Inflammation and Immunosuppression Flashcards
Which cells does substance P activate?
Mast cells
Which receptors do mast cells have?
C3a, C5a, IgE and TLRs
What is H1R coupled to and what is it for?
Gq, for inflammation
What is H2R coupled to and what is it for?
Gs for gastric acid secretion
What is H3R coupled to and what is it for?
Gi, inhibitory autoreceptor in CNS
What is H4R coupled to and what is it for?
Gi, for chemotaxis/cytokines release
What subunit of C3a/C5a causes histamine exocytosis?
Beta-gamma
Which other receptor is Gq coupled and causes histamine release?
Neurokinin
Which histamine receptor causes increased heart rate?
H2
Which histamine receptors are used for neurotransmission?
H1,2,3,4
What is somatostatin receptor coupled to?
Gi
What are EP receptors for?
Prostaglandins
What does EP 2/3 Rs do?
Decrease H+ resistance
What does EP 1/2 Rs do?
Increase bicarb release
What does EP4R do?
Increase mucin release
What cleaves pre-kallikrein to kallikrein?
Hageman factor
What is kininogen cleaved to if high molecular weight?
Bradykinin
What is kininogen cleaved to if low molecular weight?
Kallidin
What are kinins inactivated by?
Kininases
What does kininase I produce?
des-Arg-bradykinin
What does kininase II do?
Removes the two C-terminal acids and inactivates it
What are bradykinin receptors coupled to?
Gq
WHen is B1 upregulated?
During inflammation via IL1
What is the primary agonist of B1 receptors?
des-Arg-bradykinin
When is B2 expressed?
Constitutively
What are B2 receptors activated by?
Bradykinin and kallidin
How does B1 receptor activation cause vasodilation?
PGI2 diffuses to vascular smooth muscle, IP receptor causes MLCK phosphorylation
How does B2 receptor cause vasodilation?
NO diffuses to vascular smooth muscle, sGC (intracellular receptor) causes MLCK phosphorylation
What inhibits kallikrein?
C1-esterase inhibitor
What kind of receptors are most cytokines?
Tyrosine kinase
What kind of receptors are chemokines?
GPCRs
Which cells is NGF released from?
Mast cells and macropahges
Which receptors do tachykinins bind to?
Neurokinin
What is the SP receptor?
NK1R
What is the neurokinin A receptor?
NK2R
What does annexin-A1 bind to?
FMPR2/lipoxin
What is the precursor of PAF?
Lysoglycerylphorylcholine
What activates PLA2?
Ca2+, phosphorylation by bradykinin and TNFalpha
Which enzymes synthesises leukotrienes?
Lipoxygenases
What does 12-lipoxygenases produce?
12-HETE
What does 5-lipoxygenase produce?
Leukotriene A4
Which enzyme produces leukotriene B4?
LTA4 hydrolase
Which enzyme produces leukotriene C4?
LTC4 synthase
Which are the cysteinyl leukotrienes?
C4, D4 and E4
Which receptors does leukotriene B4 act at?
BLT1 and BLT2
What are the BLT receptors coupled to?
Gq
Which cells does leukotriene B4 attract?
Neutrophils and macrophages
Which receptors do the cysteinyl leukotrienes act on?
CysLT1 and CysLT2
What are the CysLT receptors coupled to?
Gq
When are the cysteinyl leukotrienes released?
In airways by mast cells and eosinophils for bronchoconstriction
What is the affinity of CysLT1?
LTD4»_space; LTC4 > LTE4
What is the affinity of CysLT2?
LTD4 = LTC4 > LTE4
How does leukotriene A4 produce a lipoxin?
12-lipoxygenase converts it to lipoxin A4
How does 15-lipoxygenase produce lipoxin A4?
It produces 15S-HETE and 5-lipoxygenase converts this to lipoxin A4
How does lipoxin A4 decrease neutrophil chemotaxis and degranulation?
Binds FPR2
What is the FPR2 receptor coupled to?
Gi
Which receptors do lipoxins antagonise?
CysLT1
Which enzyme forms PAF?
Acetyltransferase
How many double bonds do eicosatrienoic acid products have?
1
How many bonds do arachidonic acid products have?
2
How many bonds do eicosapentanoic acid products have?
3
Which PGs are found in tissues and blood vessels?
PGE2 and PGI2
Which PGs are in mast cells?
PGD2
Which PGs are in macrophages?
PGE2
Which prostaglandin receptors are Gs coupled?
DP1, EP2, EP4 and IP
Which prostaglandin receptors are Gq coupled?
EP1, FP and TP
Which prostaglandin receptors are Gi coupled?
DP2 and EP3
Which PG receptors causes relaxation of GI/uterine muscle?
DP1
Which PG receptors causes brochochonstriction?
TP when PGD2 acts on it
Which PG receptors causes bronchial and GI muscle contraction?
EP1
Which PG receptor causes bronchodilation, vasodilation and GI muscle relaxation?
EP2
Which PG receptor causes GI muscle contraction, fever, reduced gastric acid secretion, increased gastric mucous secretion?
EP3
Which PG receptor causes nociceptor sensitisation?
EP4
Which PG receptor causes vasodilation and inhibited platelet aggregation?
IP
Which PG receptor causes uterine contraction in humans and bronchoconstriction in cats and dogs?
FP receptors when PG F2a acts on it
Which receptor does TxA2 act on?
TP
What is the anti-aggregation PG released from endothelial cells?
PGI2
What can endothelial cells synthesize that platelets can’t?
COX-1
How is aspirin triggered lipoxin produced?
Aspirin caused COX-2 to produce 15R-HETE needed for lipoxin production
What is the rate limiting step of 5-HT production?
Tryptophan hydroxylase
What kind of tryptophan hydroxylase is found in enterochromaffin cells?
1
What kind of tryptophan hydroxylase is found in neurones?
2
Which serotonin transporter do platelets express?
SERT
How is 5-HT degraded?
Oxidative deamination to MAO then oxidation to 5-HIAA
Which serotonin receptors are Gi coupled?
1A-F
Which serotonin receptors are Gq coupled?
2A-C
Which serotinin receptors are ionotropic?
3
What happens to 5-HIAA and 5-HT during a migraine?
5-HIAA increases and blood 5-HT decreases
Which mutation causes familial hemiplegic migraine 1?
CACNA1C which encodes CaV1.2
Which T cell response is seen in diabetes, MS, RA?
Th1
Which T cell response in seen in asthma?
Th2
What does IL5 from Th2 cells?
Primes eosinophils
What does IL4/13 from Th2 cells do?
Causes B cells to produce IgE and induce Fcgamma RI expression
What do eosinophils release?
CysLTs and granule proteins
Where are the Th2 cells from in asthma?
Submucosal dendritic cells
What do LABA-LAMA combination inhalers contain?
B2 agonist and M3 inhibition
Why are corticosteroids ineffective in COPD?
Decreased expression of histone deacetylase 2
Why is HAT2 expression decreased in COPD?
ROS form ONOO- which nitrates the active site
Which cells release metalloproteinases in RA?
Osteoclasts and fibroblasts
Why cytokines does corticosteroids reduce transcription of?
Il2, IL1 and TNFalpha
Which cells is there a net loss of in osteoarthritis?
Chondrocytes
Which cytokines are raised in osteoarthritis?
IL1, IL6 and TNFalpha
Which substance is raised in synovial fluid in osteoarthritis?
NGF
Which cells secrete incretins?
K and L
What breaks down the incretins?
DPP-4
What can be used to measure blood glucose?
Glycated haemoglobin
What does discoid lupus affect?
SKin
What does SLE affect?
Skin, joints, organs
What are the tests for lupus?
ANA and anti-dsDNA
Which cytokines are raised in lupus?
TNFalpha, IL6, IFNs and B lymphocyte stimulator
What does Gq in muscle do?
Contraction
What does Gq in smooth muscle cause?
Vasodilation
How does cAMP cause gastric ulcer?
PKA phosphorylation of proteins which traffic K+/H+ pump
What are the mast cell agonists?
IL-1 alpha and beta
What are the mast cell antagonists?
IL-1 ralpha
What do nociceptors release during migraine?
CGRP
What does metalloproteinase activity do in a migraine?
Disrupts BBB and activates meningeal nociceptors
What do Fos/Jun bind to?
AP1
What do P65 and P50 bind to?
NFkB
What is an induction immunosuppressant?
Basiliximab
What is given long term after transplant?
Tacrolimus
What thins in early stage osteoarthritis?
Subchondral plate
What happens in late stage osteoarthritis?
Subchondral sclerosis and osteophyte formation
What happens at insulin injection site?
Lipodystrophy
Which genes affect lupus susceptibility?
Several
What are diagnostic tests for lupus?
ANA, anti-dsDNA
What does ATG do?
Polyclonal, for T cell depletion
How can Ab be modified to outcompete serum Ig?
Afucosylate the Ab to increase affinity and bond strength - decreases carb-carb interactions
