Transplantation

Question 1

Define Transplantation

Answer 1

The replacement of tissues or organs that have undergone an irreversible pathological process which threatens the patients life or, to a significant degree, considerably hampers their quality of life.

Question 2

Autograft

Answer 2

tissue from self to another place

Question 3

Isograft

Answer 3

Genetically identical individual

Question 4

Allograft

Answer 4

From another person within the same species, but not necessarilly genetically identical

Question 5

Xenograft

Answer 5

non-identical source not from the same species

Unmodified grafts -
Natural IgM human anti-swine antibody

Graft endothelial galactose residues
rejection.

Question 6

HLA Class 1

Answer 6

HLA-A,B,C
All nucleated cells
CD8+/TC cells recognise

Question 7

HLA Class 2

Answer 7

HLA-DR, DP, DQ
Only APCs
CD4+/TH cells recognise
Most important in Rejection

Question 8

Genetic Inheritance of HLA

Answer 8

codominantly expressed, which means that each individual expresses these genes from both the alleles on the cell surface. Furthermore, they are inherited as haplotypes or 2 half sets (one from each parent). This makes a person half identical to each of his or her parents with respect to the MHC complex. This also leads to a 25% chance that an individual might have a sibling who is HLA identical.

Question 9

Privileged sites

Answer 9

Areas which have no blood flow

no sensitisation / no tolerance
no requirement for tissue matching
no immunosuppression

THE CORNEA

Question 10

Graft Rejection

Answer 10

Transplant rejection occurs when transplanted tissue is rejected by the recipient’s immune system, which destroys the transplanted tissue

Question 11

Causes of Graft Rejection

Answer 11

ABO (acute rejection) or HLA Incompatible
Pre-formed Immunity (Sensitisation)
Failed Immunosupression
Including Non-compliance
Infections/Environmental Triggers

Question 12

Immediate Rejection

Answer 12

Can happen in minutes
ABO/HLA-antibodies
Complement activation damages blood vessels
Inflammation and thrombosis

Question 13

Acute Rejection (sensitisation phase)

Answer 13

CD4 and CD8 cells recognise alloantigens
T-cell receptors react with APCs via MHC Molecules
Co-stimulation via CD28, CD80 and CD4/CD40 surface ligands

Question 14

Acute rejection

Answer 14

Usually in 1st 6 months
Can be a mix of cell and antibody mediated
Cellular infiltration of graft by Tc cells, B-cells, NK cells and Macrophages
Endothelial inflammation and parenchymal cell damage

Question 15

Chronic Rejection

Answer 15

Commonest cause of Graft Failure
> 6 months
Antibody mediated with other innate components
Myointimal proliferation in arteries

Cytokines and antibodies cause a chronic inflammatory process that proliferates cell walls to protect themselves and due to turnover. This in turn blocks off blood vessels and leads to ischaemia an fibrosis

Question 16

Treatment of Rejection

Answer 16

Corticosteroids

Anti-Thymocyte Globulin

Plasma Exchange

Question 17

Other Complications of Rejection

Answer 17

Infection (including zoonotic) - opportunistic infections

Neoplasia (skin, lymphoma)

Drug side effects

Recurrence of original disease

Surgical, ethical etc problems

Question 18

Prevention of Graft Rejection

Answer 18

ABO matching
Tissue Typing (Class I & II HLA)
Prophylactic immunosuppression
(Humanised or ‘silenced’ xenografts)

Question 19

Immunosuppression

Answer 19

Coritcosteroids (Prednisolone)
Widespread anti-inflammatory
Calcineurin Inhibitors (Tacrolimus)
Block IL-2 Gene Transcription
Anti-proliferatives (MMF)
Prevent Lymphocyte Proliferation

Question 20

Graft V Host Disease

Answer 20

Principally a Bone Marrow Transplant problem
Requirements:
		1) immunocompetent cells in graft
		2) defective recipient immunity
		3) HLA differences between donor and recipient
Recipient skin, gut, liver, immune cells
Prevention
	- donor / recipient matching
	- donor marrow T cell depletion