Immune Lecture 25 Study Notes
1. What is grafting?
-autograft: self grafting (taking out BM and putting it back in)
-syngraft: genetically identical
-allograft: between different individuals
-xenograft: between species
2. What is the average have life of a graft?
3. What is the limiting factor?
4. What is a hyperacute rejection?
-tissue destruction within minutes
-antibody mediated (C’ and FcRs/NK cells) – going to bind the vascular endothelium
of the graft an initiate an inflammatory response, occluding the blood vessels
-the antibodys must be preexisting
5. Discuss blood typing.
-blood transfusions are the most common transplantation done
-blood type is determined by the carbohydrates found on your cells
-if your O – you don’t have any antibodies (your anti A and B)
6. Discuss hyperacute rejection and the xenograft
-human donors are limiting so we look to other sources for compatible tissues
-we use pigs: similar in size and physiology
7. What is the problem with pig cells?
-have another carbohydrate: alpha-Gal (galactose-alpha 1,3)
-we have pre-existing antibodies to mediate a hyperacute rejection.
8. What is the solution to this problem?
-get alpha Gal deficient pigs – get rid of the carbohydrates
9. What is the remaining problem?
-alternative pathway of compliment activation: get a “tick-over” of C3 activation
where it become semi activated and inserts into a membrane near by
-but we have proteins such as DAF to fix this
-pigs have “pig DAF” so it doesn’t fix this very well
10.Solution to THAT problem?
-regulatory proteins that are conserved aren’t identical across species
-make it so that it is alpha gal deficient and make a human form of DAF
-a-Gal -/- hDAF Tg pigs 11.What is acute rejection?
-tissue destruction within 10-13 days
-this will be faster if you were previously exposed
-T cell mediated response directed towards MHC class 1 and 2
12.What are allo-specific T cells? ***nonself MHC
-make up 1-10% of circulating T cells which lead to the discovery of MHC
-allo recognition depends on TCR binding to allo-MHC
-new MHC that was not previously selected for
13.How were they binding the T cells if they had no previous interaction?
-sometimes CDR1/2 is enough (coded in the V region)
-if this is of high enough affinity it will create a TCR
-no negative selection for allo-MHC
-the peptide doesn’t matter: can bind without but binding can also be specific
14.What is acute rejection?
-donor-derived DC migrate to the lymphatic tissues to initiate an allo-response
-activated T cells invade the donor tissue and cause