USMLE Step 1 Quiz
Practice Transplantation Immunology in USMLE Step 1 with focused quiz questions that help you check what you know, review explanations, and build confidence with test-style prompts.
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A 35-year-old man has fever and rising creatinine 2 weeks after kidney transplant while on tacrolimus, mycophenolate, and prednisone; biopsy shows interstitial lymphocytes with tubulitis. Which of the following is the best initial treatment for this patient?
This quiz focuses on Transplantation Immunology, giving you a quick way to practice the rules, question types, and explanations that matter most for USMLE Step 1.
Try each quiz question before looking at the correct answer. Use the explanations to review missed ideas, then come back to similar questions until the pattern feels familiar.
A 35-year-old man has fever and rising creatinine 2 weeks after kidney transplant while on tacrolimus, mycophenolate, and prednisone; biopsy shows interstitial lymphocytes with tubulitis. Which of the following is the best initial treatment for this patient?
Explanation: This question tests transplantation immunology concepts, focusing on rejection mechanisms and management (USMLE Step 1). Transplantation immunology involves understanding graft rejection types: hyperacute, acute, and chronic, each requiring different management. In this vignette, the patient's symptoms and lab results suggest acute cellular rejection, demonstrated by fever, rising creatinine, and biopsy showing lymphocytes with tubulitis. Choice A is correct because it reflects the appropriate initial treatment with high-dose steroids based on current clinical guidelines. Choice B is incorrect due to it being for antibody-mediated rejection, such as misinterpretation of biopsy as AMR. Teaching strategies include reviewing types of rejection and corresponding management protocols, emphasizing the importance of timely intervention and proper use of immunosuppressive therapy.
A 60-year-old woman has slowly worsening cholestatic labs 5 years after liver transplant; biopsy shows fibrosis and narrowed bile ducts; she takes tacrolimus. Which of the following is the most likely cause of the observed symptoms?
Explanation: This question tests transplantation immunology concepts, focusing on rejection mechanisms and management (USMLE Step 1). Transplantation immunology involves understanding graft rejection types: hyperacute, acute, and chronic, each requiring different management. In this vignette, the patient's symptoms and lab results suggest chronic rejection, demonstrated by slowly worsening cholestatic labs and biopsy showing fibrosis. Choice A is correct because it reflects the vascular and biliary injury of chronic rejection based on current clinical guidelines. Choice C is incorrect due to acute rejection typically occurring early, not at 5 years. Teaching strategies include reviewing types of rejection and corresponding management protocols, emphasizing the importance of timely intervention and proper use of immunosuppressive therapy.
A 40-year-old man develops diffuse maculopapular rash and watery diarrhea 3 weeks after allogeneic bone marrow transplant; bilirubin is elevated and biopsy shows apoptotic bodies; he receives tacrolimus prophylaxis. What is the most likely cause of the observed symptoms?
Explanation: This question tests transplantation immunology concepts, focusing on rejection mechanisms and management (USMLE Step 1). Transplantation immunology involves understanding graft rejection types: hyperacute, acute, and chronic, each requiring different management. In this vignette, the patient's symptoms and lab results suggest acute GVHD, demonstrated by rash, diarrhea, elevated bilirubin, and apoptotic bodies post-BMT. Choice A is correct because it reflects the donor T-cell attack in GVHD based on current clinical guidelines. Choice B is incorrect due to describing host antibodies against graft, not GVHD. Teaching strategies include reviewing types of rejection and corresponding management protocols, emphasizing the importance of timely intervention and proper use of immunosuppressive therapy. Distinguishing GVHD from host-versus-graft rejection is key in bone marrow transplant cases.
A 40-year-old man has rash and profuse diarrhea 3 weeks after allogeneic bone marrow transplant; labs show elevated bilirubin and low albumin; he takes tacrolimus and methotrexate. Which of the following mechanisms is most likely responsible for the patient's condition?
Explanation: This question tests transplantation immunology concepts, focusing on rejection mechanisms and management (USMLE Step 1). Transplantation immunology involves understanding graft rejection types: hyperacute, acute, and chronic, each requiring different management. In this vignette, the patient's symptoms and lab results suggest acute GVHD, demonstrated by rash, diarrhea, elevated bilirubin, and low albumin post-BMT. Choice A is correct because it reflects the donor T-cell mechanism in GVHD based on current clinical guidelines. Choice B is incorrect due to describing host T cells against graft, opposite of GVHD. Teaching strategies include reviewing types of rejection and corresponding management protocols, emphasizing the importance of timely intervention and proper use of immunosuppressive therapy.
A 60-year-old woman has gradual loss of graft function 5 years after liver transplant; she reports fatigue and pruritus; alkaline phosphatase is elevated and biopsy shows fibrosis with bile duct loss despite tacrolimus. Which mechanism is most likely responsible for her condition?
Explanation: This question tests transplantation immunology concepts, focusing on rejection mechanisms and management (USMLE Step 1). Transplantation immunology involves understanding graft rejection types: hyperacute, acute, and chronic, each requiring different management. In this vignette, the patient's symptoms and lab results suggest chronic rejection, demonstrated by gradual loss, fatigue, pruritus, elevated alk phos, and biopsy fibrosis. Choice A is correct because it reflects the chronic immune injury mechanism based on current clinical guidelines. Choice B is incorrect due to describing hyperacute rejection, not gradual onset. Teaching strategies include reviewing types of rejection and corresponding management protocols, emphasizing the importance of timely intervention and proper use of immunosuppressive therapy.
A 35-year-old man has fever and graft tenderness 2 weeks after kidney transplant; creatinine is 3.0 mg/dL and Doppler is normal; he takes tacrolimus and mycophenolate. What is the most appropriate next step in management?
Explanation: This question tests transplantation immunology concepts, focusing on rejection mechanisms and management (USMLE Step 1). Transplantation immunology involves understanding graft rejection types: hyperacute, acute, and chronic, each requiring different management. In this vignette, the patient's symptoms and lab results suggest acute rejection, demonstrated by fever, graft tenderness, and rising creatinine with normal Doppler. Choice C is correct because it reflects the appropriate next step of biopsy to confirm rejection type based on current clinical guidelines. Choice A is incorrect due to presuming infection without confirmation, such as misinterpretation of symptoms as solely infectious. Teaching strategies include reviewing types of rejection and corresponding management protocols, emphasizing the importance of timely intervention and proper use of immunosuppressive therapy.
A 40-year-old man develops rash and diarrhea after allogeneic bone marrow transplant; stool studies are negative and skin biopsy supports GVHD; he is on tacrolimus prophylaxis. Which of the following is the best initial treatment for this patient?
Explanation: This question tests transplantation immunology concepts, focusing on rejection mechanisms and management (USMLE Step 1). Transplantation immunology involves understanding graft rejection types: hyperacute, acute, and chronic, each requiring different management. In this vignette, the patient's symptoms and lab results suggest acute GVHD, demonstrated by rash, diarrhea, and supportive biopsy post-BMT. Choice A is correct because it reflects the initial treatment with high-dose steroids for GVHD based on current clinical guidelines. Choice B is incorrect due to plasmapheresis being for antibody-mediated issues, not GVHD. Teaching strategies include reviewing types of rejection and corresponding management protocols, emphasizing the importance of timely intervention and proper use of immunosuppressive therapy.
A 50-year-old woman is 1 year after heart transplant with stable graft function; she takes tacrolimus and mycophenolate and has normal labs. What is the most appropriate next step in management?
Explanation: This question tests transplantation immunology concepts, focusing on rejection mechanisms and management (USMLE Step 1). Transplantation immunology involves understanding graft rejection types: hyperacute, acute, and chronic, each requiring different management. In this vignette, the patient's symptoms and lab results suggest stable graft function, demonstrated by normal labs 1 year post-heart transplant. Choice A is correct because it reflects continuing immunosuppression with surveillance based on current clinical guidelines. Choice D is incorrect due to steroids not being indicated without rejection signs. Teaching strategies include reviewing types of rejection and corresponding management protocols, emphasizing the importance of timely intervention and proper use of immunosuppressive therapy.
A 50-year-old woman is 1 year after heart transplant on tacrolimus and mycophenolate; she is asymptomatic with stable echocardiogram and normal troponin. Which of the following mechanisms is most likely responsible for the patient's condition?
Explanation: This question tests transplantation immunology concepts, focusing on rejection mechanisms and management (USMLE Step 1). Transplantation immunology involves understanding graft rejection types: hyperacute, acute, and chronic, each requiring different management. In this vignette, the patient's symptoms and lab results suggest stable graft function, demonstrated by asymptomatic status and normal tests 1 year post-heart transplant. Choice A is correct because it reflects the mechanism of tacrolimus in preventing rejection based on current clinical guidelines. Choice E is incorrect due to describing recipient T cells in acute rejection, not stability. Teaching strategies include reviewing types of rejection and corresponding management protocols, emphasizing the importance of timely intervention and proper use of immunosuppressive therapy.
A 45-year-old man with end-stage renal disease due to polycystic kidney disease receives a kidney from a deceased donor. The surgical procedure is uneventful. However, within minutes of re-establishing blood flow to the transplanted kidney, it becomes cyanotic and mottled, and urine output ceases. The organ is emergently removed.
The rapid failure of this graft is most likely mediated by which of the following immunologic components?
Explanation: This patient is experiencing hyperacute rejection, which occurs within minutes to hours after transplantation. It is a type II hypersensitivity reaction caused by pre-formed recipient antibodies (IgG or IgM) against donor ABO blood group or HLA antigens. These antibodies bind to the graft endothelium, activating complement and leading to widespread thrombosis, ischemia, and rapid graft failure.
A 52-year-old woman underwent a deceased-donor kidney transplant 3 weeks ago for diabetic nephropathy. She was discharged on a regimen of tacrolimus, mycophenolate mofetil, and prednisone. She now presents with fever, graft tenderness, and a rise in serum creatinine from 1.3 mg/dL to 3.5 mg/dL. A biopsy of the allograft is performed and shows a dense interstitial infiltrate composed predominantly of lymphocytes and macrophages.
The pathologic process in this patient's graft is primarily mediated by the activation of which of the following cells?
Explanation: The clinical presentation and histologic findings are classic for acute cellular rejection, the most common type of acute rejection. This process occurs weeks to months after transplantation and is a type IV hypersensitivity reaction. It is mediated by recipient CD8+ and CD4+ T-lymphocytes that recognize donor MHC molecules as foreign, leading to infiltration and destruction of the graft parenchyma.
A 60-year-old man who received a heart transplant 7 years ago presents for his annual follow-up. He reports progressively worsening dyspnea on exertion over the past year. An echocardiogram shows signs of diastolic dysfunction, and coronary angiography reveals diffuse, concentric narrowing of the coronary arteries. An endomyocardial biopsy shows interstitial fibrosis and myocyte atrophy.
Which of the following terms best describes the vascular pathology responsible for this patient's symptoms?
Explanation: This patient's presentation is characteristic of chronic rejection of a cardiac allograft. The key pathological process is graft vasculopathy, also known as accelerated graft atherosclerosis. It is characterized by diffuse, concentric intimal thickening of graft arteries, leading to luminal stenosis, ischemia, and ultimately graft failure. This is a slow, progressive process mediated by both cellular and humoral immune responses.
A 34-year-old man with acute myeloid leukemia undergoes an allogeneic hematopoietic stem cell transplant from an HLA-matched, unrelated donor. Four weeks later, he develops a diffuse maculopapular rash on his trunk, palms, and soles. He also complains of profuse, watery diarrhea and has elevated serum bilirubin and alkaline phosphatase levels.
This patient's condition is most likely caused by the activity of which of the following?
Explanation: This patient is presenting with classic signs of acute graft-versus-host disease (GVHD), a common complication of allogeneic stem cell transplantation. GVHD occurs when immunocompetent T-cells from the donor graft recognize the recipient's tissues as foreign and mount an inflammatory attack. The primary targets are the skin (rash), gastrointestinal tract (diarrhea), and liver (jaundice, elevated liver enzymes).
A 55-year-old man received a kidney transplant 1 year ago. His immunosuppressive regimen includes mycophenolate mofetil. His recent complete blood count shows a WBC count of 2,500/mm³, and he is advised to be cautious about infections.
Mycophenolate mofetil selectively inhibits the proliferation of which of the following cell types?
Explanation: Mycophenolate mofetil is a prodrug that is converted to mycophenolic acid (MPA). MPA is a potent, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme crucial for the de novo synthesis of guanine nucleotides. Lymphocytes are highly dependent on this de novo pathway for proliferation, whereas other cell types can use salvage pathways. This selectivity makes mycophenolate an effective anti-proliferative agent for lymphocytes. A major side effect is bone marrow suppression, particularly leukopenia.
A 29-year-old woman with end-stage renal disease receives a kidney transplant. Her post-transplant medication regimen includes sirolimus. In contrast to calcineurin inhibitors, this drug does not block the production of IL-2 but rather interferes with its downstream effects.
What is the primary mechanism of action of sirolimus?
Explanation: Sirolimus (rapamycin) is an mTOR inhibitor. It binds to FKBP-12, but unlike tacrolimus, this complex does not inhibit calcineurin. Instead, the sirolimus-FKBP-12 complex binds to and inhibits the mammalian target of rapamycin (mTOR), a serine/threonine kinase. mTOR is critical for signaling downstream of the IL-2 receptor, and its inhibition blocks the progression of T-cells from the G1 to the S phase of the cell cycle, thereby preventing their proliferation.
A 30-year-old man with type 1 diabetes and end-stage renal disease is being evaluated for a combined kidney-pancreas transplant. His sister is a potential living donor for the kidney. Tissue typing is performed on both the patient and his sister to determine compatibility and predict the risk of graft rejection.
Matching which of the following sets of gene products is most critical for long-term graft survival?
Explanation: The human leukocyte antigen (HLA) system, which encodes the major histocompatibility complex (MHC) proteins, is the most important factor in determining solid organ transplant compatibility. HLA molecules (Class I: HLA-A, B, C; Class II: HLA-DR, DQ, DP) present antigens to T-cells and are highly polymorphic. Mismatches in HLA, particularly HLA-A, HLA-B, and HLA-DR, are the primary drivers of T-cell-mediated rejection. While ABO matching is essential to prevent hyperacute rejection, long-term survival is most dependent on the degree of HLA matching.
A 41-year-old woman who received a kidney transplant 12 days ago presents with decreased urine output and an increase in her serum creatinine. An allograft biopsy is performed. Histology shows neutrophils in peritubular capillaries and evidence of endothelial injury. Immunofluorescence staining reveals linear deposition of C4d along the peritubular capillaries.
The presence of C4d in this context is a specific marker for which of the following processes?
Explanation: This patient's presentation and biopsy findings are characteristic of acute antibody-mediated (humoral) rejection. This process is caused by donor-specific antibodies (DSAs) that bind to donor HLA antigens on the graft endothelium. This binding activates the classical complement pathway, leading to the covalent deposition of the complement split product C4d on the endothelial surface. C4d is a stable marker of complement activation and is considered a hallmark of antibody-mediated rejection.
During an episode of acute cellular rejection in a kidney transplant recipient, cytotoxic T-lymphocytes (CTLs) play a crucial role in destroying graft cells. These CTLs recognize foreign antigens presented on the surface of the donor's parenchymal cells.
The donor antigens that are recognized by the recipient's cytotoxic T-lymphocytes are primarily presented by which of the following molecules on the surface of donor kidney cells?
Explanation: Acute cellular rejection is largely mediated by CD8+ cytotoxic T-lymphocytes (CTLs). These cells recognize foreign peptide antigens presented by MHC class I molecules. In the context of transplantation (direct allorecognition), the recipient's CD8+ T-cells directly recognize intact donor MHC class I molecules on the surface of graft cells as foreign. This interaction, along with costimulation, leads to the activation of CTLs, which then kill the graft cells via perforin/granzyme pathways. MHC class II molecules present antigens to CD4+ helper T-cells.
A 62-year-old woman is undergoing a kidney transplant from a deceased donor. As part of her induction immunosuppressive therapy, she receives a dose of basiliximab in the operating room. This agent is a monoclonal antibody designed to prevent acute rejection in the early post-transplant period.
What is the specific molecular target of basiliximab?
Explanation: Basiliximab is a monoclonal antibody that targets the alpha chain (CD25) of the IL-2 receptor. The CD25 subunit is highly expressed on activated T-lymphocytes. By blocking the IL-2 receptor, basiliximab prevents IL-2 from binding and signaling, which in turn inhibits the proliferation and activation of T-cells that are central to the acute rejection process. It is used as an induction agent to provide early, potent immunosuppression.
A 25-year-old woman receives a kidney transplant from her HLA-identical sister. Despite the perfect HLA match and standard immunosuppression, she experiences an episode of acute cellular rejection 3 months post-transplant. The rejection is successfully treated with pulse steroids.
The T-cell response in this patient is most likely directed against which of the following targets?
Explanation: Even with a perfect match for the major histocompatibility complex (MHC, encoded by HLA genes), rejection can still occur due to differences in other proteins known as minor histocompatibility antigens. These are polymorphic, non-MHC proteins that are processed into peptides and presented by MHC molecules on donor cells. If the recipient's T-cell repertoire has not been tolerized to these specific peptides (e.g., proteins encoded on the Y chromosome in a male donor to a female recipient), they can be recognized as foreign and trigger a rejection response.