Download or read book Lymphocytes in MS and EAE More than just a CD4 World written by Manu Rangachari and published by Frontiers Media SA. This book was released on 2017-10-10 with total page 162 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is degenerative disease of the central nervous system (CNS) in which myelin destruction and axon loss leads to the accumulation of physical, cognitive, and mental deficits. MS affects more than a million people worldwide and managing this chronic disease presents a significant health challenge. Multiple lines of evidence indicate that MS is an autoimmune disorder in which immune cells launch an inflammatory attack targeting myelin antigens. Indeed, myelin-reactive T cells and antibodies have been identified in MS patients and in animal models (namely experimental autoimmune encephalomyelitis, or EAE) that recapitulate many features of human disease. Animal model studies have demonstrated that T cells are both necessary and sufficient to initiate and sustain CNS autoimmunity. However, most MS animal models rely on the role played by CD4+ T cells and partially replicate the multiple aspects of MS pathogenesis. Thus, research in the past has focused heavily on the contribution of CD4+ T cells to the disease process; searching PubMed for “MS AND CD4” yields twice the results as corresponding searches for “CD8” or “B cell” and four times that for “NK cells”. While CD4+ T cells may represent the minimum requirement to mediate CNS autoimmunity, it is clear that the immune response underlying human MS is far more complex and involves numerous other immune cells and subsets. This is well illustrated by the observation that MS patients treated with an anti-CD4 depleting antibody did not gain any clinical benefits whereas removal of several lymphocyte subsets using an anti-CD52 depleting antibody has been shown to impede disease progression. In particular, the pathogenic role(s) of non-CD4+ T cell lymphocytes is relatively poorly understood and under-researched, despite evidence that these subsets contribute to disease pathology or regulation. For example, the observed oligoclonal expansion of CD8+ T cells within the CNS compartment supports a local activation. CD8+ T cells with polarized cytolytic granules are seen in close proximity to oligodendrocytes and demyelinated axons in MS tissues. The presence of B cells in inflammatory lesions and antibodies in the CSF have long been recognized as features of MS and Rituximab, a B cell depleting therapy, has been shown to be highly effective to treat MS. Intriguingly, the putative MS therapeutic reagent Daclizumab may function in part through the expansion of a subset of immunoregulatory NK cells. NKT and γδ T cells may also play a role in CNS autoimmunity, given that they respond to lipid antigens and that myelin is lipid-rich. While different animal models recapitulate some of these aspects of human disease, identifying appropriate models and measures to investigate the role of these less well-understood lymphocytes in MS remains a challenge for the field. This Frontiers research topic aims to create a platform for both animal- and human-focused researchers to share their original data, hypotheses, future perspectives and commentaries regarding the role of these less-well understood lymphocyte subsets (CD8+ T cells, B cells, NK cells, NK T cells, γδ T cells) in the pathogenesis of CNS autoimmunity.
Download or read book Multiple Sclerosis written by Ian S. Zagon and published by . This book was released on 2017 with total page 137 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Advances in the Immunopathogenesis of Multiple Sclerosis written by Domencio Gambi and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 111 pages. Available in PDF, EPUB and Kindle. Book excerpt: P.A. MURARO, A. LUGARESI, D. GAMBI Many of the pathological aspects of multiple sclerosis (MS) lesions have been known for over a century. It is only recently, however, that different patterns of demyelination have been linked to distinct pathways of immune-mediated tissue destruction. In particular, the inter-individual heterogeneity of MS lesions has suggested that different mechanisms may act in different patients, accounting for the variability observed in clinical course, immunological findings in peripheral blood and cere brospinal fluid (CSF), and response to immunomodulatory treatments. To provide an overview of the basic mechanisms possibly involved in MS lesion initiation and development, an international meeting was organized in the context of the annual Congress of the Italian Neuroimmunology Association (AINI), held at the University of Chieti, in Chieti Italy on 29 October 1998. The high standard of presentations prompted us to report them in extended form, to highlight recent pro gress in the understanding of basic mechanisms sustaining MS immuno pathogenesis. A central role in the possible mechanisms leading to myelin destruc tion has been attributed to T lymphocytes reactive to myelin antigens. Studies on the myelin antigen-specific T cell repertoire have contributed significant advances to our knowledge of autoimmunity (Chapters 1,2).
Download or read book Lymphocytes in MS and EAE More Than Just a CD4 World written by and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is degenerative disease of the central nervous system (CNS) in which myelin destruction and axon loss leads to the accumulation of physical, cognitive, and mental deficits. MS affects more than a million people worldwide and managing this chronic disease presents a significant health challenge. Multiple lines of evidence indicate that MS is an autoimmune disorder in which immune cells launch an inflammatory attack targeting myelin antigens. Indeed, myelin-reactive T cells and antibodies have been identified in MS patients and in animal models (namely experimental autoimmune encephalomyelitis, or EAE) that recapitulate many features of human disease. Animal model studies have demonstrated that T cells are both necessary and sufficient to initiate and sustain CNS autoimmunity. However, most MS animal models rely on the role played by CD4+ T cells and partially replicate the multiple aspects of MS pathogenesis. Thus, research in the past has focused heavily on the contribution of CD4+ T cells to the disease process; searching PubMed for "MS AND CD4" yields twice the results as corresponding searches for "CD8" or "B cell" and four times that for "NK cells". While CD4+ T cells may represent the minimum requirement to mediate CNS autoimmunity, it is clear that the immune response underlying human MS is far more complex and involves numerous other immune cells and subsets. This is well illustrated by the observation that MS patients treated with an anti-CD4 depleting antibody did not gain any clinical benefits whereas removal of several lymphocyte subsets using an anti-CD52 depleting antibody has been shown to impede disease progression. In particular, the pathogenic role(s) of non-CD4+ T cell lymphocytes is relatively poorly understood and under-researched, despite evidence that these subsets contribute to disease pathology or regulation. For example, the observed oligoclonal expansion of CD8+ T cells within the CNS compartment supports a local activation. CD8+ T cells with polarized cytolytic granules are seen in close proximity to oligodendrocytes and demyelinated axons in MS tissues. The presence of B cells in inflammatory lesions and antibodies in the CSF have long been recognized as features of MS and Rituximab, a B cell depleting therapy, has been shown to be highly effective to treat MS. Intriguingly, the putative MS therapeutic reagent Daclizumab may function in part through the expansion of a subset of immunoregulatory NK cells. NKT and ?d T cells may also play a role in CNS autoimmunity, given that they respond to lipid antigens and that myelin is lipid-rich. While different animal models recapitulate some of these aspects of human disease, identifying appropriate models and measures to investigate the role of these less well-understood lymphocytes in MS remains a challenge for the field. This Frontiers research topic aims to create a platform for both animal- and human-focused researchers to share their original data, hypotheses, future perspectives and commentaries regarding the role of these less-well understood lymphocyte subsets (CD8+ T cells, B cells, NK cells, NK T cells, ?d T cells) in the pathogenesis of CNS autoimmunity.
Download or read book Multiple Sclerosis Immunology written by Takashi Yamamura and published by Springer Science & Business Media. This book was released on 2013-09-14 with total page 468 pages. Available in PDF, EPUB and Kindle. Book excerpt: The availability of powerful genome-wide association study technology, during the last five years, has shown that most of the “new” MS susceptibility loci are immune-response genes. It is clear that there is much novelty in the field of MS immunology, which has served as an impetus to invest in new therapies. Notably, most if not all of these are immunotherapies. Even the equally exciting field of cell-based therapies and neuro-regeneration may well rely on cells or growth factors that are no less immunomodulators than restorative of myelin and neural cell function. Multiple Sclerosis Immunology looks at MS immunology as the basis for the present and—even more—the future of treatments for this complex autoimmune condition. Both editors are immunologists, as well as clinical neurologists, and appreciate the importance of a sustained dialogue between basic and clinical scientists to ensure that “translation” is real and not just virtual.
Download or read book T cell Autoimmunity and Multiple Sclerosis written by Marco Londei and published by Landes Bioscience. This book was released on 1999 with total page 170 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Molecular Basis of Multiple Sclerosis written by Roland Martin and published by Springer Science & Business Media. This book was released on 2010-09-14 with total page 306 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite major efforts by the scientific community over the years, our understanding of the pathogenesis or the mechanisms of injury of multiple sclerosis is still limited. Consequently, the current strategies for treatment and management of patients are limited in their efficacy. The mechanisms of tissue protection and repair are probably even less understood. One reason for these limitations is the enormous complexity of the disease and every facet of its pathogenesis, the mechanisms of tissue injury, the diagnostic procedures and finally the efficacy of treatments and their side effects. The aim of this book is to review the most recent advances made in this highly complex field.
Download or read book Cellular and Molecular Mechanisms in Pathogenesis of Multiple Sclerosis written by Edwin Wan and published by MDPI. This book was released on 2020-11-25 with total page 182 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis (MS) is one of the most common neurological disorders in young adults. The etiology of MS is not known, but it is generally accepted that it is autoimmune in nature. Our knowledge of the pathogenesis of MS has increased tremendously in the past decade through clinical studies and the use of experimental autoimmune encephalomyelitis (EAE), a model that has been widely used for MS research. Major advances in the field, such as understanding the roles of pathogenic Th17 cells, myeloid cells, and B cells in MS/EAE, as well as cytokine and chemokine signaling that controls neuroinflammation, have led to the development of potential and clinically approved disease-modifying agents (DMAs). There are many aspects related to the initiation, relapse and remission, and progression of MS that are yet to be elucidated. For instance, what are the genetic and environmental risk factors that promote the initiation of MS, and how do these factors impact the immune system? What factors drive the progression of MS, and what are the roles of peripheral immune cells in disease progression? How do the CNS-infiltrated immune cells interact with the CNS-resident glial cells when the disease progresses? What is the role of microbiome in MS? Can we develop animal models that better represent subcategories of MS? Understanding the cellular and molecular mechanisms that govern the pathogenesis of MS will help to develop novel and more specific therapeutic strategies that will ultimately improve clinical outcomes of the treatments. This Special Issue of Cells has published original research articles, a retrospective clinical report, and review articles that investigate the cellular and molecular basis of MS.
Download or read book Regeneration in the Central Nervous System written by William Frederick Windle and published by . This book was released on 1955 with total page 600 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Multiple Sclerosis written by Institute of Medicine and published by National Academies Press. This book was released on 2001-08-10 with total page 457 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is a chronic and often disabling disease of the nervous system, affecting about 1 million people worldwide. Even though it has been known for over a hundred years, no cause or cure has yet been discovered-but now there is hope. New therapies have been shown to slow the disease progress in some patients, and the pace of discoveries about the cellular machinery of the brain and spinal cord has accelerated. This book presents a comprehensive overview of multiple sclerosis today, as researchers seek to understand its processes, develop therapies that will slow or halt the disease and perhaps repair damage, offer relief for specific symptoms, and improve the abilities of MS patients to function in their daily lives. The panel reviews existing knowledge and identifies key research questions, focusing on: Research strategies that have the greatest potential to understand the biological mechanisms of recovery and to translate findings into specific strategies for therapy. How people adapt to MS and the research needed to improve the lives of people with MS. Management of disease symptoms (cognitive impairment, depression, spasticity, vision problems, and others). The committee also discusses ways to build and financially support the MS research enterprise, including a look at challenges inherent in designing clinical trials. This book will be important to MS researchers, research funders, health care advocates for MS research and treatment, and interested patients and their families.
Download or read book Effects of Pregnancy and Hormones on T cell Immune Regulation in Multiple Sclerosis written by Sandra Hellberg and published by Linköping University Electronic Press. This book was released on 2019-10-22 with total page 118 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis (MS) is characterized by a dysregulated immune system leading to chronic inflammation in the central nervous system. Despite increasing number of treatments, many patients continue to deteriorate. A better understanding of the underlying disease mechanisms involved in driving disease is a pre-requisite for finding new biomarkers and new treatment targets. The improvement of MS during pregnancy, comparable to the beneficial effects of the most effective treatment, suggests that the transient and physiological immune tolerance established during pregnancy could serve as a model for successful immune regulation. Most likely the immune-endocrine alterations that take place during pregnancy to accommodate the presence of the semi-allogenic fetus contribute to the observed disease improvement. The aim of this thesis was to characterize the dysregulated immune system in MS and define potential factors and mechanisms established during pregnancy that could be involved in the pregnancy-induced effects in MS, focusing on CD4+ T cells as one of the main drivers in immunity and in the MS pathogenesis. Using a network-based modular approach based on gene expression profiling, we could show that CD4+ T cells from patients with MS displayed an altered dynamic gene response to activation, in line with a dysregulated immune system in MS. The resulting gene module disclosed cell activation and chemotaxis as central components in the deviating response, results that form a basis for further studies on its modulation during pregnancy. Moreover, a combination of secreted proteins (OPN+CXCL1-3+CXCL10-CCL2), identified from the module, could be used to separate patients and controls, predict disease activity after 2 years and discriminate between high and low responders to treatment, highlighting their potential use as biomarkers for predicting disease activity and response to treatment. The pregnancy hormone progesterone (P4), a potential factor involved in the pregnancy-induced amelioration of MS, was found to significantly dampen CD4+ T cell activation. Further detailed transcriptomic profiling revealed that P4 almost exclusively down-regulated immune-related pathways in activated T cells, several related to or downstream of T cell activation such as JAKSTAT signaling, T cell receptor signaling and cytokine-cytokine receptor interaction. In particular, P4 significantly affected genes of relevance to diseases known to be modulated during pregnancy, where genes associated to MS were most significantly affected, supporting a role for P4 in the pregnancy-induced immunomodulation. By using another approach, the role of thymus in T cell regulation during pregnancy was assessed. Two established measures of thymic output, CD31 expression and TREC content, were used and showed that thymic output of T cells is maintained during human pregnancy, or even possibly increased in terms of regulatory T cells. This thesis further supports a pivotal role for CD4+ T cells and T cell activation in the MS pathogenesis and adds to the knowledge of how they could be involved in driving disease. We identified a novel strategy for capturing central aspects of the deviating response to T cell activation that could be translated into potentially clinically relevant biomarkers. Further, P4 is emerging as a promising candidate for the pregnancy-induced immunomodulation that could be of importance as a future treatment option. Lastly, maintained thymic output of T cells during human pregnancy challenges the rodent-based dogma of an inactive thymus during pregnancy. Thymic dysfunction has been reported not only in MS but also in rheumatoid arthritis, another inflammatory disease that improves during pregnancy, which highlights a potential role for thymus in immune regulation that could be involved in the pregnancy-induced amelioration.
Download or read book Neuroimmune Diseases written by Hiroshi Mitoma and published by Springer. This book was released on 2019-08-13 with total page 822 pages. Available in PDF, EPUB and Kindle. Book excerpt: A translational overview of neuroimmune diseases for neuroscientists and clinicians that clarifies the pathological mechanisms underlying neuroimmune diseases and builds a comprehensive bridge between the latest research findings and their clinical implications in daily practice. The material is presented in two steps. The first section comprises a review of the pathogenic actions of immune cells in brain diseases. Here the authors discuss the mechanisms through which immune cells disrupt the functions of nerve cells. The second section explores the ways in which the brain becomes dysfunctional due to impaired nerve cell function. Based on pathogenesis, diagnostic and therapeutic strategies are discussed for each clinical category. The book will be invaluable for use in clinical practice of neuroimmune diseases
Download or read book Research on Multiple Sclerosis written by Byron H. Waksman and published by . This book was released on 1987 with total page 132 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book How the Immune System Works written by Lauren M. Sompayrac and published by John Wiley & Sons. This book was released on 2015-10-26 with total page 160 pages. Available in PDF, EPUB and Kindle. Book excerpt: How the Immune System Works has helped thousands of students understand what’s in their big, thick, immunology textbooks. In his book, Dr. Sompayrac cuts through the jargon and details to reveal, in simple language, the essence of this complex subject. In fifteen easy-to-read chapters, featuring the humorous style and engaging analogies developed by Dr. Sompayrac, How the Immune System Works explains how the immune system players work together to protect us from disease – and, most importantly, why they do it this way. Rigorously updated for this fifth edition, How the Immune System Works includes the latest information on subjects such as vaccines, the immunology of AIDS, and cancer. A highlight of this edition is a new chapter on the intestinal immune system – currently one of the hottest topics in immunology. Whether you are completely new to immunology, or require a refresher, How the Immune System Works will provide you with a clear and engaging overview of this fascinating subject. But don’t take our word for it! Read what students have been saying about this classic book: "What an exceptional book! It's clear you are in the hands of an expert." "Possibly the Best Small Text of All Time!" "This is a FUN book, and Lauren Sompayrac does a fantastic job of explaining the immune system using words that normal people can understand." "Hands down the best immunology book I have read... a very enjoyable read." "This is simply one of the best medical textbooks that I have ever read. Clear diagrams coupled with highly readable text make this whole subject easily understandable and engaging." Now with a brand new website at www.wiley.com/go/sompayrac featuring Powerpoint files of the images from the book
Download or read book B Cell Receptor Signaling written by Tomohiro Kurosaki and published by Springer. This book was released on 2015-12-26 with total page 231 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume details our current understanding of the architecture and signaling capabilities of the B cell antigen receptor (BCR) in health and disease. The first chapters review new insights into the assembly of BCR components and their organization on the cell surface. Subsequent contributions focus on the molecular interactions that connect the BCR with major intracellular signaling pathways such as Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton’s Tyrosine Kinase and MAP kinases. These elements orchestrate cytoplasmic and nuclear responses as well as cytoskeleton dynamics for antigen internalization. Furthermore, a key mechanism of how B cells remember their cognate antigen is discussed in detail. Altogether, the discoveries presented provide a better understanding of B cell biology and help to explain some B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cell tumors, while also paving the way for eventually combating these diseases.
Download or read book The Biology of Multiple Sclerosis written by Gregory Atkins and published by Cambridge University Press. This book was released on 2012-11-08 with total page 141 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis is the most common debilitating neurological disease in people under the age of forty in the developed world. Many publications cover medical and clinical approaches to the disease; however, The Biology of Multiple Sclerosis provides a clear and concise up-to-date overview of the scientific literature on the various theories of MS pathogenesis. Covering the main elements of scientific research into multiple sclerosis, the book contains chapters on the neuropathology of the disease as well as an account of the most extensively used animal model experimental autoimmune encephalomyelitis. The book contains chapters regarding the role of viruses in the development of multiple sclerosis. Viruses have long been implicated and chapters on animal models based on virus infection, as well as their possible role in the etiology of MS, are included. Of interest to MS researchers, the book is written to also be of value to postgraduate and medical students.
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.
