2. Definition
Complement means system of factors occurs in normal
serum and activated by antigen – antibody interaction.
Also present in mammals and other animals , including
birds, amphibians and fish.
Location of binding site is Fc portion
Complex of nine different fraction C1 to C9
3. Introduction
1890 , Jules Bordet and Paul Ehrlich
Heat-labile , Heat- stable
Major effector of humoral branch of immune
system
4. Function of Complement System
Opsonisation
Chemo toxic
Cell lysis
Immune clearance
Activation of inflammatory response
5.
6. Pathways
Three Major Pathways:
Classical Pathways
Lactin Pathways
Alternative Pathways
7. Classical Pathway
Activation step
Binding of C1 to Antigen – Antibody Complex
C1 binds with two molecules of IgG or one molecules
of IgM.
Presence of calcium
Once activated C1 is eventually cleaved in C4 and C2
C4b and C2a come together to form the C4b2a which is
the C3 convertase
8. Classical Pathway
Amplification
C3 convertase activates C3 to C3a and C3b.
Its bind with basophils receptors and triggers them to
release vasoactive compounds.
C3a is called anaphylatoxin
C3b serves as opsonisation
C3b comes together in the form of C4b2a3b which is
C5 convertase
9. Classical Pathway
Attack
C5 convertase cleaved in C5a and C5b
C5a is anaphylatoxin
C5b continues with the cascade and C6 and C7 join
together
C567 is a heat stable complex
C8 and C9 enters
Cell lysis
10. Alternative Pathway
C4b2a known as alternative pathways
C3b bound with factor B it is a serum protein
Also known as C3 proactivator
Complex further cleaved by factor D
Also called C3 proactivator convertase
Ba and Bb
Ba released into medium
C3bBb complex is a C3 convertase
11. Lectin pathway
Lectin are protein that recognize and bind the specific
Carbohydrate target.
The lectin pathway like the alternative pathway does
not depend on antibody for its activation
The lectin pathway is activated by the binding of
mannose – binding lectin (MBL) to mannose residues
on the surface of microorganism including certain
salmonella, listeria, and Neisseria strains.
12. Lectin Pathway
The function in complement pathway is similar to that
of C1q.
After MBL binds to the surface of a cell or pathogen ,
MBL- associated serine proteases, MASP-1 and MASP-
2, binds and form C1 like complex.
The active complex formed by this association causes
cleavage and activation of C4 and C2.
The MASP-1 and -2 proteins have structural similarity
to c1r and c1s and mimic their activities.
13. Lectin Pathway
this means of activating the C2-C4 components to
form a C5 convertase without need for specific
antibody binding represents an important defence
mechanism.
15. Role of complement system
The complement system plays a critical role in
inflammation and defence against some bacterial
infection .
Complement may also be activated during reactions
against incompatible blood transfusion, and during
the damaging immune responses that accompany
autoimmune disease
Deficiencies of individuals complement components
or inhibitors can lead to variety of disease.