Transplantation Autologous Syngeneic Allogeneic Xenogeneic

Routinely performed transplantations: Kidney Heart Liver Lungs Pancreas Small bowel Hematopoetic stem cells

Occasionally performed transplantations: Hand Face Larynx (”voice box”)

Main problem in transplantation: Immune system attacks transplant. Transplantation antigens: HLA ABO Minor histocompatibility antigens

Transplant rejection is an immunological reaction.

The genetics of graft rejection. Figure 16-2 The genetics of graft rejection. In the illustration, the two different mouse colors represent inbred strains with different MHC haplotypes. Inherited MHC alleles from both parents are codominantly expressed in the skin of an A × B offspring, and therefore these mice are represented by both colors. Syngeneic grafts are not rejected (A). Allografts are always rejected (B). Grafts from a parent of an A × B mating will not be rejected by the offspring (C), but grafts from the offspring will be rejected by either parent (D). These phenomena are due to the fact that MHC gene products are responsible for graft rejection; grafts are rejected only if they express an MHC type (represented by a color) that is not expressed by the recipient mouse. Downloaded from: StudentConsult (on 12 March 2008 09:15 AM) © 2005 Elsevier

Direct recognition: Cross-reaction by a normal TCR, which was selected to recognize self MHC plus foreign peptide.

About 2% of T-cells will react with a cell with foreign MHC molecules: One MHC can activate many T-cells Allogeneic MHC bind many peptides High density of epitopes Many memory cells activated

Direct allo-recognition. MHC MHC + peptide

Activation of alloreactive T cells.

MLR

Transplant rejection Hyperacute (preformed antibodies) Acute (T cell activation) Chronic

Immune mechanisms of graft rejection.

Prevention of hyperacute rejection: ABO typing Cross-match (recipient serum, donor leukocytes)

Organ transplant recipients need life-long immunosuppression.

Immunosuppression

Kidney transplants: Transplantation centres cooperate so that kidneys are given to patients with most similar HLA.

Influence of HLA matching on graft survival.

Once removed from the donor, the kidney must be transplanted within 24-48 hours.

Main complications of immunosuppression: Increased risk of infection Increased risk of cancer Drug toxicity

Xenografts: Still not possible. Very strong immune reactions. Preformed (natural) antibodies to carbohydrate endothelium antigens – discordant species. For instance man and pig.

Transfusion: the process of transferring whole blood or blood components from one person (donor) to another (recipient). Blood components: Red blood cells, thrombocytes or plasma.

Three allelic glycosyltransferases ; A, B and O (non-functional) determine the ABO blood type.

ABO blood group antigens.

Natural antibodies in the ABO system: A individuals: Anti B B individuals: Anti A AB individuals: None O individuals: Anti A and anti B

Transfusion of red blood cells Universal donors Universal recipients

Transfusion of plasma

Rh(D) immunization (No natural antibodies)

(Bone marrow transplantation) = Stem cell transplantation Autologous/Allogeneic Leukemia, immune deficiency, aplastic anemia

HLA, but not ABO matching essential. MLR. Bone marrow registries Conditioning, harvesting. Intravenous injection Aplasia phase – infection risk

Graft versus host disease main complication. If treatment is successful, permanent immunosuppression is not necessary, but immunodeficiency and infections may be a problem.

Two mistakes in Abbas’ textbook: Page 374: ”Today, hyperacute rejection by anti-ABO antibodies is extremely rare because all donor and recipient pairs are selected so that they have the same ABO type.” Identity is not necessary, compatibility is sufficient. For instance, a donor with blood group O can donate a kidney to a recipient with bl.gr. A.

2. Page 381: ”HLA matching in renal transplantation is possible because donor kidneys can be stored in organ banks before transplantation until a well-matched recipient can be identified..” This is just fantasy! Kidney ”organ banks” has never existed. Kidneys must be used within 24-48 hours.