Activators And Inhibitors Of Complement
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Activators And Inhibitors Of Complement
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Author : Robert B. Sim
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Activators And Inhibitors Of Complement written by Robert B. Sim and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
The complement system is a group of proteins which plays a major role in the processing and removal of microorganisms and tissue breakdown products from the circulation and extracellular spaces. The system is activated by a wide range of targets, and activation leads to the production of opsonins, chemotaxis of granulocytes, cell lysis and other biological activities. Inappropriate overactivation of the system contributes to inflammatory tissue damage in the host, while inadequate activation leads to accumulation of immune complexes and other debris in the circulation, and susceptibility to infection. The biology and biochemistry of the system is now adequately understood, and attempts can be made to manipulate the activation and activities of the system for potential therapeutic purposes. The reviews in this volume summarise what is known of the ways in which the complement system can be activated, by interaction with antibodies, microorganisms, cell debris, and complex carbohydrates and how the activities and activation of the system have been modified, accidentally or by design, in vitro or in vivo by drugs, venoms, particulate carbohydrates, specific antibodies, synthetic peptides and other reagents.
The Complement System
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Author : Janos Szebeni
language : en
Publisher: Springer Science & Business Media
Release Date : 2007-05-08
The Complement System written by Janos Szebeni and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007-05-08 with Medical categories.
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.
Current Topics In Complement Ii
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Author : John D. Lambris
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-02-04
Current Topics In Complement Ii written by John D. Lambris and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-02-04 with Medical categories.
Complement has long been regarded as a pivotal effector arm of the innate immune response, eliciting important immunoregulatory functions in the context of inflammation and also serving as a vital link between the innate and adaptive immune response. In the post-genomic era, our knowledge of the innate immune system is enriched by findings that point to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or Inflammation. Several studies indicate that complement proteins exert functions that are either more complex than previously thought, or go well beyond the innate immune character of the system. The advent of high-throughput platforms for genome and proteome-wide profiling, together with the enormous amount of raw genetic information that has accumulated in the databases, have stirred new expectations in biomedical research. They have led complementologists to revisit established biological systems, such as the complement system, from a global and integrative perspective. Complement research is now faced with the challenge of trying to integrate isolated biochemical pathways into complex gene and protein regulatory circuits. In this respect, scientists from around the world convened at the Fourth Aegean Conferences Workshop on Complement Associated Diseases, Animal Models, and Therapeutics (June 10-15, 2007), to discuss recent advances in this fast evolving field. This volume represents a collection of topics on the “novel” functions of complement, patho-physiology, protein structures, design of complement inhibitors, and complement assays discussed during the conference.
Therapeutic Modulation Of The Complement System Clinical Indications And Emerging Drug Leads
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Author : John D. Lambris
language : en
Publisher: Frontiers Media SA
Release Date : 2020-02-14
Therapeutic Modulation Of The Complement System Clinical Indications And Emerging Drug Leads written by John D. Lambris and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-02-14 with categories.
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.
Complement Therapeutics
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Author : John D. Lambris
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-09-19
Complement Therapeutics written by John D. Lambris and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-09-19 with Medical categories.
This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications. As an integral part of innate immunity and critical mediator in homeostatic and inflammatory processes, the human complement system has been identified as contributor to a large number of disorders including ocular, cardiovascular, metabolic, autoimmune, and inflammatory diseases as well as in ischemia/reperfusion injury, cancer and sepsis. In addition, complement is often involved in adverse immune reactions to biomaterials, cell and organ transplants or drug delivery systems. Although the complement cascade with its close to 50 extracellular protein targets has long been recognized as an attractive system for therapeutic modulation, the past few years have seen a particularly strong boost in interest. Fueled by novel research insight and the marketing of the first complement-targeted drugs, a plethora of highly creative treatment approaches and potent drug candidates have recently emerged and are currently evaluated in disease models and clinical trials. The chapters in this book cover a wide range of topics related to the development of complement therapeutics, ranging from the molecular and functional description of complement targets to the presentation of novel inhibitors, improved treatment strategies as well as examples of disease models and clinical applications. The broad and up-to-date overview on a highly versatile and dynamic field renders this book an indispensable source of information for researchers and clinicians dealing with therapeutic and disease-related aspects of the human complement system.
Therapeutic Interventions In The Complement System
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Author : John D. Lambris
language : en
Publisher: Springer Science & Business Media
Release Date : 2000-04-15
Therapeutic Interventions In The Complement System written by John D. Lambris and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2000-04-15 with Medical categories.
A team of expert investigators and clinical researchers comprehensively review complement's basic biology, its role in disease, methods to measure its activity, and strategies for its inhibition in patients. Each chapter focuses on a specific area of basic and applied complement biology, spelling out the activation pathways and complement receptors. Informative animal models are discussed in detail, including the relative values of each model and the important interspecies differences that can distort the interpretation of preclinical studies. The emphasis throughout is on the pros and cons of the therapeutic use of recombinant complement inhibitors in specific diseases. Cutting-edge and innovative, Therapeutic Interventions in the Complement System highlights for today's researcher and biotechnologist effective strategies of drug discovery and development that are producing valuable new complement inhibitors for the treatment of a wide variety of clinically important diseases.
Complement
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Author : H.J. Müller-Eberhard
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
Complement written by H.J. Müller-Eberhard and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
Activation of the complement system gives rise to a number of molecular species which can interact with host-derived cells and regulate their function. This interaction is mediated through distinct cell surface complement receptors, and receptor engagement produces biologic responses which can either modulate host defense reactions or enhance inflammation. Although the first complement receptor was recognized more than 30 years ago [80J, detailed biochemical information concerning the receptors has only recently become available. Currently, eight distinct complement receptors are recognized. Five receptors (CRl, CR2, CR3, C3a receptor, and C3e receptor) react with various regions on C3 while the other receptors display specificity for Clq, C5a, or Factor H. This chapter focusses on the chemistry of the various ligands and receptors and discusses the biologic activities which arise as a result of receptor-ligand interaction. II. CIQ Receptor A. The Ligand Clq is the recognition molecule of the classical complement pathway [reviewed in 20, 130]. In serum, it is part of a calcium-dependent penta molecular complex containing one molecule ofClq and two molecules each of the pro enzymes Clr and CIs. During classical pathway activation, the macromolecular complex becomes associated with the activator through the Clq subcomponent. Bound Clq undergoes a conformational change and induces the proteolytic autoactivation of Clr which in turn effects the proteolytic activation of CIs. This process is controlled by the Cl inhibitor (ClINH) which binds irreversibly to activated Clr and CIs, and inhibits their enzymatic activities.
The Complement System
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Author : K. Rother
language : en
Publisher: Springer Science & Business Media
Release Date : 2012-12-06
The Complement System written by K. Rother and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2012-12-06 with Medical categories.
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.
The Role Of Complement In Health And Disease
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Author : Maciej Cedzyński
language : en
Publisher: Frontiers Media SA
Release Date : 2019-11-18
The Role Of Complement In Health And Disease written by Maciej Cedzyński and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2019-11-18 with categories.
Complement In Autoimmunity
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Author : George C. Tsokos
language : en
Publisher: Karger Medical and Scientific Publishers
Release Date : 2004
Complement In Autoimmunity written by George C. Tsokos and has been published by Karger Medical and Scientific Publishers this book supported file pdf, txt, epub, kindle and other format this book has been release on 2004 with Medical categories.
Complement protein expression and activation control central aspects of the normal B cell response. Imbalances in these processes invariably lead to autoimmune disease. Complement activation causes tissue damage in a number of ways and may by itself lead to autoimmune disease. Although the use of complement activation inhibitors in the treatment of complement-mediated tissue injury and disease is largely in pre-clinical trials, the expectations that they will be of significant clinical value are high. This volume contains a series of review articles that address the role of complement in the pathogenesis of autoimmune disease and the ensuing tissue damage. Topics include structural and functional aspects of the CD19/CD21/CD81 complex, role of the complement system in the expression of systemic lupus erythematosus (SLE) and antiphospholipid antibody syndrome. Also featured is the role of complement activation in ischemia/reperfusion and autoimmune disease injury. Finally, indepth reviews about complement activation in the development of glomerulonephritis in autoimmune disease and the function of membranebound complement regulatory proteins in autoimmunity are presented. Students as well as basic and clinical researchers in immunology who wish to understand the role of complement in the pathogenesis of autoimmune disease will value this comprehensive and up-to-date publication.