The central event in complement activation is the splitting (by hydrolysis) of the major complement protein - C3; this is a large 2-chain molecule and hydrolysis results in the removal of a small peptide – C3a, leaving the highly reactive but very short-lived molecule - C3b. This happens, spontaneously and slowly, in plasma and the reactive C3b in rapidly inactivated. However, bacterial cell surfaces protect the reactive C3b from this rapid inactivation (it is still inactivated but more slowly) and this is the basis of the archaic complement system that is now termed the alternative pathway of complement activation. Subsequently the immune system has optimized complement activation via antibody - antigen complexes; this is now termed the classical pathway of complement activation. The difference between the two pathways only involves the mechanisms of C3 breakdown to C3b. Once C3 is hydrolysed, the later terminal pathway is the same and is often called the membrane attack complex or MAC and involves the binding of C5-C9. The complex sequence of events in both the alternative and classical pathway of complement activation (or complement fixation) is shown in Figure 1. | The central event in complement activation is the splitting (by hydrolysis) of the major complement protein - C3; this is a large 2-chain molecule and hydrolysis results in the removal of a small peptide – C3a, leaving the highly reactive but very short-lived molecule - C3b. This happens, spontaneously and slowly, in plasma and the reactive C3b in rapidly inactivated. However, bacterial cell surfaces protect the reactive C3b from this rapid inactivation (it is still inactivated but more slowly) and this is the basis of the archaic complement system that is now termed the alternative pathway of complement activation. Subsequently the immune system has optimized complement activation via antibody - antigen complexes; this is now termed the classical pathway of complement activation. The difference between the two pathways only involves the mechanisms of C3 breakdown to C3b. Once C3 is hydrolysed, the later terminal pathway is the same and is often called the membrane attack complex or MAC and involves the binding of C5-C9. The complex sequence of events in both the alternative and classical pathway of complement activation (or complement fixation) is shown in Figure 1. |