The Complement System

What You Have To Know

• How alternative and classical complement cascade are
initiated

•Distinguish the classical pathway from alternative

pathway

•Regulation of complement activation

•The biological functions of complement components

 The Complement System
•The complement system consists of a complex series of fifteen
proteins, many of which are proteineases.
•Itis a primitive form of defense against infection, being conserved
throughout evolution.
•It performs five vital biological functions:

a. B cell activation
b. Cytolysis
c. Opsonization
d. Chemoattraction of phagocytes
e. Clearance of immune complexes
•Is one of the first systems activated in the response to bacterial product
(LPS) or to antigen-antibody complex.
•The complement system can be considered as a cascade of interacting
proteins, acting in a defined manner, resulting in the initiation of
important innate biological effects.
COMPLEMENT SYSTEM
COMPLEMENT SYSTEM

Immune
cells

or Damaged tissue

6
The Classical Pathway
C1qrs Complex
The Classical Pathway
C1qrs binds Fc region of IgG

CH2
 The Classical Pathway
Formation of the Classical C3 Convertase
 The Classical Pathway
Formation of the Classical C5 Convertase

Anaphylatoxin I (weak
chemotactic factor)
Cleavage of C5

Anaphylatoxin II
(strong chemotactic
factor)
Formation of the Membrane Attack
Complex (MAC)
Membrane Attack Complex (MAC)
The Alternative Pathway
H2O
Complement Pathways
Regulation of Complement System
Regulation of Complement System
 Regulation at Assembly of
Membrane-Attack Complex (MAC)

Note: CD59 also known as protectin

Biological Functions of Complement

Neutralization
Anaphylatoxins
C3b

C3b
C3a, C4a, C5a

C5b-9

Chemotaxis
C3a, C5a, C5b67, Ba
ANAPHYLATOXINS

25
OPSONIZATION
CLEARANCE OF IMMUNE COMPLEXES
 CELLS THAT HAVE
COMPLEMENT-BINDING RECEPTORS

•Erythrocytes
•Granulocytes
•Monocytes/Macrophages
•Lymphocytes
•Dendritic cells
•Platelets
•Endothelial cells
 Summary
• Complement is a set of interacting serum proteins that enhance
inflammation (C3a, C4a, C5a) and opsonization (C3b) and cause
lysis of particulate substances (C5b-9).

•The alternative pathway of complement is activate by

interaction with microbial surfaces.

•The classical pathway is activated by antigen-antibody

complexes.

•Inappropriate activation of complement cascade is controlled at

the level of C1, C3, and C5.