Mediators Flashcards
Plasma derived mediators
Kinins
Complements
Coagulation system
Plasminolysis system
Locally produced mediators
Histamine Serotonin / 5HT Platelet activating factor (PAF) Prostaglandins Leukotrienes Nitric oxide
it is generated from the membrane phospholipids of neutrophils, monocytes, basophils, endothelium, and platelets (and other cells)by the action of phospholipase A2.
Platelet activating factor (PAF)
: are polypeptide products of many cell types (but principally activated lymphocytes and macrophages) that modulate the function of other cell types
Cytokines
platelet stimulation, vasoconstriction and vasodilation, increased vascular permeability and bronchoconstriction, enhances leukocyte adhesion, chemotaxis, leukocyte degranulation, and the oxidative burst
PAF
augmented by a number of stimuli including: bacterial endotoxin, immune complex formation, C3a, bradykinin & IL-1
cyclooxygenase pathway
**major sources in the acute inflammatory response include monocytes, macrophages, endothelial cells and platelets
Products of this pathway include prostaglandin (PGE2), PGD2, PGF2a, PGI2 (prostacyclin), and thromboxane A2 (TXA2)
cyclooxygenase pathway
may be released from endothelial cells upon stimulation by acetylcholine and bradykinin where it acts as a potent vasodilator and inhibitor of platelet aggregation
NO
synthesized and stored in mast cells, platelets and basophils
Histamine
promote pain, fever, vasodilation and increased vascular permeability
cyclooxygenase pathway
Products of this pathway include prostaglandin (PGE2), PGD2, PGF2a, PGI2 (prostacyclin), and thromboxane A2 (TXA2)
synthesized and released from neutrophils, basophils and mast cells
lipoxygenase pathway
diffuses rapidly through the blood stream
-promotes vasodilation, and increased vascular permeability
Histamine
LTA4 can be taken up by…….and converted to LTB4 and LTC4
Platelets,RBCs and endothelial cells
group of serine proteases
Kinins
Vasoconstriction
PAF,LT
neutrophil activation and chemotaxis and adhesion
LTB4
recognized by specific receptors (H1, H2 and H3)
Histamine
The functions of the complement system are mediated by
by breakdown products of C3 and other complement proteins, & by the membrane attack complex (MAC).
may also be released from macrophages upon stimulation with IFN-g and TNF-a
NO
stored in platelets, mast cells and enterochromaffin cells of the GI tract
-has vasoactive properties
Serotonin
Protein cell products that act as a message to other cells, telling them how to behave & modulate their function
Products of many cell types (principally activated lymphocytes & macrophages)
Produced during immune and inflammatory responses
Cytokines
IL-1, TNF-a and -B, IFN-y are especially important in inflammation.
Induce the systemic acute-phase responses, these include fever, lethargy, hepatic synthesis of various proteins, metabolic wasting (cachexia), neutrophil release into the circulation, and release of adrenocorticotropic hormone (inducing corticosteroid synthesis and release)
Cytokines
Thrombin
Enhancing leukocyte adhesion, vascular permeability and chemotactic
activates the complement pathway
Plasmin
As an opsonin, increases phagocytosis
C3b,C3bi
Induces smooth muscle constriction and causes increased vascular permeability, vasodilation & pain
Bradykinin (kinins)
Leukocyte chemotaxin, increases integrin avidity
C5a
Initiated by a number of by-products of tissue damage including: collagen, cartilage, basement membranes, endotoxin and plasmin
Kinins
Fever
Pg,cytokines
Activation of complement by different pathways leads to cleavage of
C3
cleaves prekallikrein to kallikrein which in turn cleaves the proenzyme kininogen to bradykinin
activated factor XII
generates plasmin from plasminogen
activated factor XII
activation of ………..ultimately results in the cleavage of fibrinogen to fibrin and smaller fibrinopeptides which serve as inflammatory mediators
……also activates the fibrinolytic system via plasmin formation
XII
Vasodilation, vascular permeability, mast cell degranulation
C3a C5a
Vasodilation
PAF, histamine,PGi2 , NO,kinins,c3a,c5a.
Permeability
: histamine, C3a, C5a, kinins, PAF, and leukotrienes C, D, and E. ,pg
Adhesion
IL8, LTB4, C5a, TNFa,PAF,thrombin
Chemotaxis
PAF,LTB4,thrombin,C5a,chemokines
Bronchoconstriction
PAF,Kinin,leukotrienes