MASTEER LEVEL PRESWENTATION

1. Complement

2. Introduction
• Complement (C)
– Is heat labile serum component that was able
to lyse bacteria.
• Complement composed of over 20
different serum proteins.

4. Complement nomenclature
• Activated components
– over-lined
• The letter “b” is usually added to name of
the larger membrane-binding fragment
and the letter “a” to the smaller fragment (
e.g. C3b and C3a)
• Exception C2

5. COMPLEMENT PATHWAYS

6. Classical Pathway

8. Classic pathway
Activated by Ag-Ab complex: IgM, IgG1, 1gG2,
1gG3 activate complement
• C1 is multi-subunit protein,having C1q, C1r and
C1s
• Ciq binds to the Fc region of IgG and IgM
antibody-antigen complex leads to C1r activation
then C1s activation.
• Then we get Activated C1qrs
• The Activated C1qrs is an enzyme cleaves C4 to
C4b, C4a
• Activated C1qrs cleaves C2 to C2a, C2b
• C4bC2a= C3 convertase

9. Classic pathway cont
• C3 cleaved to C3a, C3b
• C3b bind to the membrane
• C4bC2aC3b= C5 convertase
End of classical pathway

14. Lectin Pathway
• MBL (Mannose Binding Lectin)
• Similar to classic pathway
• Binding of MBL to a pathogen results in the association
of two serine proteases, MASP-1 and MASP-2 (MBL-
associated serine proteases).
• MASP-1 and MASP-2 are similar to C1r and C1s.
• MBL (mannose Binding Lectin) is similar to C1q.
• MBL/MASP-1/MASP-2 cleave C4 into C4a and C4b.
Also cleavesC2
• The C4b fragment binds to the membrane and the C4a
fragment is released

15. Alternative Pathway
• Activated by substances found in cell wall
of yeast and bacterial, aggregated IgA,
cobra venom.

16. C3 convertase
• Three ways:
C3 convertase in classic way
C3 convertase in alternative way
Spontaneously breaking down

18. Alternative pathway
• In serum there is low level spontaneous
hydrolysis of C3 to produce C3i.
• Factor B binds to C3i and becomes susceptible
to Factor D
• Factor D cleaves B into Bb.
• The C3iBb complex acts as a C3 convertase
– It cleaves C3 into C3a and C3b.
• Once C3b is formed, Factor B will bind to it .
• Factor D again cleaves factor B into Bb
• The resulting C3bBb complex is a C3
convertase.

19. C5 convertase of alternative
pathway
• C3b produced by C3
convertase bind to
activated C3bBb to
form C5 convertase=
C3bBbC3b
• Factor P prevent
dissociation of C3bBb

21. Regulation of Alternative pathway
• C3b binds to autologous host membranes it
interacts with DAF (decay accelerating factor).
• DAF blocks the association of Factor B with
C3b.
• DAF accelerates the dissociation of Bb from C3b
in C3 convertase
• Some cells possess complement receptor 1
(CR1). Binding of C3b to CR1 facilitates the
enzymatic degradation of C3b by Factor I.
• Binding of C3 convertase (C3bBb) to CR1 also
dissociates Bb from the complex.

22. Alternative pathway
• Can be activated by many Gram-negative
most significantly,
– Neisseria meningitidis
– N. gonorrhoea

23. Membrane attacking complex

24. Membrane attack pathway
• C5 convertase
– classical (C4b2a3b),
– lectin (C4b2a3b)
– alternative (C3bBb3b)
pathway cleaves C5 into C5a and C5b.
• C5b rapidly associates with C6 and C7 and inserts
into the membrane.
• C8 binds, followed by several molecules of C9
• The C5b6 7 complex is referred to as the
membrane attack complex (MAC).
• The C9 molecules form a pore in the membrane
through which the cellular contents leak and lysis
occurs
•

26. Function of complement
1.Opsonization by C3b targets foreign particles for
Phagocytosis .
2.Chemotaxis
3.increased permeability of the capillary
4.Solubilizing: antigen-antibody complexes
5.Lysis of antibody-coated cells.
In some cases, this causes more harm than good; complement
mediated lysis can cause such serious disorders as
– Rh Disease
– Immune hemolytic anaemia
– Immune thrombocytopenic pupura
6.Promoting antibody formation.
– Breakdown of C3b generates a fragment (C3d) that binds to
antigens enhancing their uptake by dendritic cells and B cells.