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Medical Pharmacology Exam 1 > Immunomodulators > Flashcards

Immunomodulators Flashcards

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USMLE® Step 1 flashcards
1
Q

What is the major cytokine secreted by activated T cells and what is its receptor? What is its function

A

IL2
CD25
Proliferation and clonal expansion of T cell population

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2
Q

What is the major cytokine of the TH1 reponse? What are the 2 major cell types affected? What type of pathogens are targeted?

A

IFN-gamma
Cytotoxic T cells, NK cells
Intracellular Pathogens

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3
Q

What is the major cytokine of the TH2 response? What is the end product? What type of pathogens are targeted?

A

IL4
IgE antibodies
Multicellular parasites

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4
Q

What is the major cytokine of the TH17 response? What type of pathogen is targeted?

A

IL17

Extracellular bacteria and fungi

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5
Q

What type of TH response is associated with allergic disease? Autoimmune disease?

A

TH2

TH17

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6
Q

What is the major role of immuno-stimulants? What is a general description / characteristic of these types of drugs?

A

Activate / enhance immune response

Usually normal agonists of immune system

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7
Q

What types of adverse effects are associated with immunostimulants?

A

They generally reflect systemic inflammatory response (e.g. fever / chills, flu-like symptoms)

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8
Q

What are the 2 examples of adjuvants provided in the class?

A

Alum

BCG

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9
Q

What is the use of alum in medicine? How does it exert its effects?

A

Alum is used in vaccines

Reacts with antigens, forms deposits that prolong their exposure to immune system

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10
Q

What is BCG? How does it work? What type of disease is it used to treat?

A

Attenuated bacillus calmette-guerin
Activates pattern recog. receptors on APCs
Used to treat bladder cancer (topically)

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11
Q

In what scenario can BCG be harmful?

A

Can be harmful if it administed systemically, as it can lead to septic shock

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12
Q

What are the 2 cytokines used clinically provided as examples?

A

IL2

Interferons

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13
Q

What is the use of IL2? What 2 diseases is it used for? What are 3 potential side effects with its use?

A

Proliferation of activated T cells, IFN production, cytotoxic killer cell production
Metastatic melanoma, renal cell carcinoma
Can cause capilary leak syndrome, hypotension and reduced organ perfusion. Possibly fatal

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14
Q

What are the 3 interferons used clinically?

A

Gamma
Alpha
Beta

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15
Q

What is the effect of IFN-gamma? What is it used for?

A

Stimulates cell mediated cytotoxic immune response

Used for recurrent infections

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16
Q

How are the growth inhibitor drugs comparable to antineoplastic agents? What is a general principle regarding the combination use of growth inhibitor drugs?

A

Generally the same drugs, just used in lower doses

Try to combine drugs with non-overlapping side effects

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17
Q

There are 2 adverse effects associated with all immuno-suppressants. They are _

A

Increased risk of infection

Increased risk of cancer

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18
Q

There are 5 drugs provided as examples of general growth inhibitors. They are _

A 
Cyclophosphamide
Azathioprine
Mycophenolate mofetil
Methotrexate
Leflunomide
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19
Q

How does cyclophosphamide work? What is it used for?

A

Cross links DNA, kills all proliferating cells

Autoimmune disease, bone marrow transplant

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20
Q

How does Azathioprine work? What is it used for?

A

Metabolized into thioguanine, inhibitrs purine synthesis and damages DNA.
Used for renal (and other transplantation), autoimmune diseases

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21
Q

How does xanthine oxidase affect azathioprine? How is this dealt with?

A

Xanthine oxidase inactivates azathioprine

Inactivation can be blocked with coadmin with allopurinol

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22
Q

How does mycophenolate mofetil work? What is it used for?

A

Blocks purine synthesis.

Used in solid organ transplant, autoimmune disease

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23
Q

How does methotrexate work? What is it used for?

A

Blocks dihydrofolate reductase (DHFR), blocks thymidine and purine synthesis
Used for RA, autoimmune diseases

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24
Q

How does leflunomide work? What is it used?

A

Inhibits blocks pyrimide synthesis

Used for RA, autoimmune diseases

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25
Q

Among the growth inhibitor compounds, which 2 are renown for less pronounced myelosuppression but hepatotoxicity?

A

Methotrexate

Leflunomide

26
Q

Among the growth inhibitor compounds, which is associated with infertility?

A

Cyclophosphamide

27
Q

Among the growth inhibitor compounds, myelosupression, nausea and vomiting are common to which 3?

A

Cyclosporin
Azathioprine
Mycophenolate mofetil

28
Q

Glucocorticosteroids have anti-inflammatory and immunosupressive effects. One mechanism to achieve this is to induce transcription of target genes. What is the example target gene provided and what is the next effect?

A

Increase transcription of annexins

Inhibit PLA2 and subsequently lipid derived mediators

29
Q

What is the major use of prednisone (2)

A

Immunosuppresant for solid organ and hematopoeitic stem cell transplant
Autoimmune disease treatment

30
Q

What are 5 side effects associated with Prednisone? Under what conditions would these effects be noticed?

A 
Cushing’s Syndrome
Osteoporosis
Glucose intolerance 
Hypertension
Susceptibility to infection
Daily infusion for longer than 2 weeks
31
Q

How do tacrolimus and cyclosporine work? What are their binding partners?

A

The block T-cell receptor signalling by blocking calcineurin
Cyclosporin binds cyclophilin
Tacrolimus binds FKBP12

32
Q

The major use of cyclosporine and or tacrolimus is for the transplantation of what 3 organs? What other type of disease is it used for?

A

Renal, liver, heart

Inflammatory (asthma)

33
Q

How do cyclosporin and tacrolimus compare with regards to potency?

A

Tacrolimus is 10-100 times more potent

34
Q

What are the major side effects associated with tacrolimus and cyclosporin? (4) Which is major?

A

Nephrotoxicity (major)
Hypertension
Hyperglycemia
Liver DIsfunction

35
Q

IL2 is the major immune system growth signal. What is the major drug target for modulating IL2 signaling? What drugs target this?

A

IL2 signals via MTOR. Sirolumus and everolimus block MTOR activity

36
Q

How does sirolimus (and everolimus) interact with cyclosporin and tacrolimus?

A

Sirolimus is synergistic with cyclosporin

Sirolimus is antagonistic with tacrolimus (same target (FKBP12))

37
Q

The 2 major uses of sirolimus are _

A

Preserve solid organ transplant

Treat steroid resistant graft v. host disease following hematopoeitic cell transplant

38
Q

The major side effect of sirolimus is _. Others (4) include

A

Myelosupression

Hyperlipidemia, hypertension, edema, hepatotoxicity

39
Q

How is Rh hemolytic disease caused?

A

If an originally Rh negative mother develops Rh antibodies during a previous pregnancy, these antibodies can attack the fetus and cause hemolytic disease

40
Q

What can be done to prevent hemolytic disease in a pregnant woman? How does it work?

A

Adminster RhD immunoglobulin

Binds up free D antigen, prevents initiation of immune response against D antigen

41
Q

What is belatacept? How does it work?

A

It is a igG with a high affinity B7 ligand. B7 is needed to bind along with the antigen to generate the T cell response. Block T cell binding to B7, leading to anergy

42
Q

What are 5 side effects associated with the use of belatacept?

A

Anemia, neutropenia, peripheral edema, increased risk of infection and malignancy, PTLD

43
Q

What is anti T cell globulin? What is its main effect? How often can it be used?

A

Anti-T cell globulin is made by repeated injection of human T cells into other mammals
Causes opsonization and destruction of T cells, major depletion up to a year
One time use

44
Q

Anti-T cell globulin can cause cytokine release syndrome. How can it be prevented? What are 2 other side effects of anti T cell globulin?

A

Pretreatment with acetamenophen and antihistamines

Serum sickness, anaphylaxis

45
Q

What is alemtuzumab? What is the effect?

A

A humanized anti CD52 antibody, binds CD52, which is expressed on various immune cells
Depletes call cells expressing CD52 (T and B cells, moncytes, macrophages, NK cells) for a year

46
Q

What is the major side effect of alemtuzumab?

A

Myelosupression, flu like symptoms

47
Q

What is basiliximab? How does it work?

A

It is a humanized anti CD25 antibody

Binds the alpha chain of CD25, found only on activated T cells, therefore depletes only activated T cells

48
Q

What are the 3 major antigen presenting cells in the body? What receptor subtype do they express?

A

B cells, dendritic cells, macrophages

MHC II

49
Q

What is the major coreceptors found on T cells and the APCs?

A

T cells express CD28
APC express B7

50
Q

What T helper cell response is associated with allergies? What is the associated antibody?

A

TH2 cells

IgE

51
Q

What T helper cell response is associated with autoimmune disease? What is the associated cytokine?

A

TH17

IL-17

52
Q

Why are immunostimulants considered non-specific?

A

Because they upregulate all components of the immune system, especially APCs to increase the likelihood of T-cell activation

53
Q

What is the major means by which glucocorticoids exert their antiinflammatory and immunosuppresive actions?

A

Cause the expression / suppress the expression of target proteins

54
Q

What are 2 specific notable genes that are suppressed by glucocorticoid? What are their funtions?

A

IL2 - Clonal expansion of T cells

IFN-gamma - Activation of macrophages

55
Q

What is a major advantage of glucocorticoids compared to the growth inhibitor molecules?

A

No significant myelosuppresion associated with glucocorticoids

56
Q

What is the downstream target of calcineurin? What type of activity does it have? What is the effect of this downstream target?

A

NFAT
Calcineurin (A phosphatase) dephosphorylates NFAT
NFAT translocates to nucleus, activates cytokine transcription

57
Q

What are 4 ways that antibodies can be used in human disease?

A
  • Neutralize / opsonize targets
  • Passive immunity
  • Target disease specific antigen
  • Deplete cell mediators of immune system
58
Q

What are the 3 types of antibodies used for medicines? Which can only be used once? Why?

A

Human
Animal (Single use)
Chimeric
Recognized and destroyed during subsequent uses

59
Q

What are side effects associated with repeated animal antibody use? (3)

A

Antibody destruction
Allergic reaction
Serum sickness

60
Q

What is a specific neoplasm associated with the use of belatacept? What specific population is at risk? What is belatacept used for?

A

Posttransplant lymphoproliferative disorder (PTLD)
Epstein Barr Virus negative patients
Kidney transplantation

61
Q

How does the side effects of basiliximab compare to other antibody modulating agents?

A

Mild, because its target (activated T cells) is so much narrower

Medical Pharmacology Exam 1 (15 decks)

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