Transplantation

Question 1

What are the two barriers of transplantation

Answer 1

Rejection, tissue availability

Question 2

What is the simplest medical transplant

Answer 2

Blood transfusion

Question 3

How many genes is the ABO system encoded by, what enzyme does it encode

Answer 3

• ABO system is determined by single gen encoding a glycosylation enzyme that modified cell surface antigens

Question 4

Humans produce what Ig against blood group carbohydrates you lack

Answer 4

IgM, due to cross-reactivity with bacterial antigens

Question 5

Define an autograph/autologous graft

Answer 5

Graft from one anatomical site to another of the same individual

Question 6

Example of an autograph

Answer 6

skin graft

Question 7

Allograft definition

Answer 7

Transplant from unrelated individual of the same species

Question 8

Example of allograft

Answer 8

Kidney transplant

Question 9

Define xenograft

Answer 9

Transplant using tissue from different species

Question 10

Two types of rejection of allografts

Answer 10

Allografts are initially successful (without immunosuppression), but fail after 10-14 days = acute rejection

With effective immunosuppression, allografts can last month’s/years, but degrade overtime = chronic rejection

Question 11

Type of rejection of xenografts

Answer 11

Hyperacute rejection

Question 12

What family of molecules is a major barrier to transplantation

Answer 12

MHC

Question 13

What revealed a set of linked genes determined a major component of compatibility, MHC

Answer 13

Genetic crosses- mouse model

Question 14

What primed cell response is against grafts (think of the mouse models with allografts)

Answer 14

Primed T cell response

Question 15

Allografts put on what type of mice are not rejected and why?

Answer 15

Allografts put onto nude mice (which lack T cells) are not rejected!

Question 16

MHC are the most what molecules in the human popualtion

Answer 16

MHC are most polymorphic molecules in human population.

Question 17

MHC is p_______, p______ and the alleles are co-______

Answer 17

MHC is polygenic, polymorphic and alleles are co-dominant.

Question 18

Up to the 90s there was large effort to improve ____ matching for solid organ transplantation

Answer 18

Up to 90s, big effort to improve MHC matching for solid organ transplantation. Perfect matching isn’t sufficient.

Question 19

How is donor MHC recognised as an alloantigen: (£)

Answer 19

Direct allorecognition
Indirect allorecognition
Semi-direct (similar to indirect)

Question 20

How does tissue damage occur in organ transplants

Answer 20

Immune pathways are interconnected.
CD8 cells from direct recognition attack the graft directly,

CD4 cells from indirect recognition help B cells to make anti-graft antibodies against graft

Antibodies bound to graft lead to destruction via complement and via ADCC (macrophage and NK cells) and aid further antigen presentation

CD4 T cells from indirect recognition help macrophage to become activated and damage tissue etc

Local inflammation during surgery will also attract any cells that have been primed to go back to the graft.
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Question 21

Why are large numbers of T cell eractive to all-MHC

Answer 21

• T cells are positively and negatively selected during development for those whose TCR can bind to self-MHC, but which do not react with self-peptide
• Thymic education, T cells learn self from non-self
• T cells that bind very strongly to MHC are eliminated, autoimmunity.
• However transplanted tissue presents new molecules to cells post-thymic education.

Question 22

Allo-reactivity requires what complex forming

Answer 22

allo-MHC-peptide

Question 23

What was the biggest improvement in transplantation

Answer 23

Immunosuppressive drugs which target T cells activation

Question 24

What antibody leads to rapid hyperacture rejection in xenotransplantation in pigs to humans. Why?

Answer 24

Anti-alpha-Gral antibodies. Pig organs have alpha-Gal epitopes, in humans its an pseudogene

Question 25

5 ways pigs can be genetically modified to minimise hyperacute rejection

Answer 25

Engineer transgenic pigs to express human complement regulators Inactivate alpha-1,3GT gene in pig germline Disrupt endogenous MHC class I and class II expression Add genes for negative regulators of immunity, clotting and inflammation Extesntive immunosuppresive drugs

Question 26

Animal chimaeras

Answer 26

Inject host pluripotent stem cells into animal blastocyte lacking the organ development of the needed organ, the animal then grows the organ to its relative size.

Question 27

HSC stands for

Answer 27

Haematopioetic stem cell

Question 27

HSC transplantation steps

Answer 27

Recipient endogenous HSC is destroyed Donor HSC is infused

Question 27

In HSC transplants, what is rejection known as

Answer 27

Graft versus host disease (GVHD)

Question 28

The allo-reaction in HSC trasnplantation can be beneficial in what

Answer 28

beneficial in graft versus leukaemia (GVL) effects.

Question 29

What is the most common allograft

Answer 29

A fetus, hemi-allograft

Question 30

How does the mother not reject the fetus in terms of limiting allo-MHC reaction

Answer 30

The foteal-maternal interface (trphoblast) doesn't express MHC II, low MHC , specialised MHC I class called HLA-G which inhibits NK cells

Question 31

The placenta is rich in factors that suppress

Answer 31

Suppress effector T cells and promote inhibitory Tregs

Question 32

Uterine maternal tissue has mechanisms to limit T cell attraction via what

Answer 32

chemokines