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The complement system is a protein system that combines with antibodies to form a defense against bugs and viruses. This book contains entries on all its components, including C1q and lectins, serine proteases, and terminal pathway proteins.
The aim of the former editions remains unchanged in the present updated version, namely to put forward a general and comprehensive review on complement. It is intended not only for individual investigators working in this specific field, but also for those who are less familiar with it. Students or younger scientists will hopefully be stimulated and attracted by the fascination of complement biology. Again, it was clear from the beginning that the field has experienced an explosive expansion in various directions and continues to accumulate data too large to be dealt with by a single author in a critical and coherent manner. The editors are grateful that the invited authors, all of them leading scientists in their field, helped again to make The Complement System a true mirror of the state of the art. Some parallels in the various chapters were accepted, as was a particular emphasis on newer developments in some chapters.
Immunobiology of the Complement System: An Introduction for Research and Clinical Medicine provides an introduction to the complement system. The intention was to create a primer that would provide the basic knowledge of complement required for either research or clinical medicine in diseases involving the complement system. The book begins with a historical background of complement research; it introduces certain key investigators from the past who have made important contributions. Separate chapters on the basic aspects of complement function are followed by chapters on the molecular genet ...
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.
Upon contemplating an updated version of the 1974 edition of this book and envisioning its possible organization, it immediately became evident that the new version could no longer be written by one, two, or even three authors. The field has experienced an explosive expansion in various directions, and the wealth of newer data which has been accumulated over the last decade can hardly be presented by a single author in a critical and coherent manner. On the other hand, it appears worthwhile not to abandon the attempt to come foreward with a review which describes as comprehensively as possible the progress and the state of knowledge. It is the aim of this volume to present a general and comprehensive review on complement. It is intended not only for individuals working in this area, but also for those who are less familiar with the field. Several chapters in the book describe state-of-the-art experimental methods which are helpful to critically evaluate the experimental data. Simultaneously, they may provide the necessary technical tools for those who wish to enter this highly provocative and exciting field.
As a phylogenetically old system complement is now regarded as a part of innate immunity. But it is much more than that. It bridges innate and adapted immunity, participates not only in host defense but also in many essential physiological processes, old and new diseases and adverse conditions. Indeed, complement became a term that almost defies categorization. What was for a long time a subject for a limited number of specialists has now moved into the mainstream of experimental and clinical immunology. In 1973 I visited the Basel Institute of Immunology and met its director, the eminent scientist and Nobel laureate Nils Jerne. When I entered his office he greeted me with the following words: “Complement, does that really exist?” I was never certain whether he wanted only to tease me or whether he sincerely believed that the complement system was an unimportant biological curiosity, a misstep of evolution. But, of course, missteps do not survive the evolutionary process. Little did I foresee the dramatic developments of recent years when Hans J. Müller-Eberhard and I started to unravel the specifics of the action of the cobra venom factor on the complement system in 1968 and defined a new pathway to its activation. An elucidation of the role of the system in diseases and its control for therapeutic reasons is now getting closer to actual realization in the clinic although many problems, in particular those of highly specificinhibition free of side effects, have still to be resolved.
The complement system is a multi-tasking gatekeeper of innate immunity thatintricately interacts with other key defense systems, such as the endothelial barrier,contact activation and coagulation systems, in maintaining tissue immunosurveillanceand homeostasis. Its rapid and forceful activation in the bloodstream not onlyensures the effective containment of microbial infections through potent cytolyticmechanisms, but also alerts the adaptive immune compartment to ensure the mountingof a proper humoral immune response against foreign antigens. However, there isa lurking ‘dark side’ that can lead complement astray, fueling a self-perpetuatingvicious cycle of inflammation, exuberant immune activation and irreversible tissueinjury that collectively exacerbate both acute and chronic pathologies. Indeed,complement dysregulation or excessive activation have been widely recognized askey pathogenic drivers in a wide spectrum of inflammatory or immune-mediateddiseases. Targeted modulation of the complement system at various points ofthe cascade has revealed promising therapeutic targets for ameliorating diseasescores in a number of conditions ranging from ocular, neurodegenerative andthromboinflammatory disorders, to cancer, periodontal diseases, chronic hemolyticanemias, ischemia-reperfusion organ injury, antibody-mediated transplant rejectionand hemodialysis-triggered inflammation. Elegant pre-clinical studies employing a diversified toolbox of highly specificcomplement inhibitors in rodent or primate models of disease have opened newavenues of therapeutic exploration by providing proof of concept for the therapeuticefficacy of complement modulation. At the same time, the clinical experience gainedduring this last decade with the sole complement-specific drug currently in the clinic,eculizumab, has rekindled the interest of biopharmaceutical companies in developingnew and potent complement therapeutics for complement-driven diseases. In this respect, the complement field is witnessing a new surge of clinical trialsthat are evaluating the safety, PK/PD profile and clinical efficacy of promising drugcandidates in a number of clinical conditions driven by complement imbalance orover-activation.
Immunobiology of the Complement System: An Introduction for Research and Clinical Medicine provides an introduction to the complement system. The intention was to create a primer that would provide the basic knowledge of complement required for either research or clinical medicine in diseases involving the complement system. The book begins with a historical background of complement research; it introduces certain key investigators from the past who have made important contributions. Separate chapters on the basic aspects of complement function are followed by chapters on the molecular genetics of complement and the role of complement in different diseases. Key topics discussed include the activation of complement via the classical pathway and the alternative pathway; complement mediators of inflammation; opsonization and membrane complement receptors; assembly and functions of the terminal components; and complement-dependent mechanisms of virus neutralization. This book has been written primarily for students and scientists who have not been specifically trained in complement research.
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.
Of recent, the structure of the complement system has received considerable attention, including the publication of several three-dimensional structures of complement proteins. This has led to the need for an authoritative resource to provide a complete overview of the basics, as well as an explanation of the cutting-edge work being accomplished in this emerging science. Structural Biology of the Complement System is devoted to the full exploration of structural aspects of the complement system, with special consideration of the links between molecular structure and function. Containing the work of leading authorities across the disciplines of immunology and structural biology, the book serves both as an introductory volume for newcomers to the field and as a comprehensive reference for established researchers, in particular those whose goal is the discovery of anticomplement drugs. Written in a didactic style, this volume is an appropriate resource for students in the fields of immunology and structural biology. Structural Biology of the Complement System comes with downloadable resources containing color figures, a molecular structure visualization program, and files with three-dimensional coordinates of the structures described in the book. These tools allow readers to perform tailored structural manipulation and analysis, while also serving as a starting point for further research.