Download or read book Innate Immune Induction in Influenza Infection written by Thomas Howard Oguin and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Influenza virus is a threat to public health on a global scale. Each year, millions of people are infected with influenza virus leading to hundreds of thousands of deaths. Despite progress in developing anti-influenza drugs, every antiviral compound used has caused influenza strains to mutate and become resistant to the drug. In order to improve our defenses against influenza virus, novel research strategies are needed. The innate immune system is the first line of defense against incoming pathogens. Many signaling networks are involved in coordinating an efficacious response to viral insult. We have found that lipid signaling through phospholipase D is critical to influenza pathogenesis. Influenza virus exploits this signaling to quickly infect human lung cells and evade the host antiviral response. By inhibiting this process, we observed a marked protection from infection. One of the critical molecules of the protective innate immune response after phospholipase D inhibition is interferon regulatory factor 3. Surprisingly, we found that mice missing this protein are more likely to survive a lethal influenza infection. This survival advantage depends on an amplified adaptive immune response. We are currently investigating this crosstalk between the innate and adaptive immune systems. One of the most potent direct antiviral effector molecules in the innate arsenal is myxovirus resistance gene 1. While this protein is generally considered to function by binding directly to viral proteins and inhibiting their functions, we have uncovered an unrecognized activity of this protein. We show that basal expression of this protein is critical in the induction of the innate immune response, and it is potentially involved in the signaling network that is constructed in response to influenza infection. These results help define the critical events mediating the host-virus interaction in infected epithelial cells. Future research for new antiviral strategies can exploit these novel pathways to enhance host responses and limit viral replication efficiency.
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 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 Host Innate Immune Responses to Infection by Avian and Bat borne Viruses written by Efstathios Giotis and published by Frontiers Media SA. This book was released on 2021-04-07 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Influenza Virology written by Yoshihiro Kawaoka and published by Horizon Scientific Press. This book was released on 2006 with total page 367 pages. Available in PDF, EPUB and Kindle. Book excerpt: World renowned scientists critically review the most important issues in this rapidly expanding field.
Download or read book Innate Immune Responses in Influenza A Virus Infected Cells written by Eva-Katharina Pauli and published by . This book was released on 2008 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book The Pathology of Influenza written by Milton C. Winternitz and published by . This book was released on 1920 with total page 164 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Antiviral Substances including Interferon written by and published by . This book was released on 1977 with total page 8 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Influenza Virus Vaccines and Immunotherapies written by Arun Kumar and published by Frontiers Media SA. This book was released on 2016-03-15 with total page 187 pages. Available in PDF, EPUB and Kindle. Book excerpt: Influenza virus infections lead to thousands of deaths worldwide annually and billions of dollars economic burden. Despite continuing advances in our understanding of the immune evasion mechanism, the disease remains one of the foremost threat for human being. Traditional vaccines (attenuated and inactivated) mainly provide protection by inducing virus neutralizing antibodies, targeting ever changing surface antigens: Haemagultinin (HA) and Neuraminidase (NA). Due to genetic shift and immune selection pressure, prevalence of circulating influenza virus subtypes changes every year. Therefore, mismatch between circulating strain and vaccine strain can critically affect the success rate of these conventional flu vaccines, and requires continuous monitoring of circulating influenza virus subtypes and change in the vaccine formulations accordingly. The collective limitations of existing flu vaccines urgently call for the development of a novel universal vaccines that might provide the required protective immunity to a range of influenza virus subtypes. New approaches are being investigated mainly targeting conserved regions of flu proteins. Some of these approaches include universally conserved epitopes of HA, nucleoprotein (NP), capsid protein (M1) and ion channel protein (M2) that induced strong immune responses in animal models. Some attention and progress appears to be focused on vaccines based on the M2 ectodomain (M2e) employing a variety of constructs, adjuvants and delivery systems, including M2e-hepatitis B core antigen, flagellin constructs, and virus-like particles (VLP). Animal studies with these M2e candidate vaccines demonstrated that these vaccine candidates can prevent severe illness and death but not infection, which may pose difficulties in both the evaluation of clinical efficacy and approval by the regulatory authorities. VLP vaccines appear to be promising, but still are mostly limited to animal studies. The discovery and development of new and improved vaccines have been greatly facilitated by the application of new technologies. The use of nucleic acid-based vaccines, to combine the benefits of in-situ expression of antigens with the safety of inactivated and subunit vaccines, has been a key advancement. Upon their discovery more than 20 years ago, nucleic acid vaccines promised to be a safe and effective mean to mimic immunization with a live organism vaccine, particularly for induction of T cell immunity. In addition, the manufacturing of nucleic acid-based vaccines offered the potential to be relatively simple, inexpensive and generic. Reverse Vaccinology and in-silico designing of vaccines are very innovative approaches and being considered as future of vaccines. Furthermore, various immuno-therapeutic agents also being developed to treat and minimize immuno-pathological damage in patients suffering from life threatening complications. For the treatment of such pathological conditions, various novel approaches such as administration of immune suppressive cytokines, blocking co-stimulatory signals or activating co-inhibitory signal of T cell activation, are being tested both in lab and clinics. The Research Topic on influenza virus vaccine and therapeutics will give an insight in to the current status and future scope of these new innovative approaches and technologies. Moreover, these new methods will also serve as a reference tool for the development of future vaccines against several other pathogens.
Download or read book Influenza Pathogenesis and Control Volume II written by Michael B. A. Oldstone and published by Springer. This book was released on 2014-11-06 with total page 478 pages. Available in PDF, EPUB and Kindle. Book excerpt: This two-volume work covers the molecular and cell biology, genetics and evolution of influenza viruses, the pathogenesis of infection, resultant host innate and adaptive immune response, prevention of infection through vaccination and approaches to the therapeutic control of infection.. Experts at the forefront of these areas provide critical assessments with regard to influenza virology, immunology, cell and molecular biology, and pathogenesis. Volume I provides overviews of the latest findings on molecular determinants of viral pathogenicity, virus entry and cell tropism, pandemic risk assessment, transmission and pathogenesis in animal species, viral evolution, ecology and antigenic variation, while Volume II focuses on the role of innate and adaptive immunity in pathogenesis, development of vaccines and antivirals.
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 Innate Immunity Programming and Memory in Resolving and Non Resolving Inflammation written by Liwu Li and published by Frontiers Media SA. This book was released on 2020-03-18 with total page 139 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Beneficial and Detrimental Functions of Innate Immunity Proteins During Viral Infection written by Ashley Zani and published by . This book was released on 2022 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Viral infections are an adverse occurrence that the body must work to control via the induction of a strong immune response. This generally includes the induction of a type I interferon response to halt the spread of virus early on and put the site of infection into an antiviral state. Programmed cell death pathways are also initiated as a means of clearing out infected cells and quelling further infection. However, over-activation of both of these pathways can lead to poor outcomes for the host and therefore require tight regulation of all players involved. There is perhaps no better example of the importance of immune regulation than in the context of pregnancy. Indeed, infections during pregnancy can cause a multitude of complications as the mother works to balance tolerance of the fetus with simultaneous fetal protection. A recent landmark study has indeed demonstrated that during Zika virus infection, activation of the maternal type I interferon (IFN) response is responsible for adverse fetal outcomes. We demonstrated that downstream of IFN, innate immune proteins, IFITM1, 2 and 3, block proper and necessary placental cell fusion. Specifically, cells expressing any of the IFITMs displayed decreased fusogenic ability. However, when the IFITMs were knocked down, cells fused spontaneously at high levels even in the presence of type I IFN. Our work demonstrated a negative function for typically beneficial antiviral proteins. Additionally, we have provided an evolutionary explanation as to why these proteins are tightly regulated and constantly ubiquitinated outside of the context of infection. On the other hand, the IFITMs, particularly IFITM3 continue to be critically important antiviral restriction factors in a wide array of viral infections. Indeed, individuals with single nucleotide polymorphisms (SNPs) in the IFITM3 gene are at increased risk of severe influenza virus infection. Therefore upon emergence of a new pandemic virus, SARS-CoV-2, it was critical to investigate whether individuals with IFITM3 SNPs would again be at increased risk of infection. To address this question we utilized two separate strains of SARS-CoV-2 and two separate IFITM3 KO mouse models. IFITM3 KO mice showed increases in morbidity and mortality with all of the animals succumbing to infection by day 5. KO mice displayed increases in general pathology as well as immune cell infiltration and had diffuse virus in the lungs that was distinct from the airway clustering pattern seen in the lungs of WT mice. At the RNA level, upregulation of antiviral and inflammatory pathways as well as genes associated with angiogenesis were seen in the KO animals compared to WT. Taken together our data demonstrate a key role for IFITM3 in inhibiting SARS-CoV-2 infection and suggest individuals with IFITM3 single nucleotide polymorphisms may be more at risk for severe disease. Additionally, we have previously shown that involvement of the non-canonical pyroptosis pathway, a programmed cell death pathway, is detrimental to outcomes in a mouse model of SARS-CoV-2 infection. Following this thread, we wanted to investigate the involvement of pyroptosis during influenza A virus infection. Specifically, we decided to look at the final effector protein gasdermin D (GSDMD) given its unknown role during influenza virus infection and potential as a prime antiviral target. We utilized WT and GSDMD KO mice and infected them with a semi-lethal dose of influenza A virus. Indeed KO mice survived longer and displayed decreased pathogenesis when compared to WT animals. KO mice also expressed decreases in inflammatory profiles via RNAseq analysis. Specifically, we observed that at the RNA level, neutrophil chemotaxis was among the top affected pathways and upon analysis via flow cytometry noted that KO animals had significantly decreased neutrophil infiltration in their lungs when compared to WT mice. Overall our work suggests a detrimental role for GSDMD during influenza virus infection and subsequently a negative consequence for extensive neutrophil infiltration. Together, the work presented in this dissertation demonstrates both the importance of activating a potent antiviral immune response but the equally important ability of the body to turn that response off. These insights have clinical implications that may shape future treatments of viral infections.
Download or read book Toll Like Receptors TLRs and Innate Immunity written by Stefan Bauer and published by Springer Science & Business Media. This book was released on 2007-12-11 with total page 243 pages. Available in PDF, EPUB and Kindle. Book excerpt: Overall recent research on TLRs has led to tremendous increase in our understanding of early steps in pathogen recognition and will presumably lead to potent TLR targeting therapeutics in the future. This book reviews and highlights our recent understanding on the function and ligands of TLRs as well as their role in autoimmunity, dendritic cell activation and target structures for therapeutic intervention.
Download or read book The Hypothalamus Pituitary Adrenal Axis written by and published by Elsevier. This book was released on 2008-09-12 with total page 413 pages. Available in PDF, EPUB and Kindle. Book excerpt: The hypothalamic-pituitary-adrenal axis controls reactions to stress and regulates various body processes such as digestion, the immune system, mood and sexuality, and energy usage. This volume focuses on the role it plays in the immune system and provides substantive experimental and clinical data to support current understanding in the field, and potential applications of this knowledge in the treatment of disease. Evidence presented in this book suggests that the nervous, endocrine, and immune systems form the Neuroendoimmune Supersystem, which integrates all the biological functions of higher organisms both in health and disease for their entire life cycle Contributors include both the scientists who initiated the work on the HPA axis and on the autonomic nervous system, and those who joined the field later
Download or read book Avian Influenza Virus written by Erica Spackman and published by Springer Science & Business Media. This book was released on 2008-02-28 with total page 147 pages. Available in PDF, EPUB and Kindle. Book excerpt: With the growing global fear of a major pandemic, avian influenza (AI) virus research has greatly increased in importance. In Avian Influenza Virus, an expert team of researchers and diagnosticians examine the fundamental, yet essential, virological methods for AI virus research and diagnostics as well as some of the newest molecular procedures currently used for basic and applied research. They present exciting, cutting-edge new methods that focus both on studying the virus itself and on work with avian hosts, an area greatly lacking in research.
Download or read book Crossroads Between Innate and Adaptive Immunity IV written by Peter D. Katsikis and published by Springer Science & Business Media. This book was released on 2013-03-01 with total page 144 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents a collection of reviews derived from work presented at the Aegean Conference: “4th Crossroads between innate and adaptive immunity”. This meeting was the fourth in a series, and assembled a team of scientists working on mechanisms by which the innate immune system of the host senses pathogens, the cellular and signaling networks that orchestrate the innate response and antigen presentation and adaptive immunity. The importance of the crosstalk between innate immunity and the adaptive immune response has only recently started to be appreciated. Although it is well recognized that dendritic cells, NK cells, NK-T cells and T cells are all critical for the host response to pathogens, the respective fields that study the biology of these immune cells tend to exist in parallel worlds with minimum exchange of information and ideas. This fragmentation hinders the integration of these fields towards a unified theory of host response. The Aegean Conference “Crossroads between Innate and Adaptive Immunity” brought together leading international scientists and experts to address critical areas of Innate and Adaptive immunity something necessary for the development of more efficient scientific exchange and crosspollination between these fields. This conference attracted scientists from all over the world to discuss their latest findings on the various aspects of Innate and Adaptive immunity. The conference had limited participation and a scientific and social program that maximized scientific interchange through lecture presentations, poster sessions and informal discussions.
