CCTC Transplant Immunology and Pharmacology 2 — Questions and Answers
Question 1: Which cytokine is primarily responsible for driving the differentiation of naive CD4+ T cells into Th17 cells?
- IL-2
- IL-4
- TGF-β combined with IL-6 (Correct answer)
- IFN-γ
Correct answer: TGF-β combined with IL-6
TGF-β combined with IL-6 drives naive CD4+ T cells toward the Th17 lineage, which produces IL-17 and contributes to certain rejection pathways.
Question 2: A transplant recipient on tacrolimus develops new-onset diabetes mellitus. What is the most likely mechanism?
- Direct pancreatic beta-cell toxicity reducing insulin secretion (Correct answer)
- Increased hepatic gluconeogenesis via calcineurin inhibition
- Autoimmune destruction of islet cells
- Corticosteroid-induced peripheral insulin resistance only
Correct answer: Direct pancreatic beta-cell toxicity reducing insulin secretion
Tacrolimus causes direct pancreatic beta-cell toxicity that impairs insulin secretion, leading to post-transplant diabetes mellitus (PTDM).
Question 3: What is the mechanism by which belatacept prevents T-cell activation compared to calcineurin inhibitors?
- It blocks IL-2 receptor signaling
- It inhibits the CD28-B7 costimulatory pathway (Correct answer)
- It prevents mTOR-mediated proliferation
- It depletes circulating T lymphocytes
Correct answer: It inhibits the CD28-B7 costimulatory pathway
Belatacept is a CTLA4-Ig fusion protein that blocks CD28-B7 costimulation, preventing the second signal required for full T-cell activation.
Question 4: Which HLA mismatch is most strongly associated with hyperacute rejection?
- HLA-A mismatch
- HLA-DR mismatch
- Preformed donor-specific antibodies against HLA class I (Correct answer)
- HLA-DQ mismatch in a sensitized recipient
Correct answer: Preformed donor-specific antibodies against HLA class I
Preformed donor-specific antibodies (DSAs) against HLA class I antigens bind the graft endothelium immediately upon reperfusion, triggering complement activation and hyperacute rejection.
Question 5: A kidney transplant patient on mycophenolate mofetil (MMF) is started on ciprofloxacin. Which pharmacokinetic interaction is most concerning?
- Ciprofloxacin increases MMF levels by inhibiting CYP3A4
- Ciprofloxacin reduces enterohepatic recirculation of MPA, lowering drug exposure (Correct answer)
- Ciprofloxacin competes with MMF for renal tubular secretion
- No clinically significant interaction exists between these drugs
Correct answer: Ciprofloxacin reduces enterohepatic recirculation of MPA, lowering drug exposure
Fluoroquinolones alter gut flora that normally hydrolyze MPA-glucuronide conjugates, reducing enterohepatic recirculation and lowering mycophenolic acid (MPA) exposure by up to 30%.
Question 6: Which complement pathway is primarily activated by antibody-mediated rejection?
- Alternative pathway via spontaneous C3 hydrolysis
- Lectin pathway via mannose-binding lectin
- Classical pathway via C1q binding to antigen-antibody complexes (Correct answer)
- Terminal pathway activation independent of upstream cascades
Correct answer: Classical pathway via C1q binding to antigen-antibody complexes
In antibody-mediated rejection, donor-specific antibodies form immune complexes on graft endothelium that bind C1q, activating the classical complement pathway.
Question 7: What is the primary reason sirolimus (rapamycin) is often avoided in the early post-transplant period for kidney recipients?
- It causes severe calcineurin inhibitor toxicity when combined
- It impairs wound healing and increases risk of lymphocele formation (Correct answer)
- It directly nephrotoxic in the first month
- It dramatically increases rejection rates compared to tacrolimus
Correct answer: It impairs wound healing and increases risk of lymphocele formation
Sirolimus inhibits mTOR-dependent cell proliferation required for wound healing, increasing rates of wound complications and lymphocele formation in the early post-transplant period.
CCTC Transplant Immunology and Pharmacology 2
Which cytokine is primarily responsible for driving the differentiation of naive CD4+ T cells into Th17 cells?