Transplantation

Question 1

What is transplantation?

Answer 1

Transfer of tissue/cells from one person to another

Question 2

Why do people need transplantation?

Answer 2

• Injury
• Organ failure
• Ageing
• Cancer

Question 3

Who can the donors of the transplant be?

Answer 3

• Autologous transplant
• Syngenic/allogenic trnasplant
• Xenograft

Question 4

What is an autologus transplant?

Answer 4

Stems cells are removed from a person, stored and later given back to the same person

Question 5

What is an allogeneic transplant?

Answer 5

Uses healthy blood cells from a donor to replace bone marrow not producing enough healthy blood cells

Question 6

What is a xenograft?

Answer 6

A tissue graft or organ transplant from a donor of a different species from the recipient

Question 7

What else is donated besides cells?

Answer 7

• Plasma
• Platelets
• Breast milk

Question 8

From Autologous, the chance of immune by host increases. What is the order from no rejection (autologous) to the most likely of rejection

Answer 8

Autologous -> Syngeneic -> Allogeneic -> Xenogenic

Question 9

What is Syngeneic?

Answer 9

Transplant or graft from a identical twin donor

Question 10

What is Histocompatibility?

Answer 10

The more similar you are, the less likely it is to be rejected

Question 11

What is the MHC in humans?

Answer 11

HLA

Question 12

What is the role of MHC?

Answer 12

Antigen presenting cell - takes up proteins and cuts it up into peptides to present

Question 13

How many MHC do humans have?

Answer 13

2

Question 14

Why is MHC a major target fro the immune system in the setting of transplant?

Answer 14

It is the most polymorphic

Question 15

What is alloantigens?

Answer 15

An antigen present only in some individuals of a species and capable of inducing the production of an alloantibody by indidivuals which lack it

Question 16

How does Host T cells see allo MHC?

Answer 16

• Allo-MHC (+ peptide)
• Self MHC (+ allo-MHC derieved peptide)

Question 17

What signals are produced from direct pathway and indirect pathway?

Answer 17

• Signal 1 and 2

Question 18

MHC inherited by children are…

Answer 18

Inherited co-dominantly

Question 19

What is the chance of sibling of expressing the same MHC as each other?

Answer 19

1/4

Question 20

What is HLA matching?

Answer 20

Matching donors and host to improve graft survival

Question 21

What is tissue typing?

Answer 21

Hosts and donors tested by specific mAbs or PCR to check HLA

Question 22

What happens if there is no relatives in HLA typing?

Answer 22

Find a non related donor from a large pool

Question 23

Why is immunosuppression important to prevent rejection?

Answer 23

DAMPs affect the the outcome

Question 24

Why do minor histocompatibility antigens play a important role?

Answer 24

The more minor HA differences, the higher chances of rejections

Question 25

What are examples of minor hisocompatibility antigens?

Answer 25

- 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

Question 26

What antibody is in the plasma to antigen A on RBC?

Answer 26

Anti B Antibody

Question 27

What antibody is in the plasma to antigen B on RBC?

Answer 27

Anti B Antibody

Question 28

What antibody is in the plasma of antigen A and B on RBC?

Answer 28

Neither

Question 29

What antibody is in the plasma on RBC with no antigen?

Answer 29

Both Antibodies

Question 30

What is Mixed lymphocyte reaction (MLR)?

Answer 30

Can help detect any significant CD4+ T cell response by the recipient to allo-antigen differences

Question 31

What is the function of Mixd lymphocyte reaction?

Answer 31

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

Question 32

What are different ways of performing the assay of Mixed lymphocyte reactions?

Answer 32

- Cytokine release - Proliferation - Surface marker

Question 33

What are the methods of Mixed Lymphocyte Reaction?

Answer 33

- One Way MLR (With Dendritic cell or PBMC - Mitocycin C treated, inhbits mitosis) - Two Way MLR

Question 34

What is the purpose of One Way MLR?

Answer 34

Only host cells will divide significantly

Question 35

What is the purpose of Two Way Mitosis?

Answer 35

- Both donor and the host cell can divide and determine if it contains immune cells

Question 37

What is cross matching?

Answer 37

Mix serum from the recipient (containing antibodies) with cells from the potential donor

Question 38

How does cross matching prevent rejection?

Answer 38

If donor cells are attacked, the graft is likely to b attacked

Question 39

What is Anti-human globulin?

Answer 39

Cross lins the antibodies, binding the Fc tails and clumps everything together

Question 40

What are the methods used to matching patients to prevent rejections?

Answer 40

- ABO blood testing - Tissue typing - Mixed lymphocyte reaction - Cross matching - Immunosuppressive drugs

Question 41

Examples of drugs that block mitosis?

Answer 41

- Azathioprine - Cyclophosphamide - Methotrexate

Question 42

What are immunosuppression drugs combined with?

Answer 42

Corticosteroids

Question 43

What are durgs that block NFAT (Transcription factor) causing reduced IL-2?

Answer 43

- Cyclosporin A - Rapamycin - FK506 (tracolimus)

Question 44

Why is it difficult to block the antigen specfic repsonse to prevent graft rejection?

Answer 44

Nothing to differentriate

Question 45

What are monoclonal antibodies that deplete only (activated) T cells?

Answer 45

- Anti-CD3 (OKT3) - Anti-CD25 (basilixumab)

Question 46

Monoclonal Antibodies that deplete B cells?

Answer 46

- Anti-CD20 (rituximab)

Question 47

Recombiant proteins that inhibit T cells?

Answer 47

Soluble CTLA-4-Ig (abatercept)

Question 49

What is allo-reactivity?

Answer 49

Response to an alloantigen

Question 50

Why is a graft rejected?

Answer 50

The MHC is not the same as the host's therefore it is rejected

Question 51

Why is 10% of T cells are specific for allo-MHC?

Answer 51

When T cells develop in the thymus, T cells are selected to recongise MHC and therefore others' MHC