COMPLEMENT

• The complemen system consist of

approximately 20 proteins.
• It refer to ability of these protein to
complement other component of immune
system .
• It sensitizes in liver.
 Complement

• A group of serum proteins

whose sequential activation
leads to 3 Main effects:
• 1. Stimulation of
inflammation (C3a, C5a).
• 2. opsonization for
phagocytosis (C3b) .
• 3. lysis of cell membranes
(MAC) .
• Components of complement:
• C1-C9, Factor B, Factor D, pro
protein
 Pathways of complement
activation
CLASSICAL LECTIN
PATHWAY ALTERNATIVE
PATHWAY
PATHWAY

antibody
dependent antibody
independent

Activation of C3 and
generation of C5 convertase

activation
of C5

LYTIC ATTACK
PATHWAY
 Components of the Classical
Pathway

C1r
C1s

Ca++
C1q

C2 C3 C4

C1 complex
 Classical Pathway
Generation of C3-convertase

C4a C1r
C1s C2b
a
Ca++
C2
C1q

Mg++
C4b2a is C3 convertase

C4b a
C2
 Components of mannose-binding
lectin pathway
(Mannan-binding lectin-Associated
Serine Protease1&2)

C4
MASP2

MBL C2 MASP1
 Mannose-binding lectin pathway

C4a C2b
C4b2a is C3 convertase; it will lead to the
generation of C5 convertase

MASP1 C4
C4b
MASP2 C2C2a
MBL C4b C2a
• It is initiated by the spontaneous hydrolysis of C3
to form C3(H2O).
• This change of plasma protein cleave Factor B into
Ba and Bb.
• In the present of Factor D.
• Bb remains part of the C3(H2O) to form C3(H2O)Bb.
• This complex is also known as a fluid-phase C3
convertase.
• can cleave multiple C3 proteins into C3a and C3b.
• C3-convertase become stable after binding
properdin, a serum protein
•  

11
• C3-convertase become stable after binding
properdin, a serum protein
• To form C3(H2O)BbC3b
• become C5 convertase

12
 Components of the
alternative pathway

C3 B
P
 Spontaneous C3 activation

Generation of C3 convertase
D
H2O

B b
C3 i C3 b

C3a

C3iBb complex has a very short half life

 C3-activation
the amplification loop

If spontaneously-generated
C3b is not degraded

C3a C3b B b C3 b
 C3-activation
the amplification loop

C3 b B b
C3b

C3a C3b Bb
C3a
 C3-activation
the amplification loop
D

C3 b B b Bb C3b
C3b

C3a C3b Bb
C3a
C3a
 C3-activation
the amplification loop

C3b Bb Bb C3b
C3b

C3a C3b Bb
C3a
C3a
 C3-activation
the amplification loop

Bb Bb C3b
C3b

C3a C3b Bb
C3a
C3a
 C3b stabilization and
C5 activation
C3a
C3b finds an activator
(protector) membrane
This is stable C5 convertase of the
P Dalternative pathway

B b
C3b C3 b
C3b regulation on self and
activator surfaces

C3b
 C5-convertase of the two
pathways

C5-convertase of the Alternative

C5-convertase of the Classical
Pathway
and lectin Pathways

C3b
Bb C3b
C2a C3b
C4b
 Components of the lytic pathway

C7
C5 C6

C8

C
9
Lytic pathway
C5-activation

C5a

C5 b

C3b
C4b C2 a
 Lytic pathway
assembly of the lytic complex

C6

C5 b
C7
 Lytic pathway:
insertion of lytic complex into cell membrane

C6

C8 C5 b
C7

C C
9 9 9 C
C 9
C
9 C
9
C
9 C C
9 9
Biological effects of C5a
Opsonization and phagocytosis
• Biological effects of complement :-.
• Opsonization .present of c3b receptor on the surface of many
phagocytes.
• Chemotaxis .c5a and c567attract neutrophils.c5a enhances the
adhesiveness of neutrophils to the endothelium .
• Anaphylatoxin . C3a c4a and c5a cause degranulation of the mast cells
with release of mediators .
• Cytolysis c5b6789 complex lysis cell membrane
And killing of microorganism .DAF (decay accelerating factor).

Enhancement of Antibody Production . The binding of c3b to the receptor

on the surface of B cell enhances antibody production .
C1-inhibitor (C1-inh, C1 esterase inhibitor) is a protease
inhibitor.
Its main function is the inhibition of the complement system
to prevent spontaneous activation.
C1-inhibitor irreversibly binds to and inactivates C1r and
C1s proteases in the C1 complex of classical pathway of
complement.
MASP-1 and MASP-2 proteases in MBL complexes of the
lectin pathway are also inactivated.
Deficiency of this protein is associated with hereditary
angioedema ("hereditary angioneurotic edema"), or swelling
due to leakage of fluid from blood vessels into connective
tissue