CCTC Transplant Immunology and Pharmacology 5 â Questions and Answers
Question 1: Which of the following best explains why ABO blood group compatibility is critical in solid organ transplantation?
- ABO antigens are expressed only on red blood cells and not relevant to organ transplant
- ABO antigens expressed on vascular endothelium are targeted by naturally occurring isohemagglutinins causing hyperacute rejection (Correct answer)
- ABO incompatibility triggers only T-cellâmediated rejection, which can be easily treated
- ABO matching is required only for liver but not kidney transplants
Correct answer: ABO antigens expressed on vascular endothelium are targeted by naturally occurring isohemagglutinins causing hyperacute rejection
ABO antigens are expressed on graft vascular endothelium, and preformed naturally occurring IgM isohemagglutinins cause immediate complement activation and hyperacute rejection in ABO-incompatible transplants.
Question 2: A transplant coordinator is counseling a patient about the long-term risks of calcineurin inhibitor therapy. Which of the following is a well-established chronic complication?
- Progressive pulmonary fibrosis
- Chronic allograft nephrotoxicity from afferent arteriolar vasoconstriction (Correct answer)
- Autoimmune hemolytic anemia
- Hypokalemia and metabolic alkalosis
Correct answer: Chronic allograft nephrotoxicity from afferent arteriolar vasoconstriction
Chronic CNI nephrotoxicity results from sustained afferent arteriolar vasoconstriction, causing ischemic injury and progressive interstitial fibrosis/tubular atrophy in both native and transplanted kidneys.
Question 3: What is the significance of panel reactive antibody (PRA) percentage in transplant candidate evaluation?
- It measures the candidate's overall immune competence
- It reflects the breadth of HLA sensitization, predicting difficulty finding a compatible donor (Correct answer)
- It determines ABO compatibility with potential donors
- It measures current calcineurin inhibitor levels in sensitized patients
Correct answer: It reflects the breadth of HLA sensitization, predicting difficulty finding a compatible donor
PRA (or calculated PRA, cPRA) reflects the percentage of donors against whom a candidate has preformed HLA antibodies, directly predicting wait time and crossmatch failure probability.
Question 4: Which immunologic mechanism primarily mediates chronic allograft vasculopathy (CAV) in heart transplant recipients?
- Ischemia-reperfusion injury causing direct myocyte necrosis
- Chronic alloimmune injury driven by both cellular and humoral responses causing intimal proliferation (Correct answer)
- Viral infection with CMV causing direct endothelial damage only
- Calcineurin inhibitorâinduced direct coronary artery spasm
Correct answer: Chronic alloimmune injury driven by both cellular and humoral responses causing intimal proliferation
CAV results from ongoing alloimmune injuryâboth T-cell mediated and antibody-mediatedâstimulating smooth muscle proliferation and intimal hyperplasia throughout the coronary tree.
Question 5: A liver transplant coordinator notes that a patient's tacrolimus trough has dropped from 8 ng/mL to 3 ng/mL after starting rifampin for tuberculosis. What is the mechanism?
- Rifampin chelates tacrolimus in the GI tract, reducing absorption
- Rifampin is a potent CYP3A4 and P-glycoprotein inducer, accelerating tacrolimus metabolism (Correct answer)
- Rifampin competes with tacrolimus for protein binding, increasing free drug clearance
- Rifampin inhibits FKBP12, preventing tacrolimus from binding its target
Correct answer: Rifampin is a potent CYP3A4 and P-glycoprotein inducer, accelerating tacrolimus metabolism
Rifampin potently induces CYP3A4 and P-glycoprotein, dramatically accelerating tacrolimus hepatic metabolism and intestinal efflux, often requiring 3â5 fold dose increases.
Question 6: What cellular subset is responsible for 'linked suppression' that may contribute to transplant tolerance across allogeneic barriers?
- CD8+ effector memory T cells
- Natural killer cells expressing inhibitory receptors
- FoxP3+ regulatory T cells that can suppress third-party responses linked to the original alloantigen (Correct answer)
- Plasmacytoid dendritic cells producing type I interferons
Correct answer: FoxP3+ regulatory T cells that can suppress third-party responses linked to the original alloantigen
Linked suppression occurs when Tregs induced by one alloantigen can suppress bystander responses to other antigens presented on the same APC, facilitating broader tolerogenic states.
Question 7: Which of the following calcineurin inhibitor side effects is most specific to cyclosporine compared to tacrolimus?
- Post-transplant diabetes mellitus
- Neurotoxicity with tremor
- Gingival hyperplasia and hirsutism (Correct answer)
- Nephrotoxicity via afferent arteriolar vasoconstriction
Correct answer: Gingival hyperplasia and hirsutism
Gingival hyperplasia and hirsutism are characteristic cosmetic side effects of cyclosporine that are rarely seen with tacrolimus, while PTDM and neurotoxicity are more associated with tacrolimus.
CCTC Transplant Immunology and Pharmacology 5
Which of the following best explains why ABO blood group compatibility is critical in solid organ transplantation?