Pharm Immunomodulating Drugs
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Hello and welcome to a wonderful quiz on pharmacology, where today we’ll be looking at the topic of immunomodulators – drugs used to help regulate the immune system, which are used for such ailments as asthma and angioedema. What can you tell us about these drugs? Let’s find out.
Questions and Answers
- 1.
Which of the following statements regarding immunosuppressive drugs are correct (Check all that apply)
- A.
They work better if immunosuppression is initiated before than after the exposure of the body to the antigen
- B.
Primary immune responses are more easily suppressed than secondary immune responses
- C.
They act mainly through the inhibition of antigen processing by antigen presenting cells
- D.
Some anticancer drugs are also used for maintenance immunosuppression in doses generally lower than those employed in anticancer therapy
- E.
Unlike anticancer drugs, the toxicity of the immunosuppressive agents is usually negligible
Correct Answer(s)
A. They work better if immunosuppression is initiated before than after the exposure of the body to the antigen
B. Primary immune responses are more easily suppressed than secondary immune responses
D. Some anticancer drugs are also used for maintenance immunosuppression in doses generally lower than those employed in anticancer therapyExplanation
Answer: ABD
(Hardman, pp 1464, Craig, pp 658)
Inhibition of the immune response is more likely to occur if the immunosuppressant drugs are given
before, rather than after, the exposure to the antigen. This explains why intensive immunotherapy is
given just before a solid organ transplant. Unfortunately almost always the immune disease is treated
when it is clinically evident, that is when the exposure to the antigen has already occurred.
Primary immune responses (i.e. antigen recognition, cell proliferation, lymphokine synthesis, etc.) are
most sensitive to immunosuppressant drugs. On the contrary the secondary immune response (i.e. the
response generated by memory B cells when they re-encounter the antigen) is not much affected by
immunosuppressant drugs.
Since many anticancer drugs are cytotoxic, they can also kill the cells that mediate the immune
response, and therefore several anticancer drugs do have immunosuppressant effects. Among these
only three (cyclophosphamide, methotrexate and the prodrug azathioprine) have been consistently used
clinically as immunosuppressants. When anticancer drugs are used for immunosuppression they are
given continuously (not in cycles) and the doses are generally lower than those employed in anticancer
therapy C) .Antigen presenting cells take up the antigens and subject them to proteolytic degradation.
These events are called antigen processing. and are required because, although B cell antigen
receptors bind directly to antigen, T cell antigen receptors only recognize processed antigens. This very
early step of immune response is not affected by immunosuppressant drugs.
E) The toxicity of the immunosuppressant drugs is high and death due to immunosuppressant therapy
have been reported.Rate this question:
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- 2.
Which of the following drug-induced disorders represent the major limitations to the general use of most immunosuppressant drugs ? (Check all that apply)
- A.
Kidney failure
- B.
Lymphomas
- C.
Infections
- D.
Neurologic disorders
- E.
Myelosuppression
- F.
Hepatic failure
Correct Answer(s)
B. LympHomas
C. InfectionsExplanation
Answer: BC
(Koda-Kimble, pp 35-5, 35-26, Craig, pp 658)
Since immunosuppressant drugs impair the adaptive immune system the risk of infections becomes
substantial (for example infection is the leading cause of death in the first 60 days after lung
transplantation).
Moreover therapies with these drugs require lifelong use, so exposing the patient to increased risk of
some cancers, mainly lymphomas. The overall prevalence of malignancies in the transplantation
population averages about 6% and the risk of cancer increases with time after a transplantation.
Transplanted patients are 100 times more likely to have cancer that the general population.
The frequency of the other listed disorders is increased with some immunosuppressant agents, but not
with others. Specifically:
A, D) Kidney failure and neurologic disorders are often caused by cyclosporine and tacrolimus.
E) Myelosuppression is significant with cytotoxic drugs and mycophenolic acid.
F) Hepatotoxicity can occur with cyclosporine and azathioprine but hepatic failure is extremely rare.Rate this question:
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- 3.
Which of the following statements correctly pair the immunomodulators with its appropriate mechanism of action? (Check all that apply)
- A.
Tacrolimus - increases the catabolism of IgG antibodies
- B.
Azathioprine - stimulates interleukin-2 synthesis in CD4 helper cells
- C.
Sirolimus - inhibits mammalian kinase
- D.
Cyclophosphamide - inhibits inosine monophosphate dehydrogenase
- E.
Muromonab-CD3 - inhibits calcineurin
- F.
Daclizumab - blocks interleukin-2 receptors
Correct Answer(s)
C. Sirolimus - inhibits mammalian kinase
F. Daclizumab - blocks interleukin-2 receptorsExplanation
Answer: CF
(Hardman, pp 1470, Koda-Kimble, pp 35-8)
Sirolimus is an antibiotic that, like tacrolimus, binds to a FK-binding protein. The sirolimus-protein
complex binds to mammalian kinase, an enzyme which is essential for cell-cycle progression, resulting
in cell-cycle arrest in the late G1-phase
. Daclizumab is a monoclonal antibody against the interleukin-2 receptors present on the surface of T
cells. The drug prevents the il-2 mediated T cell activation events (e.g. activation of CD4 T helper cells).
A) Glucocorticoids, not tacrolimus, increase the catabolism of IgG antibodies.
B) Azathioprine is an immunosuppressant drug. Stimulation of interleukin-2 synthesis would cause
immunostimulant effects.
D) Mycophenolate mofetil, not cyclophosphamide, inhibits inosine monophosphate dehydrogenase.
E) Cyclosporine and tacrolimus, not muromonab-CD3, inhibit calcineurinRate this question:
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- 4.
Which of the following drugs is a macrolide antibiotic that binds to a FK binding protein located in T cells, so blocking the gene expression for interleukin 2 production?
- A.
Azithromycin
- B.
Azathioprine
- C.
Tacrolimus
- D.
Cyclosporine
- E.
Tobramycin
Correct Answer
C. TacrolimusExplanation
Answer: C
(Katzung, pp 941, Koda-Kimble, pp 35-8)
Antibiotics endowed with immunostimulant properties include cyclosporine, tacrolimus and sirolimus.
They interfere with T cell function by binding to immunophilins, small intracellular proteins that play a key
role in T cell response to receptor activation and to cytokines. Cyclosporine (a macrolide antibiotic) binds
to cyclophilin, tacrolimus and sirolimus bind to FK-binding proteins. The tacrolimus-protein complex
binds to calcineurin, a cytoplasmic phosphatase, and inhibits its action. Since calcineurin regulates the
ability of a nuclear factor of activated T cells to translocate to the nucleus and increase the production of
interleukin-2, this production is suppressed.
A) Azithromycin is a macrolide antibiotic with antibacterial activity. It is devoid of immunosuppressant
properties.
B) Azathioprine is a cytotoxic drug with immunosuppressant properties.
C) Cyclosporine also inhibits calcineurin actions but it binds to cyclophilin, not to a FK-binding protein.
E) Tobramycin is an aminoglycoside antibiotic devoid of immunosuppressant properties.Rate this question:
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- 5.
Which of the following drugs can bind to and neutralize TNF alpha, so inhibiting its actions? (Check all that apply)
- A.
Etanercept
- B.
Infliximab
- C.
Muromonab CD3
- D.
Tacrolimus
- E.
Aldesleukin
Correct Answer(s)
A. Etanercept
B. InfliximabExplanation
Answer: AB
(Hardman, pp 1475, Koda-Kimble, pp 43-5)
Etanercept and infliximab are drugs that are able to neutralize TNF-alpha. Etanercept is a recombinant
form of the TNF receptor, infliximab is a monoclonal antibody against TNF-alpha. Both drugs bind to
TNF-alpha with high affinity and specificity, so inhibiting its actions. TNF-alpha is produced by
macrophages and activated T cells and plays a central part in the immune and inflammatory response.
Both drugs are used mainly in severe rheumatoid arthritis.
C) Muromonab CD3 is a monoclonal antibody against the CD3 antigen present on the surface of human
thymocytes and mature T cells.
D) Tacrolimus is an immunosuppressant antibiotic that acts by inhibiting calcineurin.
E) Aldesleukin is an immunostimulant drug.Rate this question:
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- 6.
A 28-year-old woman was admitted to the hospital with fever, a malar butterfly erythema, arthralgia, intermittent pleuritic pain and oral ulcers. Her lab tests revealed the following: serum creatinine 5.2 mg/dL, BUN 35 mg/dL, and high serum level of antinuclear antibodies. Which of the following drugs was most likely included in the therapeutic management of this patient?
- A.
Infliximab
- B.
Prednisone
- C.
BCG vaccine
- D.
Interferon-beta-1b
- E.
Aldesleukin
Correct Answer
B. PrednisoneExplanation
Answer: B
(Koda-Kimble, pp 44-3, Katzung, pp 651)
The sings and symptoms of the patients strongly indicate that she is affected by lupus erythematosus In
fact the patient shows five of the 11 sings and symptoms most often associated with this disease (malar
butterfly erythema, arthritis, oral ulcers, renal disorder, nuclear antibodies). According to the American
College of Rheumatology the diagnosis of lupus erythematosus is made when the patient has 4 or more
of these 11 signs and symptoms.
The cause of lupus erythematosus is unknown but it is thought to involve autoimmune mechanisms.
Therefore the therapy almost always includes corticosteroids that are especially valuable for the more
severe and life threatening manifestations of the disease. Since in the present case there are sings of
renal insufficiency (see creatinine and BUN values) steroid therapy is strongly indicated.
A) Infliximab is currently approved for use in rheumatoid arthritis and Crohn’s disease.
C, D, E) These are immunostimulant drugs and therefore are would be contraindicated in autoimmune
disease.Rate this question:
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- 7.
A 32-year-old woman, who has been suffering from myasthenia gravis for four years, developed progressive dyspnea several days after an upper respiratory tract infection. Physical examination disclosed bilateral ptosis, bilateral facial weakness an diminished upper and lower motor strength. An IV edrophonium injection improved muscle strength. A serum assay for anti-acetylcholine receptor antibody was 4.8 (normal < 0.5). The appropriate treatment, promptly instituted, included a parenteral injection of prednisone. Which of the following statements best explains the most likely mechanism of action of the drug in this case?
- A.
Inhibition of plasma cholinesterase
- B.
Activation of Nm receptors
- C.
Stimulation of synthesis of interleukin 2
- D.
Inhibition of T cell activation and proliferation
- E.
Stimulation of synthesis of interleukin 1
Correct Answer
D. Inhibition of T cell activation and proliferationExplanation
Answer: D
(Lane, pp 1497, Hardman, pp 1661)
Myasthenia gravis is an acquired autoimmune disease characterized by exercise-induced muscle fatigue
that resolve after rest. The pathogenesis is due to antibody mediated destruction of Nm receptor sites.
The initiating event leading to antibody production is unknown. The present patient most likely
developed a myasthenic crisis (edrophonium improved muscle strength), which may be precipitated by
infection but also can occur without apparent cause. Myasthenic crisis requires intensive management
which include selected anticholinesterase drugs (like neostigmine), and immunosuppressive treatment
with glucocorticoids and cyclosporine. The immunosuppressant effect of glucocorticoids is likely due to
multiple mechanisms of action. Especially important in this regard is the inhibition of T cells activation
(due to inhibition of synthesis of interleukin-1) and of T cell proliferation (due to inhibition of synthesis of
interleukin-2)
A, B) Glucocorticoids have no effect on plasma cholinesterase or on nicotinic receptors.
C, E) Glucocorticoids actually decrease the synthesis of these interleukins (see answer above)Rate this question:
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- 8.
A 35-year-old man, who was scheduled for a heart transplant, received a triple immunosuppressive therapy just before surgery. Which of the following three drug combinations were most likely administered?
- A.
Azathioprine, prednisone, aldesleukin
- B.
Cyclosporine, azathioprine, prednisone
- C.
Prednisone, triamcinolone, cyclosporine
- D.
Aldesleukin, infliximab, etanercept
- E.
Infliximab, etanercept, triamcinolone
Correct Answer
B. Cyclosporine, azathioprine, prednisoneExplanation
Answer: B
(Koda-Kimble, pp 35-23, )
Immunosuppressive therapy is given aggressively during the early transplant period because the risk of
organ rejection is greater at this time. Azathioprine with prednisone were associated with a 50% organ
survival rate. When cyclosporine was added, more than 80% rate of organ survival was obtained.
A) Aldesleukin is an immunostimulant drugs and therefore its use would be irrational in this setting.
C) Triamcinolone is a synthetic glucocorticoid. The combined use of prednisone and triamcinolone (two
different glucocorticoids with equivalent effects) is superfluous.
D, E) Infliximab and etanercept are immunosuppressant drugs that neutralize TNF-alpha. They are used
only in selected autoimmune diseases (Crohn’s disease, rheumatoid arthritis).Rate this question:
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- 9.
A 42-year-old man came to the clinic complaining of an extensive rash, white plaque-like lesions in his mouth, dry eyes, hyperpigmentation of the tissues surrounding the eyes, and diarrhea. Three months before the man, who was suffering from chronic myelogenous leukemia, underwent an allogeneic bone marrow transplantation from his sister and was successfully treated for his acute graft versus host disease. The patient had had no major health problems after that disease. Which of the following pairs of drugs were most likely included in the therapeutic treatment of this patient?
- A.
Prednisone and cyclosporine
- B.
Cyclosporine and erythromycin
- C.
Cyclophosphamide and doxorubicin
- D.
Vinblastine and prednisone
- E.
Doxorubicin and vinblastine
Correct Answer
A. Prednisone and cyclosporineExplanation
Answer: A
(Koda-Kimble, pp 92-24, Dipiro, pp 2440)
The patient most likely suffered from chronic graft versus host disease (GVHD) which occurs in up to
70% of allogeneic bone marrow transplanted patients. The most important risk factor for developing
chronic GVHD is a prior diagnosis of acute GVHD. The mainstay of therapy of GVHD is long-term
immunosuppressive therapy. Prednisone, azathioprine and cyclosporine have emerged as the most
commonly used agents with the best efficacy. The combination of cyclosporine and prednisone has
resulted in higher survival when compared with prednisone or cyclosporine alone.
B, C, D, E) Erythromycin, doxorubicin, and vinblastine are not immunosuppressant drugs.Rate this question:
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- 10.
A 32-year-old man suffering from extensive psoriasis resistant to topical agents and photochemotherapy, started an immunosuppressive treatment with oral cyclosporine. Which of the following cells represent the main site of action of the drug?
- A.
Macrophages
- B.
Dendritic cells
- C.
T-helper cells
- D.
Plasma cells
- E.
Natural killer cells
Correct Answer
C. T-helper cellsExplanation
Answer: C
(Hardman, pp 1466, Koda-Kimble, pp 35-8)
Cyclosporine has a very selective inhibitory effect on T helper cells, suppressing the early cellular
response to antigenic stimuli. The drug binds to a T-helper cell cytoplasmic cyclophilin and the complex
then binds to calcineurin (a phosphatase) and inhibits its action. This inhibition is thought to prevent
activation of nuclear factors involved in the gene transcription of interleukin-2 and other cytokines. Since
interleukin-2 is needed for T-cell activation and proliferation, these T cell functions are suppressed.
A, B, D, E) These cells are not direct targets for cyclosporine.Rate this question:
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- 11.
A 45-year-old man, who had received an heart transplant one month ago, was in the hospital and scheduled for endomyocardial biopsy. The patients complained of a tingling sensation in his hands and peripheral edema. Significant blood test results were: potassium 6.1 mEq/L, creatinine 3.8 mg/dL, BUN 42 mg/dL Current medications included cyclosporine, prednisone, azathioprine, theophylline, diltiazem and famotidine. Biopsy results indicated no acute rejection. If the lab results were drug related, which of the following was the most likely causative agent?
- A.
Prednisone
- B.
Cyclosporine
- C.
Azathioprine
- D.
Theophylline
- E.
Diltiazem
Correct Answer
B. CyclosporineExplanation
Answer: B
(Hardman, pp 1469, Koda-Kimble, pp 35-14)
The lab exams strongly suggest that the patient is suffering from renal insufficiency. Nephrotoxicity is
the most common adverse effect of cyclosporine, occurring in up to 80% of treated patients. The
pathophysiology of this adverse effect is still uncertain.
A, C, D, E) These drugs have a negligible risk of nephrotoxicityRate this question:
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- 12.
A 34-year-old man, who underwent liver transplantation for advanced biliary cirrhosis, has been receiving immunosuppression treatment with prednisone and cyclosporine. In spite of the therapy a liver biopsy still showed rejection 14 days after surgery. Which of the following drugs could be substituted to cyclosporine to treat this case of cyclosporine resistant rejection?
- A.
Aldesleukin
- B.
Vinblastine
- C.
Tacrolimus
- D.
Fluorouracil
- E.
Paclitaxel
Correct Answer
C. TacrolimusExplanation
Answer: C
(Koda-Kimble, pp 35-35, Dipiro, pp 745)
Several patients who receive an initial immunosuppressant therapy with cyclosporine are converted to
tacrolimus ether because of persistent drug reactions or of a poor response, like in the present case.
Tacrolimus has a mechanism of action very close to that of cyclosporine. Nevertheless patient survival
rates exceeding 80% have been reported in liver transplant patients who were converted from
cyclosporine to tacrolimus because of failure of cyclosporine therapy.
A, B, D, E) These drugs are not immunosuppressants.Rate this question:
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- 13.
A 33-year old man with an end stage renal disease underwent a kidney transplant. The therapeutic management of the patient included an IV injection of azathioprine just before surgery. Which of the following statements best explains the most likely mechanism of action of the drug in this case?
- A.
Blockade of receptors of TNF-alpha
- B.
Inhibition of clonal expansion of T and B lymphocytes
- C.
Inhibition of antigen presentation by dendritic cells
- D.
Stimulation of genetic expression of interleukin 2
- E.
Stimulation of macrophage phagocytic activity
Correct Answer
B. Inhibition of clonal expansion of T and B lympHocytesExplanation
Answer: B
(Hardman, pp 1471, Katzung, pp 944)
Azathioprine is an immunosuppressant agent often used in organ transplantation to prevent rejection. It
is a prodrug that is converted in the body to mercaptopurine, an antimetabolite anticancer drug that
blocks purine synthesis. This leads to cytotoxicity mainly towards cells with a high turnover rate which
include T and B lymphocytes. The proliferation of these lymphocytes is inhibited and this explains why
most antimetabolite anticancer drugs do have immunosuppressant actions. Azathioprine, however,
appears to be a more effective immunosuppressant than mercaptopurine itself. The basis for this
superiority is unknown.
A) Azathioprine has no blocking activity on receptors of TNT-Alpha
C) Antigen presentation by different antigen presenting cells is an early step in the adaptive immune
response. This step is not inhibited by azathioprine.
D, E) These two actions would actually increase, not decrease, the immunological defense of the body.Rate this question:
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- 14.
A 44-year-old woman, who received a heart transplant 15 days ago, is now in the coronary unit. A blood exam reveals the following: RBC 4.1 x 10 / mm , WBC 6 3 1.2 x 103/mm, platelets 40,000/mm3. Which of the following drugs most likely caused these findings?
- A.
Cyclosporine
- B.
Dobutamine
- C.
Dopamine
- D.
Azathioprine
- E.
Fluorouracil
Correct Answer
D. AzathioprineExplanation
Answer: D
(Hardman, pp 1471, Koda-Kimble, pp 35-6)
The profound leukopenia and thrombocytopenia exhibited by the patient strongly suggest bone marrow
suppression. Transplanted patients always receive immunosuppressive therapy to prevent organ
rejection. Cyclosporine, azathioprine and a glucocorticoid are the drugs most frequently used for this
purpose. Azathioprine is a prodrug that is converted in the body to mercaptopurine, an antimetabolite
anticancer drug. It is therefore a cytotoxic agent that can cause significant myelosuppression.
A) Cyclosporine is the drug most frequently given for immunosuppression in transplanted patients, but it
does not cause myelosuppression.
B, C) These drugs are often given to heart transplanted patients to increase cardiac output and renal
blood flow but they do not cause myelosuppression
E) Fluorouracil is an anticancer drug that is not used for immunosuppression.Rate this question:
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- 15.
A 32-year-old man, who underwent renal transplant, showed signs of acute allograft rejection which was resistant to corticosteroid treatment. He was treated with muromonab CD3 that was able to reverse the rejection. Which of the following statements best explains the molecular mechanism of action of the drug in this case?
- A.
It inhibits antibody formation by plasma cells
- B.
It inhibits several enzymes involved in purine metabolism
- C.
It inhibits calcineurin enzyme in T cell cytoplasm
- D.
It stimulates the synthesis of interleukin-1 in T cells
- E.
It neutralize a surface protein receptor complex in T cells
Correct Answer
E. It neutralize a surface protein receptor complex in T cellsExplanation
Answer: E
(Hardman, pp 1474, Koda-Kimble, pp 35-9)
Muromonab-CD3 is a monoclonal antibody against CD3 molecules present on the surface of human
thymocytes and mature T cells. CD3 molecules are necessary for a signal to be transduced to the
cytoplasm after the T cell receptor binds to the antigen
The drug binds and neutralizes the CD3 protein receptor complex, so causing the death of T cells
Muromonab-CD3 is used in renal allograft rejection, especially when the rejection is resistant to
corticosteroid treatment.
A) Muromonab-CD3has negligible effects on B cells.
B) This is actually the mechanism of action of azathioprine
C) This is actually the mechanism of action of cyclosporine and tacrolimus.
D) Stimulation of the synthesis of interleukin -1 would cause an immunostimulant, not an
immunosuppressant ,effect.Rate this question:
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- 16.
A 27-year-old primipara delivered a baby boy at term. The woman was Rho(D) negative and her husband was Rho(D) positive. The woman received an IV injection of Rho(D) immune globulin just after the delivery. Which of the following statements best explains the mechanism of action of the Rho(D) immune globulin?
- A.
It prevents placental crossing of Rho(D) positive erythrocytes in subsequent pregnancies
- B.
It blocks the production of maternal antibodies against Rho(D) positive erythrocytes
- C.
It prevents the hemolytic disease of the mother in subsequent pregnancies
- D.
It blocks the production of fetal Rho(D) positive erythrocytes in subsequent pregnancies
- E.
It prevents the placental crossing of fetal Rho(D) antibodies in subsequent pregnancies
Correct Answer
B. It blocks the production of maternal antibodies against Rho(D) positive erythrocytesExplanation
Answer: B
(Katzung, pp 946, Koda-Kimble, pp 46-11)
Since the woman was Rho(D) negative and her husband was Rho(D) positive, the baby had 100%
chance (if the father was homozygous) or 50% chance (if the father was heterozygous) of being Rho(D)
positive. If a Rho(D) negative mother caries a Rho(D) positive fetus she will produce antibodies against
Rho(D) positive erythrocytes if these erythrocytes leak into the maternal circulation. This can occur
during pregnancy and the risk of this fetomaternal hemorrhage increases as the pregnancy progresses.
The risk is the highest during delivery. In subsequent pregnancies these maternal antibodies are
transferred to the fetus leading to the development of hemolytic disease in the new born
(erythroblastosis fetalis).
When the Rho(D) immune globulin is given to the mother within 72 hours after the delivery, it destroys
the Rho(D) positive fetal cells in the maternal bloodstream before she has an opportunity to make her
own antibodies, so preventing erythroblastosis fetalis in subsequent pregnancies. This is an example of
passive immunization.
A) Placental crossing of Rho(D) positive erythrocytes in subsequent pregnancies of course is not
prevented, and therefore the mother must receive the Rho(D) immune globulin after each delivery to
prevent sensitization (it should be remembered that .passive immunization lasts for the life time of the
administered antibodies. The half-life of Rho(D) immune globulin is 20-25 days).
C) The drug actually prevents the hemolytic disease of the newborn, not of the mother.
D) The production of fetal erythrocytes Rho(D) positive is genetically determined.
E) Rho(D) antibodies are produced by the mother, not by the fetus.Rate this question:
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- 17.
A 42-year-old woman undergoing heart transplant received mycophenolate mofetil, cyclosporine and prednisone before surgery. Which of the following statements best explains why mycophenolate mofetil is currently substituted for azathioprine to prevent rejection in solid organ transplantation ?
- A.
Its immunosuppressant activity is definitely superior to that of azathioprine
- B.
It has significantly less adverse effects than azathioprine
- C.
It has drastically reduced the risk of graft versus host disease
- D.
It selectively inhibits macrophage-mediated production of several interleukins
- E.
It selectively inhibits antigen recognition by antigen presenting cells
Correct Answer
B. It has significantly less adverse effects than azathioprineExplanation
Answer: B
(Hardman, pp 1471, Koda-Kimble, pp 35-7)
Mycophenolate mofetil is a prodrug which is biotransformed into mycophenolic acid.
This active metabolite inhibits inosine monophosphate dehydrogenase, an enzyme involved in the de
novo pathway of purine biosynthesis. However, unlike azathioprine, it does not inhibit enzymes involved
in the salvage pathway of purine or pyrimidine biosynthesis and, therefore, it selectively inhibit the
proliferation of lymphocytes (including B and T lymphocytes) because these cells lack the enzymes of
the alternative salvage pathway. Because of this, mycophenolate mofetil is cytotoxic only for
lymphocytes, whereas azathioprine is cytotoxic for all rapidly growing cells. This explains why the drug
has significantly less adverse effects than azathioprine.
A) The immunosuppressant activity of mycophenolate and azathioprine is roughly the same since both
drugs are able to kill B and T lymphocytes.
C) Graft versus host disease is a disease that occurs after stem cell transplantation, not after solid organ
transplantation.
D) Mycophenolate mofetil has negligible effects on macrophages since these cells can utilize the
salvage pathway for purine biosynthesis.
E) Mycophenolate mofetil has no effect on antigen presenting cells.Rate this question:
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- 18.
A 53-year-old man presented with complains of enlarging, painful lymph node in his groin. One year before his admission he had undergone surgical resection of a stage II malignant melanoma. A lymph node biopsy confirmed recurrence of malignant melanoma. The patient started a course of chemotherapy which included the IV administration of aldesleukin, a recombinant formulation of interleukin-2. Which of the following statements best explains the mechanism of action of this drug?
- A.
It induces proliferation and differentiation of B and T lymphocytes
- B.
It inhibits macrophage phagocytic activity
- C.
It inhibits antigen presentation by dendritic cells
- D.
It decreases the synthesis of calcineurin
- E.
It inhibits the activity of natural killer cells
Correct Answer
A. It induces proliferation and differentiation of B and T lympHocytesExplanation
Answer: A
(Hardman, pp 1478, Craig, pp 652)
Aldesleukin is an immunostimulant drug with a mechanism of action essentially identical to that of
interleukin-2. Aldesleukin activates interleukin-2 receptors expressed on T helper cells and stimulates a
cytokine cascade involving various interferons, interleukins and tumor necrosis factors. In this way it
induces proliferation of B and T cells (including cytotoxic T cells) and activation of natural killer cells and
lymphokine-activated killer cells. The drug is indicated for the adjunctive treatment of renal cell
carcinoma and malignant melanoma. The mechanism of antitumor activity is unknown but is probably
related to the activation of cytotoxic T cells. Aldesleukin is associated with serious cardiovascular, renal
and CNS toxicity and therefore extensive monitoring is required during therapy.
B, C, D, E) All these actions would lead to immunosuppressant, not immunostimulant, effects.Rate this question:
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- 19.
A 42-year-old woman presented to her ophthalmologist because of loss of central vision and pain on movement of her left eye. She reported that in the past she had had recurrent episodes of weakness and abnormal sensations in her arms and legs. The patient was referred to the neurologic clinic where labs exams and brain MRI confirmed the diagnosis of multiple sclerosis. The patient was prescribed a supportive therapy which included a recombinant cytokine endowed with immunostimulant properties. Which of the following drugs was most likely administered?
- A.
Trastuzumab
- B.
Infliximab
- C.
Interferon beta-1b
- D.
Prednisone
- E.
Tacrolimus
Correct Answer
C. Interferon beta-1bExplanation
Answer: C
( Dipiro, pp 1023, Lane pp 1476)
Interferon beta-1b is a cytokine produced by various cells including fibroblasts and macrophages. Like
other interferons it has antiviral, immunomodulating and antiproliferative activities. Interferon beta-1b
was the first agent shown to have an effect on the course of multiple sclerosis. The exact mechanism of
its action is still unknown but it is likely related to its immunomodulating properties, including the down
regulation of the expression of class II major histocompatibility complex and of interferon gamma. It is
thought that interferon gamma is a major factor responsible for triggering the autoimmune reaction
leading to multiple sclerosis. It stimulates cytotoxic T cells and induces macrophages to produce
proteinases that degrade the myelin sheath around the spinal cord.
A, B, D, E) These drugs are not recombinant cytokines.Rate this question:
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- 20.
The immunosuppressive effect of glucocorticoids seems mainly related to which of the following mechanisms of action? (Check all that apply)
- A.
Inhibition of catabolism of IgG antibodies
- B.
Inhibition of macrophage-mediated production of interleukin 1
- C.
Activation of several immunophilins
- D.
Early activation of T lymphocytes
- E.
Activation of phospholipase A2
- F.
Inhibition of T cell-mediated production of interleukin 2
- G.
Direct lympholythic effect on cytotoxic T cells
Correct Answer(s)
B. Inhibition of macropHage-mediated production of interleukin 1
F. Inhibition of T cell-mediated production of interleukin 2
G. Direct lympHolythic effect on cytotoxic T cellsExplanation
Answer: BFG
(Hardman, pp 1661, Koda-Kimble, pp 35-7)
Most actions of glucocorticoids on leucocytes and macrophages can impair immunity. Especially
important in this regard are:
-The inhibition of macrophage-mediated production of interleukin-1 and interleukin-6 (this inhibition in
turn decreases T cells activation and impairs B cell proliferation).
-The inhibition of T cell-mediated production of interleukin-2 (this inhibition in turn decreases T cells
proliferation and impairs the activation of NK cells).
-The direct lympholythic effect on certain subset of T cells (including cytotoxic T cells)
The inhibition of other interleukins by glucocorticoids (IL-6, IL-12) also impairs immunity.
The antiinflammatory effect of glucocorticoids (due to decreased synthesis of prostaglandins,
leukotrienes, PAF, TNF, histamine, kinins and interferon gamma) also exerts an indirect
immunosuppressant effect, since it modifies tissue injury from immune responses.
A) Glucocorticoids actually stimulate the catabolism of IgG.
C, D) These actions would stimulate, not inhibit, the immune response.
E) Glucocorticoids actually inhibit phospholipase A2.Rate this question:
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