chemical mediators of immunity
DESCRIPTION
CHEMICAL MEDIATORS OF IMMUNITYTRANSCRIPT
PLASMA DERIVED MEDIATORS
CHEMICAL MEDIATORS OF IMMUNITY
Most mediators act through cell surface receptors. Exceptions are those that have a direct enzymatic effect (lysosomal enzymes) or direct toxic effect (reactive oxygen species).
Stimulus response coupling leads to biological response.
Mediators can stimulate target cells to release secondary mediators.
Mediators are short lived. They are rapidly inactivated (helps prevent harmful effects).
MECHANISM OF ACTION
Series of inactive proteins circulating in the plasma that are converted to proteolytic enzymes that activate other proteins.
Plasma Proteases:Interrelated systems that are triggered by
activation of Hageman factor (Factor XII of the coagulation cascade). Activated by endotoxin, activated platelets or contact of plasma with damaged tissue (collagen, basement membrane).
PLASMA DERIVED MEDIATORS
3 interrelated systems are active within this category
1. Kinin systemHighly vasoactive
2. Complement systemVasoactive Chemotactic
3.Clotting system VasoactiveCleaves C3
PLASMA PROTEASES
Factor XII of intrinsic coagulation cascadeActivated by
Negatively charged surfacesPlateletsProteases from inflammatory cells
CausesCoagulationActivation of fibrinolytic systemProduces bradykininActivates complementProvides an amplification system
HAGEMAN FACTOR
Activated by Hageman factor (XIIa) Bradykinin
Release of vasoactive nonapeptide bradykininGenerated from the plasma
Potent vasodilator Increased vascular permeabilityContraction of smooth muscleProduce painStimulates release of histamineActivates the arachidonic acid cascade
KININ SYSTEM
Coagulation (clotting) systemForms a fibrinous meshwork at an injured or
inflamed site Prevents the spread of infectionKeeps microorganisms and foreign bodies at the
site of greatest inflammatory cell activityForms a clot that stops bleedingProvides a framework for repair and healing
Main substance is an insoluble protein called fibrin
CLOTTING SYSTEM
results in production of thrombin, factor Xa and formation of fibrinopeptides
thrombin cleaves fibrinogen to form fibrin and enhances leukocyte adhesion
fibrinopeptides are chemotactic and increase vascular permeability
factor Xa increases vascular permeability and leukocyte emigration
CLOTTING SYSTEM
CLOTTING SYSTEMThe blood clotting system or coagulation pathway, like the
complement system, is a proteolytic cascade. Each enzyme of the pathway is present in the plasma as a
zymogen, in other words in an inactive form, which on activation undergoes proteolytic cleavage to release the active factor from the precursor molecule.
The coagulation pathway functions as a series of positive and negative feedback loops which control the activation process.
The ultimate goal of the pathway is to produce thrombin, which can then convert soluble fibrinogen into fibrin, which forms a clot.
The generation of thrombin can be divided into three phases, the intrinsic and extrinsic pathways that provide alternative routes for the generation of factor X, and the final common pathway which results in thrombin formation
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