12. Can I Have Your Kidney Please? Flashcards
What are the 4 types of grafting?
- Autograft - from one part of the body to another
- Isograft - between genetically identical individuals
- Allograft - between different members of the same species
- Xenograft - between members of different species
What are the rules of transplantation? And who invented these rules?
Peter Medawar - Host vs Graft Reactions
If you graft tissue from A strain mouse onto another A strain mice then it will be accepted.
If you graft B strain tissue onto A strain mouse it will be rejected
If you graft B strain tissue onto A X B strain mouse then it will be accepted.
IF you graft A X B strain tissue onto B strain mouse it will be rejected
What is a 2nd set rejection? What is a 1st set rejection?
2nd set rejection - a secondary immune response is caused (faster, stronger)
If you transfer T cells (from already grafted A strain mouse) to an A strain mouse with no transplant and then transplant B strain skin then causes 2nd set rejection.
1st set rejection - a primary immune response is caused
If you transplant T cells with no immunological memory then 1st set response
How do T cells recognise differences between foreign MHC and their own?
Two pathways:
Direct pathway - Donor cells have MHCI molecules which are different (allo-MHC), TCR recognises foreign MHCs and any presented peptides, activates T cells and then attack T cells
Indirect pathway - Donor cell with allo-MHC, allo-MHC is taken off by recipient APCs and chopping it up into peptides then putting it on the APC surface
What is the graft-versus-host reaction?
Where the graft attacks the host if the host immunocompromised. Unable to avoid transferring some WBCs especially if transferring bone marrow - donor tissue attacks immunosuppressed host
What organ transplant does not require matching of donor and recipient?
COOOORNEA - cornea is not vascularised (no blood supply) so immune system cells in recipient can’t react against antigens as they are hidden (also pig heart valves)
What is the major organ with the highest graft survival rate? What is the lowest?
Kidney is highest, heart and lung is lowest - but all over time have an increased rejection rate
What are the types of rejection reactions in grafts?
Hyper acute - occurs within mins/hours - recipient has preexisting antibodies which recognise foreign antigen on the donor (very rare)
Accelerated - days - reactivation of sensitised T cells
Acute - days/weeks - primary activation of T cells (rare)
Chronic - months/years - unclear causes, antibody immune complexes, cellular reaction, recurrence of disease - common
What is tissue typing?
The matching of HLA
Describe the polymorphic HLA specificities and their inheritance
One version of each HLA comes from each parent.
Beta chain of HLA-1 (MHCI) doesn’t vary but alpha chain varies hugely
Beta chain of HLA-2 (MHCII) varies much more than alpha chain
How does the number of HLA mismatches between a graft donor and recipient affect graft survival?
As the number of HLA-A/B/DR mismatches increases the graft survival decreases - varies by about 3-5%
What must you also do during transplants?
Immunosuppress people - can use cyclosporine, tacromilus or rapamycin
How do immunosuppressants work?
Interfere with T cell activation
Rapamycin - if transcription through TCR then produced IL-2 something
What is the alpha-gal problem with pig xenotransplantation?
Pig cells have two galactose sugars which are linked - humans don’t make this structure due to mutation but many microbial organisms have this structure and have many IgGs which recognise it. So need to knock out alpha-1,3-galactosyltransferase
