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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.
This book presents the discipline of immunology which studies a unique physiological phenomenon contradicting many of the generally established rules in the field: immunology of pregnancy. It provides a wide overview of the current research of this topic. Prominent and leading international groups contributed by reviewing the most significant findings in the field.
First published in 1972, The Hope of Progress presents collection of essays and lectures dealing with the history of scientific ideas and the impact of science on society. The principle piece in this volume is the author’s 1969 presidential address to the British Association ‘On The Effecting of All Things Possible’, an argument for believing in the ability of science to solve the problems it has itself created, and which too many of us believe insoluble. It contains author’s Romanes Lecture on ‘Science and Literature’ and a well known critique of J.D. Watson’s notorious account of the discovery of the molecular structure of DNA, The Double Helix. Other chapters discuss the possibility of the control and domination by science of the body and mind of Man- though the author concludes in ‘The Genetic Improvement of Man’ : ‘I think that, in the main, for many centuries to come, we shall have to put up with human beings as they are at present constituted’. This book will be useful for scholars and researchers of history of science, philosophy of science, natural science, and philosophy in general.
This work has broad applications in clinical medicine, ranging from prevention and treatment of organ and bone marrow transplant rejection, management of various autoimmune disorders (for example, rheumatoid arthritis), skin disease and asthma. Whereas traditionally only a small repertoire of immunosuppressive agents was available for clinical use, recent discoveries have significantly increased the number of approved agents, resulting in numerous trials to further evaluate their potential. There is also considerable interest in the potential of cell-based therapies (particularly hematopoietic stem and dendritic cell therapy) of allo- and autoimmunity. Important recent advances in the immunotherapy of allergic diseases are also covered in this book. This volume is intended both for practising physicians and surgeons and for biomedical scientists at the graduate/postdoctoral levels, and is designed to provide the theory behind these various approaches to immunosuppression, and to provide state-of-the-art reviews of current developments in each area.
This fully revised and significantly expanded second edition examines sex and gender differences in the immune system's response to bacterial, viral, and parasitic infections. The volume discusses both common and distinct molecular mechanisms that mediate these differences and illustrates how responses to vaccines may differ between the sexes and in pregnant individuals. Special emphasis is placed on the interplay between hormones and the immune system in the pathogenesis of HIV, SARS-CoV-2, influenza, malaria, tuberculosis, and amebiasis. This second edition includes completely rewritten chapters as well as all new contents. This book is intended for researchers in academia and industry as well as clinicians in the fields of microbiology, immunology, and pharmacology. By expanding knowledge in sex and gender medicine as a basis for developing personalized treatment strategies, the book contributes to UN Sustainable Development Goals 3 (health and well-being) and 5 (gender equality).
This comprehensive, authoritative treatise covers all aspects of mucosal vaccines including their development, mechanisms of action, molecular/cellular aspects, and practical applications. The contributing authors and editors of this one-of-a-kind book are very well known in their respective fields. Mucosal Vaccines is organized in a unique format in which basic, clinical, and practical aspects of the mucosal immune system for vaccine development are described and discussed. This project is endorsed by the Society for Mucosal Immunology. Provides the latest views on mucosal vaccines Applies basic principles to the development of new vaccines Links basic, clinical, and practical aspects of mucosal vaccines to different infectious diseases Unique and user-friendly organization
Interactions between the immune, endocrine and nervous systems seldom appear as main issues in the neurosciences and in immunology. So far this was most likely due to the need to focus on the molecular and cellular bases of single neural, endocrine and immune processes. But hormones, neurotransmitters and neuropeptides can also influence more subtle mechanisms underlying immune cell activity. The contents of this volume aim at listing some aspects which show that not only the bases for neuroendocrine control of more refined mechanisms related to the organization and functioning of the immune systems to exist, but also that the immune system can actively communicate with neuroendocrine structures. The evidence is divided into three categories: - Anatomical, cellular and molecular bases for the exchange of information between immune, endocrine and neural cells, - reciprocal effects between immune and neuroendocrine mechanisms, and - immune-neuroendocrine regulatory circuits. Immunologically triggered neuroendocrine responses can be either beneficial or deleterious for the host. A systematic approach would imply the simultaneous evaluation of neuroendocrine and immune parameters and thus provide the basis for therapeutic interventions based on antagonizing or blocking undesirable effects.
Life history theory seeks to explain the evolution of the major features of life cycles by analyzing the ecological factors that shape age-specific schedules of growth, reproduction, and survival and by investigating the trade-offs that constrain the evolution of these traits. Although life history theory has made enormous progress in explaining the diversity of life history strategies among species, it traditionally ignores the underlying proximate mechanisms. This novel book argues that many fundamental problems in life history evolution, including the nature of trade-offs, can only be fully resolved if we begin to integrate information on developmental, physiological, and genetic mechanisms into the classical life history framework. Each chapter is written by an established or up-and-coming leader in their respective field; they not only represent the state of the art but also offer fresh perspectives for future research. The text is divided into 7 sections that cover basic concepts (Part 1), the mechanisms that affect different parts of the life cycle (growth, development, and maturation; reproduction; and aging and somatic maintenance) (Parts 2-4), life history plasticity (Part 5), life history integration and trade-offs (Part 6), and concludes with a synthesis chapter written by a prominent leader in the field and an editorial postscript (Part 7).
The 4th International Symposium on Women's Health and Menopause, organized by the Giovanni Lorenzini Medical Foundation (Milan, Italy and Houston, Texas) focused on the new strategies to improve the quality of life of post-menopausal women. This volume illustrates the findings of this conference and includes information on the age-related degenerative processes occurring after menopause including cardiovascular disease, cancer, fractures and dementia.
In the last decades, several in vitro and in vivo studies have revealed the existence of a very complex network between the neuroendocrine and immune system. Important molecular mechanisms underlying these interactions, in both physiological and pathological conditions, have also been described. Indeed, hormones play a pivotal role in the development and functional regulation of the immune system – both innate and acquired responses. Immune system cells present specific hormone receptors and themselves produce some hormones, thus influencing hormone secretion. More recently, the modulation of hormone secretion has been attempted for treating associated autoimmune disorders, further supporting the strong interplay between the endocrine and immune system. Distinguished experts, who have published extensively in their fields, have contributed comprehensive chapters to this volume. The focus is on the various aspects of endocrine-neuro-immune connections, providing an updated panorama - from basics to clinical applications - of current knowledge and still debated issues.