Complement: Classical and Lectin Pathways

Abstract

The classical and lectin pathways of complement are major recognition systems of innate immunity that are found in mammals and other animal species. By means of several multimolecular proteases, each comprising a recognition protein and a protease component, pathogens and other targets are detected and thereby trigger proteolytic reactions. The classical pathway is initiated by C1, a complex of the recognition molecule C1q and two associated enzymes, C1r and C1s, whereas the lectin pathway is initiated by carbohydrate recognition molecules (mannan‐binding lectin (MBL) or one of the three ficolins or collectin‐LK) in complex with another set of enzymes, MBL‐associated serine proteases (MASPs). Both pathways converge to the formation of C3 convertase, a complex protease that cleaves C3, the central component of the complement system. Proteolytic cleavage of C3 generates a series of fragments and elicits various effector mechanisms, including inflammation and phagocytosis. These mechanisms contribute to the elimination of pathogenic microorganisms and altered host cells from blood and tissues and modulate the adaptive immune response. Key Concepts C1q, MBL, CL‐LK and ficolins are pattern‐recognition molecules able to sense motifs on pathogens and altered self‐cells. C1q is a major sensor of apoptotic cells and regulator of immune tolerance. Proteolytic cleavage of C3 is pivotal for amplification of the complement response and labelling of the target particles. Target recognition, proteolysis and complex formation generate conformational changes that underlie complement functioning. Complement activation and activity are tightly regulated to avoid noxious side‐effects on normal host cells and tissues.