Download or read book B Cells Promote Inflammatory T Cell Responses During the Initiation of Central Nervous System Autoimmune Disease written by Emily R. Pierson and published by . This book was released on 2013 with total page 110 pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) mediated by autoreactive T cells specific for myelin proteins. A recent development in MS treatment is the discovery that B cell depletion with Rituximab reduced the numbers of lesions and new relapses in MS patients. The role of B cells has been studied in the animal model of MS, experimental autoimmune encephalomyelitis (EAE), but results from these studies have been variable and contradictory, and the contribution of B cells to CNS autoimmune disease is still unclear. We examined the role of B cells in C3H mice and found that both C3HeB/Fej and C3H.SW [omega]MT mice had a reduced incidence of EAE, suggesting an important role for B cells in the initiation of disease. B cells were the predominant MHC class II+ cells in the healthy CNS and were able to secrete cytokines, indicating that they could be influencing T cell responses before inflammation is initiated. Myelin-specific T cells were able to migrate to the CNS in the absence of B cells, but were unable to initiate immune responses. The ability of the early infiltrating T cells to secrete cytokines and initiate the recruitment of additional T cells to the CNS from the periphery before onset of EAE was defective in B cell deficient mice. Recruitment of T cells from the periphery constituted the majority of the increase in T cell number in the CNS of wildtype mice prior to onset. In vitro, B cells preferentially reactivated effector Th1 cells and not Th17 cells in the absence of IL-1[beta]. Induction of EAE with Th1- or Th17-skewed cells led to reduced numbers of IFN-[gamma]- and IL-17-producing cells in the brains of B cell deficient mice after onset of EAE. However, there was a greater effect on the numbers of IFN-[gamma]-producing cells, and in B cell deficient recipients of Th1-skewed cells, the localization of inflammation changed to permit inflammation in the brain. These studies indicate that B cells are important for T cell responses in the initiation of CNS autoimmunity, and can influence the localization of inflammation in EAE.
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 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 Molecular Biology of the Cell written by and published by . This book was released on 2002 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
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 B Cell Trophic Factors and B Cell Antagonism in Autoimmune Disease written by William Stohl and published by Karger Medical and Scientific Publishers. This book was released on 2005-01-01 with total page 321 pages. Available in PDF, EPUB and Kindle. Book excerpt: The understanding of B cell biology has increased and expanded enormously in the last three decades. It is now known that B cells, in addition to just differentiating into antibody-secreting cells, serve many other vital functions. For example, their roles as antigen-presenting cells and cytokine-producing cells as well as effector cells and regulatory cells are well appreciated now. Indeed, the pathologic role of B cells in many autoimmune disorders may be largely autoantibody-independent. Today, the B cell is of considerable interest not only to immunologists but also to mainstream clinicians and scientists. The current volume covers the latest information on the functions of B cells in normal and disease states, and their therapeutic antagonism. Chapters cover cutting-edge topics from the basic to the clinical, including B cells in infection and autoimmunity, CD19-CD21 signal transduction complex, marginal zone B cell physiology and disease, B cell growth and differentiation, their role in rheumatoid arthritis, SLE treatment, the BAFF/APRIL system and B lymphocyte malignancies. This book is recommended reading for cellular and molecular immunologists as well as for rheumatologists, hematologists and clinical immunologists, and all those interested in human diseases in which B cells play an important contributory role.
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 Cell Biology in Autoimmunity written by David Ahmad Nemazee and published by Karger Medical and Scientific Publishers. This book was released on 2003 with total page 281 pages. Available in PDF, EPUB and Kindle. Book excerpt: B cells play a central role not only in adaptive immunity, but also in autoimmunity. To understand how B cells are normally prevented from reacting to self-tissue, what goes wrong in autoimmunity, and how B cells contribute to it is the aim of this book. This volume includes more than a dozen in-depth reviews by researchers specializing in various aspects of basic B cell biology that have relevance to autoimmune diseases. These up-to-date chapters present the latest information on B cell signal transduction, apoptosis, genetics and molecular biology. Also featured are chapters with special reference to particular autoimmune diseases in which B cells have been shown to play a critical role, such as type 1 diabetes, chronic graft-versus-host disease and lupus erythematosus. Further topics covered include the role of the complement system, rheumatoid factors, and anti-DNA autoantibodies as well as important related areas such as natural autoantibodies, B cell immune tolerance, Toll receptor signaling, and the immunobiology of BAFF/BLyS. Both basic researchers and clinician scientists who wish to understand the role of B lymphocytes in immune tolerance and autoimmunity will benefit from this timely publication.
Download or read book Neuro Immune Interactions in Inflammation and Autoimmunity written by Valentin A. Pavlov and published by Frontiers Media SA. This book was released on 2018-07-24 with total page 222 pages. Available in PDF, EPUB and Kindle. Book excerpt: The nervous system plays an important role in the regulation of immunity and inflammation. On the other hand unbalanced immune responses in inflammatory and autoimmune conditions may have a deleterious impact on neuronal integrity and brain function. Recent studies have characterized neural pathways communicating peripheral inflammatory signals to the CNS, and brain- and spinal cord-derived circuitries controlling various innate and adaptive immune responses and inflammation. A prototypical neural reflex circuit that regulates immunity and inflammation is the vagus nerve-based “inflammatory reflex”. Ongoing research has revealed cellular and molecular mechanisms underlying these neural circuits and indicated new therapeutic approaches in inflammatory and autoimmune disorders. Pharmacological and bioelectronic modulation of neural circuitry has been successfully explored in preclinical settings of sepsis, arthritis, inflammatory bowel disease, obesity-driven disorders, diabetes and other diseases. These studies paved the way to successful clinical trials with bioelectronic neuronal modulation in rheumatoid arthritis and inflammatory bowel disease. Dysregulated release of cytokines and other inflammatory molecules may have a severe impact on brain function. Brain inflammation (neuroinflammation), imbalances in brain neuronal integrity and neurotransmitter systems, and cognitive impairment are characteristic features of post-operative conditions, sepsis, liver diseases, diabetes and other disorders characterized by immune and metabolic dysregulation. Derangements in cytokine release also play a pivotal role in depression. Characteristic brain reactive antibodies in autoimmune conditions, including systemic lupus erythematosus and neuromyelitis optica, significantly contribute to brain pathology and cognitive impairment. These studies, and the simultaneous characterization of neuro-protective cytokines, identified new therapeutic approaches for treating neurological complications in inflammatory and autoimmune disorders. This Frontiers Research Topic is a forum for publishing research findings and methodological and conceptual advances at the intersection of immunology and neuroscience. We hope that presenting new insight into bi-directional neuro-immune communication in inflammation and autoimmunity will foster further collaborations and facilitate the development of new efficient therapeutic strategies.
Download or read book Defining Pathways that Promote and Characterize Pathogenic T Cells in CNS Autoimmunity written by Priscilla Lee and published by . This book was released on 2015 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Multiple Sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), which is though to be mediated by myelin-reactive CD4+ T cells. It reamins unclear that how these normally quiescent autoreactive T cells become encephalitogenic in MS patients. This study was designed to determine the signals that generate pathogenic T cells during differentiation and to identify the molecular pathways associated with the encephalitogenicity as a mechanism to identify potential therapeutic targets for multiple sclerosis. Using a myelin basic protein (MBP)-specific T cell receptor (TCR) transgenic mouse model, we observed that MBP-specific CD4+ T cells generated with antigen presenting cells (APCs) plus MBP antigen (Ag) were encephalitogenic; whereas T cells generated with anti-CD3/CD28 antibodies (Ab) were not, suggessting that APCs provided critical signals beyond TCR and co-stimulation molecule, contributing to the pathogenic phenotype. To recapitulate the signals provided by APCs, naive MBP-specific CD4+ T cells were activated with anti-CD3/CD28 Ab in the presence of various cytokines and were adoptively transferred into recipients to induce experimental autoimmune encephalomyelitis (EAE). The combination of IL-6/IL-23 or IL-12/IL-23 generated encephalitogenic T cells. IL-6 and IL-12 initiated the expression of IL-23R on naive T cells, and IL-23 further enhanced the expression of its own receptor and consequently the encephalitogenicity. Surprisingly, IL-23 activated STAT3, an established pathway under IL-23R, and STAT4, which was thought to be restricted to Th1 cells. There was a direct interaction between p-STAT3 and p-STAT4 upon IL-23 stimulation, suggesting that IL-23 signaled via p-STAT3/p-STAT4 heterodimers. Consistent with the pathogenic role of IL-23 observed in the mouse model, memory T cell from MS patients were hyper-reactive to IL-23, enhancing both p-STAT3 and p-STAT4. We found that not all myelin-reactive T cells were encephalitogenic. IL-6+TGF-ß-generated MBP-specific Th17 cells failed to transfer EAE; in contrast, MBP-specific Th17 cells differentaited with IL-6 plus neutralizing Ab to Th1/Th2 cytokines were encephalitogenic. Comparison of the non-encephalitogenic Th17 cells generated with two TGF-ß isoforms, TGF-ß1 or TGF-ß3, we found these cells expressed lower amounts of GM-CSF and IL-23R, both molecules necessary for encephalitogenicity. Thus TGF-ß, irrespective of isoforms, negatively regulated the differentiation of encephalitogenic Th17 cells. Similarly, MBP-specific Th1 cells differentiated with APC/Ag plus IL-12 induced severe EAE, but MBP-specific Th1 cells differentiated with anti-CD3/CD28 Ab plus IL-12 failed to efficiently transfer disease. To character the pathogenic phenotypes, we compared the gene expression profiles from encephalitogenic Th1/Th17 cells to non-encephalitogenic Th1/Th17 cells. Several molecules were shown uniquely expressed in mouse encephalitogenic Th1/Th17 cells and also highly expressed in memory T cells from MS patients. This provided potential targets that could be manipulated therapeutically as new treatments for MS. In summary, this work demonstrates several pathways that APCs influence on the encephalitogenicity of myelin-reactive T cells via cytokines. The findings also reveal the mechanisms by which naive autoreactive T cell become activated and thereby break peripheral tolarance. More broadly, these findings highlight the importance of the communication between immune cells and how this interaction shapes immune response in the context of normal settings or autoimmune diseases.
Download or read book Cytokines and the Brain written by and published by Elsevier. This book was released on 2008-06-18 with total page 609 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book opens a new page of neuro-immunobiology providing substantive experimental and clinical data to support current understanding in the field, and potential applications of this knowledge in the treatment of disease. The volume is a collection of complex, new data drawn from multiple areas of investigation in the field. The contents summarize current understanding on the presence and function of CNS cytokines and their receptors in a variety of CNS cells during health and disease. The chapters are a collection of complex, new data demonstrating the presence and synthesis of cytokines in brain cells, as well as their receptors on cell membranes in health and disease. The strength of the volume are the descriptions of the authors own investigations, together with those of others in the field pertaining to a large number of cytokines in brain function, as well as mechanisms involved in the development of CNS disorders, including multiple sclerosis and Alzheimer's disease. Also included are novel approaches to the treatment of CNS disorders based on new experimental data. The contributors to this volume are internationally known scientists and clinical researchers in their respective fields of investigation and treatment.*Opens a new page of neuro-immunobiology and provides substantive evidence for the promise of this field in the treatment of disease*Summarizes current understanding on the presence and function of central nervous system (CNS) cytokines and their receptors in a variety of CNS cells during health and disease*Includes novel approaches to the treatment of CNS disorders based on new experimental data*Offers new insight into triggers for the development of autoimmune diseases in the brain and the possibilities for treatment
Download or read book Systemic Autoimmunity written by P. E. Bigazzi and published by CRC Press. This book was released on 1991-08-30 with total page 328 pages. Available in PDF, EPUB and Kindle. Book excerpt: Surveys the biotechnologically influenced advances in the understanding of systemic autoimmune disorders, highlighting recent research using cell biology and biochemistry, the cloning of immune cells, recombinant DNA, and molecular genetics. Among the topics are the role of complement in inflammatio
Download or read book Immune Responses in the Nervous System written by Nancy Rothwell and published by Taylor & Francis. This book was released on 1995 with total page 264 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many molecules and mechanisms traditionally associated with the peripheral immune system have been found to be active within the central nervous system. The investigation of immune activation is a rapidly expanding field of research, particularly since it is directly related to acute neuronal damage and in degenerative disorders of the nervous system such as Alzheimer's disease and multiple sclerosis. This volume brings together a team of internationally recognized experts who address topics such as neuronal transplantation, leukocyte migration, the role of inflammation and immune responses in neurological diseases and brain injury, and the potential benefits of treatment with modulators of cytokine action. It will be of interest to all researchers and clinicians involved in the understanding, diagnosis and treatment of neuroimmune diseases.
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 Mind over Matter Regulation of Peripheral Inflammation by the CNS written by Michael Schäfer and published by Springer. This book was released on 2012-12-06 with total page 220 pages. Available in PDF, EPUB and Kindle. Book excerpt: Several new developments in the field of neuroimmunology with focus on the brain-to-immune system communication have been the incentive for this PIR volume. It covers topics such as brain-immune interactions, the impact of stress on the immune response, pain and immunosuppression, the modulation of inflammation and pain by the sympathetic nervous system, consequences of nerve injury for the immune system, neuronal mechanisms of immune cell recruitment, and the modulation of the immune response by corticotropin-releasing hormone or adenosine. The authors are a unique group of scientists who are all interested in brain-to-immune interactions; however, each from a different perspective. The volume will serve both neurobiologists and immunologists to understand the influence of the central nervous system on peripheral inflammation. Many aspects of this book will also be stimulating for researchers in the pain field.
Download or read book Interactions Between B Cells and CD8 T Cells in Multiple Sclerosis written by Ayman Rezk and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Previous studies have identified functionally distinct human B cell sub-populations based on distinct cytokine expression profiles and characterized the functional capacities of such B cell subsets to modulate T cell and myeloid cell effector functions. Such antibody-independent B cell functions have emerged as highly relevant to disease activity in multiple sclerosis (MS), as evidenced by the ability of B-cell depleting therapy to robustly reduce new relapsing disease activity while having minimal to no impact on the abnormal antibody profile within the central nervous system (CNS) of patients. While these results have been interpreted to reflect B cell:CD4+ T cell interactions, we noted that B-cell depleting therapy results in reduced effector functions of both CD4+ and CD8+ T cells, suggesting that B cells and CD8+ T cells may also interact in disease-relevant ways. It is noteworthy that in MS, CD8+ T cells are actually more abundant in the inflamed MS CNS than are CD4+ T cells. Furthermore, among the CNS-infiltrating T cells in MS, pathologists have identified presence of clonally expanded mucosal-associated invariant T cell receptor (MAIT) cells expressing pro-inflammatory effector molecules. The overall aim of my thesis is to characterize antibody-independent interactions between human B cells and CD8+ T (both MAIT and non-MAIT) cells, and their possible implication in MS pathophysiology. Chapter 1 introduces multiple sclerosis by summarizing the genetic and environmental factors associated with disease development, highlighting the roles of CD4+ T cells and B cells in disease pathogenesis and the implication of CD8+ T cells, including MAIT cells, in MS. In Chapter 2, I set out to optimize an approach for the simultaneous isolation of multiple rare cytokine-secreting viable human B cells. I demonstrate that the cytokine-secretion assay can be developed and applied for the detection and isolation of multiple highly-purified, viable, low-frequency cytokine-defined B cells (i.e. secreting GM-CSF or IL-10), and that isolated cell fractions are amenable for gene expression profiling and in vitro culture. The assay can be multiplexed, wherein up to three cytokines can be simultaneously detected on B cells, without any impact on cell purity, though a variable loss in yields requires assay optimization. Overall, this approach is a stepping-stone in enabling future investigations into the biology of these cytokine-defined B cell subsets. In chapter 3, I examine the interactions between B cells and both CD8+ MAIT and non-MAIT cells using a series of in vitro experiments complemented by deep immunophenotyping of CD8+ T cells within peripheral blood mononuclear cells obtained prior to and after B cell depletion therapy in patients with MS. I found that B cells have opposing effects on different CD8+T cell subsets, namely induction of proliferation, pro-inflammatory cytokine responses, and cytotoxicity of MAIT cells, yet suppression of non-MAIT cell proliferation and pro-inflammatory cytokine production. In vivo, B cell depletion in MS patients results in reduced counts and pro-inflammatory responses of MAIT cells. Overall, these observations provide novel insights into fundamental functions of human B cells in the modulation of CD8+ T cell effector responses, in both health and disease. They also add to our understanding of the complex cellular networks involving the balance between pro- and anti-inflammatory functions of different cell types and their interactions in the pathogenesis of multiple sclerosis by invoking a B cell:CD8+ T cell axis (and particularly the role of B cell: MAIT cell interactions), which may be therapeutically targeted by B cell depletion. Further characterization of cytokine-defined B cell responses and their interactions with CD8+ MAIT and non-MAIT cells could enable the development of more focused therapies that selectively impact these interactions for the treatment of autoimmune diseases"--
Download or read book Neural and Neuroendocrine Mechanisms in Host Defense and Autoimmunity written by C. Jane Welsh and published by Springer Science & Business Media. This book was released on 2007-04-05 with total page 299 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides a lucid summary of behavioral, neural and endocrine regulation of immune responses and of the effects of immune system activity on neural and endocrine functions and behavior. The underlying premise is that the brain and immune system represent a single, integrated system of defense. The discussion includes such topics and stress induced modulation of innate resistance and adaptive immunity in influenza viral infections.
