Transplantation Flashcards
Autograft
Self-tissue transplanted from one site to another on the same individual
Isograft
Tissue is transferred between genetically identical individuals
Allograft
Tissue is transferred between non-identical members of the same species
Xenograft
Tissue is transferred between individuals of two different species
Greatest barrier to transplantation
Immunological recognition of graft as foreign
Immune mediators of allograft rejection
T cells and antibodies
Immune mediators of xenograft rejection or mismatched blood antigens
Antibodies and complement
Which factors influence rate of rejection?
Closeness of genetic match
Tissue location
Solid organ vs cellular engraftment
Strongest driver of rejection
Mismatches at MHC alleles (different haplotypes)
Which subtypes of T cells contribute to allograft rejection?
CD4 and CD8
Direct allograft rejection
Dendritic cells from the donor trigger immune responses against donor tissue
Indirect allograft rejection
Recipient dendritic cells process donor cell proteins and present foreign epitopes to T cells
Minor histocompatibility antigens
Antigens involved in histocompatibility that operate outside of MHC allele matching
Hyperacute graft rejection: time for rejection
Minutes to hours
Hyperacute graft rejection: primary mediators
Natural antibodies
Complement-mediated lysis
Acute graft rejection: time for rejection
Hours to days
Acute graft rejection: primary mediators
Antibodies, NK cells, CD8 T cells
Chronic graft rejection: time for rejection
Weeks to months
Chronic graft rejection: primary mediators
Antibodies, CD4 T cells, CD8 T cells
Hyperacute rejection: cause and mechanism
Blood type mismatches, xenotransplants
Mechanism: rapid binding of antibody and complement activation
Acute rejection: cause and mechanism
Reaction against alloantigens
Damage to vascular endothelial cells and tissue cells
Chronic rejection: cause and mechanism
Type 3 or type 4 hypersensitivity
Restriction in blood supply to graft tissue as blood vessels thicken
Hematopoietic stem cell transplantation
Stem cells from donor bone marrow or blood are infused into recipient
Only curative option for blood cancers, autoimmune diseases, and certain genetic disorders
Major obstacle of hematopoietic stem cell transplantation
Chronic graft vs host disease: donor T cells attack immunocompromised host because they identify host as foreign
First match to be made for transplantation
Blood type (ABO)
Second match to be made for transplantation
MHC alleles (matched as best as possible) Can tolerate some mismatch depending on tissue
Induction of graft recipient tolerance
Give recipient donor antigens ahead of surgery
Avoiding hyperacute rejection in xenotransplantation
Create transgenic animal (eg pigs) that expresses human CD59 and decay accelerating factor
Luminex assay
Most common test for recipient antibodies against donor MHC antigens
Used to determine MHC compatibility between donor and recipient
