Категории: Все - inflammation - cytokines

по Gustas Dovainys 2 лет назад

173

Inflammation

The process of inflammation involves various cellular and chemical mediators that help manage and resolve injury or infection. Chronic inflammation, characterized by a prolonged duration, can lead to fibrosis and tissue necrosis.

Inflammation

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