Transplantation Flashcards
What situation leads to a transplant? [2]
Tissue/organ undergone an irreversible pathological process [1] which either Threatens Patient’s Life or Significantly Hampers QoL [1]
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? [2]
A state in which the donor and recipient share the same (or sufficiently similar) alleles of HLA genes [1] so that they express the same MHC proteins and so would not attack the graft [1]
Where are HLA alleles found? [1]
Describe the expression of these alleles [1]
on chromosome 6
Each person has 2 sets of alleles and they are co-dominantly expressed
How are HLA alleles inherited, how does this explain the rationale for allogenic transplantation
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? [4]
HLA match, particularly:
- HLA-A
- HLA-B
- HLA-DR
And ABO blood group
What do HLA-A & HLA-B code for? [2]
MHC 1
Found on all nucleated cells, present intracellular antigens and recognised by CD8+ T cells
What does HLA-DR code for? [2]
MHC 2
Found on APCs, presents extracellular antigens and recognised by CD4+ T cells
What are privileged sites? [1]
Give 1 eg
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? [4]
HLA/ABO incompatible
Pre-formed immunity (sensitized to donor antigen)
Failed Immunosuppression (incl non-compliance)
Infections or environmental triggers
How do we categorize rejection? [3]
Immediate
Acute
Chronic
What causes an immediate rejection? [1]
How does rejection occur?
Time frame?
HLA/ABO antibodies
They activate complement leading to inflammation and thrombosis so organ does not perfuse
Happens in minutes
Acute rejection occurs within 6 months. What happens? [2]
Cell & Ab mediated
The graft is infiltrated by cells (T, B, NK & macrophages ) –> Endothelial damage and parenchymal cell damage
What happens in chronic rejection? [3] (most common kind of rejection that occurs)
Ab mediated & innate immunity
Chronic inflammation in blood vessels- -> smooth muscle proliferation in arteries –> Vessel occlusion and eventually organ failure
How can you treat someone who’s rejecting their organ? [3]
CCS
Anti-thymocyte Globulin
Plasmapharesis - prevents antibody response by removing antibodies
how do you prevent someone rejecting an organ? [3]
ABO matching
Tissue Typing (HLA)
Prophylactic Immunosuppresants
Other than rejection what else can go wrong in a transplant? [5]
Infection Neoplasia Drug SEs Recurrence of disease Surgical complications
What are the types of immunosuppressants used in organ transplant? [3]
CCS
Calcineurin inhibitors (Tacrolimus) - inhibits IL-2 gene transcription
Anti-proliferatives (Azathioprine) - inhibit lymphocyte proliferation
What’s the difference between graft rejection and Graftvshost disease? [2]
In rejection the host attacks the graft
In GvH, white cells in the donated tissue attack the host’s body
So what is required to diagnose GvH disease? [3]
Graft must contain immunocompetent cells
Recipient must have defective immunity (pretty likely since you’re smacking them with immunosuppresants)
HLA mismatch
What can we do to prevent GvH? [2]
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 name in descending order? [4]
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? [1]
Natural IgM Human Anti-Swine Abs
Function of anti-thymocyte globulin (ATG) [2]
an antibody against human T cells that stops thymocyte response in acute response
SE of calcineurin inhibitors
Nephrotoxic
Can cause cancers eg melanoma, PTLD (Posttransplant lymphoproliferative disease)
