Transplantation

Question 1

Define the four types of grafting

Answer 1

Autograft = transfer of tissue between different sites within the same organism (e.g. skin graft) 
Isograft = transfer between genetically identical individuals, ie. identical twins, also known as syngeneic  
Allograft = transfer between genetically non-identical members of the same species  
Xenograft = transfer between species

Question 2

What happens if there is an ABO incompatibility between donor and recipient?

Answer 2

Hyperacute rejection

Question 3

Describe HLA class 1

Answer 3

o HLA-A and HLA-B (and C)
o All nucleated cells
o Recognised by cytotoxic T-cells (CD8+)

Question 4

Describe HLA class 2

Answer 4

o HLA-DR (also DP, DQ)
o Only antigen-presenting cells (APCs)
o Recognised by T-helper cells (CD4+)
(most important in rejection)

Question 5

What are privileged sites?

Answer 5

little or no blood/lymph supply, meaning that the recipient immune system is not exposed to donor antigens and no immunological sensitasation or damage response can take place.

Question 6

List the potential complications of transplantation

Answer 6

• Graft rejection
• Graft versus host disease (GVHD)
• Infection - due to immunosuppressive therapy or of transfer of infectious agent in graft)
• Neoplasia - Lymphoma, Skin tumours
• Drug side effects
• Recurrence of original disease
• Ethical, surgical problems etc.

Question 7

What measures are taken to prevent graft rejection?

Answer 7

• ABO matching & detection of pre-sensitisation to donor antigens
• Close tissue matching (Class I & II HLA - especially at HLA-A, HLA-B & HLA-DR loci)
• Prophylactic immunosuppressive therapy
• (Humanised or ‘silenced’ xenografts’)

Question 8

Describe the cause and timescale of hyperacute rejection

Answer 8

Minutes

Caused by Pre-formed antibody against donor HLA or ABO antigens

Question 9

Describe the cause and timescale of accelerated rejection

Answer 9

2 - 5 days

Caused by Pre-sensitised T-cells (to donor antigens)

Question 10

Describe the cause and timescale of acute rejection

Answer 10

7 - 21 days

Caused by Newly-sensitised T-cells (to donor antigens)

Question 11

Describe the cause and timescale of chronic rejection

Answer 11

Months - years

Multifactoral aetiology

Question 12

What is graft versus host disease?

Answer 12

Predominantly a complication of bone marrow transplant, where donor immune cells attack the recipient’s tissues

Question 13

Which tissues are most commonly damaged in GVHD?

Answer 13

Skin
Gut
Liver
Immune cells

Question 14

What circumstances must be present for GVHD to occur?

Answer 14

• The presence of functioning immunocompetent donor T-cells in the graft
• Defective immunity (particularly T-cell immunity) in the recipient  the recipient is unable to mount an immune response sufficient to eliminate the transplanted cells
• HLA differences between donor and recipient

Question 15

What is the main challenge with xenografts?

Answer 15

Humans have naturally acquired IgM class antibodies against pig endothelial galactose antigens, therefore xenografts must be modified to prevent a hyper-acute rejection.

Question 16

What are the main treatment options for autoimmune diseases?

Answer 16

• Immunosuppressive therapy
• Anti-inflammatory therapy
• Plasmapheresis
• Stem Cell/Bone Marrow Transplant
• Replacement of lost physiological factor
• Organ/tissue/mechanical graft

Question 17

Describe the measures taken to prevent GVHD

Answer 17

• Very close tissue matching

* Deplete donor marrow of T-cells in vitro prior to grafting