Complement System Summary

Complement System Overview

• Group of plasma proteins involved in inflammation, cell lysis, and phagocytosis.
• Activated by various foreign molecules, initiating a sequential cascade of reactions.
• Major components are C1 through C9, named in the order discovered.

Activation Pathways

Classical Pathway

• C1 binds to antigen-antibody complex on pathogen surface.
• Cleavage: C1 -> C2 (into C2A and C2b) and C4 (into C4a and C4b).
• C2b and C4b form C3 convertase, cleaving C3 into C3a and C3b.

Alternative Pathway

• Activated by free antigens (e.g., endotoxins, polysaccharides).
• C3b forms when free antigens interact with existing C3b.

Complement Cascade Dynamics

• Small amounts of C3a and C3b are constantly formed but quickly destroyed without activation.
• C3b reacts with factors B, D, and properidin to form C3 convertase (cleaves C3 into C3a and C3b).
• After C3 cleavage, both pathways converge:
  • C3a stimulates inflammation.
  • C3b facilitates further C3 convertase formation and opsonization, enhancing phagocytosis.

Role of C5 and Membrane Attack Complex

• C3 convertase with properidin leads to C5 convertase, cleaving C5 into C5a and C5b.
• C5a enhances inflammation and attracts phagocytes.
• C5b combines with C6, C7, C8, and C9 to form the membrane attack complex, which lyses target cells.