Complement: activation, consequences, and control

The American Journal of Medical Technology
|September 1, 1982
PubMed

Insights

Complement activation drives immune-mediated injury through classical and alternative pathways. Control proteins modulate these potentially destructive effects, highlighting key mechanisms in host defense.

Area of Science:

  • Immunology
  • Biochemistry

Background:

  • Complement activation is a key humoral effector mechanism in immune-mediated injury.
  • Two primary pathways, classical and alternative, initiate complement cascades.
  • Both pathways involve sequential protein activation, with distinct dependencies on calcium and magnesium ions.

Purpose of the Study:

  • To elucidate the mechanisms of complement activation via classical and alternative pathways.
  • To describe the protein interactions and dependencies within each pathway.
  • To highlight the role of control proteins in modulating complement's effects.

Main Methods:

  • Review of established complement pathway activation sequences.
  • Analysis of biochemical dependencies (e.g., calcium, magnesium) for key steps.
  • Identification of common and distinct proteins in classical and alternative pathways.

Main Results:

  • Classical pathway activation initiated by antigen-antibody reaction involves C1q, C1r, C1s (calcium-dependent) and C4, C2 (magnesium-dependent).
  • Alternative pathway activation is surface-dependent, involving C3b and Factor B (magnesium-dependent), leading to C3 convertase formation.
  • Both pathways converge, activating nine proteins, with six common to both.

Conclusions:

  • Complement activation, while crucial for host defense, can lead to immune-mediated injury.
  • Control proteins play a vital role in regulating the extent of complement activation and its potentially harmful consequences.

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