Transplant rejection mechanisms US Medical PG Practice Questions and MCQs
Practice US Medical PG questions for Transplant rejection mechanisms. These multiple choice questions (MCQs) cover important concepts and help you prepare for your exams.
Transplant rejection mechanisms US Medical PG Question 1: A 48-year-old Caucasian male suffering from ischemic heart disease is placed on a heart transplant list. Months later, he receives a heart from a matched donor. During an endomyocardial biopsy performed 3 weeks later, there is damage consistent with acute graft rejection. What is most likely evident on the endomyocardial biopsy?
- A. Granuloma
- B. Atherosclerosis
- C. Lymphocytic infiltrate (Correct Answer)
- D. Tissue necrosis
- E. Fibrosis
Transplant rejection mechanisms Explanation: ***Lymphocytic infiltrate***
- Acute graft rejection, especially within weeks of transplantation, is characterized by a **cellular immune response** dominated by **T lymphocytes** invading the allograft.
- These lymphocytes target donor major histocompatibility complex (MHC) molecules, leading to myocyte damage and dysfunction, which would be visible as a lymphocytic infiltrate on biopsy.
*Granuloma*
- Granulomas are aggregates of **macrophages**, often seen in chronic inflammatory conditions like tuberculosis, sarcoidosis, or fungal infections.
- They are not typical findings in the context of acute allograft rejection.
*Atherosclerosis*
- Atherosclerosis is a disease of large and medium-sized arteries characterized by **plaque formation**, primarily involving lipid deposition and inflammation, which narrows the arterial lumen.
- While it can affect transplanted organs (e.g., transplant vasculopathy, a form of chronic rejection), it is not the primary mechanism or histological finding in **acute cellular rejection** occurring three weeks post-transplant.
*Tissue necrosis*
- While acute rejection can *lead* to tissue necrosis due to severe inflammation and ischemia, necrosis alone is a broad term and not the most specific or defining histological feature of acute cellular rejection.
- The preceding and primary histopathological hallmark of acute cellular rejection is the **inflammatory cell infiltrate**, particularly lymphocytes attacking the graft.
*Fibrosis*
- Fibrosis, or the deposition of excess connective tissue, is a characteristic feature of **chronic rejection** or chronic injury processes.
- It indicates long-standing damage and repair, which is unlikely to be the predominant finding in a biopsy three weeks after transplantation indicative of acute rejection.
Transplant rejection mechanisms US Medical PG Question 2: Two weeks after undergoing allogeneic stem cell transplant for multiple myeloma, a 55-year-old man develops a severely pruritic rash, abdominal cramps, and profuse diarrhea. He appears lethargic. Physical examination shows yellow sclerae. There is a generalized maculopapular rash on his face, trunk, and lower extremities, and desquamation of both soles. His serum alanine aminotransferase is 115 U/L, serum aspartate aminotransferase is 97 U/L, and serum total bilirubin is 2.7 mg/dL. Which of the following is the most likely underlying cause of this patient's condition?
- A. Preformed cytotoxic anti-HLA antibodies
- B. Proliferating transplanted B cells
- C. Activated recipient T cells
- D. Donor T cells in the graft (Correct Answer)
- E. Newly formed anti-HLA antibodies
Transplant rejection mechanisms Explanation: ***Donor T cells in the graft***
- The symptoms (rash, GI symptoms, liver dysfunction) after an allogeneic stem cell transplant are classic signs of **acute graft-versus-host disease (GVHD)**. This condition occurs when **immunocompetent T cells from the donor graft** recognize the recipient's tissues as foreign and mount an immune attack.
- The rapid onset within two weeks post-transplant, elevated liver enzymes, jaundice (**yellow sclerae**, **elevated bilirubin**), severe pruritic rash, and GI symptoms (**abdominal cramps**, **profuse diarrhea**) are all characteristic manifestations of acute GVHD.
*Preformed cytotoxic anti-HLA antibodies*
- Preformed antibodies would typically cause **hyperacute rejection**, which occurs within minutes to hours of transplantation and involves widespread thrombosis and necrosis of the graft, not the systemic symptoms seen here.
- This reaction is mediated by the recipient's antibodies attacking donor antigens, leading to immediate graft failure.
*Proliferating transplanted B cells*
- Transplanted B cells can contribute to chronic GVHD through antibody production, but they are not the primary mediators of **acute GVHD**; acute GVHD is predominantly a T cell-mediated process.
- Proliferation of donor B cells is more commonly associated with post-transplant lymphoproliferative disorders (PTLD) or chronic GVHD, not the acute presentation described.
*Activated recipient T cells*
- In an allogeneic transplant, the recipient's immune system is usually heavily suppressed beforehand to prevent host-versus-graft rejection.
- If recipient T cells were active, they would primarily cause **rejection of the donor stem cells** (graft rejection), not the systemic symptoms of GVHD, which is a reaction of the donor cells against the host.
*Newly formed anti-HLA antibodies*
- Newly formed antibodies the recipient develops against the donor's HLA antigens would cause graft rejection, a process often delayed but not presenting as the widespread organ damage of acute GVHD.
- These antibodies are part of the host's attempt to reject the foreign graft, not the donor cells attacking the host.
Transplant rejection mechanisms US Medical PG Question 3: A researcher is studying the interactions between foreign antigens and human immune cells. She has isolated a line of lymphocytes that is known to bind antigen-presenting cells. From this cell line, she has isolated a cell surface protein that binds to class I major histocompatibility complex molecules. The continued activation, proliferation and survival of this specific cell line requires which of the following signaling molecules?
- A. Interleukin 1
- B. Interleukin 4
- C. Interleukin 2 (Correct Answer)
- D. Interleukin 8
- E. Interleukin 6
Transplant rejection mechanisms Explanation: ***Interleukin 2***
- The description of the lymphocyte binding the **constant portion of MHC class I** and requiring a signaling molecule for activation, proliferation, and survival points to a **T cell**.
- **Interleukin-2 (IL-2)** is a crucial cytokine for the proliferation, differentiation, and survival of T lymphocytes, acting in an autocrine or paracrine fashion after T cell activation.
*Interleukin 1*
- **Interleukin-1 (IL-1)** is primarily involved in inflammation and fever, produced by macrophages and other innate immune cells.
- While it can act as a costimulator for T cells, it is not the primary cytokine required for their sustained proliferation and survival after initial activation.
*Interleukin 4*
- **Interleukin-4 (IL-4)** is a key cytokine in humoral immunity, promoting B cell proliferation and differentiation, and inducing IgE class switching.
- It also plays a role in the differentiation of naive T cells into **Th2 cells**, but it is not the main cytokine for general T cell proliferation and survival.
*Interleukin 8*
- **Interleukin-8 (IL-8)**, also known as CXCL8, is a chemokine primarily responsible for attracting and activating neutrophils to sites of infection or inflammation.
- It does not have a direct role in the sustained proliferation and survival of activated lymphocytes.
*Interleukin 6*
- **Interleukin-6 (IL-6)** is a pleiotropic cytokine involved in acute phase reactions, hematopoiesis, and the immune response, particularly B cell differentiation and antibody production.
- Although it can influence T cell responses, it is not the primary growth factor for activated T lymphocytes as IL-2 is.
Transplant rejection mechanisms US Medical PG Question 4: A 10-year-old boy is presented to the hospital for a kidney transplant. In the operating room, the surgeon connects an allograft kidney renal artery to the aorta, and after a few moments, the kidney becomes cyanotic, edematous, and dusky with mottling. Which of the following in the recipient’s serum is responsible for this rejection?
- A. Macrophages
- B. CD4+ T cells
- C. IgA
- D. CD8+ T cells
- E. IgG (Correct Answer)
Transplant rejection mechanisms Explanation: ***IgG***
- The rapid onset of tissue necrosis and the immediate signs of rejection (cyanotic, edematous, dusky with mottling) upon vascular anastomosis are characteristic of **hyperacute rejection**.
- **Hyperacute rejection** is mediated by pre-formed recipient antibodies, primarily **IgG**, targeting donor ABO or HLA antigens. These antibodies activate complement, leading to rapid thrombosis and graft destruction.
*Macrophages*
- While macrophages play a role in chronic allograft rejection and delayed type hypersensitivity, they are not the primary mediators of **hyperacute rejection**.
- Their involvement typically presents with a more delayed and less immediate profound tissue damage than seen in this scenario.
*CD4+ T cells*
- **CD4+ T cells** are central to acute cellular rejection, which typically manifests days to weeks after transplantation.
- They are not responsible for the immediate, pre-formed antibody-mediated response seen in **hyperacute rejection**.
*IgA*
- **IgA antibodies** are primarily involved in mucosal immunity and are generally not implicated in solid organ transplant rejection, especially hyperacute rejection.
- While IgA can contribute to immune complex formation, it's not the main antibody type driving hyperacute allograft destruction.
*CD8+ T cells*
- **CD8+ T cells** (cytotoxic T lymphocytes) are key players in acute cellular rejection, mediating direct lysis of donor cells.
- Their action is part of a cellular immune response that takes days to weeks to develop and is not responsible for the immediate, antibody-mediated hyperacute rejection.
Transplant rejection mechanisms US Medical PG Question 5: A 43-year-old man presents to the emergency department following a work-related accident in which both arms were amputated. The patient lost a substantial amount of blood prior to arrival, and his bleeding is difficult to control due to arterial damage and wound contamination with debris. His complete blood count (CBC) is significant for a hemoglobin (Hgb) level of 5.3 g/dL. The trauma surgery resident initiates the massive transfusion protocol and orders whole blood, O negative, which she explains is the universal donor. The patient receives 6 units of O negative blood prior to admission. He subsequently develops fever, chills, hematuria, and pulmonary edema. Several hours later, the patient goes into hemodynamic shock requiring the emergent administration of vasopressors. Of the following options, which hypersensitivity reaction occurred?
- A. Type 1 hypersensitivity reaction
- B. Combined type 1 and type 4 hypersensitivity reaction
- C. Type 3 hypersensitivity reaction
- D. Type 2 hypersensitivity reaction (Correct Answer)
- E. Type 4 hypersensitivity reaction
Transplant rejection mechanisms Explanation: ***Type 2 hypersensitivity reaction***
- This scenario describes an **acute hemolytic transfusion reaction (AHTR)**, a classic example of a **Type II hypersensitivity reaction**. The recipient's antibodies (IgM) recognize and bind to antigens on the transfused red blood cells, leading to their destruction (hemolysis) via complement activation and cellular mechanisms.
- Symptoms like **fever, chills, hematuria (due to hemoglobinuria)**, and subsequent **shock** are characteristic of AHTR, even with O negative blood if other minor blood group antigens (e.g., Kell, Duffy) are incompatible or if the patient developed antibodies against these from previous transfusions or pregnancies.
*Type 1 hypersensitivity reaction*
- This type involves **IgE-mediated mast cell degranulation** and is associated with allergic reactions such as anaphylaxis, asthma, and hives.
- While anaphylaxis can cause shock, the systemic symptoms of **hemolysis and hematuria** are not characteristic of a Type 1 reaction.
*Combined type 1 and type 4 hypersensitivity reaction*
- This combination is uncommon in an acute transfusion setting and does not align with the presented symptoms.
- Type 1 is immediate allergic, and Type 4 is delayed cell-mediated, neither fully explaining the hemolytic features observed.
*Type 3 hypersensitivity reaction*
- This reaction involves the formation of **immune complexes** (antigen-antibody complexes) that deposit in tissues, leading to inflammation and damage (e.g., serum sickness, lupus nephritis).
- While immune complexes can cause systemic symptoms, the prominent hemolytic features and immediate presentation of a transfusion reaction are more indicative of Type 2.
*Type 4 hypersensitivity reaction*
- This is a **delayed type hypersensitivity** reaction mediated by **T cells**, taking 24-72 hours or longer to develop (e.g., contact dermatitis, tuberculin skin test).
- The acute onset of symptoms following transfusion makes a Type 4 reaction highly unlikely.
Transplant rejection mechanisms US Medical PG Question 6: A 48-year-old woman with alpha-1-antitrypsin deficiency undergoes a lung transplant. She tolerates the surgery well, but 3 years later develops inflammation and fibrosis in her terminal bronchioles. Which of the following best describes the pathophysiology of this patient's deterioration?
- A. Proliferation of grafted immunocompetent T cells
- B. Staphylococcus aureus pneumonia
- C. Lymphocytic inflammation of the bronchiolar wall (Correct Answer)
- D. T-cell mediated vascular damage
- E. Cytotoxic T lymphocytes reacting against foreign MHCs
Transplant rejection mechanisms Explanation: ***Lymphocytic inflammation of the bronchiolar wall***
- The development of inflammation and fibrosis in the **terminal bronchioles** years after a lung transplant, despite initial success, is highly suggestive of **chronic rejection**, also known as **bronchiolitis obliterans syndrome (BOS)**.
- Chronic rejection in lung transplantation is primarily characterized by **lymphocytic inflammation** leading to fibrosis and obliteration of the small airways, consistent with the patient's presentation.
*Proliferation of grafted immunocompetent T cells*
- This mechanism describes **graft-versus-host disease (GVHD)**, which occurs when immunocompetent cells in the graft attack recipient tissues.
- While GVHD can occur in organ transplantation, it is more commonly associated with **hematopoietic stem cell transplantation** and typically presents with a broader range of systemic symptoms, not primarily localized bronchiolar inflammation and fibrosis.
*Staphylococcus aureus pneumonia*
- **Bacterial pneumonia** would typically present with acute symptoms such as fever, cough with purulent sputum, and acute infiltrates on imaging.
- While infections are a risk post-transplant, a subacute process leading to **fibrosis** over 3 years is less typical for a bacterial pneumonia, which tends to be more acute and responsive to antibiotics.
*T-cell mediated vascular damage*
- This mechanism is characteristic of **acute humoral rejection** (antibody-mediated rejection) or some forms of acute cellular rejection, which often target the **vasculature** of the graft.
- While vascular damage can occur, the primary pathology described by inflammation and fibrosis in the **bronchioles** specifically points more towards chronic rejection affecting the airways themselves rather than predominantly the blood vessels.
*Cytotoxic T lymphocytes reacting against foreign MHCs*
- This describes the fundamental mechanism for **acute cellular rejection** in transplantation, where recipient T cells recognize foreign **MHC molecules** on donor cells.
- Acute cellular rejection typically occurs earlier (within weeks to months) post-transplant and involves prominent lymphocytic infiltrates, but the primary long-term fibrotic obstructive pathology of the bronchioles (BOS) is specifically the chronic form of T-cell mediated injury.
Transplant rejection mechanisms US Medical PG Question 7: Several weeks following a kidney transplantation, a 50-year-old Caucasian female presents for evaluation of the transplanted organ. Biopsy shows inflammation involving the endothelial cells of the kidney vasculature and the presence of mononuclear cells in the interstitium. Which cells are most likely responsible for this presentation?
- A. Recipient T-cells (Correct Answer)
- B. Donor antibodies
- C. Preformed recipient antibodies
- D. Deposition of antibody immune complexes
- E. Donor T-cells
Transplant rejection mechanisms Explanation: ***Recipient T-cells***
- The presence of **mononuclear cells in the interstitium** and inflammation of the **endothelial cells** several weeks post-transplantation is characteristic of **acute cellular rejection (ACR)**.
- ACR is primarily mediated by the recipient's **cytotoxic T-cells** recognizing donor major histocompatibility complex (MHC) molecules on graft cells.
*Donor antibodies*
- Donor antibodies are not responsible for rejection; rather, recipient antibodies (either preformed or newly formed) are implicated.
- The donor's immune system is suppressed or non-existent in the context of the transplanted organ itself after removal from the donor.
*Preformed recipient antibodies*
- While preformed recipient antibodies cause **hyperacute rejection**, which occurs minutes to hours after transplant, the presentation here is several weeks later.
- Hyperacute rejection involves widespread thrombosis and necrosis due to rapid antibody-mediated complement activation within the graft vasculature.
*Deposition of antibody immune complexes*
- Immune complex deposition typically causes a different pattern of injury (e.g., glomerulonephritis) and is not the primary mechanism of acute cellular rejection.
- This mechanism is more associated with certain autoimmune diseases or chronic transplant rejection, not the acute phase described.
*Donor T-cells*
- Donor T-cells would not be attacking the transplanted organ since it is *their own tissue*.
- Donor T-cells can cause **graft-versus-host disease (GVHD)** in bone marrow transplantation, where immunocompetent donor T-cells attack recipient tissues, but this is not applicable to solid organ transplantation.
Transplant rejection mechanisms US Medical PG Question 8: A 37-year-old man who had undergone liver transplantation 7 years ago, presents to the physician because of yellowish discoloration of the skin, sclera, and urine. He is on regular immunosuppressive therapy and is well-adherent to the treatment. He has no comorbidities and is not taking any other medication. He provides a history of similar episodes of yellowish skin discoloration 6–7 times since he underwent liver transplantation. Physical examination shows clinical jaundice. Laboratory studies show:
While blood cell (WBC) count 4,400/mm3
Hemoglobin 11.1 g/dL
Serum creatinine 0.9 mg/dL
Serum bilirubin (total) 44 mg/dL
Aspartate transaminase (AST) 1,111 U/L
Alanine transaminase (ALT) 671 U/L
Serum gamma-glutamyl transpeptidase 777 U/L
Alkaline phosphatase 888 U/L
Prothrombin time 17 seconds
A Doppler ultrasound shows significantly reduced blood flow into the transplanted liver. A biopsy of the transplanted liver is likely to show which of the following histological features?
- A. Ballooning degeneration of hepatocytes
- B. Normal architecture of bile ducts and hepatocytes
- C. Irregularly shaped nodules of regenerating hepatocytes with peripheral halo
- D. Broad fibrous septations with formation of micronodules
- E. Interstitial cellular infiltration with parenchymal fibrosis, obliterative arteritis (Correct Answer)
Transplant rejection mechanisms Explanation: ***Interstitial cellular infiltration with parenchymal fibrosis, obliterative arteritis***
- The patient's history of **repeated jaundice episodes** after liver transplantation, coupled with **elevated liver enzymes** and **significantly reduced transplanted liver blood flow** on Doppler, points to **chronic rejection**.
- **Chronic rejection** is histologically characterized by **interstitial cellular infiltration**, **parenchymal fibrosis**, and hallmark **obliterative arteritis**, which describes the progressive luminal narrowing and obliteration of hepatic arteries due to intimal proliferation.
*Ballooning degeneration of hepatocytes*
- This feature is typically associated with **acute hepatitis**, often viral or alcoholic, and indicates **hepatocyte swelling and necrosis**.
- While reflecting liver injury, it doesn't specifically point to **chronic rejection** in a transplanted liver with repeated episodes and vascular changes.
*Normal architecture of bile ducts and hepatocytes*
- This finding would suggest a **healthy liver** or a successful response to treatment, which contradicts the patient's symptoms of **jaundice**, highly elevated **liver enzymes**, and **reduced blood flow**.
- The presence of clinical symptoms and abnormal lab values rules out a normal liver architecture.
*Irregularly shaped nodules of regenerating hepatocytes with peripheral halo*
- This description is characteristic of **biliary hamartomas** (von Meyenburg complexes) or focal nodular hyperplasia, which are typically benign lesions and not indicative of the **severe liver injury** seen here.
- It does not align with the progressive nature of the patient's recurrent jaundice and vascular compromise identified.
*Broad fibrous septations with formation of micronodules*
- This histological pattern is typical of **cirrhosis**, a condition characterized by diffuse **fibrosis** and the formation of **regenerative nodules**, often resulting from chronic liver diseases like hepatitis or alcohol abuse.
- While fibrosis is part of chronic rejection, the description does not capture the specific **vascular and inflammatory changes** of **obliterative arteritis** that are central to chronic rejection.
Transplant rejection mechanisms US Medical PG Question 9: Two hours after undergoing allogeneic kidney transplantation for polycystic kidney disease, a 14-year-old girl has lower abdominal pain. Examination shows tenderness to palpation in the area the donor kidney was placed. Ultrasound of the donor kidney shows diffuse tissue edema. Serum creatinine begins to increase and dialysis is initiated. Which of the following is the most likely cause of this patient's symptoms?
- A. Preformed antibodies against class I HLA molecules (Correct Answer)
- B. Immune complex deposition in donor tissue
- C. T-lymphocyte activation by donor HLA peptides
- D. Irreversible intimal fibrosis and obstruction of vessels
- E. Proliferation of donor T lymphocytes
Transplant rejection mechanisms Explanation: ***Preformed antibodies against class I HLA molecules***
- This scenario describes **hyperacute rejection**, a rapid and severe immune response occurring minutes to hours post-transplant.
- It is mediated by **preformed antibodies** (often anti-HLA antibodies) in the recipient's circulation that bind to donor antigens, leading to complement activation, endothelial damage, and graft thrombosis.
*Immune complex deposition in donor tissue*
- This mechanism is characteristic of **Type III hypersensitivity** reactions, which are not typically involved in hyperacute rejection.
- Immune complex deposition is more common in conditions like **lupus nephritis** or **post-streptococcal glomerulonephritis**, not immediate graft failure.
*T-lymphocyte activation by donor HLA peptides*
- This describes the mechanism of **acute cellular rejection**, which is mediated by host T-lymphocytes recognizing donor HLA antigens.
- Acute rejection typically occurs days to weeks or months after transplantation, not within hours.
*Irreversible intimal fibrosis and obstruction of vessels*
- This process is characteristic of **chronic rejection**, which develops months to years after transplantation.
- Chronic rejection is a slow, progressive decline in graft function due to vascular damage, fibrosis, and ultimately graft failure.
*Proliferation of donor T lymphocytes*
- Proliferation of donor T lymphocytes is not a mechanism of transplant rejection but rather relevant to **graft-versus-host disease (GVHD)**.
- GVHD occurs when immunocompetent T-cells in the donor tissue (e.g., bone marrow transplant) attack recipient tissues.
Transplant rejection mechanisms US Medical PG Question 10: A 54-year-old man comes to the physician because of a cough with blood-tinged sputum for 1 week. He also reports fever and a 5-kg (11 lb) weight loss during the past 2 months. Over the past year, he has had 4 episodes of sinusitis. Physical examination shows palpable nonblanching skin lesions over the hands and feet. Examination of the nasal cavity shows ulceration of the nasopharyngeal mucosa and a depressed nasal bridge. Oral examination shows a painful erythematous gingival enlargement that bleeds easily on contact. Which of the following is the most likely cause of the patient's symptoms?
- A. Metalloprotease enzyme deficiency
- B. Malignant myeloid cell proliferation
- C. Arteriovenous malformation
- D. Immune complex deposition
- E. Neutrophil-mediated damage (Correct Answer)
Transplant rejection mechanisms Explanation: ***Neutrophil-mediated damage***
- The constellation of **sinusitis**, **pulmonary symptoms** (cough with blood-tinged sputum), **renal involvement** (indicated by systemic symptoms and often associated with microhematuria in this condition), and **skin lesions (palpable purpura)**, along with **nasal ulceration**, a **depressed nasal bridge**, and **gingival enlargement**, is highly characteristic of **Granulomatosis with Polyangiitis (GPA)**.
- GPA is an **ANCA-associated vasculitis** characterized by **necrotizing granulomatous inflammation** and **vasculitis** of small to medium-sized vessels, primarily driven by **neutrophil activation** and subsequent tissue damage.
*Metalloprotease enzyme deficiency*
- This description commonly refers to conditions like **alpha-1 antitrypsin deficiency**, which primarily causes **emphysema** and liver disease, not the widespread vasculitic manifestations seen here.
- It does not explain the diverse multi-organ involvement including skin, ENT, and likely renal symptoms.
*Malignant myeloid cell proliferation*
- This would suggest conditions like **leukemia** or **myelodysplastic syndromes**, which present with altered blood counts, fatigue, infections, and bleeding, but typically not this specific pattern of vasculitis and granulomatous inflammation.
- While constitutional symptoms like weight loss can occur, the localized findings like depressed nasal bridge and gingival enlargement are not characteristic.
*Arteriovenous malformation*
- An **arteriovenous malformation (AVM)** is an abnormal connection between arteries and veins; depending on its location, it can cause bleeding (e.g., hemoptysis if pulmonary) or neurological symptoms if cerebral.
- However, AVMs do not explain the systemic inflammatory symptoms, skin lesions, sinusitis, depressed nasal bridge, or gingival changes.
*Immune complex deposition*
- **Immune complex vasculitis** (e.g., IgA vasculitis, cryoglobulinemic vasculitis) often presents with palpable purpura and can affect kidneys and GI tract.
- However, the prominent **granulomatous inflammation** causing **nasal ulceration** and **depressed nasal bridge**, and the specific type of **pulmonary-renal syndrome** seen in GPA, are more indicative of **ANCA-mediated neutrophil damage** rather than immune complex deposition.
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