Canonical Question
Immuno – Inflamation, Immunity
Master answer
Definition
- Proteolytic enzyme amplification cascade system; forms part of innate + acquired immune response
- Components circulate as inactive precursors
- Activation amplifies as a cascade; regulated by regulator proteins e.g. C1 esterase inhibitor
- Proteins produced by liver
- 9 complements: C1(q, r, s), C2, C3, C4, C5, C6, C7, C8, and C9
- Also B, D, H, I and properdin
Main functions
- cell lysis of bacteria (MAC)
- opsonisation → ↑phagocytosis
- release of mediators via mast cell degranulation
- local vasodilation
- neutrophil aggregation
- chemotaxis
Components (7 functional)
| Group | Factor | Function |
|---|---|---|
| Initiators | C1q, MBL | Initiators |
| Enzymatic mediators and convertase activator | C1r, C1s, MASP2, and Factor-B | proteolytic enzymes that activate other members |
| C3 convertase C5 convertase | enzymatic mediators | |
| Membrane binding components or opsonins | larger fragments such as in C3, C3b | enhances phagocytosis |
| Inflammatory mediators | Smaller fragments like in C3, C3a | Inflammatory mediators |
| Membrane attack protein | Membrane attack complex (MAC) comprises C5b, C6, C7, C8, C9 | protein of MAC inserts and creates a hole on cell memrane so cell lysis occurs |
| Complement receptor protein | CR1 | binds to complement protein and signal-specific cell function |
| Regulatory complement components | Factor I Protectin | proteins that protect the host cell against the action of complement |
Pathways
- Classical – activation by Ag-Ab complex
- system of 11 enzymes
- pathway activated by formation of Ag-ab complexes, CRP, aggregated Ig (IgM or certain IgG)
- activates C1 → reactions involving C4+C2 → formation of enzymatic complex C4b-C2a → cleaves C3a and C3b → common pathway
- Alternate – activation by lipopolysaccharides
- C3 undergoes slow, spontaneous conversion to hydrolysed C3
- Multiple steps leading to complex ith C5 convertase → activation of common pathway
- Nil ab required
- Lectin – activation by mannose on surface of parasites, candida, viruses etc
Mechanism
following activation → triggers final common pathway → C3 activation → C3b acts as C5 convertase → C5b binds C6-C9 → forms membrane attack complex → inserted into target cell membrane → leakage of cellular material → cell lysis + destruction
Regulation
- Half of all complement proteins serve regulatory function
- goal
- to prevent complement damage to normal host tissue (inappropriate / wrong target)
- fluid-phase activation (no target)
- deficiencies lead to excessive complement activation
- Regulatory proteins inhibit system by destabilizing activation complexes and mediating specific proteolysis of actication-derived fragments
- Complement pathways are regulated at the following critical steps
- Activation (initiation) – C1 inhibitor (C1inh) in classic and lectin pathways
- Amplification (convertase formation) – e.g. binding proteins to C3 convertases
- Membrane attack (lysis) – S-protein prevents insertion of Membrane attack complex (MAC) into membrane, CD 59 (protectin) bind C8 and C9 inhibiting final steps of Membrane attack complex
- Anaphylactoids – carboxypeptidases inactivate C3a,C4a,C5a
Sources: Kerr’s notes, biosciencenotes.com
Exam appearances
| Exam | Exact wording | Relationship | Success |
|---|---|---|---|
| 2023B Q15 | Describe the components and function of the complement system including the role, activation and control? | historical_member | — |
| 2025B Q17 | Describe the complement system using the following headings: (a) components (30% of marks) (b) activation pathways (10% of marks) (c) role and functions (50% of marks) (d) control and regulation (10% of marks) | safe_repeat | 54.00% |