Transplants Flashcards
Why would you use transplants?
If someone is undergoing end stage organ failure. This includes organs such as the heart, liver, kidney etc.
What are the challenges of transplant?
Not enough donors
Loss of organs because of immune attack (rejection).
Describe the immune response to transplanted organs?
If the organ is not off the same HLA the body will recognise all graft cells as foreign and mount the innate and adaptive immune response to destroy these cells.
Also ischaemia reperfusion injury will also take place and is caused by the donor organ being in a low oxygen environment
What happens to a kidney when it undergoes ischaemic reperfusion injury?
The lack of oxygen causes immune cell activation activating cytokines which begin to destroy cells. This happens in most transplanted organs and you have between 15 and 20 hours to get the donor organ into the recipient.
How is the innate immunity response triggered in ischaemic reperfusion injury?
The lack of oxygen causes DAMPs to bind to their receptors resulting in the complement to activate and neutrophils, macrophages and NK cells
What do DC cells do in the immune response against transplanted organs?
DC’s pick up antigen and migrate the the lymph node where they upregulate and activate T-cells. These T-cells then go back and destroy the kidney cells. The main target of this immune response is the HLA antigens or the recipient.
What do grafts express high levels of which is recognised as foreign by the adaptive immune response?
ABO antigens (you need to get this right)
HLA antigens
Non-HLA antigens
Why are HLA (MHC) important?
They help the body react to foreign tissues and activate T-cells
They are the main target for the immune response
What are the subtypes in class 1 and class 2 HLA (MHC) and what are they expressed on?
Class 1 = HLA-A, HLA-B, HLA-C (expressed on all nucleated cells)
Class 2 = HLA-DR, HLA-DQ, HLA-DP (expressed only on DCs, B cells, Mac/Monocytes)
How many HLA molecules does an individual have?
6 class 1 molecules on the cell surface
12 class 2 HLA on cell surface
Do unrelated individuals have different HLA’s?
Yes
What does the recipients immune response target?
They react against the HLA which are found on all cells, involved in T cell activation and are highly variable
What would happen if you were exposed to foreign DNA?
T-cell activation = this would destroy the donated cell leading to graft rejection.
Anti-HLA antibodies could be produced through exposure to foreign HLA e.g during pregnancy, transplant, blood transfusion
What are the different types of allorecognition and how do these work?
Direct - this is not normal and is when the Donor APC shows donor HLA directly to recipient T cell
Indirect - normal - donor HLA goes into vesicles and antigen goes into recipient HLA before being shown to recipient T-cell
Semidirect - donor HLA goes into vesicles before bieng shown to recipeint T cell
Do B cells react differently than usual when shown a donor HLA, and if so, why?
No