Vital component of defense system having integral role not only in the innate immunity but also adaptive immunity. Provides good defense against harmful infectious agents by process like direct cell lysis or augmenting inflammation and phagocytosis. Complement system is composed of more than 30 serum proteins present normally as inactive zymogen form (nine central component C1-C9). Zymogen proteins are activated in a cascade manner. Complement proteins interact with each other and perform range of functions from direct cell lysis, enhancement of phagocytosis, inflammation and activation of B & T lymphocytes.

1. THE COMPLEMENT SYSTEM
M. KAMIL KHAN
MICROBIOLOGIST

2. Introduction
• Vital component of defense system having integral role not only
in the innate immunity but also adaptive immunity.
• Provides good defense against harmful infectious agents by
process like direct cell lysis or augmenting inflammation and
phagocytosis.
• Complement system is composed of more than 30 serum
proteins present normally as inactive zymogen form (nine
central component C1-C9).
• Zymogen proteins are activated in a cascade manner.
• Complement proteins interact with each other and perform
range of functions from direct cell lysis, enhancement of
phagocytosis, inflammation and activation of B & T
lymphocytes.

3. Pathway of complement system
• Complement system is activated via three pathways.
1. The classical pathway
2. The lectin pathway
3. The alternative pathway
These three pathways converge and further proceed the
terminal pathway that starts with formation of C3
convertase and ends up by formation of Membrane Attack
Complex (MAC).

11. Biological effects of complement system
• Major function of complement system is the pathogen
recognition, leading to lysis of target cell.
• The other additional biological activities are as
• Direct lysis of bacteria by MAC: Effective against G-ve bacteria
with thin cell wall.
• Anaphylatoxin: During activation of complement, smaller
cleavage products of C3 and C5 i.e. C3a and C5a are released
called anaphylatoxins.
• Opsonization: Cleavage products C3b, C4b, C5b facilitate
phagocytosis by opsonizing pathogen surface.

12. ANAPHYLATOXINS
• Smaller cleavage products of C3 and C5 i.e. C3a and C5a are continuously
released (anaphylatoxins). They interact with corresponding receptors on
immune cells (i.e. C3aR and C5aR).
• Anaphylatoxin mediate the release of different mediators that act as strong
chemoattractant for neutrophils, monocytes and macrophages.
• Anaphylatoxins also induce degranulation of mast cells and basophils
releasing histamine, prostaglandins and kinins which cause
VASODILATION AND CAPILLARY LEAKAGE -> Increasing the influx of
inflammatory mediators and leukocytes at the site of infection. Result ->
Increased phagocytosis increased inflammatory response pathogen.
• Anaphylatoxins maintain the balance between anti and pro-inflammatory
immune response by inducing or downregulating inflammatory cytokines.

13. OPSONISATION
• Process by which a pathogen is tagged by serum components for recognition
by macrophages and leukocytes.
• Cleavage products of different complement components i.e. C3b, C4b, C5b,
facilitate phagocytosis by opsonizing their surface.
• Macrophage and leukocytes have receptors like CR-1 and CR3 -> recognize
the opsonins and promote phagocytosis of pathogen.
• Opsonisation also helps in clearing immune complexes
• C3b and C4b attach immune complexes and bind to CRI on erythrocytes
transported to spleen and liver from where they are eliminated.
• Degradation products of C3b i.e., iC3b, C3c and C3dg can also act as ligands
for CD21 and CD35 on B-cells → activates B-cells and production of Abs.
• Complement also resolve inflammation by providing safe clearance of
apoptotic cells. >>>> Morphological changes in apoptotic cells results in the
breakdown of membrane integrity and loss of membrane complement
regulators on cell surface >>>> C1q, MBL, L-Ficolin and H-Ficolin bind to
these cells resulting in activation of complement increasing opsonisation →
trigger the removal of cells debris by phagocytic cell uptake.

14. Regulation of complement activation

16. • SURFACE ROUND REGULATORS
1. MEMBRANE COFACTOR PROTEIN (MCP)(CD46)
Serves as cofactor to factors-I mediated cleavage of C3b and C4b into
small cleavage products (inactive)
2. PROTECTIN (CD59)
Binds to C8 and C9 inhibiting the binding of C5b-7 preventing the formation
of MAC
3. DECAY ACCELERATING FACTOR (DAF)
Dissociates the already formed C3 convertases.

17. •Thanks