L15 Transplantation and Rejection Flashcards
Revision
What kind of screening do they do for blood donations?
There are three kinds of screening.
Mandatory screening which screens for HIV, Hep B, Hep C, Human T-Cell lymphotropic Virus, Hep E, and Syphillis.
Discretionary screening which screens for Malaria, T-Cruzi, West Nile Virus, Human Cytomegalovirus (HCMV), and Extra Hepatitis check s (HBVsAG - surface antigens, anti-HBs, HBV DNA to assess viral load.)
Bacterial screening which screens platelets only - stored at room temp.
Describe the role of alloantibodies
They target and attack foreign antigens on donor tissues, leading acute or chronic rejection of the transplanted organ.
Describe blood group matching: blood cell v antibody (Cue: body) v antigen (Cue: Genes)
Most common blood group systems: ABO and Rh determine blood types (A,B,AB,O)
Antibodies are proteins produced by the immune system and circulate in the plasma. They bind to specific antigens, initiating immune responses.
Antigens are specific markers found on the surface of RBCs that can trigger an immune response. A blood has A antigens, B blood has B antigens, AB has AB antigens, and O has neither.
In the context of transplantation, what are non self antigens?
Antigens produced by the donor, that are recognised as foreign by the recipients immune system. The donors antigens do not match the recipients, so the recipients immune system may mount an immune response against them, leading to a rejection of the graft.
Describe and explain the role of Human Leucocyte Antigen system in transplant rejection.
It enables the immune system to distinguish between self and non self. Ideally, a close match of HLA types between donor and recipient is essential to minimise the risk of transplant rejection.
When donor tissue is introduced, the recipients T cells can recognise the foreign HLA molecules on the surface on donor cells, triggering an immune response.
T-cell activation occurs when T cell receptors (TCRs) bind to peptide fragments presented by HLA molecules. If different, TCRs signal foreignness, leading to T-cell activation. This can result in cell-mediated rejection when T-cells attack donor cells and humoral rejection (antibodies against donor HLA are produced.
What does it mean to say HLA is highly polymorphic
There are many different alleles and variations within the HLA genes in the population.
This diversity is important for the immune system to recognise a wide array of pathogens.
High polymorphism can complicate transplantation due to the difficult of achieving compatible matches, susceptibility to autoimmune disease if recipient already has a high risk, and a response to donor tissue triggers an autoimmune reaction or exacerbates an existing one, extensive genotyping can strain resources and delay donor matching.
What are the four types of transplant
Autologous - self to self
syngeneic - Twins
allogeneic - same species
xenogeneic - diff species
What is Graft Verses Host Disease?
In allogeneic stem cell or bone marrow transplant, immune cells from the donor can attach the recipients tissues.
Describe and Explain why HLA-matching is important
What is cyclosporin?
What are the different kinds of donors?
Living donors
Brain Stem Death
Circulatory Death
Define ischaemia
Define warm ischaemia
Define cold ischaemia
Define and explain what is meant by reperfusion injury
Explain the degenerative changes that occur pre-transplantation
Define and explain the mechanism of EBV
Define and explain what CMV is and it’s relation to transplants and transfusion.
What are the primary factors that contribute to the safe transfusion of compatible blood?
Explain the role of the Human Leucocyte Antigen (HLA) system in organ transplantation and how it affects transplant compatibility.
Compare and contrast the types of organ donors available, including living donors and deceased donors, and discuss the complexities involved in organ allocation.
What immunological mechanisms contribute to transplant rejection, and why is HLA matching essential in this context?
How have advancements in immunosuppressive drugs since the 1960s influenced the field of organ transplantation?
Describe the importance of blood group antigens in the context of both blood transfusion and organ transplantation.
Outline the main steps involved in the processing, preservation, and transportation of organs prior to transplantation.
What are the differences between Donation after Brainstem Death (DBD) and Donation after Circulatory Death (DCD)?
Discuss the impact of donor characteristics such as age, health status, and comorbidities on transplantation outcomes.
How does the recent shift from an opt-in to an opt-out system for organ donation in the UK affect organ donation rates?
What are the potential future advancements in organ transplantation mentioned in the lecture, and how might they improve compatibility and outcomes?
Explain the significance of microbiological screening in organ donation and transplantation, and list the key infectious agents that are screened for.
Bonus: What role does Apol1 play in blood and organ transplantation?
APOL1 in an HLA variant predominantly found in certain populations - i.e., those of African descent, illustrating the evolutionary trains that can influence immune responses and transplant outcomes. Located on chromosome 22, it encodes a protein involved in lipid metabolism. It is believed to be an evolutionary trait against T.Brucei parasite conferring protection against sleeping sickness.
The most common variants are G1 and G2 - associated with some types kidney disease. The protection that was once a survival advantage, can confer the same effect, predisposing carries to some kidney disorders.
Having a close match to someone with APOL1 gene reduces the risk of transplantation rejection, minimising the likelihood of complications such as kidney disease progression.
