Inflammation

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Inflammation

Chemical Mediators of Inflammation

Cellular Mediators

histamine, serotonin, lysosomal enzymes, prostaglandins, leukotrienes, PAF, oxygen species, nitric oxide, cytokines

Cytokines

nitric oxide

potent vasodilator, reduces platelet

modulates inflammatory resonse locally

eicosanoids

can mediate virtually every step of inflammation

converted membrane lipid, short range, short 1/2 life

aspirin/NSAIDS block conversion of AA into thromboxanes, prostacyclins & prostaglandins

Interferons

IFNa, IFNb, IFNy

protect against viral infections

Platelet Activating Factor

leukocyte adhesion & chemotaxis

bronchodilation & vasoconstriction,vasodilation & vascular permebility

phospholipid, aggregate platelets

IL1 & TNF

Master cytokines

released by & act on nearby cells

short 1/2 life

allows self killing of immune response

amplification & maintenance of inflammatory response

Redundancy

Network of interacting chemicals

Mechanism of action

Plasma protein systems

complement system

C5a

activates lipoxygenase pathway; increases leukocyte

C3a & C5a: anaphylatoxins

histamine & lysosomal enzyme release

alternate pathway

common pathway

classical pathway

coagulation system

plasmin is important in lysing fibrin clots

thrombin converts fibrinogen to fibrin

plasma protein

kinin system

bradykinin

activated by hageman factor (12a)

Acute

outcomes

Resolution

immune response - chronic inflammation

Repair

regeneration, fibrosis, scar

<6 weeks

edema

neutrophils

Resolution of acute inflamation

arachadonic acid metabolism

lipoxin & resolvins generated that have anti-inflammator

Eradication of offending agent

discontinuation of inflammatory response

platelet derived GF, transforming GF B (chemokines)

Phases

Cellular

Natural Killer cells

Platelets

results in degranulation

kill by releasing granules of protein

recognize & eliminate cells w/ viruses

Phagocytosis

Monocytes, Macrophages & eosinophils

Engulfment

Microbial Killing

Macrophage activating factor

Opsonization

Recognition

Vascular

fluid loss

concentration of RBC

slowed blood flow

WBC adherence & migration

chemotaxis

Increased capillary pressure

Exudate

Vasodilation

Increased blood vessel permeability

due to endothelial contractoin

allow plasma proteins & cells in

swelling

hestamine, serotonin, bradykinin, C3a & 5a, leukotrienes, PAF

blood pooling

redness & warmth

Increased blood flow

Hemostasis (bleeding stops)

cell adherence

transmigration of phagocytic cells

elimination of insult

histamine, prostaglandins, NO

Transient vasoconstriction

caused by initial trauma & low histamine levels

Main topic

Early events

Transcriptional activation

leukotrienes & chemokines

Arachadonic acid cleaved from mast cell membrane phospholipids

Degranulation of Mast Cells

located in connective tissue/adjacent to bloodvessels

Mast cell syntehsis of mediators reinforces

through receptors for IgE, IgG, histamine, bacterial products & anaphylatoxin C5a, physical injury, cold & heat

Immediate release of chem mediators

platelet activating factor

histamine & serotonin

eosinophil chemotactic factor

eosinophils attracted

neutrophil chemotactic factor

neutrophils attracted to site

phagocytosis

histamine

histamine receptors

2: antiinflammatory

1: proinflammatory

dilation & increased permeability

exudate

cytokines

TNF a

incrased permeability & leukocyte emigration

IL-4

B cell proliferation & antibody production

tryptase

heparin

Initiation

cross-linking of surface IgE by allergen

Trauma to mast cells

Chronic

lymphocytes & macrophages

fibrosis & tissue necrosis

longer duration