The Complement System

As a phylogenetically old system complement is now regarded as a part of innate immunity. But it is much more than that.

Author: Janos Szebeni

Publisher: Springer Science & Business Media

ISBN: 1402080565

Category: Medical

Page: 565

View: 316

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

This book describes the basic regulation of the complement systems, presenting its biological functions, the target cell receptors for such functions and their interactions with ligands to induce specific cellular responses.

Author: K. Rother

Publisher: Springer Science & Business Media

ISBN: 3642587534

Category: Medical

Page: 564

View: 275

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 Complement System

Thus, in all cases thus far studied, complement reactivity leading to neutralization has been via activation of the classical pathway. Most and probably all enveloped viruses are susceptible to complement-dependent lysis.

Author: Klaus Rother

Publisher: Springer Science & Business Media

ISBN: 3642970389

Category: Medical

Page: 535

View: 875

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.

Therapeutic Modulation of the Complement System Clinical Indications and Emerging Drug Leads

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 ...

Author: John D. Lambris

Publisher: Frontiers Media SA

ISBN: 2889634701

Category:

Page:

View: 225

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.

Structural Biology of the Complement System

Structural Biology of the Complement System is devoted to a full exploration of the structural aspects of the complement system, with special consideration of the links between structure and function. The book provides a collective ...

Author: Dimitrios Morikis

Publisher: CRC Press

ISBN: 1000612082

Category: Medical

Page: 370

View: 403

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

Immunobiology of the Complement System

Initial studies with this system showed that alternative complement pathway activity with C3b deposition on the zymosan particles was required (53). Subsequent studies using complementdeficient plasmas to activate the zymosan showed ...

Author: Gordon D. Ross

Publisher: Academic Press

ISBN: 1483276392

Category: Health & Fitness

Page: 286

View: 735

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.

Structural Biology of the Complement System

Written in a didactic style, this volume is an appropriate resource for students in the fields of immunology and structural biology.

Author: Dimitrios Morikis

Publisher: CRC Press

ISBN: 0849350360

Category: Medical

Page: 370

View: 908

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

Activators and Inhibitors of Complement

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 ...

Author: Robert B. Sim

Publisher: Springer Science & Business Media

ISBN: 9401127573

Category: Medical

Page: 239

View: 549

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.

Complement

For them and those involved in complement research, this book provides a clear and concise explanation of the biochemistry, genetics and biological activity of the complement pathway, using diagrams wherever possible to aid understanding of ...

Author: B. Paul Morgan

Publisher:

ISBN:

Category: Complement (Immunology)

Page: 215

View: 398

The apparent complexity of the complement system strikes fear into many medical students and clinicians. For them and those involved in complement research, this book provides a clear and concise explanation of the biochemistry, genetics and biological activity of the complement pathway, using diagrams wherever possible to aid understanding of this fascinating arm of the immune response. From this basis, the important role of the complement system in the normal immune response and a variety of clinical disorders including rheumatoid, renal, neurological and dermatological disease are detailed.Using his experience as a senior clinical research fellow at the University of Wales College of Medicine, Dr. Morgan amply addresses the science of complement system to a medically trained audience and vice versa.

Complement Therapeutics

This book highlights progress and trends in the rapidly evolving field of complement-related drug discovery and spotlights examples of clinical applications.

Author: John D. Lambris

Publisher: Springer Science & Business Media

ISBN: 146144117X

Category: Medical

Page: 320

View: 794

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.