Complement Signaling

The complement system is an essential part of innate immunity. Three distinct activation pathways belong to the complement system: the classical, lectin, and alternative pathways. They all converge to the cleavage of C3 by C3 convertases. The downstream phases are common to the three pathways: opsonization, anaphylatoxin-mediated inflammation, and formation of terminal membrane attack complex. Classical and Lectin Pathways are shown. In the classical pathway, the cascade is initiated by the interaction between C1q and immunocomplexes, this lead to the activation of C1 that cleaves C4 to C4a and C4b, and C2 to C2a and C2b. In the lectin pathway, MBL and other ficolins are activated by pathogen molecules and up-regulate proteases MASP-1, MASP-2 that cleave intact C4 and C2. The C4b fragment combines with the lipid bilayer of the target cell and C2a to form the C3 convertase C2a4b.