Mediators of inflammation Flashcards
examples of 2 preformed granules -
vasoactive amines
Lysosomal constituents of leukocytes
2 vasoactive amines
Histamine
Serotonin
Where is histamine stored?
In connective tissue mast cells
What causes degranulation of histamine?
- physical injury
- Binding of IgE to mast cell
- binding of C3a and C5a (anaphylatoxins)
- cytokines - IL-1 and IL-8
What receptor does histamine activate
Activates H1 receptor of microvasculature
- leads to VASODILATION
- endothelial CONTRACTION
- increased permeability
Where is serotonin stored?
In platelets and neuroendocrine cells
What causes release of serotonin?
Rapid degranulation of platelets
- aggregation upon collagen or thrombin exposure
- antigen antibody complexes
What receptor does serotonin activate
Serotonin receptor on microvasculature
- leads to ENDOTHELIAL contraction - increased permeability
Where are the lysosomal constituents of leukocytes stored?
In neutrophils and macrophages
What do lysosomal constituents of leukocytes contain?
- acid proteases
- Neutral proteases
- collagenases
elastases
Phospholipases
Plasminogen activator
What activates C3 and C5
Neutral proteases
and
Plasminogen activator
- remember extracell space is neutral
What 3 mediators are synthesized de novo?
Arachidonic acid metabolites - eicosanoids
Nitric oxide
CYtokines
Where do eicosanoids get released from?
Leukocytes
and
Damaged cells
What causes the release of eicosanoids?
- injury to the cell membrane
- C5a!!!!
Which enzymes convert membrane phospholipids to arachidonic acid?
Phospholipases
What happens when arachidonic acid is acted on by COX
- produce Prostacyclin - vasodilation
- TXA2 - vasoconstriction
PGD2, PGE2 -> vasodilation and permeability
PRO-INFLAMMATORY
What happens when arachidonic acid is acted on by 5-Lipooxygense
Leukotriene B4 produced –> vasoconstriction, bronchospasm, increased permeability
Which proteins in eicosanoid cascade involved in vasodilation
prostacyclin (PGI)
PGE1
PGE2
PGD2
Which proteins in eicosanoid cascade involved in VASOCONSTRICTION
TXA2
Leukotrienes C4, D4, E4
Which proteins in eicosanoid cascade involved in vascular PERMEABILITY
Leukotrienes C4, D4, E4
Which proteins in eicosanoid cascade involved in chemotaxis and leukocyte adhesion
Leukotriene B4!!!
5-HETE
Where is nitric oxide released from?
Endothelium and
Macrophages
What is the function of NO?
Microbial killing
Vasodilation
Anti-inflammatory (reduce leukocyte adhesion, inhibit platelet aggregation)
2 main cytokines in the inflammatory cascade
IL-1
TNF-alpha
IL-1 and TNF-a lead to systemic effects such as
Fever
Leukocytosis
more Acute phase reactants
—> can result in septic shock
2 examples of Plasma protein-derived mediators of inflammation
1) complement system -
2) Coagulation and kinin systems -
Which pathway involves direct activation of complement by microbes
Alternate pathway
Which pathway involves antibody-mediated activation of complement?
Classical pathway
Which pathway involves mannose-binding activation of compelement?
Lectin pathway
Which part of the arachidonic acid pathway do C3a and C5a activate?
LIPOoxygenase –> anti-inflammatory
pro and anti-
What are the effector functions of C3a and C5a
Inflammatory
- chemoattractants
- recruit and activate white blood cells - release neutral proteases
What are the effector functions of C3b
Phagocytosis
What are the effector functions of MAC
Lysis of microbes
which complement helps form mac
C5a
What factor is involved in the Coagulation and Kinin systems?
Hageman Factor 12
- activates intrinsic clotting pathway
- activates Kinin cascade
Thrombin activation by factor 12 leads to
Activation of COX-2 -> proinflammatory state
AND
Kalikrein production and production of Bradykinin - as well as C5 activation causing pain and complement activation
Activation of COX2 leads to
Production of PGglandins and TXA2
-> inflammation - vasodilation - increased perm -> platelet aggregation -> increased APRs from the liver
3 mediators involved in vasodilation
- Prostaglandins
- Nitric oxide (early acute)
- Histamine (early acute)
3 mediators involved in vascular permeability
- Histamine and serotonin
- Leukotrienes
- C3a and C5a
Mediators involved in chemotaxis and activation
- TNF
- IL-1
- C3a and C5a
- Leukotriene B4
3 morphological hallmarks of acute inflammation
- Dilation of blood vessels
- Engorgement of vessels
- Exudation of leukocytes and fluid
3 PATTERNS of acute inflammation
- Serous
- Fibrinous
- Supparative/Purulent
Pattern of acute inflammation depends on
- Nature of injury
- Site of injury
- Severity
Features of Serous inflammation
1 - mild injury (mild burn/infection)
- Minimal vascular permeability
- Fluid»»> Leukocytes
Features of Fibrinous inflammation
- Marked vascular permeability (leakgage of fibrinogen
- Local procoagulant stimulus - cancer cells
- Typically in serous cavities - pleura
Features of Suppurative inflammation
- leukocyte recruitment»_space;»fluid extrvasation
- A collection of neutrophils
- Related to Pyogenic organisms
Steroids are
Non specific inhibitors of formation of eicosanoid metaboloties block phospholipases
When you inhibit platelet aggregation
Can inhibit inflammation via inhibiting serotonin release
