1. Vasoactive Amines

2. Kinin System

3. Clotting System

4. Complement system

5. Arachidonic acid metabolites

6. Platelet Activating factors

7. Nitric oxide, Neuropeptides and Others

8. Cytokines & Chemokines

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

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

Antigen

Ig E receptor

Ig E Ab

Degranulation

5-Hydroxytryptamine

Action similar to Histamine

Platelets, Mast cells, Enterochromaffin cells.

Causes platelet aggregation, increased permeability.

Acts along with PAF.

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

Increases vascular Permeability

Blood vessel dilatation

Contraction of Smooth muscle

Pain when injected to skin

Classic pathway - activation by immunoglobulin bound to microbial agents

Alternate pathway - activation by microbial surface proteins

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.

Complement System

C3a and C5a: Anaphylotoxins

C3b and IgG: Opsonizing agents

C5b-9: MAC—Membrane attack complex

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.

Phospholipases Steroids X

Cyclooxygenase 5 Lipooxygenase

NSAIDs X

Vasodilation Vasoconstriction

Vasodilation

Chemotaxis

Bronchospasm

Vasoconstriction

12Lipooxygenase

Vasodilation

Inhibit Chemotaxis

Inflammatory Actions of Arachidonic acid metabolites

Action Metabolite

Vasoconstriction TXA2, LTC4, D4, E4

Vasodilatation PGI2, PGE2, PGD2

Increased vascular

Permeability

LTC4, D4, E4

Chemotaxis LTB4

WBC adhesion Lipoxins A4, B4.

Fever

Increased sleep

Decreased Appetite

Shock

Neutrophilia

IL-2

secretion

T cell

NK

Increase in NK

Cell activity

B cell Stimulation

of division

T cell

Stimulation

of division and IFN gamma

release (and other

mediators)

Monocyte

Activation

IFN ال

Activated T-Lymphocyte

Activated MACROPHAGES

TISSUE INJURY Proteases

Reactive O2 species AA metabolites

Nitric oxideNCF

FIBROSIS GF: PDGF, FGF, TGF β

Fibrogenic cytokines

Angiogenesis

Remodeling Collagenases

Activated T-Lymphocyte

Activated MACROPHAGES

Macrophage & Lymphocyte interaction

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.

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.

NITRIC OXIDE: ….,

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)

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)

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)

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)

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)

Summery:

Histamine Mast cell Vasodilatation

Serotonin Platelets Vasodilatation

Prostaglandins Leukocytes Fever, Vasodil.

Leukotrienes Leukocytes Chemotaxis

PAF Leukocytes Degranulation

Nitric oxide Endothelium Killing microbes

Cytokine IL-1, TNF Macrophages Fever, Anorexia

Chemokines Leukocytes Chemotaxis

Complements Liver Activation

Kinins Liver Pain, SM contra

Chemical Mediators of INFLAMMATION: Summery

Stimuli for INFLAMMATIONPhysical Chemical Pathogen Antigen Immunological

Mast cellBasophil Platelets

Histamine

VasodilatationIncreased Vasc.

Permeability

SWELLING REDNESS PAIN HEAT LOSS OF FUNCTION

NeutrophilsMacrophages

Eosinophils

Prostaglandins

Plasma, Liver

Kinins

VasodilatationIncreased Vasc.

Permeability

Smooth m

contract

Pain

Complements

Chemotaxis WBC Adhesion

MAC-Phagocytosis

Lymphocytes Macrophages

CYTOKINES

Acute Phase RnWBC Adhesion

Chemotaxis Chemo attraction

Plasmin

Fibrin Break down