complement cascade
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Classification
Classical Pathway:
- under most conditions, initiation of the classical pathway of complement requires the interaction of antigen with C1-fixing antibody
- not all classes of immunoglobulin activate the classical pathway
- IgM & IgG subclasses IgG1, IgG2, & IgG3 bind & activate C1.
- the alternative pathway of complement activation does not have an absolute requirement for antibody & does not use C1, C2, or C4
- it is of particular importance before the appearance of antibody during the course of an infection
Mannan-binding lectin pathway:
- third early pathway of host defense also important before the appearance of antibody during the course of an infection
Classical Pathway Alternative Pathway
Ag:Ab
||
|| C3
/
|| <----- + ---
Ag:Ab-C1 Ag || --> C3a |
/ |
|| || |
|| || <------ C3b |
/ / |
|
Ag:Ab-C14b Ag-C3b |
|
|| || |
|| || <------ Factor B |
/ / |
|
Ag:Ab-C14b2b2a Ag-C3bBb |
|
|| || |
|| || <------ Properdin |
/ / |
|
Ag:Ab-C14b2b2a3b Ag-C3bBbP -----------------------
___ _/
C5 ___ _/ C5
-------> ___ /__/ <------
<------- / C5b ------>
C5a C5a
C6,C7 ||
---------> ||
/
C5b67
C8,C9 ||
---------> ||
/
C5b6789
(Membrane Attack Complex)
* also see figure A & figure B which shows regulatory interactions
Pathology
- increased susceptibility to infection with Neisseria with:
- defects the terminal components of the classical complement pathway C5-C9 & formation of the membrane attack complex
- defects in the complement alternative pathway (P & D)
- defects in the mannan-binding lectin pathway
Comparative biology
- West Nile virus infection of neurons triggers activation of the complement cascade within the hippocampus of mice[3]
- microglia then trim presynaptic terminals in response to complement activation (neurons remain viable)
More general terms
Additional terms
References
- ↑ Henry's Clinical Diagnosis & Management by Laboratory Methods, 21st edition, McPherson RA & Pincus MR (es), W.B. Saunders Co., Philadelphia, PA. 2007
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009
- ↑ 3.0 3.1 Vasek MJ, Garber C, Dorsey D et al A complement-microglial axis drives synapse loss during virus- induced memory impairment. Nature. 2016 Jun 22;534(7608):538-43. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27337340