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1 Pharm Unit > 13 Immunomodulators > Flashcards

13 Immunomodulators Flashcards

1
Q

adaptive immune response is directed by? (2)

A
  • cytokines from T helpers
  • antibodies from B cells
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2
Q

How do administered antibodies depress the immune system? (2)

A
  • opsonize & deplete T cells
  • neutralize antigens before they can elicit an immune response (Rh negative mothers)
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3
Q

What are the 3 key steps in T activation? (will be drug targets)

A
  • engagement TCR & co-receptors
  • expressions of cytokines
  • clonal expansion
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4
Q

On top of the 3 key steps in T activation (see previous card), what is the 1 additional way immune suppression is achieved in T helpers?

A

-TCR signal transduction is targeted

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5
Q

For visual people, here’s a picture of those 4 ways.

A
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6
Q

What are the 2 kinds of useful immune stimulants?

A
  • cytokines: IL-2, IFN-alpha & gamma!!
  • environmental agents that up antigen presentation (BCG, alum)
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7
Q

Activated T cells secrete what cytokine & express what receptor?

A
  • IL-2
  • CD25 (IL-2 Receptor)
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8
Q

What does IL-2 do?

A

stimulates clonal expansion of antigen-specific T cells

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9
Q

Which immune cells do T cell secreted cytokines influence?

A

all

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10
Q

Th1 response secretes _____ cytokine which increases _____ function against _____ type of pathogen

A
  • IFN-gamma
  • cell-mediated cytotoxicity
  • intracellular
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11
Q

Th2 response secretes ______ cytokine which initiates ______ action against ______ pathogen

A
  • IL-4
  • humoral (mostly IgE)
  • multicellular parasites (and allergies)
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12
Q

Th17 response secretes ______ cytokine with function _____ against _______ type of pathogen

A
  • IL-17
  • Inflammatory/neutrophil direction
  • extracellular bacteria & fungi, also autoimmune
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13
Q

What is the main problem with immunostimulants?

A

cascade effect increases release of cytokines/inflammation mediators downstream

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14
Q

What symptoms do downstream cytokines cause?

A

flu-like (fever, chills)

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15
Q

When are times you’d use an immune stimulator? (review, don’t memorize)

A

enhance vaccination response

chronic disease

immunodeficiency

cancer

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16
Q

What are the 2 adjuvants?

A

alum

BCG (bacillus calmette-guerin)

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17
Q

______ is most common adjuvant in human vaccines?

A

alum

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18
Q

How does alum work?

A

forms deposits w/ antigens and prolongs exposure to them, may increase APC activity.

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19
Q

which adjuvant has few side effects?

A

alum

20
Q

What is the main use of BCG?

A

cancer therapies

21
Q

How does BCG work? (2)

A
  • puts antigens in contact w/ pattern recognition receptors
  • direct activation of leukocytes (so strong it causes septic shock so only used topically!)
22
Q

What is IL-2 immune stimulant used for? (2)

A
  • metastatic melanoma
  • Renal cell carcinoma
23
Q

What effects does IL-2 have? (4)

A
  • proliferation T cells
  • production IFN-gamma
  • CD 8 activation
  • capillary leak ->hypotensive shock
24
Q

IFN-gamma immune stimulant is used for?

A

severe recurrent infections

25
Q

IFN-alpha immune stimulant is used for? (2)

A
  • chronic viral infection
  • Reduces frequency of episodes in multiple sclerosis (immune modulatory)
26
Q

What are the 2 key side effects of all immune suppressants?

A
  • cancer
  • infection
27
Q

What 5 drugs are general inhibitors of clonal expansion?

A
  • Cyclophosphamide
  • Azathioprine
  • Mycophenolate
  • Methotrexate
  • Leflunomide
28
Q

Which clonal expansion inhibitors are like each other?

A
  • Azathioprine and mycophenolate (for side effects)
  • Methotrexate and leflunomide (for uses)
29
Q

What is the difference in dosage for immunosuppression or anti-neoplasm drugs?

A

-lower doses for immunosuppression

30
Q

Xanthine oxidase inactivates which immunosuppressant?

A

azathioprine

31
Q

Picture what’s going on with calcineurin, NFAT, glucocorticoids, and resulting cytokines.

A
32
Q

When NFAT is active, is it 1) phosphorylated? 2)Creating or stopping inflammation?

A
  • No.
  • Creating inflammation.
33
Q

T/F cyclosporine can be found endogenously, & binds the drug cyclophilin?

A

F. Cyclophilin is endogenous, cyclosprorine is drug.

34
Q

Which drug antagonizes tacrolimus? Which drug synergizes with cyclosprine?

A

Sirolimus (both)

35
Q

What is function of calcineurin?

A

Activate NF-AT

36
Q

What is function of NF-AT?

A

go into nucleus to cause transcription cytokines

37
Q

IL-2 receptor binding leads to activation of what? which then causes?

A
  • mTOR
  • cell growth & proliferation
38
Q

What is FKBP12?

A

endogenous, it binds tacrolimus & stops activation of NF-AT by calcineurin.

[Same way cyclophilin bound to cyclosporine acts!]

39
Q

How are debilitating side effects like nephrotoxicity avoided when using immune suppressants?

A

They are used in low doses in combination with other immune suppressors

40
Q

Which 2 immune suppressant drugs combine with the same target? What is that target?

A

tacrolimus and sirolimus

[Note that tacrolimus does this to stop calcineurin activity, while sirolimus does this to stop mTOR activity!]

41
Q

What receptor is acted on by over 60 cytokines? What is the function of this receptor? (3)

A
  • Jak/Stat
  • Adaptive Immunity, Inflammation, many functions req’d for life!
42
Q

T/F Jak/stat inhibits ALL activity of cytokines required for adaptive immunity?

A

true.

43
Q

Administered Antibodies can be used as therapy in what ways (besides immune suppression, see card at beginning for that info)

A
  • Give passive immunity
  • Destroy cancer (herceptin for breast cancer)
44
Q

Which portion of a chimeric antibody is human?

A

the Fc region (constant)

45
Q

Why can’t animal Ab’s be used long-term in humans?

A

-Humans mount response against them ->allergic rxn & serum sickness

46
Q

How are Ab’s used to treat Rh neg. mothers? What happens if they aren’t used?

A
  • They bind and neutralize the baby’s Rh(D) antigens introduced to mom’s blood at time of birth.
  • Future babies get hemolytic disease
47
Q

How are Anti-T cell antibodies made?

A

T cells are injected into animals and then serum IgG is purified from them

1 Pharm Unit (14 decks)

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