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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