Innate Immunity

Immunologists today are interested in all of the diverse cell-types involved in host defense and have a deeper appreciation of the importance of innate immune mechanisms as a first line of protection against pathogens. This volume thus discusses the isolation and functional characterization of cells involved in innate immunity in mouse and man, including mast cells and eosinophils. Other focuses include natural killer cells, methods in statistics, in vivo imaging, genome engineering, and mutagenesis and culture that are adapted to the study of innate immunity in these hosts. These are complemented with a series of chapters dealing with alternative models: plants, worms, mosquitoes, flies, and fish. Together, these approaches and models are being used to dissect the complex interplay between hosts and pathogens and contribute to developing strategies to help fight infection. With chapters written by experts on the cutting-edge of this technology, Innate Immunity is an essential reference for immunologists, histologists, geneticists, and molecular biologists.

Our understanding of the complex innate immune response is increasing rapidly. Its role in the protection against viral or bacterial pathogens is essential for the survival of an organism. However, it is equally important to avoid unregulated inflammation because innate immune responses can cause or promote chronic autoinflammatory diseases such as gout, atherosclerosis, type 2 diabetes or certain aspects of the metabolic syndrome. In this book leading international experts in the field of innate immunity share their findings, define the ‚state of the art‘ in this field and evaluate how insight into the molecular basis of these diseases could help in the design of new therapies. A tremendous amount of work on the innate immune response has been done over the last fifteen years, culminating in the 2011 Nobel Prize in Physiology/Medicine awarded for the discoveries of Toll genes in immunity in flies, membrane-bound Toll-like receptors in mammals, and dendritic cells as initiators of adaptive immunity.

The Innate Immune System: A Compositional and Functional Perspective focuses on the components and functionality of the innate immune system, detailing how they work in their own right, and then progressing to cover their relevance to disease and how they interface with the adaptive response. Despite the growing appreciation of the importance of the innate immune system, many classical immunology books still focus predominantly on the adaptive immune response. Not only is this unbalanced, but it fails to reflect the growing synergy between the activation and function of the innate response and the final nature of adaptive response. This book fills the gap in knowledge that is needed to fully understand and appreciate the topic. Provides a clear, but simple picture of the main principle of innate immunity and the interlink with adaptive responses Fulfills an unmet need in the area of innate immunity Gives a constructive and progressive approach to introducing and explaining the key players in the innate immune response Introduces and explains the key players in the innate immune response with a constructive and progressive approach Presents the components of the innate response and shows how these interrelated areas connect with one another from a functional perspective Enables the reader to gradually increase their level of understanding and knowledge without the risk of becoming confused, thereby ensuring they fully comprehend the integrated signaling pathways

Innate immunity is a new branch of immunology, confirmed by three Nobel Prize winners in 2011. It is the first line of defense against pathogens and is in a way the preliminary step of adaptive immunity which occurs later, and only present in vertebrates. This book examines the way in which innate immunity was discovered in invertebrates. As a starting point, it looks at the work of Louis Pasteur on silkworm disease and the findings of Ilya Metchnikov, discoverer of phagocytosis. It also investigates André Paillot, who in 1920 demonstrated the existence of humoral immunity in insects, unrelated to the type of immunity that was initially thought to be present in all vertebrates. Finally, Innate Immunity shows how the group directed by Jules Hoffmann found strong similarities between the innate immunity response of insects and mammals. The discovery of a receptor protein in Drosophila, which is also found in humans, was what led to Jules Hoffmann being awarded the Nobel Prize in 2011. Presents the transformations experienced by the domains of innate immunity Shows the lineage of these results Bridges the gap between innate immunity of invertebrates and that of vertebrates

This book has been cunningly designed to provide an overview of our current knowledge about the innate immune systems of these three types of organisms. It not only covers the innate immune mechanisms and responses of such diverse organisms as plants, Cnidaria, Drosophila, urochordates and zebrafish, but also the major receptor systems in mammalians and humans. It delves too into the central defense mechanisms, antimicrobial peptides and the complement system.

The recent explosion of information in innate immune pathways for recognition, effect or responses, and genetic regulation has given impetus to investigations into analogous pathways in the human immune response, which in turn has produced attendant insights into both normal physiology and immunopathology. This volume presents a compendium of methods and protocols for the investigation of human innate immunity with application to the study of normal immune function, immunosenescence, autoimmunity and infectious diseases. Among the topics covered are quantitative flow cytometry for Toll-like receptor expression and function; multidimensional single cell mass cytometry (CyTOF) in complex immune interactions and tumor immunity; imaging techniques such as Imagestream high resolution microscopy coupled to flow cytometry, immune cell infiltration of organotypic, biomimetic organs; high-throughput single cell secretion profiling; multiplexed transcriptomic profiling; microsatellite and microRNA methodologies, RNA interference; and the latest bioinformatics and biostatistical methodologies, including in-depth statistical modeling, genetic mapping, and systems approaches.

The ability to remember an antigenic encounter for several decades, even for a life time, is one of the fundamental properties of the immune system. This book assembles a collection of essays from leading experts that span the entire spectrum of immunological research, from understanding the molecular mechanisms of innate immune recognition, to dendritic cell function, to the generation and maintenance of antigen-specific B and T-cell responses.

Target pattern recognition in innate immunity is responsible for the immediate, usually protective, responses shown against invading microorganisms, and it is the principal feature of self and non-self recognition by virtue of the recognition of structures on the microbial pathogens, which are not found on host cells. This is an area that has been very actively researched, over approximately the past 12 years, and therefore this volume provides a timely comprehensive, and up to date, summary of the types and range of cell surface, intracellular, and secreted, host proteins involved in the recognition of microbial products, and of the protective mechanisms triggered as a result of the recognition events. The Toll-like receptors, first described in Drosophila and now well-characterised on human cells, provide an excellent demonstration of the wide range of different microbial products recognised by this family of receptors and of the signalling pathways which are triggered thus leading to induction of inflammatory cytokines and the activation of genes producing antimicrobial products. In addition, several cell surface proteins involved in target pattern recognition have been described on the surfaces of macrophages (macrophage mannose receptor and macrophage scavenger receptors), and on dendritic cells (DEC205), and to be involved with the uptake and clearance of whole microorganisms and polyanioic ligands. Pattern recognition is also utilised by intracellular receptors, with NOD-like receptors in the cytosol recognizing microbial molecules and activating the production of inflammatory cytokines or pathways that induce the production of inflammatory molecules. Secreted proteins, such as the pentraxins, which includes the acute phase reacting, C-reactive protein (CRP) and serum amyloid protein (SAP), and the collectins (mannan binding lectin, lung surfactant protein A and D) and ficolins can also readily recruit killing and clearance systems. Indeed, the serum complement system, which is one of the major defence systems in the bloodstream, is efficiently activated by CR P on its binding to the phosphocholine groups of microbial phospholipids—and the subsequent interaction of the bound CR P with C1q—to give classical pathway activation, or MBL, or ficolin, binding to arrays of mannose or N-acetyl-glucosamine residues, respectively, on the surfaces of microorganisms—to give lectin pathway activation. Also, in addition to the activation and clearance events associated with complement activation by some of the secreted pattern recognition receptors, it is accepted that all these pattern recognition receptors can generally accelerate the uptake and clearance of microbes via phagocytic cells. In view of the growing interest in the cross-talk between innate and adaptive immunity, a thorough understanding of the initial recognition and triggering events, mediated via innate immune receptors, as addressed in this volume, is clearly very useful in helping to also fully understand the mechanisms of activation and control of the adaptive immune system—and to allow a full assessment of the relative roles played by innate immunity and adaptive immunity against a particular infection in higher organisms.

In recent years increased scientific attention has been given to immediate defense mechanisms based on non-clonal recognition of microbial components. These mechanisms constitute the innate immunity arm of the body s defense. Identification of pathogens by these mechanisms involves primarily receptors recognizing sugar moieties of various microorganisms. Innate immunity based mechanisms are essential for the existence of multicellular organisms. They are evolutionarily conserved and designed to provide immediate protection against microbial pathogens to eradicate infection. Activation of innate immunity is crucial for transition to specific immunity and for its orientation, and to assist the specific immune response in the recognition of pathogens and their destruction. Innate immunity is regularly involved in the arrest of bacterial, mycotic, viral and parasitic infections, giving the specific immune response time to become effective. It becomes critically essential in immunocompromised patients who fail to mount specific immune responses due to congenital or acquired immunodeficiencies as a result of chemotherapy, dialysis, immunosuppressive drugs, or HIV infection. The Innate Immunity arsenal constitutes polymorphonuclear and mononuclear phagocytes, mast cells, the complement system, Natural Killer cells, antimicrobial peptides, and presumably a subset of T lymphocytes with TCRl receptors.

The last decade has witnessed the delineation of innate immunity - a new area which has revolutionized our understanding of host-parasite interactions and their impact on defense mechanisms in infectious and noninfectious diseases. This volume of the book series 'Contributions to Microbiology' provides an update of the current knowledge of this expanding field of research and highlights some of its most important aspects. In eleven state-of-the-art articles, eminent international experts in the field address topics such as the innate immune system in mammals and insects, microbial protein ligands, antimicrobial peptides, complement, antibacterial chemokines, the role of neutrophils and monocytes, oxidative innate immune defenses and the effect of aging on innate immunity. The book will be a valuable resource for microbiologists, immunologists, students, scientists of other related disciplines, and clinicians with an interest in infectious or immunological diseases.

Immunobiology tells the story of the immune system. The book covers all of the material that comprises a typical immunology course. The Fifth Edition is an extensive revision which includes new material and major insights, improved logical progression of topics, and an emphasis on unifying principles. With clear, concise text and a full-color art program, this book continues to set the standard for a current and authoritative immunology textbook. Copyright © Libri GmbH. All rights reserved.

The innate immune system comprises the cells and mechanisms that are the first line of defence against infection by other organisms. This book provides a comprehensive synopsis of eye diseases, their immunological mechanisms and the role of the immune cells and mediators. Beginning with an introduction to the role of the innate immune system, the following chapters discuss the different types of immune cells in the eye and their role in the etiopathogenesis of various diseases including glaucoma and age-related macular degeneration. Edited by Manfred Zierhut, recognised expert from the University of Tuebingen Germany, this book is presented in an easy to read format, enabling practitioners to understand even the most sophisticated eye disorders from an immunological perspective. Key points Comprehensive synopsis of the role of the innate immune system in eye diseases Covers different types of immune cells Edited by internationally recognised specialist in Germany

Overall recent research on TLRs has led to tremendous increase in our understanding of early steps in pathogen recognition and will presumably lead to potent TLR targeting therapeutics in the future. This book reviews and highlights our recent understanding on the function and ligands of TLRs as well as their role in autoimmunity, dendritic cell activation and target structures for therapeutic intervention.

Until recently, innate immunity was regarded as a relatively nonspecific system designed to engulf and destroy pathogens. However, new studies show that the innate immune system is highly developed in its ability to discriminate between self and foreign entities. Understanding this mechanism can lead to therapeutic strategies based on manipulation of this previously unexploited branch of the immune system. Drawing on the research of leading experts, Nucleic Acids in Innate Immunity provides insight in this new area of immunology. The book begins by explaining the roles of nucleic acids in immunity, describing the mechanism of discrimination based on pattern-recognition receptors (PRRs), including Toll-like receptors (TLRs), Nod-like receptors (NLR), and RIG-I-like receptors (RLR). Chapters discuss how these PRRs recognize and respond to pathogen-associated molecular patterns (PAMPs) by activating specific signaling pathways. The second section focuses on the therapeutic applications of immunomodulatory DNA by manipulating released pathogenic nucleic acids as immune system stimulants. The book introduces novel therapeutics developed to prevent or treat infectious diseases, allergic disorders, and cancer, as well as clearing unnecessary or abnormal host molecules. The final section addresses how the immune system discriminates self and non-self RNA. Recent findings that host (self) nucleic acids are not inert in the immune system beg the question of exactly what elements within DNA or RNA are recognized by the innate immune system. Contributions review recent advances to understand innate immune recognition of nucleic acids and describe the resulting immune modulation. Providing a comprehensive review of nucleic acid recognition and regulation by the innate immune system, this seminal work reveals new directions for future research in immune modulation.

This book is an excellent, up-to-date reference on a relatively young area of research in which virology, cellular biology and molecular pathogenesis govern the principles of coinvestigation. Thus, the book will be of great interest to virologists, molecular immunologists and biologists, and biochemists but also to clinical pharmacologists in the long-term search for new antiviral agents. Ulrich Desselberger, Gif-sur-Yvette/Cambridge. Infection of a naïve (non-immune) host with a virus elicits an immediate response which results in a cascade of changes in the host, including an interferon response (innate immunity). The outcome of this interaction is influenced by the genes of the virus as well as the genes of the host. Interestingly, different viruses do it in different ways. Not only is there a plethora of mechanisms used by the invading organisms, but the host has also evolved a great variety of redundant and robust countermeasures. This interplay of host and virus represents one of the most significant frontiers in biology today. A clearer understanding of the mechanisms involved will arm us with better strategies to deal with viruses, including emerging pathogens and potential bioterrorism agents. This book is sure to benefit students, scientists, and physicians working in the areas of virology, immunology, microbiology, and infectious diseases. Pharmaceutical industry professionals will also find interest in this illuminating look into virus/host interactions.

The concept of innate immunity refers to the first-line host defense that serves to limit infection in the early hours after exposure to microorganisms. Recent data have highlighted similarities between pathogen recognition, signaling pathways, and effector mechanisms of innate immunity in Drosophila and mammals, pointing to a common ancestry of these defenses. In addition to its role in the early phase of defense, innate immunity in mammals appears to playa key role in stimulating the subsequent clonal response of adaptive immunity. Recent exciting information has determined that the templates that are laid down in primitive life forms, like flowering plants and insects, form the basic principles of first line host defense that are conserved in mammalian systems. The next frontier in the field is to understand the dynamic adaptive changes that occur as a result of the inter play between host defenses and infectious agents. One emerging theme is that microorganisms are constantly seeking ways to co-opt host defenses. On the other hand, host defense to infection is mediated by the coordinate action of pattern recognition molecules and receptors that, in mammals, are important and probably necessary antecedents to the development of an adaptive immune response. Innate Immunity aims to explore the intersection between host pathogen interactions across an evolutionary spectrum that will inform our understanding of the dynamic interplay between infectious agents and host defense in man.

This volume is edited by Dr. Sudhir Gupta, internationally recognized expert in Immunology, Professor of Medicine, Pathology, Microbiology and Molecular Genetics. Topics include toll receptors, dendritic cells, NK cells, and complement receptors.

Abstract : Review on the decline of immune response with age. Abstract : Immunosenescence, describing alterations, including decline of immune responses with age, is comprised of inappropriate elevations, decreases, and dysregulated immune responses, leading to more severe consequences of bacterial and viral infections and reduced responses to vaccination. In adaptive immunity, these changes include increased proportions of antigen‐experienced B and T cells at the cost of naïve cell populations. Innate immune changes in aging are complex in spanning multiple cell types, activation states, and tissue context. Innate immune responses are dampened in aging, yet there is also a paradoxical increase in certain signaling pathways and cytokine levels. Here, we review recent progress and highlight novel directions for expected advances that can lead the aging field to a new era of discovery that will embrace the complexity of aging in human populations.

The Innate Immune Response to Non-infectious Stressors: Human and Animal Models highlights fundamental mechanisms of stress response and important findings on how the immune system is affected, and in turn affects such a response. In addition, this book covers the crucial link between stress response and energy metabolism, prompts a re-appraisal of some crucial issues, and helps to define research priorities in this fascinating, somehow elusive field of investigation. Provides insights into the fundamental homeostatic processes vis-à-vis stressors to help in investigation Illustrates the depicted tenets and how to offset them against established models of response to physical and psychotic stressors in both animals and humans Covers the crucial issue of the immune response to endocrine disruptors Includes immunological parameters as reporter system of environmental adaptation Provides many illustrative examples to foster reader understanding