Download or read book Factors Promoting B Cell Activation and Accumulation in the Inflamed CNS written by Krista D. DiSano and published by . This book was released on 2017 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Central nervous system (CNS) inflammation results in the accumulation of various B cell subsets, including naive, activated, memory B cells (Bmem), and antibody secreting cells (ASC). While ASC are well studied, signals driving recruitment of B cells, their relationship to peripheral activation, and role within the CNS remain largely unknown. Using the murine neurotropic coronavirus JHMV infection model, our studies established a critical role for draining lymph node germinal center formation in driving accumulation of isotype-switched ASC/Bmem in the CNS. Divergent accumulation of isotype-unswitched B cells to perivascular/meningeal space and isotype-switched B cells to the CNS parenchyma indicated B cell differentiation state regulates localization. Multiple lymphoid chemokines guiding B cell migration are induced following CNS infection. Differing chemokine receptor expression profiles on infiltrating B cell subsets implied receptors in combination or alone regulate their migration to and within the CNS. Interestingly, B cell accumulation occurred independent of ectopic follicles during JHMV infection. A sustained CD4 T cell "helped" phenotype during both JHMV infection and autoimmune mediated inflammation indicated B cell activation in the CNS occurred independent of follicle formation. Moreover, isotype-switched B cell accumulation and activation was unaltered in the absence of CXCL13, a chemokine critical in organizing follicles. CD4 T cells supported isotype-unswitched B cell CNS accumulation, indicating a role in facilitating B cell survival and undefined effector functions in the CNS. The identification of virus-specific Bmem during persistent JHMV infection implied Bmem contribute to local Ab production. In contrast, early accumulating B cells were not virus specific, implying non-specific bystander recruitment and functions not related to antigen presentation. Nonetheless, the recruitment of isotype-unswitched B cells in multiple CNS inflammation models suggests an important, yet to be defined role in the inflamed CNS.
Download or read book B Cells in Inflammatory and Neurodegenerative Diseases of the Central Nervous System written by Francesca Gilli and published by Frontiers Media SA. This book was released on 2021-11-15 with total page 132 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book B Cell written by Hanane Touil and published by . This book was released on 2019 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Growing evidence suggests that B cells play important roles during disease relapses and possibly also during the progressive stages of multiple sclerosis (MS). A number of studies have implicated antibody-independent roles of B cells in the periphery of patients, including presence of abnormally higher proportions of pro-inflammatory B cells (Beff) compared to anti-inflammatory B cells (Breg), which is thought to induce pro-inflammatory T cell responses. In the inflamed central nervous system (CNS) of MS patients, B cells are abnormally fostered and found in different compartments, including the meningeal immune-cell collections closely linked with subpial cortical injury and progressive disease. However, there remain major gaps in our knowledge of B cell persistence and their potential contributions to CNS-compartmentalized inflammation. The aim of my doctoral thesis is to shed light on cellular mechanisms involving B cell:glial cell cross-talk and how these interactions may propagate local inflammation and injury as well as contribute to progressive disease in MS. In the first part of my thesis (Chapter 2), I demonstrate that human astrocytes support the survival of B cells through soluble factors. These soluble factors derived from pre-stimulated astrocytes not only supported B cell survival but also their activation (increased co-stimulatory molecule expression), which further induced T cell proliferation. I further demonstrate that astrocyte-secreted factors supported survival and activation of MS-relevant B cell subsets derived from relapsing remitting MS (RRMS) and secondary progressive MS (SPMS) patients. In chapter 3, I investigated the bi-directional interaction between B cells and myeloid cells (microglia and macrophages) to determine how these interactions may impact the propagation of CNS-compartmentalized inflammation. First, I show that soluble factors derived from M1-activated microglia supported B cell activation, whereas M2c microglia induced B apoptotic death of MS-relevant B cell subsets. I further demonstrate that soluble factors derived from pro-inflammatory (Beff) B cells (abnormally implicated in the periphery of MS) substantially increased the secretion of the pro-inflammatory cytokines (IL-12, IL-6 & TNF) and diminished IL-10 production by microglia and macrophage. Interestingly, this secretion of pro-inflammatory cytokines by macrophages was dependent on B cell-derived GM-CSF. Lastly, I demonstrate that supernatants derived from distinct B cell subsets (Beff & Breg) were capable of modulating microglia and macrophage phenotype (expression of CD80 & TREM-2), while reciprocally modulating myeloid phagocytosis of myelin.My overall doctoral investigations enhances our understanding of cellular mechanisms that may be associated with progressive disease. My findings indicate that B cells and glial cells have the capacity to interact and that they may contribute to cascades of pro-inflammatory events. In related work to which I have contributed, we demonstrated a selective cytotoxic effect to oligodendrocytes and neurons in response to soluble factors of B cells derived from MS patients but B cells from matching controls. If these interactions occur in vivo they may propagate CNS-compartmentalized inflammation and subpial injury. Taken together, these findings constitute a conceptual advance pointing to novel cellular mechanisms that may contribute to subpial cortical pathology and progressive MS. Future work will aim to elucidate the molecular mechanisms underlying these B cell:glial cell interactions. I am hopeful that my results will eventually help the development of more targeted therapies that can limit or modulate these interaction in a way that is beneficial for progressive MS - a major unmet clinical need. " --
Download or read book Peripheral Germinal Centers Regulate Virus specific B Cell Accumulation in the CNS written by Jeffrey Ross Atkinson and published by . This book was released on 2018 with total page 212 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple B cell subsets with phenotypes characteristic of naive, non-isotype-switched, memory (Bmem), and antibody-secreting cells (ASC), accumulate in various models of central nervous system (CNS) inflammation. However, how peripheral activation events, including germinal center (GC) formation, contribute to the dynamics of humoral immune responses in the inflamed CNS is poorly delineated. To address the role of GC formation in driving CNS humoral responses we are using a well-established model of mouse hepatitis virus (MHV) encephalomyelitis. Following MHV-induced CNS infection, T and B cell responses are initiated in cervical lymph nodes and local CNS antibody (Ab) production is crucial for control of viral persistence following initial T cell-mediated immune control. Our overall hypothesis is that antigen (Ag)-driven, peripheral GC formation is critical for development of Ag-specific B cells, as well as accumulation and maintenance in the inflamed CNS following MHV-induced encephalomyelitis. The findings of this thesis strongly support that GC reactions are critical for imprinting migration of virus-specific B cells, particularly ASC, to the CNS. They further imply that accumulation of ASC and Bmem is differentially regulated, with early GC reactions supporting preferential Bmem egress and accumulation in the CNS, and late GC reactions preferentially mediating ASC migration to the CNS during viral persistence. Our studies also do not provide any evidence for local de novo synthesis of Ag-specific B cells in the CNS, or local conversion of Bmem to ASC. Moreover, the results demonstrate that the survival factor APRIL, which maintains long-lived ASC in the bone marrow, is also important in maintaining virus-specific ASC in the CNS during MHV infection.
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 Inflammation and the Microcirculation written by D. Neil Granger and published by Morgan & Claypool Publishers. This book was released on 2010 with total page 99 pages. Available in PDF, EPUB and Kindle. Book excerpt: The microcirculation is highly responsive to, and a vital participant in, the inflammatory response. All segments of the microvasculature (arterioles, capillaries, and venules) exhibit characteristic phenotypic changes during inflammation that appear to be directed toward enhancing the delivery of inflammatory cells to the injured/infected tissue, isolating the region from healthy tissue and the systemic circulation, and setting the stage for tissue repair and regeneration. The best characterized responses of the microcirculation to inflammation include impaired vasomotor function, reduced capillary perfusion, adhesion of leukocytes and platelets, activation of the coagulation cascade, and enhanced thrombosis, increased vascular permeability, and an increase in the rate of proliferation of blood and lymphatic vessels. A variety of cells that normally circulate in blood (leukocytes, platelets) or reside within the vessel wall (endothelial cells, pericytes) or in the perivascular space (mast cells, macrophages) are activated in response to inflammation. The activation products and chemical mediators released from these cells act through different well-characterized signaling pathways to induce the phenotypic changes in microvessel function that accompany inflammation. Drugs that target a specific microvascular response to inflammation, such as leukocyte-endothelial cell adhesion or angiogenesis, have shown promise in both the preclinical and clinical studies of inflammatory disease. Future research efforts in this area will likely identify new avenues for therapeutic intervention in inflammation. Table of Contents: Introduction / Historical Perspectives / Anatomical Considerations / Impaired Vasomotor Responses / Capillary Perfusion / Angiogenesis / Leukocyte-Endothelial Cell Adhesion / Platelet-Vessel Wall Interactions / Coagulation and Thrombosis / Endothelial Barrier Dysfunction / Epilogue / References
Download or read book Role of Inflammation in Neurodegenerative Diseases written by Maya Koronyo-Hamaoui and published by Frontiers Media SA. This book was released on 2022-07-13 with total page 461 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Arrest chemokines written by Klaus Ley and published by Frontiers Media SA. This book was released on 2015-05-20 with total page 109 pages. Available in PDF, EPUB and Kindle. Book excerpt: Arrest chemokines are a small group of chemokines that promote leukocyte arrest from rolling by triggering rapid integrin activation. Arrest chemokines have been described for neutrophils, monocytes, eosinophils, naïve lymphocytes and effector memory T cells. Most arrest chemokines are immobilized on the endothelial surface by binding to heparin sulfate proteoglycans. Whether soluble chemokines can promote integrin activation and arrest is controversial (Alon-Gerszten). Many aspects of the signaling pathway from the GPCR chemokine receptor to integrin activation are the subject of active investigation. Leukocyte adhesion deficiency III is a human disease in which chemokine-triggered integrin activation is defective because of a mutation in the cytoskeletal protein kindlin-3. About 10 different such mutations have been described. The defects seen in patients with LAD-III elucidate the importance of rapid integrin activation for host defense in humans. We welcome reports that help clarifying this crucial first step in the process of leukocyte transendothelial migration.
Download or read book Inflammation Oxidative Stress and Cancer written by Ah-Ng Tony Kong and published by CRC Press. This book was released on 2016-04-19 with total page 631 pages. Available in PDF, EPUB and Kindle. Book excerpt: Increasing scientific evidence suggests that the majority of diseases including cancer are driven by oxidative stress and inflammation, attributed to environmental factors. These factors either drive genetic mutations or epigenetically modify expression of key regulatory genes. These changes can occur as early as gestational fetal development, and
Download or read book Mitochondrial Dysfunction written by Lawrence H. Lash and published by Elsevier. This book was released on 2013-10-22 with total page 527 pages. Available in PDF, EPUB and Kindle. Book excerpt: Methods in Toxicology, Volume 2: Mitochondrial Dysfunction provides a source of methods, techniques, and experimental approaches for studying the role of abnormal mitochondrial function in cell injury. The book discusses the methods for the preparation and basic functional assessment of mitochondria from liver, kidney, muscle, and brain; the methods for assessing mitochondrial dysfunction in vivo and in intact organs; and the structural aspects of mitochondrial dysfunction are addressed. The text also describes chemical detoxification and metabolism as well as specific metabolic reactions that are especially important targets or indicators of damage. The methods for measurement of alterations in fatty acid and phospholipid metabolism and for the analysis and manipulation of oxidative injury and antioxidant systems are also considered. The book further tackles additional methods on mitochondrial energetics and transport processes; approaches for assessing impaired function of mitochondria; and genetic and developmental aspects of mitochondrial disease and toxicology. The text also looks into mitochondrial DNA synthesis, covalent binding to mitochondrial DNA, DNA repair, and mitochondrial dysfunction in the context of developing individuals and cellular differentiation. Microbiologists, toxicologists, biochemists, and molecular pharmacologists will find the book invaluable.
Download or read book Inflammation and Cancer written by Bharat B. Aggarwal and published by Springer. This book was released on 2014-05-12 with total page 489 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.
Download or read book Cooperation of Liver Cells in Health and Disease written by Z. Kmiec and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 154 pages. Available in PDF, EPUB and Kindle. Book excerpt: It is only during the last decade that the functions of sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, pit cells and other intrahepatic lymphocytes have been better understood. The development of methods for isolation and co-culturing various types of liver cells has established that they communicate and cooperate via secretion of various intercellular mediators. This monograph summarizes multiple data that suggest the important role of cellular cross-talk for the functions of both normal and diseased liver. Special features of the book include concise presentation of the majority of detailed data in 19 tables. Original schemes allow for the clear illustration of complicated intercellular relationships. This is the first ever presentation of the newly emerging field of liver biology, which is important for hepatic function in health and disease and opens new avenues for therapeutic interventions.
Download or read book Liver Immunology written by M. Eric Gershwin and published by Springer Science & Business Media. This book was released on 2013-11-19 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: Liver Immunology: Principles and Practice, Second Edition begins with important information about the epidemiology and mortality of liver disease worldwide. This information is followed by chapters related to basic immunology, application of liver immunology for diagnosis, and several excellent chapters that provide a solid foundation for understanding immune-mediated liver disease, including those associated with the biliary tree. A chapter on non-hepatic manifestations of immune mediated liver disease helps provide context for how these diseases affect the patient overall. In addition, chapters discuss various discrete immunologically-mediated infectious liver disorders including those related to bacteria, parasites, and all of the classic viruses. Chapters on the traditional autoimmune liver diseases -- primary biliary cirrhosis, autoimmune hepatitis, primary sclerosing cholangitis as well as overlap syndrome – are also included. The breadth of this comprehensive second edition is highlighted by chapters on alcoholic liver disease, non-alcoholic fatty liver disease, and drug-induced liver disease, among others. This invaluable new edition ends with a forward-looking view of future directions and how the field might meet the challenge of refractory patients. Developed by a renowned group of authors, Liver Immunology: Principles and Practice, Second Edition will again serve as a comprehensive textbook by providing an excellent overview for this rapidly evolving field. It greatly adds to the understanding of the pathogenesis of these diseases, while also providing novel insights that can be harnessed into helping improve the care of patients afflicted with various immune-mediated diseases. This volume will again be a must-read for clinicians at all levels, investigators and students.
Download or read book White Matter Diseases written by Massimo Filippi and published by Springer Nature. This book was released on 2020-02-13 with total page 215 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides cutting-edge information on the epidemiology, etiopathogenesis, clinical manifestations, diagnostic procedures and treatment approaches for the main white matter (WM) disorders of the central nervous system (CNS). WM lesions are associated with many neurological conditions, and with aging. The diagnostic work-up of neurological diseases characterized by the presence of these lesions has changed dramatically over the past few years. This is mainly due on the one hand to the discovery of specific pathogenetic factors in some of these conditions, and on the order to the optimized use of diagnostic tools. All of this has resulted in new diagnostic algorithms, and in the identification of new neurological conditions. The book offers neurologists essential guidance in the diagnosis and treatment of the most frequent WM conditions, promoting their correct and cost-saving diagnosis and management. By integrating neurological, laboratory and imaging concepts with the demands of accurate diagnosis, this reference guide provides a state-of-the-art overview of the current state of knowledge on these conditions, as well as practical guidelines for their diagnosis and treatment.
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 233 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 Normal and Malignant B Cell written by Mourad Aribi and published by BoD – Books on Demand. This book was released on 2020-02-26 with total page 163 pages. Available in PDF, EPUB and Kindle. Book excerpt: Normal and Malignant B-Cell is a collection of harmonious chapters contributed by different authors. This book sets out to describe the B-cell during different stages of ontogeny and the molecular mechanisms of its antigen receptor diversity. It also discusses the main clinical and etiopathogenic aspects when it is transformed into a malignant cell. The book will be interesting and useful for clinicians, biologists, researchers, teachers, and graduate students of both doctoral and master's degrees in the field of immunology.
Download or read book Hematopoietic Stem Cell Biology written by Motonari Kondo and published by Springer Science & Business Media. This book was released on 2009-12-04 with total page 260 pages. Available in PDF, EPUB and Kindle. Book excerpt: In the summer of 1988, my developmental biology professor announced to the class that hematopoietic stem cells (HSCs) had finally been purified. Somehow, I never forgot the professor’s words. When I started working in Dr. Irv Weissman’s labo- tory at Stanford as a postdoctoral fellow, I realized that the findings mentioned by the professor were from Weissman’s laboratory and had been published in a 1988 edition of the journal Science. It has been over 20 years since the publication of that seminal paper, and since then tremendous advances in understanding the biology and maturation of HSCs, namely the process of hematopoiesis, which includes lymphocyte development, have been made. These discoveries were made possible in part by advancements in technology. For example, recent availability of user friendly fluorescence activated cell sorting (FACS) machines and monoclonal an- bodies with a variety of fluorescent labels has allowed more scientists to sort and analyze rare populations in the bone marrow, such as HSCs. All classes of hematopoietic cells are derived from HSCs. Stem cell biology draws enormous attention not only from scientists, but also from ordinary people because of the tremendous potential for development of new therapeutic application to diseases that currently lack any type of effective therapy. Thus, this type of “regenerative medicine” is a relatively new and attractive field in both basic science and clinical medicine.
