"Complement" describes a system of about 20 proteins, many of which are enzyme precursors. The principal actors in this system are 11 proteins designated C1 through C9, B, and D, All these are present normally among the plasma proteins in the blood as well as among the proteins that leak out of the capillaries into the tissue spaces. The enzyme precursors are normally inactive, but they can be activated mainly by the so-called classic pathway.

1. ‫بسم اللة الرحمن الرحيم‬

2. 2

3. Complement System

4. Complement System for Antibody Action
• "Complement" describes a system of about 20
proteins, many of which are enzyme precursors.
The principal actors in this system are 11
proteins designated C1 through C9, B, and D,
• All these are present normally among the
plasma proteins in the blood as well as among
the proteins that leak out of the capillaries into
the tissue spaces.
• The enzyme precursors are normally inactive,
but they can be activated mainly by the so-called
classic pathway.

5. Complement
Synthesis : in liver – appear in fetal circulation during 1st 13 W
Function : Responsible for certain aspects of
immune response and inflammatory response
Activation : antigen-antibody complex or endotoxin, capsule
series of proteins activated sequentially
Inactivation: inhibitors in plasma (short lived)
Biological effects: either beneficial or harmful to host

6. Complement pathway
A) Classical pathway:
- Complement is activated by antigen –antibody
complex (IgM or IgG)
- Fc portion of the antibody form a binding site for C1q
- The numerical sequence of the complement factors in the
classic pathway is:
C1, C4, C2, C3, C5, C6, C7, C8, C9

7. Complement Activation
Classical Pathway C1
C4 C2
C3 Alternative pathway
C5
C6
C7
C8
C9
Membrane damage

8. Classic Pathway.
 The classic pathway is initiated by
an antigen-antibody reaction.
 a specific reactive site on the
"constant" portion of the antibody
becomes uncovered, or "activated,"
and this in turn binds directly with
the C1 molecule of the complement
system, setting into motion a
"cascade" of sequential reactions,,
 beginning with activation of the
proenzyme C1 itself.
 The C1 enzymes that are formed
then activate successively
increasing quantities of enzymes in
the later stages of the system, so
that from a small beginning, an
extremely large "amplified" reaction
occurs.

9. proteins of the classical pathway
• C1
• C1 exists in blood serum as a molecular
complex containing:
• 1 molecules of C1q
• 2 molecules of C1r
• 2 molecules of C1s

10.  The constant regions of
Antibody contain a
binding site for C1q. (A
single molecule of IgM
is enough to initiate the
pathway.

11.  Binding of C1q
activates C1s and C1r.
 Activated C1s (a serine
protease) cleaves two
serum proteins:
C4 is cleaved into a large
fragment
 C4b, which binds
covalently to sugar
residues on cell-surface
glycoproteins,
 and a smaller, inactive,
fragment of C4a which
diffuses away.

12. C2 is cleaved into
• C2b, which binds
noncovalently to a site on
C4b, leaving a smaller,
inactive, fragment of
• C2a which diffuses away.
The complex of C4b•2b is
called "C3 convertase"
because it catalyzes the
cleavage of C3.

13. • C3
• C3 is the most abundant protein of the
complement system (~1.3 mg/ml).

14. • C4b•2b cuts C3 into two
major fragments:
– C3b, which binds covalently to
glycoproteins scattered across
the cell surface.
– Macrophages and neutrophils
have receptors for C3b and
can bind the C3b-coated cell or
particle preparatory to
phagocytosis. This effect
qualifies C3b as an opsonin.

15. – C3a This small
fragment is released
into the surrounding
fluids. It can bind to
receptors on basophils
and mast cells
triggering them to
release their
vasoactive contents
(e.g., histamine).
Because of the role of
these materials in
anaphylaxis, C3a is
called an
anaphylatoxin.

16. • Some of the C3b binds to molecules of C5
exposes them to cleavage by C4b•2b
(which is thus a "C3/C5 convertase".)

17. • C5
• Cleavage of C5 by
the C3/C5 convertase
initiates the assembly
of a set of
complement proteins
that make up the
membrane attack
complex.

18. • C5b, which serves as the
anchor for the assembly of a
single molecule each of
– C6;
– C7, and
– C8.
• The resulting complex
C5b•6•7•8 guides the
polymerization of as many as
18 molecules of C9 into a tube
inserted into the lipid bilayer of
the plasma membrane. This
tube forms a channel allowing
the passage of ions and small
molecules. Water enters the
cell by osmosis and the cell
lyses.

19. B) Alternative pathway
This pathway is initiated by:
* Bacterial endotoxin, polysaccharide capsule,
aggregates of IgE and properdin
* It starts at C3 then C5, C6, C7, C8, C9
* The complement compon. C1, C4, C2 are by-passed
* Antibodies are not required to initiate activation of
this pathway
* This pathway provides a means of non-specific
resistance

20. Classical pathway
The classical pathway is activated
at C1 and requires antibodies that
have bound to antigens.
The alternative pathway is activated
when complement protein C3
becomes spontaneously active and
combines with foreign substances
Alternative pathway and factors B, D, and P.
Activated Complement proteins
C3 – C7 promote
phagocytosis,
inflammation, and
chemotaxis (attract
immune system cells).
They can be activated
by either the classical
or alternative pathway.
Complement
Plasma proteins form
membrane a membrane
attack complex
Complement proteins C5 – C9 (yellow)
combine to form a hole in the plasma
membrane of target cells, causing the
cells to lyse.

21. selected Complement System s.flv

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