complement alternate pathway

Function

• particularly important before the appearance of antibody in the response to infection
• does NOT use C1, C2 or C4
• activation begins with deposition of active C3, generating C3b
• depends upon the carbonyl group of the exposed thiolester of C3b to interact with an amide or hydroxyl group of a protein or a carbohydrate on the surface of the target
• initiation C3 convertase cleaves C3 to generate metastable C3b at a rate of 0.2-0.4% of plasma pool per hour
• C3b can bind covalently to an activator surface then bind properdin factor B
• properdin factor D cleaves factor B to generate the cell-bound C3 convertase C3bBb
• C3bBb decays rapidly, but is stabilized by binding of properdin increasing 1/2life from 1-18 minutes
• stabilized C3 convertase C3bBb cleaves more C3 to C3b that binds target
• amplification of C3b deposition on the activator surface leads to formation of the C5 convertase C3b2BbP that can trigger activation of the terminal components of complement C5-C9 resulting in formation of the membrane attack complex (MAC)

Pathology

Defects in alternate pathway:

• etiology
  • sickle cell disease
• pathogens
  • Streptococcus pneumoniae
  • Salmonella species

More general terms

• cascade

Additional terms

• complement cascade
• sickle cell (hemoglobin SS) disease