8 and 9- Complement

• Classical Pathway

  1. Initiated by antibody binding (IgM or IgG)

  2. C1 complex then binds to Ig

  3. C1s cleave complement proteins C4 and C2

  4. C4b binds to membrane --> c4b2a is the C3 convertase

  5. C3 convertase generate C3b ( C5 convertase)

  6. C5 cleaved: recruits C6-C9 : MAC formation
• Alternative Pathway


  1. Initiated by spontaneous hydrolysis of C3

  2. Binds to factor B to form complex, then cleaved by Factor D

  3. Results in C3(H2O)Bb a C3 convertase

  4. C3b bind to membrane of target cell

  5. Factor B and D do jobs again

  6. Active form of C3b bond to molecules to make C3bBbC3b: a C5 convertase

  7. C5 convertase cleaves C5s: C5b binds to membrane

  8. C5b initiates generation of MAC
• Lectin Pathway


  1. Initiated when soluble proteins recognize microbial polysaccharides (lectin)

  2. Mannose binding lectins bind to microbial surface

  3. MASPs bind to MBL and cleave C4 and C2

  4. Forms C3 convertase on membrane: C4b2a

  5. C3 is cleaved and pieces will combine with C3 convertase to form C5 convertase

  6. C5b initiates MAC complex