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
how do you prevent someone rejecting an organ?
ABO matching
Tissue Typing (HLA)
Prophylactic Immunosuppresants
Other than rejection what else can go wrong in a transplant?
Infection Neoplasia Drug SEs Recurrence of disease Surgical complications
What are the types of immunosuppresants used in organ transplant?
Corticosteroids
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)
HLA mismatch
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
Xenogenic transplant
Transplant between species, thus carrying a high risk of rejection
How do we chose a recipient for an organ?
ABO compatibility
Negative serum cross match with Donor’s T-lymphocytes
HLA match
What happens in autologous SCT?
Marrow is removed, frozen and reinfused after potent chemotherapy has been given
What is wrong with allogenic SCT?
MUCH RISKIER
Mortality is as high as 20%
When is allogenic SCT carried out?
SCID
Aplastic aneamia
Stem cells sources
Bone marrow
Peripheral blood
Cord blood
How do we condition the patient before stem cell therapy?
High dose Chemo
High dose radio
To destroy diseased/damaged stem cells already present
What is GVHD and when does it occur?
Graft versus Host disease occurs when donor T cells from allogenic graft react to recipient antigens due to a mismatch in either minor or major histocompatibility antigens. Can occur up to 4 weeks later Multisystemic Acute = 70% mortality Minimise T cells in donation
