Transplant Immunology Flashcards
(28 cards)
Define autograft
Self-tissue transferred from one body site to another in the same individual
Define isograft
Tissue transferred between genetically identical individuals
Define allograft
Tissue transferred between genetically different members of the same species.
*Most common
Define xenograft
Tissue transferred between different species
Differentiate host vs. graft disease
Differentiate graft vs. host disease
Host-vs-Graft: Transplanted tissue is rejected by HOST; host attacks transplanted tissue (typical rejection)
Graft-vs-Host: Host is attacked by transplanted T-cells
- Happens when someone is immuno-compromised
- Example: Newborn baby given bone marrow transplant, T-cells from the donor could attack the host (baby)
Recognize significance of immunologically protected sites in transplantation
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Recognize the role of CD4 and CD8 cells in tissue graft rejection
CD4 plays leading role in rejection: increases time period between transplant and rejection from 15 days to 30 days.
CD8 plays minimal/no role alone, but larger role when combined with CD4. Together, CD4 and CD8 increase the time period before rejection from 15 days to 60 days.
Identify the two stages of tissue graft rejection and explain the roles of IFNg and TNFb in the effector stage
- Sensitization: Antigen-reactive lymphocytes activated by graft alloantigens (every immune system starts with this)
- Effector stage: Immune-destruction of the graft
- INF-gamma activates cell-mediated response; up regulates MHC-I and MHC-II due to the presence of foreign tissue; activation of CD8 and influx of macrophages
- TNF-beta lyses foreign cells (cytotoxic)
State the 3 types of tissue rejection.
What is the expected time from graft to rejection of each?
What is the cause of each?
- Hyper Acute: 0-3 days; due to pre-existing host antibodies to HLA (antibody mediated); could be from previous blood transfusion, multiple pregnancies, or previous transplants
- Acute: 3 days-6 months; caused by infiltration of the grafts by mononuclear cells, CD4 (cell mediated)
- Chronic: Over 6 months-years; antibody/humoral and cell mediated
State why transplant patients are at increased risk for complications, such as infection and malignancy.
CMV?
Recall why cytomegalovirus is of particular concern in a transplant patient
??
Explain how to identify the best and worst matches for tissue transplants (given ABO/Rh and microcytotoxicity test results)
If ABO compatible, then compare the number of “blue circles” that match between the recipient and the donor (blue circle represents a dead cell that has the MHC antigen on it)
Explain the significance of MHC-I (HLA-A and HLA-B) and MHC-II (HLA-DR) on graft survival
Which class is most important to be matched for best survival rate?
- 1 or 2 mismatches with MHC-1 (HLA-A and HLA-B) does not affect survival rate much
- 1 or 2 mismatches with MHC-2 (HLA-DR) drops survival rate significantly
- HLA-DR is most important
Interpret a one-way mixed lymphocyte response assay to predict the most and least compatible tissues
Compatibility is determined by mixing killed donor lymphocytes (MHC) with live recipient lymphocytes to see if the recipient’s will recognize the donor’s as foreign.
Mixed Lymph Response (MLR) will give you a signal number. Lower number means the host is “happy” with the transplant and higher number means the host is not happy with the transplant (bad match)
CASE: Patient with end-stage renal failure received kidney transplant. Patient was A+ and tissue type was HLA-A1, A9, B8, Cw1, Cw3, DR3 and DR7. Donor was A- and was matched for one HLA-DR antigen and 4/6 HLA-ABC antigens. Patient passed 5L of urine 2 days post-op and his BUN/CRE fell significantly. On day 7, graft became tender, BUN/CRE increased and had low grade fever. Fine needle aspiration revealed lymphocytic infilration of renal cortex. After 1 day of steroid, BUN/CRE fell and urine volume increased.
*What type of transplant rejection does this suggest?
Acute - his kidney was initially functioning (making urine and passing it) but eventually began failing (increased BUN/CRE) and kidney was flooded by lymphocytes.
What is the most common classification/type of graft?
Define.
Allograft - Tissue transferred between genetically different members of the same species
If a patient has a bad burn and it is treated with a graft taken from somewhere else on his own body, what type of graft is this called?
Autograft
What is the most common transplanted tissue?
Second most common?
- Blood
2. Cornea
What specific element (important when considering transplants) does the Cornea not express?
MHC
True or False: Every nucleated cell has HLA typing.
True
Are all HLA genes equal in transplant rejection?
If so, list all of them in any order.
If not, list them in order of most importance to least.
They are not equal.
Most important: HLA-DR (MHC-II)
Second: HLA-A and HLA-B (MHC-I)
Which type of cells plays the leading role in transplant rejection?
CD4
In a transplant, what happens when... CD8 is blocked? CD4 is blocked? Both CD8 and CD4 are blocked? What do the results tell you?
CD8: No change in period of time to reject tissue
CD4: Period of time to reject tissue increases from 15 days to 30 days
Both: Period of time increases from 15 days to 60 days
- CD4 plays the leading role in tissue rejection, but CD8 is also very important based on the result of blocking both CD4 and CD8 together.
What type of cell recognizes MHC-I? MHC-II?
MHC-I: CD8
MHC-II: CD4
