Definitions, Allotransplantation Antigens, Skin Transplants Research Example, Mechanisms of Graft Rejection, Types of Rejection, Preventing Rejection, Xenotransplantation, Stem Cells, Pregnancy
Definitions
● Transplantation = living donor tissues transferred to recipient organism
● Graft = transplanted tissue
● Autograft = one part of an individual’s body transferred to another
● Isograft = between monozygotic twins (genetically identical)
● Allograft = between different members of the same species
● Xenograft = between members of different species
● Immune privilege site = where there are less immune cells [under normal circumstances] and so
transplants are more successful eg cornea
Allotransplantation Antigens
1. Major ABO blood groups
2. MHC class I and II (HLA for humans). HLA is very polymorphic (from multiple alleles) so it is very
unlikely to have an exact match between unrelated individuals. MHC mismatches cause rejection.
MHC II is more deleterious to a graft than 1 or 2 MHC I mismatches
3. Minor antigen incompatibility from SNPs. SNPs cause a difference of one amino acid in the
sequence of a protein. When proteins are broken down by proteasomes they are displayed by APC
on the cell surface. A non-self protein in the case of a transplant will cause that cell to be
recognised as foreign
Skin Transplants Research Example
● 1st graft is vascularised but falls off after 10 days. Rejected by cell mediated immune response
● 2nd graft doesn’t incorporate and falls off after 6-7 days, suggesting memory cells
● If T cells are transferred to an organism which has never had a graft before, the response is fast and
similar to giving a 2nd graft
● Transplanted organs are not likely to last a lifetime. A 5 year graft survival % is often used to
measure success rate
Mechanisms of Graft Rejection
● Recognising the graft as foreign by T cells predominantly → T H cells activate MAC.
Other cytokines can activate TH cells and other enzymes → graft is destroyed
● Direct recognition - foreign APC are recognised by recipient T cells. After a few weeks the APC will
die off as no haemopoiesis
● Indirect recognition - recipient APCs recognised by donor T cells
Types of Rejection
● Hyperacute ~ mins/hrs = from already present, preformed antibodies
● Accelerated ~ days = reactivation of sensitised T cells
● Acute ~ days/weeks = primary activation of T cells
● Chronic ~ months/years = caused by multiple problems eg fibrosis, antibodies, disease, immune
complexes
● With each successive transplant, an individual creates preformed antibodies each time. This makes
it difficult to stop rejection for the next response
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