40.2 Transplantation

Question 1

What is an allograft?

Answer 1

Tissues or organs taken from unrelated members of the same species that can be used for transplantation.

Question 2

What is an isograft?

Answer 2

Tissues or organs harvested from an identical twin that can be used for transplantation and for which immune intervention is not required.

Question 3

What is a Xenograft?

Answer 3

Organs harvested from an unrelated species that can be used for transplantation. (e.g. the use of replacement heart valves harvested from pigs)

Question 4

What is tissue typing?

Answer 4

Procedure done to determine the compatibility of tissues/ organs from different individuals based on the similarity of histocompatibility antigens. It is done to help avoid rejection.

Question 5

Describe the concept of major and minor histocompatibility antigens.

Answer 5

The immunogenicity of an allograft is determined by:

Major histocompatibility antigens -> These are the MHC molecules that are the most important determinant of whether an allograft will be rejected.
Minor histocompatibility antigens -> These include various other antigens.

Question 6

How many of the major and minor histocompatibility system components need to match?

Answer 6

3 (acceptable minimised risk of allograft rejection)

Question 7

What are the major and minor histocompatibility systems?

Answer 7

These are the MHC1 HLA-A and HLA-B molecules, and the MHC2 HLA-DR subtype (with HLA-C, HLA-DP and HLA-DQ having a minor role in comparison), for which 2 (1 from each parent, in most cases) alleles are expressed from possible hundreds. If these match, a transplant can be carried out as the risk of immune recognition and targeting is quite low

Question 8

What are the 4 different types of allograft rejection?

Answer 8

• Hyperacute rejection
• Acute rejection
• Chronic rejection
• Graft vs Host Disease (GvHD)

Question 9

What is GvHD (Graft vs Host Disease)?

Answer 9

• Opposite of allograft rejection, since the allograft attacks the recipient
  
  • Some mature T cells from the donor are reactive with recipient proteins, leading to expansion and cytokine release

Question 10

When might graft-versus-host disease be useful?

Answer 10

GvHD may prove beneficial for eradication of leukaemias, known as the Graft vs Leukaemia (GVL) effect

Question 11

How can a graft be acutely rejected?

Answer 11

• The allograft contain donor antigen-presenting cells (APCs) that have donor MHC molecules on them
• Since transplants don’t usually involve joining up lymphatics, the APCs exit the allograft via the blood and enter the spleen
• The donor MHC molecules presented by the donor APCs are recognised by the recipient T cells in spleen, leading to their activation -> About 1 in 10 T cell precursors can recognise the MHC molecule
• This only happens acutely because the donor APCs die after some time

Question 12

How can a graft be chronically rejected?

Answer 12

• When donor APCs in the allograft die, they release antigens, such as the donor MHC molecules
• These molecules are taken up by recipient APCs, just like with any other antigens
• The donor MHC molecules are processed into peptides, which are then presented on the recipient APCs for T cells, activating them
• Only about 1 in 10⁶ T cells can recognise the donor peptide this way, so the immune response in weaker chronically, but it is continuous because donor cells keep dying over time

Question 13

What are the pathological consequences of a chronic rejection?

Answer 13

• Occurs over months/years
  
  • Involves the indirect pathway (see flashcard) where allograft cells die and release antigens, such as the donor MHC molecules, which are taken up and presented by recipient APCs as peptides to T cells
  • The reaction may be precipitated by infection
  • Involves T cells and alloantibodies, which can lead to occlusion of blood vessels due to thickening of arteriolar walls
  • The response is weak because only a small fraction of T cells can recognise the donor peptide this way, but it is continuous because donor cells keep dying over time

Question 14

What is hyperacute rejection of a graft?

Answer 14

• Occurs over hours
  
  • Caused by antibodies that exist within the host before transplantation
  • The antibodies bind to ABO blood group antigens (in the case of blood group mismatch) causing RBC lysis and complement activation
  • When endothelial cells are bound to, there are thrombi and organ infarcts