Dr.
Hala kamal
Objectives
To define the component of complement
system.
To determine the three pathways of
activation.
To specify the function of complement
system.
To determine the regulation of
complement function.
The complement system is a part of the
immune system that helps or
complements the ability of antibodies
and phagocytic cells to kill pathogens.
- It is a part of the innate immune system
, but it can be activated by the adaptive
immune system.
Functions of the complement
1- Opsonisation :coating the Ag.
2- Chemotaxis – attracting macrophages
and neutrophils.
3- Cell Lysis – killing process by rupturing
membranes of foreign cells.
4- Agglutination – clustering and binding
of pathogens together (sticking) to block
them from attach to tissues.
- The complement system consists of a
number of small proteins found in the
blood, synthesized by the liver, and
normally circulating as inactive precursors
(pro-proteins).
-when they are activated , any one activate
the second one by protease action in a
cascade mechanism.
-The end result of this activation is
activation of the cell-killing component
(membrane attack complex MAC).
-Three biochemical pathways activate the
complement system: -
1-the classical pathway,
2- the alternative pathway,
3-the lectin pathway.
-each pathway need different type of
activation, but at the end all of them
activate the membrane attack complex.
Classical pathway
-The main activator of this pathway is the
{Ag-Ab} complex.
-This pathway start by activation of C1
complex (C1qrs) by [Ag-Ab] complex.
Activated C1 break C2 in to C2a and
C2b,C2a released and c2b attach to the
membrane.
Activated C1 break C4 in to C4a and
C4b,C4a released and c4b attach to the
membrane.
C2b attach to C4b to make a complex
[C4bC2b] which is called C3 convertase.
C3 convertase break C3 in to C3a and
C3b,C3a released and C3b attach to
[C4bC2bC3b] which activates C5 in to C5a
and C5b,C5a released and C5b attach to
C6,C7,C8,C9 to form MAC.
Activation of C5 is a goal of the three
pathways and is called terminal pathway.
MAC is the end of each path way.
It is a lytic component that makes pores
in cell membrane that lead to its rupture
and death.
Lectin pathway
It is similar to the classical pathway
different in the activator , which is binding
of the mannan-binding lectin, a serum
protein, to mannose-containing
carbohydrates on bacteria or viruses’
So it is a part of innate immunity.
Alternative pathway
-This is apart of innate immunity activated
directly by the Ag.
The C3 is spontaneously cleaved in C3a and
C3b, C3b bind to the Ag and to factor B,
which is activated and broke by factor D
into Ba and Bb, Bb attach to C3b to break
more C3 and is called C3 convertase of
alternative pathway.
C3bBb complex is un stable until it binds
to Properdin, a serum protein to form
C3bBbP, a stable compound which form
alternative pathway C5-
convertase.(terminal pathway)
C2a,C4a,C3a,C5a are inflammatory
component attract the neutrophils and
monocytes.
C3b is opsnin that is important in
opsonisation and phagocytic activation.
Regulation of complement
system
Some plasma proteins are bind to the
complement component to stop the
cascade activation to prevent tissue
damage.
Regulatory proteins
C1 inhibiter (C1 INH) : inhibit the classical
pathway.
factor H : inhibit the alternative pathway.
factor I:-inhibit all the pathways.
Decay Accelerating Factor (DAF):- inhibit
the alternative pathway also.