1. Chemical Mediators of INFLAMMATION

2. Classes of Chemical mediators
Vasoactive Amines
Kinin System
Clotting System
Complement system
Arachidonic acid metabolites
Platelet Activating factors
Nitric oxide, Neuropeptides and Others
Cytokines & Chemokines

3. Chemical Mediators of Inflammation: Properties
They are preformed chemicals
Bind to specific receptors and act
Stimulate the release of other mediators
Can act on one or few target cell types
Once activated these are short lived

4. Vasoactive amines-Histamine
Present as Preformed stores in cells
First among the chemical mediator to be released
Present in Mast cells, basophils & Platelets
Causes Arteriolar dilatation, increases permeability.
Acts on H1 receptors on endothelial cells

5. Mast cell Basophil B Lymphocyte Plasma cell LGL Monocyte
NK cell/ Virocytes
Macrophage/ Histiocyte
Liver- Kuffer cell
Brain- Microglial cell
Spleen- Sinusoidal Macroph
Skin- Dendritic cell
Bone- Osteoclasts
Joint- Sinoviocytes
Lung- Dust cells
Monocyte

7. Membrane Phospholipids Breakdown
Antigen
Ig E Ab
Ig E receptor
Membrane Phospholipids Breakdown
Degranulation
Histamine
Protease
ECF
NCF
Leucotrienes : B4,C4,D4
Prostaglandins

8. Vasoactive Amines-Serotonin
5-Hydroxytryptamine
Action similar to Histamine
Platelets, Mast cells, Enterochromaffin cells.
Causes platelet aggregation, increased permeability.
Acts along with PAF.

9. Allergies Histamine causes blood vessels to widen and become leaky.
Fluid and white blood cells leave capillaries.
The area of leakage becomes hot, red and inflamed

10. Pain when injected to skin
Bradykinin functions
Increases vascular Permeability
Blood vessel dilatation
Contraction of Smooth muscle
Pain when injected to skin

11. Classic pathway - activation by immunoglobulin bound to microbial agents

12. Alternate pathway - activation by microbial surface proteins

13. Biological Functions of Complements.
C3a, C5a Mast cell and platelet Anaphylaxis Degranulation
C5a Activates Lipoxygenase Pathway
C3b Potentiating of Ab response, Opsonisation of cells and lysis.
C5b-9 (MAC) Cell lysis.

14. Complement System C3a and C5a: Anaphylotoxins
C3b and IgG: Opsonizing agents
C5b-9: MAC—Membrane attack complex

15. Disorders of Complement System:
Deficiency of MAC: Increased Neisseria infection.
Deficiency of C1 Inhibitor: Her. Angioneuritic edema
Def. of DAF and CD 59 (MIRL): PNH
Def. of C2 & C4: Increased SLE association.
Def. of C3: Increased infections.

16. Cell membrane PhospholipidsX
Phospholipases
Steroids
Arachidonic acid X
NSAIDs
5 Lipooxygenase
Cyclooxygenase
12Lipooxygenase
Leukotriens b4
Prostaglandins g 2, h2
Chemotaxis
Prostacyclin, pg I 2
Thromboxane a2
Leukotriens c4d4e4
Vasoconstriction
Vasodilation
Bronchospasm
Vasoconstriction
Lipoxins a4, b4
Pg d2, e2, f2 alpha
Vasodilation
Inhibit Chemotaxis
Vasodilation

17. Bronchial Asthma
Leukotrienes,
Histamine
Effects

18. Inflammatory Actions of Arachidonic acid metabolites
Vasoconstriction
TXA2, LTC4, D4, E4
Vasodilatation
PGI2, PGE2, PGD2
Increased vascular Permeability
LTC4, D4, E4
Chemotaxis
LTB4
WBC adhesion
Lipoxins A4, B4.

19. Acute Phase Reactions Fever Increased sleep Decreased Appetite Shock
Neutrophilia

20. Cytokines: Lymphokines Monokines Interleukins Chemokines
Autocrine action
Paracrine action
Endocrine effect

21. of division and IFN gamma release (and other mediators)
Interleukin-2 (IL-2)
IL-2
secretion
T cell NK
Increase in NK
Cell activity
B cell
Stimulation
of division
of division and IFN gamma
release (and other mediators)
Monocyte
Activation

22. Remodeling Collagenases
Macrophage- T lymphocyte Interaction
Activated
T-Lymphocyte
IFN ﻻ
Activated
MACROPHAGES
TISSUE INJURY
Proteases
Reactive O2 species
AA metabolites
Nitric oxide
NCF
FIBROSIS
GF: PDGF, FGF, TGF β
Fibrogenic cytokines
Angiogenesis
Remodeling Collagenases

23. Macrophage & Lymphocyte interaction
IL-12
Activated
T-Lymphocyte
Activated
MACROPHAGES
IFN γ
TNF
TNF
IL-1

24. NITRIC OXIDE Called EDRF (Endothelium derived relaxing factor).
Soluble gas produced by endothelium, macrophages & neurons
Induces cyclic GMP which mediated relaxation of smooth muscle cells.
Half life is only in seconds.
NO is synthesized from L-arginine by enzyme NO synthase.

25. NITRIC OXIDE: …., Potent vasodilator Reduces platelet aggregation
Inhibits mast cell induced inflammation
Abnormalities in endothelial NO production leads to Atherosclerosis, Diabetes, Hypertension.
NO is also Microbicidal: Reactive nitrogen intermediates acts like free radicals, which are antimicrobial.

26. Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators
Vasodilation
Increased blood flow
Extravasation of fluid (permeability)
Cellular influx (chemotaxis)
Elevated cellular metabolism
heat (calore)
redness (rubor)
swelling (tumor)
pain (dolore)

27. Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators
Vasodilation
Increased blood flow
Extravasation of fluid (permeability)
Cellular influx (chemotaxis)
Elevated cellular metabolism
heat (calore)
redness (rubor)
swelling (tumor)
pain (dolore)

28. Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators
Vasodilation
Increased blood flow
Extravasation of fluid (permeability)
Cellular influx (chemotaxis)
Elevated cellular metabolism
heat (calore)
redness (rubor)
swelling (tumor)
pain (dolore)

29. Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators
Vasodilation
Increased blood flow
Extravasation of fluid (permeability)
Cellular influx (chemotaxis)
Elevated cellular metabolism
heat (calore)
redness (tubor)
swelling (tumor)
pain (dolore)

30. Acute Inflammation Components
Physiology Symptoms
Release of soluble mediators
Vasodilation
Increased blood flow
Extravasation of fluid (permeability)
Cellular influx (chemotaxis)
Elevated cellular metabolism
heat (calore)
redness (tubor)
swelling (tumor)
pain (dolore)

31. Summery: Histamine Mast cell Vasodilatation Serotonin Platelets
Prostaglandins
Leukocytes
Fever, Vasodil.
Leukotrienes
Chemotaxis
PAF
Degranulation
Nitric oxide
Endothelium
Killing microbes
Cytokine IL-1, TNF
Macrophages
Fever, Anorexia
Chemokines
Complements
Liver
Activation
Kinins
Pain, SM contra

32. SWELLING REDNESS PAIN HEAT LOSS OF FUNCTION
Chemical Mediators of INFLAMMATION: Summery
Stimuli for INFLAMMATION
Physical Chemical Pathogen Antigen Immunological
Mast cell
Basophil
Platelets
Lymphocytes
Macrophages
Neutrophils
Macrophages
Eosinophils
Plasma, Liver
Histamine
Prostaglandins
Kinins
Complements
Plasmin
CYTOKINES
Vasodilatation
Increased Vasc. Permeability
Vasodilatation
Increased Vasc. Permeability
Smooth m contract Pain
Chemotaxis
WBC Adhesion
MAC-Phagocytosis
Fibrin
Break down
Acute Phase Rn
WBC Adhesion
Chemotaxis
Chemo attraction
SWELLING REDNESS PAIN HEAT LOSS OF FUNCTION

33. Thank You