Transplantation Flashcards
What situation leads to a transplant?
“Tissue/organ undergone an Irreversible Pathological Process which either Threatens Patient’s Life or Significantly Hampers QoL
What are the 4 major types of graft?
Xenograft - From an animal
Allograft - From another person
Isograft - From someone genetically identical
Autograft - From yourself
Define Histocompatibility?
State in which the donor and recipient share the same (or sufficiently similar) alleles of HLA genes that they express the same MHC proteins and so would not attack the graft
Where are HLA alleles found?
on chromosome 6
Each person has 2 sets of alleles and they are co-dominantly expressed
How are HLA alleles inherited
As Haplotypes (meaning 2 half sets, one from each parent)
Hence each person is 1/2 identical to each parent and so has a 1/4 chance of being identical to a sibling
What are the major requirements for tissue typing?
HLA match, particularly:
- HLA-A
- HLA-B
- HLA-DR
And ABO blood group
What do HLA-A & HLA-B code for?
MHC 1
Found on all nucleated cells, present intracellular antigens and recognised by CD8+ T cells
What does HLA-DR code for?
MHC 2
Found on APCs, presents extracellular antigens and recognised by CD4+ T cells
What are privileged sites?
Places with little to no blood flow and so no immunity. They don’t require tissue matching or immunosuppression
E.g. Cornea
What are the major causes of rejection?
HLA/ABO incompatible
Pre-formed immunity (sensitized to donor antigen)
Failed Immunosuppression (incl non-compliance)
Infections or environmental triggers
How do we categorize rejection?
Immediate
Acute
Chronic
What causes an immediate rejection?
HLA/ABO antibodies
They activate complement leading to inflammation and thrombosis
Happens in minutes
Acute rejection occurs within 6 months. What happens?
Cell & Ab mediated
The graft is infiltrated by cells (T, B, NK & macrophages ) –> Endothelial damage and parenchymal cell damage
What happens in chronic rejection?
Ab mediated & innate immunity
This is the most common kind
Chronic inflammation in blood vessels- -> smooth muscle proliferation –> Vessel occlusion and eventually organ failure
How can you treat someone who’s rejecting their organ?
Corticosteroids
Anti-thymocyte Globulin
Plasmapharesis