Complement Regulatory Proteins

From small beginnings in the early 1970s, the study of complement regulatory proteins has grown in the last decade to the point where it dominates the complement field. This growth has been fueled by the discovery of new regulators, the cloning of old and new regulators, the discovery that many of the regulators are structurally and evolutionarily related to each other and the development of recombinant forms for use in therapy. There are now more proteins known to be involved in controlling the complement system than there are components of the system and the list continues to grow. The time is ripe for a comprehensive review of our current knowledge of these intriguing proteins. This book does just that. The first few chapters discuss the "nuts-and-bolts" of the complement regulators, describing their structures, functional roles and modes of action. The roles of the complement regulators in vivo are then described, focusing on the consequences of deficiency, roles in the reproductive system, interactions with pathogens and exploitation for therapy. The interesting developments in defining the complement regulators expressed in other species are also discussed. The book is written as a monograph, albeit by two people. The text is as readable as possible without compromising on scientific accuracy and completeness. The conversational style very evident in some sections is deliberate! Placing all references in a single bibliography at the end of the text further improves readability. The reader will go to the book to discover a specific fact but be persuaded to read more and derive pleasure from the process. The authors' enthusiasm for the subject comes over strongly in the text, and this enthusiasm proves infectious. Complement regulators--structure, functional roles and mode of action Comprehensive reviews of each of the individual regulators Roles of Complement regulators in vivo,in health and disease: Consequences of deficiency Roles in the reproductive system Interactions with pathogens Exploitation for therapy Complement regulators in other species

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 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 . . . . . . . . . . . . .

The Complement FactsBook contains entries on all components of the Complement System, including C1q and Lectins, C3 Family, Serine Proteases, Serum Regulators of Complement Activation, Cell Surface Proteins, and Terminal Pathway Proteins. Domain Structure diagrams are incorporated to clearly illustrate the relationships between all the complement proteins, both within families and between families. The FactsBook also includes the cDNA sequences, marked with intron/exon boundaries, which will facilitate genetic studies. Includes the cDNA sequences, marked with intron/exon boundaries, facilitating genetic studies Presents detailed structural information including cDNA and gene structure for all proteins Introduces complement function, simply described for each function Data is as up-to-date as possible, including unpublished work from many contributors Incorporates domain structures diagrams, which beautifully illustrate the relationship between all the complement proteins, both within, and between, familiesEach chapter has been written by an expert in the field Data is as up-to-date as possible, including unpublished work from many contributors Entries provide information on: Alternative nomenclature, Physiochemical properties, Structure and function, Tissue distribution and regulation expression, Protein sequence/modules, Chromosomal location, Genomic structure, Database accession numbers, Deficiency and polymorphic variants, Key references

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.