Flashcards in Transplantation Deck (35)
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
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:
And ABO blood group
What do HLA-A & HLA-B code for?
Found on all nucleated cells, present intracellular antigens and recognised by CD8+ T cells
What does HLA-DR code for?
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
What are the major causes of rejection?
Pre-formed immunity (sensitized to donor antigen)
Failed Immunosuppression (incl non-compliance)
Infections or environmental triggers
How do we categorize rejection?
What causes an immediate rejection?
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?
how do you prevent someone rejecting an organ?
Tissue Typing (HLA)
Other than rejection what else can go wrong in a transplant?
Recurrence of disease
What are the types of immunosuppresants used in organ transplant?
Cyclosporinfor solid organ graft transplantation (by interferring with T cell signalling)
Calcineurin inhibitors (Tacrolimus) - inhibits IL-2 gene transcription
RIpamycin - interacts with signalling downstream of the IL-2 receptor
Anti-proliferatives (Azathioprine) - inhibit lymphocyte proliferation
What's the difference between graft rejection and Graftvshost disease?
In rejection the host attacks the graft
In GvH, white cells in the donated tissue attack the host's body
So what is required for GvH disease?
Graft must contain immunocompetent cells
Recipient must have defective immunity (pretty likely since you're smacking them with immunosuppresants)
What can we do to prevent GvH?
Tissue Typing (HLA)
Can do Donor Marrow T cell Depletion
What kind of donors are associated with the longest life, least rejection and best health?
1) Living Donors (Related or unrelated)
2) Living donors altruistic
3) Brain Death Donors (DBD)
4) Cadaveric Death Donors (DCD)
So 4 are the least healthy transplants and 1 the most
What causes hyperacute rejection in unmodified xenografts?
Natural IgM Human Anti-Swine Abs
Define Autologous transplant
Tissue returning to same individual after period outside the body, usually frozen, stem cells, skin graft, ovaries etc
Synergeneic transplant definition
Transplant between identical twins (isograft)
Allogenic transplant definition
transplant between genetically nonidentical members of the same species providing a risk of rejection
Cadaveric transplant definition
Uses organs from a dead donor
Transplant between species, thus carrying a high risk of rejection
How do we chose a recipient for an organ?
Negative serum cross match with Donor's T-lymphocytes