The complement system: pathways, regulation and consequences of deficiency
Classical, lectin and alternative pathways, the regulators that stop complement attacking self, how to read C3, C4, CH50 and AH50, the diseases of deficiency and dysregulation, and how complement inhibitors work and what they cost in infection risk.
Tier 1Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Complement is about 30 plasma and membrane proteins, mostly made in the liver. Three activation pathways converge on C3 convertase, then C5 convertase and the membrane attack complex (C5b-9).
- Three jobs: opsonisation (C3b, iC3b), inflammation (C3a and C5a anaphylatoxins, C5a recruits neutrophils) and lysis (MAC, which matters mainly for Neisseria). A fourth: clearing immune complexes and apoptotic debris.
- The alternative pathway idles all the time ("tickover"). Regulators on host cells and in plasma stop it attacking self. Failure of regulation causes PNH, aHUS and C3 glomerulopathy.
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Sources
- Janeway's Immunobiology (10th ed.)W. W. Norton (Murphy, Weaver and Berg), 2022
- Complement. First of two partsNew England Journal of Medicine (Walport, 2001;344:1058-66), 2001
- Australian Immunisation Handbook: Meningococcal diseaseAU/NZAustralian Government Department of Health, Disability and Ageing, 2025
- Immunisation for people with medical risk conditions (NIP-funded MenACWY and MenB for complement inhibitor therapy)AU/NZAustralian Government Department of Health, Disability and Ageing, 2025
- Iptacopan: Public Summary Document, July 2024 PBAC meeting (PNH)AU/NZPharmaceutical Benefits Advisory Committee, 2024
- Pegcetacoplan: Public Summary Document, May 2025 PBAC meeting (PNH, C5 inhibitor-naive extension)AU/NZPharmaceutical Benefits Advisory Committee, 2025
- Infectious diseases associated with complement deficienciesClinical Microbiology Reviews (Figueroa and Densen, 1991;4:359-95), 1991
- High risk for invasive meningococcal disease among patients receiving eculizumab despite receipt of meningococcal vaccineAU/NZMMWR (McNamara et al., 2017;66:734-7), 2017
- Avacopan: Public Summary Document, March 2024 PBAC meetingAU/NZPharmaceutical Benefits Advisory Committee, 2024
- Withdrawal of TAVNEOS (avacopan)AU/NZTherapeutic Goods Administration, 16 October 2026
- Last updated
- 14 November 2026
What changed
- 14 November 2026 Personal emails, About story and Australian-style copy