Immune Lecture 25 Study Notes.docx

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Microbiology and Immunology
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Microbiology and Immunology 3300B

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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? -8 years 3. What is the limiting factor? -having organs 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
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