Where it is found
Many circulating components are liver-derived; immune and tissue cells also produce complement locally.
The Complement System
Tag. Recruit. Eliminate. Protect.
The complement system is a network of circulating and cell-associated proteins that recognizes threats, marks targets for clearance, recruits immune cells and can damage susceptible microbes. Tight regulation helps protect healthy tissue.
Explore the complement system →Complement at a glance
Main role
Tags targets, supports clearance and helps coordinate inflammation.
Speed
Pre-existing proteins allow rapid activation and amplification.
Why regulation matters
Healthy host surfaces need protection from inappropriate activation.
Three pathways of activation
Different triggers converge on C3 cleavage and the common downstream cascade.
Classical pathway
C1 can recognize clustered antibodies bound to targets and certain other recognition molecules.
Lectin pathway
Mannose-binding lectin or ficolins recognize microbial carbohydrate patterns.
Alternative pathway
Basal C3 activation and surface-bound complexes amplify responses on suitable targets.
Three pathways→C3 convertases→C3a + C3b→C5 convertases→C5a + C5b→C5b–9 (MAC)
What complement does
Opsonization
C3b and its fragments coat targets, helping phagocytes recognize and ingest them.
Inflammation and recruitment
C3a and especially C5a influence inflammation and leukocyte responses.
Direct killing (MAC)
C5b–9 forms membrane pores that can lyse susceptible targets.
Clearance of immune complexes and damaged cells
Complement supports disposal of immune complexes and cellular debris.
From recognition to elimination
1. Recognition
Recognition initiates one or more activation pathways.
2. Activation and amplification
Convertases generate additional active fragments.
3. Opsonization and inflammation
C3 fragments mark targets; anaphylatoxins influence recruitment.
4. C5 activation
C5 cleavage generates C5a and C5b.
5. Elimination
Phagocytosis and terminal complexes help clear targets.
Complement must be controlled
Soluble and membrane-bound regulators limit activation on healthy host cells.
- Factor H restrains alternative-pathway activity and supports factor I.
- Factor I cleaves C3b or C4b with appropriate cofactors.
- CD46 acts as a membrane cofactor.
- CD55 accelerates convertase decay.
- CD59 inhibits terminal pore assembly.
Complement connects innate and adaptive immunity
Complement fragments can enhance B-cell responses through complement receptors. Complement also influences antigen handling and immune-cell signaling, linking rapid recognition with adaptive responses.
When complement goes wrong
Excess or dysregulation
Can contribute to tissue injury in conditions such as atypical hemolytic uremic syndrome and complement-mediated kidney disease.
Deficiency
Can increase susceptibility to selected infections. Terminal-component deficiency particularly raises risk from Neisseria infections.
Complement and aging
Complement production, activation and regulation can change with age and disease. Effects depend on tissue and context; there is no single uniform age-related change.
Learn more about aging & immunity →Key takeaways
- Three activation pathways converge on C3.
- C3 fragments mark targets for clearance.
- C3a and C5a influence inflammation.
- C5b–9 can damage susceptible membranes.
- Regulators protect healthy host cells.
- Both deficiency and excessive activation can be harmful.
Selected sources and references
- Complement: immune surveillance and homeostasis
- Complement pathways and inhibitors
- Complement and T-cell responses
Artwork illustrates the main mechanisms schematically; molecular sizes, colors and distances are not literal.