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NBME Micro > Immunology: Immunosuppressants > Flashcards

Immunology: Immunosuppressants Flashcards

1
Q

A patient is given a recombinant form of IL-2. Which 2 types of cancer can this recombinant drug be used to treat?

A

Renal cell carcinoma, metastatic melanoma (both treated with aldesleukin)

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2
Q

Which 2 hematologic malignancies are glucocorticoids often used to treat?

A

Non-Hodgkin lymphoma and chronic lymphocytic leukemia

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3
Q

A patient with Crohn disease who is receiving natalizumab therapy develops rapidly progressive paralysis and hyperreflexia. What virus is the probable culprit?

A

JC virus, which can cause progressive multifocal leukoencephalopathy (PML); the risk of PML is increased in patients treated with natalizumab

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4
Q

Sirolimus (rapamycin) binds FKBP in the cell and subsequently inhibits what protein kinase?

A

mTOR (mechanistic target of rapamycin)

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5
Q

A man taking allopurinol for gout starts taking an immunosuppressive agent for Crohn disease. Pancytopenia develops rapidly. What happened?

A

Azathioprine’s metabolite, 6-MP, is metabolized by xanthine oxidase; allopurinol inhibits xanthine oxidase, resulting in toxic levels of 6-MP

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6
Q

Which 2 factors can amplify the nephrotoxicity of calcineurin inhibitors?

A

Administration at higher doses and poor baseline renal function

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7
Q

A patient scheduled for kidney transplantation receives a monoclonal antibody against IL-2R for immunosuppression. Which side effects should be monitored?

A

Edema, hypertension, tremor (the prescribed drug is basiliximab)

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8
Q

mTOR is responsible for driving the transcription of what types of genes?

A

Proliferation genes

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9
Q

An elderly patient is diagnosed with CLL. What are the 2 molecular targets of the therapeutic antibodies commonly used to treat this disease?

A

CD-20 (targeted by rituximab) and CD52 (targeted by alemtuzumab); think “alymtuzumab” for chronic lymphocytic leukemia and “ri2Ximab” to target CD20

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10
Q

6-Mercaptopurine (6-MP) inhibits what specific protein involved in nucleotide synthesis?

A

PRPP amidotransferase

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11
Q

A patient develops severe hirsutism while taking cyclosporine for post-transplant immunosuppression. Which alternative drug with a similar mechanism of action may be ideal for her?

A

Tacrolimus (which does not cause the hirsutism or gingival hyperplasia associated with cyclosporine)

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12
Q

What are the 2 main cancers that may be treated with trastuzumab?

A

Breast and gastric cancers (if positive for a HER2 mutation)

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13
Q

Long-term use of immunosuppressants increases the risk of which 2 conditions?

A

Cancers and infections (immunosuppressants such as cyclosporine disrupt lymphocyte activation and growth)

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14
Q

Apart from transplant rejection prophylaxis, what are the 3 main clinical indications for azathioprine?

A

Rheumatoid arthritis, glomerulonephritis, Crohn disease (and other autoimmune conditions)

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15
Q

A patient is receiving long-term prednisone therapy for severe SLE. What are 2 potential effects of this medication on the bone?

A

Osteoporosis (predisposing to vertebral fracture), avascular/ischemic osteonecrosis (often of femoral head)

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16
Q

Azathioprine inhibits proliferation of lymphocytes by blocking nucleotide synthesis. For which antimetabolite is azathioprine a precursor?

A

6-Mercaptopurine; “azathiopurine” interferes with nucleic acid synthesis (toxic to proliferating lymphocytes)

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17
Q

With which 2 CD markers is the T-helper cell receptor associated?

A

CD3 and CD4

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18
Q

Which 2 recombinant cytokines could be used to treat chemotherapy-induced leukopenia?

A

Filgrastim (G-CSF) and sargramostim (GM-CSF), which aid in the recovery of granulocyte and monocyte counts

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19
Q

Which immunosuppressant medication is synergistic with cyclosporine?

A

Sirolimus (rapamycin); although cyclosporine can be used alone, sirolimus is not nephrotoxic (the kidney “sirvives”) and can enhance its efficacy

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20
Q

A patient with NADPH oxidase deficiency has recurrent bacterial infections. What cytokine can be used to treat his condition?

A

IFN-γ (used to treat chronic granulomatous disease or CGD)

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21
Q

What 3 types of cancer is bevacizumab commonly used to treat?

A

Renal cell carcinoma, non–small cell lung cancer, and colorectal cancer

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22
Q

What recombinant antibody mimics the function of osteoprotegerin to prevent further bone loss in osteoporosis?

A

Denosumab (which, like osteoprotegerin, targets RANKL and inhibits osteoclast maturation)

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23
Q

What is the molecular target of abciximab?

A

Abciximab targets platelet glycoproteins IIb/IIIa (ABC is as easy as 123), preventing platelet aggregation

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24
Q

Both mycophenolate mofetil and azathioprine inhibit the de novo production of what type of nucleotides?

A

Purines (adenine, guanine)

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25
Q

What are 3 clinical indications for treatment with interferon-α (IFN-α)?

A

Chronic hepatitis B, chronic hepatitis C (not preferred), renal cell carcinoma

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26
Q

Which messenger, directly downstream from the T-cell receptor, is activated to promote inflammatory cytokine (eg, IL-2) gene transcription?

A

NFAT, which is generated from NFAT-P by calcineurin-mediated dephosphorylation (NFAT then enters the nucleus and promotes transcription)

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27
Q

Apart from transplant rejection, what are the 2 main clinical indications for cyclosporine?

A

Psoriasis, rheumatoid arthritis

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28
Q

A patient with psoriasis begins taking an immunosuppressant. After several months, she develops gingival hyperplasia and hirsutism. What drug is she taking?

A

Cyclosporine (tacrolimus has the same toxicity as cyclosporine but does not cause gingival hyperplasia or hirsutism)

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29
Q

What is the primary molecular target inhibited by mycophenolate?

A

IMP dehydrogenase, which promotes purine synthesis

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30
Q

A patient with optic neuritis and asymmetric neurologic deficits is treated with an antibody targeting α4-integrin. What immunosuppressive agent is she taking?

A

Natalizumab, which is used to treat multiple sclerosis (by targeting α4-integrin to impair leukocyte adhesion) is

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31
Q

What is the mechanism of action of mycophenolate mofetil?

A

Mycophenolate mofetil reversibly inhibits IMP dehydrogenase, preventing purine synthesis in T and B cells

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32
Q

A patient with severe persistent allergic asthma has frequent exacerbations despite high-dose inhaled steroid and long-acting β-agonist therapy. Which medication may be indicated?

A

Omalizumab, a recombinant antibody targeting IgE (used in treatment of refractory allergic asthma)

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33
Q

Which 2 medications must bind FKBP to inhibit cellular immunity?

A

Tacrolimus and sirolimus

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34
Q

A patient receiving a high maintenance dose of prednisone for several months runs out of her medication and cannot obtain a refill. For what complication is she at risk?

A

Adrenal insufficiency, which can develop as a result of abrupt steroid cessation (due to adrenal axis suppression in long-term steroid use)

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35
Q

What is the mechanism of action of tacrolimus (FK506)?

A

FK506 binds to FK506 binding protein (FKBP) and inhibits calcineurin, thereby preventing IL-2 transcription and thus inhibiting T-cell activation

36
Q

Sirolimus (rapamycin) inhibits which target to exert its immunosuppressive effect?

A

mTOR

37
Q

Which 2 immunosuppressants are commonly associated with drug-induced kidney failure?

A

Cyclosporine and tacrolimus (calcineurin inhibitors)

38
Q

A patient presents with petechiae and is diagnosed with severe thrombocytopenia. Which 2 recombinant cytokines may be useful in treatment?

A

Romiplostim (thrombopoietin analog) and eltrombopag (thrombopoietin receptor agonist), which are platelet stimulators

39
Q

A patient presents with intermittently red urine and anemia. Flow cytometry shows deficient CD55 and CD59 on RBCs. What recombinant antibody may be used to treat this condition?

A

Eculizumab (used to treat paroxysmal nocturnal hemoglobinuria)

40
Q

A patient with an asthma exacerbation is treated with IV steroids. The next day, CBC shows a WBC count of 15,000. What is the mechanism behind this effect?

A

Glucocorticoids cause demargination of WBCs in the vasculature, producing an apparent (artificial) leukocytosis on blood testing

41
Q

How does the inhibition of NF-κB by steroids lead to immune system suppression?

A

NF-κB inhibition decreases cytokine transcription, suppressing B- and T-cell function while inducing T-cell apoptosis

42
Q

A premature infant has chronic lung disease. What is the target of the antibody that may be given to this infant to prevent RSV infection?

A

RSV F protein, which is targeted by palivizumab (paliVIzumab—VIrus) for RSV prophylaxis in high-risk infants

43
Q

What are 2 adverse effects that are more pronounced with use of tacrolimus compared with use of cyclosporine?

A

Diabetes (metabolic side effects) and neurotoxicity

44
Q

A patient experiences loss of vision and pain in her left eye. Brain MRI shows periventricular plaques. Which cytokine may be used in treatment?

A

IFN-β (often used to treat multiple sclerosis)

45
Q

Glucocorticoids inhibit the transcription of what types of genes?

A

Inflammatory cytokine genes

46
Q

A patient with high-risk unstable angina undergoes percutaneous coronary intervention. Which agent may be given to prevent additional ischemic complications?

A

Abciximab, an antiplatet agent targeting glycoproteins IIb/IIIa (ABC is as easy as 123)

47
Q

A patient presents with right-sided flank pain and hematuria. CT of the abdomen shows a complex renal mass. Which 2 recombinant cytokines can treat this condition?

A

Aldesleukin (recombinant IL-2) and IFN-α (interferon-α), both of which treat renal cell carcinoma

48
Q

Which immunosuppressant is often found in drug-eluting stents?

A

Sirolimus (rapamycin)

49
Q

A liver transplant recipient develops a buffalo hump, hyperglycemia, striae, and acne. Which drug class can cause such symptoms?

A

Glucocorticoids

50
Q

What are the 2 monoclonal antibodies that bind to and inhibit the IL-2 receptor (IL-2R)?

A

Daclizumab, basiliximab

51
Q

Which 2 recombinant antibodies are notorious for increasing the risk of PML in patients with latent JC virus infection?

A

Natalizumab and rituximab

52
Q

What are the 2 main indications for treatment with natalizumab?

A

Crohn disease and multiple sclerosis

53
Q

What molecule does the antibody omalizumab target?

A

IgE (thus preventing IgE from binding to FcεRI), useful in patients with refractory allergic asthma

54
Q

What are 3 benign ocular conditions that bevacizumab may be used to treat?

A

Macular edema, neovascular (“wet”) age-related macular degeneration, and proliferative diabetic retinopathy

55
Q

A 65-year-old woman is found to have a T-score of -3.0 on a screening DEXA scan. Which therapeutic antibody would help to reduce her fracture risk?

A

Denosumab (denosumab helps make dense bones)

56
Q

Aldesleukin is a recombinant form of which cytokine?

A

Interleukin-2 (IL-2)

57
Q

A patient with end-stage renal disease presents with anemia and an MCV of 86 fL. What biologic agent can be used in treatment?

A

Epoetin alfa (an erythropoietin or EPO analog) which is useful in renal failure-associated anemias

58
Q

What are the 2 main indications for treatment with ustekinumab?

A

Psoriasis and psoriatic arthritis

59
Q

What is the mechanism of action of cyclosporine?

A

Cyclosporine inhibits calcineurin and binds cyclophilin, preventing IL-2 transcription and thus blocking T-cell activation

60
Q

Cyclosporine has several adverse effects. Which of these is most common and concerning?

A

Nephrotoxicity is most concerning (others include hypertension, hyperlipidemia, neurotoxicity, hirsutism, and gingival hyperplasia)

61
Q

What is the mechanism of action of sirolimus (rapamycin)?

A

Rapamycin inhibits mTOR, blocking T-cell activation and B-cell differentiation by inhibiting the cellular response to IL-2

62
Q

After “doing some reading” about rituximab therapy, a patient diagnosed with T-cell lymphoma asks you whether he would qualify for it. How do you respond?

A

Tell the patient he is not a candidate for this therapy, as rituximab targets CD20 on B cells (and is therefore used to treat B-cell non-Hodgkin lymphoma and CLL)

63
Q

Glucocorticoids inhibit what cellular protein complex implicated in DNA transcription and cytokine production?

A

NF-κB (nuclear factor κ-light chain enhancer of activated B cells)

64
Q

Which 2 immunosuppressants are specifically preferred for kidney transplant rejection prophylaxis?

A

Sirolimus and Basiliximab (think Sir Basil’s kidney transplant)

65
Q

Which immunosuppressant may be specifically preferred for the treatment of lupus nephritis?

A

Mycophenolate mofetil

66
Q

A patient with Burkitt lymphoma is treated with a recombinant antibody targeting CD20. What is this agent?

A

Rituximab, which targets CD20 (“ri2Ximab”) on B cells

67
Q

What 2 conditions may be treated with alemtuzumab?

A

CLL (“alymtuzumab” for chronic lymphocytic leukemia), multiple sclerosis (MS)

68
Q

What 2 recombinant antibodies have been developed to treat autoimmune diseases by targeting soluble TNF-α?

A

Infliximab and adalimumab

69
Q

A woman with progressive jaundice, ascites, and altered mental status tests positive for HBsAg and HBeAg. Which recombinant cytokine could help treat her condition?

A

Interferon-α (may be used in the treatment of chronic hepatitis B infection)

70
Q

A woman has breast cancer that is positive for a HER2 mutation. Which monoclonal antibody can be used in treatment?

A

Trastuzumab (HER2—”tras2zumab”)

71
Q

What is the mechanism of action of basiliximab?

A

Basiliximab is a monoclonal antibody that blocks the IL-2 receptor

72
Q

What is the molecular target of eculizumab in the treatment of paroxysmal nocturnal hemoglobinuria (PNH)?

A

Complement protein C5

73
Q

What drug is a decoy TNF-α receptor that may be used to treat rheumatoid arthritis, IBD, psoriasis, and ankylosing spondylitis?

A

Etanercept (not a monoclonal antibody)

74
Q

What downstream messenger is activated by IL-2R signaling?

A

mTOR

75
Q

What are the 2 molecular targets of ustekinumab?

A

IL-12 and IL-23

76
Q

What are 2 key advantages associated with the use of mycophenolate mofetil for immunosuppression?

A

The drug is less nephrotoxic and less neurotoxic

77
Q

A patient presents with melena. Barium enema reveals an “apple core” sign. Colon cancer is diagnosed. Which recombinant antibody may be used in the therapy for this disease?

A

Bevacizumab, which targets VEGF to treat malignancies such as colorectal cancer

78
Q

What are 4 potential side effects of mycophenolate mofetil?

A

Hypertension, hyperglycemia, pancytopenia, gastrointestinal disturbance

79
Q

A man is diagnosed with age-related macular degeneration. Fundoscopic exam shows neovascularization. Using antibodies to inhibit which target may help?

A

VEGF (targeted by bevacizumab)

80
Q

What is the clinical advantage of combining different immunosuppressants?

A

Combining immunosuppressants increases their net efficacy while minimizing their individual toxicities

81
Q

A patient with lupus nephritis begins taking mycophenolate mofetil and subsequently develops an invasive viral infection. Which virus is the likely pathogen?

A

Cytomegalovirus (CMV); mycophenolate mofetil is associated with invasive CMV infection

82
Q

What is the molecular target of denosumab?

A

RANKL (like osteoprotegerin, denosumab inhibits osteoclast maturation by binding RANKL)

83
Q

Which 3 toxicities should a patient who is taking sirolimus (rapamycin) be warned about?

A

Pancytopenia, insulin resistance, hyperlipidemia (sirolimus causes “pansirtopenia”)

84
Q

What 3 autoimmune conditions can rituximab be used to treat?

A

ITP, multiple sclerosis, and rheumatoid arthritis

85
Q

What are 4 clinical indications for treatment with adalimumab, infliximab, and etanercept?

A

Inflammatory bowel disease (Crohn disease or ulcerative colitis), rheumatoid arthritis, psoriasis, ankylosing spondylitis

NBME Micro (36 decks)

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