Park Lec 2 Flashcards
what are the functions of histamines
- First mediator released upon acute inflammation but transient
- Binds to type 1 receptor on endothelial cells and causes vasodilation and increases vascular permeability
- H1 receptor antagonists are used as antihistamine drugs
what are the roles of PAF
- Generated from phospholipids by phospholipase A2
- Induces platelet aggregation
- 100-1000 times more potent than histamine in inducing inflammation reactions
what are the roles of eicosanoids
- Derived from polyunsaturated fatty acids such as arachidonic acid
- has COX pathway
- has lipoxygenase pathway
what is the cox pathway
- Prostaglandins
- Complex inflammatory responses including fever and pain - Thromboxane
- Vasoconstriction, platelet aggregation
- Inhibited by NSAIDs
what is the lipoxygenase pathway
- Leukotrienes
- Similar to histamine but more potent and long acting
- Significant contributors to allergic reactions
what are the 3 roles of plasma membranes
- thrombin and fibrinopeptides in clotting system
- bradykinin in the kinin system
- C3a, C5a, C3b in the complement system
describe the thrombin and fibrinopeptides in clotting system
- Thrombin activates leukocytes
- Fibrinopeptides, produced from digestion of fibrinogen by thrombin, increase vascular permeability; chemotactic
describe the C3a, C5a, C3b in the complement system pathway
- C3a and C5a increase vascular permeability and cause vasodilation (anaphylatoxins)
- C5a activates leukocytes; chemotactic
- C3b acts as opsonin
describe the bradykinin in the kinin system process
- Formed by cleavage of kinogens by a protease kallikreins
- Increases vascular permeability and causes vasodilation
- Causes pain
what is the function of cytokines
- Serotonin is transient and tightly regulated
- Have pleiotropic and redundant functions
- TNF-a and IL-1 and chemokines
describe TNF-a and IL-1
- The major cytokines that mediate inflammation
- Produced by many cells, but activated macrophages are the major source
- Generate cellular and systemic responses
describe chemokines
- Chemotactic cytokines
- Recruit and direct the migration of immune and inflammatory cells
- Generate a persistent chemotactic gradient
describe nitric oxide
- Short lived, local acting (seconds)
- Synthesized by inducible NO synthase (iNOS), which is induced by inflammatory cytokines and mediators
- Relaxation of vascular smooth muscle (vasodilation)
- Antimicrobial agent in activated macrophages
describe reactive oxygen species
- Short lived
- Synthesized by NADH oxidase pathway
- Superoxide radical, hydrogen peroxide, and hydroxyl radical
- Released extracellularly by neutrophils and macrophages after stimulation
- May cause tissue injury
describe tissue injury by lysosomal proteases
- Release of lysosomal constituents into the extracellular space
–> Matrix degradation
–> Destructive tissue injury - Antiproteases inhibit lysosomal proteases
–> A2-macroglobulin, al- antitrypsin, etc.
–> Exist in the serum and extracellular matrix
what are the causes of lysosomal proteases
- Premature degranulation of lysosomes
- Phagocytosis attempts of large, flat surfaces (frustrated phagocytosis)
- Damage of leukocytes (ex. Urate crystals of gout)
what mediators are responsbile for plasma
- Factor 7
- Complement proteins
- acute-phase
what mediaotrs are responsible for cell derived
- performed
- newly synthesized
what mediators are responsible for vasodilation
Histamine, serotonin, PAF, kinins, complement
what mediators are responsible for increase vascular permeability
Histamine, serotonin, leukotrienes, PAF, kinins, prostaglandins
what mediators are responsible for chemotaxis
Leukotrienes, prostaglandins, chemokines, complement
what mediators are responsible for vascular smooth muscle relaxation
nitric oxide
what mediators are responsible for leukocyte activation
Leukotrienes, complement
what mediators are responsible for local endothelial activation
Cytokines (TNF, IL-1)