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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

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2
Q

what are 3 therapy example types of immunosuppressive agents

A

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

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3
Q

what are 3 main examples of small molecule immunosuppressive agents

A
  • glucocorticoids
  • calcineurin inhibitors
  • mTOR inhibitors
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4
Q

what are GCs (general)

A

corticosteroid hormones

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5
Q

what are GCs widely used for

A

their anti-inflammatory and immunosuppressive properties

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6
Q

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

A

pleiotropic (dw)

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7
Q

where are most glucocorticoids inactive

A

in the extracellular space

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8
Q

how do GCs get into cells

A

through cell membranes

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9
Q

what do cytosolic (not nuclear) GCs do

A

exert non genomic effects

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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

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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)
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12
Q

what do GCs do to PRR genes

A

upregulate the expression

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13
Q

what do GCs do to cytokine receptors

A

upregulate

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14
Q

what do GCs do to complement factors

A

upregulate

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15
Q

what do GCs do to genes involved in adaptive immunity

A

inhibit

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16
Q

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

A

inhibit

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17
Q

what are 3 things that GCs upregulate in innate immunity

A
  • expression of PRR genes
  • cytokine receptors
  • complement factors
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18
Q

what are 3 things that GCs inhibit in innate immunity

A
  • genes in adaptive immunity
  • pro-inflammatory cytokines
  • chemokines
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19
Q

what do GCs do to CD4+ T cells and how

A

suppress their activation indirectly by modulating DC function

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20
Q

what do GCs do to DC maturation + how

A

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

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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

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22
Q

what are 2 things that GCs do to DCs

A

inhibit maturation and reduce their capacity to activate T cells

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23
Q

what do GCs promote to T cells

A

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

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24
Q

how good are GCs for anti inflammation

A

good for short term treatment

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25
what happens with chronic GCs for inflammation
side effects and can reduce GC sensitivity
26
what are 3 uses for GCs
- RA - Asthma - MS (not so much anymore)
27
how are GCs good for RA
they are DMARDs(Disease-modifying anti-rheumatic drugs), GCs + standard therapy can substantially reduce bone erosion
28
what are calcineurin inhibitors (general what they do)
immunosuppressive drugs that inhibit normal T-cell signal transduction
29
how do calcineurin inhibitors work
target intracellular Ca++ signalling pathways activated downstream of T cell receptors
30
what are the structures of calcineurin inhibitors like
they are all structurally unrelated, bind to distinct molecular targets
31
what does NFAT require to be able to go into the nucleus
it to be dephosphorylated
32
what does calcineurin usually do and why
dephosphorylates NFAT so it can go into the nucleus and make IL 2
33
what is cyclosporine A
lipid soluble antibiotic
34
what does cyclosporine A do once its inside the T cell
forms a complex with immunophilins called cyclophilins (cyclophilin A)
35
what does cyclosporine A make a complex with
cyclophilins (cyclophilin A)
36
what is the mechanism of cyclosporine A
inhibits the phosphatase activity of calcineurin, preventing the nuclear translocation of NFAT
37
what are 3 examples of calcineurin inhibitors
cyclosporine A, tacrolimus, rapamycin
38
what is an example of mTOR inhibitors
rapamycin
39
what is NFAT + what does it do
a transcription factor that regulates several genes IL-2, IL-4, IF gamma
40
what does cyclosporine A do to interleukins
inhibits its productions
41
what does cyclosporine A do to proliferation of naive T cells and why
inhibits because it inhibits IL 2
42
what does cyclosporine A do to primed T cells
it doesnt block the effect of ILs
43
what are primed T cells
ones that have been activated following a primary recognition of specific peptide
44
what is a good thing about cyclosporine A toxicity wise
it has very little bone marrow toxicity
45
what kind of immunity is cyclosporine A good for
cell mediated immunity
46
what does cyclosporine A suppress
some humoral immunity and maybe affects the innate immunity
47
what is tacrolimus
antibiotic
48
what is the mechanism of tacrolimus
forms a complex in the cells with immunophilins called FKBP12 -causing inhibition of phosphatase activity of calcineurin preventing nuclear translocation of NFAT
49
what is the effect of tacrolimus like compared to cyclosporine
the same but tacrolimus is 100 fold more potent
50
what does tacrolimus bind to
FKBP12
51
what does FKBP12-tacrolimus do
inhibits calcineurin
52
when are calcineurin inhibitors used clinically
to treat autoimmune diseases and to prevent graft rejection
53
are calcineurin inhibitors specific
not super, they can affect numerous other calcineurin targets, which acconunts for nephro and neurotoxicities
54
what does mTOR stand for
mammalian target of rapamycin
55
what is the general function of mTOR
regulates innate and adaptive immune cells
56
what does mTOR couple (2 things)
cellular activation to the environmental and intracellular nutritional status
57
how many complexes does mTOR exist in
2
58
what are the 2 mTOR complexes
mTORC1 and mTORC2
59
what does the subunit composition of the mTOR complexes dictate
its substrate specificity
60
what is the prototypical mTOR inhibitor
rapamycin
61
what is rapamycin (very basic)
mTOR inhibitor
62
what is the mechanism of rapamycin
binds to FKBP12, the complex binds to mTOR which uncouples mTORC1 from its substrates (allosteric)
63
does rapamycin impair mTOR kinase activity directly + explanation
no, it binds to FKBP12 and the complex uncouples mTORC1 from its substrates (allosteric)
64
what is FKBP12
cytoplasmic receptor, binds rapamycin to form a complex
65
what does the rapamycin-FKBP12 complex do
binds to mTOR to uncouple mTORC1 from its substrates
66
what does rapamycin do to T cell stimulation by DCs
reduce
67
what does rapamycin do to antigen endocytosis by DCs
inhibits
68
what does rapamycin do to cell proliferation + which cells
inhibit, B and T cells
69
what does rapamycin do to antibody production
inhibits
70
what does what does rapamycin do to interleukins (2)
suppresses their production and release
71
what does rapamycin do to chemokine receptors
NOTHING no effect
72
what does rapamycin do to DC migration
NOTHING no effect
73
what does rapamycin do to CD80/86 expression
inhibits
74
what does rapamycin do to DC activation
inhibits
75
what does rapamycin do to T cell response to cytokines
inhibits
76
what does rapamycin do to stimulation of T cells by DCs
reduces
77
what is another name for rapamycin
sirolimus
78
what is another name for sirolimus
rapamycin
79
what is a common use for sirolimus/rapamycin
prevention of transplant rejection (renal) | -alone or with calcineurin inhibitors or corticosteroids
80
what is mycophenolate mofetil
a prodrug which is rapidly hydrolyzed to mycophenolic acid
81
what is the mechanism of mycophenolic acid/ mycophenolate mofetil
non competitive, reversible inhibitor of inosine monophosphate dehydrogenase -blocks purine synthesis (and GMP synthesis too)
82
what happens when you inhibit inosine monophosphate dehydrogenase
you block purine synthesis
83
which drug inhibits inosine monophosphate dehydrogenase and blocks purine synthesis
mycophenolic acid/ mycophenolate mofetil
84
why is mycophenolic acid effective
because B and T lymphocytes depend on this pathway for proliferation (need lots purine because theyre rapidly dividing)
85
besides blocking purine synthesis, what is another thing that mycophenolic acid does
inhibits DC maturation
86
what is the use for mycophenolate mofetil
in transplants and autoimmune disease
87
what kind of general effects does methotrexate have
immunosuppressive

PMCOL 344 (27 decks)

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