The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Ruslan Medzhitov - One of the best experts on this subject based on the ideXlab platform.
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control of Adaptive Immunity by the innate immune system
Nature Immunology, 2015Co-Authors: Akiko Iwasaki, Ruslan MedzhitovAbstract:Iwasaki and Mezhitov provide an update of their classic 2004 Review looking at the control of Adaptive Immunity by the innate immune system
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Control of Adaptive Immunity by the innate immune system
Nature Immunology, 2015Co-Authors: Akiko Iwasaki, Ruslan MedzhitovAbstract:Microbial infections are recognized by the innate immune system both to elicit immediate defense and to generate long-lasting Adaptive Immunity. To detect and respond to vastly different groups of pathogens, the innate immune system uses several recognition systems that rely on sensing common structural and functional features associated with different classes of microorganisms. These recognition systems determine microbial location, viability, replication and pathogenicity. Detection of these features by recognition pathways of the innate immune system is translated into different classes of effector responses though specialized populations of dendritic cells. Multiple mechanisms for the induction of immune responses are variations on a common design principle wherein the cells that sense infections produce one set of cytokines to induce lymphocytes to produce another set of cytokines, which in turn activate effector responses. Here we discuss these emerging principles of innate control of Adaptive Immunity.
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pattern recognition receptors and control of Adaptive Immunity
Immunological Reviews, 2009Co-Authors: Noah W Palm, Ruslan MedzhitovAbstract:Summary: The mammalian immune system effectively fights infection through the cooperation of two connected systems, innate and Adaptive Immunity. Germ-line encoded pattern recognition receptors (PRRs) of the innate immune system sense the presence of infection and activate innate Immunity. Some PRRs also induce signals that lead to the activation of Adaptive Immunity. Adaptive Immunity is controlled by PRR-induced signals at multiple checkpoints dictating the initiation of a response, the type of response, the magnitude and duration of the response, and the production of long-term memory. PRRs thus instruct the Adaptive immune system on when and how to best respond to a particular infection. In this review, we discuss the roles of various PRRs in control of Adaptive Immunity.
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innate control of Adaptive Immunity via remodeling of lymph node feed arteriole
Proceedings of the National Academy of Sciences of the United States of America, 2005Co-Authors: Kelly A Soderberg, Geoffrey W Payne, Ayuko Sato, Ruslan Medzhitov, Steven S Segal, Akiko IwasakiAbstract:The Adaptive immune system relies on rare cognate lymphocytes to detect pathogen-derived antigens. Naive lymphocytes recirculate through secondary lymphoid organs in search of cognate antigen. Here, we show that the naive-lymphocyte recirculation pattern is controlled at the level of innate immune recognition, independent of antigen-specific stimulation. We demonstrate that inflammation-induced lymphocyte recruitment to the lymph node is mediated by the remodeling of the primary feed arteriole, and that its physiological role is to increase the efficiency of screening for rare antigen-specific lymphocytes. Our data reveal a mechanism of innate control of Adaptive Immunity: by increasing the pool of naive lymphocytes for detection of foreign antigens via regulation of vascular input to the local lymph node.
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toll like receptors linking innate and Adaptive Immunity
Advances in Experimental Medicine and Biology, 2005Co-Authors: Chandrashekhar Pasare, Ruslan MedzhitovAbstract:Work in recent years has shown an essential role for Toll-like receptors (TLRs) in the activation of innate and Adaptive Immunity in vertebrate animals. These germ-line encoded receptors, expressed on a diverse variety of cells and tissues, recognize conserved molecular products derived from various classes of pathogens, including Gram-positive and -negative bacteria, DNA and RNA viruses, fungi and protozoa. Ligand recognition induces a conserved host defense program, which includes production of inflammatory cytokines, upregulation of costimulatory molecules, and induction of antimicrobial defenses. Importantly, activation of dendritic cells by TLR ligands is necessary for their maturation and consequent ability to initiate Adaptive immune responses. How responses are tailored by individual TLRs to contain specific classes of pathogens is not yet clear.
David Abraham - One of the best experts on this subject based on the ideXlab platform.
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Innate and Adaptive Immunity to the nematode Strongyloides stercoralis in a mouse model
Immunologic Research, 2011Co-Authors: Sandra Bonne-année, Jessica A Hess, David AbrahamAbstract:Mice have been used to the study the mechanisms of protective innate and Adaptive Immunity to larval Strongyloides stercoralis. During primary infection, neutrophils and eosinophils are attracted by parasite components and kill the larvae by release of granule products. Eosinophils also function as antigen-presenting cells for the induction of a Th2 response. B cells produce both IgM and IgG that collaborate with neutrophils to kill worms in the Adaptive immune response. Vaccine studies have identified a recombinant diagnostic antigen that induced high levels of Immunity to infection with S. stercoralis in mice. These studies demonstrate that there are redundancies in the mechanisms used by the immune response to kill the parasite and that a vaccine with a single antigen may be suitable as a prophylactic vaccine to prevent human strongyloidiasis.
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complement component c3 is required for protective innate and Adaptive Immunity to larval strongyloides stercoralis in mice
Journal of Immunology, 2006Co-Authors: Laura A Kerepesi, Jessica A Hess, Thomas J Nolan, Gerhard A Schad, David AbrahamAbstract:This study examines the role of complement components C3 and C5 in innate and Adaptive protective Immunity to larval Strongyloides stercoralis in mice. Larval survival in naive C3−/− mice was increased as compared with survival in wild-type mice, whereas C3aR−/− and wild-type mice had equivalent levels of larval killing. Larval killing in naive mice was shown to be a coordinated effort between effector cells and C3. There was no difference between survival in wild-type and naive C5−/− mice, indicating that C5 was not required during the innate immune response. Naive B cell-deficient and wild-type mice killed larvae at comparable levels, suggesting that activation of the classical complement pathway was not required for innate Immunity. Adaptive Immunity was equivalent in wild-type and C5−/− mice; thus, C5 was also not required during the Adaptive immune response. Larval killing was completely ablated in immunized C3−/− mice, even though the protective parasite-specific IgM response developed and effector cells were recruited. Protective Immunity was restored to immunized C3−/− mice by transferring untreated naive serum, but not C3-depleted heat-inactivated serum to the location of the parasites. Finally, immunized C3aR−/− mice killed larvae during the Adaptive immune response as efficiently as wild-type mice. Therefore, C3 was not required for the development of Adaptive Immunity, but was required for the larval killing process during both protective innate and Adaptive immune responses in mice against larval S. stercoralis.
Beverly L Davidson - One of the best experts on this subject based on the ideXlab platform.
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Platelet-Mediated Modulation of Adaptive Immunity: A Communication Link between Innate and Adaptive Immune Compartments
Immunity, 2003Co-Authors: Bennett D. Elzey, Axel K. Swanson, Jason R. Lees, Colleen S Stein, Steven R. Lentz, Bernhard Nieswandt, Robert J. Jensen, Yiqiang Wang, Jun Tian, Beverly L DavidsonAbstract:Abstract Platelets are highly reactive components of the circulatory system with well-documented hemostatic function. Recent studies extend platelet function to modulation of local inflammatory events through the release of chemokines, cytokines, and a number of immunomodulatory ligands, including CD154. We hypothesized that platelet-derived CD154 modulates Adaptive Immunity. The data reported herein demonstrate that platelets, via CD154, induce dendritic cell maturation, B cell isotype switching, and augment CD8 + T cell responses both in vitro and in vivo. Platelet transfusion studies demonstrate that platelet-derived CD154 alone is sufficient to induce isotype switching and augment T lymphocyte function during viral infection, leading to enhanced protection against viral rechallenge. Additionally, depletion of platelets in normal mice results in decreased antigen-specific antibody production.
Jay K Kolls - One of the best experts on this subject based on the ideXlab platform.
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conserved natural igm antibodies mediate innate and Adaptive Immunity against the opportunistic fungus pneumocystis murina
Journal of Experimental Medicine, 2010Co-Authors: Rekha R Rapaka, David M Ricks, John F Alcorn, Kong Chen, Shabaana A Khader, Mingquan Zheng, Scott Plevy, Eva Bengten, Jay K KollsAbstract:Host defense against opportunistic fungi requires coordination between innate and Adaptive Immunity for resolution of infection. Antibodies generated in mice vaccinated with the fungus Pneumocystis prevent growth of Pneumocystis organisms within the lungs, but the mechanisms whereby antibodies enhance antifungal host defense are poorly defined. Nearly all species of fungi contain the conserved carbohydrates β-glucan and chitin within their cell walls, which may be targets of innate and Adaptive Immunity. In this study, we show that natural IgM antibodies targeting these fungal cell wall carbohydrates are conserved across many species, including fish and mammals. Natural antibodies bind fungal organisms and enhance host defense against Pneumocystis in early stages of infection. IgM antibodies influence recognition of fungal antigen by dendritic cells, increasing their migration to draining pulmonary lymph nodes. IgM antibodies are required for Adaptive T helper type 2 (Th2) and Th17 cell differentiation and guide B cell isotype class-switch recombination during host defense against Pneumocystis. These experiments suggest a novel role for the IgM isotype in shaping the earliest steps in recognition and clearance of this fungus. We outline a mechanism whereby serum IgM, containing ancient specificities against conserved fungal antigens, bridges innate and Adaptive Immunity against fungal organisms.
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th17 cells at the crossroads of innate and Adaptive Immunity against infectious diseases at the mucosa
Mucosal Immunology, 2009Co-Authors: Shabaana A Khader, Sarah L Gaffen, Jay K KollsAbstract:T helper type 17 (Th17) cells are a distinct lineage of T cells that produce the effector molecules IL-17, IL-17F, IL-21, and IL-22. Although the role of Th17 cells in autoImmunity is well documented, there is growing evidence that the Th17 lineage and other interleukin (IL)-17-producing cells are critical for host defense against bacterial, fungal, and viral infections at mucosal surfaces. Here we summarize recent progress in our understanding of the function of IL-17-producing cells as a bridge between innate and Adaptive Immunity against infectious diseases at the mucosa.
Jian-zhong Shao - One of the best experts on this subject based on the ideXlab platform.
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b cells in teleost fish act as pivotal initiating apcs in priming Adaptive Immunity an evolutionary perspective on the origin of the b 1 cell subset and b7 molecules
Journal of Immunology, 2014Co-Authors: Lv-yun Zhu, Li Nie, Li-xin Xiang, Aifu Lin, Tong Shao, Weiren Dong, Jian-zhong ShaoAbstract:The long-held paradigm that B cells cannot uptake nonspecific particulate Ags for the initiation of primary Adaptive Immunity has been challenged by the recent discovery that teleost B cells have potent phagocytic and microbicidal abilities. This discovery provides preliminary clues that primitive B cells might act as initiating APCs in priming Adaptive Immunity. In this study, zebrafish B cells clearly showed a potent Ag-presenting ability to both soluble Ags and bacterial particles to prime naive CD4(+) T cell activation. This finding demonstrates the innate-like nature of teleost B cells in the interface of innate and Adaptive Immunity, indicating that they might consist of a major population of initiating APCs whose performance is similar to that of dendritic cells. Given the functional similarities between teleost B cells and the mammalian B-1 subset, we hypothesize that B-1 lineage and teleost B cells might originate from a common ancestor with potent phagocytic and initiating APC capacities. In addition, CD80/86 and CD83 costimulatory signals were identified as being essential for B cell-initiated Adaptive Immunity. This result suggests that the costimulatory mechanism originated as early as the origin of Adaptive Immunity and is conserved throughout vertebrate evolution. In fish, only a single CD80/86 copy exists, which is similar to mammalian CD86 rather than to CD80. Thus, CD86 might be a more primordial B7 family member that originated from fish. This study provides valuable insights into the evolutionary history of professional APCs, B cell lineages, and the costimulatory mechanism underlying Adaptive Immunity as a whole.
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Advances in research of fish immune-relevant genes: a comparative overview of innate and Adaptive Immunity in teleosts.
Developmental and comparative immunology, 2012Co-Authors: Lv-yun Zhu, Li Nie, Guan Zhu, Li-xin Xiang, Jian-zhong ShaoAbstract:Fish is considered to be an important model in comparative immunology studies because it is a representative population of lower vertebrates serving as an essential link to early vertebrate evolution. Fish immune-relevant genes have received considerable attention due to its role in improving understanding of both fish immunology and the evolution of immune systems. In this review, we discuss the current understanding of teleost immune-relevant genes for both innate and Adaptive Immunity, including pattern recognition receptors, antimicrobial peptides, complement molecules, lectins, interferons and signaling factors, inflammatory cytokines, chemokines, Adaptive Immunity relevant cytokines and negative regulators, major histocompatibility complexes, immunoglobulins, and costimulatory molecules. The implications of these factors on the evolutionary history of immune systems were discussed and a perspective outline of innate and Adaptive Immunity of teleost fish was described. This review may provide clues on the evolution of the essential defense system in vertebrates.