Chronic diseases are the leading cause of deaths worldwide and according to the World Economics Council and the Harvard School of Public Health, the cost of chronic diseases is expected to reach a staggering 48% of global gross domestic product by the year 2030. The urgency of the issue was demonstrated in 2011 when for only the second time in its existence, the U.N. General Assembly brought a health issue to the floor for consideration: chronic diseases. To date, most considerations of the issue have approached the topic from the vantage point that chronic diseases are a myriad of largely unconnected diseases and conditions arising in diverse tissues, organs and physiological systems. This book, Immunotoxicity, Immune Dysfuction, and Chronic Disease, deviates from that prior model. It considers the interconnectivity of chronic diseases with both environmental insult of the immune system and subsequent immune dysfunction and inflammatory dysregulation as the underlying basis for many, if not most, chronic diseases. This change in the perception of environment-immune linkages to chronic disease is significant and has immediate implications both for the prevention of disease as well as for the development of more effective therapeutic approaches. Rather than considering environmental factors and types of reported immune alterations (e.g., depressed humoral immunity) as is common in books involving immunotoxicity, the present book approaches the environment-immune-disease triad from the standpoint of the disease. Each chapter emphasizes one or more specific immune dysfunction-based chronic disease(s) or condition(s) (e.g., asthma, atherosclerosis, multiple sclerosis, lupus) and describes: 1) the suggested environmental risk factors, 2) the underlying immune dysfunction(s) associated with the disease and 3) the overall health consequences of the disease. This book is an early entry for a new Toxicology book series for Springer titled: Molecular and Integrative Toxicology (MaIT). The series will feature detailed research information, but in the context of a more integrative or holistic framework. As part of this framework, the chapters will contain a section on ”Key Points” as well as “Recommendations” where appropriate. The goal is to cover the most timely, state-of-the-art issues in toxicology as well as to ensure that the information is maximally accessible for research scientists, teachers, physicians and students. We are particularly grateful to the numerous chapter authors for providing comprehensive and expert disease-oriented contributions. We are also appreciative of their willingness to consider their material not as disparate pieces of what has become a major health crisis, but rather as key pieces in a network of apparently interconnected health challenges.

NETosis is a unique form of cell death that is characterized by the release of decondensed chromatin and granular contents to the extracellular space. The initial observation of NETosis placed the process within the context of the innate immune response to infections. Neutrophils, the most numerous leukocytes that arrive quickly at the site of an infection, were the first cell type shown to undergo extracellular trap formation. However, subsequent studies showed that other granulocytes are also capable of releasing nuclear chromatin following stimulation. The extracellular chromatin acts to immobilize microbes and prevent their dispersal in the host. Bacterial breakdown products and inflammatory stimuli induce NETosis and the release of NETs requires enzyme activities. Histones in NET chromatin become modified by peptidylarginine deiminase 4 (PAD4) and cleaved at specific sites by proteases. NETs serve for attachment of bactericidal enzymes including myeloperoxidase, leukocyte proteases, and the cathelicidin LL-37. While the benefit of NETs in an infection appears clear, NETs also figure prominently at the center of various pathologic states. Therefore, it is important for NETs to be efficiently cleared; else digestive enzymes may gain access to tissues where inflammation takes place. Persistent NET exposure at sites of inflammation may lead to a further complication: NET antigens may provoke acquired immune responses and, over time, could initiate autoimmune reactions. Recent studies identified aberrant NET synthesis and/or clearance in inflammatory/autoimmune conditions such as systemic lupus erythematosus (SLE), psoriasis, ANCA-positive vasculitis, gout and Felty’s syndrome. In the case of SLE, for example, it appears that LL-37 exposed in the NETs may be a significant trigger of type I Interferon responses in this disease. Recent evidence also implicates aberrant NET formation in the development of endothelial damage, atherosclerosis and thrombosis. NETosis is thus of interest to researchers who investigate innate immune responses, host-pathogen interactions, chronic inflammatory disorders, cell and vascular biology, biochemistry, and autoimmunity. As we approach the 10-year-anniversary of the initial discovery of NETosis, it is useful and timely to review the so far identified mechanisms and pathways of NET formation, their role in bacterial and fungal defense and their putative importance as inducers of autoimmune responses. We look forward to a rich and rigorous discussion of these and related issues that benefit from interdisciplinary approaches, collaborations and exciting discoveries.

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.

This authoritative handbook covers all aspects of immunosenescence, with contributions from experts in the research and clinical areas. It examines methods and models for studying immunosenescence; genetics; mechanisms including receptors and signal transduction; clinical relevance in disease states including infections, autoimmunity, cancer, metabolic syndrome, neurodegenerative diseases, frailty and osteoporosis; and much more.

Stiehm’s Immune Deficiencies: Inborn Errors in Immunity, Second Edition, is ideal for physicians and other caregivers who specialize in immunology, allergies, infectious diseases and pulmonary medicine. It provides a validated source of information for care delivery to patients, covering approaches to diagnosis that use both new genetic information and emphasize screening strategies. Management has changed dramatically over the past five years, so approaches to infection and autoimmunity are emphasized in an effort to improve outcomes and disseminate new information on the uses of targeted therapy. Covers immune deficiencies that are presented in a practical way, providing helpful information for active clinicians Fills an increasingly deep gap in the information available to clinicians Presents both clinical management and scientific advances for immune deficiencies Provides a primary resource for physicians in the field of immunodeficiencies Includes website access to a range of videos relevant to the topics discussed

The book focuses on various aspects and properties of innate immunity, whose deep understanding is integral for safeguarding the human race from further loss of resources and economies due to innate immune response-mediated diseases. Throughout this book, we examine the individual mechanisms by which the innate immune response acts to protect the host from pathogenic infectious agents and other non-communicable diseases. Written by experts in the field, the volume discusses the significance of macrophages in infectious disease, tumor metabolism, and muscular disorders. Chapters cover such topics as the fate of differentiated macrophages and the molecular pathways that are important for the pathologic role of macrophages.

Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.

The first edition of this publication was aimed at defining the current concepts of trauma induced coagulopathy by critically analyzing the most up-to-date studies from a clinical and basic science perspective. It served as a reference source for any clinician interested in reviewing the pathophysiology, diagnosis, and management of the coagulopathic trauma patient, and the data that supports it. By meticulously describing the methodology of most traditional as well as state of the art coagulation assays the reader is provided with a full understanding of the tests that are used to study trauma induced coagulopathy. With the growing interest in understanding and managing coagulation in trauma, this second edition has been expanded to 46 chapters from its original 35 to incorporate the massive global efforts in understanding, diagnosing, and treating trauma induced coagulopathy. The evolving use of blood products as well as recently introduced hemostatic medications is reviewed in detail. The text provides therapeutic strategies to treat specific coagulation abnormalities following severe injury, which goes beyond the first edition that largely was based on describing the mechanisms causing coagulation abnormalities. Trauma Induced Coagulopathy 2nd Edition is a valuable reference to clinicians that are faced with specific clinical challenges when managing coagulopathy.

This manual is for use by doctors, senior nurses and other senior health workers who are responsible for the care of young children at the first referral level in developing countries. It presents up-to-date expert clinical guidelines for both inpatient and outpatient care in small hospitals where basic laboratory facilities and essential drugs and inexpensive medicines are available. The manual focuses on the inpatient management of the major causes of childhood mortality, such as pneumonia, diarrhoea, severe malnutrition,, malaria, meningitis, measles, and related conditions. Descriptions of expensive treatment options are deliberately omitted from the manual.