Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PMCOL 344 > Immune-5 > Flashcards

Immune-5 Flashcards

1
Q

what do immunosuppressive agents do (generally)

A

inhibit in a controlled fashion one or more steps in the immune response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what are 3 therapy example types of immunosuppressive agents

A

t-cell directed, b-cell directed, cytokine-directed

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

what are 3 main examples of small molecule immunosuppressive agents

A
  • glucocorticoids
  • calcineurin inhibitors
  • mTOR inhibitors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what are GCs (general)

A

corticosteroid hormones

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are GCs widely used for

A

their anti-inflammatory and immunosuppressive properties

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

what kind of effects do GCs have on the immune system (1 word)

A

pleiotropic (dw)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

where are most glucocorticoids inactive

A

in the extracellular space

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

how do GCs get into cells

A

through cell membranes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what do cytosolic (not nuclear) GCs do

A

exert non genomic effects

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

what does cytoplasmic cortisol do (2 options)

A

binds to the GC receptor which translocated to the nucleus to have genomic effects
OR
non genomic effects in the cytoplasm or mito

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what are 3 ways that GCs act within the nucleus

A
  • direct binding to GC response elements (inhibit or activate)
  • interactions with other transcription factors
  • binding to DNA and TFs (Interacts with another TF, they regulate together genes that respond to GCs)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

what do GCs do to PRR genes

A

upregulate the expression

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

what do GCs do to cytokine receptors

A

upregulate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what do GCs do to complement factors

A

upregulate

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

what do GCs do to genes involved in adaptive immunity

A

inhibit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what do GCs do to expression of pro-inflammatory cytokines and chemokines

A

inhibit

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

what are 3 things that GCs upregulate in innate immunity

A
  • expression of PRR genes
  • cytokine receptors
  • complement factors
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

what are 3 things that GCs inhibit in innate immunity

A
  • genes in adaptive immunity
  • pro-inflammatory cytokines
  • chemokines
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what do GCs do to CD4+ T cells and how

A

suppress their activation indirectly by modulating DC function

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

what do GCs do to DC maturation + how

A

inhibit maturation by decreasing expression of MHC class 2 and CD80/86

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

what do GCs do to DCs in activating T cells + how

A

reduce their capacity by decreasing production of cytokines that activate T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

what are 2 things that GCs do to DCs

A

inhibit maturation and reduce their capacity to activate T cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

what do GCs promote to T cells

A

the production of anti-inflammatory cytokines (IL-10)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

how good are GCs for anti inflammation

A

good for short term treatment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what happens with chronic GCs for inflammation

A

side effects and can reduce GC sensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

what are 3 uses for GCs

A
  • RA
  • Asthma
  • MS (not so much anymore)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

how are GCs good for RA

A

they are DMARDs(Disease-modifying anti-rheumatic drugs), GCs + standard therapy can substantially reduce bone erosion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what are calcineurin inhibitors (general what they do)

A

immunosuppressive drugs that inhibit normal T-cell signal transduction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

how do calcineurin inhibitors work

A

target intracellular Ca++ signalling pathways activated downstream of T cell receptors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what are the structures of calcineurin inhibitors like

A

they are all structurally unrelated, bind to distinct molecular targets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what does NFAT require to be able to go into the nucleus

A

it to be dephosphorylated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what does calcineurin usually do and why

A

dephosphorylates NFAT so it can go into the nucleus and make IL 2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what is cyclosporine A

A

lipid soluble antibiotic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

what does cyclosporine A do once its inside the T cell

A

forms a complex with immunophilins called cyclophilins (cyclophilin A)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what does cyclosporine A make a complex with

A

cyclophilins (cyclophilin A)

36
Q

what is the mechanism of cyclosporine A

A

inhibits the phosphatase activity of calcineurin, preventing the nuclear translocation of NFAT

37
Q

what are 3 examples of calcineurin inhibitors

A

cyclosporine A, tacrolimus, rapamycin

38
Q

what is an example of mTOR inhibitors

A

rapamycin

39
Q

what is NFAT + what does it do

A

a transcription factor that regulates several genes IL-2, IL-4, IF gamma

40
Q

what does cyclosporine A do to interleukins

A

inhibits its productions

41
Q

what does cyclosporine A do to proliferation of naive T cells and why

A

inhibits because it inhibits IL 2

42
Q

what does cyclosporine A do to primed T cells

A

it doesnt block the effect of ILs

43
Q

what are primed T cells

A

ones that have been activated following a primary recognition of specific peptide

44
Q

what is a good thing about cyclosporine A toxicity wise

A

it has very little bone marrow toxicity

45
Q

what kind of immunity is cyclosporine A good for

A

cell mediated immunity

46
Q

what does cyclosporine A suppress

A

some humoral immunity and maybe affects the innate immunity

47
Q

what is tacrolimus

A

antibiotic

48
Q

what is the mechanism of tacrolimus

A

forms a complex in the cells with immunophilins called FKBP12
-causing inhibition of phosphatase activity of calcineurin preventing nuclear translocation of NFAT

49
Q

what is the effect of tacrolimus like compared to cyclosporine

A

the same but tacrolimus is 100 fold more potent

50
Q

what does tacrolimus bind to

A

FKBP12

51
Q

what does FKBP12-tacrolimus do

A

inhibits calcineurin

52
Q

when are calcineurin inhibitors used clinically

A

to treat autoimmune diseases and to prevent graft rejection

53
Q

are calcineurin inhibitors specific

A

not super, they can affect numerous other calcineurin targets, which acconunts for nephro and neurotoxicities

54
Q

what does mTOR stand for

A

mammalian target of rapamycin

55
Q

what is the general function of mTOR

A

regulates innate and adaptive immune cells

56
Q

what does mTOR couple (2 things)

A

cellular activation to the environmental and intracellular nutritional status

57
Q

how many complexes does mTOR exist in

A

2

58
Q

what are the 2 mTOR complexes

A

mTORC1 and mTORC2

59
Q

what does the subunit composition of the mTOR complexes dictate

A

its substrate specificity

60
Q

what is the prototypical mTOR inhibitor

A

rapamycin

61
Q

what is rapamycin (very basic)

A

mTOR inhibitor

62
Q

what is the mechanism of rapamycin

A

binds to FKBP12, the complex binds to mTOR which uncouples mTORC1 from its substrates (allosteric)

63
Q

does rapamycin impair mTOR kinase activity directly + explanation

A

no, it binds to FKBP12 and the complex uncouples mTORC1 from its substrates (allosteric)

64
Q

what is FKBP12

A

cytoplasmic receptor, binds rapamycin to form a complex

65
Q

what does the rapamycin-FKBP12 complex do

A

binds to mTOR to uncouple mTORC1 from its substrates

66
Q

what does rapamycin do to T cell stimulation by DCs

A

reduce

67
Q

what does rapamycin do to antigen endocytosis by DCs

A

inhibits

68
Q

what does rapamycin do to cell proliferation + which cells

A

inhibit, B and T cells

69
Q

what does rapamycin do to antibody production

A

inhibits

70
Q

what does what does rapamycin do to interleukins (2)

A

suppresses their production and release

71
Q

what does rapamycin do to chemokine receptors

A

NOTHING no effect

72
Q

what does rapamycin do to DC migration

A

NOTHING no effect

73
Q

what does rapamycin do to CD80/86 expression

A

inhibits

74
Q

what does rapamycin do to DC activation

A

inhibits

75
Q

what does rapamycin do to T cell response to cytokines

A

inhibits

76
Q

what does rapamycin do to stimulation of T cells by DCs

A

reduces

77
Q

what is another name for rapamycin

A

sirolimus

78
Q

what is another name for sirolimus

A

rapamycin

79
Q

what is a common use for sirolimus/rapamycin

A

prevention of transplant rejection (renal)

-alone or with calcineurin inhibitors or corticosteroids

80
Q

what is mycophenolate mofetil

A

a prodrug which is rapidly hydrolyzed to mycophenolic acid

81
Q

what is the mechanism of mycophenolic acid/ mycophenolate mofetil

A

non competitive, reversible inhibitor of inosine monophosphate dehydrogenase
-blocks purine synthesis (and GMP synthesis too)

82
Q

what happens when you inhibit inosine monophosphate dehydrogenase

A

you block purine synthesis

83
Q

which drug inhibits inosine monophosphate dehydrogenase and blocks purine synthesis

A

mycophenolic acid/ mycophenolate mofetil

84
Q

why is mycophenolic acid effective

A

because B and T lymphocytes depend on this pathway for proliferation (need lots purine because theyre rapidly dividing)

85
Q

besides blocking purine synthesis, what is another thing that mycophenolic acid does

A

inhibits DC maturation

86
Q

what is the use for mycophenolate mofetil

A

in transplants and autoimmune disease

87
Q

what kind of general effects does methotrexate have

A

immunosuppressive

PMCOL 344 (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions