Medicine & USMLE

Alternative Complement Pathway

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


The Alternative Complement Pathway is one of three initiating pathways of the complement system. In this pathway, circulating C3 is spontaneously cleaved to form C3b, which is stabilized by microbial surfaces. C3b bound to a surface recruits Factor B, which is then cleaved by Factor D. Together, this forms a C3bBb complex, which is a C3 convertase. Formation of the C3 Convertase kicks off the Common Complement Pathway, which ultimately results in the death of the microbe.

Key Points

  • Alternative Complement Activation
    • One of three initiating pathways of the complement system 
    • End goal is to kill foreign cells without alternative complement inhibitors
    • Begins with spontaneous cleavage of C3
      • C3 is inherently unstable
    • C3b stabilized by microbial surfaces
      • Normal cell surfaces express inhibitors Factors H and I
        • Prevent excess complement activation on normal cells
    • C3b cleaves Factor D and Factor B in turn
    • Cleaved Factor B combines with C3b → C3 convertase