The Complement System

Complement System:
The complement system consists of approximately 20 proteins that
are present in normal human (and other animal) serum. The term
"complement" refers to the ability of these proteins to complement, i.e.,
augment, the effects of other components of the immune system, e.g.,
antibody. Complement is an important component of our innate host
defenses.
Activation of Complement:
There are three complement activation pathways:
? Classical Pathway – Activation by ‘antigen-antibody complexes’
and C-reactive protein
? Lectin Pathway – Activation by ‘Mannose Binding Lectin’
binding to mannose residues on bacterial proteins and
polysaccharides
? Alternative Pathway – aggregates of many foreign ‘patterns’ such
as lipopolysaccharide and fungal cell walls that act as ‘protective
surfaces’ to shield C3b degradation
All three pathways lead to the production of ‘C3 convertase’!!!
? Once this happens, all three pathways are essentially the same:
o Cleave C3 into C3a (anaphylatoxin) and C3b
o C3b then binds to some of the previous components to form
a ‘C5 convertase’
? This cleaves C5 into C5a (anaphylatoxin) and C5b
o C5b is the nucleating principle for the ‘terminal
pathway’ which forms the ‘Membrane Attack
2
Complex’ or ‘MAC’ which leads to the lysis of the ‘target
cell’.
Biologic Effects of Complement:
1- Target cell lysis.
2- Opsonization via complement receptors (CR1, CR3, CR4)
3- Inflammation and chemotaxis mediated via the anaphylatoxins
(C4a, C3a, C5a)
4- Enhance B-cell responses – B-cells have a receptor (CR2) for C3d
(a breakdown product of C3b)
5- Enhance dendritic cell responses – Dendritic cells also have the
C3d receptor (CR2)
6- Helps with antigen clearance – keeps immune complexes small
making clearance by macrophages easier. Also helps attach small
immune complexes to RBC’s to assist in clearance
7- Helps in the removal of dead or dying ‘host’ cells – Dead host cells
activate complement. (This could be bad after a heart attack or if
blood flow is cut off to an area).