The Complement System:An Overview
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The complement (C) system consists of a group of 12 soluble plasma proteins that interact with one another in two distinct enzymatic activation cascades (the classical and alternative pathways) and in the nonenzymatic assembly of a cytolytic complex (the membrane attack pathway) (Fig. 1 ; Table 1 ). A third activation pathway, termed the lectin pathway, has recently been described (
1
,
2
). Control of these enzymatic cascades, essential to prevent rapid consumption of C in vivo, is provided by 10 or more plasma and membrane -bound inhibitory proteins acting at multiple stages of the system. C plays a central role in innate immune defense, which provides a system for the rapid destruction of a wide range of invading microorganisms.
Fig. 1.
The complement system and its control. The constituent pathways of the C system and the component proteins are shown. Enzymatic cleavages are represented by thick arrows. The lectin pathway differs from the CP only in that the MBP-MASP complex replaces the Cl complex. Regulators act to inhibit either the enzymes of the activation pathways (activated Cl, C3 convertases, C5 convertases) or assembly of the MAC.
Table 1
The Component Proteins of the Complement System
|
Component |
Structure |
Plasma conc (mg/L) |
|---|---|---|
|
Classical Pathway |
||
|
C1 |
Complicated molecule, composed of 3 subunits, C1q (460 kDa), C1r (80 kDa), C1s (80 kDa) in a complex (C1qr 2 s 2 ) |
180 |
|
C4 |
3 chains (α, 97 kDa; β, 75 kDa, γ, 33 kDa); from a single precursor |
600 |
|
C2 |
single chain, 102 kDa |
20 |
|
Alternative Pathway |
||
|
fB |
single chain, 93 kDa |
210 |
|
fD |
single chain, 24 kDa |
2 |
|
Properdin Common: |
oligomers of identical 53 kDa chains |
5 |
|
C3 |
2 chains: α, 110 kDa, β, 75 kDa |
1300 |
|
Terminal Pathway |
||
|
C5 |
2 chains: 115 kDa, 75 kDa |
70 |
|
C6 |
single chain, 120 kDa |
65 |
|
C7 |
single chain, 110 kDa |
55 |
|
C8 |
3 chains: α, 65 kDa, β, 65 kDa γ, 22 kDa |
55 |
|
C9 |
single chain, 69kDa |
60 |
The proteins that constitute the classical, alternative, and membrane attack pathways are listed together with their approximate concentration in plasma. Modified from: Morgan, B.P. and Harris, C. L. (1999)
Complement Regulatory Proteins.
Academic, London.
