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Classical activation of the complement cascade

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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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.

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