Immunology 4: Transplantation Flashcards
define a transplant
- a procedure in which an organ/s, tissue or group of cells are removed from one person (the donor) and transplanted into another person (the recipient), or moved from one site to another in the same person.
define Graft
- piece of tissue that is transplanted
what are the different types of grafts?
- autograft
- allograft
- isograft
- xenograft
what is an autograft?
tissue grafted back on to the original donor
what is an allograft?
- graft between aloogeneic individuals (i.e., members of the same species but different genetic constitution), for example, human to human
- risk of GHVD/rejection
what is an isograft?
- graft between syngeneic individuals (i.e. of identical genetic constitution) such as identical twins
- no GVHD/rejection
what is a xenograft?
- graft between xenogenic individuals (i.e. of different species), for example, pig to human
what is the most common type of ‘allograft’?
blood transfusion
which donor antigens can trigger graft rejection?
- major histocompatibility antigens: MHC i.e. HLA in humans
- others: minor histocompatibility antigens e.g. HY, HA1 and ABO blood groups
describe the inheritance of HLA
- each child inherits one HLA haplotype from each parent.
- each parent has two different haplotypes (paternal = ab and maternal = cd) > 4 different combinations are possible in offspring (ac, ad, bc, bd)
- 25% chance of having HLA-identical or sero haplotype matched siblind donor
- 50% chance of having a one-haplotype matched sibling donor
describe the different types of graft rejection
- hyperacute: rejection within minutes
- acute: rejection within several days
- chronic: rejection within months to years
what is the pathogenesis of hyperacute graft rejection?
- circulating antibodies specific for antigens on the graft endothelial cells
- antibodies are present in the circulation prior to transplant, most are anti-HLA antibodies
- these bind to the vascular endothelium, activating the complement and clotting cascades
what is the pathogenesis of acute transplant rejection?
- graft infiltration with cytotoxic T cells
- cytokines help recruit other cells such as macrophages and promote T-cell proliferation (TNF, IL1, IL2, IFN)
the release of effector molecules granzyme and perforin via exocytosis leading to cell death - think like a type IV delayed hypersensitivity
- can also involve antibodies (humoral response)
what is the pathogenesis of chronic graft rejection?
- mechanisms not fully understood
- can involve lymphocytes, phagocytes, antibody and complement
how might we prevent graft rejection?
- closer ‘matching’ (HLA testing)
- immunosuppression
what are the ways in which HLA alleles and antibodies can be identified?
alleles:
1. serology
2. sequencing or ‘typing’
You can also identify HLA antibodies by cross-matchibng:
- detects antibodies binding to individual HLA antigens
- these antibodies are important in hyperacute rejection
define crossmatching
- a technique used to investigate whether the recipient has previously reacted to the HLA molecules that will be presented on the donor organ after transplantation e.g. pregnancy, previous transplants, blood transfusions
- trying to reduce risk of hyperacute rejection
How do cylosporin and tacrolimus work in immunosuppression?
They are calcineurin inhibitors that block IL-2 transcription and inhibit T-cell activation
what are some sources of haematopoietic stem cells?
- bone marrow
- peripheral blood
- umbilical cord
Graft vs Host Disease (GVHD) treatment
- high dose steroids
- immunosuppressants
- faecal microbial transplant
- ruxolitinib
what is graft vs host disease (GVHD)? how does it happen?
- A severe complication that can occur following haematopoietic stem cell transplantation.
- immunocompetent T lymphocytes from the donor graft recognise the recipient’s tissues as foreign due to histocompatibility differences and initiate an immune response against them.
