Inflammation--Exam 2 Flashcards
Why is initial vasconstriction with acute inflammation important?
allows for coagulation
Name 4(5) mediators of vasodilation in acute inflammation
histamine
serotonin
Nitric Oxide
Prostaglandins D2 and E2
Principle mediator of vasodilation in acute inflammation? Its source?
Histamine; mast cells
Name the 3 histamine receptor subtypes, their location, and if it’s “go” or “stop”
H1–on endothelium; “go”
H2–GI tract; “go”
H3–nerve terminals; “stop”
What is the stimulus for serotonin release
platelet stimulation and aggregation
3 sources of nitric oxide?
endothelial cells–eNOS
macrophages–iNOS
neurons–nNOS
Primary target and action of NO?
Targets vascular smooth muscle; causes relaxation (vasodilation)
Name 3 important products of COX pathway?
1) Prostacyclin (PGI2)
2) Thromboxane (TXA2)
3) Prostaglandins (PGD2/E2)
Function of PGI2 (prostacyclin)
inhibits platelet aggregation; potentiates permeability
Function of TXA2 (thromboxane)
STOP SIGNAL
causes platelet aggregation and vasoconstriction
Which neurotransmitter can stimulate nNOS release?
Glutamate
What are 3 mechanisms to increase endothelial cell permeability?
1) endothelial gap formation
2) non-leukocyte mediated damage
3) leukocyte mediated damage
Uses neurokinin receptors to cause contraction of endothelial cells
Substance P
What substance from leukocytes and endothelial cells helps regulate permeability?
Bradykinin
Leukotriene that is a chemotactic agent and activator of neutrophils?
LTB4
Cyteinyl-containing leukotrienes…cause bronchospasms and increase permeability
LTC4, C4, and E4
Where does endothelial gap formation occur?
Post-capillary venules
Mechanisms of endothelial gap formation
1) cellular contraction
2) increased transcytosis
3) new blood vessel formation
Differentiate btwn the two length of responses
1) immediate sustained
2) delayed prolonged
1) directly damages cells causing immediate death and loss of function
2) accumulation of damage induces cell apoptosis
How is fibrin formed?
Fibrinogen is cleaved by thrombin to form fibrin
two mechanisms for exudate formation?
1) endothelial cell damage
2) increased permeability
Bacterial infections are associated with what type of exudate?
Suppurative/purulent
Which type of exudate is associated with mucosal surfaces?
Catarrhal
L-selectins:
expressed on which cells?
Bind to what?
Expressed on activated leukocytes
bind to glycoproteins on endothelial cells
P-selectins
expressed on which cells?
stored?
expressed on endothelium
stored in weibel-palade bodies
What two things bind to form a strong bond btwn leukocyte and endothelial cell?
Integrins on leukocyte bind to ICAMs on endothelial cells (Ig superfamily)
Beta-2 integrins are found on?
CD11d/CD18 found on?
beta–>on ALL leukocytes
CD11d/CD18–> macrophages and cytotoxic T-cells
Which molecule is upregulated during emigration and mediated diapedesis?
PECAM-1 (CD31)
An exogenous mediator (AA) unique to prokaryotes that can bind leukocyte receptors
N-formyl methionine
Name 3 important ENDOGENOUS mediators for leukocyte chemotaxis
C5a
LTB4
IL-8 (from activated lymphocytes and macrophages)
What important molecule is made available when leukocytes undergo an oxidative burst
NADPH
What two products can be made from H2O2?
1) HOCL (using myeloperoxidase)
2) OH (fenton reaction)
Which non-oxygen dependent mechanisms share the same mechanism?
Bactericidal permeability increasing proteins
Defensins
What cytokines do lymphocytes and macrophages use to communicate with each other?
Macrophage secretes IL-1 and TNF to activate lymphocyte
Lymphcytes secrete INF-y to activate macrophages
Classic activation of macrophages:
Driving mediators?
Type of response stimulated?
Mediators–>IFN-y & IL-12
Th1 response
Alternative activation of macrophages:
Driving mediators?
Type of response stimulated?
Mediators–>IL-4, IL-13
Th2 response
Which lymphocytes are the first to arrive with chronic inflammation? Purpose?
Gamma/delta T-lymphocytes
contribute to granuloma formation
Which lymphocytes (general) regulate the type of immune response that ensues
Alpha/beta lymphocytes (CD4, CD8)
Important products of T regulatory lymphocytes
IL-10, TGF-b
Dendritic cells express:
1) when naive
2) when mature
1) CCR6
2) CCR7
CCR7 binds what cytokine in the paracortical region?
CCL21
Type 1 interferon induces what response?
Th1 response
Granuloma with central necrosis; Langhan’s giant cells have nuclei around periphery
Immune granuloma
Granuloma due to foreign material; giants cells have nucei in center of cell
Foreign body granuloma
What 3 things do PPARs inhibit to stop inflammation?
NFkB
STATs
AP-1
4 possible outcomes of inflammation
resolution
regeneration
repair by fibrosis
abscess formation
Interaction in ECM are mediated by what?
Integrins
What is copper required for?
Cross-linking of procollagen via lysyl hydroxylase
Role of HIF in angiogenesis?
in hypoxic conditions, HIF is NOT hydroxylated and goes on to stimulate genes necessary for angiogenesis
Order of events in angiogenesis
Digestion Migration Proliferation Maturation Perivascular cell migration
Response produced when:
1) VEGF–>VEGF-R1
2) VEGF–>VEGF-R2
3) Ang1–>tie 2
4) Ang2–>Tie 2
1) tube formation
2) proliferation
3) maturation of vessel
4) inhibitory to VEGF
Function of MMPs? What inhibits them?
degrade ECM in organized manner; inhibited by TIMPs
Which growth factor, from macrophages and platelets, is central in fibroblast activity and collagen deposition
TGF-b
How do corticosteroids inhibit healing?
inhibit TGF-b
