Infection and Inflammation I Flashcards
Vessel permeability due to 3 responses
Immediate transient response mediated by 5-HT, prostaglandin and histamine. Venule permeability is increased and endothelial cells separate. The response is immediate, peaks at 5-10mins and subsides in 30mins
Immediate prolonged period occurs if there is direct damage to endothelial cells in which case the process continues until clotting cascade causes it to cease
Delayed prolonged leakage occurs hours/day and permeability occurs due to apoptosis of endothelial cells
Platelet mediators (4)
Prostaglandin
Histamine
Serotonin
Leukotrienes
Acute inflammation processes (I)
1) Tissue injury
2) Platelet activation
2a) Nitric oxide
Prostaglandins
3) Vasodilation—> Rubor and callor
4) Neutrophil recruitment (also from endothelial activation)
4a) Phagocytosis
4b) Degranulation of lysosomes and release of chemical mediators—> Dolor
Acute inflammation processes (II)
1) Tissue injury
2) Platelet activation
2a) Complement cascade
Leukotrienes, Histamine, Serotonin release
3) Endothelial activation–>Neutrophil recruitment (also from permeability secondary to NO and PG)
4) Vascular permeability
4a) Tissue oedema–>”Tumour”
4b) Clotting cascade and haemostasis
Inflammatory cell recruitment
Blood flow stasis promotes migration of leucocytes from vessel centre to periphery.
Integrins (leucocytes) bind to molecules on endothelial cells (ICAM-1)
All adhesion molecules are upregulated by TNF, C5a and IL-1
Diapedesis/emigration occurs-neutrophils first (24hrs) then macrocytes (48hrs)
Chemotaxis: Leucocytes move to the site of injury along a chemical gradient (bacterial components, leukotriene 4, complement etc)
Phagocytosis: IgG and C3b act as opsonins to bacteria-neutrophils and macrophages bind to cells via Fc and C3b
ICAM-1 and 2
ICAM 1 and 2 are adhesion molecules present on endothelial cells which bind to b2-integrin (neutrophils, eosinphils and macrophages etc)
Upregulation in disease, infection, allergy
Downregulation in diabetes, alcoholism, steroid use
Complement system
Classic pathway initated by ag to ab complexes
Alternative pathway activated by endotoxins and aggregated Ig’s
C3 is converted to C3a and C3b
C3b initiates MAC whilst C3a and C5a increases vascular permeability by activating granulocytes, mast cells and platelets to produce histamine.
C5a is also chemotactic
C3b acts as an opsonin
Classic pathway
Ag-Ab complex
Activated C1
C3–>C3a and C3b
Alternative pathway
Endotoxin and aggregated Ig
C3–>C3a and C3b
C3a and C3b
C3a–>Vascular permeabilty and histamine release
C3b—>C5–>C5a and C5b
C5a–>Chemotaxis
C5b–>MAC
Kinin system
Factor XII–>XIIa
XIIa converts prekallikrein into kallikrein
Kallikrein converts kininogen into bradykinin
Bradykinin–>potent vasodilator and increases permeability
histamine and serotonin
Released from platelets, mast cells and basophils
Stimulated by Ig E, IL-1, C3a and C5a
Platelets also stimulated by contact with collagen, ADP, thrombin and PAF
NO
Synthesised by nitric oxide synthase during oxidation of arginine to citrulline
NOS genes found in neurones, endothelial cells and immune cells
Reduces intracellular calcium
Arachidonic acid (COX)
Cell membrane phospholipids
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Stimulation by phospholipase A2
Inhibition by corticosteroids
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COX Pathway (inhibited by aspirin)
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- Thromboxane (Vasoconstrictor, platelet aggregation)
- PGI2: Vasodilator, platelet aggregation
- PGE/PGD2: Vasodilation, hyperalgesicArachidonic acid (Lipoxygenase)
Cell membrane phospholipids
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Stimulation by phospholipase A2
Inhibition by corticosteroids
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Lipoxygenase pathway
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LTA4-->LTB4 (Chemotactic and neutrophil adherent to endothelium
LTC4
LTD4
LTE4
Chemotaxis, vasoconstriction, bronchoconstriction and vascular permeability
