Mediators Of Inflammation Flashcards
What are the important mediators of acute inflammation?
Vasoactive amines
Lipid products
Cytokines
Products of complement activation
Mediators are either ——— by cells or generated from——
Secreted
Plasma proteins
Cell derived mediators are normally sequestered in —— and can be rapidly secreted by ———. E.g ———
Or
Are synthesized —— E.g —,—,— in response to ——
Intracellular granules
Granule exocytosis
Histamine in mast cell granules
De novo
Prostaglandins, leukotrienes, cytokines
In response to a stimulus
What are the sources of Histamine
Mast cells, basophils, platelets
Action of Histamine
Vasodilation
Endothelial activation
Increased vascular permeability
What are the sources of Prostaglandins ?
Mast cells, leukocytes
What are the actions of prostaglandins?
Vasodilation, pain, fever
What are the sources of Leukotrienes?
Mast cells, leukocytes
What are the actions of leukotrienes?
Increased vascular permeability
Chemotaxis
Leukocyte adhesion and activation
What are the sources of cytokines(TNF, IL-1, IL-6)
Macrophages
Endothelial cells
Mast cells
What are the functions of Cytokines(systemic and local)
Local;endothelial activation
Systemic;fever, metabolic abnormalities, hypotension(shock)
What are the sources of Chemokines?
Leukocytes, activated macrophages
What are the actions of Chemokines?
Chemotaxis, leukocyte activation
What are the sources of platelet activating factors?
Leukocytes
Mast cells
What are the actions of PAF?
Vasodilation
Increased vascular permeability
Leukocytes adhesion
Chemotaxis
Degranulation
Oxidative burst
What is the source of the complement system?
Plasma(produced in the liver)
What are the actions of Complement system?
Leukocyte Chemotaxis and activation
Direct target killing(membrane atttacj complex)
Vasodilation (mast cell smooth muscle)
What are the sources of Kinins?
Plasma(produced in the liver)
What are the actions of Kinins
Increased vascular permeability
Smooth muscle contraction
Vasodilation
Pain
The major cells that produce mediators of acute inflammation are the —— that detect invaders and damage in tissues
Sentinels
——— mediators are produced mainly in the liver and are present in the circulation as —— precursors that must be activated
Plasma derived
Inactive
Most mediators are short lived. T/F
True
The secondary mediators can only have the same actions as the initial mediators and no different or opposing activities
False. They may have the same actions but may also have different and opposing activities
What are the richest sources of Histamine?
Mast cells
Mast cells are normally present where?
CT adjacent to blood vessels
Where can Histamine be found apart from Mast cells?
Basophils and platelets
Histamine can be released in response to?
Physical injury(heat, cold, trauma)
Binding of antibodies to mast cells which underlies immediate hypersensitivity(allergic) reactions
Products of complement called anaphylatoxins(C3a and C5a)
Histamine can be released in response to products of complements called?
Anaphylatoxins(C3a and C5a)
——— secrets histamine releasing proteins
Leukocytes
Neuropeptides(—) and cytokines(—) may also trigger the release of ——
Substance P
IL-1, IL-8
Histamine
Histamine causes dilation of smooth muscles
False. Contraction
Antihistamine drugs are histamine receptor agonists. T/F
False. Antagonist
What substance is a preformed vasoactive mediator present in platelets and certain neuroendocrine cells such as GIT
Serotonin
What is the primary function of Serotonin and where is it found?
Other functions?
Neurotransmitter in the GIT
Also a vasoconstrictor
Prostaglandins and Leukotrienes are produced from?
Arachidonic acid present in membrane lipids
AA is a 20-carbon ——— acid(——)
Derived from?
Polyunsaturated fatty acid(5, 8, 11, 14-eicosatetraenoic acid)
Dietary sources or by conversion from essential fatty acid linoleic acid
AA occurs in free cells. T/F
False. It doesn’t but it’s normally esterified in membrane phospholipids
Mechanical, chemical, and physical stimuli or other mediators (e.g.,
C5a) release AA from membrane phospholipids through ——
action of cellular phospholipases, mainly phospholipase A2
AA-derived mediators, are synthesized by two major classes of
enzymes what are they are?
Cyclooxygenases which generate prostaglandins and thromboxanes and
Lipooxygenases which generate Leukotrienes and lipotoxins
AA-derived metabolites bind to G protein-coupled receptors on
many cell types and can mediate virtually every step of ——
Inflammation
What ecosanoids are responsible for the action of vasodilation?
PGI2(prostacyclin), PGE1, PGE2, PGD2
What ecosanoids are responsible for the action of vasoconstriction?
Thromboxane A2, Leukotrienes C4, D4, E4
What ecosanoids are responsible for the action of increased vascular permeability?
Leukotrienes C4, D4, E4
What ecosanoids are responsible for the action of Chemotaxis, leukocyte adhesion?
Leukotrienes B4, HETE
Prostaglandins are produced by?
Mast cells
Leukocytes
Macrophages
Endothelial cells
PGs are involved in vascular and systemic reactions of inflammation. T/F
True
PGs are generated by the actions of two ——
Cyclooxygenases(COX-1 and COX-2)
What COX is constitutively expressed in most tissues?
Cox-1
What COX generates prostaglandins involved in inflammatory reactions but is low and absent in most normal tissues?
COX-2
What COX has homeostatic function e.g fluid and electrolyte balance in kidneys, cytoprotection in the GIT?
COX-1
What are the different structural features of PG?
PGD, PGE, PGF, PGG, PGH
What are the most important PG?
Thromboxane A2, PGD2, PGE2, PGF2a, PGI2
Platelets contain the enzyme —— and hence —— is the major product in these cells?
Thromboxane synthase
Thromboxane A2
TxA2 is a potent platelet activating agent and a vasodilator. T/F
False. It’s a vasoconstrictor
TxA2 is unstable(T/F) and rapidly converts into its inactive form ——
True
TxB2
Vascular endothelium lacks —— but possesses ——
Thromboxane synthese
Prostacyclin synthase
Vascular endothelium is respond for the formation of prostacyclin(—) and it’s stable end product ——
PGI2
PGFIa
