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