Transplant - Immunology - Medbullets Step 1

Snapshot

A 60-year-old-man presents with nausea and vomiting to his primary care physician. Medical history is significant for a liver transplantation approximately 2 weeks prior to presentation. On physical examination there is scleral icterus and mild ascites. A liver biopsy shows lymphocytic infiltrates in the interstitium. (Acute rejection)

Introduction

Transplantation is a process by which
- cells, tissues, or organs (a graft) from the donor are transplanted into a host (or recipient)
The immune system's ability to recognize and respond to foreign antigens bring challenges to transplantation
There are several types of grafts
- autograft
  - tissue is moved from one location to another in the same person
    - e.g., skin graft and using the saphenous vein to replace a coronary artery
  - the graft will not be considered foreign and thus
    - will not require lifelong immunosuppresion
- syngeneic graft (isograft)
  - tissue is transplanted from one genetically identical donor to the host
    - e.g., transplantation between monozygotic twins
- allograft
  - tissue is transplanted from one genetically different donor of the same species to the host
    - e.g., kidney transplant
- xenograft
  - tissue is transplanted from a donor of a different species to the host
    - e.g., porcine heart valve

Transplant Rejection

Transplant Rejection
Rejection Type	Pathogenesis	Comments
Hyperacute	Type II hypersensitivity reaction where pre-existing recipient antibodies attack the donor antigen resulting in complement activation endothelial damage inflammation thrombosis	Time minutes to hours Findings capillary thrombosis which prevents graft vascularization
Acute	Cellular rejection type IV hypersensitivity reaction where recipient CD8+ T-cells react to donor antigens after activation by antigen presenting cells Humoral rejection just like in hyperacute rejection; however, the antibodies are formed after transplantation occured	Time weeks to months Findings graft vessel vasculitis with lymphocytic infiltrates
Chronic	Type II and IV hypersensitivity reaction secondary to CD4+ T-cells responding to the host's antigen presenting cells	Time months to years Findings cytokine secretion after T-cell activation leads to smooth muscle proliferation interstitial fibrosis parenchymal atrophy
Graft-versus-host disease	Type IV hypersensitivity reaction secondary to the donor's T-cells attacking the recipient's cells leading to organ dysfunction	Time variable Findings maculopapular rash jaundice diarrhea hepatosplenomegaly

Tissue Compatibility Testing

ABO blood typing
Tissue typing
- used to see if HLA antigens match and focuses on
  - HLA-A
  - HLA-B
  - HLA-DR