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Complement system - Classical pathway

Classical pathway:
Here complement system is activated by antibodies bound to pathogen surface or antibody-antigen complexes, thus involved in specific and acquired immunity.
Classical and Alternative pathway
Classical and Alternative pathway
Classical pathway step wise explanation:
Step 1: Activation of C1 by binding of Antigen antibody complex.
Step 2: activated C1 is a protease which cleaves C2 and C4 to form C4b2b complex.
Step 3: C4b2b complex is a C3 convertase that cleaves C3 molecule into two fragments C3a and C3b. C3a ia an anaphylatoxin(not involved in the down pathways).
Step 4: C3b forms complex with C4b2b producing C5 convertase (C4b2b3b).
Step 5: C5 convertasecleaves C5 to C5a and C5b. C5a is an anaphylatoxin and chemotactic factor (not involved in the down pathways).
Step 6: C5b binds to C6 and C7 to form a complex initially then interacts with C8 and C9 to produce the membrane attack complex (MAC)” (C5b6789). This membrane attack complex causes cell lysis.
Additional points:
  • Calcium is required for C1 activation
  • Normally ‘b’ fragments continue in the main pathway and ‘a’ fragments split off and has specific activities.
  • Anaphylotoxins: induces the release of inflammatory mediators like histamines from the mast cells. C3a, C4a and C5a are the anaphylatoxins of which C5a is the most potent.
  • Chemotaxis: C5a attract neutrophils and also enhances adhesiveness of neutrophils to the endothelium. 
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