Non-clinical sciences/Immunology · Complement

Classical complement pathway

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What it means

Triggered by antibody (IgG/IgM)–antigen complexes binding C1 → C4+C2 → C3 convertase (C4b2a) → C3b (opsonin) + C3a → C5 convertase → C5b initiates MAC; C3a/C5a are anaphylatoxins, C5a chemotactic. C4 and C3 are consumed in active autoimmune disease.

Worked example

Low C3 AND C4 in an SLE flare = classical-pathway consumption by immune complexes. C1-esterase-inhibitor deficiency → hereditary angio-oedema.

In the exam

During an active lupus flare both C3 and C4 fall because antibody–antigen complexes are consuming this antibody-triggered pathway.

What settles it

Classical = antibody-triggered (C1, C4 consumed); alternative = spontaneous/antibody-independent on microbial surfaces (C4 normal).

Classically confused with

Alternative complement pathway

Source: StatPearls — Complement