Transplants Flashcards
what is organ transplantation?
- a crucial treatment for patients with end-stage organ failure, offering life-saving benefits by replacing a failing organ with a healthy one
- typically patients need to take immuno-suppresive drugs for the duration of their lives to prevent rejection
what are the most successful organ transplants?
- kidneys
- heart
- lung
- liver
what are the types of transplants?`
1) autograft
- transplant from one part of the body to another (i.e skin graft or bypass surgery)
2) isograft
- transplant a tissue from one identical twin to another (within twin set)
3) allograft
- transplant between different members of the same species (i.e 2 humans)
4) xenograft
- transplant between members of different species, typically from those genetically similar (i.e pig heart valve –> human)
what type of transplant has the highest and lowest risk for rejection?
highest risk of rejection = xenograft
lowest risk of rejection = autograft
what is the difference between first set rejection and second set rejection in organ transplantation?
first set rejection = first exposure to a transplant takes 10-14 days to reject the tissue
second set rejection = second exposure to a transplant takes 3-7 days to reject the tissue
How does adaptive immunity explain the difference in rejection times between first set rejection and second set rejection in organ transplantation?
in first set rejection:
- immune system needs time to learn about the foreign tissue and generate a response
- the body doesn’t have any prior memory of the transplanted tissue so immune response is slower
in second set rejection:
- If the body is exposed to the same transplanted tissue again, it responds much more quickly
- faster rejection occurs because the immune system “remembers” the first exposure and has developed memory cells that recognize the foreign tissue
- allows for quicker and stronger immune response for rejection
how do CD4 and CD8 T cells contribute to transplant rejection?
- CD8 T cells are cytotoxic and directly attack transplanted tissue, but their depletion alone doesn’t significantly delay rejection.
- CD4 T cells help activate the immune response, speeding up rejection. Depleting CD4 cells reduces the time to rejection.
- combined depletion of CD4 and CD8 T cells further extends the time to rejection, showing that both T cell types work together to mediate transplant rejection.
–> This demonstrates that the immune system’s rejection of the transplant depends on the combined actions of both CD4 and CD8 T cells
what are the 2 methods t-cells detect non-self tissues?
1) direct allorecognition
2) indirect allorecognition
what is direct allorecognition?
- donor antigen-antigen presenting cells (APCs) in transplanted tissue (ie kidney) present antigens to recipient t-cells
- recipient t-cells recognize non-MHC on donor APC and mount a response
*t-cells directly recognize non-MHC and do something
what is indirect allorecognition?
- during transplantation, donor MHC molecules are shed from the transplanted tissue.
- the non-self MHC molecules are taken up by the recipient’s antigen-presenting cells (APCs).
- the recipient’s APCs present the non-self MHC peptides in their own MHC molecules.
- the recipient’s T-cells recognize the “non self’ MHC peptides and mount an immune response, leading to transplant rejection
what criteria is used to match transplant donor and recipient?
1) blood type
2) HLA type
3) cross-matching
how is blood type used to match for transplants?
- there are four main blood types based on the presence of A, B, or O antigens, which are found on red blood cells, as well as epithelial and endothelial cells.
- the blood group of the donor and recipient must match to prevent immune reactions.
- if the recipient has antibodies against the donor’s blood-group antigens, hyperacute rejection will occur, leading to immediate rejection of the transplanted tissue.
how is HLA type used to match for transplants?
- transplant programs aim to match the HLA haplotypes of the donor and recipient as closely as possible
–> this means you want to have the same HLA alleles in both donor and recipient, particularly HLA A, HLA B (MHC class I), and HLA DR (MHC class II) - matching is more important in bone marrow transplants than in other solid organ transplants
–> you need donor APC and t-cells to recognize your recipients MHC
why is HLA matching difficult?
- there is significant diversity and polymorphism in the MHC, making a perfect match challenging.
–> closer HLA match reduces the chance of rejection
–> a bad HLA match increases the likelihood of rejection
why is it important to match HLA A, HLA B (MHC class I), and HLA DR (MHC class II)?
how is cross-matching using for matching transplants?
cross-matching involves testing the recipients blood for any pre-circulating antibodies that could attack the donors tissue
- this includes antibodies against other blood types
- they are looking for anti-non self HLA antbodies
- these antibodies may have arised from past events like blood transfusions, pregnancy or previous transplants
-
how does cross matching work?
- blood of the recipient, lymphocytes from the donor and complement are mixed
–> if there are no donor-specific HLA antibodies present in recipient blood = no antibody binds to lymphocyte = compatible match & PROCEED
–> if there are donor-specific HLA antibodies present in recipient blood = antibody binds and activates complement + lysis = match not compatiable & DON’T PROCEED
what are the types of transplant rejection?
1) hyperacute rejection
2) acute rejection
3) chronic rejection
what happens in hyperacute transplant rejection?
- pre-formed antibodies and complement act against transplanted tissue and
destroy it - occurs within hours to days (FAST)
- rare due to blood typing and cross-matching
what happens in acute transplant rejection?
- acute rejection is primarily cell-mediated and involves a Th1/Th17 immune response and the release of pro-inflammatory cytokines.
- it is an example of delayed-type hypersensitivity (DTH), where the immune system responds to the transplanted tissue as if it were foreign
- typically occurs within 10 days of transplantation, but can often be reversed by immune-suppressive drugs
what is the mechanism of acute transplant rejection?
- CD4+ T cells recognize the non-self MHC on the transplanted organ and release pro-inflammatory cytokines
- CD8+ T cells directly kill the donor cells by recognizing the non-self MHC on the transplanted tissue
- anti-donor antibodies can also be generated, triggering antibody-dependent cellular cytotoxicity (ADCC) by NK cells and activating complement, which further damages the transplanted organ.
what happens in chronic transplant rejection?
chronic rejection is not as well understood as acute rejection but is thought to be linked to Th2 responses
- leads to tissue remodeling and fibrosis in the transplanted organ, which results in loss of organ function
- very common
- rejection can take months to years to develop
- chronic rejection cannot be reversed with current treatments
- most challenges aspect of clinical transplantation
what are immunotherapies?
A type of therapy that uses substances to stimulate or suppress the immune system
*considered a tightrope because you don’t want to suppress immune system too much because you become more vulnerable other pathogens/infections
2 types of immunotherapies
1) generalized immunosuppressive drugs
- target all T and B cells
- used before and after transplantation
2) specific immunosuppressive drugs
- use monoclonal antibodies that target specific aspects of the immune response to the tissue rejection process
