Download or read book Type I Interferon Directly Regulates B Cell Function During the Response to Influenza Virus Infection written by Stephen Omeade Priest and published by . This book was released on 2013 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Type I interferon (IFN-I) is a potent antiviral cytokine, whose pleotropic effects makes it a key signal in the regulation of both the innate and adaptive arms of the immune response to virus infection. Its innate effects, which include antiproliferative and pro-apoptotic effects, have been characterized in extensive studies, as has its immunomodulatory role enhancing NK cell, macrophage, and dendritic cell fuction. Recent findings indicate type I IFN also directly stimulates B cells during virus infection, affecting the subsequent antibody response. The mechanisms by which it regulates B cells are unclear. Here I began by exploring two potential direct effects of IFN-I on B cells and their responses to influenza virus infection. Following a summary in Chapter 1 of existing literature linking innate signals in the regulation of B cell responses to influenza virus infection, I define in Chapter 2 the effects of Type I IFN-signaling on B cell proliferation and survival. I examine these effects both in vitro with and without BCR stimulation, and in vivo in the context of homeostatic expansion and influenza virus infection. The study shows that the balance of IFN-I's effects on apoptosis and cell cycle regulation determine the outcome of B cell proliferative responses, with the net effect dependent on the context of the mitogenic stimuliation. Specifically, IFN-enhanced survival was reversed in proliferating B cells, enhancing apoptosis following both in vitro and in vivo stimulation. In BCR-stimulated B cell in vitro, the net effect was negative as cell cycle entry and proliferation was reduced by IFN-I. However the net effect was neutral in vivo during homeostatic expansion and influenza virus infection, as cell cycle entry was enhanced by IFN-I signaling, suggesting the involvement of additional IFN-I-mediated signals in regulating B cell proliferation. In Chapter 3 the role of type I IFN-mediated induction of TLR7 by B cells is considered in the context of influenza virus infection. We show that B cell functional responses to influenza virus infection are enhanced by locally generated IFN-I, corresponding with its ability to directly increase TLR7 expression in B cells. Furthermore, we show close correllations between IFN-I and TLR7 signaling in regulating B cell proliferation and antibody responses to influenza virus infection. Together, these findings establish IFN-I's key role in promoting B cell clonal expansion during virus infection, likely through enhanced sensitivity to TLR7-mediate stimulation. Notably, studies in BXSB mice, a strain in which male mice overexpress TLR7 due to an additional copy of the gene on the Y-chromosome, demonstrate the aparent presence of a threshold of TLR7 expression that cannot be overcome by IFN-I signaling, and thereby indicate the tight regulation of this innate receptor in B cells. Overall, this study demonstrates that type I IFN directly regulates B cell function during steady-state, homeostatic expansion, and influenza virus infection, through its combined effects on apoptosis, cell cycle progression, and TLR7 expression.

Download or read book The Innate Regulation of B 1 Lymphocyte Responses to Influenza Virus Infection written by Elizabeth Emlika Waffarn and published by . This book was released on 2014 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple B lymphocyte subsets contribute to immune responses to pathogens. Among these, B-1 cells are a small subset of innate-like B cells whose development, phenotype, tissue distribution, and functions are distinct from those of conventional B-2 cells, and whose responses are crucial to protection against mucosal bacterial and viral pathogens. B-1 cells contribute to protective responses even before infection, by secreting natural antibody, a polyspecific repertoire of mostly IgM antibodies produced constitutively in the absence of foreign antigens. In response to influenza virus infection, B-1 cells actively respond by accumulating locally in draining mediastinal lymph nodes (MedLN), where they differentiate to secrete both virus-binding and non virus-binding IgM. Multiple details from those earlier studies suggest that the regulation of B-1a cell responses differs from that of conventional B-2 cells and that infection-induced but antigen-independent mechanisms contribute to B-1a cell activation and function. This dissertation explores the hypothesis that B-1 cells are regulated by the quality and magnitude of local infection-induced innate immune signals, including type I interferon (IFNs) and IL-1, critical mediators of anti-viral responses and pro-inflammatory signaling. Previous studies of IL1R-/- mice showed that IL-1 signaling was required for maximal secretion of IgM and IgA after influenza infection. Because B-1 cells contribute at least half of influenza-induced IgM, we investigated the effects of IL-1 on B-1 cell redistribution and activation for IgM secretion. The studies outlined in the Second Chapter revealed that direct IL-1 stimulation did not contribute to the redistribution of B-1 cells to the lymph nodes, as it was neither directly chemotactic for B-1 cells, did not mobilize B-1 cells in vivo, nor altered the ability of B-1 cells to respond to the lymph node homing chemokines CXCL12 and CXCL13 in vitro. Instead, we found that IL-1 treatment alone modestly induced their IgM secretion in vitro. Using chimeric mice in which only B-1 cells lacked the IL-1R and which are distinguishable from B-2 cells based on Ig-allotypic differences, we investigated the ability of B-1 cells to respond to influenza virus infection. The data showed that these signals were required for maximum induction not only of CD5- B-1 cells, but also of the mostly B-2 cell-derived plasma blasts. Consistent with these findings we found IgM production both by B-1 and B-2 cells reduced. To begin to determine the mechanism by which B-1 cell IL-1 stimulation causes B-2 cell differentiation, we found that IL-1 stimulation selectively induced GM-CSF stimulation by B-1 cells. Furthermore, supernatants of IL-1-stimulated B-1 cells were able to induce IgM secretion by B-2 cells in vitro. Together, these findings suggest that activated B-1 cells play a regulatory role within lymph nodes by guiding conventional B-2 cell responses. In the Third Chapter, we took a genome-wide gene expression array approach to conduct an unbiased analysis of B-1a cell populations in the peritoneal and pleural cavity and the spleen, before and at two time points after infection. The goal was to identify all signals that affect B-1a cells following influenza infection in vivo and to identify a likely source from which lymph node B-1 cells were recruited. Somewhat surprisingly, the results revealed strong gene expression differences present before infection between B-1 cells from different tissues. Influenza virus infection further altered gene expression from all three sites, but the strongest changes occurred in pleural cavity B-1a cells within 2 days of infection, indicating that rapidly induced, locally elaborated infection signals impact B-1a cells. Based on the affected genes, type I IFN was identified as a strong early innate factor providing site-specific signaling to B-1a cells. These results suggest that B-1a cells receive site-specific signals even prior to infection and that infection-induced local signals strongly affect pleural cavity B-1a cells, likely shaping their antiviral response. The Fourth Chapter investigates the tissue origins of B-1a cells accumulating at the site of influenza infection and the role of type I IFN in their migration and differentiation. Labeled B-1a cells preferentially redistributed from pleural cavity sites to the draining MedLN after influenza infection, consistent with the results of our microarray analyses. However, in mice in which only B cells, or only B-1 cells lacked IFNR-expression, this enhanced accumulation was absent suggesting a role for type I IFN signaling B-1 cell redistribution. An in vitro vascular mimetic chamber model was used to evaluate the adherence of B-1 cells to a substrate consisting of ICAM-1 and CXCL13. Strikingly, type I IFN treatment or in vivo influenza infection stimulated B-1 cells to arrest on the substrate. Antibody-blocking studies showed that this was due to the increased integrin-mediated binding to ICAM-1. In vivo competition experiments designed to measure the ability of B-1 cells, from wildtype and CD11b or CD11a integrin-deficient mice, to accumulate in the MedLN in response to influenza infection after transfer into the pleural cavity of recipient mice, demonstrated the importance of CD11b in the B-1 cell redistribution process. Further studies suggested that type I IFN acts to enhance CD11b-mediated lymph node accumulation by activating the conformation state of CD11b. These studies identify a novel axis of type I IFN mediated integrin activation for rapid regulation of innate lymphocyte redirection. Together, these studies provide two examples of innate-signaling mediated regulation of B-1 cell responses during influenza infection. The results indicate that B-1 cells in the body cavities are optimally positioned to rapidly respond to an infection and that their characteristic expression of CD11b aids in rapid migration and accumulation in regional lymphoid tissues. Finally, the results of this study also suggest that B-1a cells broadly regulate the adaptive antiviral response by providing non-redundant signals to conventional B-2 cells for maximal induction of virus-specific antibody responses.

Download or read book The Role of Il 17a in Modulating B Cell Response During Influenza Virus Infection written by Xiaohui Wang and published by . This book was released on 2017-01-27 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: This dissertation, "The Role of IL-17A in Modulating B Cell Response During Influenza Virus Infection" by Xiaohui, Wang, 王晓辉, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Interleukin-17A (IL-17A)is an important pro-inflammatory cytokine that plays a critical role in host defenses against diverse pathogens. Studies have shown that IL-17Aplays protective role against sub-lethal H1 and H3 subtypes influenza infections, but it is unclear about the role of IL-17A in the highly pathogenic H5N1 and lethal H1N1 influenza virus infection. B cell is an important effector cell type in anti-influenza immunity. Although roles of B cell in influenza infection have been extensively investigated, it is unclear whether and how IL-17AregulatesB cell response during influenza infection. I examined the role of IL-17A against influenza infection by challengingIL-17A knockout (KO) and wild-type (WT) mice with highly pathogenic H5N1 and lethal H1N1 influenza viruses. Following challenge, IL-17AKO mice exhibited significantly lower survival rate, profoundly reduced body weight, more severe tissue damage and higher viral burden in the lung tissues. These evidences suggest that IL-17Aplays a protective role in lethal influenza infection. To study whether IL-17Amodulates B cell response against influenza, I found that both B-1a and B-2 cells were detected in the lung tissue and pulmonary draining lymph node, Mediastinal lymph node (MedLN), as early as 2days post-infection. Meanwhile, B-1a cells predominantly contributed to the early virus-specific IgM in the respiratory tract. However, virus-specific IgM markedly reduced in IL-17A KO mice when compared with WT controls. Adoptive transfer of B-1a cells or B-1a cell-derived antibodies conferred protection in IL-17A KO mice. These results demonstrate that IL-17A plays a critical role in modulating early antibody production of B-1a cells against lethal influenza infection. To further elucidate how IL-17A regulates B-1a cell response, I observed that B-1a cells migrated into MedLN and lung tissues during infection and underwent plasmacytic differentiation with increased antibody production in airways. IL-17A deficiency impaired these processes of B-1a cells, while intra-nasally instillation of IL-17A restored B-1a cell response by promoting both B-1a cell migration and plasmacytic differentiation. By inducing blimp-1 expression in B-1a cells in an NF-κB dependent pathway, IL-17A directly promoted plasmacytic differentiation of B-1a cells both in vivo and in vitro. Furthermore, chromatin immuno-precipitation analysis confirmed that NF-κB directly bound to the promoter of blimp-1 gene and promoted blimp-1 expression in B-1a cells following IL-17A stimulation. To determine the functional significance of IL-17A signaling in modulating B cell response against influenza infection, I first uncovered markedly reduced B cell response, predominantly B-1a cell response in IL-17A KO mice, showing reduced local migration and impaired plasmacytic differentiation in the early stage of infection. Next, intra-nasal administration of IL-17A into IL-17A KO mice significantly restored this B-1a cell response. Moreover, I detected expression of IL-17A receptor in B-1a cells. IL-17A treatment could promote antibody production from B-1a cells by inducing blimp-1 expression in an NF-κB dependent pathway. Taken together, these findings identify a novel role of IL-17A in actingas an immune modulator of B cell response against influenza infection, which will contribute to a fuller understanding of B cell biology and anti-vi

Download or read book Janeway s Immunobiology written by Kenneth Murphy and published by Garland Science. This book was released on 2010-06-22 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The Janeway's Immunobiology CD-ROM, Immunobiology Interactive, is included with each book, and can be purchased separately. It contains animations and videos with voiceover narration, as well as the figures from the text for presentation purposes.

Download or read book Human Herpesviruses written by Ann Arvin and published by Cambridge University Press. This book was released on 2007-08-16 with total page 1325 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive account of the human herpesviruses provides an encyclopedic overview of their basic virology and clinical manifestations. This group of viruses includes human simplex type 1 and 2, Epstein–Barr virus, Kaposi's Sarcoma-associated herpesvirus, cytomegalovirus, HHV6A, 6B and 7, and varicella-zoster virus. The viral diseases and cancers they cause are significant and often recurrent. Their prevalence in the developed world accounts for a major burden of disease, and as a result there is a great deal of research into the pathophysiology of infection and immunobiology. Another important area covered within this volume concerns antiviral therapy and the development of vaccines. All these aspects are covered in depth, both scientifically and in terms of clinical guidelines for patient care. The text is illustrated generously throughout and is fully referenced to the latest research and developments.

Download or read book Viral Gastroenteritis written by Shunzo Chiba and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 301 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recently, rapid developments have occurred in the field of viral gastroenteritis. This book is an update of fundamental and practical aspects of viral gastroenteritis. Among the various agents that cause viral gastroenteritis, group A rotaviruses and caliciviruses are the focus of this volume because of their clinical impact and the significance of new findings about them.

Download or read book Persistent Viral Infections written by R. Ahmed and published by Wiley-Blackwell. This book was released on 1999 with total page 754 pages. Available in PDF, EPUB and Kindle. Book excerpt: Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.

Download or read book Molecular Virology of Human Pathogenic Viruses written by Wang-Shick Ryu and published by Academic Press. This book was released on 2016-03-30 with total page 441 pages. Available in PDF, EPUB and Kindle. Book excerpt: Molecular Virology of Human Pathogenic Viruses presents robust coverage of the key principles of molecular virology while emphasizing virus family structure and providing key context points for topical advances in the field. The book is organized in a logical manner to aid in student discoverability and comprehension and is based on the author’s more than 20 years of teaching experience. Each chapter will describe the viral life cycle covering the order of classification, virion and genome structure, viral proteins, life cycle, and the effect on host and an emphasis on virus-host interaction is conveyed throughout the text. Molecular Virology of Human Pathogenic Viruses provides essential information for students and professionals in virology, molecular biology, microbiology, infectious disease, and immunology and contains outstanding features such as study questions and recommended journal articles with perspectives at the end of each chapter to assist students with scientific inquiries and in reading primary literature. Presents viruses within their family structure Contains recommended journal articles with perspectives to put primary literature in context Includes integrated recommended reading references within each chapter Provides access to online ancillary package inclusive of annotated PowerPoint images, instructor’s manual, study guide, and test bank

Download or read book Fields Virology Emerging Viruses written by Peter M. Howley and published by Lippincott Williams & Wilkins. This book was released on 2020-02-11 with total page 2597 pages. Available in PDF, EPUB and Kindle. Book excerpt: Now in four convenient volumes, Field’s Virology remains the most authoritative reference in this fast-changing field, providing definitive coverage of virology, including virus biology as well as replication and medical aspects of specific virus families. This volume of Field’s Virology: Emerging Viruses, 7th Edition covers recent changes in emerging viruses, providing new or extensively revised chapters that reflect these advances in this dynamic field.

Download or read book Mucosal Vaccines written by Hiroshi Kiyono and published by Elsevier. This book was released on 1996-10-23 with total page 501 pages. Available in PDF, EPUB and Kindle. Book excerpt: This comprehensive, authoritative treatise covers all aspects of mucosal vaccines including their development, mechanisms of action, molecular/cellular aspects, and practical applications. The contributing authors and editors of this one-of-a-kind book are very well known in their respective fields. Mucosal Vaccines is organized in a unique format in which basic, clinical, and practical aspects of the mucosal immune system for vaccine development are described and discussed. This project is endorsed by the Society for Mucosal Immunology. Provides the latest views on mucosal vaccines Applies basic principles to the development of new vaccines Links basic, clinical, and practical aspects of mucosal vaccines to different infectious diseases Unique and user-friendly organization

Download or read book Immunity to Listeria Monocytogenes written by E R Unanue and published by Academic Press. This book was released on 2012-01-24 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt: Advances in Immunology, a long-established and highly respected publication, presents current developments as well as comprehensive reviews in immunology. Articles address the wide range of topics that comprise immunology, including molecular and cellular activation mechanisms, phylogeny and molecular evolution, and clinical modalities. Edited and authored by the foremost scientists in the field, each volume provides up-to-date information and directions for the future. Contributions from leading authorities Informs and updates on all the latest developments in the field

Download or read book Interferon s New Regulators of Inflammatory Processes written by Ivan Zanoni and published by Frontiers Media SA. This book was released on 2020-01-14 with total page 120 pages. Available in PDF, EPUB and Kindle. Book excerpt:

Download or read book Zika and Other Neglected and Emerging Flaviviruses E Book written by Lisa A. Beltz and published by Elsevier Health Sciences. This book was released on 2021-02-23 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: Offering up-to-date coverage of familiar flaviviruses that are spreading into new regions or are causing increasingly severe disease, as well as viruses that are almost unknown in most developed nations, Zika and Other Neglected and Emerging Flaviviruses brings together information that allows for easy comparison of similarities and differences of this viral group in a single, convenient volume. Each chapter includes a brief Introduction, history, the diseases, the virus, the immune response, prevention or treatment, an extensive list of references, and a summary overview. The book concludes with a chapter tying together information about flaviviruses and other potential new microbial threats. Covers familiar flaviviruses that are spreading into new regions or are causing increasingly severe disease (such as Zika, dengue and West Nile viruses), as well as lesser-knowns viruses such as tick-borne encephalitis virus, Powassan virus, Omsk hemorrhagic fever, and Murray Valley encephalitis virus. Allows health-related personnel to search for potential treatments and protective responses by examining what measure did or did not work with other, related flaviviruses. Helps readers understand how to prevent or contain newly emerging viral threats—a particularly timely topic regarding the global spread of COVID-19 and the potential of tick-borne encephalitis to rapidly spread and cause severe illness, panic, and disruption of economies. Consolidates today’s available information on this timely topic into a single, convenient resource.

Download or read book Virus Dynamics Mathematical Principles of Immunology and Virology written by Martin Nowak and published by Oxford University Press, UK. This book was released on 2000-11-23 with total page 253 pages. Available in PDF, EPUB and Kindle. Book excerpt: This groundbreaking book describes the emerging field of theoretical immunology, in particular the use of mathematical models to describe the spread of infectious diseases within patients. It reveals fascinating insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. Structured around the examples of HIV/AIDS and hepatitis B, Nowak and May show how mathematical models can help researchers to understand the detailed dynamics of infection and the effects of antiviral therapy. Models are developed to describe the dynamics of drug resistance, immune responses, viral evolution and mutation, and to optimise the design of therapy and vaccines. - ;We know, down to the tiniest details, the molecular structure of the human immunodeficiency virus (HIV). Yet despite this tremendous accomplishment, and despite other remarkable advances in our understanding of individual viruses and cells of the immune system, we still have no agreed understanding of the ultimate course and variability of the pathogenesis of AIDS. Gaps in our understanding like these impede our efforts towards developing effective therapies and preventive vaccines. Martin Nowak and Robert M May describe the emerging field of theoretical immunology in this accessible and well- written text. Using mathematical modelling techniques, the authors set out their ideas about how populations of viruses and populations of immune system cells may interact in various circumstances, and how infectious diseases spread within patients. They explain how this approach to understanding infectious diseases can reveal insights into the dynamics of viral and other infections, and the interactions between infectious agents and immune responses. The book is structured around the examples of HIV/AIDS and Hepatitis B virus, although the approaches described will be more widely applicable. The authors use mathematical tools to uncover the detailed dynamics of the infection and the effects of antiviral therapy. Models are developed to describe the emergence of drug resistance, and the dynamics of immune responses, viral evolution, and mutation. The practical implications of this work for optimisation of the design of therapy and vaccines are discussed. The book concludes with a glance towards the future of this fascinating, and potentially highly useful, field of study. - ;... an excellent introduction to a field that has the potential to advance substantially our understanding of the complex interplay between virus and host - Nature

Download or read book Biological DNA Sensor written by Ken Ishii and published by Academic Press. This book was released on 2013-10-30 with total page 369 pages. Available in PDF, EPUB and Kindle. Book excerpt: Biological DNA Sensor defines the meaning of DNA sensing pathways and demonstrates the importance of the innate immune responses induced by double stranded DNA (dsDNA) through its influencing functions in disease pathology and immune activity of adjuvants for vaccines. Though discussed in specific subsections of existing books, dsDNA and its immunogenic properties has never received the complete treatment given in this book. Biological DNA Sensor approaches the impact of dsDNA's immunogenicity on disease and vaccinology holistically. It paints a complete and concise picture on the topic so you can understand this area of study and make more informed choices for your respective research needs. Chapters are authored by researchers who are renowned for their research focus, ensuring that this book provides the most complete views on the topics. Multi-authored by a distinguished panel of world-class experts Ideal source of information for those wanting to learn about DNA sensing Provides in-depth explanations of DNA sensing pathways and the innate immune system, bridging the gap between them

Download or read book Encyclopedia of Virology written by Allan Granoff and published by Academic Press. This book was released on 1999-09-03 with total page 926 pages. Available in PDF, EPUB and Kindle. Book excerpt: Reference source of current virological knowledge. It is also the first to bring together all aspects of the subject for a wide variety of readers. Unique in its use of concise 'mini-review' articles, the mate rial covers biological, molecular, and medical topics concerning viruses in animals, plants, bacteria, and insects. More general articles focus on the effects of viruses on the immune system, the role of viruses in disease, oncology, gene therapy, and evolution, plus a wide range of related topics.

Download or read book Viruses and Man A History of Interactions written by Milton W. Taylor and published by Springer. This book was released on 2014-07-21 with total page 433 pages. Available in PDF, EPUB and Kindle. Book excerpt: Milton Taylor, Indiana University, offers an easy-to-read and fascinating text describing the impact of viruses on human society. The book starts with an analysis of the profound effect that viral epidemics had on world history resulting in demographic upheavals by destroying total populations. It also provides a brief history of virology and immunology. Furthermore, the use of viruses for the treatment of cancer (viral oncolysis or virotherapy) and bacterial diseases (phage therapy) and as vectors in gene therapy is discussed in detail. Several chapters focus on viral diseases such as smallpox, influenza, polio, hepatitis and their control, as well as on HIV and AIDS and on some emerging viruses with an interesting story attached to their discovery or vaccine development. The book closes with a chapter on biological weapons. It will serve as an invaluable source of information for beginners in the field of virology as well as for experienced virologists, other academics, students, and readers without prior knowledge of virology or molecular biology.