complement system

1. Complement system
Dr.T.Arivazhagan
Department of pathology

2. Introduction
1. The term complement refers to a system of factors that occurs in
normal serum and is activated characteristically by Ag-Ab
interaction
2. The system consists of more than 20 proteins
3. Numbered C1 through C9
4. Functions in both innate & adaptive immunity
5. Defense against microbial pathogens

3. Definition
• It is a collection of soluble proteins & membrane
receptors that function mainly in host defense
against microbes and in pathologic inflammatory
reactions

4. During the process many intermediate products are elaborated
Increased
vascular
permeability
Chemotaxis Opsonaisation

5. Complement system works as a cascade system
One reaction triggers the other reaction which triggers others and
so on

6. Complement proteins present as inactive forms
Once activated its became a proteolytic
enzymes that will degrade the other
complement proteins

7. Most important step in complement
activation is
Cleavage
of C3

8. Pathway
1. Alternative pathway
2. Classical pathway
3. Lectin pathway

10. Classical pathway

12. Alternate pathway
Triggered by microbial surface molecules
1. Endotoxin
2. LPS
3. Cobra venom
No need of
presence of
antibodies

13. Lectin pathway
1. Lectin present in the plasma membrane binds to
the carbohydrate on microbes
2. Directly activates the C1

14. All 3 pathways leads to formation of an active enzyme
called C3 convertase
Split the C3
into C3a,C3b

15. C3b
Activate C5
convertase
Cleave C5
into
C5a,C5b

16. 1. C3a,C5a – Inflammation
2. C3b – Phagocytosis
3. C5b bind with late components C6-C9
Membrane attack
complex

17. Complement will kill the microbes by 3 ways
1. Opsonaisation
2. Inflammation
3. Cytolysis

18. Opsonaisation
C3b and its cleavage products
Attach to the microbial cell wall
Acts as a Opsonins and promote the
phagocytosis
by neutrophils and macrophages

19. Inflammation
C3a,C5a products stimulate the histamine
release from mast cells
Anaphylatoxins
Increased
vascular
permeability
and
vasodilatation

20. Cytolysis
Deposition of MAC on cells makes them
More permeable to water and ions
Cell death
Important
mechanism in
killing of
microbes with
thin cell walls
like Neisseria
Deficiency of terminal
complement
predispose to
Neisseria infections

21. • Complement activation tightly regulated by cell associated and
circulating regulatory proteins
• C1 inhibitors
• Blocks the activation of C1
• Deficiency – hereditary angioedema
• DAF & CD 59
• DAF inhibit the formation of C3 convertase
• CD59 inhibit the formation of MAC
• Deficiency - PNH