Flashcards in L23: Fetal Transplant Deck (18):
ID twin to twin
Person to person (not ID twins)
Species to species
Individual providing the organ. In bone marrow transplantation
and selected forms of liver, lung and kidney transplantation the donor may be a living, usually but not always related, individual.
This gene cluster is nature's way of providing a unique, immunological signature for each individual that provides the means by which the immune system can demarcate self from non-self, provide effective immune surveillance, and identify altered or infected host cells.
Major histocompatibility complex (MHC) (also designated the HLA complex in humans)
Primary barrier to successful organ transplantation?
(In the randomly outbred human being, an organ transplanted from one individual to another (other than identical twins) will be immediately RECOGNIZED AS NON-SELF or foreign and this event sets in motion MULTIPLE immunologic pathways of destruction that culminate in rejection of the transplanted organ.)
What cell typing method is the most effective, for predicting # of matched MHC loci, and thus graft acceptance?
The more loci matched the better, but MHC Class 2 (DR) matches are the most strongly predictive of graft survival.
Originally, the source of the antibodies used to detect HLA specificities were usually from women with
multiple pregnancies who reacted to a paternal HLA antigen.
Note: More recently, tailored monoclonal antibodies are available against specific MHC loci.
Recipients won't make antibodies for their own HLA's. Describe a technique that harnesses this premise, to determine the HLA specificity of a potential organ recipient.
Complement-Dependent Cytotoxicity Assay
1. Extract recipient serum
2. Incubate serum with lymphocytes of known HLA
3. Add complement
4. Lymphocytes that formed immune complexes will lyse via complement-mediated MAC
Conclusion: lymphocytes that were NOT lysed by recipient antibodies (plus complement) are have no foreign HLA to recipient.
Other high-tech methods for assessing HLA status?
Tissue Typing Laboratories are now using flow cytometry, ELISA and molecular methods to decrease time of analysis and increase sensitivity and decrease costs but you need to understand the fundamentals of detecting HLA antibodies.
What is the basic premise of the mixed lymphocyte culture (MLC)?
"In Vitro Transplant"
If HLA from Joe's lymphocytes (responder/recipient) DIFFER from HLA from Jim's lymphocytes (stimulator/donor), there will be a REACTION measurable by DNA synthesis (responder cells try to divide).
In the MLC, which lymphocyte population should be irradiated?
Stimulator lymphocytes, not responder. We don't want the stimulator cells to divide if HLA differs, just the responder cells.
In a solid organ transplant scenario (eg. heart, kidney) the responder cells are the
recipient cells and the stimulator cells are from a potential donor.
Passenger leukocyte example?
Pre-existing antibodies that react immediately upon graft. What type of rejection?
Sudden 10-90 day appearance of effector mononuclear cells in the graft. Vigor depends on DR mismatch, gender, intensity of immunosuppression. What type of rejection is this?