The Alternative (indirect) complement pathway or Properdin pathway

THE ALTERNATIVE (INDIRECT) COMPLEMENT PATHWAY

  • In alternative pathway C3 is activated and form a stable attachment of C3b   to microbial cell surface without the involvement of antibody.
  • Normally C3 in plasma breaks down spontaneously into C3a and C3b. The newly formed C3b binds covalently through thioester bonds to the surface of cells including microbes.
  • Under normal condition cell bound C3b binds to H factor.
  • H factor binds with sialic acid or other neutral and anionic polysaccharides present in cell surfaces.
  • Binding of H factor activate I factor (protease) and C3b is destroyed thus complement activation stops.
  • Since mammalian cell surface glycoproteins are heavily sialylated, it does not trigger the alternative complement pathway.
  • Bacterial cell walls, bacterial lipopolysaccharides, viruses, aggregated immunoglobulin (IgA), cobra venom etc. permit activation of C3b. Thus activation can occur by both immunologically and non immunologically.
  • The bound C3b binds to a plasma protein called B factor and once bound, factor B is cleaved by a plasma serine protease (called factor D) to generate a bound fragment called Bb (also a soluble fragment Ba).
  • Factor D acts only on B factor after it is bound to C3b (another example of substrate modulation).
  • The complex C3bBb is the alternative pathway C3 convertase and cleaves C3 to C3b and C3a. C3a is released and C3b remain attached to cells. Half-life of C3b is only 5 minutes.
  • Another protein called properdin (factor P) binds to the complex to form C3b BbP and increase the half-life to 30 minutes. Microbial cells favour the attachment of Properdin.
  • C3b may also be generated by other protease from activated phagocytic cells and there is generation of C3b at the site of inflammation.
  • Some C3b molecules generated by alternative pathway bind to C3 convertase itself and form C3bBb3b, which function as the alternative pathway C5 convertase and cleave C5 to initiate the terminal steps of complement activation.
Last modified: Wednesday, 25 August 2010, 11:30 AM