Transplantation and Immunosuppressive Drugs Flashcards
Define transplantation.
Transplantation can be defined as the introduction of biological material (e.g. organs, tissue, cells) into an organism.
The problem with that is that the immune system has evolved to remove anything it regards as non-self.
List the different types of donor/recipient relationships.
- autologous
- syngeneic
- allogeneic
- xenogeneic
Describe autologous donor/recipient relationships.
Autologous transplantation is the transplantation of tissue from one part of an organism into another part of the same organism.
Describe syngeneic donor/recipient relationships.
Syngeneic transplantation is when a donor donates part of their tissue to a recipient, but they are genetically identical.
Describe allogeneic donor/recipient relationships.
Allogenic transplantation is when a donor donates part of their tissue to a recipient, but they are genetically different.
An example of this would be siblings, or relatives.
Describe xenogeneic donor/recipient relationships.
This is the transfer of tissue from an organism of one species to another.
This is not common; there have only been a few cases where this happens with success.
Describe the importance of MHCs in transplants.
MHCS are major histocompatibility antigens.
The human MHC is called HLA, Human Leukocyte antigen. It defines tissue compatibility.
Immune responses to transplant are caused by genetic differences between the donor and the recipient.
The most important are differences between the antigens forming the major histocompatibility complex (MHC).
Describe HLA diversity (where it is found in the genome).
The HLA gene is found on chromosome 6.
The alleles are split up into Class I (consisting of 3 alleles) and II (consisting of 6 alleles). The Class II molecules are heterodimers, while Class I are monomers.
Almost all nucleated cells present HLA Class I, while immune cells present both Class I and Class II.
What is the importance of epitopes on donor MHC?
At the current time, HLA are typed, and the donor and recipient are matched based on typing information. There are many ways of doing it, sequencing being the best one. The trouble is that there are 1000s of HLA.
NGS can be used to identify the epitopes on the HLA, rather than the HLA themselves. There could be two HLAs that have genetic differences, but don’t have any different epitopes. It’s possible that the actual number of epitopes that are important in rejection is far fewer than the HL alleles. In terms of matching, we are moving from matching HLA to matching alleles on HLA.
This could be much better, but NGS is more expensive so cannot be done routinely.
Describe how APCs activate different T-cells.
Antigen-presenting cells will express MHC Class I and MHC Class II; this is where the variation is in the molecule.
The TCR detects a combination of both the peptide and the MHC, so it is a peptide-MHC or peptide-HLA complex that the TCR is detecting.
MHC Class I will activate TCR in CD8 T Cells, and MHC Class II will activate TCR in CD4 T Cells.
Describe MHC II loading in cells.
This is only on professional APCs.
These cells are good at taking up external material, which they will process in the phagolysosome into peptides. These peptides interact with the vesicle containing MHC and CLIP (maintains the shape of HLA until the peptides arrive).
When the peptides bind, the complex goes to the cell surface to activate CD4 T cells.
What is the key point about the differences in which cells have which class of MHC?
All cells have the MHC Class I, which means that if they are infected by a virus or bacteria, they can alert the immune system of it so that they are targeted or removed by CD8 cytotoxic cells.
MHC Class II is only on immune cells, so that when those cells have got to the site of infection and internalised the infectious material, they can present them to CD4 T cells to orchestrate a more robust and long-lasting immune response. Thus, they need more regulation.
As a recap, what is the difference between helper T cells and cytotoxic T cells?
Helper T cells – information and support for other immune cells via cytokine production
(helper T cells are required to produce antibody and cytotoxic T cell response)
Cytotoxic T cells – highly specific killer cells
What are the two ways in which foreign bodies can be recognised?
There can be direct recognition of the HLA, or indirect recognition of the peptide as foreign.
Describe indirect and direct recognition.
If the patient has had a transplantation, the HLA can present a non-self antigen, and you get indirect allo-recognition.
When you have an unmatched donor HLA, you will get direct allo-recognition because the TCR of the recipient T cells will detect this MHC.
You may also have a donor peptide in there, but even if the peptide itself isn’t recognised as foreign, the fact that the HLA is unmatched means that the combination of peptide-HLA is different, and TCR will get activated.
