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MODA > Inflammation and Immunosuppression > Flashcards

Inflammation and Immunosuppression Flashcards

1
Q

Which cells does substance P activate?

A

Mast cells

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2
Q

Which receptors do mast cells have?

A

C3a, C5a, IgE and TLRs

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3
Q

What is H1R coupled to and what is it for?

A

Gq, for inflammation

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4
Q

What is H2R coupled to and what is it for?

A

Gs for gastric acid secretion

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5
Q

What is H3R coupled to and what is it for?

A

Gi, inhibitory autoreceptor in CNS

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6
Q

What is H4R coupled to and what is it for?

A

Gi, for chemotaxis/cytokines release

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7
Q

What subunit of C3a/C5a causes histamine exocytosis?

A

Beta-gamma

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8
Q

Which other receptor is Gq coupled and causes histamine release?

A

Neurokinin

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9
Q

Which histamine receptor causes increased heart rate?

A

H2

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10
Q

Which histamine receptors are used for neurotransmission?

A

H1,2,3,4

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11
Q

What is somatostatin receptor coupled to?

A

Gi

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12
Q

What are EP receptors for?

A

Prostaglandins

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13
Q

What does EP 2/3 Rs do?

A

Decrease H+ resistance

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14
Q

What does EP 1/2 Rs do?

A

Increase bicarb release

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15
Q

What does EP4R do?

A

Increase mucin release

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16
Q

What cleaves pre-kallikrein to kallikrein?

A

Hageman factor

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17
Q

What is kininogen cleaved to if high molecular weight?

A

Bradykinin

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18
Q

What is kininogen cleaved to if low molecular weight?

A

Kallidin

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19
Q

What are kinins inactivated by?

A

Kininases

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20
Q

What does kininase I produce?

A

des-Arg-bradykinin

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21
Q

What does kininase II do?

A

Removes the two C-terminal acids and inactivates it

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22
Q

What are bradykinin receptors coupled to?

A

Gq

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23
Q

WHen is B1 upregulated?

A

During inflammation via IL1

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24
Q

What is the primary agonist of B1 receptors?

A

des-Arg-bradykinin

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25
Q

When is B2 expressed?

A

Constitutively

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26
Q

What are B2 receptors activated by?

A

Bradykinin and kallidin

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27
Q

How does B1 receptor activation cause vasodilation?

A

PGI2 diffuses to vascular smooth muscle, IP receptor causes MLCK phosphorylation

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28
Q

How does B2 receptor cause vasodilation?

A

NO diffuses to vascular smooth muscle, sGC (intracellular receptor) causes MLCK phosphorylation

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29
Q

What inhibits kallikrein?

A

C1-esterase inhibitor

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30
Q

What kind of receptors are most cytokines?

A

Tyrosine kinase

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31
Q

What kind of receptors are chemokines?

A

GPCRs

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32
Q

Which cells is NGF released from?

A

Mast cells and macropahges

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33
Q

Which receptors do tachykinins bind to?

A

Neurokinin

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34
Q

What is the SP receptor?

A

NK1R

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35
Q

What is the neurokinin A receptor?

A

NK2R

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36
Q

What does annexin-A1 bind to?

A

FMPR2/lipoxin

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37
Q

What is the precursor of PAF?

A

Lysoglycerylphorylcholine

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38
Q

What activates PLA2?

A

Ca2+, phosphorylation by bradykinin and TNFalpha

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39
Q

Which enzymes synthesises leukotrienes?

A

Lipoxygenases

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40
Q

What does 12-lipoxygenases produce?

A

12-HETE

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41
Q

What does 5-lipoxygenase produce?

A

Leukotriene A4

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42
Q

Which enzyme produces leukotriene B4?

A

LTA4 hydrolase

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43
Q

Which enzyme produces leukotriene C4?

A

LTC4 synthase

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44
Q

Which are the cysteinyl leukotrienes?

A

C4, D4 and E4

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45
Q

Which receptors does leukotriene B4 act at?

A

BLT1 and BLT2

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46
Q

What are the BLT receptors coupled to?

A

Gq

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47
Q

Which cells does leukotriene B4 attract?

A

Neutrophils and macrophages

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48
Q

Which receptors do the cysteinyl leukotrienes act on?

A

CysLT1 and CysLT2

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49
Q

What are the CysLT receptors coupled to?

A

Gq

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50
Q

When are the cysteinyl leukotrienes released?

A

In airways by mast cells and eosinophils for bronchoconstriction

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51
Q

What is the affinity of CysLT1?

A

LTD4&raquo_space; LTC4 > LTE4

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52
Q

What is the affinity of CysLT2?

A

LTD4 = LTC4 > LTE4

53
Q

How does leukotriene A4 produce a lipoxin?

A

12-lipoxygenase converts it to lipoxin A4

54
Q

How does 15-lipoxygenase produce lipoxin A4?

A

It produces 15S-HETE and 5-lipoxygenase converts this to lipoxin A4

55
Q

How does lipoxin A4 decrease neutrophil chemotaxis and degranulation?

A

Binds FPR2

56
Q

What is the FPR2 receptor coupled to?

A

Gi

57
Q

Which receptors do lipoxins antagonise?

A

CysLT1

58
Q

Which enzyme forms PAF?

A

Acetyltransferase

59
Q

How many double bonds do eicosatrienoic acid products have?

A

1

60
Q

How many bonds do arachidonic acid products have?

A

2

61
Q

How many bonds do eicosapentanoic acid products have?

A

3

62
Q

Which PGs are found in tissues and blood vessels?

A

PGE2 and PGI2

63
Q

Which PGs are in mast cells?

A

PGD2

64
Q

Which PGs are in macrophages?

A

PGE2

65
Q

Which prostaglandin receptors are Gs coupled?

A

DP1, EP2, EP4 and IP

66
Q

Which prostaglandin receptors are Gq coupled?

A

EP1, FP and TP

67
Q

Which prostaglandin receptors are Gi coupled?

A

DP2 and EP3

68
Q

Which PG receptors causes relaxation of GI/uterine muscle?

A

DP1

69
Q

Which PG receptors causes brochochonstriction?

A

TP when PGD2 acts on it

70
Q

Which PG receptors causes bronchial and GI muscle contraction?

A

EP1

71
Q

Which PG receptor causes bronchodilation, vasodilation and GI muscle relaxation?

A

EP2

72
Q

Which PG receptor causes GI muscle contraction, fever, reduced gastric acid secretion, increased gastric mucous secretion?

A

EP3

73
Q

Which PG receptor causes nociceptor sensitisation?

A

EP4

74
Q

Which PG receptor causes vasodilation and inhibited platelet aggregation?

A

IP

75
Q

Which PG receptor causes uterine contraction in humans and bronchoconstriction in cats and dogs?

A

FP receptors when PG F2a acts on it

76
Q

Which receptor does TxA2 act on?

A

TP

77
Q

What is the anti-aggregation PG released from endothelial cells?

A

PGI2

78
Q

What can endothelial cells synthesize that platelets can’t?

A

COX-1

79
Q

How is aspirin triggered lipoxin produced?

A

Aspirin caused COX-2 to produce 15R-HETE needed for lipoxin production

80
Q

What is the rate limiting step of 5-HT production?

A

Tryptophan hydroxylase

81
Q

What kind of tryptophan hydroxylase is found in enterochromaffin cells?

A

1

82
Q

What kind of tryptophan hydroxylase is found in neurones?

A

2

83
Q

Which serotonin transporter do platelets express?

A

SERT

84
Q

How is 5-HT degraded?

A

Oxidative deamination to MAO then oxidation to 5-HIAA

85
Q

Which serotonin receptors are Gi coupled?

A

1A-F

86
Q

Which serotonin receptors are Gq coupled?

A

2A-C

87
Q

Which serotinin receptors are ionotropic?

A

3

88
Q

What happens to 5-HIAA and 5-HT during a migraine?

A

5-HIAA increases and blood 5-HT decreases

89
Q

Which mutation causes familial hemiplegic migraine 1?

A

CACNA1C which encodes CaV1.2

90
Q

Which T cell response is seen in diabetes, MS, RA?

A

Th1

91
Q

Which T cell response in seen in asthma?

A

Th2

92
Q

What does IL5 from Th2 cells?

A

Primes eosinophils

93
Q

What does IL4/13 from Th2 cells do?

A

Causes B cells to produce IgE and induce Fcgamma RI expression

94
Q

What do eosinophils release?

A

CysLTs and granule proteins

95
Q

Where are the Th2 cells from in asthma?

A

Submucosal dendritic cells

96
Q

What do LABA-LAMA combination inhalers contain?

A

B2 agonist and M3 inhibition

97
Q

Why are corticosteroids ineffective in COPD?

A

Decreased expression of histone deacetylase 2

98
Q

Why is HAT2 expression decreased in COPD?

A

ROS form ONOO- which nitrates the active site

99
Q

Which cells release metalloproteinases in RA?

A

Osteoclasts and fibroblasts

100
Q

Why cytokines does corticosteroids reduce transcription of?

A

Il2, IL1 and TNFalpha

101
Q

Which cells is there a net loss of in osteoarthritis?

A

Chondrocytes

102
Q

Which cytokines are raised in osteoarthritis?

A

IL1, IL6 and TNFalpha

103
Q

Which substance is raised in synovial fluid in osteoarthritis?

A

NGF

104
Q

Which cells secrete incretins?

A

K and L

105
Q

What breaks down the incretins?

A

DPP-4

106
Q

What can be used to measure blood glucose?

A

Glycated haemoglobin

107
Q

What does discoid lupus affect?

A

SKin

108
Q

What does SLE affect?

A

Skin, joints, organs

109
Q

What are the tests for lupus?

A

ANA and anti-dsDNA

110
Q

Which cytokines are raised in lupus?

A

TNFalpha, IL6, IFNs and B lymphocyte stimulator

111
Q

What does Gq in muscle do?

A

Contraction

112
Q

What does Gq in smooth muscle cause?

A

Vasodilation

113
Q

How does cAMP cause gastric ulcer?

A

PKA phosphorylation of proteins which traffic K+/H+ pump

114
Q

What are the mast cell agonists?

A

IL-1 alpha and beta

115
Q

What are the mast cell antagonists?

A

IL-1 ralpha

116
Q

What do nociceptors release during migraine?

A

CGRP

117
Q

What does metalloproteinase activity do in a migraine?

A

Disrupts BBB and activates meningeal nociceptors

118
Q

What do Fos/Jun bind to?

A

AP1

119
Q

What do P65 and P50 bind to?

A

NFkB

120
Q

What is an induction immunosuppressant?

A

Basiliximab

121
Q

What is given long term after transplant?

A

Tacrolimus

122
Q

What thins in early stage osteoarthritis?

A

Subchondral plate

123
Q

What happens in late stage osteoarthritis?

A

Subchondral sclerosis and osteophyte formation

124
Q

What happens at insulin injection site?

A

Lipodystrophy

125
Q

Which genes affect lupus susceptibility?

A

Several

126
Q

What are diagnostic tests for lupus?

A

ANA, anti-dsDNA

127
Q

What does ATG do?

A

Polyclonal, for T cell depletion

128
Q

How can Ab be modified to outcompete serum Ig?

A

Afucosylate the Ab to increase affinity and bond strength - decreases carb-carb interactions

MODA (10 decks)

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