Solid organ transplant (SOT)

What are the types of transplant?

- Heart

- Lung

- Liver

- SPK

- Pancrease

- Kidney

- Vowel

- Multivisceral

What are the aim of solid organ transplant?

- Increased life expectancy

- Increased quality of life

What are the aims of immunosuppression?

- Prevent graft rejection

- Induction of tolerance

- Reduce risks of side effects, malignancy.

What are the types of graft?

- Xenografts

- Autografts

- Isografts

- Allografts

What are xenografts?

Grafts taken from a different species. Greatest chance of rejection

What are autografts?

Grafts taken from one part of the body to another. No rejection

What are isografts?

Grafts between genetically identical individuals. No rejection

What are allografts?

Grafts between members of the same species. May reject or may not.

What are MHC complexes and what are the classes?

- MHC complexes are molecules which present antigens to T-cells.

- T-cells are central in the rejection of grafts.

- Classes include MHC 1 and MHC 2.

Describe MHC 1 complexes.

- Present on all nucleated cells in the body.

- Present antigens to CD8 T-cells.

- Signals for the removal of self-cells that are infected or abnormal, not foreign cells.

Describe MHC 2 complexes.

- Present on (APCs) like dendritic cells, macrophages, and B cells.

- Present antigens to CD4 T cells.

- Triggers immune responses against foreign extracellular antigens, not self-cells.

How do T-cells cause rejection of grafts?

- T-cell recognises the foreign graft through antigen presentation.

- Signal 1 occurs as TCR binds to MHC2 on APC.

- Signal 2 then occurs as Co-stimulatory interactions:CD28 (T-cell) binds to B7-1/B7-2 (APC) as well as CD40-CD40L interaction enhances activation.

- This activates signalling pathways which activate transcription factors.

- Signal 3 then occurs as Growth signals trigger T-cell proliferation via: PI3K-mTOR pathway, activating the cell cycle.

What signalling pathways are activated in order to activate transcription factors when T-cells reject grafts?

- Calcium-calcineurin pathway

- MAP kinase pathway

- Protein kinase C-NFκB pathway

How can immune response be minimised?

- HLA compatibility

- Immunosuppression

What is HLA and HLA compatibility?

- HLA are proteins on cell surfaces that help the immune system recognise self cells from non-self cells.

- The matching of HLAs between the donor and recipient to reduce the risk of immune rejection of the transplanted organ.

What HLA types are strong determinants for transplant rejection?

- HLA-DR

- HLA-B

- HLA-A

What are the benefits of having good HLA compatibility?

- Better graft function

- Fewer episodes of rejection

- Longer graft survival.

- Possibility of reduced immunosuppression

What happens if there is poor HLA compatibility?

Immunosuppression is required.