Cascade of plasma proteins providing rapid innate immune response through three activation pathways (classical, alternative, lectin) converging on terminal pathway to create Membrane Attack Complex (Membrane Attack Complex), opsonize pathogens, and amplify inflammation.
graph TD
subgraph "Classical Pathway"
A["Ab-Ag complex"] --> B["C1 activation<br/>(C1q/C1r/C1s)"]
B --> C["C4b2a<br/>(C3 convertase)"]
end
subgraph "Lectin Pathway"
D["Pathogen<br/>carbohydrates"] --> E["[mannose](/en/concepts/mannose.md)-binding<br/>lectin (MBL)"]
E --> F["C4b2a<br/>(C3 convertase)"]
end
subgraph "Alternative Pathway"
G["Spontaneous C3<br/>hydrolysis on<br/>pathogen surfaces"] --> H["C3bBb<br/>(C3 convertase)"]
end
C --> I["C3 cleavage"]
F --> I
H --> I
subgraph "Amplification"
I --> J["C3a<br/>(anaphylatoxin)"]
I --> K["C3b<br/>(opsonin)"]
K --> L["C5 convertase<br/>(C4b2a3b / C3bBb3b)"]
end
subgraph "Terminal Pathway → MAC"
L --> M["C5a<br/>(anaphylatoxin)"]
L --> N["C5b"]
N --> O["C5b-C6-C7-C8"]
O --> P["C5b-C6-C7-C8-C9n<br/>[Membrane Attack Complex](/en/concepts/membrane-attack-complex.md)<br/>(~10nm pore)"]
end
J --> Q["[inflammation](/en/concepts/inflammation.md)<br/>recruitment"]
M --> Q
K --> R["[opsonization](/en/opsonization)<br/>→ phagocytosis"]
P --> S["Target cell lysis"]
style A fill:#f8d7da,stroke:#dc3545
style D fill:#f8d7da,stroke:#dc3545
style G fill:#f8d7da,stroke:#dc3545
style I fill:#fff3cd,stroke:#ffc107
style L fill:#fff3cd,stroke:#ffc107
style K fill:#cce5ff,stroke:#004085
style J fill:#cce5ff,stroke:#004085
style M fill:#cce5ff,stroke:#004085
style P fill:#d4edda,stroke:#28a745
style Q fill:#d4edda,stroke:#28a745
style R fill:#d4edda,stroke:#28a745
style S fill:#d4edda,stroke:#28a745
graph LR
subgraph "Dysregulation"
A["Complement<br/>deficiency"] --> B["Susceptibility to<br/>encapsulated bacteria"]
C["Excessive<br/>activation"] --> D["Tissue damage<br/>in [chronic inflammation](/en/concepts/chronic-inflammation.md)"]
E["Regulator<br/>failure"] --> F["Self-attack<br/>([autoimmune diseases](/en/concepts/autoimmune-diseases.md))"]
end
subgraph "Regulators (prevent self-damage)"
G["Factor H / Factor I<br/>CD46 / CD55 / CD59"]
end
G -.->|inhibit| C
style A fill:#f8d7da,stroke:#dc3545
style C fill:#f8d7da,stroke:#dc3545
style E fill:#f8d7da,stroke:#dc3545
style G fill:#cce5ff,stroke:#004085
style B fill:#d4edda,stroke:#28a745
style D fill:#d4edda,stroke:#28a745
style F fill:#d4edda,stroke:#28a745
Three activation pathways: (1) Classical - antibody-antigen complexes activate C1, (2) Alternative - spontaneous C3 hydrolysis on pathogen surfaces, (3) Lectin - mannose-binding lectin recognizes pathogen carbohydrates. All converge on C3 convertase formation → C3a/C3b generation → C5 convertase → C5a/C5b → terminal pathway forming C5b-C6-C7-C8-C9 Membrane Attack Complex that lyses target cells. C3a and C5a are potent anaphylatoxins promoting inflammation.
Complement activation is immediate wound response preceding cellular immune system. Dysregulation contributes to autoimmune diseases, transplant rejection, and septic shock. Deficiencies increase infectious disease susceptibility (particularly encapsulated bacteria). Excessive activation in chronic inflammation drives tissue damage. C5a is key target for anti-inflammatory interventions. Understanding complement informs wound healing optimization and inflammatory disease management.
- Activated within seconds to minutes of injury
- C3 most abundant complement protein (~1.2 mg/mL in plasma)
- C3a and C5a are anaphylatoxins - potent inflammatory signals
- Membrane Attack Complex (Membrane Attack Complex) creates ~10nm pores in cell membranes causing lysis
- Alternative pathway provides constant low-level surveillance
- Regulators (Factor H, Factor I, CD46, CD55, CD59) prevent self-damage