classical activation of the complement cascade
Last reviewed 01/2018
When IgG or IgM antibodies bind to an antigen on the surface of a bacterium or virally-infected cell, the immune complex formed interacts with the early complement components:
- C1q binds to the antigen-antibody complex and is thus activated
- C1r and C1s subunits then bind with C1q, are activated and the whole complex cleaves both C4 and C2
- C4 is split into C4a and C4b
- C2 is split into C2a and C2b
- C4b binds to the target cell membrane and forms a complex with C2b
- the C4b/C2b complex cleaves C3
- C3 is converted to C3a and C3b
- C3b forms a complex with C4b/C2b to cleave C5
- C5 is converted to C5a and C5b
- C5b binds to the target cell membrane and sequentially binds C6 to C9
The complex of C5b to C9 within the cell membrane is the membrane attack complex (MAC), a circular pore which damages the target cell. A number of the components produced in the pathway have independent roles in inflammation.