Figure 1.

Alternative pathway of the complement system.

The activation of the alternative pathway of the complement system depends on spontaneous hydrolysis of complement factor 3 (C3) in plasma leading to the formation of C3(H₂O) [Berger et al. 2005]. This molecule binds to factor B. Subsequent activation by factor D results in the formation of C3(H₂O)Bb. This complex cleaves additional C3 to C3a and C3b (split products of C3) constantly and at a low rate. In the presence of an activating surface (e.g. a bacterial wall), C3b is protected from inactivation by circulating regulatory proteins like factor I and factor H or by membrane co-factor protein (MCP) which is a protein anchored to the cell’s membrane. As a result the more active alternative pathway C3 convertase C3bBb is formed, which is further stabilized by properdin. The binding of C3b to the C3 convertase results in the formation of the C5 convertases (C3bBbC3b) for the alternative pathway [Berger et al. 2005]. The C5 convertases initiate the formation of the membrane attack complex (MAC) by cleavage of C5 to C5a (anaphylatoxin, split product of complement factor 5) and C5b. C5b binds to respectively C6, C7, C8 and multiple molecules of C9 to form MAC. MAC is able to incorporate to cell membranes and to provoke cell activation or even cell lysis [Berger et al. 2005].