The Human Complement System: Basic Concepts and Clinical Relevance

Abstract The complement systemis a key player in innate immunity and a major effector arm 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, fibrinolytic, and contact pathways. Complementactivation is linked to cellular responses by the recognition of cleaved complementprotein fragments by receptors on leukocytes and vascular cells. The three primary roles of complementin host defense against infection are to (1) activate an inflammatory response; (2) opsonize microbial pathogens for immune adherence; and (3) damage membranes, including lysis of susceptible organisms. The complementcascade is amplified at several steps so that it has the potential to induce a rapid and massive opsonic and inflammatory response. Complementactivation is normally highly targeted and strictly regulated to focus this response. However, complementactivation 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 brief review of complement deficiency, and discussion of the role of complementin diseases of inflammation, autoimmunity, and debris disposal.