Mediators Of Inflammation Flashcards
Mediators of Inflammation
The mediators of inflammation are the substances that ________________ inflammatory reactions.
initiate and regulate
The most important mediators of acute inflammation are
vasoactive _____,
lipid products (_______ and ______),
_______ (including _______),
products of _________
amines
prostaglandins and leukotrienes
cytokines; chemokines
complement activation
Mediators are either secreted by ____ or generated from _______
cells
plasma proteins.
Cell-derived mediators are normally sequestered in _______ and can be rapidly secreted by __________(e.g., histamine in mast cell granules) or are
Synthesized ______ (e.g., prostaglandins and leukotrienes, cytokines) in response to a stimulus.
intracellular granules
granule exocytosis
de novo
Source of histamine ?
Mast cells
Basophils
Platelets
Source of prostaglandins
Mast cells
Leukocytes
Source of leukotrienes
Mast cells
Leukocytes
Source of Cytokines
Macrophages
Endothelial cell
Mast cells
Examples of cytokines
TNF
IL-1
IL-6, etc
Source of chemokines
Leukocytes
Activated macrophages
Source of Platelet activating factor
Mast cells
Leukocytes
Source of complement protein
Plasma
Produced in the liver
Source of kinins
Plasma
Produced in the liver
Mention 5 broad mediators involved in vascular dilation
Histamine
Prostaglandins
Complement protein
Kinin
PAF
Mention 4 broad mediators involved in increasing membrane permeability
Histamine
Leukotrienes
PAF
Kinins
Mention 2 broad mediators involved in pain
Kinins( bradykinin)
Prostaglandins
Mention broad mediators involved in
Leukocyte adhesion
Leukocyte activation
Leukocyte chrmotaxis
Leukotrienes and PAF
Leukotrienes and chemokines
Chemokines,PAF, complement protein
Mention broad mediators involved in endothelial activation
Histamine
Cytokines
The major cell types that produce mediators of acute inflammation are the sentinels that detect invaders and damage in tissues -
_____,________, and ________, but _______,_________,_________, and most epithelia can also be induced to elaborate some of the mediators.
macrophages, dendritic cells, and mast cells
platelets, neutrophils, endothelial cells
Plasma derived mediators are produced mainly in the ____ and are present in the circulation as _______ that must be ______.
liver
inactive precursors
activated
Most of the mediators are (short or long?) -lived.
Short
One mediator can stimulate the release of other mediators.
T/F
T
Vasoactive Amines: Histamine and Serotonin
They have important actions on ______
They are stored as preformed molecules in cells and are among the ___________ to be released during inflammation.
The richest sources of histamine are the ______ that are normally present in the connective tissue adjacent to blood vessels.
It is also found in blood ______ and _____
blood vessels.
first mediators
mast cells
basophils and platelets.
Histamine is stored in ______ and is released by _________ in response to a variety of stimuli, including
(1) physical injury, such as trauma, cold, or heat, by unknown mechanisms;
(2) binding of _____ to mast cells, which underlies ________ reactions and
(3) products of complement called _____ (_________).
mast cell granules
mast cell degranulation
antibodies; immediate hypersensitivity (allergic) ; anaphylatoxins
C3a and C5a
_______ are thought to secrete some histamine-releasing
proteins.
leukocytes
Neuropeptides (e.g., substance P) and cytokines (IL-1, IL-8) may also trigger release of histamine.
T/F
T
Histamine
It causes ______ or _____ and ——— of ——-
dilation of arterioles and increases the permeability of venules.
_______ is considered to be the principal mediator of the immediate transient phase of increased vascular permeability, producing interendothelial gaps in venules.
Histamine
Histamine’s vasoactive effects are mediated mainly via binding to ___ receptors on microvascular endothelial cells.
H1
Histamine also causes (contraction or relaxation ?) of some smooth muscles.
Contraction
Serotonin (__________)
It is a preformed vasoactive mediator present in ______ and certain neuroendocrine cells, such as in the _________, and in _____ cells in _____ but not ______.
It function primarily as a neurotransmitter in the GIT. It is also a vaso (constrictor or dilator?)
5-hydroxytryptamine
platelets
gastrointestinal tract (GIT)
mast; rodents; humans
constrictor
The lipid mediators prostaglandins and leukotrienes are produced from ________ present in ____________
arachidonic acid (AA)
membrane phospholipids
Arachidonic acid is a ___-carbon ______ fatty acid (5,8,11,14- eicosatetraenoic acid) that is derived from ______ sources or by conversion from the essential fatty acid linoleic acid.
20
polyunsaturated
dietary
Arachidonic acid occurs free in the cell
T/F
F
It does not occur free in the cell but is normally esterified in membrane phospholipids.
Mechanical, chemical, and physical stimuli or other mediators (e.g., C5a) release AA from membrane phospholipids through the action of cellular ______, mainly _________.
phospholipases
phospholipase A2
AA-derived mediators, are synthesized by two major classes of enzymes:
________(which generate _______) and
__________ (which produce ________ and ______).
cyclooxygenases; prostaglandins
lipoxygenases; leukotrienes and lipoxins
AA-derived metabolites bind to _________ receptors on many cell types and can mediate virtually every step of inflammation
G protein-coupled
Which AA metabolites are involved in vasodilation
Prostaglandins I2
PGE1
PGE2
PGD2
Which AA metabolites are involved in vasoconstriction
Thromboxane
LT C4, D4, E4
Which AA metabolites are involved in increasing membrane permeability?
LT C4, D4, E4
Basically all the LT except B4
Which AA metabolites are involved in chemotaxis and leukocyte adhesion?
LT B4
Prostaglandins (PGs) are produced by _____,_______,_______, and many other cell types, and They are involved in the vascular and systemic reactions of inflammation.
mast cells, macrophages, endothelial cells
Prostaglandins are generated by the actions of two ______, called ______ and _____
cyclooxgenases
COX-1 and COX-2.
COX-1 is produced in response to _____ stimuli and is also constitutively expressed in _____ tissues, where it may serve a _____ function (e.g., fluid and electrolyte balance in the kidneys, cytoprotection in the gastrointestinal tract).
,
inflammatory
most
homeostatic
COX-2 is induced by _____ stimuli and thus generates the prostaglandins that are involved in inflammatory reactions, but it is (low or high?) or (present or absent?) in ________ tissues.
inflammatory
Low
Absent
most normal
Prostaglandins are divided into series based on structural features as coded by a letter (___________) and a subscript numeral (e.g., 1, 2), which indicates the ________ in the compound.
PGD, PGE, PGF, PGG, and PGH
number of double bonds
platelets contain the enzyme ________ synthase, and hence ____ is the major product in these cells.
thromboxane
TxA2
TxA2, a potent ________ agent and vaso______, is (stable or unstable?) and is rapidly converted to its inactive form _____.
platelet-aggregating
constrictor
Unstable
Thromboxane B2
Vascular endothelium lacks _____ synthase but possesses _____ synthase, which is responsible for the formation of _______ and its stable end product ______
thromboxane
prostacyclin
prostacyclin (PGI2)
PGF1a.
Prostacyclin is a vaso______, potent inhibitor of platelet aggregation, and also markedly potentiates the ______ and ________ effects of other mediators.
Dilator
permeability-increasing and chemotactic
_______ is the major prostaglandin made by mast cells; along with ______
it causes _______ and _______, thus potentiating ____ formation.
PGD2
PGE2
vasodilation and increases the permeability of postcapillary venules
edema
Which prostaglandin is most widely distributed
PGE2
PG____ stimulates the contraction of uterine and bronchial smooth muscle and small arterioles.
PG___ is a chemoattractant for neutrophils.
PG__ is hyperalgesic and makes the skin hypersensitive to painful stimuli, such as intradermal injection of suboptimal concentrations of histamine and bradykinin.
F2a; D2
E2
PG___ is I nvolved in cytokine-induced fever during infections
E2
Leukotrienes are produced by ______ and ______ by the action of ________.
They are involved in ——— and ______ reactions and _____ recruitment.
leukocytes and mast cells
lipoxygenase
vascular and smooth muscle
leukocyte
There are three different lipoxygenases, _________ being the predominant one in neutrophils.
This enzyme converts AA to ____________________ acid, which is chemotactic for neutrophils, and is the precursor of the leukotrienes.
5-lipoxygenase
5-hydroxyeicosatetraenoic
LT____ is a potent chemotactic agent and activator of neutrophils, causing aggregation and adhesion of the cells to venular endothelium, generation of ROS, and release of lysosomal enzymes.
B4