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.
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* The central event in complement activation is the hydrolysis of the major complement protein, C3.
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** C3 is a large 2-chain molecule.
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** Hydrolysis results in the removal of a small peptide, C3a.
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*** This leaves C3b.
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**** C3b is highly reactive but very short-lived.
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* The hydrolysis of C3 occurs spontaneously and slowly in plasma.
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** The reactive C3b formed is rapidly inactivated.
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* Some substances can interact to alter aspects of the complement system.
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** '''Bacterial cell surfaces'''.
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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.