tissue transplantation Flashcards

Question

Serology (Commercial Antibody Test)

Answer 1

The original method involved collecting peripheral blood from the donor and enriching the lymphocytes for HLA typing using commercial anti-HLA antibodies in the presence of complement (i.e. rabbit) looking for lysis. This test was simple, quick and cost effective. It was limited by the available commercial antibodies employed. Given the HLA phenotypes were highly diverse, the assay missed other epitopes and thus, was not always accurate.

Answer 2

These molecular tests have largely replaced serology as they are more accurate and sensitive. Both of these tests, take time and have to be evaluated in light of result turn-around time. RT-PCR is also an accurate and fast test, but as with the other molecular tests relatively expensive. Still, is there really a need to put a cost value on a test to help decide whether a graft is going to take or be rejected

Answer 3

molecular test used for HLA typing. The test takes the donor’s sample is mixed with a commercial reference HLA allele and run on a gel electrophoresis. Similar to the serology test, there is only a limited number of reference HLA alleles available making it a less attractive test

Answer 4

determining the nucleotide sequence or order of nucleotides within a DNA segment. This currently is the most accurate method for HLA typing. There are 2 approaches: Sanger sequencing or next generation (Next-Gen) sequencing. The Sanger sequencing employs selective chain-terminating dideoxynucleotides via DNA polymerase during DNA replication, in vitro. Next-Gen sequencing is the new gold standard that has revolutionized genomic research.

Answer 5

enriched peripheral blood leukocytes (specifically lymphocytes) from both the donor and recipient are co-cultured together to determine if they will mount a response against each other. If you look at Table 19.2, you can see the various ways in which the assay can be setup. From the stand point of assessing for tissue rejection, the best procedure would be to chemically inactivate (I.e. using Mitomycin C) the donor lymphocytes and determine if the recipient lymphocytes (i.e. cytotoxic T cell) would react and kill the donor lymphocytes. I use to run these assays. They are labor intensive and time consuming. The assay I use to run also included a radioactive probe which involved a lot more regulations and expensive equipment. With the advent of the DNA tests, it is highly likely that this assay is not used on a routine basis

Answer 6

Hematopoietic stem cell (HCT) transplantation is the procedure in which donor stem cells are transplanted to the recipient bone marrow in order to re-establish normal, healthy hematopoietic stem cell lineage that will yield normal and healthy blood cells. This type of transplantation occurs when the recipient’s own HCT is defective (I.e. SCIDs) or diseased (i.e. leukemia). In both situations, the recipient is usually irradiated or administered chemotherapy at high enough doses to destroy the existing bone marrow. As with all grafts, tissue typing is extremely critical here as incorrect or sloppy HLA typing can lead to a condition known as Graft-Versus-Host Disease

Answer 7

GVHD is a unique disease in which the donated bone marrow or stem cells upon differentiation and maturation into mature immune cells (i.e. lymphocytes) recognize the recipient’s cells in the body as foreign and mount a response against them. There are 2 forms of GVHD: acute GVHD and chronic GVHD. The clinical signs and severity can vary by patient, but skin inflammation and jaundice are common clinical signs. The acute form usually occurs within the first 100 days of the transplant. The acute form is usually associated with skin rash, liver involvement (i.e. jaundice), nausea and diarrhea. The chronic form appears later and typically involves multiple organ systems

Answer 8

As organ transplantation has become a more common treatment for a large number of diseases, the demand for these organs has outpaced the supply. As a result, tens of thousands of people on the transplant list die each year, that roughly 20-25% of the patients on the organ transplant list. This has pushed transplantation medicine to focus on other organ sources, such as xenogeneic transplants or animal to human transplants. To be honest, it is an ethical dilemma not to mention a medical dilemma. It is an ethical dilemma, because select animal species are raised for the purpose of harvesting their organs. This logically doesn’t sit well with animal rights groups, in particular species that are closely related to man or that are companion animals. Food animals, such as the bovine (cow) or porcine (pig) don’t seem to generate the same level of opposition. Presently, pigs are the most animals used in xenogeneic transplants. Similar to allografts, xenografts are immunogenic and will mobilize the recipient’s immune system to reject the graft. What scientists are now focusing on is using genetic engineering to manipulate the pig donor organ’s immunogenicity. The only other medical concern regarding xenogeneic organ transplants is the potential risk of the transplant carrying infectious agents (i.e. porcine viruses) to the recipient. Currently, there is no data that shows porcine viruses pose a risk to humans who have received pig organ transplants

Answer 9

developing fetus evade the maternal immune system: the maternal immune system cannot detect the developing fetus. The placenta serves as a major barrier to the maternal immune system. The fetal cells that make up the outer trophoblast of the placenta lack discernible MHC Class I and Class II molecules, which prevents T cell recognition. They do possess a special class Ib MHC, HLA-G, which can function as a ligand for the killer inhibitory receptor on NK cells and block their activation. In addition, the uterine environment, under in part by maternal hormones, secretes a number of different proteins and cytokines that suppress immune response

tissue transplantation Flashcards

(33 cards)