3. inflammation chemical mediators -dr. sinhasan- mdzah
TRANSCRIPT
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