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Obesity and its co-morbidities, including atherosclerosis, insulin resistance and diabetes, are a world-wide epidemic. Inflammatory immune responses in metabolic tissues have emerged as a universal feature of these metabolic disorders. While initial work highlighted the contribution of macrophages to tissue inflammation and insulin resistance, recent studies demonstrate that cells of the adaptive immune compartment, including T and B lymphocytes and dendritic cells also participate in obesity-induced pathogenesis of these conditions. However, the molecular and cellular pathways by which the innate and adaptive branches of immunity control tissue and systemic metabolism remain poorly understood. To engage in growth and activation, cells need to increase their biomass and replicate their genome. This process presents a substantial bioenergetic challenge: growing and activated cells must increase ATP production and acquire or synthesize raw materials, including lipids, proteins and nucleic acids. To do so, they actively reprogram their intracellular metabolism from catabolic mitochondrial oxidative phosphorylation to glycolysis and other anabolic pathways. This metabolic reprogramming is under the control of specific signal transduction pathways whose underlying molecular mechanisms and relevance to physiology and disease are subject of considerable current interest and under intense study. Recent reports have elucidated the physiological role of metabolic reprogramming in macrophage and T cell activation and differentiation, B- and dendritic cell biology, as well as in the crosstalk of immune cells with endothelial and stem cells. It is also becoming increasingly evident that alterations of metabolic pathways play a major role in the pathogenesis of chronic inflammatory disorders. Due to the scientific distance between immunologists and experts in metabolism (e.g., clinicians and biochemists), however, there has been limited cross-talk between these communities. This collection of articles aims at promoting such cross-talk and accelerating discoveries in the emerging field of immunometabolism.
Obesity and its co-morbidities, including atherosclerosis, insulin resistance and diabetes, are a world-wide epidemic. Inflammatory immune responses in metabolic tissues have emerged as a universal feature of these metabolic disorders. While initial work highlighted the contribution of macrophages to tissue inflammation and insulin resistance, recent studies demonstrate that cells of the adaptive immune compartment, including T and B lymphocytes and dendritic cells also participate in obesity-induced pathogenesis of these conditions. However, the molecular and cellular pathways by which the innate and adaptive branches of immunity control tissue and systemic metabolism remain poorly understood. To engage in growth and activation, cells need to increase their biomass and replicate their genome. This process presents a substantial bioenergetic challenge: growing and activated cells must increase ATP production and acquire or synthesize raw materials, including lipids, proteins and nucleic acids. To do so, they actively reprogram their intracellular metabolism from catabolic mitochondrial oxidative phosphorylation to glycolysis and other anabolic pathways. This metabolic reprogramming is under the control of specific signal transduction pathways whose underlying molecular mechanisms and relevance to physiology and disease are subject of considerable current interest and under intense study. Recent reports have elucidated the physiological role of metabolic reprogramming in macrophage and T cell activation and differentiation, B- and dendritic cell biology, as well as in the crosstalk of immune cells with endothelial and stem cells. It is also becoming increasingly evident that alterations of metabolic pathways play a major role in the pathogenesis of chronic inflammatory disorders. Due to the scientific distance between immunologists and experts in metabolism (e.g., clinicians and biochemists), however, there has been limited cross-talk between these communities. This collection of articles aims at promoting such cross-talk and accelerating discoveries in the emerging field of immunometabolism.
This book offers a broad overview of the concepts and research findings in immunometabolism. The immune system is made up of numerous different cell types, pathways, and components that must be able to respond rapidly to a pathogen or cancer, but must also remain quiescent in the absence of challenges. Immune cells rely on metabolic pathways to adapt to changing environments and stimuli. Additionally, these cells can be modified in function or fate by fluctuations in available nutrients. The chapters in this book describe ways in which immune cells utilize and are regulated by metabolic pathways. Topics include how immune-cell metabolism shapes immune homeostasis, and how dysregulation of these pathways can lead to immune disorders. In different contexts, such as a tumor microenvironment, immune-cell function and identity may be modified not only by cytokines and checkpoint molecules, but also by nutrient availability and other metabolic stimuli. Transcriptional reprogramming confers many of the changes in immune cell metabolism that are seen when a T-cell, for example, undergoes activation or functional adaptation to different environments. Lastly, immune cells can destructively or protectively participate in human metabolic homeostasis or disorders. This book summarizes immune-metabolism from a variety of different perspectives, including the ways in which metabolic cues, pathways, and requirements of immune cells change in conditions of homeostasis and activation. The exploration of the significance of metabolic checkpoints and other cues, particularly in the context of cancer and immune disorders, may form the foundation for the development of therapeutics.
This book explains how stress – either psychological or physical – can activate and/or paralyse human innate or adaptive immunity. Adequate immunity is crucial for maintaining health, both on Earth and in space. During space flight, human physiology is specifically challenged by complex environmental stressors, which are most pronounced during lunar or interplanetary missions. Adopting an interdisciplinary approach, the book identifies the impact of these stressors – the space exposome – on immunity as a result of (dys-)functions of specific cells, organs and organ networks. These conditions (e.g. gravitation changes, radiation, isolation/confinement) affect immunity, but at the same time provide insights that may help to prevent, diagnose and address immune-related health alterations. Written by experts from academia, space agencies and industry, the book is a valuable resource for professionals, researchers and students in the field of medicine, biology and technology. The chapters “The Impact of Everyday Stressors on the Immune System and Health”, “Stress and Radiation Responsiveness” and “Assessment of Radiosensitivity and Biomonitoring of Exposure to Space adiation” are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Stress of either psychological or physical nature can activate and/or paralyse humans’ innate and adaptive immunity. However, adequate immunity is crucial to the maintenance of health on earth and in space. During space flight, human physiology and health are challenged by complex environmental stressors which might be at their most pronounced during lunar or interplanetary missions. While previous publications have addressed the physiological changes that occur during space flight, this book goes further, by adopting an interdisciplinary approach to analyze the complex interaction of living conditions in space, the immune system, and astronauts’ health. It is explained how such analysis of the consequences of stress for the immune system may help in preventing, diagnosing, and counteracting immune-related alterations in health on earth as well as in space
Metabolism is central to maintaining health and homeostasis during all challenges a mammal may face. This is true for infections as well and the field of immunometabolism has emerged for determining how metabolism influences the immune system during disease. Lipids are a major source of carbon and energy for cells while having been found to influence immune cells in a variety of systems. Here we explore novel roles for triglycerides through the interactions of adaptive immune and adipose tissue along with fatty acid utilization in myeloid cells. This dissertation describes original work demonstrating how adaptive immune system leads to sickness-induced anorexia and fat wasting. We found that fat wasting was dependent on lipolysis and that this fat wasting had no impact on inflammation within the adipose tissue. Further, we found that the fat wasting and sickness-induced anorexia are likely linked and CD4+ T cells are necessary to mediate both processes. Surprisingly, these metabolic perturbations do not have any tangible benefit to the host and preventing them did not change parasitemia or survival. Indeed, we found that CD4+ T cells were entirely dispensable in the infection, with mice lacking these immune cells surviving as long as wild type mice with similar parasitemia. Only B cells seemed necessary for mediating survival and parasitemia in wild type mice and CD8+ T cells were detrimental to survival. When looking specifically at lipid utilization in myeloid cells rather than lipid availability, we found beta oxidation in myeloid cells is detrimental to survival. There were no differences between knockout mice and wild type mice in parasitemia, indicating that immunopathology caused by the myeloid cells likely contributes to death and knocking out beta oxidation may alleviate the immunopathology. We found a slight rescue in anemia in the knockout mice, which is a major contributor for host death during a T. brucei infection. Thus, we have found novel roles for the adaptive immune system in mediating fat wasting and surprisingly this increase in lipid availability led to no difference in health while also finding a novel role for beta oxidation in myeloid cells for decreasing tolerance in the host. This work expands upon our understanding of how lipids availability is influenced by immune cells and how lipid utilization impacts health during a disease.
The book addresses controversies related to the origins of cancer and provides solutions to cancer management and prevention. It expands upon Otto Warburg's well-known theory that all cancer is a disease of energy metabolism. However, Warburg did not link his theory to the "hallmarks of cancer" and thus his theory was discredited. This book aims to provide evidence, through case studies, that cancer is primarily a metabolic disease requring metabolic solutions for its management and prevention. Support for this position is derived from critical assessment of current cancer theories. Brain cancer case studies are presented as a proof of principle for metabolic solutions to disease management, but similarities are drawn to other types of cancer, including breast and colon, due to the same cellular mutations that they demonstrate.
Written by a renowned figure in the field of immunology and compiling a wealth of scientific information, Stress, Immune Function, and Health: The Connection looks at the long-term effects of stress on human health from a psychoneuroimmunological approach. The recent changes in dietary modifications, clinical applications, and evolution in the field of immunology have created the need for a book which addresses the growing awareness of health benefits that can be achieved by buffering the effects of stress on the immune system. Emphasizing the importance of the interaction among the mind, the body, and physical health, this reference includes important developmental procedures that can be used to resist stress on the immune system. By examining components of the immune system, along with the effects of psychological stress and the capacity for hormonal response, author Bruce Rabin demonstrates, in a concise, accessible manner, the ability of an individual's immune system to alter susceptibility to immune-mediated diseases. In addition, the book examines several key issues in this rapidly expanding field, including: * Information and examples that illustrate how distinct areas of the brain that perceive the presence of a stressor are able to communicate with the cells of the immune system * The correlation between stress-related changes in health practices and stressor-induced risks of disease development * The effect on the immune system due to stress from an increased concentration of neuropeptides and hormones * Behaviors and beliefs that can reduce the harmful effects of stress on the immune system by interfering with the stress-responsive areas of the brain * The issue of stress during pregnancy and the early period of development on behaviors and immune functions in children An authoritative guide for all researchers and students in the fields of immunology, neuroscience, and psychology, Stress, Immune Function, and Health: The Connection is also an essential reference for physicians and nurses concerned with stress and immune-related diseases.
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.
Addressing metabolic health is complex, and it requires the right information about diet, nutrition, exercise, sleep, and the body's natural tendency to default to its highest weight due to insulin resistance and powerful evolutionary factors. This guide provides you with the current science and research on metabolic health including insulin resistance, blood sugar, prediabetes and diabetes, high blood pressure and cholesterol, and weight management/weight loss.This introductory book in the Metabolic Health Publication series also outlines how this group of inexpensive, accessible books provides you with a series of pragmatic solutions to metabolic health problems rooted in high blood sugar and insulin resistance, including weight problems. Written by an historian of science, the Metabolic Health Publications series addresses*Metabolic syndrome*Reversing prediabetes and diabetes*burning glucose and burning fat (keto diet)*Reversing high blood pressure, high "bad" cholesterol, and high triglycerides*Reversing insulin resistance*Achieving permanent weight loss through improved metabolic health, not fad diets, supplements, or calorie-restricting diets*Improving metabolic nutrition through easily-available food staples, food timing, and food combinations* How to regain metabolic health through a complex, nutrient-dense, low-carb diet*Accessible ways to engage in functional exercise, resistance training, and HIIT *How to ensure macronutrient and micronutrient dietary balance in order to improve insulin sensitivity and weight loss* Importance of stress reduction in relation to blood sugar and weight management* How sleep deprivation affects blood sugar and weight* The HbA1c test (its purpose and limitations), fasting glucose and insulin sensitivity testing* Importance of fiber and fat in the diet*Microbiome health in relation insulin resistance/high blood sugar* How and why specific fats improve metabolic health This guide includes a description of each book in the Metabolic Health Publication series.