Transplant Immunology Flashcards
Autograft
Graft from one area to another on same individual
Isograft (syngraft)
Graft from one individual to another who is genetically identical (syngeneic) to the donor
Allograft
Graft between unrelated or allogeneic individuals
Xenograft
Graft between a donor and recipient from different species
Hyperacute Rejection
• Occurs within a few minutes to a few hours of transplant (fever,
tenderness and pain)
• Pre-existing antibodies to ABO, MHC, or endothelial antigens
• Antibodies bind vascular endothelium & activate complement
• Platelet deposition &; thrombi in capillaries;vascular congestion
• Transplanted organ must be removed
graft becomes enlarged and purple due to hemorrhage
Acute Rejection
- Mainly T cell mediated damage of graft
- Fever and graft tenderness, edema
- Occurs a few days to a few weeks after transplantation
- Interstitial infiltrates of T lymphocytes and macrophages
- CD4 TH1 and CD8 T cells induce DTH response
- CTL (CD8 T cell) mediated killing of graft cells; (Direct recognition)
- CD4 T cells secrete cytokines that induce inflammation & vessel damage (vasculitis)
- Alloantibodies that bind to alloantigens (HLA molecules) on endothelial cells of graft can also cause endothelial injury and intravascular thrombosis
- Classical pathway of complement activated and complement mediated tissue injury ensues
- Can be reversed with immunosuppressive therapy
Chronic Rejection
• Mediated by T cells and alloantibodies
• Occurs months or years after transplantation
• T cells react against graft alloantigens; mostly CD4
• secrete cytokines that cause inflammation and damage graft
• Cytokines stimulate fibroblasts resulting in FIBROSIS
• Inflammation of arteries causing OBSTRUCTION and fibrosis
(vascular occlusion); arteriosclerosis
• Mononuclear infiltrates in interstitium
• Alloantibodies contribute to vascular destruction by recruiting complement (classical pathway) and promoting inflammatory response
• Patients do not respond to therapy
• Graft usually has to be removed
Graft Versus Host Reaction
- Consequence of transferring allogeneic bone marrow or stem cells to an immunocompromised host
- Initiated by residual mature donor T lymphocytes in the bone marrow
- Donor T cells recognize and react to MHC and minor H antigens on recipient’s dendritic cells unless they are removed
- Waisting syndrome
- Splenomegaly, hepatomegaly, lymphadenopathy, anemia, weight loss, chronic
O Blood group (O-)
universal Donors
Agglutination assay used to test ABO blood group • Patient’s blood mixed with antiserum to A or B
AB blood groupd (AB +)
universal recipients
Agglutination assay used to test ABO blood group • Patient’s blood mixed with antiserum to A or B
Alloreactivity
Happens bc some T cells get through that can respond to allogenic (foreign) MHC and
basis for graft rejection..looks like SELF MHC plus foreign peptide because these stupid t cells recognize foriegn MHC
Direct Graft recognition
in lymph nodes t cells get activated by donor APCs from the graft, that display alloreactive MHC and forigen peptide
activated t cells move to graft and destroy graft cells
DONOR APC presents peptide from graft to RECIEPIENT T CELLS
Indirect Graft Recognition
Graft cells may be ingested by recipient dendritic cells + then donor alloantigens are presented by self MHC molecules on reciepeint APCs to CD4 cells
- may play a greater role in chronic rejection