questions 9

Transplant

Topic updated on 04/14/17 3:52pm

Graft types
  • Autograft 
    • moved from one location to another in self
      • only type that does not require immunosuppresants to prevent rejection
        • e.g. skin graft, vessel graft
  • Isograft/Syngenic graft
    • from genetically identical source
    • although same genotype, different MHC recombinations
      • e.g. monozygotic twin
  • Allograft
    • from nonidentical/genetically different individual of the same species
      • e.g. blood transfusion from blood bank
  • Xenograft
    • from different species
      • e.g. porcine heart valve  
Rejection
  • Effector mechanisms 
    • CTLs, macrophages, CD4 lymphocytes
      • secrete inflammatory cytokines
    • antibodies
  • Types of rejection
    • hyperacute 
      • antibody mediated due to the presence of preformed antidonor antibodies in the transplant recipient
        • type II hypersensitivity 
      • occurs within minutes after transplantation
      • results in complement activation -> endothelial damage -> inflammation -> thrombosis
    • acute 
      • cell mediated due to cytotoxic T lymphocytes reacting against foreign MHCs 
      • occurs weeks after transplantation
      • results in parenchymal cell damage or graft vasculitis
    • chronic  
      • T cell- and antibody-mediated vascular damage
        • obliterative vascular fibrosis >> intimal smooth muscle proliferation >> vessel occlusion >> organ atrophy
      • occurs months to years after transplantation
      • irreversible
  • Graft-versus-host disease 
    • donor immunocompetent T cells spread in the irradiated immunocompromised host 
      • reject host cells with "foreign" proteins
    • leads to severe organ dysfunction/failure
      • maculopapular rash, jaundice, hepatosplenomegaly, and diarrhea
    • necessary to remove mature T cells before implantation
Tissue compatibility testing
  • Must match
    • ABO blood group
      • expressed by RBCs as well as endothelial cells
    • HLA type
      • focused on
        • HLA-A
        • HLA-B
        • HLA-DR
  • Tests
    • class I
      • microcytotoxicity test
        • donor cells added to antisera containing specific antibodies against a certain HLA type
        • if cells contain that antibody type, antibodies will bind
        • cell becomes leaky and takes up a dye
        • cells without antibody will not take up the dye
        • same process done for the host
    • class II
      • mixed lymphocyte reaction
        • donor cells irradiated to prevent division
        • host blood added
        • if T-cells respond to antigens on donor cells they will proliferate
        • radio active thymidine in the test mixture will be taken up and can be measured
          • if no thymidine is taken up, there is no rejection
Prevention and treatment of tissue rejection
  • Immunosuppressant drugs 
    • see "Immunosuppressant drugs" topic
  • Graft recipient risks infection from immunosuppression
  • Certain tissue grafts do not require immunosuppression
    • e.g. the eye is an immunoprivileged site
      • corneal transplants do not require immunosuppression

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Qbank (6 Questions)

TAG
(M1.IM.18) A 32-year-old Caucasian female required a kidney transplant 3 years ago. She presents with elevated creatinine levels (2.6 mg/dl) and an elevated blood pressure (160/90 mmHg). A biopsy is taken of the transplanted kidney. Following histological findings, a diagnosis of chronic graft rejection is made. Which of the following is NOT a likely finding? Topic Review Topic

1. Interstitial fibrosis
2. Glomerular destruction
3. Tubular atrophy
4. Graft arteriosclerosis
5. Glomerular crescents

PREFERRED RESPONSE ▶
TAG
(M1.IM.42) A 40-year-old male with a history of chronic alcoholism recently received a liver transplant. Two weeks following the transplant, the patient presents with a skin rash and frequent episodes of bloody diarrhea. A colonoscopy is performed and biopsy reveals apoptosis of colonic epithelial cells. What is most likely mediating these symptoms? Topic Review Topic

1. Donor T-cells
2. Recipient T-cells
3. Donor B-cells
4. Recipient B-cells
5. Recipient antibodies

PREFERRED RESPONSE ▶
TAG
(M1.IM.52) 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? Topic Review Topic

1. Donor T-cells
2. Recipient T-cells
3. Preformed recipient antibodies
4. Donor antibodies
5. Deposition of antibody immune complexes

PREFERRED RESPONSE ▶
TAG
(M1.IM.74) A 45-year-old female is undergoing renal transplantation for management of chronic renal failure secondary to glomerulonephritis. The transplant surgeon placed the donor kidney in the recipient and anastamosed the donor renal artery to the recipient's external iliac artery as well as the donor ureter to the recipient's bladder. After removing the clamps on the external iliac artery, the recipient's blood is allowed to perfuse the transplanted kidney. Within 3 minutes, the surgeon notes that the kidney does not appear to be sufficiently perfused. Upon further investigation, an inflammatory reaction is noted that led to clotting off of the donor renal artery, preventing blood flow to the transplanted organ. Which of the following best describes the pathophysiology of this complication? Topic Review Topic

1. Type I hypersensitivity reaction
2. Type II hypersensitivity reaction
3. Type III hypersensitivity reaction
4. Type IV hypersensitivity reaction
5. Graft-versus-host disease

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TAG
(M1.IM.76) A 62-year-old female with a history of uncontrolled hypertension undergoes kidney transplantation. One month following surgery she has elevated serum blood urea nitrogen and creatinine and the patient complains of fever and arthralgia. Her medications include tacrolimus and prednisone. If the patient were experiencing acute, cell-mediated rejection, which of the following would you most expect to see upon biopsy of the transplanted kidney? Topic Review Topic

1. Sloughing of proximal tubular epithelial cells
2. Lymphocytic infiltrate of the tubules and interstitium
3. Drug precipitation in the renal tubules
4. Granular immunofluorescence around the glomerular basement membrane
5. Crescent formation in Bowman’s space

PREFERRED RESPONSE ▶
TAG
(M1.IM.77) A physician is describing a case to his residents where a kidney transplant was rapidly rejected from the recipient minutes after graft perfusion. The physician most likely describes all of the following manifestations EXCEPT? Topic Review Topic

1. Graft mottling
2. Graft cyanosis
3. Low urine output with evidence of blood
4. Histological evidence of arteriosclerosis
5. Histological evidence of vascular damage

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