Innate Immunity

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

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

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.

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.

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.

An in-depth look at cutting-edge research on the body's innate immune system Innate immunity is the body's first line of protection against potential microbial, viral, and environmental attacks, and the skin and oral mucosa are two of the most powerful barriers that which we rely on to stay well. The definitive book on the subject, Innate Immune System of Skin and Oral Mucosa: Properties and Impact in Pharmaceutics, Cosmetics, and Personal Care Products provides a comprehensive overview of these systems, including coverage of antimicrobial peptides and lipids and microbial challenges and stressors that can influence innate immunity. Designed to help experts and newcomers alike in fields like dermatology, oral pathology, cosmetics, personal care, and pharmaceuticals, the book is filled with suggestions to assist research and development. Looking at the many challenges facing the innate immune system, including the impact of topically applied skin products and medications, Innate Immune System of Skin and Oral Mucosa paves the way for next generation treatment avenues, preventative approaches, and drug development.

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

This second edition presents methods and protocols to aid readers in the design and execution of experiments used to define critical elements associated with innate immune system function. New and updated chapters detail protocols on in vitro and ex vivo studies in key cell types associated with innate immunity and with in vivo protocols used to study immune system function in the mouse. Additionally, chapters describe methods to evaluate innate immune function and new protocols associated with autism, cancer, microfluidics platforms, and CRISPR systems. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and easy to use, Mouse Models of Innate Immunity: Methods and Protocols, Second Edition will serve the research community by providing expert advice and protocols that allow both experienced and novice investigators to successfully plan, implement, and assess disease processes associated with the innate immune system.

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.

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.

Mounting evidence in the past decade indicates that innate immunity mediates functions above and beyond first-line defense against infection. It is now appreciated that innate immune mechanisms are critically involved in the development of adaptive immunity and, moreover, the regulation of diverse physiological and homeostatic processes. The latter explains why deregulation of innate immunity may lead to pathological disorders that are not necessarily or directly related to host defense. This Volume compiles the latest advances in this rapidly evolving field as presented by eminent scientists at the 7th International Aegean Conference on Innate Immunity in Rhodes, Greece. It includes topics related to the biology and function of Toll-like and other pattern-recognition receptors, complement and its crosstalk with other physiological systems, inflammatory mechanisms and diseases, natural killer cells, and the cooperative interplay between innate and adaptive immune cells. This book is an excellent source of information for researchers and clinicians with interests in immunology, host-microbe interactions, and infectious and inflammatory diseases.

The innate immune system is rapidly activated in response to infection and injury. It is a generic rather than pathogen-specific response that recruits immune cells, promotes inflammation, and mobilizes the adaptive immune system. Excessive or chronic inflammation may cause tissue damage, so a careful balance is required to restore homeostasis. Written and edited by experts in the field, this collection from Cold Spring Harbor Perspectives in Biology reviews the cellular and molecular mechanisms involved in innate immunity and all types of inflammation. The contributors examine the cell types that make up the innate immune system, their use of pattern recognition receptors (e.g., Toll-like receptors) to identify pathogens and damaged tissues, and how they trigger signaling pathways that culminate in inflammation, pathogen destruction, and tissue repair. The numerous chemical signals and factors involved in innate immunity and inflammation are described, as are those that keep inflammation in check. The authors also discuss the diseases that can result when these processes go awry, such as rheumatoid arthritis and cancer. This volume is therefore a valuable reference for all immunologists, cell biologists, and medical scientists wishing to understand these protective processes and their implications for human health and disease.

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.

Long-lasting T cell immunity is delivered by an array of individual T lymphocytes expressing clonally distributed and highly specific antigen receptors recognizing an almost infinite number of antigens that might enter in contact with the host. Following antigen-specific priming in lymphnodes, naïve CD4 and CD8 T lymphocytes proliferate generating clones of effector cells that migrate to peripheral tissues and deliver unique antigen-specific effector functions. Moreover, a proportion of these effector lymphocytes survive as memory T cells that can be rapidly mobilized upon new exposure to the same antigen, even years after their primary induction. Innate immune cells play crucial roles in the induction and maintenance of this efficient protection system. Following the seminal discovery of Steinman and Cohen in 1974 describing a rare cell type capable of initiating antigen-specific responses in lymphnodes, Dendritic Cells (DC) have taken up the stage for several decades as professional Antigen Presenting Cells (APC). Although DC possess all attributes to prime naïve T lymphocytes, other immune cell subsets become crucial accessory cells during secondary and even primary activation. For instance, Monocytes (Mo) are rapidly recruited to inflammatory sites and have recently been recognized as capable of shaping T cell immunity, either directly through Ag presentation, or indirectly through the secretion of soluble factors. In addition, upon sensing of T cell-derived cytokines, Mo differentiate into functionally different APC types that further impact on the quality and persistence of memory T cell responses in peripheral tissues. Other innate immune cells, including Myeloid Derived Suppressor Cells, Granulocytes and iNKT lymphocytes, are known to modulate T cell activation by interacting with and modifying the function of professional APC. Notably, innate immune cell determinants also account for the tissue-specific regulation of T cell immunity. Hence, the newly discovered family of Innate Lymphoid Cells, has been recognized to shape CD4+ T cell responses at mucosal surfaces. Although the actions of innate immune cells fulfills the need of initiating and maintaining protective T cell responses, the excessive presence or activity of individual determinants may be detrimental to the host, because it could promote tissue destruction as in autoimmunity and allergy, or conversely, prevent the induction of immune responses against malignant tissues, and even modulate the response to therapeutic agents. Thus, understanding how defined innate immune cell subsets control T cell immunity is of fundamental relevance to understand human health, and of practical relevance for preventing and curing human diseases. In this research topic, we intend to provide an excellent platform for the collection of manuscripts addressing in depth how diverse innate immune cell subsets impact on T cell responses through molecularly defined pathways and evaluating the rational translation of basic research into clinical applications.

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 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.

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.