COMPLEMENT

Definition
A system of serum and cell
surface protein that interact one
another and with other immune
system’ molecules to generate
important effectors of innate and
adaptive immune responses.
It is activated by antigen-antibody
complexes or microbial surfaces
The system
The complement system
consists of more than 20
proteins circulating in blood
plasma.
Most of these are inactive until
they are cleaved by aprotease,
which, in turn, converts them
into a protease.
Continued…

Thus many components of the

system serve as the substrate of a
prior component and then as an
enzyme to activate a subsequent
component.
This pattern of sequential activation
produces an expanding cascade of
activity (reminiscent of the operation
of the blood clotting system)
Summary of Complement
Pathways

3 pathways for activation:

1. classical: most specific (antibody
dependent activation, binds C1)
2. lectin binding: some specificity
(mannose binding protein, binds
C4)
3. alternative: most primitive (non-
specific, auto-activation of C3)
 Complement System

Activation

Regulation Amplification

Biologic Function
Blood protein component (complement, other mediators of inflammation)
Blood protein component (complement, other
mediators of inflammation)
 C1qrs C2
C4 C3
antibody
C5
C4b

C4a

Bacteria

Classical Complement Pathway

 C1qrs C2
C4 C3
antibody
C5
C4b
C2b
C4a

C2a
Bacteria

Classical Complement Pathway

 C1qrs C2
C4 C3
antibody
C5
C4b
C2b
C3b C4a

C2a
Bacteria C3a

Classical Complement Pathway

 C1qrs C2
C4 C3
antibody
C5
C4b
C2b
C3b C4a
C5b
C2a
Bacteria C3a

C5a

Classical Complement Pathway

Animation complete
 C1qrs

antibody

C4b C6
C2b
C3b C7
C5b C8
Bacteria C6
C9
C7
C8
C9 C9
C9 C9
C9 C9

Classical Complement Pathway

Animation complete
 C3 convertase: binds and cleaves
multiple C3 molecules on surface
to form C3b & C3a

- classical: C4b2b
- alternative: C3bBb

Amplification:
 MBP C2
C4 C3
C5
C4b

C4a

Bacteria

Lectin Binding Complement Pathway

 MBP C2
C4 C3
C5
C4b
C2b
C4a

C2a
Bacteria

Lectin Binding Complement Pathway

 MBP C2
C4 C3
C5
C4b
C2b
C3b C4a

C2a
Bacteria C3a

Lectin Binding Complement Pathway

 MBP C2
C4 C3
C5
C4b
C2b
C3b C4a
C5b
C2a
Bacteria C3a

C5a

Lectin Binding Complement

Animation complete Pathway
 MBP

C4b C6
C2b
C3b C7
C5b C8
Bacteria C6
C9
C7
C8
C9 C9
C9 C9
C9 C9

Lectin Binding Complement

Animation complete Pathway
Alternative Complement Pathway

C3
B
C5

C3b

C3a

Bacteria
Alternative Complement Pathway

C3
B
C5

C3b
Bb
C3a

Bacteria
Alternative Complement Pathway

C3
B
C5

C3b
Bb
C5b C3a

Bacteria C5a

Animation complete
 C6
C3b C7
Bb
C5b C8
C6
C9
C7
Bacteria
C8
C9
C9 C9
C9 C9
C9 C9

Alternative Complement Pathway

Animation complete
 MAC PORES

Source: Source:
undetermined undetermined

Source:
www.wikimedia.org
Regulation:
Inhibit activation: classical pathway
◦ C1 inhibitor (C1INA): plasma protein
spontaneous decay (hydrolysis) of C3
convertases:
 inhibit C3 convertase:
◦ Plasma proteins: Factor I
◦ Cell membrane proteins:
- decay accelerating factor
(DAF):
- membrane co-factor protein
(MCP):
Inactivate anaphylatoxins: cleave
C3a and C5a
◦ serum carboxypeptidase N (SCPN):
Inhibit MAC:
◦ Protectin (CD59): cell associated
protein

Regulation
SUMMARY OF COMPLEMENT ACTIVATION

Classical Alternative
Lectin-Binding
Pathway Pathway
Pathway

C1q MBP C3

[C4b2 [C3bBbP]
b]
C3 Convertase

C3b C3b, C3bi

C3a (opsonlzation)
anaphylatoxin
s
C5a
C5b

C5b-C 9
(membrane attack
complex)

Cell
Injury
 Y O U
AN K
TH