The complement system is a set of plasma proteins that work together to attack extracellular pathogens. It consists of approximately 30 serum molecules that are synthesized in the liver. The complement system has three main functions: opsonizing pathogens to promote phagocytosis, recruiting inflammatory cells to sites of infection, and directly killing pathogens via membrane attack complexes. It can be activated through the classical, lectin, or alternative pathways and plays an important role in both innate and acquired immunity.

1. IMMUNOLOGY

2.  C was discovered several years ago as a heat
labile of normal plasma that augment
opsonozation of bacteria by Ab.coplement the
antibacterial activity of Ab
 Consist of approximately 30 serum molecules
 10% of the total serum proteins
 One of the major defense system of the body

3. Overview of the Complement System
The complement system is a set of plasma
proteins that work together to attack
extracelluar pathogens.
While the most important role of the
complement system is to opsonize pathogens,
it also recruits inflammatory cells and kills
pathogens directly through membrane attack
complexes.

4. All components of the classical complement
pathway and membrane attack complex are
designated by the letter C followed by a number.
What is confusing is that the components were
numbered in order of their discovery rather than
the sequence of reactions.
The reaction sequence is C1, C4, C3, C5, C6, C7,
C8, and C9.

5. Complement
Definition : series of heat-labile serum proteins
Site : serum and all tissue fluids except
urine and Cerebrospinal fluid (CSF)
Synthesis : in liver – appear in fetal circulation
during 1st 13 W.
Function : Responsible for certain aspects of
immune response and inflammatory
response

6. 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

7. Major function of the complement system
* Control of inflammatory reaction and
chemotaxis
* Clearance of the immune complexes
* Cellular activation and antimicrobial
defense
* It is a major effector in immuno-
pathological diseases

8. Complement System activation
The complement system can be activated
through three pathways: the classical
pathway, the alternative pathway, and
the mannose-binding (MB) lectin
pathway.

9. 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:
C1q,r,s , C4, C2, C3, C5, C6, C7, C8, C9

10. 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:
C1q,r,s , C4, C2, C3, C5, C6, C7, C8, C9

11. Classic And Alterenative pathways
Classic Pathway Alternative pathway
* Specific acquired immunity * Non-specific innate immunity
* Initiated by antibody * Bacterial endotoxin, capsule
* Interaction of all components * C1, C4, C2 are by-passed
* Properdin system not involved * Properdin system is involved

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

13. Complement activation

14. consequences of the complement activation
1-it generate large numbers of activated
complement proteins that bind covalently to
pathogens, opsonizing them for engulfment
by phagocytes bearing receptors for
complement

15. 2-the small fragments of some complement
proteins act as chemo-attractants to recruit
more phagocytes to the site of complement
activation and also to activate these
phagocytes
3-the terminal complement components
damage certain bacteria by creating pores in
the bacterial membrane

16. Biological Effects of Complement
Beneficial effects:
1) Cytolysis:
- activated complement proteins polymerize on cell
surfaces of bacteria or erythrocyte to form pores
in its membrane (killing by osmotic lysis)

17. 2) Opsonization:
- binding of complement proteins opsonin
(C3b)
to surfaces of foreign organisms or
particles
- Phagocytic cells express specific
receptors for opsonins, so promote
phagocytosis

18. 3) Inflammatory response :
Small fragments released during complement
activation have several inflammatory actions:
a) C5a is chemotactic and attract neutrophiles and
macrophages
b) C5a activate phagocytes and neutrophils
C) C3,C4 and C5 are anaphylatoxins
Cause degranulation of mast cells and release of
histamine and other inflammatory mediators

19. 4) Immune complex clearance:
- C3b facilitate binding of immune complex to several
surfaces (erythrocytes) and enhance removal by liver
and spleen
- binds erythrocytes to blood vessels , make them as
easy prey for phagocytosis
- C3 deficiency associated with Immunocomplex
disease and susceptibility to recurrent infections

20. 5- Enhancement of antibody production:
- Binding of C3b to its receptors on activated
B cells
(CR2) greatly enhances antibody
production
- Patient who are deficient in C3b produce
much less antibody than normal
individuals
and more susceptible to pyogenic infection

21. Schematic representation of the roles of C3b and
antibody in opsonization.

22. The multiple activities of the complement
system

23. The complement system neutralizes viral infectivity
• formation of larger viral aggregates
- reduce the net number of infectious viral particles
• a coating of Ab and/or complement to the surface
of a viral particle
- blocking attachment to susceptible host cells
- lysing most enveloped viruses

24. Control without
antibody
Antibodycoated
particles
Particles coated with
antibody and complement

25. Complement deficiencies
• immune-complex diseases (genetic
deficiencies)
• recurrent infection
• C3 deficiencies:
- with the most severe clinical manifestations
• hereditary angioedema:
- deficiency of C1Inh
- localized edema of the tissue
• paroxymal nocturnal hemoglobinuria