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.

In the post genomic era, understanding of the innate immune system is enriched by findings on the specificity of innate immune reactions as well as to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or inflammation. This volume covers natural killer cells, mast cells, phagocytes, toll-like receptors, complement, host defense in plants and invertebrates, evasion strategies of microorganisms, pathophysiology, protein structures, design of therapeutics, and experimental approaches.

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.

The Third Aegean Conferences Workshop on Complement-Associated Diseases, Animal Models, and Therapeutics convened to discuss progress in complement research as it pertains to human disease pathogenesis and therapeutics. The rapid pace of research and new experimental approaches allow an integrated view of the in vivo biology of the complement system. This book collects writings on the functions of complement, pathophysiology, protein structures, design of complement inhibitors, and complement assays discussed at the conference.

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.

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.

Numerous studies have pointed to the key role of complement in the pathogenesis of retinal disease, particularly age-related macular degeneration (AMD). Reports about new gene associations and links to other physiological pathways are emerging almost on a weekly base. Several promising clinical candidates covering a wide area of potential treatment applications are in the pipelines of both industrial and academic groups. This indicates an increasing interest in complement as a therapeutic target. In view of these exciting discoveries, scientists from around the world convened at the First Aegean Conferences Conference on Inflammation and Retinal Disease: Complement Biology and Pathology (June 10-17, 2007) in Crete, Greece, to discuss recent advances in this rapidly-evolving field. This volume represents a collection of topics on the functions of complement in eye diseases, pathophysiology, protein structures, and complement therapeutics discussed during the conference. Our sincere thanks to the contributing authors for the time and effort they have devoted to writing what I consider exceptionally informative chapters in a book that will have a significant impact on the complement field. We would also like to express my thanks to Rodanthi Lambris for her assistance in collating the chapters and preparing the documents for publication and I gratefully acknowledge the generous help provided by Dimitrios Lambris in managing the organization of this meeting. Finally, I also thank Andrea Macaluso of Springer Publishers for her supervision in this book's production. John D. Lambris Anthony P.

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.

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.

The Third Aegean Conferences Workshop on Complement-Associated Diseases, Animal Models, and Therapeutics convened to discuss progress in complement research as it pertains to human disease pathogenesis and therapeutics. The rapid pace of research and new experimental approaches allow an integrated view of the in vivo biology of the complement system. This book collects writings on the functions of complement, pathophysiology, protein structures, design of complement inhibitors, and complement assays discussed at the conference.

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.

Numerous studies have pointed to the key role of complement in the pathogenesis of retinal disease, particularly age-related macular degeneration (AMD). Reports about new gene associations and links to other physiological pathways are emerging almost on a weekly base. Several promising clinical candidates covering a wide area of potential treatment applications are in the pipelines of both industrial and academic groups. This indicates an increasing interest in complement as a therapeutic target. In view of these exciting discoveries, scientists from around the world convened at the First Aegean Conferences Conference on Inflammation and Retinal Disease: Complement Biology and Pathology (June 10-17, 2007) in Crete, Greece, to discuss recent advances in this rapidly-evolving field. This volume represents a collection of topics on the functions of complement in eye diseases, pathophysiology, protein structures, and complement therapeutics discussed during the conference. Our sincere thanks to the contributing authors for the time and effort they have devoted to writing what I consider exceptionally informative chapters in a book that will have a significant impact on the complement field. We would also like to express my thanks to Rodanthi Lambris for her assistance in collating the chapters and preparing the documents for publication and I gratefully acknowledge the generous help provided by Dimitrios Lambris in managing the organization of this meeting. Finally, I also thank Andrea Macaluso of Springer Publishers for her supervision in this book's production. John D. Lambris Anthony P.

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.

The third component of complement, C3, is one of the most versatile proteins and an important participant in immune surveillance and immune response pathways. Its multifunctio nality is based on its ability to interact specifically with multiple serum complement proteins, cell surface receptors, and mem brant;-associated regulatory proteins. One of its most intriguing strategies of interaction with cell surfaces is the covalent binding of activated C3 through the internal thioester. The field has expanded over the past 10 years and a wealth of information has accumulated. C3 from various species and many of the human C3 binding proteins have been cloned and expressed. Numerous cellular responses mediated by the diffe rent fragments of C3 have been described. The findings that C3 interacts in a ligand-receptor-like fashion with proteins of nonself origin such as the gC of herpes simplex virus, a 70-kDa protein from Candida albicans, proteins from Epstein-Barr virus, etc. has opened a new field of investigation. The papers assembled in this volume summarize the wealth of data on the various aspects of the C3 interactions; together they bring to the reader new information on the chemistry, molecular gene tics, biology, and pathophysiology of C3 and C3-binding proteins. Emphasis is given to structural features as they relate to functions. Spring 1989 JOHN D. LAMBRIS, HANS J. MULLER-EBERHARD Table of Contents J. E. VOLANAKIS: Participation of C3 and Its Ligands in Complement Activation . . . . . . . . . . . 1 S. R. BARNUM, G. FEY, and B. F. TACK: Biosynthesis and Genetics of C3 . . . . . . . . . . . . .

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.

Innate Immunity has long been regarded as the non-specific arm of immune response, acting immediately and in a generic way, to defend the host from infections. In the post genomic era, our knowledge of the innate immune system is enriched by findings on the specificity of innate immune reactions as well as to novel functions that do not strictly correlate with immunological defense and surveillance, immune modulation or inflammation. Several studies indicate that molecules involved in innate immunity 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 scientists to revisit established biological systems from a global and integrative perspective. Innate Immunity 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 4th International Conference on Innate Immunity (June 4 - 9, 2006), in Corfu, Greece to discuss recent advances in this fast evolving field.

This volume represents a collection of topics on natural killer cells, mast cells, phagocytes, toll like receptors, complement, host defense in plants and invertebrates, evasion strategies of microorganisms, pathophysiology, protein structures, design of therapeutics, and experimental approaches discussed during the conference.