basic knowledge

1. Cellular and Biochemical
mediators of Inflammation
and Immune response
PRESENTED BY: DINAM GYATSO LEPCHA
1 M.PHARM(Pharmacology)
20HMPL03

2. DEFINATION
Any messenger
that acts on
Blood vessels, inflammatory, other cells
that contribute to inflammatory response

3. CLASSIFICATION
I. Cell derived Mediators
II. Plasma derived Mediators

4. I. Cell derived Mediators
1. Vasoactive amines( Serotonin, Histamine)
2. Arachidonic acid metabolites
i) Cyclooxygenase pathway
ii) Lipoxygenase pathway
3. Lysosomal components
4. Platelets activating factors
4. Cytokines(IL-1, TNF-α, TNF-β, IF-γ, Chemokines)
5. Free radicals: Nitric oxide & Oxygen metabolites

6. 1. Vasoactive Amines
A. Histamine
• Releasing Factors: stimuli of various agents like heat, cold,
irradiation, irritant chemicals, Anaphilatoxins,
interleukin etc….
• Storage: Granules of mast cells , basophils & platelets.
• Actions : Vasodilation, increases permeability, itching and pain

7. B. Serotonin/5- Hydroxy tryptamine
• present in Chromafin cells of GIT, Spleen, Nervous Tissue, Mast cells,
Platelets
• Actions: Similar to histamine, but less potent vasodilation and vascular permeability
than Histamine.

8. 2. Arachidonic acid metabolites
• Cyclo-oxygenase pathway

9. • Lipo-oxygenase pathway

10. 3. Lysosomal components
• Granules of Neutrophils:
i) Primary/ large azurophil granules: Myeloperoxidase,
acid hydrolase, protease.
ii) Secondary/Specific: Lysosome, alkaline phosphatase,
Collagenase
iii) Tertiary: Gelatinase
• Granules of monocyte and tissue macrophages: Acid protease,
Collagenase elastase etc..

11. 4. Platelets activating Factor
• Phospholipid derived mediator
• Released: IgE- sensitised basophils , mast cells, leukocytes, endothelium,
platelets.
• Functions: Platelets aggregation, increases vascular permeability,
Bronchoconstriction,Chemotxis

12. 5. Cytokines:
“ Cytokines are a diverse group of small protein molecules with
potent biological activity whose main function is in the regulation of
immune response
Cytokines is a Polypeptides substances – mainly Lymphokines, monokines.
• IL-1, TNF α, β = increases leucocyte adherence to endothelium
• IF-ϒ= activates macrophages, neutrophils
• Chemokines= IL-8(stimulates phagocytosis), Platelet factor-4.= is a chemotactic
factor for monocytes & eosinophils.
.

13. 6. Free radicals: nitric oxide & oxygen
metabolites:
• Endothelium derived relaxing factor: Nitric oxide
function: vasodilation, microbicidal action.
• Oxygen metabolites- produced by activated neutrophils&
macrophages
Eg: H2O2, OH’, O’2
Functions:- endothelial damage,
Tissue damage, increases vascular permeability

14. II.Plasma derived Mediators
1. The kinin system
2. The clotting system
3. The fibrinolytic system
4. The complement system

15. • 4 interlinked systems
Kinin, clotting, fibrinolytic, complement.
• Hageman factor (Factor XII)
• activation in vitro ( contact with glass, kaolin, in vivo- activation (contact with
bacterial endotoxin).

16. 1. Kinin system:
• Bradykinin:
• slow smooth muscle contraction
• Vasodilatation
• Increases Vascular permeability
• Pain

17. 2. Clotting system:
• Fibrinopeptides
FUNCTIONS
• Increases Vascular
permeability
• Chemotaxis for leucocyte
• Anticoagulant activity

18. 3. Fibrinolytic system:
Plasmin
ACTIONS
i. Activation of factor XII to form prekallikrein activator, to stimulate
kinin system to generate bradykinin
ii. Split off complement C3 to C3a (permeability factor)
iii. Degrade fibrin to form split products (increase vascular
permeability)

19. 4. Complement system:
• Activated by:
a. Classical pathway: Ag-Ab complex
b. Alternate pathway: non immunological agents-
bacterial toxin, cobra venom etc.
• Activated products: C3a, C5a (chemotactic for
leukocytes) , C4a, MAC.
Actions: release histamine from mast cells ,increases
vascular permeability, phagocytosis.

20. THANK YOU