Term
What kinds of grafts are;
-From self?
-From identical twin?
-From same species?
-From different species?
Which will be rejected by recipient? |
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Definition
-Autograft
-Isografts/syngrafts
-Allogeneic grafts
-Xenogeneic grafts
-All but autografts (even isografts) will eventually be rejected by the recipient; thus, all but autografts will require lifelong immunosuppression |
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Term
| What main cytokine increases MHC molecule expression in the graft? |
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Definition
| -IFN-gamma (for both class I and II) |
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Term
| What are the four classes of graft rejection, their time frame, and what mediates them? |
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Definition
Hyperacute;
-minutes to hours
-mediated by preexisting antibodies
Accelerated acute;
-days
-mediated by memory T cells (like hyperacute, but antibodies aren't still around)
Acute;
-days to weeks
-T cells are exposed for the first time and mediate; a cellular or humoral response may ensue (humoral can't be helped)
-This is the normal/most common response
Chronic;
-months to years
-can be mediated by all immune effector mechanisms (esp. the humoral response)
-would be for something like an unmedicated syngraft
- Causes gradual occlusion of blood vessels
-After humoral response sets in, immunosuppressants won't work
-Note; these are all unmedicated responses |
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Term
| What is the last special example of transplant rejection? What causes it? How do we prevent it? What are the symptoms? |
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Definition
-Graft-versus-host disease
-From transplanting immunocompetent tissues that contain mature *T cells; only example transplanted is BONE MARROW
-The transplanted T cells in the bone marrow will recognize and attack the recipient
-We prevent this by removing the mature T cells and also by making sure the donor and recipient are close matches
-Symptoms are rash, jaundice, diarrhea, and GI hemorrhage brought on by widespread epithelial damage |
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Term
| How do we do ABO blood typing? For what types of transplants do we do it? |
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Definition
-We treat patient blood with serum of known blood types; so if you have serum from type A, you know it has anti-B antibodies and will agglutinate types B & AB
-We do this for ALL TRANSPLANT TYPES (as apposed to MHC typing, which isn't as important because of available drugs) |
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Term
| When do we do MHC typing? |
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Definition
-When there is not an immediate need and the tissue is coming from a live donor
-We always still do it for bone marrow transplants as well
-Reason is that we don't have time with a cadaver donor, or if there is an immediate need (MHC typing is slow and drugs are good) |
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Term
| What are isohemagglutinins? Why/how are they produced? |
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Definition
-They are IgM antibodies that will bind ABO blood group antigens on RBCs and endothelial cells of non-self cells
-They arise because of carbohydrates similar to the AB antigens on intestinal flora
-This is why type A people have anti-B antibodies
-Note; they are IgM so they will not cross placenta! |
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Term
| What are the HLA molecules we test for? |
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Definition
-We do HLA-A, HLA-B, and **HLA-DR**
-The rest don't seem matter in rejection |
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Term
| What test to we run for MHC-type 1 matching? Explain the test method? |
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Definition
-We use microcytotoxicity tests
-We would have a bunch of HLA-A&B antibodies to each allotype (many exist) in serum; called ANTISERA
-We would treat patient cells with all these antisera, do a wash, treat with COMPLIMENT, and then use dye (typan blue or eosin) that would be taken up by leaky cells
-In practice you would have a bunch of wells, from HLA-A1 to HLA-A(n), and you would look for dark wells |
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Term
| What test to we run for MHC-type 2 matching? Explain the test method? What measure do we derive from this? |
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Definition
-Can use a microcytotoxicity test, but more often we use a mixed lymphocyte reaction (MLR)
-The test is simple; you irradiate one persons lymphocytes, mix them together with another persons lymphocytes, and add in titrated thymidine
-Uptake of the radioactive thymidine is a sign of proliferation of the un-irradiated cells
-The irradiated cells cannot proliferate and simply serve as a source of HLAs to react with (namely HLA-DR)
-We use this to make a stimulation index; ratio of proliferation relative to control (so 1 is best) |
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Term
| What immunosuppression drugs do we use? What is their goal? When would we not use immunosuppression? |
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Definition
-Cyclosporin A is a big one; inhibits IL-2 and IL-2 receptor production
-Cyclophosphamide (mitotic inhibitor), azathioprine & mercaptopurine (block proliferation), and corticosteroids (inhibit inflammation) are also typically used
-All of these are taken life long
-In general, they act to block T cell proliferation/action
-We wouldn't need to use immunosuppression in autografts or in transplant of IMMUNOPRIVILEGED SITES which do not have lymphatics (*cornea, testes, uterus, and brain) |
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Term
| What is anergy? How could we stimulate it in immunosuppression? |
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Definition
-Anergy happens when there is a lack of second activating signal for T cells and they become unresponsive to antigen
-We could block CD28 |
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Term
| The following are for Lima (blood immunology); |
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Definition
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Term
| What is the most and least common blood group? |
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Definition
-Most common is O, least is AB
-Overall the order is AB B A O (Abba O)
-Note that the O group has the nonimmunogenic H antigen |
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Term
| Which antigen is the one that matters in the Rh blood group system? |
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Definition
-The Rh (Rhesus) system is the second most important blood group system after ABO
-The D antigen is the most important and is what the Rh-/+ designation is referring to
-This is why RhoGAM is anti-RhD IgG |
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Term
| Do ABO groups cause HDNB? |
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Definition
-They can (about 50%), but it is much less severe
-The natural ones in the mother are actually IgM, but she can produce some IgG type when exposed to fetal blood (but remember the IgM will still be there to lessen the sensitization)
-This is the greatest cause of neonatal jaundice
-Hydrops fetalis and kernicterus are extremely rare |
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Term
| Why is it good for mother and fetus to have mismatched blood type if HDNB from RhD is a possibility? |
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Definition
-The mother naturally can have anti A or B IgMs that can clear any fetal cells before sensitization
-Likewise, the mother will not have natural anti-RhD |
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Term
| And now a few from Freund; |
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Definition
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Term
| What chromosomes are the MHC and B2 microglobulin on? |
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Definition
-The MHC genes are on 6 (all of them)
-The B2 microglobulin is on 15 |
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Term
| What is the difference in notation between haplotype, genotype, and phenotype? |
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Definition
-Haplotype; A1,B8,Cw4,D12/A1,B14,Cw4,D6 (most info)
-Genotype; A1 A1, B8 B14, Cw4 Cw4, D6 D12 (less info)
-Phenotype; A1, B8 B14, Cw4, D6 D12 (least info)
-Notice how the order in genotype and phenotype may not reflect what chromosome the alleles reside on
-note also that with a receccive genotype (above are codom), you do not include the rec one in the phenotype (such as BO--->B) |
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Term
| What are the two alleles giving a proclivity to type 1 diabetes (IDDM)? |
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Definition
-DQ2, DQ8 heterozygosity
-These are more convenient names for the individual α/β allele sets that typically are inherited together
-However, the α from DQ8 and β from DQ2 can hook up and are the actual cause of the problem
-The heterodimer caused by heterozygosity is less present than the DQ2 and DQ8, but causes the increased susceptibility to IDDM more than the other two alone |
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Term
| What is the difference between direct and indirect recognition in allograft rejection (Lima)? |
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Definition
-Direct; Host T cell + donor APC (dendrite usually)
-Indirect; Host T cell + host APC (B cell usually)
-Indirect is going to be more relevant in humor response which is involved in hyperacute and chronic, but not so much in the acute response |
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