Transplantation Flashcards
What is transplantation?
Transfer of tissue/cells from one person to another
Why do people need transplantation?
- Injury
- Organ failure
- Ageing
- Cancer
Who can the donors of the transplant be?
- Autologous transplant
- Syngenic/allogenic trnasplant
- Xenograft
What is an autologus transplant?
Stems cells are removed from a person, stored and later given back to the same person
What is an allogeneic transplant?
Uses healthy blood cells from a donor to replace bone marrow not producing enough healthy blood cells
What is a xenograft?
A tissue graft or organ transplant from a donor of a different species from the recipient
What else is donated besides cells?
- Plasma
- Platelets
- Breast milk
From Autologous, the chance of immune by host increases. What is the order from no rejection (autologous) to the most likely of rejection
Autologous -> Syngeneic -> Allogeneic -> Xenogenic
What is Syngeneic?
Transplant or graft from a identical twin donor
What is Histocompatibility?
The more similar you are, the less likely it is to be rejected
What is the MHC in humans?
HLA
What is the role of MHC?
Antigen presenting cell - takes up proteins and cuts it up into peptides to present
How many MHC do humans have?
2
Why is MHC a major target fro the immune system in the setting of transplant?
It is the most polymorphic
What is alloantigens?
An antigen present only in some individuals of a species and capable of inducing the production of an alloantibody by indidivuals which lack it
How does Host T cells see allo MHC?
- Allo-MHC (+ peptide)
- Self MHC (+ allo-MHC derieved peptide)
What signals are produced from direct pathway and indirect pathway?
- Signal 1 and 2
MHC inherited by children are…
Inherited co-dominantly
What is the chance of sibling of expressing the same MHC as each other?
1/4
What is HLA matching?
Matching donors and host to improve graft survival
What is tissue typing?
Hosts and donors tested by specific mAbs or PCR to check HLA
What happens if there is no relatives in HLA typing?
Find a non related donor from a large pool
Why is immunosuppression important to prevent rejection?
DAMPs affect the the outcome
Why do minor histocompatibility antigens play a important role?
The more minor HA differences, the higher chances of rejections
What are examples of minor hisocompatibility antigens?
- ABO blood systems (series of proteins presented on the RBC)
- H-Y gender (HY can be recongised by females as foreign)
- HA-1
- Around 40 loci but mainly differ at 1 or 2 amino acid residue
What antibody is in the plasma to antigen A on RBC?
Anti B Antibody
What antibody is in the plasma to antigen B on RBC?
Anti B Antibody
What antibody is in the plasma of antigen A and B on RBC?
Neither
What antibody is in the plasma on RBC with no antigen?
Both Antibodies
What is Mixed lymphocyte reaction (MLR)?
Can help detect any significant CD4+ T cell response by the recipient to allo-antigen differences
What is the function of Mixd lymphocyte reaction?
Mix blood cells from donor and host, looking for repsonding T cells from the host
- If present these are recognising allo-antigens from the donor which may cause rejection
What are different ways of performing the assay of Mixed lymphocyte reactions?
- Cytokine release
- Proliferation
- Surface marker
What are the methods of Mixed Lymphocyte Reaction?
- One Way MLR (With Dendritic cell or PBMC - Mitocycin C treated, inhbits mitosis)
- Two Way MLR
What is the purpose of One Way MLR?
Only host cells will divide significantly
What is the purpose of Two Way Mitosis?
- Both donor and the host cell can divide and determine if it contains immune cells
What is cross matching?
Mix serum from the recipient (containing antibodies) with cells from the potential donor
How does cross matching prevent rejection?
If donor cells are attacked, the graft is likely to b attacked
What is Anti-human globulin?
Cross lins the antibodies, binding the Fc tails and clumps everything together
What are the methods used to matching patients to prevent rejections?
- ABO blood testing
- Tissue typing
- Mixed lymphocyte reaction
- Cross matching
- Immunosuppressive drugs
Examples of drugs that block mitosis?
- Azathioprine
- Cyclophosphamide
- Methotrexate
What are immunosuppression drugs combined with?
Corticosteroids
What are durgs that block NFAT (Transcription factor) causing reduced IL-2?
- Cyclosporin A
- Rapamycin
- FK506 (tracolimus)
Why is it difficult to block the antigen specfic repsonse to prevent graft rejection?
Nothing to differentriate
What are monoclonal antibodies that deplete only (activated) T cells?
- Anti-CD3 (OKT3)
- Anti-CD25 (basilixumab)
Monoclonal Antibodies that deplete B cells?
- Anti-CD20 (rituximab)
Recombiant proteins that inhibit T cells?
Soluble CTLA-4-Ig (abatercept)
What is allo-reactivity?
Response to an alloantigen
Why is a graft rejected?
The MHC is not the same as the host’s therefore it is rejected
Why is 10% of T cells are specific for allo-MHC?
When T cells develop in the thymus, T cells are selected to recongise MHC and therefore others’ MHC
