Inflammation

Purpose

prevent & limit further infection

prepare area of injury for healing

limit & control inflammatory process

interact w/ components of adaptive immune system

Second Line of defense

Symptoms

Redness

Pain

prostaglandins & bradykinin

Swelling

Loss of Function

Fever

pyrogens; IL1, IL8, TNF, prostglandins

Causes

Infection

Mechanical damage

ischemia

nutrient deprivation

temperature extremes

longer duration

fibrosis & tissue necrosis

lymphocytes & macrophages

Initiation

Trauma to mast cells

cross-linking of surface IgE by allergen

Degranulation of Mast Cells

Immediate release of chem mediators

tryptase

heparin

cytokines

IL-4

B cell proliferation & antibody production

TNF a

incrased permeability & leukocyte emigration

histamine

dilation & increased permeability

exudate

histamine receptors

1: proinflammatory

2: antiinflammatory

neutrophil chemotactic factor

neutrophils attracted to site

phagocytosis

eosinophil chemotactic factor

eosinophils attracted

phagocytosis

platelet activating factor

histamine & serotonin

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

Mast cell syntehsis of mediators reinforces

located in connective tissue/adjacent to bloodvessels

Transcriptional activation

Arachadonic acid cleaved from mast cell membrane phospholipids

leukotrienes & chemokines

Vascular

Transient vasoconstriction

caused by initial trauma & low histamine levels

Vasodilation

histamine, prostaglandins, NO

Hemostasis (bleeding stops)

cell adherence

transmigration of phagocytic cells

elimination of insult

Increased blood flow

blood pooling

redness & warmth

Increased blood vessel permeability

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

allow plasma proteins & cells in

swelling

due to endothelial contractoin

Increased capillary pressure

Exudate

WBC adherence & migration

chemotaxis

fluid loss

concentration of RBC

slowed blood flow

Cellular

Phagocytosis

Recognition

Opsonization

Microbial Killing

Macrophage activating factor

Engulfment

Monocytes, Macrophages & eosinophils

Natural Killer cells

recognize & eliminate cells w/ viruses

kill by releasing granules of protein

Platelets

results in degranulation

discontinuation of inflammatory response

lipoxin & resolvins generated that have anti-inflammator

neutrophils

edema

<6 weeks

outcomes

regeneration, fibrosis, scar

kinin system

activated by hageman factor (12a)

bradykinin

coagulation system

plasma protein

thrombin converts fibrinogen to fibrin

plasmin is important in lysing fibrin clots

complement system

classical pathway

common pathway

alternate pathway

C3a & C5a: anaphylatoxins

histamine & lysosomal enzyme release

C5a

activates lipoxygenase pathway; increases leukocyte

Mechanism of action

Network of interacting chemicals

Redundancy

amplification & maintenance of inflammatory response

short 1/2 life

allows self killing of immune response

Cellular Mediators

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

Cytokines

released by & act on nearby cells

IL1 & TNF

Master cytokines

Platelet Activating Factor

phospholipid, aggregate platelets

bronchodilation & vasoconstriction,vasodilation & vascular permebility

leukocyte adhesion & chemotaxis

Interferons

protect against viral infections

IFNa, IFNb, IFNy

eicosanoids

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

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

can mediate virtually every step of inflammation

nitric oxide

modulates inflammatory resonse locally

potent vasodilator, reduces platelet