Transplantation - graft rejection

again theres a bunch of diagrams from the lectures and textbook that dont translate well to flashcards

what is graft rejection?

an immunological responses mainly mediated by T cells, but antibodies also play a role in graft rejection.

what are the different types of grafts?

• autograft

• synergenic graft

• allograft

• xenograft

what is an autograft?

Grafts between different sites of the same animal or person – no graft rejection

what is a synergenic graft?

Grafts between genetically identical animals or people – no graft rejection

what is an allograft?

Grafts between unrelated or allogeneic members of the same species – graft rejection

what is a xenograft?

Grafts between members of different species – graft rejection

Allograft rejection

Antigens that differ between members of the same species are known as alloantigens, and the immune response against such antigens is known as an alloreactive response

alloreactive T cells

Approx. 1-10% of T cells in an individual are said to be alloreactive. they will respond to stimulation by cells from another, unrelated, member of the same species due to the recognition of allelic polymorphism in MHC molecules. In most tissues these are predominantly MHC class I.

MHC matching in transplants

MHC matching of recipient and donor may prevent or slow down the transplant rejection process. Even completely MHC matching does not ensure allograft survival

what are minor histocompatibility (minor H) antigens?

In MHC identical grafts, rejection is caused by immune responses against peptides from other alloantigens due to differences in other genetic loci.

Graft rejection due to minor H incompatibility

slower than the rejection of MHC-disparate grafts.

Self proteins are routinely processed and presented as peptide:MHC class I complexes. If a polymorphic protein defers between the graft donor and the recipient, it can give rise to an antigenic peptide that can be recognized by the recipient T cells as non-self.

what are the 2 ways of presenting transplant alloantigens to the recipient’s T cells?

1. direct allorecognition

2. indirect allorecognition

Direct allorecognition

Antigens are presented by APCs of donor origin also called passenger leukocytes. Donor APCs leave the organ graft and migrate to secondary lymphoid tissues of the recipient where they can activate host T cells. Migration of the APCs occur via the blood and not the lymphatics.

Indirect allorecognition

Uptake of allogenic proteins by the recipient’s APC and their presentation to T cells by self MHC molecules. Indirect allorecognition contributes to the development of an antibody response to a graft. Antibodies produced against alloantigens are called alloantibodies

what is hyperacute graft rejection?

Existence of pre-existing alloantibodies against blood group antigens or polymorphic MHC can cause rapid rejection of transplanted organs.

Alloantibodies can bind to antigens on the vascular endothelial cells of the graft and initiate the complement and blood clotting cascades,
causing blocking and destruction of blood vessels and hemorrhage in the transplanted organ. This reaction is very rapid and can occur within minutes of transplantation.

how can hyperacute graft rejection be avoided?

cross-matching donor and recipient to determine whether the recipient has pre-existing alloantibdoies.

what is chronic allograft vasculophathy?

A chronic reaction and a major component of late failure of transplanted organs. Characterized by concentric arteriosclerosis of graft blood vessels, leading to hypoperfusion of the graft and its eventual death.

what is the cause of chronic allograft vasculophathy?

thought to be recurring, subclinical acute rejection events due to the development of alloantibodies against the graft vascular endothelium or alloreactive effector T cells.

what is Graft-versus-host disease (GVHD)?

GVHD is caused when mature donor T cells present in the HSC preparations recognize the tissues of the recipient as foreign, causing a severe inflammatory disease involving many organs, in particular the skin, intestines and liver.