Denzin. - Transplantation Flashcards
Allograft
Xenograft
Alloantigens or xenoantigens
Alloreactive and xenoreactive
Allograft - allogenic graft
Xenograft - Xenogenic graft
Alloantigens or xenoantigens - antigens that are the target of rejection
Alloreactive and xenoreactive - antibodies and T cells that react against the alloantigens or xenoantigens
First vs. second allograft rejection
In general, in an allograft what happens is that when you get the great, there will be revascularization in 3-7 days. Then healing in 7-10 days and it will be resolved in 12-14 days. In a graft rejection though, with revasculrization/blood supply comes immune system cells and they will make sure to cut off the blood supply and the graft will die. In a second allograft rejection it will occur even faster.
what is the main target for graft rejection?
The HLA/MHC molecules. If you get a graft someone,, your body will immediately see the MHC molecules as non-self.
Why is it that a graft infection is much worse than a regular infection?
Because usually when you have an infection it is only a small percentage of the MHC molecules that present non-self antigen. However, when you have a graft, you are introducing thousands of non-self MHC molecules. This will set of a massive T cell reaction, so it is very dangerous.
Minor Histocompatibility Antigen
Also causes problems in graft rejection but not as much as the major histocompatibility antigens. These are just proteins that are highly polymorphic, are different in different people. Like my IL-1 receptor can be 2 AAs different that yours.
Direct recognition
The DCs from the donor tissue leave the graft and travel to the host lymph nodes presenting the alloantigens from the donor to host T cells.
- The DCs can also provide co-stimulation (for some reason doesn’t really make sense)
Indirect recognition
The hosts DCs recognize the MHC molecules (or other molecules) on the donor graft cells to be foreign. They phagocytize them and present them on their surface. CD4 T cells then secrete cytokines to injure the graft and promote inflammation
- DCs also provide co-stimulation of course
- Abs are involved in this pathway
Hyperacute rejection
Rejection occurs within minutes of transplantation. This is mediated by circulating Abs that are specific to graft endothelial cells that are present before transplantation. Usually due to different blood types, we have circulating IgMs naturally to protect us from this stuff. It can happen in other situations as well if you already have Abs to this specific antigen.
Acute rejection
- days to week after transplantation
- T cells and A specific for alloantigens in graft
- CTL and CD4 T Helpers both involved
Chronic rejection
- months to years
- fibrosis to the graft and narrowing of the blood vessels in the graft (atherosclorosis)
- T cells will make more fibroblasts.
- Abs contribute also
Prevention and treatment of graft rejection
Drugs to suppress immune system
Matching HLA subtypes
Cyclosporine
Inhibits T cell activation by clocking the downstream effects of TCR at the level of calcineurin. This will stop IL-2 production
Rapamycin
Inhibits T cell proliferation by blocking the downstream affects of the IL-2 receptor so T cells will not proliferate.
Graft vs. Host Disease (GvHD)
- The issue is that the host is immunocomprimised. So, when you have a graft the T cells from that donors graft will take over the hosts body and wreak havoc.
- Another issue with the patient being immunocomprimised is that there are a small number CTLs introduced which ordinarily wouldn’t be a problem because the immune system can get rid of them but because this patient is immunocomprimised the CTLs can kill the patient.
Autologous
Syngenic
Allogenic
Xenogenic
Autologous - self to self
Syngenic - identical twins
Allogenic - one human to another
Xenogenic - one species to another
