Figure 1.

The complement system. The complement system can be activated by three pathways. The classical (CP) and lectin (LP) pathways involve recognition of target-bound antibody or pathogen-specific carbohydrates by C1q or MBL, respectively. In the alternative pathway (AP), continuous, low-level activation of C3 by spontaneous hydrolysis of the internal C3 thioester, or C3 cleavage by plasma proteases, generates C3(H₂O) or C3b. Activation by any of the three pathways leads to the generation of C3 convertase complexes (C4b2a in the CP/LP and C3bBb in the AP) that cleave C3 into C3a and C3b. Additionally, the AP C3 convertase can bind properdin (P), a positive regulator that stabilizes the enzyme, extending its half-life more than 10-fold. The C3b generated can, in turn, forms more AP C3 convertase, allowing amplification of complement activation. The binding of a new C3b molecule to the C3 convertases creates the C5 convertases (C4b2aC3b or C3bBbC3b), which cleave C5 into C5a and C5b. C5b then initiates the terminal complement pathway, which eventually leads to the formation of the membrane attack complex (C5b-9) and lysis of the target cells. Complement activation is controlled at various levels by different soluble and membrane regulatory proteins (indicated within boxes).