integration of new spacers, the processing of CRISPR transcripts to yield mature CRISPR RNAs (crRNAs), and the targeting and cleavage...... of foreign nucleic acid. The primary target appears to be the DNA of foreign genetic elements, but the CRISPR/Cmr system that is widespread amongst archaea also specifically targets and cleaves RNA in vitro. The archaeal CRISPR systems tend to be both diverse and complex. Here we examine evidence...... of CRISPR loci and the evidence for intergenomic exchange of CRISPR systems....

  9. The role of the class A scavenger receptors, SR-A and MARCO, in the immune system. Part 1. The structure of receptors, their ligand binding repertoires and ability to initiate intracellular signaling

    Directory of Open Access Journals (Sweden)

    Szczepan Józefowski

    2012-02-01

    Full Text Available  Recognition of pathogens by innate immune cells is mediated by pattern recognition receptors (PRR, which include scavenger receptors (SR. The class A SR, SR-A/CD204 and MARCO, are characterized by the presence of collagenous and SR cysteine-rich domains in their extracellular portions. Both receptors are expressed mainly on macrophages and dendritic cells. Thanks to their ability to bind to a wide range of polyanionic ligands, the class A SR may participate in numerous functions of these cells, such as endocytosis, and adhesion to extracellular matrix and to other cells. Among SR-A ligands are oxidized lipoproteins and β-amyloid fibrils, which link SR-A to the pathogenesis of arteriosclerosis and Alzheimer’s disease. Despite the demonstration of class A SR involvement in so many processes, the lack of selective ligands precluded reaching definite conclusions concerning their signaling abilities. Using specific receptor ligation with antibodies, we showed that SR-A and MARCO trigger intracellular signaling, modulating pro-inflammatory and microbicidal activities of macrophages. Surprisingly, despite similarities in structure and ligand binding repertoires, SR-A and MARCO exert opposite effects on interleukin-12 (IL-12 production in macrophages. SR-A ligation also stimulated H2O2 and IL-10 production, but had no effect on the release of several other cytokines. These limited effects of specific SR-A ligation contrast with generalized enhancement of immune responses observed in SR-A-deficient mice. Recent studies have revealed that many of these effects of SR-A deficiency may be caused by compensatory changes in the expression of other receptors and/or disinhibition of signal transduction from receptors belonging to the Toll/IL-1R family, rather than by the loss of the receptor function of SR-A.

  10. Organization of an optimal adaptive immune system

    Science.gov (United States)

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

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

  11. Materials to Engineer the Immune System

    Science.gov (United States)

    2011-04-01

    alone (Lysate), or with GM-CSF and lysate (GM+Lys), and 14 days later 200,000 NT1 cells were injected into the mammary pad. Mice survival was...followed over time. Fig. 2. Therapeutic vaccination against NT1 transplantable tumors. NT1 cells (200,000) were injected into the mammary...Engineer the Immune System David Mooney Harvard College Cambridge, MA 02136 Dendritic cells , GM-CSF, CpG, poly(lactide-co-glycolide) The

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

    Science.gov (United States)

    Abnave, Prasad; Ghigo, Eric

    2018-04-09

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

  13. Recovery of the immune system after exercise.

    Science.gov (United States)

    Peake, Jonathan M; Neubauer, Oliver; Walsh, Neil P; Simpson, Richard J

    2017-05-01

    The notion that prolonged, intense exercise causes an "open window" of immunodepression during recovery after exercise is well accepted. Repeated exercise bouts or intensified training without sufficient recovery may increase the risk of illness. However, except for salivary IgA, clear and consistent markers of this immunodepression remain elusive. Exercise increases circulating neutrophil and monocyte counts and reduces circulating lymphocyte count during recovery. This lymphopenia results from preferential egress of lymphocyte subtypes with potent effector functions [e.g., natural killer (NK) cells, γδ T cells, and CD8 + T cells]. These lymphocytes most likely translocate to peripheral sites of potential antigen encounter (e.g., lungs and gut). This redeployment of effector lymphocytes is an integral part of the physiological stress response to exercise. Current knowledge about changes in immune function during recovery from exercise is derived from assessment at the cell population level of isolated cells ex vivo or in blood. This assessment can be biased by large changes in the distribution of immune cells between blood and peripheral tissues during and after exercise. Some evidence suggests that reduced immune cell function in vitro may coincide with changes in vivo and rates of illness after exercise, but more work is required to substantiate this notion. Among the various nutritional strategies and physical therapies that athletes use to recover from exercise, carbohydrate supplementation is the most effective for minimizing immune disturbances during exercise recovery. Sleep is an important aspect of recovery, but more research is needed to determine how sleep disruption influences the immune system of athletes. Copyright © 2017 the American Physiological Society.

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

    Science.gov (United States)

    Ghiringhelli, François; Apetoh, Lionel

    2014-01-01

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

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

    Science.gov (United States)

    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.

  16. Systemic activation of the immune system in HIV infection: The role of the immune complexes (hypothesis).

    Science.gov (United States)

    Korolevskaya, Larisa B; Shmagel, Konstantin V; Shmagel, Nadezhda G; Saidakova, Evgeniya V

    2016-03-01

    Currently, immune activation is proven to be the basis for the HIV infection pathogenesis and a strong predictor of the disease progression. Among the causes of systemic immune activation the virus and its products, related infectious agents, pro-inflammatory cytokines, and regulatory CD4+ T cells' decrease are considered. Recently microbial translocation (bacterial products yield into the bloodstream as a result of the gastrointestinal tract mucosal barrier integrity damage) became the most popular hypothesis. Previously, we have found an association between immune complexes present in the bloodstream of HIV infected patients and the T cell activation. On this basis, we propose a significantly modified hypothesis of immune activation in HIV infection. It is based on the immune complexes' participation in the immunocompetent cells' activation. Immune complexes are continuously formed in the chronic phase of the infection. Together with TLR-ligands (viral antigens, bacterial products coming from the damaged gut) present in the bloodstream they interact with macrophages. As a result macrophages are transformed into the type II activated forms. These macrophages block IL-12 production and start synthesizing IL-10. High level of this cytokine slows down the development of the full-scale Th1-response. The anti-viral reactions are shifted towards the serogenesis. Newly synthesized antibodies' binding to viral antigens leads to continuous formation of the immune complexes capable of interacting with antigen-presenting cells. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. JAK/STAT signaling pathway-mediated immune response in silkworm (Bombyx mori) challenged by Beauveria bassiana.

    Science.gov (United States)

    Geng, Tao; Lv, Ding-Ding; Huang, Yu-Xia; Hou, Cheng-Xiang; Qin, Guang-Xing; Guo, Xi-Jie

    2016-12-20

    Innate immunity was critical in insects defensive system and able to be induced by Janus kinase/signal transducer and activator of transcription cascade transduction (JAK/STAT) signaling pathway. Currently, it had been identified many JAK/STAT signaling pathway-related genes in silkworm, but little function was known on insect innate immunity. To explore the roles of JAK/STAT pathway in antifungal immune response in silkworm (Bombyx mori) against Beauveria bassiana infection, the expression patterns of B. mori C-type lectin 5 (BmCTL5) and genes encoding 6 components of JAK/STAT signaling pathway in silkworm challenged by B. bassiana were analyzed using quantitative real time PCR. Meanwhile the activation of JAK/STAT signaling pathway by various pathogenic micro-organisms and the affect of JAK/STAT signaling pathway inhibitors on antifungal activity in silkworm hemolymph was also detected. Moreover, RNAi assay of BmCTL5 and the affect on expression levels of signaling factors were also analyzed. We found that JAK/STAT pathway could be obviously activated in silkworm challenged with B. bassiana and had no response to bacteria and B. mori cytoplasmic polyhedrosis virus (BmCPV). However, the temporal expression patterns of JAK/STAT signaling pathway related genes were significantly different. B. mori downstream receptor kinase (BmDRK) might be a positive regulator of JAK/STAT signaling pathway in silkworm against B. bassiana infection. Moreover, antifungal activity assay showed that the suppression of JAK/STAT signaling pathway by inhibitors could significantly inhibit the antifungal activity in hemolymph and resulted in increased sensitivity of silkworm to B. bassiana infection, indicating that JAK/STAT signaling pathway might be involved in the synthesis and secretion of antifungal substances. The results of RNAi assays suggested that BmCTL5 might be one pattern recognition receptors for JAK/STAT signaling pathway in silkworm. These findings yield insights for better

  18. Integration of the immune system: a complex adaptive supersystem

    Science.gov (United States)

    Crisman, Mark V.

    2001-10-01

    Immunity to pathogenic organisms is a complex process involving interacting factors within the immune system including circulating cells, tissues and soluble chemical mediators. Both the efficiency and adaptive responses of the immune system in a dynamic, often hostile, environment are essential for maintaining our health and homeostasis. This paper will present a brief review of one of nature's most elegant, complex adaptive systems.

  19. The deconvolution of complex spectra by artificial immune system

    Science.gov (United States)

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

    2017-11-01

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

  20. Gut Microbiota-Immune System Crosstalk and Pancreatic Disorders

    Directory of Open Access Journals (Sweden)

    D. Pagliari

    2018-01-01

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

  1. THE NOISE IMMUNITY OF THE DIGITAL DEMODULATOR MFM-AM SIGNAL USED IN DATA COMMUNICATIONS SYSTEMS OF AIR TRAFFIC CONTROL WITH AUTOMATIC DEPENDENT SURVEILLANCE AGAINST A NON-GAUSSIAN NOISE

    Directory of Open Access Journals (Sweden)

    A. L. Senyavskiy

    2015-01-01

    Full Text Available The article analyzes the robustness of the digital demodulator of the signal with the lowest frequency shift keying at a subcarrier frequency with respect to non-Gaussian interference type of atmospheric, industrial noise and interfering frequency -and phase-shift keyed signals. This type of demodulator is used for the transmission of navigation data in the systems of air traffic control with automatic dependent surveillance.

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

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

    2017-07-01

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

  4. Implications of central immune signaling caused by drugs of abuse: mechanisms, mediators and new therapeutic approaches for prediction and treatment of drug dependence.

    Science.gov (United States)

    Coller, Janet K; Hutchinson, Mark R

    2012-05-01

    In the past two decades a trickle of manuscripts examining the non-neuronal central nervous system immune consequences of the drugs of abuse has now swollen to a significant body of work. Initially, these studies reported associative evidence of central nervous system proinflammation resulting from exposure to the drugs of abuse demonstrating key implications for neurotoxicity and disease progression associated with, for example, HIV infection. However, more recently this drug-induced activation of central immune signaling is now understood to contribute substantially to the pharmacodynamic actions of the drugs of abuse, by enhancing the engagement of classical mesolimbic dopamine reward pathways and withdrawal centers. This review will highlight the key in vivo animal, human, biological and molecular evidence of these central immune signaling actions of opioids, alcohol, cocaine, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). Excitingly, this new appreciation of central immune signaling activity of drugs of abuse provides novel therapeutic interventions and opportunities to identify 'at risk' individuals through the use of immunogenetics. Discussion will also cover the evidence of modulation of this signaling by existing clinical and pre-clinical drug candidates, and novel pharmacological targets. Finally, following examination of the breadth of central immune signaling actions of the drugs of abuse highlighted here, the current known common immune signaling components will be outlined and their impact on established addiction neurocircuitry discussed, thereby synthesizing a common neuroimmune hypothesis of addiction. Copyright © 2012 Elsevier Inc. All rights reserved.

  5. Prenatal Alcohol Exposure and the Developing Immune System

    OpenAIRE

    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 comprehensiv...

  6. Effects of chromium on the immune system.

    Science.gov (United States)

    Shrivastava, Richa; Upreti, R K; Seth, P K; Chaturvedi, U C

    2002-09-06

    Chromium is a naturally occurring heavy metal found commonly in the environment in trivalent, Cr(III), and hexavalent, Cr(VI), forms. Cr(VI) compounds have been declared as a potent occupational carcinogen among workers in chrome plating, stainless steel, and pigment industries. The reduction of Cr(VI) to Cr(III) results in the formation of reactive intermediates that together with oxidative stress oxidative tissue damage and a cascade of cellular events including modulation of apoptosis regulatory gene p53, contribute to the cytotoxicity, genotoxicity and carcinogenicity of Cr(VI)-containing compounds. On the other hand, chromium is an essential nutrient required to promote the action of insulin in body tissues so that the body can use sugars, proteins and fats. Chromium is of significant importance in altering the immune response by immunostimulatory or immunosuppressive processes as shown by its effects on T and B lymphocytes, macrophages, cytokine production and the immune response that may induce hypersensitivity reactions. This review gives an overview of the effects of chromium on the immune system of the body. Copyright 2002 Federation of European Microbiological Societies

  7. Complement System Part II: Role in Immunity

    Science.gov (United States)

    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

  8. Functional aspects of the adaptive immune system in arthritis

    NARCIS (Netherlands)

    Jansen, D.T.S.L.

    2017-01-01

    The adaptive immune system is the part of the immune system that is highly specific and generates memory resulting in a fast and specific immune response upon a second infection with the same pathogen. However, when this response is specific for a part of the body itself instead of a pathogen,

  9. IMMUNE SYSTEM MATURITY AND SENSITIVITY TO CHEMICAL EXPOSURE

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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.

  11. State of immune system lesions eymeriozo turkey-invasions histomonoznoyu

    OpenAIRE

    CHARIV I.

    2011-01-01

    The immune system of animals and birds provides resistance against bacterial and viral infections. In the intestinal mucosa and eymeriyi histomonady produce metabolic products that are toxic to different systems and tissues of turkeys. They parasitizing in the intestine, suppress specific phase of immunity provided by antibodies (humoral type), reduce activity sensitized cells (cell type), slow phase of nonspecific immunity, which is represented by various immune cells.

  12. Prenatal Alcohol Exposure and the Developing Immune System.

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2018-05-01

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

  14. Approaches Mediating Oxytocin Regulation of the Immune System.

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

  16. Metabolic gene expression changes in astrocytes in Multiple Sclerosis cerebral cortex are indicative of immune-mediated signaling

    KAUST Repository

    Zeis, T.

    2015-04-01

    Emerging as an important correlate of neurological dysfunction in Multiple Sclerosis (MS), extended focal and diffuse gray matter abnormalities have been found and linked to clinical manifestations such as seizures, fatigue and cognitive dysfunction. To investigate possible underlying mechanisms we analyzed the molecular alterations in histopathological normal appearing cortical gray matter (NAGM) in MS. By performing a differential gene expression analysis of NAGM of control and MS cases we identified reduced transcription of astrocyte specific genes involved in the astrocyte–neuron lactate shuttle (ANLS) and the glutamate–glutamine cycle (GGC). Additional quantitative immunohistochemical analysis demonstrating a CX43 loss in MS NAGM confirmed a crucial involvement of astrocytes and emphasizes their importance in MS pathogenesis. Concurrently, a Toll-like/IL-1β signaling expression signature was detected in MS NAGM, indicating that immune-related signaling might be responsible for the downregulation of ANLS and GGC gene expression in MS NAGM. Indeed, challenging astrocytes with immune stimuli such as IL-1β and LPS reduced their ANLS and GGC gene expression in vitro. The detected upregulation of IL1B in MS NAGM suggests inflammasome priming. For this reason, astrocyte cultures were treated with ATP and ATP/LPS as for inflammasome activation. This treatment led to a reduction of ANLS and GGC gene expression in a comparable manner. To investigate potential sources for ANLS and GGC downregulation in MS NAGM, we first performed an adjuvant-driven stimulation of the peripheral immune system in C57Bl/6 mice in vivo. This led to similar gene expression changes in spinal cord demonstrating that peripheral immune signals might be one source for astrocytic gene expression changes in the brain. IL1B upregulation in MS NAGM itself points to a possible endogenous signaling process leading to ANLS and GGC downregulation. This is supported by our findings that, among others

  17. Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus

    Directory of Open Access Journals (Sweden)

    Takayuki Katsuyama

    2018-05-01

    Full Text Available Systemic lupus erythematosus (SLE is a chronic multi-organ debilitating autoimmune disease, which mainly afflicts women in the reproductive years. A complex interaction of genetics, environmental factors and hormones result in the breakdown of immune tolerance to “self” leading to damage and destruction of multiple organs, such as the skin, joints, kidneys, heart and brain. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Dendritic cells, neutrophils, and innate lymphoid cells are important in initiating antigen presentation and propagating inflammation at lymphoid and peripheral tissue sites. Autoantibodies produced by B lymphocytes and immune complex deposition in vital organs contribute to tissue damage. T lymphocytes are increasingly being recognized as key contributors to disease pathogenesis. CD4 T follicular helper cells enable autoantibody production, inflammatory Th17 subsets promote inflammation, while defects in regulatory T cells lead to unchecked immune responses. A better understanding of the molecular defects including signaling events and gene regulation underlying the dysfunctional T cells in SLE is necessary to pave the path for better management, therapy, and perhaps prevention of this complex disease. In this review, we focus on the aberrations in T cell signaling in SLE and highlight therapeutic advances in this field.

  18. Aberrant T Cell Signaling and Subsets in Systemic Lupus Erythematosus

    Science.gov (United States)

    Katsuyama, Takayuki; Tsokos, George C.; Moulton, Vaishali R.

    2018-01-01

    Systemic lupus erythematosus (SLE) is a chronic multi-organ debilitating autoimmune disease, which mainly afflicts women in the reproductive years. A complex interaction of genetics, environmental factors and hormones result in the breakdown of immune tolerance to “self” leading to damage and destruction of multiple organs, such as the skin, joints, kidneys, heart and brain. Both innate and adaptive immune systems are critically involved in the misguided immune response against self-antigens. Dendritic cells, neutrophils, and innate lymphoid cells are important in initiating antigen presentation and propagating inflammation at lymphoid and peripheral tissue sites. Autoantibodies produced by B lymphocytes and immune complex deposition in vital organs contribute to tissue damage. T lymphocytes are increasingly being recognized as key contributors to disease pathogenesis. CD4 T follicular helper cells enable autoantibody production, inflammatory Th17 subsets promote inflammation, while defects in regulatory T cells lead to unchecked immune responses. A better understanding of the molecular defects including signaling events and gene regulation underlying the dysfunctional T cells in SLE is necessary to pave the path for better management, therapy, and perhaps prevention of this complex disease. In this review, we focus on the aberrations in T cell signaling in SLE and highlight therapeutic advances in this field. PMID:29868033

  19. Sphingosine-1-Phosphate Signaling in Immune Cells and Inflammation: Roles and Therapeutic Potential

    Directory of Open Access Journals (Sweden)

    Masayo Aoki

    2016-01-01

    Full Text Available Sphingosine-1-phosphate (S1P is a bioactive sphingolipid metabolite involved in many critical cell processes. It is produced by the phosphorylation of sphingosine by sphingosine kinases (SphKs and exported out of cells via transporters such as spinster homolog 2 (Spns2. S1P regulates diverse physiological processes by binding to specific G protein-binding receptors, S1P receptors (S1PRs 1–5, through a process coined as “inside-out signaling.” The S1P concentration gradient between various tissues promotes S1PR1-dependent migration of T cells from secondary lymphoid organs into the lymphatic and blood circulation. S1P suppresses T cell egress from and promotes retention in inflamed peripheral tissues. S1PR1 in T and B cells as well as Spns2 in endothelial cells contributes to lymphocyte trafficking. FTY720 (Fingolimod is a functional antagonist of S1PRs that induces systemic lymphopenia by suppression of lymphocyte egress from lymphoid organs. In this review, we summarize previous findings and new discoveries about the importance of S1P and S1PR signaling in the recruitment of immune cells and lymphocyte retention in inflamed tissues. We also discuss the role of S1P-S1PR1 axis in inflammatory diseases and wound healing.

  20. Immunizing digital systems against electromagnetic interference

    International Nuclear Information System (INIS)

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

    1993-01-01

    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. Second, 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

  1. Immunizing digital systems against electromagnetic interference

    International Nuclear Information System (INIS)

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

    1993-01-01

    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

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

    Science.gov (United States)

    Ameri, Pietro; Ferone, Diego

    2012-01-01

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

  3. Aryl hydrocarbon receptor signaling modulates antiviral immune responses: ligand metabolism rather than chemical source is the stronger predictor of outcome.

    Science.gov (United States)

    Boule, Lisbeth A; Burke, Catherine G; Jin, Guang-Bi; Lawrence, B Paige

    2018-01-29

    The aryl hydrocarbon receptor (AHR) offers a compelling target to modulate the immune system. AHR agonists alter adaptive immune responses, but the consequences differ across studies. We report here the comparison of four agents representing different sources of AHR ligands in mice infected with influenza A virus (IAV): TCDD, prototype exogenous AHR agonist; PCB126, pollutant with documented human exposure; ITE, novel pharmaceutical; and FICZ, degradation product of tryptophan. All four compounds diminished virus-specific IgM levels and increased the proportion of regulatory T cells. TCDD, PCB126 and ITE, but not FICZ, reduced virus-specific IgG levels and CD8 + T cell responses. Similarly, ITE, PCB126, and TCDD reduced Th1 and Tfh cells, whereas FICZ increased their frequency. In Cyp1a1-deficient mice, all compounds, including FICZ, reduced the response to IAV. Conditional Ahr knockout mice revealed that all four compounds require AHR within hematopoietic cells. Thus, differences in the immune response to IAV likely reflect variances in quality, magnitude, and duration of AHR signaling. This indicates that binding affinity and metabolism may be stronger predictors of immune effects than a compound's source of origin, and that harnessing AHR will require finding a balance between dampening immune-mediated pathologies and maintaining sufficient host defenses against infection.

  4. Innate immune signalling at the intestinal epithelium in homeostasis and disease

    Science.gov (United States)

    Pott, Johanna; Hornef, Mathias

    2012-01-01

    The intestinal epithelium—which constitutes the interface between the enteric microbiota and host tissues—actively contributes to the maintenance of mucosal homeostasis and defends against pathogenic microbes. The recognition of conserved microbial products by cytosolic or transmembrane pattern recognition receptors in epithelial cells initiates signal transduction and influences effector cell function. However, the signalling pathways, effector molecules and regulatory mechanisms involved are not yet fully understood, and the functional outcome is poorly defined. This review analyses the complex and dynamic role of intestinal epithelial innate immune recognition and signalling, on the basis of results in intestinal epithelial cell-specific transgene or gene-deficient animals. This approach identifies specific epithelial cell functions within the diverse cellular composition of the mucosal tissue, in the presence of the complex and dynamic gut microbiota. These insights have thus provided a more comprehensive understanding of the role of the intestinal epithelium in innate immunity during homeostasis and disease. PMID:22801555

  5. Plant immune and growth receptors share common signalling components but localise to distinct plasma membrane nanodomains.

    Science.gov (United States)

    Bücherl, Christoph A; Jarsch, Iris K; Schudoma, Christian; Segonzac, Cécile; Mbengue, Malick; Robatzek, Silke; MacLean, Daniel; Ott, Thomas; Zipfel, Cyril

    2017-03-06

    Cell surface receptors govern a multitude of signalling pathways in multicellular organisms. In plants, prominent examples are the receptor kinases FLS2 and BRI1, which activate immunity and steroid-mediated growth, respectively. Intriguingly, despite inducing distinct signalling outputs, both receptors employ common downstream signalling components, which exist in plasma membrane (PM)-localised protein complexes. An important question is thus how these receptor complexes maintain signalling specificity. Live-cell imaging revealed that FLS2 and BRI1 form PM nanoclusters. Using single-particle tracking we could discriminate both cluster populations and we observed spatiotemporal separation between immune and growth signalling platforms. This finding was confirmed by visualising FLS2 and BRI1 within distinct PM nanodomains marked by specific remorin proteins and differential co-localisation with the cytoskeleton. Our results thus suggest that signalling specificity between these pathways may be explained by the spatial separation of FLS2 and BRI1 with their associated signalling components within dedicated PM nanodomains.

  6. Microbial-immune cross-talk and regulation of the immune system.

    Science.gov (United States)

    Cahenzli, Julia; Balmer, Maria L; McCoy, Kathy D

    2013-01-01

    We are all born germ-free. Following birth we enter into a lifelong relationship with microbes residing on our body's surfaces. The lower intestine is home to the highest microbial density in our body, which is also the highest microbial density known on Earth (up to 10(12) /g of luminal contents). With our indigenous microbial cells outnumbering our human cells by an order of magnitude our body is more microbial than human. Numerous immune adaptations confine these microbes within the mucosa, enabling most of us to live in peaceful homeostasis with our intestinal symbionts. Intestinal epithelial cells not only form a physical barrier between the bacteria-laden lumen and the rest of the body but also function as multi-tasking immune cells that sense the prevailing microbial (apical) and immune (basolateral) milieus, instruct the underlying immune cells, and adapt functionally. In the constant effort to ensure intestinal homeostasis, the immune system becomes educated to respond appropriately and in turn immune status can shape the microbial consortia. Here we review how the dynamic immune-microbial dialogue underlies maturation and regulation of the immune system and discuss recent findings on the impact of diet on both microbial ecology and immune function. © 2012 The Authors. Immunology © 2012 Blackwell Publishing Ltd.

  7. A Plant Phytosulfokine Peptide Initiates Auxin-Dependent Immunity through Cytosolic Ca2+ Signaling in Tomato.

    Science.gov (United States)

    Zhang, Huan; Hu, Zhangjian; Lei, Cui; Zheng, Chenfei; Wang, Jiao; Shao, Shujun; Li, Xin; Xia, Xiaojian; Cai, Xinzhong; Zhou, Jie; Zhou, Yanhong; Yu, Jingquan; Foyer, Christine H; Shi, Kai

    2018-03-01

    Phytosulfokine (PSK) is a disulfated pentapeptide that is an important signaling molecule. Although it has recently been implicated in plant defenses to pathogen infection, the mechanisms involved remain poorly understood. Using surface plasmon resonance and gene silencing approaches, we showed that the tomato ( Solanum lycopersicum ) PSK receptor PSKR1, rather than PSKR2, functioned as the major PSK receptor in immune responses. Silencing of PSK signaling genes rendered tomato more susceptible to infection by the economically important necrotrophic pathogen Botrytis cinerea Analysis of tomato mutants defective in either defense hormone biosynthesis or signaling demonstrated that PSK-induced immunity required auxin biosynthesis and associated defense pathways. Here, using aequorin-expressing tomato plants, we provide evidence that PSK perception by tomato PSKR1 elevated cytosolic [Ca 2+ ], leading to auxin-dependent immune responses via enhanced binding activity between calmodulins and the auxin biosynthetic YUCs. Thus, our data demonstrate that PSK acts as a damage-associated molecular pattern and is perceived mainly by PSKR1, which increases cytosolic [Ca 2+ ] and activates auxin-mediated pathways that enhance immunity of tomato plants to B. cinerea . © 2018 American Society of Plant Biologists. All rights reserved.

  8. Distributed Computations Environment Protection Using Artificial Immune Systems

    Directory of Open Access Journals (Sweden)

    A. V. Moiseev

    2011-12-01

    Full Text Available In this article the authors describe possibility of artificial immune systems applying for distributed computations environment protection from definite types of malicious impacts.

  9. Immune genes undergo more adaptive evolution than non-immune system genes in Daphnia pulex

    Directory of Open Access Journals (Sweden)

    McTaggart Seanna J

    2012-05-01

    Full Text Available Abstract Background Understanding which parts of the genome have been most influenced by adaptive evolution remains an unsolved puzzle. Some evidence suggests that selection has the greatest impact on regions of the genome that interact with other evolving genomes, including loci that are involved in host-parasite co-evolutionary processes. In this study, we used a population genetic approach to test this hypothesis by comparing DNA sequences of 30 putative immune system genes in the crustacean Daphnia pulex with 24 non-immune system genes. Results In support of the hypothesis, results from a multilocus extension of the McDonald-Kreitman (MK test indicate that immune system genes as a class have experienced more adaptive evolution than non-immune system genes. However, not all immune system genes show evidence of adaptive evolution. Additionally, we apply single locus MK tests and calculate population genetic parameters at all loci in order to characterize the mode of selection (directional versus balancing in the genes that show the greatest deviation from neutral evolution. Conclusions Our data are consistent with the hypothesis that immune system genes undergo more adaptive evolution than non-immune system genes, possibly as a result of host-parasite arms races. The results of these analyses highlight several candidate loci undergoing adaptive evolution that could be targeted in future studies.

  10. The immune system vs. Pseudomonas aeruginosa biofilms

    DEFF Research Database (Denmark)

    Jensen, Peter Østrup; Givskov, Michael; Bjarnsholt, Thomas

    2010-01-01

    Ilya Metchnikoff and Paul Ehrlich were awarded the Nobel price in 1908. Since then, numerous studies have unraveled a multitude of mechanistically different immune responses to intruding microorganisms. However, in the vast majority of these studies, the underlying infectious agents have appeared...... in the planktonic state. Accordingly, much less is known about the immune responses to the presence of biofilm-based infections (which is probably also due to the relatively short period of time in which the immune response to biofilms has been studied). Nevertheless, more recent in vivo and in vitro studies have...... revealed both innate as well as adaptive immune responses to biofilms. On the other hand, measures launched by biofilm bacteria to achieve protection against the various immune responses have also been demonstrated. Whether particular immune responses to biofilm infections exist remains to be firmly...

  11. The CD47-SIRPα signaling axis as an innate immune checkpoint in cancer.

    Science.gov (United States)

    Matlung, Hanke L; Szilagyi, Katka; Barclay, Neil A; van den Berg, Timo K

    2017-03-01

    Immune checkpoint inhibitors, including those targeting CTLA-4/B7 and the PD-1/PD-L1 inhibitory pathways, are now available for clinical use in cancer patients, with other interesting checkpoint inhibitors being currently in development. Most of these have the purpose to promote adaptive T cell-mediated immunity against cancer. Here, we review another checkpoint acting to potentiate the activity of innate immune cells towards cancer. This innate immune checkpoint is composed of what has become known as the 'don't-eat me' signal CD47, which is a protein broadly expressed on normal cells and often overexpressed on cancer cells, and its counter-receptor, the myeloid inhibitory immunoreceptor SIRPα. Blocking CD47-SIRPα interactions has been shown to promote the destruction of cancer cells by phagocytes, including macrophages and neutrophils. Furthermore, there is growing evidence that targeting of the CD47-SIRPα axis may also promote antigen-presenting cell function and thereby stimulate adaptive T cell-mediated anti-cancer immunity. The development of CD47-SIRPα checkpoint inhibitors and the potential side effects that these may have are discussed. Collectively, this identifies the CD47-SIRPα axis as a promising innate immune checkpoint in cancer, and with data of the first clinical studies with CD47-SIRPα checkpoint inhibitors expected within the coming years, this is an exciting and rapidly developing field. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Science.gov (United States)

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

    2017-12-01

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

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

    Science.gov (United States)

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

    2017-08-01

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

  14. Immune response induction in the central nervous system

    DEFF Research Database (Denmark)

    Owens, Trevor; Babcock, Alicia

    2002-01-01

    The primary function of the immune response is protection of the host against infection with pathogens, including viruses. Since viruses can infect any tissue of the body, including the central nervous system (CNS), it is logical that cells of the immune system should equally have access to all...... tissues. Nevertheless, the brain and spinal cord are noted for their lack of immune presence. Relative to other organ systems, the CNS appears immunologically privileged. Furthermore, when immune responses do occur in the CNS, they are frequently associated with deleterious effects such as inflammatory...

  15. Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type 1 Diabetes.

    Science.gov (United States)

    Kronenberg-Versteeg, Deborah; Eichmann, Martin; Russell, Mark A; de Ru, Arnoud; Hehn, Beate; Yusuf, Norkhairin; van Veelen, Peter A; Richardson, Sarah J; Morgan, Noel G; Lemberg, Marius K; Peakman, Mark

    2018-04-01

    The signal peptide region of preproinsulin (PPI) contains epitopes targeted by HLA-A-restricted (HLA-A0201, A2402) cytotoxic T cells as part of the pathogenesis of β-cell destruction in type 1 diabetes. We extended the discovery of the PPI epitope to disease-associated HLA-B*1801 and HLA-B*3906 (risk) and HLA-A*1101 and HLA-B*3801 (protective) alleles, revealing that four of six alleles present epitopes derived from the signal peptide region. During cotranslational translocation of PPI, its signal peptide is cleaved and retained within the endoplasmic reticulum (ER) membrane, implying it is processed for immune recognition outside of the canonical proteasome-directed pathway. Using in vitro translocation assays with specific inhibitors and gene knockout in PPI-expressing target cells, we show that PPI signal peptide antigen processing requires signal peptide peptidase (SPP). The intramembrane protease SPP generates cytoplasm-proximal epitopes, which are transporter associated with antigen processing (TAP), ER-luminal epitopes, which are TAP independent, each presented by different HLA class I molecules and N-terminal trimmed by ER aminopeptidase 1 for optimal presentation. In vivo, TAP expression is significantly upregulated and correlated with HLA class I hyperexpression in insulin-containing islets of patients with type 1 diabetes. Thus, PPI signal peptide epitopes are processed by SPP and loaded for HLA-guided immune recognition via pathways that are enhanced during disease pathogenesis. © 2018 by the American Diabetes Association.

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

    Science.gov (United States)

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

    2014-05-01

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

  17. how to evade the immune system?

    Indian Academy of Sciences (India)

    HCV usually induces robust immune responses, but it frequently escapes the immune defense to establish persistent infection. The fact that HCV exists as an evolving quasispecies plays an important role in the selection of escape mutants. Furthermore, several viral proteins interfere with cellular functions, in particular, ...

  18. The Immune System and Bodily Defence

    Indian Academy of Sciences (India)

    perhaps, with others, but together, these characteristics make the immune ..... 1 year. 2 days. 0. 0. 0. 0. 0. 0. 0. 0. • •. •. 0. 0. 0. vV\\NVv. RESONANCE I January 1997 ... can maintain immune memory and make vaccines possible. Of course, the ...

  19. The activation of the adaptive immune system: cross-talk between antigen-presenting cells, T cells and B cells.

    Science.gov (United States)

    den Haan, Joke M M; Arens, Ramon; van Zelm, Menno C

    2014-12-01

    The adaptive immune system consists of T and B cells that express clonally distributed antigen receptors. To achieve functional adaptive immune responses, antigen-specific T cell populations are stimulated by professional antigen-presenting cells like dendritic cells (DCs), which provide crucial stimulatory signals for efficient expansion and development of effector functions. Antigen-specific B cells receive costimulatory signals from helper T cells to stimulate affinity maturation and isotype switching. Here we elaborate on the interactions between DCs, T cells and B cells, and on the important signals for efficient induction of adaptive immune responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Engineering Plant Immunity via CRISPR/Cas13a System

    KAUST Repository

    Aljedaani, Fatimah R.

    2018-01-01

    systems function as an adaptive immune system to provide bacteria with resistance against invading phages and conjugative plasmids. Interestingly, CRISPR/Cas9 system was shown to interfere with eukaryotic DNA viruses and confer resistance against plant DNA

  1. The Role of the Immune System in Obesity and Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Payal S. Patel

    2013-01-01

    Full Text Available The innate immune system provides organisms with rapid and well-coordinated protection from foreign pathogens. However, under certain conditions of metabolic dysfunction, components of the innate immune system may be activated in the absence of external pathogens, leading to pathologic consequences. Indeed, there appears to be an intimate relationship between metabolic diseases and immune dysfunction; for example, macrophages are prime players in the initiation of a chronic inflammatory state in obesity which leads to insulin resistance. In response to increases in free fatty acid release from obese adipose depots, M1-polarized macrophages infiltrate adipose tissues. These M1 macrophages trigger inflammatory signaling and stress responses within cells that signal through JNK or IKKβ pathways, leading to insulin resistance. If overnutrition persists, mechanisms that counteract inflammation (such as M2 macrophages and PPAR signaling are suppressed, and the inflammation becomes chronic. Although macrophages are a principal constituent of obese adipose tissue inflammation, other components of the immune system such as lymphocytes and mast cells also contribute to the inflammatory cascade. Thus it is not merely an increased mass of adipose tissue that directly leads to attenuation of insulin action, but rather adipose tissue inflammation activated by the immune system in obese individuals that leads to insulin resistance.

  2. The role of intestinal microbiota and the immune system.

    Science.gov (United States)

    Purchiaroni, F; Tortora, A; Gabrielli, M; Bertucci, F; Gigante, G; Ianiro, G; Ojetti, V; Scarpellini, E; Gasbarrini, A

    2013-02-01

    The human gut is an ecosystem consisting of a great number of commensal bacteria living in symbiosis with the host. Several data confirm that gut microbiota is engaged in a dynamic interaction with the intestinal innate and adaptive immune system, affecting different aspects of its development and function. To review the immunological functions of gut microbiota and improve knowledge of its therapeutic implications for several intestinal and extra-intestinal diseases associated to dysregulation of the immune system. Significant articles were identified by literature search and selected based on content, including atopic diseases, inflammatory bowel diseases and treatment of these conditions with probiotics. Accumulating evidence indicates that intestinal microflora has protective, metabolic, trophic and immunological functions and is able to establish a "cross-talk" with the immune component of mucosal immunity, comprising cellular and soluble elements. When one or more steps in this fine interaction fail, autoimmune or auto-inflammatory diseases may occur. Furthermore, it results from the data that probiotics, used for the treatment of the diseases caused by the dysregulation of the immune system, can have a beneficial effect by different mechanisms. Gut microbiota interacts with both innate and adaptive immune system, playing a pivotal role in maintenance and disruption of gut immune quiescence. A cross talk between the mucosal immune system and endogenous microflora favours a mutual growth, survival and inflammatory control of the intestinal ecosystem. Based on these evidences, probiotics can be used as an ecological therapy in the treatment of immune diseases.  

  3. Immune evasion of porcine enteric coronaviruses and viral modulation of antiviral innate signaling.

    Science.gov (United States)

    Zhang, Qingzhan; Yoo, Dongwan

    2016-12-02

    Porcine epidemic diarrhea virus (PEDV) and porcine deltacoronavirus (PDCoV) are emerged and reemerging viruses in pigs, and together with transmissible gastroenteritis virus (TGEV), pose significant economic concerns to the swine industry. These viruses infect epithelial cells of the small intestine and cause watery diarrhea, dehydration, and a high mortality in neonatal piglets. Type I interferons (IFN-α/β) are major antiviral cytokines forming host innate immunity, and in turn, these enteric coronaviruses have evolved to modulate the host innate immune signaling during infection. Accumulating evidence however suggests that IFN induction and signaling in the intestinal epithelial cells differ from other epithelial cells, largely due to distinct features of the gut epithelial mucosal surface and commensal microflora, and it appears that type III interferon (IFN-λ) plays a key role to maintain the antiviral state in the gut. This review describes the recent understanding on the immune evasion strategies of porcine enteric coronaviruses and the role of different types of IFNs for intestinal antiviral innate immunity. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Interleukin-36 cytokines may overcome microbial immune evasion strategies that inhibit interleukin-1 family signaling.

    Science.gov (United States)

    Jensen, Liselotte E

    2017-08-15

    Pathogens deploy immune evasion strategies to successfully establish infections within their hosts. Naturally, the host responds by acquiring mechanisms to counter these strategies. There is increasing evidence that the three interleukin-36 (IL-36) cytokines, IL-36α, IL-36β and IL-36γ, play important roles in host immunity. With a focus on the skin as a target for microbial and viral invasion, the current knowledge of IL-36 functions is reviewed. Furthermore, the hypothesis that the IL-36s have evolved to counteract virulence factors is presented using viruses as an example. The IL-36s are related to IL-1α, IL-1β, IL-18, and IL-33. Numerous viruses affecting the skin have developed immune evasion strategies that neutralize IL-1α, IL-1β, or IL-18 signaling or combinations of these pathways. Through small differences in activation mechanisms and receptor utilization, it is possible that IL-36 signaling may proceed unhindered in the presence of these viral inhibitors. Thus, one physiological function of the IL-36s may be to counteract microbial immune evasion. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  5. Notch1 Signaling Regulates the Th17/Treg Immune Imbalance in Patients with Psoriasis Vulgaris.

    Science.gov (United States)

    Ma, Lei; Xue, HaiBo; Gao, Tianqin; Gao, MeiLan; Zhang, YuJie

    2018-01-01

    To evaluate the regulating effect of Notch1 signaling on Th17/Treg immune imbalance in psoriasis vulgaris (PV). Notch1, Hes-1, ROR γ t, Foxp3, IL-17, and IL-10 mRNA expression, as well as Th17 and Treg cell percentages in peripheral CD4 + T cells, were detected by real-time quantitative RT-PCR and flow cytometry, and serum concentrations of IL-17 and IL-10 were detected by ELISA in 36 PV patients and 32 healthy controls. Additionally, CD4 + T cells from 12 PV patients were treated with γ -secretase inhibitor DAPT, and the above indexes were measured. PV patients presented distinct Th17/Treg immune imbalance and highly expressed Notch1 and Hes-1 mRNA levels, which were positively correlated with psoriasis area and severity index (PASI) and the ratios of Th17/Treg and ROR γ t/Foxp3. DAPT treatment resulted in the obvious downregulation of Th17 cell percentage in cocultured CD4 + T cells, ROR γ t and IL-17 mRNA levels, and IL-17 concentration in cell-free supernatant from cocultured CD4 + T cells of PV patients in a dose-dependent manner, while there was no significant influence on Treg cell percentage, Foxp3, and IL-10 expression, therefore leading to the recovery of Th17/Treg immune imbalance. Notch1 signaling may contribute to the pathogenesis of PV by regulating Th17/Treg immune imbalance.

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

    Science.gov (United States)

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

    2018-01-01

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

  7. Breakdown of the innate immune system by bacterial proteases

    NARCIS (Netherlands)

    Laarman, A.J.

    2011-01-01

    Bacteria have developed many strategies to circumvent our immune system to survive and colonize human tissues. One of these strategies is by secreting proteases that specifically target the innate immune system. Aureolysin is a metalloprotease from Staphylococcus aureus which target the main

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

    Science.gov (United States)

    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

  9. The University Immune System: Overcoming Resistance to Change

    Science.gov (United States)

    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.

  10. The reaction of the immune system of fish to vaccination

    NARCIS (Netherlands)

    Lamers, C.H.J.

    1985-01-01

    The studies presented in this thesis deal with the effect of bacterial antigens of Yersinia ruckeri and Aeromonashydrophila on the immune system of carp. The antigens were administered by injection or by bath treatment. The effect on the immune system was studied by

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

    Science.gov (United States)

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

    2017-06-01

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

  12. Single-cell network profiling of peripheral blood mononuclear cells from healthy donors reveals age- and race-associated differences in immune signaling pathway activation.

    Science.gov (United States)

    Longo, Diane M; Louie, Brent; Putta, Santosh; Evensen, Erik; Ptacek, Jason; Cordeiro, James; Wang, Ena; Pos, Zoltan; Hawtin, Rachael E; Marincola, Francesco M; Cesano, Alessandra

    2012-02-15

    A greater understanding of the function of the human immune system at the single-cell level in healthy individuals is critical for discerning aberrant cellular behavior that occurs in settings such as autoimmunity, immunosenescence, and cancer. To achieve this goal, a systems-level approach capable of capturing the response of the interdependent immune cell types to external stimuli is required. In this study, an extensive characterization of signaling responses in multiple immune cell subpopulations within PBMCs from a cohort of 60 healthy donors was performed using single-cell network profiling (SCNP). SCNP is a multiparametric flow cytometry-based approach that enables the simultaneous measurement of basal and evoked signaling in multiple cell subsets within heterogeneous populations. In addition to establishing the interindividual degree of variation within a broad panel of immune signaling responses, the possible association of any observed variation with demographic variables including age and race was investigated. Using half of the donors as a training set, multiple age- and race-associated variations in signaling responses in discrete cell subsets were identified, and several were subsequently confirmed in the remaining samples (test set). Such associations may provide insight into age-related immune alterations associated with high infection rates and diminished protection following vaccination and into the basis for ethnic differences in autoimmune disease incidence and treatment response. SCNP allowed for the generation of a functional map of healthy immune cell signaling responses that can provide clinically relevant information regarding both the mechanisms underlying immune pathological conditions and the selection and effect of therapeutics.

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

    Science.gov (United States)

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

    2016-05-01

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

  14. The Notch Signaling Pathway Is Balancing Type 1 Innate Lymphoid Cell Immune Functions

    Directory of Open Access Journals (Sweden)

    Thibaut Perchet

    2018-06-01

    Full Text Available The Notch pathway is one of the canonical signaling pathways implicated in the development of various solid tumors. During carcinogenesis, the Notch pathway dysregulation induces tumor expression of Notch receptor ligands participating to escape the immune surveillance. The Notch pathway conditions both the development and the functional regulation of lymphoid subsets. Its importance on T cell subset polarization has been documented contrary to its action on innate lymphoid cells (ILC. We aim to analyze the effect of the Notch pathway on type 1 ILC polarization and functions after disruption of the RBPJk-dependent Notch signaling cascade. Indeed, type 1 ILC comprises conventional NK (cNK cells and type 1 helper innate lymphoid cells (ILC1 that share Notch-related functional characteristics such as the IFNg secretion downstream of T-bet expression. cNK cells have strong antitumor properties. However, data are controversial concerning ILC1 functions during carcinogenesis with models showing antitumoral capacities and others reporting ILC1 inability to control tumor growth. Using various mouse models of Notch signaling pathway depletion, we analyze the effects of its absence on type 1 ILC differentiation and cytotoxic functions. We also provide clues into its role in the maintenance of immune homeostasis in tissues. We show that modulating the Notch pathway is not only acting on tumor-specific T cell activity but also on ILC immune subset functions. Hence, our study uncovers the intrinsic Notch signaling pathway in ILC1/cNK populations and their response in case of abnormal Notch ligand expression. This study help evaluating the possible side effects mediated by immune cells different from T cells, in case of multivalent forms of the Notch receptor ligand delta 1 treatments. In definitive, it should help determining the best novel combination of therapeutic strategies in case of solid tumors.

  15. Signaling mechanisms underlying the robustness and tunability of the plant immune network

    Science.gov (United States)

    Kim, Yungil; Tsuda, Kenichi; Igarashi, Daisuke; Hillmer, Rachel A.; Sakakibara, Hitoshi; Myers, Chad L.; Katagiri, Fumiaki

    2014-01-01

    Summary How does robust and tunable behavior emerge in a complex biological network? We sought to understand this for the signaling network controlling pattern-triggered immunity (PTI) in Arabidopsis. A dynamic network model containing four major signaling sectors, the jasmonate, ethylene, PAD4, and salicylate sectors, which together explain up to 80% of the PTI level, was built using data for dynamic sector activities and PTI levels under exhaustive combinatorial sector perturbations. Our regularized multiple regression model had a high level of predictive power and captured known and unexpected signal flows in the network. The sole inhibitory sector in the model, the ethylene sector, was central to the network robustness via its inhibition of the jasmonate sector. The model's multiple input sites linked specific signal input patterns varying in strength and timing to different network response patterns, indicating a mechanism enabling tunability. PMID:24439900

  16. Retinoic acid signaling in B-cells is essential for oral immunization and microflora composition

    Science.gov (United States)

    Pantazi, Eirini; Marks, Ellen; Stolarczyk, Emilie; Lycke, Nils; Noelle, Randolph J.; Elgueta, Raul

    2015-01-01

    Retinoic acid (RA)3 is a critical regulator of the intestinal adaptive immune response. However, the intrinsic impact of RA on B cell differentiation in the regulation of gut humoral immunity in vivo has never been directly shown. To address this issue, we have been able to generate a mouse model where B-cells specifically express a dominant negative receptor α for RA. Here, we show that the silencing of RA signaling in B-cells reduces the numbers of IgA+ antibody secreting cells (ASC) both in vitro and in vivo, suggesting that RA has a direct effect on IgA plasma cell (PC) differentiation. Moreover, the lack of RA signaling in B-cells abrogates Ag-specific IgA responses after oral immunization and affects the microbiota composition. In conclusion, these results suggest that RA signaling in B-cells through the RA receptor α is important to generate an effective gut humoral response and to maintain a normal microbiota composition. PMID:26163586

  17. Cutting Edge: Retinoic Acid Signaling in B Cells Is Essential for Oral Immunization and Microflora Composition.

    Science.gov (United States)

    Pantazi, Eirini; Marks, Ellen; Stolarczyk, Emilie; Lycke, Nils; Noelle, Randolph J; Elgueta, Raul

    2015-08-15

    Retinoic acid (RA) is a critical regulator of the intestinal adaptive immune response. However, the intrinsic impact of RA on B cell differentiation in the regulation of gut humoral immunity in vivo has never been directly shown. To address this issue, we have been able to generate a mouse model where B cells specifically express a dominant-negative receptor α for RA. In this study, we show that the silencing of RA signaling in B cells reduces the numbers of IgA(+) Ab-secreting cells both in vitro and in vivo, suggesting that RA has a direct effect on IgA plasma cell differentiation. Moreover, the lack of RA signaling in B cells abrogates Ag-specific IgA responses after oral immunization and affects the microbiota composition. In conclusion, these results suggest that RA signaling in B cells through the RA receptor α is important to generate an effective gut humoral response and to maintain a normal microbiota composition. Copyright © 2015 by The American Association of Immunologists, Inc.

  18. Innate immune receptor Toll-like receptor 4 signalling in neuropsychiatric diseases.

    Science.gov (United States)

    García Bueno, B; Caso, J R; Madrigal, J L M; Leza, J C

    2016-05-01

    The innate immunity is a stereotyped first line of defense against pathogens and unspecified damage signals. One of main actors of innate immunity are the Toll-like receptors (TLRs), and one of the better characterized members of this family is TLR-4, that it is mainly activated by Gram-negative bacteria lipopolysaccharide. In brain, TLR-4 organizes innate immune responses against infections or cellular damage, but also possesses other physiological functions. In the last years, some evidences suggest a role of TLR-4 in stress and stress-related neuropsychiatric diseases. Peripheral and brain TLR-4 activation triggers sickness behavior, and its expression is a risk factor of depression. Some elements of the TLR-4 signaling pathway are up-regulated in peripheral samples and brain post-mortem tissue from depressed and suicidal patients. The "leaky gut" hypothesis of neuropsychiatric diseases is based on the existence of an increase of the intestinal permeability which results in bacterial translocation able to activate TLR-4. Enhanced peripheral TLR-4 expression/activity has been described in subjects diagnosed with schizophrenia, bipolar disorder and in autistic children. A role for TLR-4 in drugs abuse has been also proposed. The therapeutic potential of pharmacological/genetic modulation of TLRs signaling pathways in neuropsychiatry is promising, but a great preclinical/clinical scientific effort is still needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Role of Cortistatin in the Stressed Immune System.

    Science.gov (United States)

    Delgado, Mario; Gonzalez-Rey, Elena

    2017-01-01

    The immune system is faced with the daunting job of defending the organism against invading pathogens, while at the same time preserving the body integrity and maintaining tolerance to its own tissues. Loss of self-tolerance compromises immune homeostasis and leads to the onset of autoimmune disorders. The identification of endogenous factors that control immune tolerance and inflammation is a key goal for immunologists. Evidences from the last decade indicate that the neuropeptide cortistatin is one of the endogenous factors. Cortistatin is produced by immune cells and through its binding to various receptors, it exerts potent anti-inflammatory actions and participates in the maintenance of immune tolerance at multiple levels, especially in immunological disorders. Cortistatin emerges as a key element in the bidirectional communication between the neuroendocrine and immune systems aimed at regulating body homeostasis. © 2017 S. Karger AG, Basel.

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

    Science.gov (United States)

    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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Effects of microbes on the immune system

    National Research Council Canada - National Science Library

    Fujinami, Robert S; Cunningham, Madeleine W

    2000-01-01

    .... The book synthesizes recent discoveries on the various mechanisms by which microbes subvert the immune response and on the role of these immunologic mechanisms in the pathogenesis of infectious diseases...

  2. Immunization

    Science.gov (United States)

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

  3. SMAD regulatory networks construct a balanced immune system.

    Science.gov (United States)

    Malhotra, Nidhi; Kang, Joonsoo

    2013-05-01

    A balanced immune response requires combating infectious assaults while striving to maintain quiescence towards the self. One of the central players in this process is the pleiotropic cytokine transforming growth factor-β (TGF-β), whose deficiency results in spontaneous systemic autoimmunity in mice. The dominant function of TGF-β is to regulate the peripheral immune homeostasis, particularly in the microbe-rich and antigen-rich environment of the gut. To maintain intestinal integrity, the epithelial cells, myeloid cells and lymphocytes that inhabit the gut secrete TGF-β, which acts in both paracrine and autocrine fashions to activate its signal transducers, the SMAD transcription factors. The SMAD pathway regulates the production of IgA by B cells, maintains the protective mucosal barrier and promotes the balanced differentiation of CD4(+) T cells into inflammatory T helper type 17 cells and suppressive FOXP3(+) T regulatory cells. While encounters with pathogenic microbes activate SMAD proteins to evoke a protective inflammatory immune response, SMAD activation and synergism with immunoregulatory factors such as the vitamin A metabolite retinoic acid enforce immunosuppression toward commensal microbes and innocuous food antigens. Such complementary context-dependent functions of TGF-β are achieved by the co-operation of SMAD proteins with distinct dominant transcription activators and accessory chromatin modifiers. This review highlights recent advances in unravelling the molecular basis for the multi-faceted functions of TGF-β in the gut that are dictacted by fluid orchestrations of SMADs and their myriad partners. © 2013 Blackwell Publishing Ltd.

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

    Science.gov (United States)

    Avrameas, S

    2016-04-01

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

  5. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    International Nuclear Information System (INIS)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C.; Ballestas, Mary E.; Elmets, Craig A.; Robbins, David J.; Matalon, Sadis; Deshane, Jessy S.; Afaq, Farrukh; Bickers, David R.; Athar, Mohammad

    2013-01-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions

  6. Unfolded protein response (UPR) signaling regulates arsenic trioxide-mediated macrophage innate immune function disruption

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, Ritesh K.; Li, Changzhao; Chaudhary, Sandeep C. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Ballestas, Mary E. [Department of Pediatrics Infectious Disease, Children' s of Alabama, School of Medicine, University of Alabama at Birmingham, AL (United States); Elmets, Craig A. [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Robbins, David J. [Department of Surgery, Molecular Oncology Program, Miller School of Medicine, University of Miami, Miami (United States); Matalon, Sadis [Department of Anesthesiology, University of Alabama at Birmingham, Birmingham, AL (United States); Deshane, Jessy S. [Department of Medicine, Division of Pulmonary, Allergy and Critical Care Medicine, University of Alabama at Birmingham, Birmingham, AL (United States); Afaq, Farrukh [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States); Bickers, David R. [Department of Dermatology, Columbia University Medical Center, New York (United States); Athar, Mohammad, E-mail: mathar@uab.edu [Department of Dermatology and Skin Diseases Research Center, University of Alabama at Birmingham, Birmingham, AL (United States)

    2013-11-01

    Arsenic exposure is known to disrupt innate immune functions in humans and in experimental animals. In this study, we provide a mechanism by which arsenic trioxide (ATO) disrupts macrophage functions. ATO treatment of murine macrophage cells diminished internalization of FITC-labeled latex beads, impaired clearance of phagocytosed fluorescent bacteria and reduced secretion of pro-inflammatory cytokines. These impairments in macrophage functions are associated with ATO-induced unfolded protein response (UPR) signaling pathway characterized by the enhancement in proteins such as GRP78, p-PERK, p-eIF2α, ATF4 and CHOP. The expression of these proteins is altered both at transcriptional and translational levels. Pretreatment with chemical chaperon, 4-phenylbutyric acid (PBA) attenuated the ATO-induced activation in UPR signaling and afforded protection against ATO-induced disruption of macrophage functions. This treatment also reduced ATO-mediated reactive oxygen species (ROS) generation. Interestingly, treatment with antioxidant N-acetylcysteine (NAC) prior to ATO exposure, not only reduced ROS production and UPR signaling but also improved macrophage functions. These data demonstrate that UPR signaling and ROS generation are interdependent and are involved in the arsenic-induced pathobiology of macrophage. These data also provide a novel strategy to block the ATO-dependent impairment in innate immune responses. - Highlights: • Inorganic arsenic to humans and experimental animals disrupt innate immune responses. • The mechanism underlying arsenic impaired macrophage functions involves UPR signaling. • Chemical chaperon attenuates arsenic-mediated macrophage function impairment. • Antioxidant, NAC blocks impairment in arsenic-treated macrophage functions.

  7. Obesity, Fat Mass and Immune System: Role for Leptin

    Directory of Open Access Journals (Sweden)

    Vera Francisco

    2018-06-01

    Full Text Available Obesity is an epidemic disease characterized by chronic low-grade inflammation associated with a dysfunctional fat mass. Adipose tissue is now considered an extremely active endocrine organ that secretes cytokine-like hormones, called adipokines, either pro- or anti-inflammatory factors bridging metabolism to the immune system. Leptin is historically one of most relevant adipokines, with important physiological roles in the central control of energy metabolism and in the regulation of metabolism-immune system interplay, being a cornerstone of the emerging field of immunometabolism. Indeed, leptin receptor is expressed throughout the immune system and leptin has been shown to regulate both innate and adaptive immune responses. This review discusses the latest data regarding the role of leptin as a mediator of immune system and metabolism, with particular emphasis on its effects on obesity-associated metabolic disorders and autoimmune and/or inflammatory rheumatic diseases.

  8. Immune System and Its Link to Rheumatic Diseases

    Science.gov (United States)

    ... system, which contributes to the illness. So therapy targeting our own immune system can help alleviate the ... by the American College of Rheumatology Communications and Marketing Committee. This information is provided for general education ...

  9. Signals and systems primer with Matlab

    CERN Document Server

    Poularikas, Alexander D

    2006-01-01

    Signals and Systems Primer with MATLAB® equally emphasizes the fundamentals of both analog and digital signals and systems. To ensure insight into the basic concepts and methods, the text presents a variety of examples that illustrate a wide range of applications, from microelectromechanical to worldwide communication systems. It also provides MATLAB functions and procedures for practice and verification of these concepts.Taking a pedagogical approach, the author builds a solid foundation in signal processing as well as analog and digital systems. The book first introduces orthogonal signals,

  10. The immune system strikes back: cellular immune responses against indoleamine 2,3-dioxygenase

    DEFF Research Database (Denmark)

    Sørensen, Rikke Baek; Berge-Hansen, Linda; Junker, Niels

    2009-01-01

    BACKGROUND: The enzyme indoleamine 2,3-dioxygenase (IDO) exerts an well established immunosuppressive function in cancer. IDO is expressed within the tumor itself as well as in antigen-presenting cells in tumor-draining lymph nodes, where it promotes the establishment of peripheral immune tolerance...... to tumor antigens. In the present study, we tested the notion whether IDO itself may be subject to immune responses. METHODS AND FINDINGS: The presence of naturally occurring IDO-specific CD8 T cells in cancer patients was determined by MHC/peptide stainings as well as ELISPOT. Antigen specific cytotoxic T...... of the major immune suppressive cell populations. CONCLUSION: IDO may serve as an important and widely applicable target for anti-cancer immunotherapeutic strategies. Furthermore, as emerging evidence suggests that IDO constitutes a significant counter-regulatory mechanism induced by pro-inflammatory signals...

  11. Evaluation of mucosal and systemic immune responses elicited by GPI-0100- adjuvanted influenza vaccine delivered by different immunization strategies.

    Directory of Open Access Journals (Sweden)

    Heng Liu

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2013-09-01

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

  14. Evolution of JAK-STAT pathway components: mechanisms and role in immune system development.

    Directory of Open Access Journals (Sweden)

    Clifford Liongue

    Full Text Available BACKGROUND: Lying downstream of a myriad of cytokine receptors, the Janus kinase (JAK-Signal transducer and activator of transcription (STAT pathway is pivotal for the development and function of the immune system, with additional important roles in other biological systems. To gain further insight into immune system evolution, we have performed a comprehensive bioinformatic analysis of the JAK-STAT pathway components, including the key negative regulators of this pathway, the SH2-domain containing tyrosine phosphatase (SHP, Protein inhibitors against Stats (PIAS, and Suppressor of cytokine signaling (SOCS proteins across a diverse range of organisms. RESULTS: Our analysis has demonstrated significant expansion of JAK-STAT pathway components co-incident with the emergence of adaptive immunity, with whole genome duplication being the principal mechanism for generating this additional diversity. In contrast, expansion of upstream cytokine receptors appears to be a pivotal driver for the differential diversification of specific pathway components. CONCLUSION: Diversification of JAK-STAT pathway components during early vertebrate development occurred concurrently with a major expansion of upstream cytokine receptors and two rounds of whole genome duplications. This produced an intricate cell-cell communication system that has made a significant contribution to the evolution of the immune system, particularly the emergence of adaptive immunity.

  15. Nociception and role of immune system in pain.

    Science.gov (United States)

    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.

  16. Focusing on Ciona intestinalis (Tunicata) innate immune system. Evolutionary implications

    OpenAIRE

    N Parrinello

    2009-01-01

    Phylogenetic analyses based on molecular data provide compelling evidence that ascidians are of critical importance for studying chordate immune system evolution. The Ciona intestinalis draft genome sequence allows searches for phylogenetic relationships, gene cloning and expression of immunorelevant molecules. Acidians lack of the pivotal components of the vertebrate recombinatory adaptive immunity, i.e., MHC, TCRs and dimeric immunoglobulins. However, bioinformatic sequence analyses recogni...

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

    Science.gov (United States)

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

    2017-10-01

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

  18. Gaseous 3-pentanol primes plant immunity against a bacterial speck pathogen, Pseudomonas syringae pv. tomato via salicylic acid and jasmonic acid-dependent signaling pathways in Arabidopsis.

    Science.gov (United States)

    Song, Geun C; Choi, Hye K; Ryu, Choong-Min

    2015-01-01

    3-Pentanol is an active organic compound produced by plants and is a component of emitted insect sex pheromones. A previous study reported that drench application of 3-pentanol elicited plant immunity against microbial pathogens and an insect pest in crop plants. Here, we evaluated whether 3-pentanol and the derivatives 1-pentanol and 2-pentanol induced plant systemic resistance using the in vitro I-plate system. Exposure of Arabidopsis seedlings to 10 μM and 100 nM 3-pentanol evaporate elicited an immune response to Pseudomonas syringae pv. tomato DC3000. We performed quantitative real-time PCR to investigate the 3-pentanol-mediated Arabidopsis immune responses by determining Pathogenesis-Related (PR) gene expression levels associated with defense signaling through salicylic acid (SA), jasmonic acid (JA), and ethylene signaling pathways. The results show that exposure to 3-pentanol and subsequent pathogen challenge upregulated PDF1.2 and PR1 expression. Selected Arabidopsis mutants confirmed that the 3-pentanol-mediated immune response involved SA and JA signaling pathways and the NPR1 gene. Taken together, this study indicates that gaseous 3-pentanol triggers induced resistance in Arabidopsis by priming SA and JA signaling pathways. To our knowledge, this is the first report that a volatile compound of an insect sex pheromone triggers plant systemic resistance against a bacterial pathogen.

  19. Gaseous 3-pentanol primes plant immunity against a bacterial speck pathogen, Pseudomonas syringae pv. tomato via salicylic acid and jasmonic acid-dependent signaling pathways in Arabidopsis

    Directory of Open Access Journals (Sweden)

    Geun Cheol eSong

    2015-10-01

    Full Text Available 3-Pentanol is an active organic compound produced by plants and is a component of emitted insect sex pheromones. A previous study reported that drench application of 3-pentanol elicited plant immunity against microbial pathogens and an insect pest in crop plants. Here, we evaluated whether 3-pentanol and the derivatives 1-pentanol and 2-pentanol induced plant systemic resistance using the in vitro I-plate system. Exposure of Arabidopsis seedlings to 10 M and 100 nM 3-pentanol evaporate elicited an immune response to Pseudomonas syringae pv. tomato DC3000. We performed quantitative real-time PCR to investigate the 3-pentanol-mediated Arabidopsis immune responses by determining Pathogenesis-Related (PR gene expression levels associated with defense signaling through SA, JA, and ethylene signaling pathways. The results show that exposure to 3-pentanol and subsequent pathogen challenge upregulated PDF1.2 and PR1 expression. Selected Arabidopsis mutants confirmed that the 3-pentanol-mediated immune response involved salicylic acid (SA and jasmonic acid (JA signaling pathways and the NPR1 gene. Taken together, this study indicates that gaseous 3-pentanol triggers induced resistance in Arabidopsis by priming SA and JA signaling pathways. To our knowledge, this is the first report that a volatile compound of an insect sex pheromone triggers plant systemic resistance against a bacterial pathogen.

  20. Signals, systems, transforms, and digital signal processing with Matlab

    CERN Document Server

    Corinthios, Michael

    2009-01-01

    Continuous-Time and Discrete-Time Signals and SystemsIntroductionContinuous-Time SignalsPeriodic FunctionsUnit Step FunctionGraphical Representation of FunctionsEven and Odd Parts of a FunctionDirac-Delta ImpulseBasic Properties of the Dirac-Delta ImpulseOther Important Properties of the ImpulseContinuous-Time SystemsCausality, StabilityExamples of Electrical Continuous-Time SystemsMechanical SystemsTransfer Function and Frequency ResponseConvolution and CorrelationA Right-Sided and a Left-Sided FunctionConvolution with an Impulse and Its DerivativesAdditional Convolution PropertiesCorrelation FunctionProperties of the Correlation FunctionGraphical InterpretationCorrelation of Periodic FunctionsAverage, Energy and Power of Continuous-Time SignalsDiscrete-Time SignalsPeriodicityDifference EquationsEven/Odd DecompositionAverage Value, Energy and Power SequencesCausality, StabilityProblemsAnswers to Selected ProblemsFourier Series ExpansionTrigonometric Fourier SeriesExponential Fourier SeriesExponential versus ...

  1. Colorectal cancer cells suppress CD4+ T cells immunity through canonical Wnt signaling.

    Science.gov (United States)

    Sun, Xuan; Liu, Suoning; Wang, Daguang; Zhang, Yang; Li, Wei; Guo, Yuchen; Zhang, Hua; Suo, Jian

    2017-02-28

    Understanding how colorectal cancer escapes from immunosurveillance and immune attack is important for developing novel immunotherapies for colorectal cancer. In this study we evaluated the role of canonical Wnt signaling in the regulation of T cell function in a mouse colorectal cancer model. We found that colorectal cancer cells expressed abundant Wnt ligands, and intratumoral T cells expressed various Frizzled proteins. Meanwhile, both active β-catenin and total β-catenin were elevated in intratumoral T cells. In vitro study indicated that colorectal cancer cells suppressed IFN-γ expression and increased IL-17a expression in activated CD4+ T cells. However, the cytotoxic activity of CD8+ T cells was not altered by colorectal cancer cells. To further evaluate the importance of Wnt signaling for CD4+ T cell-mediated cancer immunity, β-catenin expression was enforced in CD4+ T cells using lentiviral transduction. In an adoptive transfer model, enforced expression of β-catenin in intratumoral CD4+ T cells increased IL-17a expression, enhanced proliferation and inhibited apoptosis of colorectal cancer cells. Taken together, our study disclosed a new mechanism by which colorectal cancer impairs T cell immunity.

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

    Science.gov (United States)

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

    2015-09-01

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

  3. HIF-mediated innate immune responses: cell signaling and therapeutic implications

    Directory of Open Access Journals (Sweden)

    Harris AJ

    2014-05-01

    Full Text Available Alison J Harris, AA Roger Thompson, Moira KB Whyte, Sarah R Walmsley Academic Unit of Respiratory Medicine, Department of Infection and Immunity, University of Sheffield, Sheffield, UK Abstract: Leukocytes recruited to infected, damaged, or inflamed tissues during an immune response must adapt to oxygen levels much lower than those in the circulation. Hypoxia inducible factors (HIFs are key mediators of cellular responses to hypoxia and, as in other cell types, HIFs are critical for the upregulation of glycolysis, which enables innate immune cells to produce adenosine triphosphate anaerobically. An increasing body of evidence demonstrates that hypoxia also regulates many other innate immunological functions, including cell migration, apoptosis, phagocytosis of pathogens, antigen presentation and production of cytokines, chemokines, and angiogenic and antimicrobial factors. Many of these functions are mediated by HIFs, which are not only stabilized posttranslationally by hypoxia, but also transcriptionally upregulated by inflammatory signals. Here, we review the role of HIFs in the responses of innate immune cells to hypoxia, both in vitro and in vivo, with a particular focus on myeloid cells, on which the majority of studies have so far been carried out. Keywords: hypoxia, neutrophils, monocytes, macrophages

  4. Biological Immune System Applications on Mobile Robot for Disabled People

    Directory of Open Access Journals (Sweden)

    Songmin Jia

    2014-01-01

    Full Text Available To improve the service quality of service robots for the disabled, immune system is applied on robot for its advantages such as diversity, dynamic, parallel management, self-organization, and self-adaptation. According to the immune system theory, local environment condition sensed by robot is considered an antigen while robot is regarded as B-cell and possible node as antibody, respectively. Antibody-antigen affinity is employed to choose the optimal possible node to ensure the service robot can pass through the optimal path. The paper details the immune system applications on service robot and gives experimental results.

  5. The Immune System Bridges the Gut Microbiota with Systemic Energy Homeostasis: Focus on TLRs, Mucosal Barrier, and SCFAs.

    Science.gov (United States)

    Spiljar, Martina; Merkler, Doron; Trajkovski, Mirko

    2017-01-01

    The gut microbiota is essential for the development and regulation of the immune system and the metabolism of the host. Germ-free animals have altered immunity with increased susceptibility to immunologic diseases and show metabolic alterations. Here, we focus on two of the major immune-mediated microbiota-influenced components that signal far beyond their local environment. First, the activation or suppression of the toll-like receptors (TLRs) by microbial signals can dictate the tone of the immune response, and they are implicated in regulation of the energy homeostasis. Second, we discuss the intestinal mucosal surface is an immunologic component that protects the host from pathogenic invasion, is tightly regulated with regard to its permeability and can influence the systemic energy balance. The short chain fatty acids are a group of molecules that can both modulate the intestinal barrier and escape the gut to influence systemic health. As modulators of the immune response, the microbiota-derived signals influence functions of distant organs and can change susceptibility to metabolic diseases.

  6. Signal-regulated systems and networks

    CSIR Research Space (South Africa)

    Van Zyl, TL

    2010-07-01

    Full Text Available The article presents the use of signal regulatory networks (SRNs), a biologically inspired model based on gene regulatory networks. SRNs are a way of understanding a class of self-organizing IT systems, signal-regulated systems (SRSs). This article...

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

    Science.gov (United States)

    Proserpio, Valentina; Mahata, Bidesh

    2016-02-01

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

  8. Immune algorithm based active PID control for structure systems

    International Nuclear Information System (INIS)

    Lee, Young Jin; Cho, Hyun Cheol; Lee, Kwon Soon

    2006-01-01

    An immune algorithm is a kind of evolutional computation strategies, which is developed in the basis of a real immune mechanism in the human body. Recently, scientific or engineering applications using this scheme are remarkably increased due to its significant ability in terms of adaptation and robustness for external disturbances. Particularly, this algorithm is efficient to search optimal parameters against complicated dynamic systems with uncertainty and perturbation. In this paper, we investigate an immune algorithm embedded Proportional Integral Derivate (called I P ID) control, in which an optimal parameter vector of the controller is determined offline by using a cell-mediated immune response of the immunized mechanism. For evaluation, we apply the proposed control to mitigation of vibrations for nonlinear structural systems, cased by external environment load such as winds and earthquakes. Comparing to traditional controls under same simulation scenarios, we demonstrate the innovation control is superior especially in robustness aspect

  9. The Immune System and Bodily Defence

    Indian Academy of Sciences (India)

    We have argued earlier that the c10nally diverse model of immune target recognition ... not guarantee that nothing new will be met in the future. So the sky is the limit ... Such random DNA change is a very risky business for the cell to indulge in ...

  10. Modeling evolution and immune system by cellular automata

    International Nuclear Information System (INIS)

    Bezzi, M.

    2001-01-01

    In this review the behavior of two different biological systems is investigated using cellular automata. Starting from this spatially extended approach it is also tried, in some cases, to reduce the complexity of the system introducing mean-field approximation, and solving (or trying to solve) these simplified systems. It is discussed the biological meaning of the results, the comparison with experimental data (if available) and the different features between spatially extended and mean-field versions. The biological systems considered in this review are the following: Darwinian evolution in simple ecosystems and immune system response. In the first section the main features of molecular evolution are introduced, giving a short survey of genetics for physicists and discussing some models for prebiotic systems and simple ecosystems. It is also introduced a cellular automaton model for studying a set of evolving individuals in a general fitness landscape, considering also the effects of co-evolution. In particular the process of species formation (speciation) is described in sect. 5. The second part deals with immune system modeling. The biological features of immune response are discussed, as well as it is introduced the concept of shape space and of idiotypic network. More detailed reviews which deal with immune system models (mainly focused on idiotypic network models) can be found. Other themes here discussed: the applications of CA to immune system modeling, two complex cellular automata for humoral and cellular immune response. Finally, it is discussed the biological data and the general conclusions are drawn in the last section

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

    Science.gov (United States)

    Veiga-Fernandes, Henrique; Freitas, António A

    2017-10-01

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

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

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

    2018-02-15

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

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

    Science.gov (United States)

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

    2017-11-10

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

  15. The IRS-1 signaling system.

    Science.gov (United States)

    Myers, M G; Sun, X J; White, M F

    1994-07-01

    Insulin-receptor substrate 1 (IRS-1) is a principal substrate of the receptor tyrosine kinase for insulin and insulin-like growth factor 1, and a substrate for a tyrosine kinase activated by interleukin 4. IRS-1 undergoes multisite tyrosine phosphorylation and mediates downstream signals by 'docking' various proteins that contain Src homology 2 domains. IRS-1 appears to be a unique molecule; however, 4PS, a protein found mainly in hemopoietic cells, may represent another member of this family.

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

    Science.gov (United States)

    Kradin, R L

    1995-01-01

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

  17. Comparative Genomics Reveals the Origins and Diversity of Arthropod Immune Systems.

    Science.gov (United States)

    Palmer, William J; Jiggins, Francis M

    2015-08-01

    Insects are an important model for the study of innate immune systems, but remarkably little is known about the immune system of other arthropod groups despite their importance as disease vectors, pests, and components of biological diversity. Using comparative genomics, we have characterized the immune system of all the major groups of arthropods beyond insects for the first time--studying five chelicerates, a myriapod, and a crustacean. We found clear traces of an ancient origin of innate immunity, with some arthropods having Toll-like receptors and C3-complement factors that are more closely related in sequence or structure to vertebrates than other arthropods. Across the arthropods some components of the immune system, such as the Toll signaling pathway, are highly conserved. However, there is also remarkable diversity. The chelicerates apparently lack the Imd signaling pathway and beta-1,3 glucan binding proteins--a key class of pathogen recognition receptors. Many genes have large copy number variation across species, and this may sometimes be accompanied by changes in function. For example, we find that peptidoglycan recognition proteins have frequently lost their catalytic activity and switch between secreted and intracellular forms. We also find that there has been widespread and extensive duplication of the cellular immune receptor Dscam (Down syndrome cell adhesion molecule), which may be an alternative way to generate the high diversity produced by alternative splicing in insects. In the antiviral short interfering RNAi pathway Argonaute 2 evolves rapidly and is frequently duplicated, with a highly variable copy number. Our results provide a detailed analysis of the immune systems of several important groups of animals for the first time and lay the foundations for functional work on these groups. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  18. Signals and systems laboratory with Matlab

    CERN Document Server

    Palamides, Alex

    2010-01-01

    Introduction to MATLAB®Working EnvironmentGetting StartedMemory ManagementVectorsMatricesPlotting with MATLABComplex NumbersM-FilesInput-Output CommandsFile ManagementLogical-Relational OperatorsControl FlowSymbolic VariablesPolynomials(Pseudo)Random NumbersSignalsCategorization by the Variable TypeBasic Continuous-Time SignalsDiscrete-Time SignalsProperties of SignalsTransformations of the Time Variable for Continuous-Time SignalsTransformations of the Time Variable for Discrete-Time SignalsSystemsSystems ClassificationProperties of SystemsTime Domain System AnalysisImpulse ResponseContinuous Time Convolution Convolution PropertiesInterconnections of SystemsStabilityDiscrete-Time ConvolutionSystems Described by Difference EquationsFiltersStability Criterion for Discrete-Time SystemsSystems Described by Differential EquationsStep Response of a SystemFourier SeriesOrthogonality of Complex Exponential SignalsComplex Exponential Fourier SeriesTrigonometric Fourier SeriesFourier Series in the Cosine with Phase F...

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

    Science.gov (United States)

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

    2017-08-15

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

  20. Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity

    Directory of Open Access Journals (Sweden)

    Stephan Menzel

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP and nicotinamide adenine dinucleotide (NAD+ are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD+ is converted by CD38, CD203 and other ecto-enzymes to the Ca2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies – single domain antibodies derived from heavy chain antibodies that naturally occur in camelids – display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

  1. Nanobody-Based Biologics for Modulating Purinergic Signaling in Inflammation and Immunity.

    Science.gov (United States)

    Menzel, Stephan; Schwarz, Nicole; Haag, Friedrich; Koch-Nolte, Friedrich

    2018-01-01

    Adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide (NAD + ) are released as danger signals from cells during infection and sterile inflammation. In the extracellular compartment ATP is converted by CD39, CD73, and other ecto-enzymes into metabolites that modulate the activity of T cells and macrophages. While ATP mediates pro-inflammatory signals via P2X7 and other P2 receptors, adenosine triggers anti-inflammatory signaling via the adenosine 2a receptor (Adora2a) and other P1 receptors. The latter also plays a role in maintaining an immunosuppressive tumor microenvironment. NAD + is converted by CD38, CD203 and other ecto-enzymes to the Ca 2+ mobilizing messengers cyclic ADP-ribose and ADP-ribose, and to adenosine. Recent findings on the roles of CD38, CD39, CD73, CD203, P2X7, and Adora2a in inflammation and immunity underscore the potential of these proteins as drug targets. However, available small molecule inhibitors often lack specificity and mediate unwanted off-target toxicity. Nanobodies - single domain antibodies derived from heavy chain antibodies that naturally occur in camelids - display a propensity to bind functional epitopes not accessible to conventional antibodies. Like conventional antibodies, nanobodies and nanobody-based biologics are highly specific and have well-understood, tunable in vivo pharmacodynamics with little if any toxicity. Nanobodies thus represent attractive alternatives to small molecule inhibitors for modulating purinergic signaling in inflammation and immunity. Here we review recent progress made in developing nanobodies against key targets of purinergic signaling.

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

    Science.gov (United States)

    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....

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

    NARCIS (Netherlands)

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

    2010-01-01

    P>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

  4. A mathematical model of radiation effect on the immunity system

    International Nuclear Information System (INIS)

    Smirnova, O.A.

    1984-01-01

    A mathematical model, simulating the effect of ionizing radiation on the dynamics of humoral immune reaction is suggested. It represents the system of nonlinear differential equations and is realized in the form of program in Fortran computer language. The model describes the primary immune reaction of nonirradiated organism on T-independent antigen, reflects the postradiation lymphopoiesis dynamics in nonimmunized mammals, simulates the processes of injury and recovery of the humoral immunity system under the combined effect of ionizing radiation and antigenic stimulation. The model can be used for forecasting imminity state in irradiated mammals

  5. Arthropod Innate Immune Systems and Vector-Borne Diseases.

    Science.gov (United States)

    Baxter, Richard H G; Contet, Alicia; Krueger, Kathryn

    2017-02-21

    Arthropods, especially ticks and mosquitoes, are the vectors for a number of parasitic and viral human diseases, including malaria, sleeping sickness, Dengue, and Zika, yet arthropods show tremendous individual variation in their capacity to transmit disease. A key factor in this capacity is the group of genetically encoded immune factors that counteract infection by the pathogen. Arthropod-specific pattern recognition receptors and protease cascades detect and respond to infection. Proteins such as antimicrobial peptides, thioester-containing proteins, and transglutaminases effect responses such as lysis, phagocytosis, melanization, and agglutination. Effector responses are initiated by damage signals such as reactive oxygen species signaling from epithelial cells and recognized by cell surface receptors on hemocytes. Antiviral immunity is primarily mediated by siRNA pathways but coupled with interferon-like signaling, antimicrobial peptides, and thioester-containing proteins. Molecular mechanisms of immunity are closely linked to related traits of longevity and fertility, and arthropods have the capacity for innate immunological memory. Advances in understanding vector immunity can be leveraged to develop novel control strategies for reducing the rate of transmission of both ancient and emerging threats to global health.

  6. The immune system and the impact of zinc during aging

    Directory of Open Access Journals (Sweden)

    Haase Hajo

    2009-06-01

    Full Text Available Abstract The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence.

  7. [The role of protein glycosylation in immune system].

    Science.gov (United States)

    Ząbczyńska, Marta; Pocheć, Ewa

    2015-01-01

    Glycosylation is one of the most frequent post-translational modifications of proteins. The majority of cell surface and secreted proteins involved in immune response is glycosylated. The structural diversity of glycans depends on monosaccharide composition, type of glycosidic linkage and branching. These structural modifications determine a great variability of glycoproteins. The oligosaccharide components of proteins are regulated mostly by expression of glycosyltransferases and glycosidases and many environmental factors. Glycosylation influences the function of all immune cells. Glycans play a crucial role in intercellular contacts and leukocytes migration. These interactions are important in activation and proliferation of leukocytes and during immune response. The key immune proteins, such as TCR, MHC, TLR and antibodies are glycosylated. Sugars on the surface of pathogens and self-surface glycoproteins are recognized by special carbohydrate binding proteins called lectins. Changes of glycan structure are common in many pathological processes occurring in immune system, therefore they are used as molecular markers of different diseases.

  8. Conducted Interference Immunity Characteristics to High-speed Power Line Communication System

    Science.gov (United States)

    Tokuda, Masamitsu; Hosoya, Satoshi; Yamagata, Toru; Matsuo, Takashi

    In this paper, we measured the immunity characteristics to the conducted interference wave, from the aspect of PHY rate (physical layer data rate) of PLC (Power Line Communication) system, and compared with simulation results by MATLAB/ Simulink. When the interference signal is impressed to the OFDM (Orthogonal Frequency Division Multiplexing) signal, the PHY rate decrease rapidly below C/I (Carrier / Interference) = 25dB and become nearly zero around C/I = -35dB, and so it turns out that the PLC System with OFDM signal has a good narrowband interference immunity characteristic. In addition, it is revealed that the PHY rate of PLC modem can be calculated by MATLAB/Simulink even when the narrowband interference signal is impressed through the power line. Furthermore, we examined the improving effect of the notch band for the immunity characteristics to the conducted interference wave. As a result, it is revealed that the PHY rate normalized by the maximum value increases by 15∼25% by inserting the notch when impressing the interference signal in the notch band and C/I is improved by 10∼15dB by inserting the notch.

  9. Regulation of TGFβ in the immune system: an emerging role for integrins and dendritic cells.

    Science.gov (United States)

    Worthington, John J; Fenton, Thomas M; Czajkowska, Beata I; Klementowicz, Joanna E; Travis, Mark A

    2012-12-01

    Regulation of an immune response requires complex crosstalk between cells of the innate and adaptive immune systems, via both cell-cell contact and secretion of cytokines. An important cytokine with a broad regulatory role in the immune system is transforming growth factor-β (TGF-β). TGF-β is produced by and has effects on many different cells of the immune system, and plays fundamental roles in the regulation of immune responses during homeostasis, infection and disease. Although many cells can produce TGFβ, it is always produced as an inactive complex that must be activated to bind to the TGFβ receptor complex and promote downstream signalling. Thus, regulation of TGFβ activation is a crucial step in controlling TGFβ function. This review will discuss how TGFβ controls diverse immune responses and how TGFβ function is regulated, with a focus on recent work highlighting a critical role for the integrin αvβ8 expressed by dendritic cells in activating TGFβ. Copyright © 2012 Elsevier GmbH. All rights reserved.

  10. Comprehensive Transcriptome Profiling and Functional Analysis of the Frog (Bombina maxima) Immune System

    Science.gov (United States)

    Zhao, Feng; Yan, Chao; Wang, Xuan; Yang, Yang; Wang, Guangyin; Lee, Wenhui; Xiang, Yang; Zhang, Yun

    2014-01-01

    Amphibians occupy a key phylogenetic position in vertebrates and evolution of the immune system. But, the resources of its transcriptome or genome are still little now. Bombina maxima possess strong ability to survival in very harsh environment with a more mature immune system. We obtained a comprehensive transcriptome by RNA-sequencing technology. 14.3% of transcripts were identified to be skin-specific genes, most of which were not isolated from skin secretion in previous works or novel non-coding RNAs. 27.9% of transcripts were mapped into 242 predicted KEGG pathways and 6.16% of transcripts related to human disease and cancer. Of 39 448 transcripts with the coding sequence, at least 1501 transcripts (570 genes) related to the immune system process. The molecules of immune signalling pathway were almost presented, several transcripts with high expression in skin and stomach. Experiments showed that lipopolysaccharide or bacteria challenge stimulated pro-inflammatory cytokine production and activation of pro-inflammatory caspase-1. These frog's data can remarkably expand the existing genome or transcriptome resources of amphibians, especially immunity data. The entity of the data provides a valuable platform for further investigation on more detailed immune response in B. maxima and a comparative study with other amphibians. PMID:23942912

  11. [Saccharomyces boulardii CNCM I-745 influences the gut-associated immune system].

    Science.gov (United States)

    Stier, Heike; Bischoff, Stephan C

    2017-06-01

    The impact of the intestinal microbiome is increasing steadily with regard to the immune function und the defense against pathogens. The medicinal yeast Saccharomyces boulardii CNCM I-745 (S. boulardii) has been used as probiotic for the prevention and treatment of infectious diarrhea since more than 50 years. Meta-analyses confirm the clinical efficacy of S. boulardii to treat diarrhea of various origins in children and adults. This review article summarizes experimental studies on molecular and immunological mechanisms which explain the proven clinical efficacy of S. boulardii. Thereby the focus is on the gut-associated immune system. S. boulardii stimulates the release of immunoglobulins and cytokines and also induces the maturation of immune cells. This suggests that S. boulardii is capable of activating the unspecific immune system. In case of an infection, S. boulardii is able to bind pathogenic bacteria and to neutralize their toxins. Moreover, the medicinal yeast can attenuate the overreacting inflammatory immune response, by interfering with the signaling cascade, which is induced by the infection, and that way influences the innate and adaptive immune system. Thanks to these mechanisms the pathogens' potential of adhesion is lessened. Thus the intestinal epithelial layer is protected and diarrhea-induced fluid loss is reduced. The different molecular and immunological mechanisms investigated in the experimental studies prove the already confirmed very good clinical efficacy of S. boulardii in infectious diarrhea caused by pathogens such as bacteria, viruses, and fungi.

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

    Science.gov (United States)

    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.

  13. Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

    Science.gov (United States)

    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-01-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

  14. Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

    Science.gov (United States)

    An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A; Leak, Rehana K; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

    2014-04-01

    Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

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

    Science.gov (United States)

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

    2016-01-01

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

  16. Honest sexual signaling in turtles: experimental evidence of a trade-off between immune response and coloration in red-eared sliders Trachemys scripta elegans.

    Science.gov (United States)

    Ibáñez, Alejandro; Polo-Cavia, Nuria; López, Pilar; Martín, José

    2014-10-01

    Sexual signals can be evolutionarily stable if they are honest and condition dependent or costly to the signaler. One possible cost is the existence of a trade-off between maintaining the immune system and the elaboration of ornaments. This hypothesis has been experimentally tested in some groups of animals but not in others such as turtles. We experimentally challenged the immune system of female red-eared sliders Trachemys scripta elegans, with a bacterial antigen (lipopolysaccharide (LPS)) without pathogenic effects to explore whether the immune activation affected visual colorful ornaments of the head. The LPS injection altered the reflectance patterns of color ornaments. In comparison to the control animals, the yellow chin stripes of injected animals exhibited (1) reduced brightness, (2) lower long wavelength (>470 nm) reflectance, and (3) lower values for carotenoid chroma. The postorbital patches of injected individuals also showed reduced very long wavelength (>570 nm) reflectance but did not change in carotenoid chroma. Thus, experimental turtles showed darker and less "yellowish" chin stripes and less "reddish" postorbital patches at the end of the experiment, whereas control turtles did not change their coloration. This is the first experimental evidence supporting the existence of a trade-off between the immune system and the expression of visual ornaments in turtles. We suggest that this trade-off may allow turtles to honestly signal individual quality via characteristics of coloration, which may have an important role in intersexual selection processes.

  17. Honest sexual signaling in turtles: experimental evidence of a trade-off between immune response and coloration in red-eared sliders Trachemys scripta elegans

    Science.gov (United States)

    Ibáñez, Alejandro; Polo-Cavia, Nuria; López, Pilar; Martín, José

    2014-10-01

    Sexual signals can be evolutionarily stable if they are honest and condition dependent or costly to the signaler. One possible cost is the existence of a trade-off between maintaining the immune system and the elaboration of ornaments. This hypothesis has been experimentally tested in some groups of animals but not in others such as turtles. We experimentally challenged the immune system of female red-eared sliders Trachemys scripta elegans, with a bacterial antigen (lipopolysaccharide (LPS)) without pathogenic effects to explore whether the immune activation affected visual colorful ornaments of the head. The LPS injection altered the reflectance patterns of color ornaments. In comparison to the control animals, the yellow chin stripes of injected animals exhibited (1) reduced brightness, (2) lower long wavelength (>470 nm) reflectance, and (3) lower values for carotenoid chroma. The postorbital patches of injected individuals also showed reduced very long wavelength (>570 nm) reflectance but did not change in carotenoid chroma. Thus, experimental turtles showed darker and less "yellowish" chin stripes and less "reddish" postorbital patches at the end of the experiment, whereas control turtles did not change their coloration. This is the first experimental evidence supporting the existence of a trade-off between the immune system and the expression of visual ornaments in turtles. We suggest that this trade-off may allow turtles to honestly signal individual quality via characteristics of coloration, which may have an important role in intersexual selection processes.

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

    Science.gov (United States)

    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. © 2016 Levy et al.; Published by Cold Spring Harbor Laboratory Press.

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

    Science.gov (United States)

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The TLR13-MyD88-NF-κB signalling pathway of Cyclina sinensis plays vital roles in innate immune responses.

    Science.gov (United States)

    Ren, Yipeng; Ding, Dan; Pan, Baoping; Bu, Wenjun

    2017-11-01

    Toll-like receptors, the best known pattern recognition receptors, play important roles in recognizing non-self molecules and binding pathogen-associated molecular patterns in the innate immune system. In the present research, the cDNA and protein characterization of the TLR signalling pathway genes including IRAK4, TRAK6 and IKKα (named CsIRAK4, CsTRAF6 and CsIKKα, respectively) with the typical motifs from Cyclina sinensis showed significant similarity with their homologues from other shellfish. Furthermore, the mRNA transcripts of these three genes are ubiquitously expressed in all tissues tested and are dominantly expressed in C. sinensis haemocytes (P sinensis by RNA interference and immune challenges. The results suggested the mRNA expression patterns of CsMyD88, CsIRAK4, CsTRAF6, CsIKKα, CsIκB, CsNF-κB, CsC-LYZ and CsAMP were all down-regulated (P sinensis haemocytes, revealing the involvement of the TLR13-MyD88-NF-κB signalling pathway in innate immunity by positively adjusting internal signalling factors and immune-related genes. In summary, a TLR13-MyD88-NF-κB signalling pathway exists and plays vital roles in innate immune responses in C. sinensis. These findings collectively lay the foundation for studying the functional characterization of internal signalling factors and establishing a regulatory network for the TLR signalling pathway in molluscs. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Phosphoproteomics-based systems analysis of signal transduction networks

    Directory of Open Access Journals (Sweden)

    Hiroko eKozuka-Hata

    2012-01-01

    Full Text Available Signal transduction systems coordinate complex cellular information to regulate biological events such as cell proliferation and differentiation. Although the accumulating evidence on widespread association of signaling molecules has revealed essential contribution of phosphorylation-dependent interaction networks to cellular regulation, their dynamic behavior is mostly yet to be analyzed. Recent technological advances regarding mass spectrometry-based quantitative proteomics have enabled us to describe the comprehensive status of phosphorylated molecules in a time-resolved manner. Computational analyses based on the phosphoproteome dynamics accelerate generation of novel methodologies for mathematical analysis of cellular signaling. Phosphoproteomics-based numerical modeling can be used to evaluate regulatory network elements from a statistical point of view. Integration with transcriptome dynamics also uncovers regulatory hubs at the transcriptional level. These omics-based computational methodologies, which have firstly been applied to representative signaling systems such as the epidermal growth factor receptor pathway, have now opened up a gate for systems analysis of signaling networks involved in immune response and cancer.

  2. Electrical Signaling, Photosynthesis and Systemic Acquired Acclimation

    Directory of Open Access Journals (Sweden)

    Magdalena Szechyńska-Hebda

    2017-09-01

    Full Text Available Electrical signaling in higher plants is required for the appropriate intracellular and intercellular communication, stress responses, growth and development. In this review, we have focus on recent findings regarding the electrical signaling, as a major regulator of the systemic acquired acclimation (SAA and the systemic acquired resistance (SAR. The electric signaling on its own cannot confer the required specificity of information to trigger SAA and SAR, therefore, we have also discussed a number of other mechanisms and signaling systems that can operate in combination with electric signaling. We have emphasized the interrelation between ionic mechanism of electrical activity and regulation of photosynthesis, which is intrinsic to a proper induction of SAA and SAR. In a special way, we have summarized the role of non-photochemical quenching and its regulator PsbS. Further, redox status of the cell, calcium and hydraulic waves, hormonal circuits and stomatal aperture regulation have been considered as components of the signaling. Finally, a model of light-dependent mechanisms of electrical signaling propagation has been presented together with the systemic regulation of light-responsive genes encoding both, ion channels and proteins involved in regulation of their activity. Due to space limitations, we have not addressed many other important aspects of hormonal and ROS signaling, which were presented in a number of recent excellent reviews.

  3. Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.

    Science.gov (United States)

    Gaya, Mauro; Barral, Patricia; Burbage, Marianne; Aggarwal, Shweta; Montaner, Beatriz; Warren Navia, Andrew; Aid, Malika; Tsui, Carlson; Maldonado, Paula; Nair, Usha; Ghneim, Khader; Fallon, Padraic G; Sekaly, Rafick-Pierre; Barouch, Dan H; Shalek, Alex K; Bruckbauer, Andreas; Strid, Jessica; Batista, Facundo D

    2018-01-25

    B cells constitute an essential line of defense from pathogenic infections through the generation of class-switched antibody-secreting cells (ASCs) in germinal centers. Although this process is known to be regulated by follicular helper T (TfH) cells, the mechanism by which B cells initially seed germinal center reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical for the induction of B cell immunity upon viral infection. The positioning of NKT cells at the interfollicular areas of lymph nodes facilitates both their direct priming by resident macrophages and the localized delivery of innate signals to antigen-experienced B cells. Indeed, NKT cells secrete an early wave of IL-4 and constitute up to 70% of the total IL-4-producing cells during the initial stages of infection. Importantly, the requirement of this innate immunity arm appears to be evolutionarily conserved because early NKT and IL-4 gene signatures also positively correlate with the levels of neutralizing antibodies in Zika-virus-infected macaques. In conclusion, our data support a model wherein a pre-TfH wave of IL-4 secreted by interfollicular NKT cells triggers the seeding of germinal center cells and serves as an innate link between viral infection and B cell immunity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Anopheles gambiae antiviral immune response to systemic O'nyong-nyong infection.

    Directory of Open Access Journals (Sweden)

    Joanna Waldock

    Full Text Available Mosquito-borne viral diseases cause significant burden in much of the developing world. Although host-virus interactions have been studied extensively in the vertebrate host, little is known about mosquito responses to viral infection. In contrast to mosquitoes of the Aedes and Culex genera, Anopheles gambiae, the principal vector of human malaria, naturally transmits very few arboviruses, the most important of which is O'nyong-nyong virus (ONNV. Here we have investigated the A. gambiae immune response to systemic ONNV infection using forward and reverse genetic approaches.We have used DNA microarrays to profile the transcriptional response of A. gambiae inoculated with ONNV and investigate the antiviral function of candidate genes through RNAi gene silencing assays. Our results demonstrate that A. gambiae responses to systemic viral infection involve genes covering all aspects of innate immunity including pathogen recognition, modulation of immune signalling, complement-mediated lysis/opsonisation and other immune effector mechanisms. Patterns of transcriptional regulation and co-infections of A. gambiae with ONNV and the rodent malaria parasite Plasmodium berghei suggest that hemolymph immune responses to viral infection are diverted away from melanisation. We show that four viral responsive genes encoding two putative recognition receptors, a galectin and an MD2-like receptor, and two effector lysozymes, function in limiting viral load.This study is the first step in elucidating the antiviral mechanisms of A. gambiae mosquitoes, and has revealed interesting differences between A. gambiae and other invertebrates. Our data suggest that mechanisms employed by A. gambiae are distinct from described invertebrate antiviral immunity to date, and involve the complement-like branch of the humoral immune response, supressing the melanisation response that is prominent in anti-parasitic immunity. The antiviral immune response in A. gambiae is thus

  5. Milk fermentation products of L. helveticus R389 activate calcineurin as a signal to promote gut mucosal immunity

    Directory of Open Access Journals (Sweden)

    Perdigón Gabriela

    2007-09-01

    at sites of infection. Conclusion The oral administration of the supernatant of milk fermented by L. helveticus R389 enhanced the gut mucosal immunity by improving the mechanisms that reinforce the epithelial and non-specific barriers and the gut functioning at sites of infection, with an improvement in the expression of the enzyme calcineurin, an important signal in the network that activates the gut immune system. The results of this work contribute to revealing the mechanisms underlying the immunomodulation of the gut immune function by fermented milks with probiotic bacteria.

  6. Effects of ionizing radiation on the immune system

    International Nuclear Information System (INIS)

    Dubois, J.B.

    1986-01-01

    After reviewing the different lymphoid organs and the essential phases of the immune response, we studied the morphological and functional effects of ionizing radiation on the immunological system. Histologic changes in the lymph nodes, spleen, thymus, and different lymphocyte subpopulations were studied in relation with the radiation dose and irradiated volume (whole body irradiation, localized irradiation). Functional changes in the immune system induced by ionizing radiation were also investigated by a study of humoral-mediated immunity (antibody formation) and cell-mediated immunity (behavior of macrophages, B-cells, T suppressor cells, T helper cells, T effector cells, and natural killer cells). A study into the mechanisms of action of ionizing radiation and the immune processes it interferes with suggests several likely hypotheses (direct action on the immune cells, on their precursors, on seric mediators or on cell mediators). The effects on cancer patients' immune reactions of low radiation doses delivered to the various lymphoid organs are discussed, as well as the relationships between the host and the evolution of the tumor [fr

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

    Science.gov (United States)

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

    2008-01-01

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

  8. Introduction to the role of the immune system in melanoma.

    Science.gov (United States)

    Margolin, Kim

    2014-06-01

    The concept of immunosurveillance of cancer has been widely accepted for many years, but only recently have the precise mechanisms of tumor-host immune interactions been revealed. Inflammatory and immune reactions play a role in melanomagenesis, and may contribute to the eradication of tumor as well as potentiating its growth and proliferation. Studies of the role of tumor-immune system interactions are providing insights into the pathogenesis and opportunities for highly effective therapeutic strategies. Some patients, even with advanced disease, are now cured with immunotherapy, and increasing numbers of such cures are likely in future. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Perinatal Environmental Effects on the Neonatal Immune System

    DEFF Research Database (Denmark)

    Thysen, Anna Hammerich

    2014-01-01

    are thought to be programmed in utero supporting a role of the early environment. The aim of the present PhD thesis was to study if known risk factors are imprinted in the immune system of newborns. The hypotheses were that cesarean section and season of birth would influence the immune signature in early...... life. Both are known to be associated with disease. We analyzed the distribution of circulating immune cells from cord blood in the children part of the ongoing unselected COPSAC2010 birth cohort by multi-color flow cytometry. Moreover, airway mucosal cytokines and chemokines of 1-month-old children...

  10. Radiation-induced effects and the immune system in cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kaur, Punit; Asea, Alexzander, E-mail: aasea@msm.edu [Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA (United States)

    2012-12-17

    Chemotherapy and radiation therapy (RT) are standard therapeutic modalities for patients with cancers, and could induce various tumor cell death modalities, releasing tumor-derived antigens as well as danger signals that could either be captured for triggering anti-tumor immune response. Historic studies examining tissue and cellular responses to RT have predominantly focused on damage caused to proliferating malignant cells leading to their death. However, there is increasing evidence that RT also leads to significant alterations in the tumor microenvironment, particularly with respect to effects on immune cells and infiltrating tumors. This review will focus on immunologic consequences of RT and discuss the therapeutic reprogramming of immune responses in tumors and how it regulates efficacy and durability to RT.

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

    Science.gov (United States)

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

    2018-06-01

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

  12. Cyclic LTI Systems in Digital Signal Processing

    National Research Council Canada - National Science Library

    Vaidyanathan, P

    1998-01-01

    .... While circular convolution has been the centerpiece of many algorithms in signal processing for decades, such freedom, especially from the viewpoint of linear system theory, has not been studied in the past...

  13. Small and long regulatory RNAs in the immune system and immune diseases

    NARCIS (Netherlands)

    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

  14. Optimal approximation of linear systems by artificial immune response

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    This paper puts forward a novel artificial immune response algorithm for optimal approximation of linear systems. A quaternion model of artificial immune response is proposed for engineering computing. The model abstracts four elements, namely, antigen, antibody, reaction rules among antibodies, and driving algorithm describing how the rules are applied to antibodies, to simulate the process of immune response. Some reaction rules including clonal selection rules, immunological memory rules and immune regulation rules are introduced. Using the theorem of Markov chain, it is proofed that the new model is convergent. The experimental study on the optimal approximation of a stable linear system and an unstable one show that the approximate models searched by the new model have better performance indices than those obtained by some existing algorithms including the differential evolution algorithm and the multi-agent genetic algorithm.

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

    Science.gov (United States)

    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

  16. Recommendation system for immunization coverage and monitoring.

    Science.gov (United States)

    Bhatti, Uzair Aslam; Huang, Mengxing; Wang, Hao; Zhang, Yu; Mehmood, Anum; Di, Wu

    2018-01-02

    Immunization averts an expected 2 to 3 million deaths every year from diphtheria, tetanus, pertussis (whooping cough), and measles; however, an additional 1.5 million deaths could be avoided if vaccination coverage was improved worldwide. 1 1 Data source for immunization records of 1.5 M: http://www.who.int/mediacentre/factsheets/fs378/en/ New vaccination technologies provide earlier diagnoses, personalized treatments and a wide range of other benefits for both patients and health care professionals. Childhood diseases that were commonplace less than a generation ago have become rare because of vaccines. However, 100% vaccination coverage is still the target to avoid further mortality. Governments have launched special campaigns to create an awareness of vaccination. In this paper, we have focused on data mining algorithms for big data using a collaborative approach for vaccination datasets to resolve problems with planning vaccinations in children, stocking vaccines, and tracking and monitoring non-vaccinated children appropriately. Geographical mapping of vaccination records helps to tackle red zone areas, where vaccination rates are poor, while green zone areas, where vaccination rates are good, can be monitored to enable health care staff to plan the administration of vaccines. Our recommendation algorithm assists in these processes by using deep data mining and by accessing records of other hospitals to highlight locations with lower rates of vaccination. The overall performance of the model is good. The model has been implemented in hospitals to control vaccination across the coverage area.

  17. The receptor kinase CERK1 has dual functions in symbiosis and immunity signalling.

    Science.gov (United States)

    Zhang, Xiaowei; Dong, Wentao; Sun, Jongho; Feng, Feng; Deng, Yiwen; He, Zuhua; Oldroyd, Giles E D; Wang, Ertao

    2015-01-01

    The establishment of symbiotic interactions between mycorrhizal fungi, rhizobial bacteria and their legume hosts involves a common symbiosis signalling pathway. This signalling pathway is activated by Nod factors produced by rhizobia and these are recognised by the Nod factor receptors NFR1/LYK3 and NFR5/NFP. Mycorrhizal fungi produce lipochitooligosaccharides (LCOs) similar to Nod factors, as well as short-chain chitin oligomers (CO4/5), implying commonalities in signalling during mycorrhizal and rhizobial associations. Here we show that NFR1/LYK3, but not NFR5/NFP, is required for the establishment of the mycorrhizal interaction in legumes. NFR1/LYK3 is necessary for the recognition of mycorrhizal fungi and the activation of the symbiosis signalling pathway leading to induction of calcium oscillations and gene expression. Chitin oligosaccharides also act as microbe associated molecular patterns that promote plant immunity via similar LysM receptor-like kinases. CERK1 in rice has the highest homology to NFR1 and we show that this gene is also necessary for the establishment of the mycorrhizal interaction as well as for resistance to the rice blast fungus. Our results demonstrate that NFR1/LYK3/OsCERK1 represents a common receptor for chitooligosaccharide-based signals produced by mycorrhizal fungi, rhizobial bacteria (in legumes) and fungal pathogens. It would appear that mycorrhizal recognition has been conserved in multiple receptors across plant species, but additional diversification in certain plant species has defined other signals that this class of receptors can perceive. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  18. Maintenance of systemic immune functions prevents accelerated presbycusis.

    Science.gov (United States)

    Iwai, Hiroshi; Baba, Susumu; Omae, Mariko; Lee, Shinryu; Yamashita, Toshio; Ikehara, Susumu

    2008-05-07

    There is no effective therapy for progressive hearing loss such as presbycusis, the causes of which remain poorly understood because of the difficulty of separating genetic and environmental contributions. In the present study, we show that the age-related dysfunctions of the systemic immune system in an animal model of accelerated presbycusis (SAMP1, senescence-accelerated mouse P1) can be corrected by allogeneic bone marrow transplantation (BMT). We also demonstrate that this presbycusis can be prevented; BMT protects the recipients from age-related hearing impairment and the degeneration of spiral ganglion cells (SGCs) as well as the dysfunctions of T lymphocytes, which have a close relation to immune senescence. No donor cells are infiltrated to the spiral ganglia, confirming that this experimental system using BMT is connected to the systemic immune system and does not contribute to transdifferentiation or fusion by donor hematopoietic stem cells (HSCs), or to the direct maintenance of ganglion cells by locally infiltrated donor immunocompetent cells. Therefore, another procedure which attempts to prevent the age-related dysfunctions of the recipient immune system is the inoculation of syngeneic splenocytes from young donors. These mice show no development of hearing loss, compared with the recipient mice with inoculation of saline or splenocytes from old donors. Our studies on the relationship between age-related systemic immune dysfunctions and neurodegeneration mechanisms open up new avenues of treatment for presbycusis, for which there is no effective therapy.

  19. Retroviruses as tools to study the immune system.

    Science.gov (United States)

    Lois, C; Refaeli, Y; Qin, X F; Van Parijs, L

    2001-08-01

    Retrovirus-based vectors provide an efficient means to introduce and express genes in cells of the immune system and have become a popular tool to study immune function. They are easy to manipulate and provide stable, long-term gene expression because they integrate into the genome. Current retroviral vectors do have limitations that affect their usefulness in certain applications. However, recent advances suggest a number of ways in which these vectors might be improved to extend their utility in immunological research.

  20. Immunity to transplantable nitrosourea-induced neurogenic tumors. III. Systemic adoptive transfer of immunity

    International Nuclear Information System (INIS)

    Shibuya, N.; Hochgeschwender, U.; Kida, Y.; Hochwald, G.M.; Thorbecke, G.J.; Cravioto, H.

    1984-01-01

    The effect of intravenously injected tumor immune spleen cells on growth of 3 X 10 5 gliosarcoma T 9 cells injected intradermally (ID) or intracerebrally (IC) into sublethally irradiated CDF rats was evaluated. Spleen cells from donor rats with sufficient immunity to reject 5 X 10 5 T 9 cells inhibited the growth of T 9 cells mixed with spleen cells in a ratio of 1:25 and injected ID, but could not act after intravenous transfer. However, donor rats which had rejected increasing T 9 challenge doses up to 1 X 10 7 cells produced immune spleen cells which, upon IV transfer, could inhibit growth of ID T 9 challenge but not of EB-679, an unrelated glioma, in recipient rats. Rejection of IC T 9 challenge was also obtained after IV transfer, in recipients of such ''hyperimmune'' spleen cells, but was less (60% maximum) than that noted after ID T 9 challenge (100% maximum). The removal of B cells from the transferred spleen cells did not affect the results, suggesting that the specific immunity was mediated by T cells. The authors conclude that the special immunological circumstances of tumors growing in the brain renders them less accessible to rejection by systemically transferred immune cells, but it is nevertheless possible to effect a significant incidence of rejection of syngeneic tumor growth in the brain by the intravenous transfer of hyperimmune spleen cells

  1. Modulation of innate immune responses by Yersinia type III secretion system translocators and effectors.

    Science.gov (United States)

    Bliska, James B; Wang, Xiaoying; Viboud, Gloria I; Brodsky, Igor E

    2013-10-01

    The innate immune system of mammals responds to microbial infection through detection of conserved molecular determinants called 'pathogen-associated molecular patterns' (PAMPs). Pathogens use virulence factors to counteract PAMP-directed responses. The innate immune system can in turn recognize signals generated by virulence factors, allowing for a heightened response to dangerous pathogens. Many Gram-negative bacterial pathogens encode type III secretion systems (T3SSs) that translocate effector proteins, subvert PAMP-directed responses and are critical for infection. A plasmid-encoded T3SS in the human-pathogenic Yersinia species translocates seven effectors into infected host cells. Delivery of effectors by the T3SS requires plasma membrane insertion of two translocators, which are thought to form a channel called a translocon. Studies of the Yersinia T3SS have provided key advances in our understanding of how innate immune responses are generated by perturbations in plasma membrane and other signals that result from translocon insertion. Additionally, studies in this system revealed that effectors function to inhibit innateimmune responses resulting from insertion of translocons into plasma membrane. Here, we review these advances with the goal of providing insight into how a T3SS can activate and inhibit innate immune responses, allowing a virulent pathogen to bypass host defences. © 2013 John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Aki Takahashi

    2018-03-01

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

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

    Science.gov (United States)

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

    2018-01-01

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

  4. Role of the Immune System in Diabetic Kidney Disease.

    Science.gov (United States)

    Hickey, Fionnuala B; Martin, Finian

    2018-03-12

    The purpose of this review is to examine the proposed role of immune modulation in the development and progression of diabetic kidney disease (DKD). Diabetic kidney disease has not historically been considered an immune-mediated disease; however, increasing evidence is emerging in support of an immune role in its pathophysiology. Both systemic and local renal inflammation have been associated with DKD. Infiltration of immune cells, predominantly macrophages, into the kidney has been reported in a number of both experimental and clinical studies. In addition, increased levels of circulating pro-inflammatory cytokines have been linked to disease progression. Consequently, a variety of therapeutic strategies involving modulation of the immune response are currently being investigated in diabetic kidney disease. Although no current therapies for DKD are directly based on immune modulation many of the therapies in clinical use have anti-inflammatory effects along with their primary actions. Macrophages emerge as the most likely beneficial immune cell target and compounds which reduce macrophage infiltration to the kidney have shown potential in both animal models and clinical trials.

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

    Science.gov (United States)

    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.

  6. Signals and transforms in linear systems analysis

    CERN Document Server

    Wasylkiwskyj, Wasyl

    2013-01-01

    Signals and Transforms in Linear Systems Analysis covers the subject of signals and transforms, particularly in the context of linear systems theory. Chapter 2 provides the theoretical background for the remainder of the text. Chapter 3 treats Fourier series and integrals. Particular attention is paid to convergence properties at step discontinuities. This includes the Gibbs phenomenon and its amelioration via the Fejer summation techniques. Special topics include modulation and analytic signal representation, Fourier transforms and analytic function theory, time-frequency analysis and frequency dispersion. Fundamentals of linear system theory for LTI analogue systems, with a brief account of time-varying systems, are covered in Chapter 4 . Discrete systems are covered in Chapters 6 and 7.  The Laplace transform treatment in Chapter 5 relies heavily on analytic function theory as does Chapter 8 on Z -transforms. The necessary background on complex variables is provided in Appendix A. This book is intended to...

  7. Emergency automatic signalling system using time scheduling

    Science.gov (United States)

    Rayavel, P.; Surenderanath, S.; Rathnavel, P.; Prakash, G.

    2018-04-01

    It is difficult to handle traffic congestion and maintain roads during traffic mainly in India. As the people migrate from rural to urban and sub-urban areas, it becomes still more critical. Presently Roadways is a standout amongst the most vital transportation. At the point when a car crash happens, crisis vehicles, for example, ambulances and fire trucks must rush to the mischance scene. There emerges a situation where a portion of the crisis vehicles may cause another car crash. Therefore it becomes still more difficult for emergency vehicle to reach the destination within a predicted time. To avoid that kind of problem we have come out with an effective idea which can reduce the potential in the traffic system. The traffic system is been modified using a wireless technology and high speed micro controller to provide smooth and clear flow of traffic for ambulance to reach the destination on time. This is achieved by using RFID Tag at the ambulance and RFID Reader at the traffic system i.e., traffic signal. This mainly deals with identifying the emergency vehicle and providing a green signal to traffic signal at time of traffic jam. — By assigning priorities to various traffic movements, we can control the traffic jam. In some moments like ambulance emergency, high delegates arrive people facing lot of trouble. To overcome this problem in this paper we propose a time priority based traffic system achieved by using RFID transmitter at the emergency vehicle and RFID receiver at the traffic system i.e., traffic signal. The signal from the emergency vehicle is sent to traffic system which after detecting it sends it to microcontroller which controls the traffic signal. If any emergency vehicle is detected the system goes to emergency system mode where signal switch to green and if it is not detected normal system mode.

  8. Early Microbes Modify Immune System Development and Metabolic Homeostasis-The "Restaurant" Hypothesis Revisited.

    Science.gov (United States)

    Nash, Michael J; Frank, Daniel N; Friedman, Jacob E

    2017-01-01

    The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the "Restaurant" hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate's gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.

  9. Early Microbes Modify Immune System Development and Metabolic Homeostasis—The “Restaurant” Hypothesis Revisited

    Directory of Open Access Journals (Sweden)

    Michael J. Nash

    2017-12-01

    Full Text Available The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD. This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research.

  10. Early Microbes Modify Immune System Development and Metabolic Homeostasis—The “Restaurant” Hypothesis Revisited

    Science.gov (United States)

    Nash, Michael J.; Frank, Daniel N.; Friedman, Jacob E.

    2017-01-01

    The developing infant gut microbiome affects metabolism, maturation of the gastrointestinal tract, immune system function, and brain development. Initial seeding of the neonatal microbiota occurs through maternal and environmental contact. Maternal diet, antibiotic use, and cesarean section alter the offspring microbiota composition, at least temporarily. Nutrients are thought to regulate initial perinatal microbial colonization, a paradigm known as the “Restaurant” hypothesis. This hypothesis proposes that early nutritional stresses alter both the initial colonizing bacteria and the development of signaling pathways controlled by microbial mediators. These stresses fine-tune the immune system and metabolic homeostasis in early life, potentially setting the stage for long-term metabolic and immune health. Dysbiosis, an imbalance or a maladaptation in the microbiota, can be caused by several factors including dietary alterations and antibiotics. Dysbiosis can alter biological processes in the gut and in tissues and organs throughout the body. Misregulated development and activity of both the innate and adaptive immune systems, driven by early dysbiosis, could have long-lasting pathologic consequences such as increased autoimmunity, increased adiposity, and non-alcoholic fatty liver disease (NAFLD). This review will focus on factors during pregnancy and the neonatal period that impact a neonate’s gut microbiome, as well as the mechanisms and possible links from early infancy that can drive increased risk for diseases including obesity and NAFLD. The complex pathways that connect diet, the microbiota, immune system development, and metabolism, particularly in early life, present exciting new frontiers for biomedical research. PMID:29326657

  11. Connecting the immune system, systemic chronic inflammation and the gut microbiome: The role of sex.

    Science.gov (United States)

    Rizzetto, Lisa; Fava, Francesca; Tuohy, Kieran M; Selmi, Carlo

    2018-05-31

    Unresolved low grade systemic inflammation represents the underlying pathological mechanism driving immune and metabolic pathways involved in autoimmune diseases (AID). Mechanistic studies in animal models of AID and observational studies in patients have found alterations in gut microbiota communities and their metabolites, suggesting a microbial contribution to the onset or progression of AID. The gut microbiota and its metabolites have been shown to influence immune functions and immune homeostasis both within the gut and systematically. Microbial derived-short chain fatty acid (SCFA) and bio-transformed bile acid (BA) have been shown to influence the immune system acting as ligands specific cell signaling receptors like GPRCs, TGR5 and FXR, or via epigenetic processes. Similarly, intestinal permeability (leaky gut) and bacterial translocation are important contributors to chronic systemic inflammation and, without repair of the intestinal barrier, might represent a continuous inflammatory stimulus capable of triggering autoimmune processes. Recent studies indicate gender-specific differences in immunity, with the gut microbiota shaping and being concomitantly shaped by the hormonal milieu governing differences between the sexes. A bi-directional cross-talk between microbiota and the endocrine system is emerging with bacteria being able to produce hormones (e.g. serotonin, dopamine and somatostatine), respond to host hormones (e.g. estrogens) and regulate host hormones' homeostasis (e.g by inhibiting gene prolactin transcription or converting glucocorticoids to androgens). We review herein how gut microbiota and its metabolites regulate immune function, intestinal permeability and possibly AID pathological processes. Further, we describe the dysbiosis within the gut microbiota observed in different AID and speculate how restoring gut microbiota composition and its regulatory metabolites by dietary intervention including prebiotics and probiotics could help in

  12. Always one step ahead: How pathogenic bacteria use the type III secretion system to manipulate the intestinal mucosal immune system

    Directory of Open Access Journals (Sweden)

    Marchès Olivier

    2011-05-01

    Full Text Available Abstract The intestinal immune system and the epithelium are the first line of defense in the gut. Constantly exposed to microorganisms from the environment, the gut has complex defense mechanisms to prevent infections, as well as regulatory pathways to tolerate commensal bacteria and food antigens. Intestinal pathogens have developed strategies to regulate intestinal immunity and inflammation in order to establish or prolong infection. The organisms that employ a type III secretion system use a molecular syringe to deliver effector proteins into the cytoplasm of host cells. These effectors target the host cell cytoskeleton, cell organelles and signaling pathways. This review addresses the multiple mechanisms by which the type III secretion system targets the intestinal immune response, with a special focus on pathogenic E. coli.

  13. Targeting cFMS signaling to restore immune function and eradicate HIV reservoirs

    Science.gov (United States)

    Gerngross, Lindsey

    While combination anti-retroviral therapy (cART) has improved the length and quality of life of individuals living with HIV-1 infection, the prevalence of HIV-associated neurocognitive disorders (HAND) has increased and remains a significant clinical concern. The neuropathogenesis of HAND is not completely understood, however, latent HIV infection in the central nervous system (CNS) and chronic neuroinflammation are believed to play a prominent role. CNS-associated macrophages and resident microglia are significant contributors to CNS inflammation and constitute the chief reservoir of HIV-1 infection in the CNS. Previous studies from our lab suggest monocyte/macrophage invasion of the CNS in HIV may be driven by altered monocyte/macrophage homeostasis. We have reported expansion of a monocyte subset (CD14+CD16 +CD163+) in peripheral blood of HIV+ patients that is phenotypically similar to macrophages/microglia that accumulate in the CNS as seen in post-mortem tissue. The factors driving the expansion of this monocyte subset are unknown, however, signaling through cFMS, a type III receptor tyrosine kinase (RTK), may play a role. Macrophage-colony stimulating factor (M-CSF), a ligand of cFMS, has been shown to be elevated in the cerebral spinal fluid (CSF) of individuals with the most severe form of HAND, HIV-associated dementia (HAD). M-CSF promotes a Macrophage-2-like phenotype and increases CD16 and CD163 expression in cultured monocytes. M-CSF has also been shown to increase the susceptibility of macrophages to HIV infection and enhance virus production. These findings, in addition to the known function of M-CSF in promoting macrophage survival, supports a role for M-CSF in the development and maintenance of macrophage viral reservoirs in tissues where these cells accumulate, including the CNS. Interestingly, a second ligand for cFMS, IL-34, was recently identified and reported to share some functions with M-CSF, suggesting that both ligands may contribute to HIV

  14. Modulation of systemic immune responses through commensal gastrointestinal microbiota.

    Directory of Open Access Journals (Sweden)

    Kyle M Schachtschneider

    Full Text Available Colonization of the gastrointestinal (GI tract is initiated during birth and continually seeded from the individual's environment. Gastrointestinal microorganisms play a central role in developing and modulating host immune responses and have been the subject of investigation over the last decades. Animal studies have demonstrated the impact of GI tract microbiota on local gastrointestinal immune responses; however, the full spectrum of action of early gastrointestinal tract stimulation and subsequent modulation of systemic immune responses is poorly understood. This study explored the utility of an oral microbial inoculum as a therapeutic tool to affect porcine systemic immune responses. For this study a litter of 12 pigs was split into two groups. One group of pigs was inoculated with a non-pathogenic oral inoculum (modulated, while another group (control was not. DNA extracted from nasal swabs and fecal samples collected throughout the study was sequenced to determine the effects of the oral inoculation on GI and respiratory microbial communities. The effects of GI microbial modulation on systemic immune responses were evaluated by experimentally infecting with the pathogen Mycoplasma hyopneumoniae. Coughing levels, pathology, toll-like receptors 2 and 6, and cytokine production were measured throughout the study. Sequencing results show a successful modulation of the GI and respiratory microbiomes through oral inoculation. Delayed type hypersensitivity responses were stronger (p = 0.07, and the average coughing levels and respiratory TNF-α variance were significantly lower in the modulated group (p<0.0001 and p = 0.0153, respectively. The M. hyopneumoniae infection study showed beneficial effects of the oral inoculum on systemic immune responses including antibody production, severity of infection and cytokine levels. These results suggest that an oral microbial inoculation can be used to modulate microbial communities, as well as

  15. The interplay between the gut microbiota and the immune system.

    Science.gov (United States)

    Geuking, Markus B; Köller, Yasmin; Rupp, Sandra; McCoy, Kathy D

    2014-01-01

    The impact of the gut microbiota on immune homeostasis within the gut and, importantly, also at systemic sites has gained tremendous research interest over the last few years. The intestinal microbiota is an integral component of a fascinating ecosystem that interacts with and benefits its host on several complex levels to achieve a mutualistic relationship. Host-microbial homeostasis involves appropriate immune regulation within the gut mucosa to maintain a healthy gut while preventing uncontrolled immune responses against the beneficial commensal microbiota potentially leading to chronic inflammatory bowel diseases (IBD). Furthermore, recent studies suggest that the microbiota composition might impact on the susceptibility to immune-mediated disorders such as autoimmunity and allergy. Understanding how the microbiota modulates susceptibility to these diseases is an important step toward better prevention or treatment options for such diseases.

  16. Thermodynamics as the driving principle behind the immune system

    Directory of Open Access Journals (Sweden)

    Eduardo Finger

    2012-09-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

  18. Systems biology of neutrophil differentiation and immune response

    DEFF Research Database (Denmark)

    Theilgaard-Mönch, Kim; Porse, Bo T; Borregaard, Niels

    2005-01-01

    Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies. These stu......Systems biology has emerged as a new scientific field, which aims at investigating biological processes at the genomic and proteomic levels. Recent studies have unravelled aspects of neutrophil differentiation and immune responses at the systems level using high-throughput technologies....... These studies have identified a plethora of novel effector proteins stored in the granules of neutrophils. In addition, these studies provide evidence that neutrophil differentiation and immune response are governed by a highly coordinated transcriptional programme that regulates cellular fate and function...

  19. New insights into innate immune control of systemic candidiasis

    Science.gov (United States)

    Lionakis, Michail S.

    2014-01-01

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

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

    Science.gov (United States)

    Meltzer, Amory; Van de Water, Judy

    2017-01-01

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

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

    Science.gov (United States)

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

    2016-10-01

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

  2. La protéine CG4572 de Drosophile et la propagation du signal ARNi immun antiviral

    OpenAIRE

    Karlikow , Margot

    2015-01-01

    During viral infection, cell survival will depend on adequately giving, receiving and processing information to establish an efficient antiviral immune response. Cellular communication is therefore essential to allow the propagation of immune signals that will confer protection to the entire organism.The major antiviral defense in insects is the RNA interference (RNAi) mechanism that is activated by detection of viral double-stranded RNA (dsRNA). The antiviral RNAi mechanism can be divided in...

  3. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System.

    Science.gov (United States)

    Withers, David R; Hepworth, Matthew R

    2017-01-01

    The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of "exogenous" signals, such as dietary metabolites and commensal microbes, and "endogenous" host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a "communications hub" in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell-cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

  4. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

    Directory of Open Access Journals (Sweden)

    David R. Withers

    2017-10-01

    Full Text Available The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3 are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases.

  5. Group 3 Innate Lymphoid Cells: Communications Hubs of the Intestinal Immune System

    Science.gov (United States)

    Withers, David R.; Hepworth, Matthew R.

    2017-01-01

    The maintenance of mammalian health requires the generation of appropriate immune responses against a broad range of environmental and microbial challenges, which are continually encountered at barrier tissue sites including the skin, lung, and gastrointestinal tract. Dysregulated barrier immune responses result in inflammation, both locally and systemically in peripheral organs. Group 3 innate lymphoid cells (ILC3) are constitutively present at barrier sites and appear to be highly specialized in their ability to sense a range of environmental and host-derived signals. Under homeostatic conditions, ILC3 respond to local cues to maintain tissue homeostasis and restrict inflammatory responses. In contrast, perturbations in the tissue microenvironment resulting from disease, infection, or tissue damage can drive dysregulated pro-inflammatory ILC3 responses and contribute to immunopathology. The tone of the ILC3 response is dictated by a balance of “exogenous” signals, such as dietary metabolites and commensal microbes, and “endogenous” host-derived signals from stromal cells, immune cells, and the nervous system. ILC3 must therefore have the capacity to simultaneously integrate a wide array of complex and dynamic inputs in order to regulate barrier function and tissue health. In this review, we discuss the concept of ILC3 as a “communications hub” in the intestinal tract and associated lymphoid tissues and address the variety of signals, derived from multiple biological systems, which are interpreted by ILC3 to modulate the release of downstream effector molecules and regulate cell–cell crosstalk. Successful integration of environmental cues by ILC3 and downstream propagation to the broader immune system is required to maintain a tolerogenic and anti-inflammatory tone and reinforce barrier function, whereas dysregulation of ILC3 responses can contribute to the onset or progression of clinically relevant chronic inflammatory diseases. PMID:29085366

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

    Directory of Open Access Journals (Sweden)

    Litian Duan

    2016-11-01

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

  7. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Libregts, Sten F.W.M.; Nolte, Martijn A., E-mail: m.nolte@sanquin.nl

    2014-12-10

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function.

  8. Parallels between immune driven-hematopoiesis and T cell activation: 3 signals that relay inflammatory stress to the bone marrow

    International Nuclear Information System (INIS)

    Libregts, Sten F.W.M.; Nolte, Martijn A.

    2014-01-01

    Quiescence, self-renewal, lineage commitment and differentiation of hematopoietic stem cells (HSCs) towards fully mature blood cells are a complex process that involves both intrinsic and extrinsic signals. During steady-state conditions, most hematopoietic signals are provided by various resident cells inside the bone marrow (BM), which establish the HSC micro-environment. However, upon infection, the hematopoietic process is also affected by pathogens and activated immune cells, which illustrates an effective feedback mechanism to hematopoietic stem and progenitor cells (HSPCs) via immune-mediated signals. Here, we review the impact of pathogen-associated molecular patterns (PAMPs), damage-associated molecular patterns (DAMPs), costimulatory molecules and pro-inflammatory cytokines on the quiescence, proliferation and differentiation of HSCs and more committed progenitors. As modulation of HSPC function via these immune-mediated signals holds an interesting parallel with the “three-signal-model” described for the activation and differentiation of naïve T-cells, we propose a novel “three-signal” concept for immune-driven hematopoiesis. In this model, the recognition of PAMPs and DAMPs will activate HSCs and induce proliferation, while costimulatory molecules and pro-inflammatory cytokines confer a second and third signal, respectively, which further regulate expansion, lineage commitment and differentiation of HSPCs. We review the impact of inflammatory stress on hematopoiesis along these three signals and we discuss whether they act independently from each other or that concurrence of these signals is important for an adequate response of HSPCs upon infection. - Highlights: • Inflammation and infection have a direct impact on hematopoiesis in the bone marrow. • We draw a striking parallel between immune-driven hematopoiesis and T cell activation. • We review how PAMPs and DAMPs, costimulation and cytokines influence HSPC function

  9. The Ubiquitin System and Jasmonate Signaling

    Directory of Open Access Journals (Sweden)

    Astrid Nagels Durand

    2016-01-01

    Full Text Available The ubiquitin (Ub system is involved in most, if not all, biological processes in eukaryotes. The major specificity determinants of this system are the E3 ligases, which bind and ubiquitinate specific sets of proteins and are thereby responsible for target recruitment to the proteasome or other cellular processing machineries. The Ub system contributes to the regulation of the production, perception and signal transduction of plant hormones. Jasmonic acid (JA and its derivatives, known as jasmonates (JAs, act as signaling compounds regulating plant development and plant responses to various biotic and abiotic stress conditions. We provide here an overview of the current understanding of the Ub system involved in JA signaling.

  10. Physical activity influences the immune system of breast cancer patients

    Directory of Open Access Journals (Sweden)

    Thorsten Schmidt

    2017-01-01

    Full Text Available It has been suggested that physical activity in breast cancer patients can not only improve quality of life. Influences on physical and psychological levels have been evaluated, but effects on the immune system of breast cancer patients are hardly known. A PubMed search identified relevant trials and meta-analyses from 1970 to 2013. This review summarizes the results of international studies and the current discussion of effects of physical activity on the immune system of breast cancer patients. Highlighted are effects of physical activity on the immune system. Seven original articles and 14 reviews included in this review. Two original and the review articles includes other tumor entities besides breast cancer.Evaluated methods such as dose-response relationships for exercise in oncology, hardly exist. Increased immunological anti-cancer activity due to physical activity is probably mediated via an increase in number and cytotoxicity of monocytes and natural killer cells and cytokines.

  11. Innate immune responses: Crosstalk of signaling and regulation of gene transcription

    International Nuclear Information System (INIS)

    Zhong Bo; Tien Po; Shu Hongbing

    2006-01-01

    Innate immune responses to pathogens such as bacteria and viruses are triggered by recognition of specific structures of invading pathogens called pathogen-associated molecular patterns (PAMPs) by cellular pattern recognition receptors (PRRs) that are located at plasma membrane or inside cells. Stimulation of different PAMPs activates Toll-like receptor (TLR)-dependent and -independent signaling pathways that lead to activation of transcription factors nuclear factor-κB (NF-κB), interferon regulatory factor 3/7 (IRF3/7) and/or activator protein-1 (AP-1), which collaborate to induce transcription of a large number of downstream genes. This review focuses on the rapid progress that has recently improved our understanding of the crosstalk among the pathways and the precise regulation of transcription of the downstream genes

  12. Neem leaf glycoprotein prophylaxis transduces immune dependent stop signal for tumor angiogenic switch within tumor microenvironment.

    Directory of Open Access Journals (Sweden)

    Saptak Banerjee

    Full Text Available We have reported that prophylactic as well as therapeutic administration of neem leaf glycoprotein (NLGP induces significant restriction of solid tumor growth in mice. Here, we investigate whether the effect of such pretreatment (25µg/mice; weekly, 4 times benefits regulation of tumor angiogenesis, an obligate factor for tumor progression. We show that NLGP pretreatment results in vascular normalization in melanoma and carcinoma bearing mice along with downregulation of CD31, VEGF and VEGFR2. NLGP pretreatment facilitates profound infiltration of CD8+ T cells within tumor parenchyma, which subsequently regulates VEGF-VEGFR2 signaling in CD31+ vascular endothelial cells to prevent aberrant neovascularization. Pericyte stabilization, VEGF dependent inhibition of VEC proliferation and subsequent vascular normalization are also experienced. Studies in immune compromised mice confirmed that these vascular and intratumoral changes in angiogenic profile are dependent upon active adoptive immunity particularly those mediated by CD8+ T cells. Accumulated evidences suggest that NLGP regulated immunomodulation is active in tumor growth restriction and normalization of tumor angiogenesis as well, thereby, signifying its clinical translation.

  13. Transmission of innate immune signaling by packaging of cGAMP in viral particles.

    Science.gov (United States)

    Gentili, Matteo; Kowal, Joanna; Tkach, Mercedes; Satoh, Takeshi; Lahaye, Xavier; Conrad, Cécile; Boyron, Marilyn; Lombard, Bérangère; Durand, Sylvère; Kroemer, Guido; Loew, Damarys; Dalod, Marc; Théry, Clotilde; Manel, Nicolas

    2015-09-11

    Infected cells detect viruses through a variety of receptors that initiate cell-intrinsic innate defense responses. Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is a cytosolic sensor for many DNA viruses and HIV-1. In response to cytosolic viral DNA, cGAS synthesizes the second messenger 2'3'-cyclic GMP-AMP (cGAMP), which activates antiviral signaling pathways. We show that in cells producing virus, cGAS-synthesized cGAMP can be packaged in viral particles and extracellular vesicles. Viral particles efficiently delivered cGAMP to target cells. cGAMP transfer by viral particles to dendritic cells activated innate immunity and antiviral defenses. Finally, we show that cell-free murine cytomegalovirus and Modified Vaccinia Ankara virus contained cGAMP. Thus, transfer of cGAMP by viruses may represent a defense mechanism to propagate immune responses to uninfected target cells. Copyright © 2015, American Association for the Advancement of Science.

  14. Evolution and integration of innate immune systems from fruit flies to man: lessons and questions.

    Science.gov (United States)

    Martinelli, Cosimo; Reichhart, Jean-Marc

    2005-01-01

    Despite broad differences in morphology, ecology and behavior, the fruit fly Drosophila melanogaster and humans show a remarkably high degree of conservation for many molecular, cellular, and developmental aspects of their biology. During the last decade, similarities have also been discovered in some of the mechanisms regulating their innate immune system. These parallels regard mainly the Toll-like receptor family and the intracellular signaling pathways involved in the control of the immune response. However, if the overall similarities are important, the detailed pathogen recognition mechanisms differ significantly between fly and humans, highlighting a complicated evolutionary history of the metazoan innate defenses. In this review, we will discuss the main similarities and differences between the two types of organisms. We hope that this current knowledge will be used as a starting point for a more comprehensive view of innate immunity within the broad variety of metazoan phyla.

  15. Schizophrenia and the immune system: pathophysiology, prevention, and treatment.

    Science.gov (United States)

    Richard, Michelle D; Brahm, Nancy C

    2012-05-01

    Published evidence on established and theoretical connections between immune system dysfunction and schizophrenia is reviewed, with a discussion of developments in the search for immunologically-targeted treatments. A growing body of evidence indicates that immunologic influences may play an important role in the etiology and course of schizophrenia. A literature search identified more than 100 articles pertaining to suspected immunologic influences on schizophrenia published over the past 15 years. Schizophrenia researchers have explored a wide range of potential immune system-related causal or contributory factors, including neurobiological and neuroanatomical disorders, genetic abnormalities, and environmental influences such as maternal perinatal infection. Efforts to establish an immunologic basis for schizophrenia and identify reliable immune markers continue to be hindered by sampling challenges and methodological problems. In aggregate, the available evidence indicates that at least some cases of schizophrenia have an immunologic component, suggesting that immune-focused prevention strategies (e.g., counseling of pregnant women to avoid immune stressors) and close monitoring of at-risk children are appropriate. While antipsychotics remain the standard treatments for schizophrenia, a variety of drugs with immunologic effects have been investigated as adjunctive therapies, with variable and sometimes conflicting results; these include the cyclooxygenase-2 inhibitor celecoxib, immune-modulating agents (e.g., azathioprine and various anticytokine agents such as atlizumab, anakinra, and tumor necrosis factor-α blockers), and an investigational anti-interferon-γ agent. The published evidence indicates that immune system dysfunction related to genetic, environmental, and neurobiological influences may play a role in the etiology of schizophrenia in a subset of patients.

  16. The effect of ionizing radiation on immune system

    International Nuclear Information System (INIS)

    Gyuleva, I.

    1999-01-01

    Delayed radiation effects of irradiation at relatively high doses - 0.52- 2 Gy in result of severe accidents are discussed. The immune response of lymphocyte populations manifested in formation of different kind of mutant cells at Hiroshima-A-bombing and Chernobyl accident are presented. It is of great interest the hypothesis presented launched by RERF (Japanese Foundation for Radiation Effect Research, Hiroshima) for radiation induced predominant of T H2 -lymphocytes in comparison to T H1 as delayed immune response at the Hiroshima-A-bomb survivors. The aspect of immune status is quite different at low doses irradiation (0.02 - 0.2 Gy). There is some stimulation in immune response known as hormesis effect. It is suggested that T-cell activation has key role in immune system stimulation at doses under 0.2 Gy. There is also activation of DNA-reparation mechanisms. Suppression of the hypothalamus-hypophysis-suprarenal axis brings to enhancing of immune potential. Chinese people living in a region with three-times higher background radiation, X-ray examined patients as well as occupationally exposed personnel have been investigated. Radioprotective effect of some cytokines and their influence on the individual radiosensitivity are also discussed.The investigations have to be continued because of some inconsistent results

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

    Science.gov (United States)

    Shinde, Snehal B; Kurhekar, Manish P

    2018-06-01

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

  18. Specific recycling receptors are targeted to the immune synapse by the intraflagellar transport system

    Science.gov (United States)

    Finetti, Francesca; Patrussi, Laura; Masi, Giulia; Onnis, Anna; Galgano, Donatella; Lucherini, Orso Maria; Pazour, Gregory J.; Baldari, Cosima T.

    2014-01-01

    ABSTRACT T cell activation requires sustained signaling at the immune synapse, a specialized interface with the antigen-presenting cell (APC) that assembles following T cell antigen receptor (TCR) engagement by major histocompatibility complex (MHC)-bound peptide. Central to sustained signaling is the continuous recruitment of TCRs to the immune synapse. These TCRs are partly mobilized from an endosomal pool by polarized recycling. We have identified IFT20, a component of the intraflagellar transport (IFT) system that controls ciliogenesis, as a central regulator of TCR recycling to the immune synapse. Here, we have investigated the interplay of IFT20 with the Rab GTPase network that controls recycling. We found that IFT20 forms a complex with Rab5 and the TCR on early endosomes. IFT20 knockdown (IFT20KD) resulted in a block in the recycling pathway, leading to a build-up of recycling TCRs in Rab5+ endosomes. Recycling of the transferrin receptor (TfR), but not of CXCR4, was disrupted by IFT20 deficiency. The IFT components IFT52 and IFT57 were found to act together with IFT20 to regulate TCR and TfR recycling. The results provide novel insights into the mechanisms that control TCR recycling and immune synapse assembly, and underscore the trafficking-related function of the IFT system beyond ciliogenesis. PMID:24554435

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

    Science.gov (United States)

    Bronsart, Laura L; Contag, Christopher H

    2016-01-01

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

  20. [Environmental pollutants as adjuvant factors of immune system derived diseases].

    Science.gov (United States)

    Lehmann, Irina

    2017-06-01

    The main task of the immune system is to protect the body against invading pathogens. To be able to do so, immune cells must be able to recognize and combat exogenous challenges and at the same time tolerate body-borne structures. A complex regulatory network controls the sensitive balance between defense and tolerance. Perturbation of this network ultimately leads to the development of chronic inflammation, such as allergies, autoimmune reactions, and infections, because the immune system is no longer able to efficiently eliminate invading pathogens. Environmental pollutants can cause such perturbations by affecting the function of immune cells in such a way that they would react hypersensitively against allergens and the body's own structures, respectively, or that they would be no longer able to adequately combat pathogens. This indirect effect is also known as adjuvant effect. For pesticides, heavy metals, wood preservatives, or volatile organic compounds such adjuvant effects are well known. Examples of the mechanism by which environmental toxins contribute to chronic inflammatory diseases are manifold and will be discussed along asthma and allergies.While the immune system of healthy adults is typically well able to distinguish between foreign and endogenous substances even under adverse environmental conditions, that of children would react much more sensible upon comparable environmental challenges. To prevent priming for diseases by environmental cues during that highly sensitive period of early childhood children are to be particularly protected.

  1. Hopf bifurcation for tumor-immune competition systems with delay

    Directory of Open Access Journals (Sweden)

    Ping Bi

    2014-01-01

    Full Text Available In this article, a immune response system with delay is considered, which consists of two-dimensional nonlinear differential equations. The main purpose of this paper is to explore the Hopf bifurcation of a immune response system with delay. The general formula of the direction, the estimation formula of period and stability of bifurcated periodic solution are also given. Especially, the conditions of the global existence of periodic solutions bifurcating from Hopf bifurcations are given. Numerical simulations are carried out to illustrate the the theoretical analysis and the obtained results.

  2. Stochastic responses of tumor–immune system with periodic treatment

    International Nuclear Information System (INIS)

    Li Dong-Xi; Li Ying

    2017-01-01

    We investigate the stochastic responses of a tumor–immune system competition model with environmental noise and periodic treatment. Firstly, a mathematical model describing the interaction between tumor cells and immune system under external fluctuations and periodic treatment is established based on the stochastic differential equation. Then, sufficient conditions for extinction and persistence of the tumor cells are derived by constructing Lyapunov functions and Ito’s formula. Finally, numerical simulations are introduced to illustrate and verify the results. The results of this work provide the theoretical basis for designing more effective and precise therapeutic strategies to eliminate cancer cells, especially for combining the immunotherapy and the traditional tools. (paper)

  3. Linking the microbiota, chronic disease and the immune system

    Science.gov (United States)

    Hand, Timothy W.; Vujkovic-Cvijin, Ivan; Ridaura, Vanessa K.; Belkaid, Yasmine

    2016-01-01

    Chronic inflammatory diseases are the most important causes of mortality in the world today and are on the rise. We now know that immune-driven inflammation is critical in the etiology of these diseases, though the environmental triggers and cellular mechanisms that lead to their development are still mysterious. Many chronic inflammatory diseases are associated with significant shifts in the microbiota towards inflammatory configurations, which can affect the host both by inducing local and systemic inflammation and by alterations in microbiota-derived metabolites. This review discusses recent findings suggesting that shifts in the microbiota may contribute to chronic disease via effects on the immune system. PMID:27623245

  4. Signal transduction of Helicobacter pylori during interaction with host cell protein receptors of epithelial and immune cells

    Science.gov (United States)

    Pachathundikandi, Suneesh Kumar; Tegtmeyer, Nicole; Backert, Steffen

    2013-01-01

    Helicobacter pylori infections can induce pathologies ranging from chronic gastritis, peptic ulceration to gastric cancer. Bacterial isolates harbor numerous well-known adhesins, vacuolating cytotoxin VacA, protease HtrA, urease, peptidoglycan, and type IV secretion systems (T4SS). It appears that H. pylori targets more than 40 known host protein receptors on epithelial or immune cells. A series of T4SS components such as CagL, CagI, CagY, and CagA can bind to the integrin α5β1 receptor. Other targeted membrane-based receptors include the integrins αvβ3, αvβ5, and β2 (CD18), RPTP-α/β, GP130, E-cadherin, fibronectin, laminin, CD46, CD74, ICAM1/LFA1, T-cell receptor, Toll-like receptors, and receptor tyrosine kinases EGFR, ErbB2, ErbB3, and c-Met. In addition, H. pylori is able to activate the intracellular receptors NOD1, NOD2, and NLRP3 with important roles in innate immunity. Here we review the interplay of various bacterial factors with host protein receptors. The contribution of these interactions to signal transduction and pathogenesis is discussed. PMID:24280762

  5. Regular Exercise Enhances the Immune Response Against Microbial Antigens Through Up-Regulation of Toll-like Receptor Signaling Pathways

    Directory of Open Access Journals (Sweden)

    Qishi Zheng

    2015-09-01

    Full Text Available Background/Aims: Regular physical exercise can enhance resistance to many microbial infections. However, little is known about the mechanism underlying the changes in the immune system induced by regular exercise. Methods: We recruited members of a university badminton club as the regular exercise (RE group and healthy sedentary students as the sedentary control (SC group. We investigated the distribution of peripheral blood mononuclear cell (PBMC subsets and functions in the two groups. Results: There were no significant differences in plasma cytokine levels between the RE and SC groups in the true resting state. However, enhanced levels of IFN-γ, TNF-α, IL-6, IFN-α and IL-12 were secreted by PBMCs in the RE group following microbial antigen stimulation, when compared to the SC group. In contrast, the levels of TNF-α and IL-6 secreted by PBMC in the RE group were suppressed compared with those in SC group following non-microbial antigen stimulation (concanavalin A or α-galactosylceramide. Furthermore, PBMC expression of TLR2, TLR7 and MyD88 was significantly increased in the RE group in response to microbial antigen stimulation. Conclusion: Regular exercise enhances immune cell activation in response to pathogenic stimulation leading to enhanced cytokine production mediated via the TLR signaling pathways.

  6. Mechanistic insights into the role of C-type lectin receptor/CARD9 signaling in human antifungal immunity

    Directory of Open Access Journals (Sweden)

    Rebecca A. Drummond

    2016-04-01

    Full Text Available Human CARD9 deficiency is an autosomal recessive primary immunodeficiency disorder caused by biallelic mutations in the gene CARD9, which encodes a signaling protein that is found downstream of many C-type lectin receptors (CLRs. CLRs encompass a large family of innate recognition receptors, expressed predominantly by myeloid and epithelial cells, which bind fungal carbohydrates and initiate antifungal immune responses. Accordingly, human CARD9 deficiency is associated with the spontaneous development of persistent and severe fungal infections that primarily localize to the skin and subcutaneous tissue, mucosal surfaces and/or central nervous system (CNS. In the last few years, more than 15 missense and nonsense CARD9 mutations have been reported which associate with the development of a wide spectrum of fungal infections caused by a variety of fungal organisms. The mechanisms by which CARD9 provides organ-specific protection against these fungal infections are now emerging. In this review, we summarize recent immunological and clinical advances that have provided significant mechanistic insights into the pathogenesis of human CARD9 deficiency. We also discuss how genetic mutations in CARD9-coupled receptors (Dectin-1, Dectin-2 and CARD9-binding partners (MALT1, BCL10 affect human antifungal immunity relative to CARD9 deficiency, and we highlight major understudied research questions which merit future investigation.

  7. Behavioural fever is a synergic signal amplifying the innate immune response.

    Science.gov (United States)

    Boltaña, Sebastian; Rey, Sonia; Roher, Nerea; Vargas, Reynaldo; Huerta, Mario; Huntingford, Felicity Anne; Goetz, Frederick William; Moore, Janice; Garcia-Valtanen, Pablo; Estepa, Amparo; Mackenzie, S

    2013-09-07

    Behavioural fever, defined as an acute change in thermal preference driven by pathogen recognition, has been reported in a variety of invertebrates and ectothermic vertebrates. It has been suggested, but so far not confirmed, that such changes in thermal regime favour the immune response and thus promote survival. Here, we show that zebrafish display behavioural fever that acts to promote extensive and highly specific temperature-dependent changes in the brain transcriptome. The observed coupling of the immune response to fever acts at the gene-environment level to promote a robust, highly specific time-dependent anti-viral response that, under viral infection, increases survival. Fish that are not offered a choice of temperatures and that therefore cannot express behavioural fever show decreased survival under viral challenge. This phenomenon provides an underlying explanation for the varied functional responses observed during systemic fever. Given the effects of behavioural fever on survival and the fact that it exists across considerable phylogenetic space, such immunity-environment interactions are likely to be under strong positive selection.

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

    OpenAIRE

    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...

  9. Immune system handling time may alter the outcome of competition between pathogens and the immune system.

    Science.gov (United States)

    Greenspoon, Philip B; Banton, Sydney; Mideo, Nicole

    2018-06-14

    Predators may be limited in their ability to kill prey (i.e., have type II or III functional responses), an insight that has had far-reaching consequences in the ecological literature. With few exceptions, however, this possibility has not been extended to the behaviour of immune cells, which kill pathogens much as predators kill their prey. Rather, models of the within-host environment have tended to tacitly assume that immune cells have an unlimited ability to target and kill pathogens (i.e., a type I functional response). Here we explore the effects of changing this assumption on infection outcomes (i.e., pathogen loads). We incorporate immune cell handling time into an ecological model of the within-host environment that considers both the predatory nature of the pathogen-immune cell interaction as well as competition between immune cells and pathogens for host resources. Unless pathogens can preempt immune cells for host resources, adding an immune cell handling time increases equilibrium pathogen load. We find that the shape of the relationship between energy intake and pathogen load can change: with a type I functional response, pathogen load is maximised at intermediate inputs, while for a type II or III functional response, pathogen load is solely increasing. With a type II functional response, pathogen load can fluctuate rather than settling to an equilibrium, a phenomenon unobserved with type I or III functional responses. Our work adds to a growing literature highlighting the role of resource availability in host-parasite interactions. Implications of our results for adaptive anorexia are discussed. Copyright © 2018 Elsevier Ltd. All rights reserved.

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

    Science.gov (United States)

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

    2017-08-01

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

  11. Why the Immune System Should Be Concerned by Nanomaterials?

    Directory of Open Access Journals (Sweden)

    Marc J. Pallardy

    2017-05-01

    Full Text Available Particles possess huge specific surface area and therefore nanomaterials exhibit unique characteristics, such as special physical properties and chemical hyper-reactivity, which make them particularly attractive but also raise numerous questions concerning their safety. Interactions of nanomaterials with the immune system can potentially lead to immunosuppression, hypersensitivity (allergy, immunogenicity and autoimmunity, involving both innate and adaptive immune responses. Inherent physical and chemical NP characteristics may influence their immunotoxicity, i.e., the adverse effects that can result from exposure. This review will focus on the possible interaction of nanomaterials including protein aggregates with the innate immune system with specific emphasis on antigen-presenting cells, i.e., dendritic cells, macrophages and monocytes.

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

    Science.gov (United States)

    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. © 2014 American Society of Plant Biologists. All Rights Reserved.

  13. Investigating immune system aging: system dynamics and agent-based modeling

    OpenAIRE

    Figueredo, Grazziela; Aickelin, Uwe

    2010-01-01

    System dynamics and agent based simulation models can\\ud both be used to model and understand interactions of entities within a population. Our modeling work presented here is concerned with understanding the suitability of the different types of simulation for the immune system aging problems and comparing their results. We are trying to answer questions such as: How fit is the immune system given a certain age? Would an immune boost be of therapeutic value, e.g. to improve the effectiveness...

  14. The Role of Epigenetic Regulation in Transcriptional Memory in the Immune System.

    Science.gov (United States)

    Woodworth, A M; Holloway, A F

    The immune system is exquisitely poised to identify, respond to, and eradicate pathogens from the body, as well as to produce a more rapid and augmented response to a subsequent encounter with the pathogen. These cellular responses rely on the highly coordinated and rapid activation of gene expression programs as well as the ability of the cell to retain a memory of the initial gene response. It is clear that chromatin structure and epigenetic mechanisms play a crucial role in determining these gene responses, and in fact the immune system has proved an instructive model for investigating the multifaceted mechanisms through which the chromatin landscape contributes to gene expression programs. These mechanisms include modifications to the DNA and histone proteins, the positioning, composition, and remodeling of nucleosomes, as well as the formation of higher-order chromatin structures. Moreover, it is now apparent that epigenetic mechanisms also provide an instrument by which cells can retain memory of the initial transcriptional response, "priming" the genome so that it can respond more quickly to subsequent exposure to the signal. Here, we use the immune system as a model to demonstrate the complex interplay between transcription factors and the chromatin landscape required to orchestrate precise gene responses to external stimuli and further to demonstrate how these interactions can establish memory of past transcriptional events. We focus on what we have learnt from the immune system and how this can inform our understanding of other cellular systems. © 2017 Elsevier Inc. All rights reserved.

  15. The Adaptive Immune System of Haloferax volcanii

    Directory of Open Access Journals (Sweden)

    Lisa-Katharina Maier

    2015-02-01

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

  16. The role of glycans in immune evasion: the human fetoembryonic defence system hypothesis revisited.

    Science.gov (United States)

    Clark, Gary F

    2014-03-01

    Emerging data suggest that mechanisms to evade the human immune system may be shared by the conceptus, tumour cells, persistent pathogens and viruses. It is therefore timely to revisit the human fetoembryonic defense system (Hu-FEDS) hypothesis that was proposed in two papers in the 1990s. The initial paper suggested that glycoconjugates expressed in the human reproductive system inhibited immune responses directed against gametes and the developing human by employing their carbohydrate sequences as functional groups. These glycoconjugates were proposed to block specific binding interactions and interact with lectins linked to signal transduction pathways that modulated immune cell functions. The second article suggested that aggressive tumour cells and persistent pathogens (HIV, H. pylori, schistosomes) either mimicked or acquired the same carbohydrate functional groups employed in this system to evade immune responses. This subterfuge enabled these pathogens and tumour cells to couple their survival to the human reproductive imperative. The Hu-FEDS model has been repeatedly tested since its inception. Data relevant to this model have also been obtained in other studies. Herein, the Hu-FEDS hypothesis is revisited in the context of these more recent findings. Far more supportive evidence for this model now exists than when it was first proposed, and many of the original predictions have been validated. This type of subterfuge by pathogens and tumour cells likely applies to all sexually reproducing metazoans that must protect their gametes from immune responses. Intervention in these pathological states will likely remain problematic until this system of immune evasion is fully understood and appreciated.

  17. The contribution of the immune system to parturition

    Directory of Open Access Journals (Sweden)

    R. De Jongh

    1996-01-01

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

  18. A Novel Automatic Detection System for ECG Arrhythmias Using Maximum Margin Clustering with Immune Evolutionary Algorithm

    Directory of Open Access Journals (Sweden)

    Bohui Zhu

    2013-01-01

    Full Text Available This paper presents a novel maximum margin clustering method with immune evolution (IEMMC for automatic diagnosis of electrocardiogram (ECG arrhythmias. This diagnostic system consists of signal processing, feature extraction, and the IEMMC algorithm for clustering of ECG arrhythmias. First, raw ECG signal is processed by an adaptive ECG filter based on wavelet transforms, and waveform of the ECG signal is detected; then, features are extracted from ECG signal to cluster different types of arrhythmias by the IEMMC algorithm. Three types of performance evaluation indicators are used to assess the effect of the IEMMC method for ECG arrhythmias, such as sensitivity, specificity, and accuracy. Compared with K-means and iterSVR algorithms, the IEMMC algorithm reflects better performance not only in clustering result but also in terms of global search ability and convergence ability, which proves its effectiveness for the detection of ECG arrhythmias.

  19. Oxysterol-EBI2 signaling in immune regulation and viral infection

    DEFF Research Database (Denmark)

    Daugvilaite, Viktorija; Arfelt, Kristine Niss; Benned-Jensen, Tau

    2014-01-01

    The seven transmembrane G protein-coupled receptor Epstein-Barr virus (EBV) induced gene 2 (EBI2; also known as GPR183) was identified in 1993 on the basis of its substantial upregulation in EBV-infected cells. It is primarily expressed in lymphoid cells; most abundantly in B cells. EBI2 is central...... in the EBV life cycle. We also summarize the structural and functional properties of EBI2 interaction with oxysterol agonists and small molecule antagonists and discuss EBI2 as therapeutic target for diseases of the immune system....

  20. Signal conditioning circuitry design for instrumentation systems.

    Energy Technology Data Exchange (ETDEWEB)

    Larsen, Cory A.

    2012-01-01

    This report details the current progress in the design, implementation, and validation of the signal conditioning circuitry used in a measurement instrumentation system. The purpose of this text is to document the current progress of a particular design in signal conditioning circuitry in an instrumentation system. The input of the signal conditioning circuitry comes from a piezoresistive transducer and the output will be fed to a 250 ksps, 12-bit analog-to-digital converter (ADC) with an input range of 0-5 V. It is assumed that the maximum differential voltage amplitude input from the sensor is 20 mV with an unknown, but presumably high, sensor bandwidth. This text focuses on a specific design; however, the theory is presented in such a way that this text can be used as a basis for future designs.

  1. Power systems signal processing for smart grids

    CERN Document Server

    Ribeiro, Paulo Fernando; Ribeiro, Paulo Márcio; Cerqueira, Augusto Santiago

    2013-01-01

    With special relation to smart grids, this book provides clear and comprehensive explanation of how Digital Signal Processing (DSP) and Computational Intelligence (CI) techniques can be applied to solve problems in the power system. Its unique coverage bridges the gap between DSP, electrical power and energy engineering systems, showing many different techniques applied to typical and expected system conditions with practical power system examples. Surveying all recent advances on DSP for power systems, this book enables engineers and researchers to understand the current state of the art a

  2. Artificial immune system algorithm in VLSI circuit configuration

    Science.gov (United States)

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

    2017-08-01

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

  3. The immune system as a target for antibiotics

    NARCIS (Netherlands)

    Grondel, J.L.

    1986-01-01

    Studies on antibiotics, oxytetracycline (OxyTC) in particular, are presented in this thesis with respect to the influence of these drugs on the immune system of carp and chickens. Special attention was paid to the pharmacokinetic behaviour of

  4. Periodontitis: from microbial immune subversion to systemic inflammation

    Science.gov (United States)

    Hajishengallis, George

    2014-01-01

    Periodontitis is a dysbiotic inflammatory disease with an adverse impact on systemic health. Recent studies have provided insights into the emergence and persistence of dysbiotic oral microbial communities, which can mediate inflammatory pathology at local as well as distant sites. This Review discusses mechanisms of microbial immune subversion that tip the balance from homeostasis to disease in oral or extraoral sites. PMID:25534621

  5. BRAF inhibition improves tumor recognition by the immune system

    DEFF Research Database (Denmark)

    Donia, Marco; Fagone, Paolo; Nicoletti, Ferdinando

    2012-01-01

    to be poorly efficient. By characterizing the immunological interactions between T cells and cancer cells in clinical material as well as the influence of the FDA-approved BRAF inhibitor vemurafenib on the immune system, we aimed at unraveling new strategies to expand the efficacy of adoptive T-cell transfer...

  6. The immune system of cyprinid fish = Immunologie van de karper

    NARCIS (Netherlands)

    Rijkers, G.T.

    1980-01-01

    This study deals with several aspects of the immune system of cyprinid fish.

    Some observations on the development of cellular and humoral responsiveness in rosy barb (Barbus conchonius) are described in appendix I. A humoral anti-sheep red blood cell (SRBC) response was demonstrated in

  7. Immune system as a vital partner in cancer treatment

    Czech Academy of Sciences Publication Activity Database

    Říhová, Blanka; Etrych, Tomáš; Šírová, Milada; Šubr, Vladimír; Ulbrich, Karel

    2015-01-01

    Roč. 8, Supplement 1 (2015), s. 37 ISSN 1875-2292. [7th International Conference on Tumor Microenvironment. 11.10.2015-15.10.2015, Tel Aviv] Institutional support: RVO:61388971 ; RVO:61389013 Keywords : Immune system * cancer treatment * nanomedicines Subject RIV: EC - Immunology OBOR OECD: Immunology

  8. Antioxidant status, immune system, blood metabolites and carcass ...

    African Journals Online (AJOL)

    This experiment was conducted to evaluate the effects of dietary turmeric rhizome powder (TP) on performance, blood metabolite, immune system, antioxidant status, and relative weight of organs in pre and post heat stressed broilers. Two hundred and sixty-four (264) day-old male Arian broiler chicks were randomly ...

  9. Targeting the humoral immune system of patients with rheumatoid arthritis

    NARCIS (Netherlands)

    Teng, Yoe Kie Onno

    2008-01-01

    The aim of this thesis was to unravel the role of the humoral immune system in rheumatoid arthritis patients by employing new immunosuppressive strategies, i.e. specific B-cell depletion with Rituximab and non-specific lymfoablative treatment with high dose chemotherapy and hematopoeietic stem cell

  10. For better or worse: Immune system involvement in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Emma L. Walton

    2018-02-01

    Full Text Available In this issue of the Biomedical Journal, we explore the key role of the immune system in the development of Alzheimer's disease. We also learn more about the link between two disorders related to metabolic imbalances, with findings that could help to inform future screening programs. Finally, we would like to highlight some big news for our journal: the Biomedical Journal will be indexed in the Science Citation Index and receive its first official impact factor from this year. Keywords: Alzheimer's disease, Tau, Immune responses, Subclinical hypothyroidism, Metabolic disease

  11. Power systems signal processing for smart grids

    NARCIS (Netherlands)

    Ribeiro, P.F.; Duque, C.A.; Da Silveira, P.M.; Cerqueira, A.S.

    2013-01-01

    With special relation to smart grids, this book provides clear and comprehensive explanation of how Digital Signal Processing (DSP) and Computational Intelligence (CI) techniques can be applied to solve problems in the power system. Its unique coverage bridges the gap between DSP, electrical power

  12. The Role of Innate Immune System Receptors in Epilepsy Research.

    Science.gov (United States)

    Cordero-Arreola, Jessica; West, Rachel M; Mendoza-Torreblanca, Julieta; Mendez-Hernandez, Edna; Salas-Pacheco, Jose; Menendez-Gonzalez, Manuel; Freire, Rafael C; Machado, Sergio; Murillo-Rodriguez, Eric; Nardi, Antonio E; Arias-Carrion, Oscar

    2017-01-01

    Epilepsy is one of the most complex neurological disorders and its study requires a broad knowledge of neurology and neuroscience. It comprises a diverse group of neurological disorders that share the central feature of spontaneous recurrent seizures, and are often accompanied by cognitive deficits and mood disorder. This condition is one of the most common neurological disorders. Until recently, alterations of neuronal activities had been the focus of epilepsy research. This neurocentric emphasis did not address issues that arise in more complex models of epileptogenesis. An important factor in epilepsy that is not regulated directly by neurons is inflammation and the immune response of the brain. Recent evidence obtained in rodent epilepsy models supports the role of immune responses in the initiation and maintenance of epilepsy. Recognition of exogenous pathogens by the innate immune system is mediated by some pattern recognition receptors such as Toll-like receptors leading to cell activation and cytokine production. Currently, these receptors have been the focus of epilepsy studies looking to determine whether the innate immune activation is neuroprotective or neurotoxic for the brain. Here, we present the evidence in the literature of the involvement of key innate immune receptors in the development of epilepsy. We address some of the contradictory findings in these studies and also mention possible avenues for research into epilepsy treatments that target these receptors. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. Haptic teleoperation systems signal processing perspective

    CERN Document Server

    Lee, Jae-young

    2015-01-01

    This book examines the signal processing perspective in haptic teleoperation systems. This text covers the topics of prediction, estimation, architecture, data compression, and error correction that can be applied to haptic teleoperation systems. The authors begin with an overview of haptic teleoperation systems, then look at a Bayesian approach to haptic teleoperation systems. They move onto a discussion of haptic data compression, haptic data digitization and forward error correction.   ·         Presents haptic data prediction/estimation methods that compensate for unreliable networks   ·         Discusses haptic data compression that reduces haptic data size over limited network bandwidth and haptic data error correction that compensate for packet loss problem   ·         Provides signal processing techniques used with existing control architectures.

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

    Science.gov (United States)

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

    2017-05-01

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

  15. Regulation of TGFβ in the immune system: An emerging role for integrins and dendritic cells

    OpenAIRE

    Worthington, John J.; Fenton, Thomas M.; Czajkowska, Beata I.; Klementowicz, Joanna E.; Travis, Mark A.

    2012-01-01

    Regulation of an immune response requires complex crosstalk between cells of the innate and adaptive immune systems, via both cell?cell contact and secretion of cytokines. An important cytokine with a broad regulatory role in the immune system is transforming growth factor-? (TGF-?). TGF-? is produced by and has effects on many different cells of the immune system, and plays fundamental roles in the regulation of immune responses during homeostasis, infection and disease. Although many cells ...

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

    International Nuclear Information System (INIS)

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

    2016-01-01

    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 15 years of research on the immunotoxicity of engineered nanomaterials. - Graphical abstract: API — active pharmaceutical ingredient; NP — nanoparticles; PCP — physicochemical properties, CARPA — complement activation-related pseudoallergy, ICH — International Conference on Harmonization. Display Omitted - Highlights: • Achievements, disappointments and lessons learned over past decade are reviewed. • Areas in focus include characterization, immunotoxicity and utility in drug delivery. • Future direction focusing on mechanistic immunotoxicity studies is proposed.

  17. Salmonella enterica Induces And Subverts The Plant Immune System

    Directory of Open Access Journals (Sweden)

    Ana Victoria Garcia

    2014-04-01

    Full Text Available Infections with Salmonella enterica belong to the most prominent causes of food poisoning and infected fruits and vegetables represent important vectors for salmonellosis. Whereas it was shown that plants raise defense responses against Salmonella, these bacteria persist and proliferate in various plant tissues. Recent reports shed light into the molecular interaction between plants and Salmonella, highlighting the defense pathways induced and the means used by the bacteria to escape the plant immune system and accomplish colonization. It was recently shown that plants detect Salmonella pathogen-associated molecular patterns (PAMPs, such as the flagellin peptide flg22, and activate hallmarks of the defense program known as PAMP-triggered immunity (PTI. Interestingly, certain Salmonella strains carry mutations in the flg22 domain triggering PTI, suggesting that a strategy of Salmonella is to escape plant detection by mutating PAMP motifs. Another strategy may rely on the type III secretion system (T3SS as T3SS mutants were found to induce stronger plant defense responses than wild type bacteria. Although Salmonella effector delivery into plant cells has not been shown, expression of Salmonella effectors in plant tissues shows that these bacteria also possess powerful means to manipulate the plant immune system. Altogether, the data gathered suggest that Salmonella triggers PTI in plants and evolved strategies to avoid or subvert plant immunity.

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

    Energy Technology Data Exchange (ETDEWEB)

    Dobrovolskaia, Marina A., E-mail: marina@mail.nih.gov [Nanotechnology Characterization Laboratory, Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, NCI at Frederick, Frederick, MD 21702 (United States); Shurin, Michael [Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Department of Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213 (United States); Shvedova, Anna A., E-mail: ats1@cdc.gov [Health Effects Laboratory Division, National Institute of Occupational Safety and Health, Centers for Disease Control and Prevention, Morgantown, WV 26505 (United States); Department of Physiology and Pharmacology, West Virginia University, Morgantown, WV 26506 (United States)

    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 15 years of research on the immunotoxicity of engineered nanomaterials. - Graphical abstract: API — active pharmaceutical ingredient; NP — nanoparticles; PCP — physicochemical properties, CARPA — complement activation-related pseudoallergy, ICH — International Conference on Harmonization. Display Omitted - Highlights: • Achievements, disappointments and lessons learned over past decade are reviewed. • Areas in focus include characterization, immunotoxicity and utility in drug delivery. • Future direction focusing on mechanistic immunotoxicity studies is proposed.

  19. Salmonella enterica induces and subverts the plant immune system

    KAUST Repository

    García, Ana V.

    2014-04-04

    Infections with Salmonella enterica belong to the most prominent causes of food poisoning and infected fruits and vegetables represent important vectors for salmonellosis. Although it was shown that plants raise defense responses against Salmonella, these bacteria persist and proliferate in various plant tissues. Recent reports shed light into the molecular interaction between plants and Salmonella, highlighting the defense pathways induced and the means used by the bacteria to escape the plant immune system and accomplish colonization. It was recently shown that plants detect Salmonella pathogen-associated molecular patterns (PAMPs), such as the flagellin peptide flg22, and activate hallmarks of the defense program known as PAMP-triggered immunity (PTI). Interestingly, certain Salmonella strains carry mutations in the flg22 domain triggering PTI, suggesting that a strategy of Salmonella is to escape plant detection by mutating PAMP motifs. Another strategy may rely on the type III secretion system (T3SS) as T3SS mutants were found to induce stronger plant defense responses than wild type bacteria. Although Salmonella effector delivery into plant cells has not been shown, expression of Salmonella effectors in plant tissues shows that these bacteria also possess powerful means to manipulate the plant immune system. Altogether, these data suggest that Salmonella triggers PTI in plants and evolved strategies to avoid or subvert plant immunity. 2014 Garca and Hirt.

  20. Engineering Plant Immunity via CRISPR/Cas13a System

    KAUST Repository

    Aljedaani, Fatimah R.

    2018-05-01

    Viral diseases constitute a major threat to the agricultural production and food security throughout the world. Plants cope with the invading viruses by triggering immune responses and small RNA interference (RNAi) systems. In prokaryotes, CRISPR/Cas systems function as an adaptive immune system to provide bacteria with resistance against invading phages and conjugative plasmids. Interestingly, CRISPR/Cas9 system was shown to interfere with eukaryotic DNA viruses and confer resistance against plant DNA viruses. The majority of the plant viruses have RNA genomes. The aim of this study is to test the ability of the newly discovered CRISPR/Cas13a immune system, that targets and cleaves single stranded RNA (ssRNA) in prokaryotes, to provide resistance against RNA viruses in plants. Here, I employ the CRISPR/Cas13a system for molecular interference against Turnip Mosaic Virus (TuMV), a plant RNA virus. The results of this study established the CRISPR/Cas13a as a molecular interference machinery against RNA viruses in plants. Specifically, my data show that the CRISPR/Cas13a machinery is able to interfere with and degrade the TuMV (TuMV-GFP) RNA genome. In conclusion, these data indicate that the CRISPR/Cas13 systems can be employed for engineering interference and durable resistance against RNA viruses in diverse plant species.

  1. Control of an automated mobile manipulator using artificial immune system

    Science.gov (United States)

    Deepak, B. B. V. L.; Parhi, Dayal R.

    2016-03-01

    This paper addresses the coordination and control of a wheeled mobile manipulator (WMM) using artificial immune system. The aim of the developed methodology is to navigate the system autonomously and transport jobs and tools in manufacturing environments. This study integrates the kinematic structures of a four-axis manipulator and a differential wheeled mobile platform. The motion of the developed WMM is controlled by the complete system of parametric equation in terms of joint velocities and makes the robot to follow desired trajectories by the manipulator and platform within its workspace. The developed robot system performs its action intelligently according to the sensed environmental criteria within its search space. To verify the effectiveness of the proposed immune-based motion planner for WMM, simulations as well as experimental results are presented in various unknown environments.

  2. Effects of PM2.5 exposure on the Notch signaling pathway and immune imbalance in chronic obstructive pulmonary disease

    International Nuclear Information System (INIS)

    Gu, Xing-yu; Chu, Xu; Zeng, Xiao-Li; Bao, Hai-Rong; Liu, Xiao-Ju

    2017-01-01

    Chronic Obstructive Pulmonary Disease (COPD) is associated with T lymphocytes subset (Th1/Th2, Th17/Treg) imbalance. Notch signaling pathway plays a key role in the development of the adaptive immunity. The immune disorder induced by fine particulate matter (PM2.5) is related to COPD. The aim of this study was to investigate the mechanism by which PM2.5 influences the Notch signaling pathway leading to worsening immune disorder and accelerating COPD development. A COPD mouse model was established by cigarette smoke exposure. PM2.5 exposure was performed by aerosol inhalation. γ-secretase inhibitor (GSI) was given using intraperitoneal injection. Splenic T lymphocytes were purified using a density gradient centrifugation method. CD4 + T lymphocyte subsets (Th1/Th2, Th17/Treg) were detected using flow cytometry. mRNA and proteins of Notch1/2/3/4, Hes1/5, and Hey1 were detected using RT-PCR and Western blot. Serum INF-γ, IL-4, IL-17 and IL-10 concentrations were measured using ELISA. The results showed that in COPD mice Th1% and Th17%, Th1/Th2 and Th17/Treg were increased, and the levels of mRNA and protein in Notch1/2/3/4, Hes1/5, and Hey1 and serum INF-γ and IL-17 concentrations were significantly increased, and Th2%, Treg%, and serum IL-4 and IL-10 concentrations were significantly decreased. COPD Mice have Th1- and Th17-mediated immune disorder, and the Notch signaling pathway is in an overactivated state. PM2.5 promotes the overactivation of the Notch signaling pathway and aggravates the immune disorder of COPD. GSI can partially inhibit the activation of the Notch signaling pathway and alleviate the immune disorder under basal state and the immune disorder of COPD caused by PM2.5. This result suggests that PM2.5 is involved in the immune disorder of mice with COPD by affecting the Notch signaling pathway and that PM2.5 aggravates COPD. - Highlights: • The COPD mice demonstrated Th1 and Th17 dominant immune imbalance. • PM2.5 aggravates the Th1/Th2 and Th

  3. Ovarian cancer and the immune system - The role of targeted therapies.

    Science.gov (United States)

    Turner, Taylor B; Buchsbaum, Donald J; Straughn, J Michael; Randall, Troy D; Arend, Rebecca C

    2016-08-01

    The majority of patients with epithelial ovarian cancer are diagnosed with advanced disease. While many of these patients will respond initially to chemotherapy, the majority will relapse and die of their disease. Targeted therapies that block or activate specific intracellular signaling pathways have been disappointing. In the past 15years, the role of the immune system in ovarian cancer has been investigated. Patients with a more robust immune response, as documented by the presence of lymphocytes infiltrating within their tumor, have increased survival and better response to chemotherapy. In addition, a strong immunosuppressive environment often accompanies ovarian cancer. Recent research has identified potential therapies that leverage the immune system to identify and destroy tumor cells that previously evaded immunosurveillance mechanisms. In this review, we discuss the role of the immune system in ovarian cancer and focus on specific pathways and molecules that show a potential for targeted therapy. We also review the ongoing clinical trials using targeted immunotherapy in ovarian cancer. The role of targeted immunotherapy in patients with ovarian cancer represents a field of growing research and clinical importance. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Up in arms: Immune and nervous system response to sea star wasting disease

    Science.gov (United States)

    Fuess, Lauren E; Eiselord, Morgan E.; Closek, Collin J.; Tracy, Allison M.; Mauntz, Ruth; Gignoux-Wolfsohn, Sarah; Moritsch, Monica M; Yoshioka, Reyn; Burge, Colleen A.; Harvell, Drew; Friedman, Carolyn S.; Hershberger, Paul K.; Roberts, Steven B.

    2015-01-01

    Echinoderms, positioned taxonomically at the base of deuterostomes, provide an important system for the study of the evolution of the immune system. However, there is little known about the cellular components and genes associated with echinoderm immunity. The 2013–2014 sea star wasting disease outbreak is an emergent, rapidly spreading disease, which has led to large population declines of asteroids in the North American Pacific. While evidence suggests that the signs of this disease, twisting arms and lesions, may be attributed to a viral infection, the host response to infection is still poorly understood. In order to examine transcriptional responses of the sea star Pycnopodia helianthoides to sea star wasting disease, we injected a viral sized fraction (0.2 μm) homogenate prepared from symptomatic P. helianthoides into apparently healthy stars. Nine days following injection, when all stars were displaying signs of the disease, specimens were sacrificed and coelomocytes were extracted for RNA-seq analyses. A number of immune genes, including those involved in Toll signaling pathways, complement cascade, melanization response, and arachidonic acid metabolism, were differentially expressed. Furthermore, genes involved in nervous system processes and tissue remodeling were also differentially expressed, pointing to transcriptional changes underlying the signs of sea star wasting disease. The genomic resources presented here not only increase understanding of host response to sea star wasting disease, but also provide greater insight into the mechanisms underlying immune function in echinoderms.

  5. Helmet-based physiological signal monitoring system.

    Science.gov (United States)

    Kim, Youn Sung; Baek, Hyun Jae; Kim, Jung Soo; Lee, Haet Bit; Choi, Jong Min; Park, Kwang Suk

    2009-02-01

    A helmet-based system that was able to monitor the drowsiness of a soldier was developed. The helmet system monitored the electrocardiogram, electrooculogram and electroencephalogram (alpha waves) without constraints. Six dry electrodes were mounted at five locations on the helmet: both temporal sides, forehead region and upper and lower jaw strips. The electrodes were connected to an amplifier that transferred signals to a laptop computer via Bluetooth wireless communication. The system was validated by comparing the signal quality with conventional recording methods. Data were acquired from three healthy male volunteers for 12 min twice a day whilst they were sitting in a chair wearing the sensor-installed helmet. Experimental results showed that physiological signals for the helmet user were measured with acceptable quality without any intrusions on physical activities. The helmet system discriminated between the alert and drowsiness states by detecting blinking and heart rate variability (HRV) parameters extracted from ECG. Blinking duration and eye reopening time were increased during the sleepiness state compared to the alert state. Also, positive peak values of the sleepiness state were much higher, and the negative peaks were much lower than that of the alert state. The LF/HF ratio also decreased during drowsiness. This study shows the feasibility for using this helmet system: the subjects' health status and mental states could be monitored without constraints whilst they were working.

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

    Science.gov (United States)

    Barrangou, Rodolphe; Marraffini, Luciano A

    2014-04-24

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

  7. The Microbiota, the Immune System and the Allograft

    Science.gov (United States)

    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

  8. Controlling Cytomegalovirus: Helping the Immune System Take the Lead

    Directory of Open Access Journals (Sweden)

    Patrick J. Hanley

    2014-05-01

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

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

    Science.gov (United States)

    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. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Intestinal epithelial cell-specific RARα depletion results in aberrant epithelial cell homeostasis and underdeveloped immune system.

    Science.gov (United States)

    Jijon, H B; Suarez-Lopez, L; Diaz, O E; Das, S; De Calisto, J; Yaffe, M B; Pittet, M J; Mora, J R; Belkaid, Y; Xavier, R J; Villablanca, E J

    2018-05-01

    Retinoic acid (RA), a dietary vitamin A metabolite, is crucial in maintaining intestinal homeostasis. RA acts on intestinal leukocytes to modulate their lineage commitment and function. Although the role of RA has been characterized in immune cells, whether intestinal epithelial cells (IECs) rely on RA signaling to exert their immune-regulatory function has not been examined. Here we demonstrate that lack of RA receptor α (RARα) signaling in IECs results in deregulated epithelial lineage specification, leading to increased numbers of goblet cells and Paneth cells. Mechanistically, lack of RARα resulted in increased KLF4 + goblet cell precursors in the distal bowel, whereas RA treatment inhibited klf4 expression and goblet cell differentiation in zebrafish. These changes in secretory cells are associated with increased Reg3g, reduced luminal bacterial detection, and an underdeveloped intestinal immune system, as evidenced by an almost complete absence of lymphoid follicles and gut resident mononuclear phagocytes. This underdeveloped intestinal immune system shows a decreased ability to clear infection with Citrobacter rodentium. Collectively, our findings indicate that epithelial cell-intrinsic RARα signaling is critical to the global development of the intestinal immune system.

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

    Science.gov (United States)

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

    2016-11-01

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

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

    Science.gov (United States)

    Zheng, Qianqian; Shen, Jianwei; Wang, Zhijie

    2018-01-01

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

  13. Purinergic signaling pathways in endocrine system.

    Science.gov (United States)

    Bjelobaba, Ivana; Janjic, Marija M; Stojilkovic, Stanko S

    2015-09-01

    Adenosine-5'-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5'-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5'-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5'-triphosphate hydrolysis to adenosine-5'-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. Published by Elsevier B.V.

  14. Purinergic Signaling Pathways in Endocrine System

    Science.gov (United States)

    Bjelobaba, Ivana; Janjic, Marija M.; Stojilkovic, Stanko S.

    2015-01-01

    Adenosine-5′-triphosphate is released by neuroendocrine, endocrine, and other cell types and acts as an extracellular agonist for ligand-gated P2X cationic channels and G protein-coupled P2Y receptors in numerous organs and tissues, including the endocrine system. The breakdown of ATP by ectonucleotidases not only terminates its extracellular messenger functions, but also provides a pathway for the generation of two additional agonists: adenosine 5′-diphosphate, acting via some P2Y receptors, and adenosine, a native agonist for G protein-coupled adenosine receptors, also expressed in the endocrine system. This article provides a review of purinergic signaling pathways in the hypothalamic magnocellular neurosecretory cells and neurohypophysis, hypothalamic parvocellular neuroendocrine system, adenohypophysis, and effector glands organized in five axes: hypothalamic-pituitary-gonadal, hypothalamic-pituitary-thyroid, hypothalamic-pituitary-adrenal, hypothalamic-pituitary-growth hormone, and hypothalamic-pituitary-prolactin. We attempted to summarize current knowledge of purinergic receptor subtypes expressed in the endocrine system, including their roles in intracellular signaling, hormone secretion, and other cell functions. We also briefly review the release mechanism for adenosine-5′-triphosphate by neuroendocrine, endocrine and surrounding cells, the enzymes involved in adenosine-5′-triphosphate hydrolysis to adenosine-5′-diphosphate and adenosine, and the relevance of this pathway for sequential activation of receptors and termination of signaling. PMID:25960051

  15. Role of immune system in type 1 diabetes mellitus pathogenesis.

    Science.gov (United States)

    Szablewski, Leszek

    2014-09-01

    The immune system is the body's natural defense system against invading pathogens. It protects the body from infection and works to communicate an individual's well-being through a complex network of interconnected cells and cytokines. This system is an associated host defense. An uncontrolled immune system has the potential to trigger negative complications in the host. Type 1 diabetes results from the destruction of pancreatic β-cells by a β-cell-specific autoimmune process. Examples of β-cell autoantigens are insulin, glutamic acid decarboxylase, tyrosine phosphatase, and insulinoma antigen. There are many autoimmune diseases, but type 1 diabetes mellitus is one of the well-characterized autoimmune diseases. The mechanisms involved in the β-cell destruction are still not clear; it is generally believed that β-cell autoantigens, macrophages, dendritic cells, B lymphocytes, and T lymphocytes are involved in the β-cell-specific autoimmune process. It is necessary to determine what exact factors are causing the immune system to become unregulated in such a manner as to promote an autoimmune response. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Effects of traffic noise on tree frog stress levels, immunity, and color signaling.

    Science.gov (United States)

    Troïanowski, Mathieu; Mondy, Nathalie; Dumet, Adeline; Arcanjo, Caroline; Lengagne, Thierry

    2017-10-01

    During the last decade, many studies have focused on the detrimental effects of noise pollution on acoustic communication. Surprisingly, although it is known that noise exposure strongly influences health in humans, studies on wildlife remain scarce. In order to gain insight into the consequences of traffic noise exposure, we experimentally manipulated traffic noise exposure as well as the endocrine status of animals to investigate physiological and phenotypic consequences of noise pollution in an anuran species. We showed that noise exposure increased stress hormone level and induced an immunosuppressive effect. In addition, both traffic noise exposure and stress hormone application negatively impacted H. arborea vocal sac coloration. Moreover, our results suggest profound changes in sexual selection processes because the best quality males with initial attractive vocal sac coloration were the most impacted by noise. Hence, our study suggests that the recent increases in anthropogenic noise worldwide might affect a broader range of animal species than previously thought, because of alteration of visual signals and immunity. Generalizing these results to other taxa is crucial for the conservation of biodiversity in an increasingly noisy world. © 2017 Society for Conservation Biology.

  17. The Role of Non-specific and Specific Immune Systems in Poultry against Newcastle Disease

    Directory of Open Access Journals (Sweden)

    Dyah Ayu Hewajuli

    2015-09-01

    Full Text Available Newcastle disease (ND is caused by avian paramyxovirus-1 which belong to Avulavirus genus and Paramyxoviridae family. The birds have abnormalities in humoral (bursa fabricius and cellular (thymus and spleen lymphoid organs. Lesions decrease the immune system. Immune system consists of non-specific and specific immune systems. The main components of non-specific immunity are physical and chemical barrier (feather and skin or mucosa, phagocytic cells (macrophages and natural killer, protein complement and the mediator of inflammation and cytokines. Interferons (IFNs belong to a group of cytokines that play a major role in the nonspecific or innate (natural immunity. The virulent ND virus encodes protein of V gene can be suppressed IFN type I. This leads to non-specific immune system fail to respond to the virulent strains resulting in severe pathogenicity. The defense mechanism of the host is replaced by specific immunity (adaptive immunity when natural immunity fails to overcome the infection. The specific immune system consists of humoral mediated immunity (HMI and cell-mediated immunity (CMI. The cells of immune system that react specifically with the antigen are B lymphocytes producing the antibodies, T lymphocytes that regulate the synthesis of antibodies and T cells as effector or the direct cytotoxic cells. Both non-specific and specific immunities are complementary against the invasion of ND virus in the birds. The objective of this article is to discuss the role of non specific and specific immune system in ND.

  18. Persisting injuries in immune system and their effects on health in a-bomb survivors

    International Nuclear Information System (INIS)

    Kusunoki, Yoichiro; Hayashi, Tomonori; Kyoizumi, Seishi

    2000-01-01

    This review describes findings concerning persisting effects of A-bomb radiation on immune cells and their relation to diseases. Injuries in immune system are mainly the depression of cellular immunity mediated by T-lymphocytes, especially CD4 T-cells, and the elevation of humoral immunity by B-cells. These are conceivably the imbalance results in immune system of incomplete recovery of those T-cells after exposure and thymus retraction by aging and of consequently affecting the functional differentiation of CD4 T-cells to lower the cellular immunity and to elevate the humoral immunity. Lowered cellular immunity in the survivors can be related to their liver and cardiovascular diseases caused by infection and cancer caused by tumor antigens and oncoviruses. Thus immunological investigations of the survivors are revealing not only the effect of radiation on the immune system but also the correlation between immunity and diseases. (K.H.)

  19. Persisting injuries in immune system and their effects on health in a-bomb survivors

    Energy Technology Data Exchange (ETDEWEB)

    Kusunoki, Yoichiro; Hayashi, Tomonori; Kyoizumi, Seishi [Radiation Effects Research Foundation, Hiroshima (Japan)

    2000-12-01

    This review describes findings concerning persisting effects of A-bomb radiation on immune cells and their relation to diseases. Injuries in immune system are mainly the depression of cellular immunity mediated by T-lymphocytes, especially CD4 T-cells, and the elevation of humoral immunity by B-cells. These are conceivably the imbalance results in immune system of incomplete recovery of those T-cells after exposure and thymus retraction by aging and of consequently affecting the functional differentiation of CD4 T-cells to lower the cellular immunity and to elevate the humoral immunity. Lowered cellular immunity in the survivors can be related to their liver and cardiovascular diseases caused by infection and cancer caused by tumor antigens and oncoviruses. Thus immunological investigations of the survivors are revealing not only the effect of radiation on the immune system but also the correlation between immunity and diseases. (K.H.)

  20. Correlation between obesity, adipokines and the immune system

    Directory of Open Access Journals (Sweden)

    Marcos Regini Silveira

    2009-09-01

    Full Text Available Obesity is a worldwide health problem and the increase in its incidence, risks and consequences are a matter of growing concern. Obesity is characterized by the accumulation of fat in the body. Many studies are currently investigating obesity and associated comorbidities in an attempt to clarify the mechanisms involved. Fat tissue is a dynamic organ that secretes several factors, including adipokines. Adipokines are bioactive peptides secreted by fat cells, which are important for energy regulation and inflammatory and immune responses. Leptin, adiponectin and resistin are the most studied adipokines. The aim of this review was to gather information about these adipokines (leptin, adiponectin and resistin and their relationship with the immune response in obese individuals, as well as the susceptibility of these patients to infections. The results of the literature review permit some observations. The circulating levels of these adipokines are directly involved in the degree of obesity of the patient. High or low circulating concentrations of these adipokines may have beneficial or negative effects on immune competence, with obese patients being more susceptible to infection and inflammation than eutrophic individuals.Key words: Obesity; Adipokines; Leptin; Adiponectin; Resistin; Immune system.

  1. Bim: guardian of tissue homeostasis and critical regulator of the immune system, tumorigenesis and bone biology.

    Science.gov (United States)

    Akiyama, Toru; Tanaka, Sakae

    2011-08-01

    One of the most important roles of apoptosis is the maintenance of tissue homeostasis. Impairment of apoptosis leads to a number of pathological conditions. In response to apoptotic signals, various proteins are activated in a pathway and signal-specific manner. Recently, the pro-apoptotic molecule Bim has attracted increasing attention as a pivotal regulator of tissue homeostasis. The Bim expression level is strictly controlled in both transcriptional and post-transcriptional levels. This control is dependent on cell, tissue and apoptotic stimuli. The phenotype of Bim-deficient mice is a systemic lupus erythematosus-like autoimmune disease with an abnormal accumulation of hematopoietic cells. Bim is thus a critical regulator of hematopoietic cells and immune system. Further studies have revealed the critical roles of Bim in various normal and pathological conditions, including bone homeostasis and tumorigenesis. The current understanding of Bim signaling and roles in the maintenance of tissue homeostasis is reviewed in this paper, focusing on the immune system, bone biology and tumorigenesis to illustrate the diversified role of Bim.

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

    Science.gov (United States)

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

    2016-04-01

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

  3. High-Density Lipoproteins and the Immune System

    Directory of Open Access Journals (Sweden)

    Hidesuke Kaji

    2013-01-01

    Full Text Available High-density lipoprotein (HDL plays a major role in vasodilation and in the reduction of low-density lipoprotein (LDL oxidation, inflammation, apoptosis, thrombosis, and infection; however, HDL is now less functional in these roles under certain conditions. This paper focuses on HDL, its anti-inflammation behavior, and the mechanisms by which HDL interacts with components of the innate and adaptive immune systems. Genome-wide association studies (GWAS and proteomic studies have elucidated important molecules involved in the interaction between HDL and the immune system. An understanding of these mechanisms is expected to be useful for the prevention and treatment of chronic inflammation due to metabolic syndrome, atherosclerosis, or various autoimmune diseases.

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

    Science.gov (United States)

    Schaller, Mark

    2011-12-12

    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.

  5. Polio Endgame: Lessons Learned From the Immunization Systems Management Group.

    Science.gov (United States)

    Zipursky, Simona; Vandelaer, Jos; Brooks, Alan; Dietz, Vance; Kachra, Tasleem; Farrell, Margaret; Ottosen, Ann; Sever, John L; Zaffran, Michel J

    2017-07-01

    The Immunization Systems Management Group (IMG) was established to coordinate and oversee objective 2 of the Polio Eradication and Endgame Strategic Plan 2013-2018, namely, (1) introduction of ≥1 dose of inactivated poliovirus vaccine in all 126 countries using oral poliovirus vaccine (OPV) only as of 2012, (2) full withdrawal of OPV, starting with the withdrawal of its type 2 component, and (3) using polio assets to strengthen immunization systems in 10 priority countries. The IMG's inclusive, transparent, and partnership-focused approach proved an effective means of leveraging the comparative and complementary strengths of each IMG member agency. This article outlines 10 key factors behind the IMG's success, providing a potential set of guiding principles for the establishment and implementation of other interagency collaborations and initiatives beyond the polio sphere. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

  6. The adaptor molecule RIAM integrates signaling events critical for integrin-mediated control of immune function and cancer progression.

    Science.gov (United States)

    Patsoukis, Nikolaos; Bardhan, Kankana; Weaver, Jessica D; Sari, Duygu; Torres-Gomez, Alvaro; Li, Lequn; Strauss, Laura; Lafuente, Esther M; Boussiotis, Vassiliki A

    2017-08-22

    Lymphocyte activation requires adhesion to antigen-presenting cells. This is a critical event linking innate and adaptive immunity. Lymphocyte adhesion is accomplished through LFA-1, which must be activated by a process referred to as inside-out integrin signaling. Among the few signaling molecules that have been implicated in inside-out integrin activation in hematopoietic cells are the small guanosine triphosphatase (GTPase) Rap1 and its downstream effector Rap1-interacting molecule (RIAM), a multidomain protein that defined the Mig10-RIAM-lamellipodin (MRL) class of adaptor molecules. Through its various domains, RIAM is a critical node of signal integration for activation of T cells, recruits monomeric and polymerized actin to drive actin remodeling and cytoskeletal reorganization, and promotes inside-out integrin signaling in T cells. As a regulator of inside-out integrin activation, RIAM affects multiple functions of innate and adaptive immunity. The effects of RIAM on cytoskeletal reorganization and integrin activation have implications in cell migration and trafficking of cancer cells. We provide an overview of the structure and interactions of RIAM, and we discuss the implications of RIAM functions in innate and adaptive immunity and cancer. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

  7. An Immune-inspired Adaptive Automated Intrusion Response System Model

    Directory of Open Access Journals (Sweden)

    Ling-xi Peng

    2012-09-01

    Full Text Available An immune-inspired adaptive automated intrusion response system model, named as , is proposed. The descriptions of self, non-self, immunocyte, memory detector, mature detector and immature detector of the network transactions, and the realtime network danger evaluation equations are given. Then, the automated response polices are adaptively performed or adjusted according to the realtime network danger. Thus, not only accurately evaluates the network attacks, but also greatly reduces the response times and response costs.

  8. Multi-Modal Intelligent Traffic Signal Systems Signal Plans for Roadside Equipment

    Data.gov (United States)

    Department of Transportation — Data were collected during the Multi-Modal Intelligent Transportation Signal Systems (MMITSS) study. MMITSS is a next-generation traffic signal system that seeks to...

  9. Signals and Systems in Biomedical Engineering Signal Processing and Physiological Systems Modeling

    CERN Document Server

    Devasahayam, Suresh R

    2013-01-01

    The use of digital signal processing is ubiquitous in the field of physiology and biomedical engineering. The application of such mathematical and computational tools requires a formal or explicit understanding of physiology. Formal models and analytical techniques are interlinked in physiology as in any other field. This book takes a unitary approach to physiological systems, beginning with signal measurement and acquisition, followed by signal processing, linear systems modelling, and computer simulations. The signal processing techniques range across filtering, spectral analysis and wavelet analysis. Emphasis is placed on fundamental understanding of the concepts as well as solving numerical problems. Graphs and analogies are used extensively to supplement the mathematics. Detailed models of nerve and muscle at the cellular and systemic levels provide examples for the mathematical methods and computer simulations. Several of the models are sufficiently sophisticated to be of value in understanding real wor...

  10. Physiological and pathophysiological bone turnover - role of the immune system.

    Science.gov (United States)

    Weitzmann, M Neale; Ofotokun, Ighovwerha

    2016-09-01

    Osteoporosis develops when the rate of osteoclastic bone breakdown (resorption) exceeds that of osteoblastic bone formation, which leads to loss of BMD and deterioration of bone structure and strength. Osteoporosis increases the risk of fragility fractures, a cause of substantial morbidity and mortality, especially in elderly patients. This imbalance between bone formation and bone resorption is brought about by natural ageing processes, but is frequently exacerbated by a number of pathological conditions. Of importance to the aetiology of osteoporosis are findings over the past two decades attesting to a deep integration of the skeletal system with the immune system (the immuno-skeletal interface (ISI)). Although protective of the skeleton under physiological conditions, the ISI might contribute to bone destruction in a growing number of pathophysiological states. Although numerous research groups have investigated how the immune system affects basal and pathological osteoclastic bone resorption, recent findings suggest that the reach of the adaptive immune response extends to the regulation of osteoblastic bone formation. This Review examines the evolution of the field of osteoimmunology and how advances in our understanding of the ISI might lead to novel approaches to prevent and treat bone loss, and avert fractures.

  11. The Pathology of Orthopedic Implant Failure Is Mediated by Innate Immune System Cytokines

    Directory of Open Access Journals (Sweden)

    Stefan Landgraeber

    2014-01-01

    Full Text Available All of the over 1 million total joint replacements implanted in the US each year are expected to eventually fail after 15–25 years of use, due to slow progressive subtle inflammation at the bone implant interface. This inflammatory disease state is caused by implant debris acting, primarily, on innate immune cells, that is, macrophages. This slow progressive pathological bone loss or “aseptic loosening” is a potentially life-threatening condition due to the serious complications in older people (>75 yrs of total joint replacement revision surgery. In some people implant debris (particles and ions from metals can influence the adaptive immune system as well, giving rise to the concept of metal sensitivity. However, a consensus of studies agrees that the dominant form of this response is due to innate reactivity by macrophages to implant debris where both danger (DAMP and pathogen (PAMP signalling elicit cytokine-based inflammatory responses. This paper discusses implant debris induced release of the cytokines and chemokines due to activation of the innate (and the adaptive immune system and the subsequent formation of osteolysis. Different mechanisms of implant-debris reactivity related to the innate immune system are detailed, for example, danger signalling (e.g., IL-1β, IL-18, IL-33, etc., toll-like receptor activation (e.g., IL-6, TNF-α, etc., apoptosis (e.g., caspases 3–9, bone catabolism (e.g., TRAP5b, and hypoxia responses (Hif1-α. Cytokine-based clinical and basic science studies are in progress to provide diagnosis and therapeutic intervention strategies.

  12. The Pathology of Orthopedic Implant Failure Is Mediated by Innate Immune System Cytokines

    Science.gov (United States)

    Landgraeber, Stefan; Jäger, Marcus; Jacobs, Joshua J.; Hallab, Nadim James

    2014-01-01

    All of the over 1 million total joint replacements implanted in the US each year are expected to eventually fail after 15–25 years of use, due to slow progressive subtle inflammation at the bone implant interface. This inflammatory disease state is caused by implant debris acting, primarily, on innate immune cells, that is, macrophages. This slow progressive pathological bone loss or “aseptic loosening” is a potentially life-threatening condition due to the serious complications in older people (>75 yrs) of total joint replacement revision surgery. In some people implant debris (particles and ions from metals) can influence the adaptive immune system as well, giving rise to the concept of metal sensitivity. However, a consensus of studies agrees that the dominant form of this response is due to innate reactivity by macrophages to implant debris where both danger (DAMP) and pathogen (PAMP) signalling elicit cytokine-based inflammatory responses. This paper discusses implant debris induced release of the cytokines and chemokines due to activation of the innate (and the adaptive) immune system and the subsequent formation of osteolysis. Different mechanisms of implant-debris reactivity related to the innate immune system are detailed, for example, danger signalling (e.g., IL-1β, IL-18, IL-33, etc.), toll-like receptor activation (e.g., IL-6, TNF-α, etc.), apoptosis (e.g., caspases 3–9), bone catabolism (e.g., TRAP5b), and hypoxia responses (Hif1-α). Cytokine-based clinical and basic science studies are in progress to provide diagnosis and therapeutic intervention strategies. PMID:24891761

  13. Role for sumoylation in systemic inflammation and immune homeostasis in Drosophila larvae.

    Directory of Open Access Journals (Sweden)

    Indira Paddibhatla

    2010-12-01

    Full Text Available To counter systemic risk of infection by parasitic wasps, Drosophila larvae activate humoral immunity in the fat body and mount a robust cellular response resulting in encapsulation of the wasp egg. Innate immune reactions are tightly regulated and are resolved within hours. To understand the mechanisms underlying activation and resolution of the egg encapsulation response and examine if failure of the latter develops into systemic inflammatory disease, we correlated parasitic wasp-induced changes in the Drosophila larva with systemic chronic conditions in sumoylation-deficient mutants. We have previously reported that loss of either Cactus, the Drosophila (IκB protein or Ubc9, the SUMO-conjugating enzyme, leads to constitutive activation of the humoral and cellular pathways, hematopoietic overproliferation and tumorogenesis. Here we report that parasite infection simultaneously activates NF-κB-dependent transcription of Spätzle processing enzyme (SPE and cactus. Endogenous Spätzle protein (the Toll ligand is expressed in immune cells and excessive SPE or Spätzle is pro-inflammatory. Consistent with this function, loss of Spz suppresses Ubc9⁻ defects. In contrast to the pro-inflammatory roles of SPE and Spätzle, Cactus and Ubc9 exert an anti-inflammatory effect. We show that Ubc9 maintains steady state levels of Cactus protein. In a series of immuno-genetic experiments, we demonstrate the existence of a robust bidirectional interaction between blood cells and the fat body and propose that wasp infection activates Toll signaling in both compartments via extracellular activation of Spätzle. Within each organ, the IκB/Ubc9-dependent inhibitory feedback resolves immune signaling and restores homeostasis. The loss of this feedback leads to chronic inflammation. Our studies not only provide an integrated framework for understanding the molecular basis of the evolutionary arms race between insect hosts and their parasites, but also offer

  14. Critical role of macrophages and their activation via MyD88-NFκB signaling in lung innate immunity to Mycoplasma pneumoniae.

    Directory of Open Access Journals (Sweden)

    Jen-Feng Lai

    2010-12-01

    Full Text Available Mycoplasma pneumoniae (Mp, a common cause of pneumonia, is associated with asthma; however, the mechanisms underlying this association remain unclear. We investigated the cellular immune response to Mp in mice. Intranasal inoculation with Mp elicited infiltration of the lungs with neutrophils, monocytes and macrophages. Systemic depletion of macrophages, but not neutrophils, resulted in impaired clearance of Mp from the lungs. Accumulation and activation of macrophages were decreased in the lungs of MyD88(-/- mice and clearance of Mp was impaired, indicating that MyD88 is a key signaling protein in the anti-Mp response. MyD88-dependent signaling was also required for the Mp-induced activation of NFκB, which was essential for macrophages to eliminate the microbe in vitro. Thus, MyD88-NFκB signaling in macrophages is essential for clearance of Mp from the lungs.

  15. Influence of Saccharomyces boulardii CNCM I-745 on the gut-associated immune system

    Directory of Open Access Journals (Sweden)

    Stier H

    2016-09-01

    Full Text Available Heike Stier,1 Stephan C Bischoff2 1analyze & realize GmbH, Berlin, 2Department of Clinical Nutrition, University of Hohenheim, Stuttgart, Germany Background: The probiotic Saccharomyces boulardii CNCM I-745 (also known as Saccharomyces cerevisiae HANSEN CBS 5926; in the following S. boulardii has proven its effectiveness in preventive and therapeutic treatment of many gastrointestinal diseases, especially diseases associated with acute diarrhea. In particular, antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, traveller’s diarrhea, as well as acute diarrhea due to common viral and bacterial infections in children and adults.Aim: The aim of this review is to summarize the experimental studies elucidating the molecular and immunological mechanisms by which these clinically proven effects are archived, with an emphasis on the gut-associated immune system. The main focus is laid on anti-inflammatory and immune-modulatory action of S. boulardii involved in bacterial or enterotoxin-mediated diarrhea and inflammation. An attempt is made to differentiate between the effects associated with cellular versus soluble factors and between prophylactic and therapeutic effects.Methods: A literature search was performed in PubMed/PubMed Central for the effects of S. boulardii on the gut-associated immune system (focus acute diarrhea. Results and conclusion: S. boulardii exhibits its positive effect by the direct effects on pathogens or their toxins as well as by influencing the host’s infection-induced signaling cascades and its innate and adaptive immune system. The combination of these mechanisms results in a reduction of the pathogens’ ability for adhesion or colonization and an attenuation of the overreacting inflammatory immune response. Thereby, the integrity of the intestinal epithelial cell layer is preserved or restored, and the diarrheic leakage of fluids into the intestinal lumen is attenuated. Keywords: mode of action

  16. Influence of Saccharomyces boulardii CNCM I-745on the gut-associated immune system.

    Science.gov (United States)

    Stier, Heike; Bischoff, Stephan C

    2016-01-01

    The probiotic Saccharomyces boulardii CNCM I-745 (also known as Saccharomyces cerevisiae HANSEN CBS 5926; in the following S. boulardii ) has proven its effectiveness in preventive and therapeutic treatment of many gastrointestinal diseases, especially diseases associated with acute diarrhea. In particular, antibiotic-associated diarrhea, Clostridium difficile -associated diarrhea, traveller's diarrhea, as well as acute diarrhea due to common viral and bacterial infections in children and adults. The aim of this review is to summarize the experimental studies elucidating the molecular and immunological mechanisms by which these clinically proven effects are archived, with an emphasis on the gut-associated immune system. The main focus is laid on anti-inflammatory and immune-modulatory action of S. boulardii involved in bacterial or enterotoxin-mediated diarrhea and inflammation. An attempt is made to differentiate between the effects associated with cellular versus soluble factors and between prophylactic and therapeutic effects. A literature search was performed in PubMed/PubMed Central for the effects of S. boulardii on the gut-associated immune system (focus acute diarrhea). S. boulardii exhibits its positive effect by the direct effects on pathogens or their toxins as well as by influencing the host's infection-induced signaling cascades and its innate and adaptive immune system. The combination of these mechanisms results in a reduction of the pathogens' ability for adhesion or colonization and an attenuation of the overreacting inflammatory immune response. Thereby, the integrity of the intestinal epithelial cell layer is preserved or restored, and the diarrheic leakage of fluids into the intestinal lumen is attenuated.

  17. Mechanism for maintaining homeostasis in the immune system of the intestine.

    Science.gov (United States)

    Taniguchi, Yoshie; Yoshioka, Noriko; Nakata, Kazue; Nishizawa, Takashi; Inagawa, Hiroyuki; Kohchi, Chie; Soma, Gen-Ichiro

    2009-11-01

    Every organism possesses a mechanism for maintaining homeostasis. We have focused on the immune system as a system that helps maintain homeostasis of the body, and particularly on the intestine as the largest organ of immunity in the body. We have also focused our research on the mechanism that responds to foreign substances in the intestine, especially the toll-like receptors (TLR). The activation of myeloid differentiation primary response gene 88 (MyD88) signal transduction as a response to TLR in the intestine is believed to contribute to the maintenance of homeostasis of the body through the homeostasis of the intestine. Furthermore, significant findings were reported in which signal transduction from TLR4 was essential for the maintenance and regulation of the intestine. These results strongly suggest the possibility that homeostasis in the intestine is maintained by TLR4, and signaling by TLR4 after exposure to lipopolysaccharide (LPS) probably has a role in regulating homeostasis. It is expected that the prevention and treatment of various diseases using TLR4 will continue to develop. As LPS is a substance that enhances the activity of TLR4, it will also attract attention as a valuable substance in its own right.

  18. General programmed system for physiological signal processing

    Energy Technology Data Exchange (ETDEWEB)

    Tournier, E; Monge, J; Magnet, C; Sonrel, C

    1975-01-01

    Improvements made to the general programmed signal acquisition and processing system, Plurimat S, are described, the aim being to obtain a less specialized system adapted to the biological and medical field. In this modified system the acquisition will be simplified. The standard processings offered will be integrated to a real advanced language which will enable the user to create his own processings, the loss of speed being compensated by a greater flexibility and universality. The observation screen will be large and the quality of the recording very good so that a large signal fraction may be displayed. The data will be easily indexed and filed for subsequent display and processing. This system will be used for two kinds of task: it can either be specialized, as an integral part of measurement and diagnostic preparation equipment used routinely in clinical work (e.g. vectocardiographic examination), or its versatility can be used for studies of limited duration to gain information in a given field or to study new diagnosis or treatment methods.

  19. Human IgG repertoire of malaria antigen-immunized human immune system (HIS) mice.

    Science.gov (United States)

    Nogueira, Raquel Tayar; Sahi, Vincent; Huang, Jing; Tsuji, Moriya

    2017-08-01

    Humanized mouse models present an important tool for preclinical evaluation of new vaccines and therapeutics. Here we show the human variable repertoire of antibody sequences cloned from a previously described human immune system (HIS) mouse model that possesses functional human CD4+ T cells and B cells, namely HIS-CD4/B mice. We sequenced variable IgG genes from single memory B-cell and plasma-cell sorted from splenocytes or whole blood lymphocytes of HIS-CD4/B mice that were vaccinated with a human plasmodial antigen, a recombinant Plasmodium falciparum circumsporozoite protein (rPfCSP). We demonstrate that rPfCSP immunization triggers a diverse B-cell IgG repertoire composed of various human VH family genes and distinct V(D)J recombinations that constitute diverse CDR3 sequences similar to humans, although low hypermutated sequences were generated. These results demonstrate the substantial genetic diversity of responding human B cells of HIS-CD4/B mice and their capacity to mount human IgG class-switched antibody response upon vaccination. Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  20. Impacts of Low Temperature on the Teleost Immune System

    Directory of Open Access Journals (Sweden)

    Quinn H. Abram

    2017-11-01

    Full Text Available As poikilothermic vertebrates, fish can experience changes in water temperature, and hence body temperature, as a result of seasonal changes, migration, or efflux of large quantities of effluent into a body of water. Temperature shifts outside of the optimal temperature range for an individual fish species can have negative impacts on the physiology of the animal, including the immune system. As a result, acute or chronic exposure to suboptimal temperatures can impair an organisms’ ability to defend against pathogens and thus compromise the overall health of the animal. This review focuses on the advances made towards understanding the impacts of suboptimal temperature on the soluble and cellular mediators of the innate and adaptive immune systems of fishes. Although cold stress can result in varying effects in different fish species, acute and chronic suboptimal temperature exposure generally yield suppressive effects, particularly on adaptive immunity. Knowledge of the effects of environmental temperature on fish species is critical for both the optimal management of wild species and the best management practices for aquaculture species.

  1. Interaction of the tick immune system with transmitted pathogens

    Directory of Open Access Journals (Sweden)

    Ondrej eHajdusek

    2013-07-01

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

  2. Threshold for extinction and survival in stochastic tumor immune system

    Science.gov (United States)

    Li, Dongxi; Cheng, Fangjuan

    2017-10-01

    This paper mainly investigates the stochastic character of tumor growth and extinction in the presence of immune response of a host organism. Firstly, the mathematical model describing the interaction and competition between the tumor cells and immune system is established based on the Michaelis-Menten enzyme kinetics. Then, the threshold conditions for extinction, weak persistence and stochastic persistence of tumor cells are derived by the rigorous theoretical proofs. Finally, stochastic simulation are taken to substantiate and illustrate the conclusion we have derived. The modeling results will be beneficial to understand to concept of immunoediting, and develop the cancer immunotherapy. Besides, our simple theoretical model can help to obtain new insight into the complexity of tumor growth.

  3. Effects of TNF antagonists on immune and neuroendocrine system

    Directory of Open Access Journals (Sweden)

    M. Cutolo

    2011-09-01

    Full Text Available In the article, the literature on the effects of TNFa-antagonists (etanercept, infliximab and adalimumab on the immune system is reviewed. These biologic agents are employed in chronic inflammatory diseases such as rheumatoid arthritis, seronegative spondyloarthritides, as well as psoriasis and Crohn’s disease. The differences of these drugs, testified by the different effects on the immune response, are discussed. These molecules exert their effect through cytokine inhibition, but they present striking differences since they can modulate macrophage activity, T cells apoptosis, leukocyte migration, and angiogenesis to a different degree. Some studies showed that these agents also affect the hypothalamo- pituitary-adrenal axis. The potential immunogenicity of these biologic agents is also discussed.

  4. Energy efficient security in MANETs: a comparison of cryptographic and artificial immune systems

    International Nuclear Information System (INIS)

    Mazhar, N.

    2010-01-01

    MANET is characterized by a set of mobile nodes in an inherently insecure environment, having limited battery capacities. Provisioning of energy efficient security in MANETs is, therefore, an open problem for which a number of solutions have been proposed. In this paper, we present an overview and comparison of the MANET security at routing layer by using the cryptographic and Artificial Immune System (AIS) approaches. The BeeAdHoc protocol, which is a Bio-inspired MANET routing protocol based on the foraging principles of honey bee colony, is taken as case study. We carry out an analysis of the three security frameworks that we have proposed earlier for securing BeeAdHoc protocol; one based on asymmetric key encryption, i.e BeeSec, and the other two using the AIS approach, i.e BeeAIS based on self non-self discrimination from adaptive immune system and BeeAIS-DC based on Dendritic Cell (DC) behavior from innate immune system. We extensively evaluate the performance of the three protocols through network simulations in ns-2 and compare with BeeAdHoc, the base protocol, as well as with state-of-the-art MANET routing protocols DSR and AODV. Our results clearly indicate that AIS based systems provide security at much lower cost to energy as compared with the cryptographic systems. Moreover, the use of dendritic cells and danger signals instead of the classical self non-self discrimination allows to detect the non-self antigens with greater accuracy. Based on the results of this investigation, we also propose a composite AIS model for BeeAdHoc security by combining the concepts from both the adaptive and the innate immune systems by modelling the attributes and behavior of the B-cells and DCs. (author)

  5. MECHANISMS OF VITAMIN D ACTION ON THE IMMUNE SYSTEM

    Directory of Open Access Journals (Sweden)

    S. A. Snopov

    2014-01-01

    Full Text Available Besides the well-known effects upon bone metabolism, vitamin D (VD plays important roles in many other processes in the body, including immune regulation. VD action is carried out through its cellular membrane receptor, which is expressed in a variety of human organs and tissues, e.g., most cells of immune system, as well as epithelial cells lining the mucous membranes. The cell-membrane bound VD receptor is transferred to the cytoplasm, to form a functional complex with vitamin A and its receptor. This complex provides either inhibiting, or enhancing effect upon transcription of hundreds genes in the nuclear DNA, including those that regulate cell growth, differentiation, apoptosis, thus preventing malignancy and angiogenesis. The following effects of VD are supposed with respect to immune system: VD inhibits antigen presentation by dendritic cells, supresses Th1-cell differentiation and the production of Th1-cytokines, shifts the balance of Th1/Th2 cell responses towards the Th2 response, exerts inhibitory effect upon Th17 cells, promotes Treg cell development, and increases their activity. In addition, VD boosts production of «endogenous antibiotics» that may provide powerful effects upon Gram-positive and Gram-negative bacteria, fungi and viruses. Therefore, VD seems quite important for prevention of autoimmune and atopic diseases: multiple sclerosis, rheumatoid arthritis, type 1 diabetes, Crohn’s disease, ulcerative colitis, development of asthma in children and chronic obstructive pulmonary disease. VD protects from a wide range of infections, including tuberculosis, leprosy and respiratory infections, and prevents the development of several tumors. Almost half the population of different countries has a VD hypovitaminosis, often hidden and undiagnosed, and this can be a leading cause of weakened immunity and increased morbidity. The diagnostics of VD hypovitaminosis, prevention and treatment of hypovitaminosis should be among the

  6. The receptor kinase FER is a RALF-regulated scaffold controlling plant immune signaling

    NARCIS (Netherlands)

    Stegmann, Martin; Monaghan, Jacqueline; Smakowska-Luzan, Elwira; Rovenich, Hanna; Lehner, Anita; Holton, Nicholas; Belkhadir, Youssef; Zipfel, Cyril

    2017-01-01

    In plants, perception of invading pathogens involves cell-surface immune receptor kinases. Here, we report that the Arabidopsis SITE-1 PROTEASE (S1P) cleaves endogenous RAPID ALKALINIZATION FACTOR (RALF) propeptides to inhibit plant immunity. This inhibition is mediated by the malectin-like receptor

  7. Immune system modulation in the central nervous system: A possible role for endocannabinoids

    International Nuclear Information System (INIS)

    Abd-Allah, Adel R.A.

    2007-01-01

    The immune system is designed to protect the body from infection and tumor formation. To perform this function, cells of the immune system can be dangerous for the survival and function of the neuronal network in the brain under the influence of infection or immune imbalance. An attack of immune cells inside the brain includes the potential for severe neuronal damage or cell death and therefore impairment of the CNS function. To avoid such undesirable action of the immune system, the CNS performs a cascade of cellular and molecular mechanisms enabling strict control of immune reactions i mmune privilege . Under inflammatory and patholological conditions, uncontrolled immune system results in the activation of neuronal damage that is frequently associated with neurological diseases. On the other hand, processes of neuroprotection and neurorepair after neuronal damage depend on a steady and tightly controlled immunesurvelliance. Many immunoprotectants play a role to imbalance the immune reactions in the CNS and other organs which presents an important therapeutic target. It has been reported recently that endocannabinoids are secreted in abundance in the CNS following neuronal insult, probably for its protection. There are at least two types of cannabinoid receptors, CB1 and CB2. Both are coupled to G proteins. CB1 receptors exist primarily on central and peripheral neurons. CB2 receptors are present mainly on immune cells. Endogenous agonists for cannabinoid receptors (endocannabinoids), have been discovered, the most important being arachidonoyl ethanolamide (anandamide), 2-arachidonoyl glycerol (2AG), and 2-archidonyl glyceryl ether. Following their release, endocannabinoids are removed from the extracellular space and then degraded by intracellular enzymic hydrolysis. Therapeutic uses of cannabinoid receptor agonists/antagonists include the management of many disease conditions. They are also involved in immune system suppression and in cell to cell communication

  8. Reciprocal Inflammatory Signaling Between Intestinal Epithelial Cells and Adipocytes in the Absence of Immune Cells

    Directory of Open Access Journals (Sweden)

    Yu Takahashi

    2017-09-01

    Full Text Available Visceral fat accumulation as observed in Crohn's disease and obesity is linked to chronic gut inflammation, suggesting that accumulation of gut adipocytes can trigger local inflammatory signaling. However, direct interactions between intestinal epithelial cells (IECs and adipocytes have not been investigated, in part because IEC physiology is difficult to replicate in culture. In this study, we originally prepared intact, polarized, and cytokine responsive IEC monolayers from primary or induced pluripotent stem cell-derived intestinal organoids by simple and repeatable methods. When these physiological IECs were co-cultured with differentiated adipocytes in Transwell, pro-inflammatory genes were induced in both cell types, suggesting reciprocal inflammatory activation in the absence of immunocompetent cells. These inflammatory responses were blocked by nuclear factor-κB or signal transducer and activator of transcription 3 inhibition and by anti-tumor necrosis factor- or anti-interleukin-6-neutralizing antibodies. Our results highlight the utility of these monolayers for investigating IEC biology. Furthermore, this system recapitulates the intestinal epithelium–mesenteric fat signals that potentially trigger or worsen inflammatory disorders such as Crohn's disease and obesity-related enterocolitis.

  9. Identification of Systemic Acquired Resistance–Related Volatile Organic Compounds and their Role in Plant Immunity

    OpenAIRE

    Bichlmeier, Marlies

    2017-01-01

    Systemic acquired resistance (SAR) is an inducible immune response that depends on ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1), which is essential for SAR signalling. In contrast to SAR, local resistance remains intact in Arabidopsis (Arabidopsis thaliana) eds1-2 mutant plants in response to Pseudomonas syringae delivering the effector protein AvrRpm1. I utilized the SAR-specific phenotype of the eds1-2 mutant to identify volatile organic compounds (VOCs) related to SAR. To this end, SAR was indu...

  10. Purinergic signalling in the musculoskeletal system.

    Science.gov (United States)

    Burnstock, Geoffrey; Arnett, Timothy R; Orriss, Isabel R

    2013-12-01

    It is now widely recognised that extracellular nucleotides, signalling via purinergic receptors, participate in numerous biological processes in most tissues. It has become evident that extracellular nucleotides have significant regulatory effects in the musculoskeletal system. In early development, ATP released from motor nerves along with acetylcholine acts as a cotransmitter in neuromuscular transmission; in mature animals, ATP functions as a neuromodulator. Purinergic receptors expressed by skeletal muscle and satellite cells play important pathophysiological roles in their development or repair. In many cell types, expression of purinergic receptors is often dependent on differentiation. For example, sequential expression of P2X5, P2Y1 and P2X2 receptors occurs during muscle regeneration in the mdx model of muscular dystrophy. In bone and cartilage cells, the functional effects of purinergic signalling appear to be largely negative. ATP stimulates the formation and activation of osteoclasts, the bone-destroying cells. Another role appears to be as a potent local inhibitor of mineralisation. In osteoblasts, the bone-forming cells, ATP acts via P2 receptors to limit bone mineralisation by inhibiting alkaline phosphatase expression and activity. Extracellular ATP additionally exerts significant effects on mineralisation via its hydrolysis product, pyrophosphate. Evidence now suggests that purinergic signalling is potentially important in several bone and joint disorders including osteoporosis, rheumatoid arthritis and cancers. Strategies for future musculoskeletal therapies might involve modulation of purinergic receptor function or of the ecto-nucleotidases responsible for ATP breakdown or ATP transport inhibitors.

  11. Titanium dioxide nanoparticles stimulate sea urchin immune cell phagocytic activity involving TLR/p38 MAPK-mediated signalling pathway

    Science.gov (United States)

    Pinsino, Annalisa; Russo, Roberta; Bonaventura, Rosa; Brunelli, Andrea; Marcomini, Antonio; Matranga, Valeria

    2015-01-01

    Titanium dioxide nanoparticles (TiO2NPs) are one of the most widespread-engineered particles in use for drug delivery, cosmetics, and electronics. However, TiO2NP safety is still an open issue, even for ethical reasons. In this work, we investigated the sea urchin Paracentrotus lividus immune cell model as a proxy to humans, to elucidate a potential pathway that can be involved in the persistent TiO2NP-immune cell interaction in vivo. Morphology, phagocytic ability, changes in activation/inactivation of a few mitogen-activated protein kinases (p38 MAPK, ERK), variations of other key proteins triggering immune response (Toll-like receptor 4-like, Heat shock protein 70, Interleukin-6) and modifications in the expression of related immune response genes were investigated. Our findings indicate that TiO2NPs influence the signal transduction downstream targets of p38 MAPK without eliciting an inflammatory response or other harmful effects on biological functions. We strongly recommend sea urchin immune cells as a new powerful model for nano-safety/nano-toxicity investigations without the ethical normative issue. PMID:26412401

  12. Immune Modulation of NYVAC-Based HIV Vaccines by Combined Deletion of Viral Genes that Act on Several Signalling Pathways

    Directory of Open Access Journals (Sweden)

    Carmen Elena Gómez

    2017-12-01

    Full Text Available An HIV-1 vaccine continues to be a major target to halt the AIDS pandemic. The limited efficacy of the RV144 phase III clinical trial with the canarypox virus-based vector ALVAC and a gp120 protein component led to the conclusion that improved immune responses to HIV antigens are needed for a more effective vaccine. In non-human primates, the New York vaccinia virus (NYVAC poxvirus vector has a broader immunogenicity profile than ALVAC and has been tested in clinical trials. We therefore analysed the HIV immune advantage of NYVAC after removing viral genes that act on several signalling pathways (Toll-like receptors—TLR—interferon, cytokines/chemokines, as well as genes of unknown immune function. We generated a series of NYVAC deletion mutants and studied immune behaviour (T and B cell to HIV antigens and to the NYVAC vector in mice. Our results showed that combined deletion of selected vaccinia virus (VACV genes is a valuable strategy for improving the immunogenicity of NYVAC-based vaccine candidates. These immune responses were differentially modulated, positive or negative, depending on the combination of gene deletions. The deletions also led to enhanced antigen- or vector-specific cellular and humoral responses. These findings will facilitate the development of optimal NYVAC-based vaccines for HIV and other diseases.

  13. Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints.

    Science.gov (United States)

    Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

    2015-06-01

    Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system-with its capacity for memory, exquisite specificity and central and universal role in human biology-immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer.

  14. Simulation of traffic control signal systems

    Science.gov (United States)

    Connolly, P. J.; Concannon, P. A.; Ricci, R. C.

    1974-01-01

    In recent years there has been considerable interest in the development and testing of control strategies for networks of urban traffic signal systems by simulation. Simulation is an inexpensive and timely method for evaluating the effect of these traffic control strategies since traffic phenomena are too complex to be defined by analytical models and since a controlled experiment may be hazardous, expensive, and slow in producing meaningful results. This paper describes the application of an urban traffic corridor program, to evaluate the effectiveness of different traffic control strategies for the Massachusetts Avenue TOPICS Project.

  15. Hepatitis B virus polymerase blocks pattern recognition receptor signaling via interaction with DDX3: implications for immune evasion.

    Directory of Open Access Journals (Sweden)

    Haifeng Wang

    Full Text Available Viral infection leads to induction of pattern-recognition receptor signaling, which leads to interferon regulatory factor (IRF activation and ultimately interferon (IFN production. To establish infection, many viruses have strategies to evade the innate immunity. For the hepatitis B virus (HBV, which causes chronic infection in the liver, the evasion strategy remains uncertain. We now show that HBV polymerase (Pol blocks IRF signaling, indicating that HBV Pol is the viral molecule that effectively counteracts host innate immune response. In particular, HBV Pol inhibits TANK-binding kinase 1 (TBK1/IkappaB kinase-epsilon (IKKepsilon, the effector kinases of IRF signaling. Intriguingly, HBV Pol inhibits TBK1/IKKepsilon activity by disrupting the interaction between IKKepsilon and DDX3 DEAD box RNA helicase, which was recently shown to augment TBK1/IKKepsilon activity. This unexpected role of HBV Pol may explain how HBV evades innate immune response in the early phase of the infection. A therapeutic implication of this work is that a strategy to interfere with the HBV Pol-DDX3 interaction might lead to the resolution of life-long persistent infection.

  16. Olive oil and immune system functions: potential involvement in immunonutrition

    Directory of Open Access Journals (Sweden)

    Álvarez de Cienfuegos, Gerardo

    2004-03-01

    Full Text Available Olive oil plays a crucial role as a main component of the Mediterranean diet, which has shown important benefits for the human health. According to the current knowledge, the administration of diets containing olive oil exerts some beneficial effects on the immune system functions due likely to the action of oleic acid rather than other substances contained in this fat. In the last few years, epidemiological, clinical and experimental studies have evidenced the potential of certain dietary lipids (containing polyunsaturated or monounsaturated fatty acids as modulators of immune system functions due to their ability to suppress several functions of immune system in both humans and animals. As a result, these fats have been applied in the reduction of symptoms from diseases characterized by an overactivation of the immune system (autoimmune diseases or in the reduction of cancer risk. Here, we review several relevant experimental and clinical data associated with the beneficial effects of olive oil upon the health, the mechanisms of action and the immune function susceptible of being be altered by the administration of dietary lipids and particularly of olive oil. In addition, we will also discuss the detrimental effects on the immune system functions caused by the administration of certain dietary lipids attributed mainly to a reduction of host natural resistance against infectious microorganisms as well as the involvement of olive oil diets in the regulation of immune resistance.El aceite de oliva tiene un papel crucial como componente de la dieta Mediterránea, con importantes beneficios sobre la salud humana. Dietas conteniendo aceite de oliva actúan de manera favorable en las funciones del sistema inmune por la acción sobretodo del ácido oleico. Los estudios epidemiológicos, clínicos y experimentales publicados en los últimos años demuestran que ciertos lípidos de la dieta [ácidos grasos monoinsaturados (MUFA y poliinsaturados (PUFA

  17. Threonine modulates immune response, antioxidant status and gene expressions of antioxidant enzymes and antioxidant-immune-cytokine-related signaling molecules in juvenile blunt snout bream (Megalobrama amblycephala).

    Science.gov (United States)

    Habte-Tsion, Habte-Michael; Ren, Mingchun; Liu, Bo; Ge, Xianping; Xie, Jun; Chen, Ruli

    2016-04-01

    A 9-week feeding trial was conducted to investigate the effects of graded dietary threonine (Thr) levels (0.58-2.58%) on the hematological parameters, immune response, antioxidant status and hepatopancreatic gene expression of antioxidant enzymes and antioxidant-immune-cytokine-related signaling molecules in juvenile blunt snout bream. For this purpose, 3 tanks were randomly arranged and assigned to each experimental diet. Fish were fed with their respective diet to apparent satiation 4 times daily. The results indicated that white blood cell, red blood cell and haemoglobin significantly responded to graded dietary Thr levels, while hematocrit didn't. Complement components (C3 and C4), total iron-binding capacity (TIBC), immunoglobulin M (IgM), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) increased with increasing dietary Thr levels up to 1.58-2.08% and thereafter tended to decrease. Dietary Thr regulated the gene expressions of Cu/Zn-SOD, Mn-SOD and CAT, GPx1, glutathione S-transferase mu (GST), nuclear factor erythroid 2-related factor 2 (Nrf2), heat shock protein-70 (Hsp70), tumor necrosis factor-alpha (TNF-α), apolipoprotein A-I (ApoA1), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and fructose-bisphosphate aldolase B (ALDOB); while the gene expression of peroxiredoxin II (PrxII) was not significantly modified by graded Thr levels. These genes are involved in different functions including antioxidant, immune, and defense responses, energy metabolism and protein synthesis. Therefore, this study could provide a new molecular tool for studies in fish immunonutrition and shed light on the regulatory mechanisms that dietary Thr improved the antioxidant and immune capacities of fish. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Treatment of autoimmune inflammation by a TLR7 ligand regulating the innate immune system.

    Directory of Open Access Journals (Sweden)

    Tomoko Hayashi

    Full Text Available The Toll-like receptors (TLR have been advocated as attractive therapeutic targets because TLR signaling plays dual roles in initiating adaptive immune responses and perpetuating inflammation. Paradoxically, repeated stimulation of bone marrow mononuclear cells with a synthetic TLR7 ligand 9-benzyl-8-hydroxy-2-(2-methoxyethoxy adenine (called 1V136 leads to subsequent TLR hyporesponsiveness. Further studies on the mechanism of action of this pharmacologic agent demonstrated that the TLR7 ligand treatment depressed dendritic cell activation, but did not directly affect T cell function. To verify this mechanism, we utilized experimental allergic encephalitis (EAE as an in vivo T cell dependent autoimmune model. Drug treated SJL/J mice immunized with proteolipid protein (PLP(139-151 peptide had attenuated disease severity, reduced accumulation of mononuclear cells in the central nervous system (CNS, and limited demyelination, without any apparent systemic toxicity. Splenic T cells from treated mice produced less cytokines upon antigenic rechallenge. In the spinal cords of 1V136-treated EAE mice, the expression of chemoattractants was also reduced, suggesting innate immune cell hyposensitization in the CNS. Indeed, systemic 1V136 did penetrate the CNS. These experiments indicated that repeated doses of a TLR7 ligand may desensitize dendritic cells in lymphoid organs, leading to diminished T cell responses. This treatment strategy might be a new modality to treat T cell mediated autoimmune diseases.

  19. Effects of hyperthermia on the hamster immune system

    International Nuclear Information System (INIS)

    Gangavalli, R.; Cain, C.A.; Tompkins, W.A.F.

    1984-01-01

    In previous studies, the authors have shown that hyperthermia can enhance antibody-complement chytotoxicity of hamster and human tumor cells. Moreover, whole body microwave exposure of hamsters resulted in activation of peritoneal macrophages to a viricidal state and transient suppression of natural killer (NK) cell activity. In this study, the authors compare the effects of whole body heating by microwaves or by an environmental chamber (hot air) on the hamster immune system. Microwave exposure (25mW/cm/sup 2/; 1 hr) caused viricidal activation of peritoneal macrophages which resulted in restriction of vaccinia and vesicular stomatitis virs (VSV) growth. However, heating in an environmental chamber (41 0 C; 1 hr) did not activate macrophages to a viricidal state. Both microwave and hot air hyperthermia caused significant augmentation of antibody producing spleen cell response to sheep red blood cells (SRBC), using the Jerne hymolytic plaque assay, four days post exposure and immunization with SRBC. Natural killer spleen cell cytotoxicity was suppressed by microwave and hot air hyperthermia showing that NK lymphocytes are extremely sensitive to changes in temperature. These alterations in cellular immune response due to hyperthermia could be of significance in treatment of tumors and viral infections

  20. A systems biology approach reveals that tissue tropism to West Nile virus is regulated by antiviral genes and innate immune cellular processes.

    Directory of Open Access Journals (Sweden)

    Mehul S Suthar

    2013-02-01

    Full Text Available The actions of the RIG-I like receptor (RLR and type I interferon (IFN signaling pathways are essential for a protective innate immune response against the emerging flavivirus West Nile virus (WNV. In mice lacking RLR or IFN signaling pathways, WNV exhibits enhanced tissue tropism, indicating that specific host factors of innate immune defense restrict WNV infection and dissemination in peripheral tissues. However, the immune mechanisms by which the RLR and IFN pathways coordinate and function to impart restriction of WNV infection are not well defined. Using a systems biology approach, we defined the host innate immune response signature and actions that restrict WNV tissue tropism. Transcriptional profiling and pathway modeling to compare WNV-infected permissive (spleen and nonpermissive (liver tissues showed high enrichment for inflammatory responses, including pattern recognition receptors and IFN signaling pathways, that define restriction of WNV replication in the liver. Assessment of infected livers from Mavs(-/- × Ifnar(-/- mice revealed the loss of expression of several key components within the natural killer (NK cell signaling pathway, including genes associated with NK cell activation, inflammatory cytokine production, and NK cell receptor signaling. In vivo analysis of hepatic immune cell infiltrates from WT mice demonstrated that WNV infection leads to an increase in NK cell numbers with enhanced proliferation, maturation, and effector action. In contrast, livers from Mavs(-/- × Ifnar(-/- infected mice displayed reduced immune cell infiltration, including a significant reduction in NK cell numbers. Analysis of cocultures of dendritic and NK cells revealed both cell-intrinsic and -extrinsic roles for the RLR and IFN signaling pathways to regulate NK cell effector activity. Taken together, these observations reveal a complex innate immune signaling network, regulated by the RLR and IFN signaling pathways, that drives tissue

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

    NARCIS (Netherlands)

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

    Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system.

  2. Linking autoimmunity to the origin of the adaptive immune system.

    Science.gov (United States)

    Bayersdorf, Robert; Fruscalzo, Arrigo; Catania, Francesco

    2018-01-01

    In jawed vertebrates, the adaptive immune system (AIS) cooperates with the innate immune system (IIS) to protect hosts from infections. Although targeting non-self-components, the AIS also generates self-reactive antibodies which, when inadequately counter-selected, can give rise to autoimmune diseases (ADs). ADs are on the rise in western countries. Why haven't ADs been eliminated during the evolution of a ∼500 million-year old system? And why have they become more frequent in recent decades? Self-recognition is an attribute of the phylogenetically more ancient IIS and empirical data compellingly show that some self-reactive antibodies, which are classifiable as elements of the IIS rather then the AIS, may protect from (rather than cause) ADs. Here, we propose that the IIS's self-recognition system originally fathered the AIS and, as a consequence of this relationship, its activity is dampened in hygienic environments. Rather than a mere breakdown or failure of the mechanisms of self-tolerance, ADs might thus arise from architectural constraints.

  3. Mechanisms for eco-immunity in a changing enviroment: how does the coral innate immune system contend with climate change?

    Science.gov (United States)

    Traylor-Knowles, N. G.

    2016-02-01

    Innate immunity plays a central role in maintaining homeostasis, and within the context of impending climate change scenarios, understanding how this system works is critical. However, the actual mechanisms involved in the evolution of the innate immune system are largely unknown. Cnidaria (including corals, sea anemones and jellyfish) are well suited for studying the fundamental functions of innate immunity because they share a common ancestor with bilaterians. This study will highlight the transcriptomic changes during a heat shock in the coral Acropora hyacinthus of American Samoa, examining the temporal changes, every half an hour for 5 hours. We hypothesize that genes involved in innate immunity, and extracellular matrix maintenance will be key components to the heat stress response. This presentation will highlight the novel role of the tumor necrosis factor receptor gene family as a responder to heat stress and present future directions for this developing field in coral reef research.

  4. Understanding the function and dysfunction of the immune system in lung cancer: the role of immune checkpoints

    International Nuclear Information System (INIS)

    Karachaliou, Niki; Cao, Maria Gonzalez; Teixidó, Cristina; Viteri, Santiago; Morales-Espinosa, Daniela; Santarpia, Mariacarmela; Rosell, Rafael

    2015-01-01

    Survival rates for metastatic lung cancer, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), are poor with 5-year survivals of less than 5%. The immune system has an intricate and complex relationship with tumorigenesis; a groundswell of research on the immune system is leading to greater understanding of how cancer progresses and presenting new ways to halt disease progress. Due to the extraordinary power of the immune system—with its capacity for memory, exquisite specificity and central and universal role in human biology—immunotherapy has the potential to achieve complete, long-lasting remissions and cures, with few side effects for any cancer patient, regardless of cancer type. As a result, a range of cancer therapies are under development that work by turning our own immune cells against tumors. However deeper understanding of the complexity of immunomodulation by tumors is key to the development of effective immunotherapies, especially in lung cancer

  5. Multi-Modal Intelligent Traffic Signal Systems GPS

    Data.gov (United States)

    Department of Transportation — Data were collected during the Multi-Modal Intelligent Transportation Signal Systems (MMITSS) study. MMITSS is a next-generation traffic signal system that seeks to...

  6. Signal systems asset management state-of-the-practice review

    Science.gov (United States)

    2004-04-01

    The purpose of this project is to obtain a better understanding of operations-level asset management by examining the specific case of signal systems. Key products will include: a synthesis of existing signal systems asset management practices; a gen...

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

    Science.gov (United States)

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

    2017-02-01

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

  8. Modulation of IL-33/ST2-TIR and TLR signalling pathway by fingolimod and analogues in immune cells.

    Science.gov (United States)

    Rüger, K; Ottenlinger, F; Schröder, M; Zivković, A; Stark, H; Pfeilschifter, J M; Radeke, H H

    2014-12-01

    For the immune modulatory drug fingolimod (FTY720), lymphocyte sequestration has been extensively studied and accepted as mode of action. Further, direct effects on immune cell signalling are incompletely understood. Herein, we used the parent drug and newly synthesized analogues to investigate their effects on dendritic cell (DC) calcium signalling and on Th1, Th2 and Th17 responses. DC calcium signalling was determined with a single cell-based confocal assay and IL-33/ST2-TIR Th2-like response with ST2-transduced EL4-6.1 thymoma cells. The Th1/Th17 responses were examined with a LPS/TLR-enhanced antigen presentation assay with OVA-TCRtg CD4 and CD8 spleen cells. Our results revealed a comparable influence of fingolimod and S1P on intracellular calcium level in DC, while an oxy-derivative of fingolimod exhibited an EC50 of 3.3 nm, being 14 times more potent than FTY720-P. The IL-33/ST2-TIR Th2-like response in ST2-EL4 cells was inhibited by fingolimod and analogues at varying degrees. Using the OVA-TCRtg LPS/TLR-enhanced spleen cell assay, we found that fingolimod inhibited both IL-17 and IFN-γ production. In contrast, fingolimod phosphate failed to decrease Th1 cytokines. Interestingly, the effects of the parent compound fingolimod were modulated by the PP2A inhibitor okadaic acid, thus suggesting PP2A as relevant intracellular target. These studies describe detailed immune-modulating properties of fingolimod, including interference with a prototypical Th2 response via IL-33/ST2-TIR. Moreover, differential effects of fingolimod versus its phosphorylated derivative on TLR-activated and antigen-dependent Th1 activation suggest PP2A as an additional target of fingolimod immune therapy. Together with the analogues tested, these data may guide the development of more specific fingolimod derivatives. © 2014 John Wiley & Sons Ltd.

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

    Science.gov (United States)

    Karmakar, Souvik; Reilly, Karlyne M

    2017-01-01

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

  10. System and method for traffic signal timing estimation

    KAUST Repository

    Dumazert, Julien; Claudel, Christian G.

    2015-01-01

    A method and system for estimating traffic signals. The method and system can include constructing trajectories of probe vehicles from GPS data emitted by the probe vehicles, estimating traffic signal cycles, combining the estimates, and computing the traffic signal timing by maximizing a scoring function based on the estimates. Estimating traffic signal cycles can be based on transition times of the probe vehicles starting after a traffic signal turns green.

  11. System and method for traffic signal timing estimation

    KAUST Repository

    Dumazert, Julien

    2015-12-30

    A method and system for estimating traffic signals. The method and system can include constructing trajectories of probe vehicles from GPS data emitted by the probe vehicles, estimating traffic signal cycles, combining the estimates, and computing the traffic signal timing by maximizing a scoring function based on the estimates. Estimating traffic signal cycles can be based on transition times of the probe vehicles starting after a traffic signal turns green.

  12. IMMUNITY AND INFECTION IN WOMEN WITH HYPERPLASTIC STATES OF IMMUNE SYSTEM

    Directory of Open Access Journals (Sweden)

    A. A. Lukach

    2008-01-01

    Full Text Available Abstract. One hundred and ninety-nine patients with hyperplastic processes of reproductive system were examined, and 131 (66.16% of them were found to be infected with Chlamydia or Ureaplasma. The mean age of female patients was 42,7±1,35 years. Different infectious agents (e.g. Chlamydia trachomatis, Ureaplasma urealiticum, Mycoplasma hominis were identified in cervical canal of uterine cervix and surgical specimens (biopsy samples of excised myoma, adenomyosis or endometrial hyperplasia. The infected patients were found to have decreased monocytes and neutrophils in blood counts, lower phagocytic activity of monocytes and neutrophils, and decreased bactericidal activity of leukocytes. Other findings included lower CD20+, CD8+ and rFAS CD 95 lymphocytes. Assessment of cytokine-synthesizing activity of CD3+ lymphocytes showed a decrease in both spontaneous and stimulated response (р < 0,001. A weakest spontaneous and stimulated response was found in CD3+/IL-4+ lymphocytes. Analysis of results obtained shows systemic immune disorders and impaired cytokine-synthesizing activity of CD3+ lymphocytes correlating with infection factors in the women with hyperplastic processes of reproductive system. (Med. Immunol., 2008, vol. 10, N 2-3, pp 223-228.

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

    OpenAIRE

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

    2009-01-01

    This study is a systematic review of mind-body interventions that used immune outcomes in order to: 1) characterize mind-body medicine studies that assessed immune outcomes, 2) evaluate the quality of mind-body medicine studies measuring immune system effects, and 3) systematically evaluate the evidence for mind-body interventions effect on immune system outcomes using existing formal tools. 111 studies with 4,777 subjects were reviewed. The three largest intervention type categories were Rel...

  14. The postnatal development of the mucosal immune system and mucosal tolerance in domestic animals

    OpenAIRE

    Bailey , Mick; Haverson , Karin

    2006-01-01

    International audience; The mucosal immune system is exposed to a range of antigens associated with pathogens, to which it must mount active immune responses. However, it is also exposed to a large number of harmless antigens associated with food and with commensal microbial flora, to which expression of active, inflammatory immune responses to these antigens is undesirable. The mucosal immune system must contain machinery capable of evaluating the antigens to which it is exposed and mounting...

  15. Artificial immune system for effective properties optimization of magnetoelectric composites

    Science.gov (United States)

    Poteralski, Arkadiusz; Dziatkiewicz, Grzegorz

    2018-01-01

    The optimization problem of the effective properties for magnetoelectric composites is considered. The effective properties are determined by the semi-analytical Mori-Tanaka approach. The generalized Eshelby tensor components are calculated numerically by using the Gauss quadrature method for the integral representation of the inclusion problem. The linear magnetoelectric constitutive equation is used. The effect of orientation of the electromagnetic materials components is taken into account. The optimization problem of the design is formulated and the artificial immune system is applied to solve it.

  16. Multicriteria vehicle routing problem solved by artificial immune system

    Directory of Open Access Journals (Sweden)

    Bogna MRÓWCZYŃSKA

    2015-09-01

    Full Text Available Vehicles route planning in large transportation companies, where drivers are workers, usually takes place on the basis of experience or intuition of the employees. Because of the cost and environmental protection, it is important to save fuel, thus planning routes in an optimal way. In this article an example of the problem is presented solving delivery vans route planning taking into account the distance and travel time within the constraints of vehicle capacities, restrictions on working time of drivers and having varying degrees of movement. An artificial immune system was used for the calculations.

  17. CYLD Limits Lys63- and Met1-Linked Ubiquitin at Receptor Complexes to Regulate Innate Immune Signaling

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    Matous Hrdinka

    2016-03-01

    Full Text Available Innate immune signaling relies on the deposition of non-degradative polyubiquitin at receptor-signaling complexes, but how these ubiquitin modifications are regulated by deubiquitinases remains incompletely understood. Met1-linked ubiquitin (Met1-Ub is assembled by the linear ubiquitin assembly complex (LUBAC, and this is counteracted by the Met1-Ub-specific deubiquitinase OTULIN, which binds to the catalytic LUBAC subunit HOIP. In this study, we report that HOIP also interacts with the deubiquitinase CYLD but that CYLD does not regulate ubiquitination of LUBAC components. Instead, CYLD limits extension of Lys63-Ub and Met1-Ub conjugated to RIPK2 to restrict signaling and cytokine production. Accordingly, Met1-Ub and Lys63-Ub were individually required for productive NOD2 signaling. Our study thus suggests that LUBAC, through its associated deubiquitinases, coordinates the deposition of not only Met1-Ub but also Lys63-Ub to ensure an appropriate response to innate immune receptor activation.

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

    Science.gov (United States)

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

    2017-11-01

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

  19. Current status of research on radiation hormesis in the immune system after low level radiation

    International Nuclear Information System (INIS)

    Liu Shuzheng

    1995-01-01

    The paper highlights the chief results of experimental studies recently carried out in the author's laboratory on the stimulatory effects of low level radiation on immunity. The intercellular relationship within the immune system after whole-body irradiation (WBI) with low doses of X- and gamma-rays was briefly outlined with the emphasis on the potential effect of low dose radiation (LDR) on the helper T cells which was thought to occupy a pivotal position in the process of immuno-stimulation. Data suggesting the facilitation by LDR of the signal transduction process within the T cells were presented. Some hypotheses prevailing in the literature for the explanation of the stimulatory effect of LDR were critically evaluated. Existing experimental data both from the literature and from the author's laboratory were analysed giving no strong support to the speculation of either the preferential deletion of the radiosensitive suppressor T subset or the increased apoptosis of the T cell 'precursors' in the thymus leading to secondary immunologic augmentation by low doses which stimulate immune functions. The possible influence of systemic changes, especially those in the neuroendocrine regulation, on the T cell potentiation following LDR was suggested. Finally the biological implications of the hermetic effects of LDR were discussed

  20. Molecular mechanism and function of CD40/CD40L engagement in the immune system.

    Science.gov (United States)

    Elgueta, Raul; Benson, Micah J; de Vries, Victor C; Wasiuk, Anna; Guo, Yanxia; Noelle, Randolph J

    2009-05-01

    During the generation of a successful adaptive immune response, multiple molecular signals are required. A primary signal is the binding of cognate antigen to an antigen receptor expressed by T and B lymphocytes. Multiple secondary signals involve the engagement of costimulatory molecules expressed by T and B lymphocytes with their respective ligands. Because of its essential role in immunity, one of the best characterized of the costimulatory molecules is the receptor CD40. This receptor, a member of the tumor necrosis factor receptor family, is expressed by B cells, professional antigen-presenting cells, as well as non-immune cells and tumors. CD40 binds its ligand CD40L, which is transiently expressed on T cells and other non-immune cells under inflammatory conditions. A wide spectrum of molecular and cellular processes is regulated by CD40 engagement including the initiation and progression of cellular and humoral adaptive immunity. In this review, we describe the downstream signaling pathways initiated by CD40 and overview how CD40 engagement or antagonism modulates humoral and cellular immunity. Lastly, we discuss the role of CD40 as a target in harnessing anti-tumor immunity. This review underscores the essential role CD40 plays in adaptive immunity.

  1. CD95-CD95L: can the brain learn from the immune system?

    DEFF Research Database (Denmark)

    Becher, B; Barker, P A; Owens, T

    1998-01-01

    being recognized that CD95 signaling by immune cells mediates effects other than apoptosis, such as cell survival and under inflammatory conditions expression of this protein promotes neural-immune interactions. Both neuroscientists and immunologists can contribute to defining the mechanisms underlying...

  2. Simple biophysical model of tumor evasion from immune system control

    Science.gov (United States)

    D'Onofrio, Alberto; Ciancio, Armando

    2011-09-01

    The competitive nonlinear interplay between a tumor and the host's immune system is not only very complex but is also time-changing. A fundamental aspect of this issue is the ability of the tumor to slowly carry out processes that gradually allow it to become less harmed and less susceptible to recognition by the immune system effectors. Here we propose a simple epigenetic escape mechanism that adaptively depends on the interactions per time unit between cells of the two systems. From a biological point of view, our model is based on the concept that a tumor cell that has survived an encounter with a cytotoxic T-lymphocyte (CTL) has an information gain that it transmits to the other cells of the neoplasm. The consequence of this information increase is a decrease in both the probabilities of being killed and of being recognized by a CTL. We show that the mathematical model of this mechanism is formally equal to an evolutionary imitation game dynamics. Numerical simulations of transitory phases complement the theoretical analysis. Implications of the interplay between the above mechanisms and the delivery of immunotherapies are also illustrated.

  3. The effects of cocoa on the immune system

    Directory of Open Access Journals (Sweden)

    Francisco J. Pérez-Cano

    2013-06-01

    Full Text Available Cocoa is a food relatively rich in polyphenols, which makes it a potent antioxidant. Due to its activity as an antioxidant, as well as through other mechanisms, cocoa consumption has been reported to be beneficial for cardiovascular health, brain functions, and cancer prevention. Furthermore, cocoa influences the immune system, in particular the inflammatory innate response and the systemic and intestinal adaptive immune response. Preclinical studies have demonstrated that a cocoa-enriched diet modifies T-cell functions that conduce to a modulation of the synthesis of systemic and gut antibodies. In this regard, it seems that a cocoa diet in rats produces changes in the lymphocyte composition of secondary lymphoid tissues and the cytokines secreted by T cells. These results suggest that it is possible that cocoa could inhibit the function of Th2 cells, and in line with this, the preventive effect of cocoa on IgE synthesis in a rat allergy model has been reported, which opens up new perspectives when considering the beneficial effects of cocoa compounds. On the other hand, cocoa intake modifies the functionality of gut-associated lymphoid tissue by means of modulating IgA secretion and intestinal microbiota. The mechanisms involved in these influences are discussed here. Further research may elucidate the cocoa compounds involved in such an effect and also the possible medical approaches to these repercussions.

  4. The effects of cocoa on the immune system.

    Science.gov (United States)

    Pérez-Cano, Francisco J; Massot-Cladera, Malen; Franch, Angels; Castellote, Cristina; Castell, Margarida

    2013-01-01

    Cocoa is a food relatively rich in polyphenols, which makes it a potent antioxidant. Due to its activity as an antioxidant, as well as through other mechanisms, cocoa consumption has been reported to be beneficial for cardiovascular health, brain functions, and cancer prevention. Furthermore, cocoa influences the immune system, in particular the inflammatory innate response and the systemic and intestinal adaptive immune response. Preclinical studies have demonstrated that a cocoa-enriched diet modifies T cell functions that conduce to a modulation of the synthesis of systemic and gut antibodies. In this regard, it seems that a cocoa diet in rats produces changes in the lymphocyte composition of secondary lymphoid tissues and the cytokines secreted by T cells. These results suggest that it is possible that cocoa could inhibit the function of T helper type 2 cells, and in line with this, the preventive effect of cocoa on IgE synthesis in a rat allergy model has been reported, which opens up new perspectives when considering the beneficial effects of cocoa compounds. On the other hand, cocoa intake modifies the functionality of gut-associated lymphoid tissue by means of modulating IgA secretion and intestinal microbiota. The mechanisms involved in these influences are discussed here. Further research may elucidate the cocoa compounds involved in such an effect and also the possible medical approaches to these repercussions.

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

    Science.gov (United States)

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

    2018-01-12

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

  6. Extracts of Porphyra tenera (Nori Seaweed) Activate the Immune Response in Mouse RAW264.7 Macrophages via NF-κB Signaling.

    Science.gov (United States)

    Song, Ji-Hye; Kang, Hee-Bum; Park, Seung-Ho; Jeong, Ji-Hoon; Park, Jeongjin; You, Yanghee; Lee, Yoo-Hyun; Lee, Jeongmin; Kim, Eungpil; Choi, Kyung-Chul; Jun, Woojin

    2017-12-01

    Porphyra tenera, also known as nori, is a red algal species of seaweed. It is cultivated in Asia for culinary purposes. We report that P. tenera extract (PTE) enhances the immune response in mouse macrophages. We found that P. tenera extract regulates the NF-κB IκB kinase (IKK) signaling pathway, and we assessed the expression and translocation of p65, a subunit of NF-κB, in RAW264.7 mouse macrophage cells after treatment with PTE. We also investigated the effects of 10% ethanol PTE (PTE10) in RAW264.7 cells. The production of IL-10, IL-6, TNF-α, and IFN-γ was induced by PTE treatment of the macrophages, and PTE also enhanced p-IκB and p-AKT. PTE10 showed no cytotoxicity at 10-20 μg/mL in RAW264.7 cells. PTE10, in fact, increased cell viability at 24 h, stimulated macrophage cells, and induced the phosphorylation of Akt. Akt stimulates IKK activity through the phosphorylation of IKKα and enhances immune activity through the activation of NF-κB. In this study, NF-κB activation was induced by increasing p-NF-κB and p-IKK. A subunit of NF-κB, p65, was located in the nucleus and increased the expression of various cytokines. PTE thus enhanced the immune response through IκB-α immunostimulation signaling in RAW264.7 cells. PTE10 has potential therefore for development of future treatments requiring immune system stimulation.

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

    Science.gov (United States)

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

    2009-04-01

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

  8. Phase transition signals of finite systems

    International Nuclear Information System (INIS)

    Duflot-Flandrois, Veronique

    2001-01-01

    Phase transitions are universal properties of interacting matter. They are well described if the considered system is infinite, by using standard thermodynamics. But in the case of small systems like atomic nuclei, this formalism cannot be applied anymore. Our aim is to propose a statistical mechanics approach in order to define the thermodynamical features of small open systems subject to non-saturating forces. We concentrate in particular on the definition and characterization for such systems of phase transitions belonging to the liquid gas universality class. Theoretical and experimental observables are defined to signal the occurrence and the order of this transition without any ambiguity. One of the most relevant and experimentally accessible observables consists in the study of kinetic energy fluctuations for a fixed value of the total deposited energy. In a first order phase transition such fluctuations become anomaly high and at the same time the size distribution appears to behave critically. All our results are obtained within numerical simulations of the lattice gas model with a nearest neighbors attractive interaction. Finally we check the influence of non-saturating forces, developing the specific example of the Coulomb interaction in the nucleus. Future improvements and perspectives at this work consist in the analysis of specific effects occurring in nuclei: isospin and quantum mechanics. (author) [fr

  9. Modulation of the immune system for the treatment of glaucoma.

    Science.gov (United States)

    Bell, Katharina; Und Hohenstein-Blaul, Nadine von Thun; Teister, Julia; Grus, Franz H

    2017-07-19

    At present intraocular pressure (IOP) lowering therapies are the only approach to treat glaucoma. Neuroprotective strategies to protect the retinal ganglion cells (RGC) from apoptosis are lacking to date. Results from clinical studies revealed altered immunoreactivities against retinal and optic nerve antigens in sera and aqueous humor of glaucoma patients and point toward an autoimmune involvement in glaucomatous neurodegeneration and RGC death. IgG accumulations along with plasma cells were found localised in human glaucomatous retinae in a pro-inflammatory environment possibly maintained by microglia. Animal studies show that antibodies (e.g. anti- heat shock protein 60 and anti-myelin basic protein) elevated in glaucoma patients provoke autoaggressive RGC loss and are associated with IgG depositions and increased microglial cells. We demonstrate that intermittent IOP elevation in a rat model is sufficient to provoke glaucoma-like neurodegeneration and elicits correlating changes of IgG autoantibody reactivities. On the other hand, antibodies (e.g. anti-glial fibrillary acidic protein and anti-gamma-Synuclein) found decreased in glaucoma patients hold neuroprotective potential on immortalised neuroretinal cells and RGC in an adolescent porcine retina organ culture. We believe that our work not only demonstrates an autoimmune component in glaucoma, but also opens up new options for glaucoma diagnostics and treatment. Nevertheless the immune system also consists of other cells involved not only in the adaptive, but also innate immune system. Studies addressing changes in T lymphocytes, macrophages but also local immune responses in the retina have been performed and also hold promising results. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Science.gov (United States)

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

    2009-05-01

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

  11. Polyclonal immune responses to antigens associated with cancer signaling pathways and new strategies to enhance cancer vaccines.

    Science.gov (United States)

    Clay, Timothy M; Osada, Takuya; Hartman, Zachary C; Hobeika, Amy; Devi, Gayathri; Morse, Michael A; Lyerly, H Kim

    2011-04-01

    Aberrant signaling pathways are a hallmark of cancer. A variety of strategies for inhibiting signaling pathways have been developed, but monoclonal antibodies against receptor tyrosine kinases have been among the most successful. A challenge for these therapies is therapeutic unresponsiveness and acquired resistance due to mutations in the receptors, upregulation of alternate growth and survival pathways, or inadequate function of the monoclonal antibodies. Vaccines are able to induce polyclonal responses that can have a multitude of affects against the target molecule. We began to explore therapeutic vaccine development to antigens associated with these signaling pathways. We provide an illustrative example in developing therapeutic cancer vaccines inducing polyclonal adaptive immune responses targeting the ErbB family member HER2. Further, we will discuss new strategies to augment the clinical efficacy of cancer vaccines by enhancing vaccine immunogenicity and reversing the immunosuppressive tumor microenvironment.

  12. Applying Statistical and Complex Network Methods to Explore the Key Signaling Molecules of Acupuncture Regulating Neuroendocrine-Immune Network

    Directory of Open Access Journals (Sweden)

    Kuo Zhang

    2018-01-01

    Full Text Available The mechanisms of acupuncture are still unclear. In order to reveal the regulatory effect of manual acupuncture (MA on the neuroendocrine-immune (NEI network and identify the key signaling molecules during MA modulating NEI network, we used a rat complete Freund’s adjuvant (CFA model to observe the analgesic and anti-inflammatory effect of MA, and, what is more, we used statistical and complex network methods to analyze the data about the expression of 55 common signaling molecules of NEI network in ST36 (Zusanli acupoint, and serum and hind foot pad tissue. The results indicate that MA had significant analgesic, anti-inflammatory effects on CFA rats; the key signaling molecules may play a key role during MA regulating NEI network, but further research is needed.

  13. Ejercicio y sistema inmune Exercise and the immune system

    Directory of Open Access Journals (Sweden)

    Pablo Javier Patiño Grajales

    2006-01-01

    Full Text Available Se ha demostrado que el ejercicio hecho a diferentes intensidades cumple una función moduladora sobre diversos sistemas, y que su acción sobre la respuesta inmune es de gran importancia. Por lo tanto, es necesario esclarecer si estos cambios constituyen efectos benéficos o perjudiciales en cuanto a las adaptaciones del hospedero frente a diversos agentes patógenos. El estudio de estos cambios inducidos por el estrés físico puede tener un impacto grande en la comprensión y prevención de algunas enfermedades que involucran la respuesta del sistema inmune como las alergias, las infecciones, las inmunodeficiencias y el cáncer. En este artículo se presenta una revisión actualizada de la información existente al respecto, con el propósito de aportar elementos que ayuden a comprender este fenómeno biológico, así como sus implicaciones para la salud humana. Se han estudiado varios parámetros de la respuesta inmune durante el ejercicio físico, entre ellos su relación con la respuesta hormonal al estrés y el comportamiento de las diferentes hormonas de acuerdo con la intensidad de aquél. También se han evaluado los cambios en las poblaciones de células sanguíneas (linfocitos, monocitos y neutrófilos así como el comportamiento de las citoquinas y la síntesis de inmunoglobulinas específicas. Todo esto ha permitido establecer una relación entre los sistemas inmune y neuroendocrino, la cual explicaría en It has been demonstrated that physical exercise, carried out at diverse intensities, modulates the function of different human body systems, and that it plays a major role in the immune response. Therefore, it is necessary to find out if these changes have benefic or harmful effects on the host adaptation against several pathogenic agents. The study of these physical-stress-induced changes might have a great impact on the comprehension and prevention of some diseases that involve activation of the immune system such as allergies

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

    Directory of Open Access Journals (Sweden)

    Céline Pomié

    2016-06-01

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

  15. Effect of oral administration of Lactobacillus paracasei L9 on mouse systemic immunity and the immune response in the intestine

    Directory of Open Access Journals (Sweden)

    Zhu Yuanbo

    2016-01-01

    Full Text Available A probiotic strain Lactobacillus paracasei L9,which was isolated from human intestine, was investigated for its immunomodulatory activity in vivo. Results showed that L9 improved systemic immunity by enhancing the phagocytic activity of peritoneal macrophages, the proliferation ratio of splenocytes, the IgG level in the serum and the level of IgA in the mucosa. Further, L9induced theTh1-polarized immune response by elevating the IFN-γ/IL-4 ratio in the mucosa. This effect was confirmed by the enhanced IL-12-inducing activity of macrophages after in vitro stimulation of L9. Also detected was increased expression of TLR-2mRNA in the mucosa. We predict that L9 could enhance innate immunity by activating TLR-2 in the mucosa, and enhance acquired immunity by promoting Th1 polarization through induced production of IL-12 by macrophages.

  16. The Innate Immune System in Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Allal Boutajangout

    2013-01-01

    Full Text Available Alzheimer’s disease (AD is the leading cause for dementia in the world. It is characterized by two biochemically distinct types of protein aggregates: amyloid β (Aβ peptide in the forms of parenchymal amyloid plaques and congophilic amyloid angiopathy (CAA and aggregated tau protein in the form of intraneuronal neurofibrillary tangles (NFT. Several risk factors have been discovered that are associated with AD. The most well-known genetic risk factor for late-onset AD is apolipoprotein E4 (ApoE4 (Potter and Wisniewski (2012, and Verghese et al. (2011. Recently, it has been reported by two groups independently that a rare functional variant (R47H of TREM2 is associated with the late-onset risk of AD. TREM2 is expressed on myeloid cells including microglia, macrophages, and dendritic cells, as well as osteoclasts. Microglia are a major part of the innate immune system in the CNS and are also involved in stimulating adaptive immunity. Microglia express several Toll-like receptors (TLRs and are the resident macrophages of the central nervous system (CNS. In this review, we will focus on the recent advances regarding the role of TREM2, as well as the effects of TLRs 4 and 9 on AD.

  17. Can the Immune System Perform a t-Test?

    Science.gov (United States)

    Faria, Bruno Filipe; Mostardinha, Patricia

    2017-01-01

    The self-nonself discrimination hypothesis remains a landmark concept in immunology. It proposes that tolerance breaks down in the presence of nonself antigens. In strike contrast, in statistics, occurrence of nonself elements in a sample (i.e., outliers) is not obligatory to violate the null hypothesis. Very often, what is crucial is the combination of (self) elements in a sample. The two views on how to detect a change seem challengingly different and it could seem difficult to conceive how immunological cellular interactions could trigger responses with a precision comparable to some statistical tests. Here it is shown that frustrated cellular interactions reconcile the two views within a plausible immunological setting. It is proposed that the adaptive immune system can be promptly activated either when nonself ligands are detected or self-ligands occur in abnormal combinations. In particular we show that cellular populations behaving in this way could perform location statistical tests, with performances comparable to t or KS tests, or even more general data mining tests such as support vector machines or random forests. In more general terms, this work claims that plausible immunological models should provide accurate detection mechanisms for host protection and, furthermore, that investigation on mechanisms leading to improved detection in “in silico” models can help unveil how the real immune system works. PMID:28046042

  18. Dietary fatty acids affect the immune system in male mice sensitized to ovalbumin or vaccinated with influenza

    NARCIS (Netherlands)

    Hogenkamp, Astrid; van Vlies, Naomi; Fear, Alison L.; van Esch, Betty C.; Hofman, Gerard A.; Garssen, Johan; Calder, Philip C.

    2011-01-01

    PUFA are precursor molecules for eicosanoids such as leukotrienes and prostaglandins and may influence immune function through other mechanisms involving membranes, cell signaling, and gene expression. Immune-modulating properties of diets containing different oils [sunflower oil, rich in linoleic

  19. Immunobiotic Bifidobacteria Strains Modulate Rotavirus Immune Response in Porcine Intestinal Epitheliocytes via Pattern Recognition Receptor Signaling.

    Directory of Open Access Journals (Sweden)

    Takamasa Ishizuka

    Full Text Available In this work, we aimed to characterize the antiviral response of an originally established porcine intestinal epithelial cell line (PIE cells by evaluating the molecular innate immune response to rotavirus (RVs. In addition, we aimed to select immunomodulatory bacteria with antiviral capabilities. PIE cells were inoculated with RVs isolated from different host species and the infective titers and the molecular innate immune response were evaluated. In addition, the protection against RVs infection and the modulation of immune response by different lactic acid bacteria (LAB strains was studied. The RVs strains OSU (porcine and UK (bovine effectively infected PIE cells. Our results also showed that RVs infection in PIE cells triggered TLR3-, RIG-I- and MDA-5-mediated immune responses with activation of IRF3 and NF-κB, induction of IFN-β and up-regulation of the interferon stimulated genes MxA and RNase L. Among the LAB strains tested, Bifidobacterium infantis MCC12 and B. breve MCC1274 significantly reduced RVs titers in infected PIE cells. The beneficial effects of both bifidobacteria were associated with reduction of A20 expression, and improvements of IRF-3 activation, IFN-β production, and MxA and RNase L expressions. These results indicate the value of PIE cells for studying RVs molecular innate immune response in pigs and for the selection of beneficial bacteria with antiviral capabilities.

  20. Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

    Directory of Open Access Journals (Sweden)

    Jessica M. F. Hall

    2012-01-01

    Full Text Available Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity and alters antigen presentation by epidermal Langerhans cells (adaptive immunity. Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune