Complement and Complement Disorders

The complement system is a key player in innate immunity and a major effector of humoral immunity. Its activating components are a group of plasma proteins, whose triggering consists of a series of sequential protease-based steps similar to the coagulation, fibrinolysis, and contact pathways. Complement activation is linked to cellular responses by the recognition of cleaved complement protein fragments by receptors on leukocytes and vascular cells. The three primary roles of complement in host defense against infection are to (1) activate an immuno-inflammatory response; (2) opsonize microbial pathogens for immune adherence and ingestion; and (3) damage membranes, including those of susceptible organisms, to induce lysis. The complement cascade is amplified at several steps so that it has the potential to induce a rapid and massive opsonic and inflammatory response. Complement activation is normally highly targeted and strictly regulated to focus this response. However, undesirable or excessive complement activation also contributes to tissue injury in infectious, autoimmune, and acute and chronic inflammatory diseases. This chapter gives an overview of the “workings” of the complement system, a concise review of complement deficiency, and a discussion of the role of complement in diseases of inflammation, autoimmunity, and disposal of debris.