Classical pathway of complement activation

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Classical and alternative pathways of complement activation

The classical complement activation pathway is evolutionarily younger than the alternative.

Initiated on surfaces where antibodies are bound (mainly IgG, IgM). Binding to a surface (e.g. bacteria) changes the conformation of the antibody molecule → reveals the binding site for C1. It starts by binding C1q to the Fc fragment of the immunoglobulin. C1 (= C1q + x C1r + 2xC1s) also changes shape and becomes proteolytically active upon binding to the antibody → begins to cleave C4 and C2. C4b and C2a bind to the surface of the challenged microorganism → forms classic C3-convertase → cleaves a lot of C3 into C3a and C3b. Then another enzyme is formed - classic C5-convertase (C4bC3bC2a) → cleaves C5 into C5a and C5b.

Pentraxins can also start the classical pathway: CRP, serum amyloid P (acute phase reactants).

Terminal (lytic) phase of the complement cascade

C5b forms a complex with other components - C6, C7, C8. This complex burrows into the surface of the lipid membrane of the attacked cell and attaches to a ring of 13-18 C9 molecules. A pore is formed in the membrane - cytoplasmic components leak out, osmotic balance is disturbed, cells can lyse.

Most microorganisms are resistant (protection by the cell wall).

Links

Related articles

• Complement system
• Alternative pathway for complement activation
• Mannose-binding lectin deficiency
• Lectin pathway of complement activation

External links

• HOŘEJŠÍ, Václav – BARTŮŇKOVÁ, Jiřina. Základy imunologie. 3. edition. Praha : Triton, 2008. 280 pp. ISBN 80-7254-686-4.