Medicine & USMLE

Common Complement Pathway

  1. Common Complement Pathway
  2. Classical Complement Pathway
  3. Alternative Complement Pathway
  4. Lectin Complement Pathway


The Common Complement Pathway is a common set of steps that make up the final part of complement activation.

It begins with C3 convertase attached to a surface, the common end-product of the classical, alternative, or lectin pathways. This C3 convertase cleaves C3 into two parts: C3a and C3b. C3a is the smaller part that is released into the bloodstream, where it promotes anaphylaxis and inflammation. C3b is the larger piece that remains bound to the surface to promote opsonization. C3b also activates downstream proteins to produce a C5 convertase.

C5 convertase takes C5 and cleaves it into two parts: C5a and C5b. C5a is the smaller part that is released to promote anaphylaxis and chemotaxis, while C5b is the bigger piece that remains bound to the surface. C5b later combines with C6 through C9 to form the Membrane Attack Complex (MAC). MAC is responsible for punching holes in the activating surface, which ultimately results in cell death. 

Key Points

  • Common Complement Activation
    • Goals is to kill cells with activating surfaces and induce local inflammation
    • Other activation pathways → C3 convertase
      • Cleaves C3 into C3a and C3b 
        • C3a is released as an anaphylatoxin
        • C3b remains bound to improve opsonization 
          • Stimulates phagocytosis by neutrophils/macrophages
    • C3b combines with other proteins → C5 convertase
      • Cleaves C5 into C5a and C5b
        • C5a is released as an anaphylatoxin and promotes chemotaxis
        • C5b remains bound
    • C5b combines with C6 through C9 → Membrane Attack Complex (MAC)
      • MAC forms holes in activating membrane → cell / pathogen death
      • C6 through C9 are known as terminal complement proteins
        • Deficiency leads to susceptibility to bacteria (e.g. Neisseria)