Immunology Review Corner

Immunology Review Corner: Chapter 56 of the 6th edition of Middleton’s Allergy Principles and Practice, edited by N. Franklin Adkinson, et al.

Prepared by Dr. Thao N. Tran, Puget Sound Allergy, Asthma and Immunology, and Dr. Karla Lowe, Walter Reed Medical Center.

Chapter 56:  Immunomodulators

1. Which of the following statements best describes methotrexate’s (MTX) mechanism of action?
a. MTX binds to amino-imidazole-carboxy-amido-ribonucleotide (AICAR) transformylase, resulting in inhibition of adenosine release.
b. MTX activates thymidylate synthetase.
c. MTX binds to the active site of dihydrofolate reductase, blocking the reduction of folic acid.
d. MTX enhances the methylation of homocysteine to methionine.

2. Which of the following is considered a common adverse effect associated with methotrexate therapy?
a. Methotrexate pneumonitis
b. Alopecia
c. Myelosuppression
d. Oral ulcerations

3. Which of the following statements is correct about the use of methotrexate (MTX)?
a. MTX is considered a teratogen and is strictly contraindicated in pregnancy.
b. Folic acid, even at low dosages (e.g., 1 mg/day), can significantly decrease the efficacy of MTX.
c. Serum homocysteine levels often decrease during MTX therapy.
d. Monitoring of liver function is unnecessary since hepatic fibrosis is an uncommon adverse effect.

4. Which of the following is structurally distinct, but shares its mechanism of action with cyclosporine (CsA)?
a. Methotrexate
b. Tacrolimus
c. Rapamycin
d. Sirolimus

5. Which of the following statements about CsA is most accurate?
a. Typical intravenous doses of CsA are about 1/2 of the oral preparations of CsA.
b. CsA is hydrophilic.
c. CsA is primarily eliminated through renal metabolism.
d. Advancing age does not appear to be an important factor affecting the pharmacokinetics of CsA.

6. Which of the following immunologic effects is associated with the use of cyclosporine and tacrolimus?
a. Up-regulation of the expression of the high-affinity receptor for immunoglobulin E
b. Up-regulation of fas-ligand expression on mast cells and basophils, promoting their apoptosis
c. Block degranulation of mast cells and basophils
d. Increase the transcriptional activation of genes encoding IL-2, IL-3 and IL-5 in T-cells

7. Which of the following intervals represents the half-life of intravenous immunoglobulins (IVIG) in patients with humoral immunodeficiencies?
a. 10-14 days
b. 14-24 days
c. 26-35 days
d. 40-60 days

8. A patient complains of chills and flushing while receiving IVIG. Your next step is to:
a. Do a lumbar puncture to obtain cerebral spinal fluid to evaluate for aseptic meningitis.
b. Draw blood to check for immunoglobulin A deficiency.
c. Add methylprednisolone to the IVIG infusion.
d. Interrupt the infusion and resume at a slower rate.

9. CpG-rich (cytosine guanosine) immunostimulatory DNA sequences up-regulate the expression of which of the following cytokines?
a. IL-5
b. IL-10
c. IL-12
d. IL-13

10. CpG-rich (cytosine guanosine) immunostimulatory DNA sequences inhibit the production of which of the following cytokines?
a. IL-5
b. IL-18
c. Interferon-gamma
d. Interferon-alpha

11. Antisense oligodeoxynucleotide therapy prevents which of the following?
a. Transcription of DNA sequence into mRNA
b. Translation of the mRNA into a protein
c. Degradation of the mRNA sequence, consequently enhancing protein production
d. Unwinding of the DNA double helix by helicases

Answers
1. c, pages 957-958
2. d, page 958
3. a, page 959
4. b, page 960
5. d, page 960
6. c, pages 960-961
7. c, page 963
8. d, page 963
9. c, pages 966-967
10. a, page 967
11. b, pages 968-969