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27 Cards in this Set

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  • Back
Which genes are involved in the rejection of transplants?
MHC locus
What is the transplant of tissue from the same individual to a different part of the body called?
Autograft
What is it called when a transplant is done between identical twins?
Isograft
What is it called when a transplant is done between two different individuals that are the same species?
Allograft
What type of transplant is a blood transfusion?
Allograft
What happens when blood from someone from a different blood type is transfused into someone?
Transplant-like rejection

Clumping of RBCs followed by classical complement activation
What type of difference is found between people with different ABO blood types?
Sugar modification (all have H antigen and then either N-acetyl galactose if A, galactose if B, or both if AB or neither O)
What is hyperacute rejection?
Rejection that happen in minutes in sensitized patients (ppl with previous transplant or blood transfusion, prev bacterial infections, or multiparous women)

Antibody-mediated

Results in thrombotic occlusion
Do B cells carry, HLA-I, HLA-II, or both?

What about T cells?
B cells - both
T cell - HLA-I
What mediates the rejection most likely to be a problem with transplants?
T cells
What is the direct pathway of rejection?
T-cell mediated rejection
No need for processing of antigens (recognizes the MHC themselves)
How long after transplantation does T-cell mediated acute graft rejection happen?
One week later
What happens in T cell mediated acute graft rejection?
T cells of recipient recognize MHC molecules from donor regardless of peptide presented by it, secrete IFN-gamma which activates macrophages to become foam macrophages and occlude transplant
---TH1 response, fast
What does hyperacute rejection result in?
Thrombotic occlusion
Why does the indirect pathway of T-cell mediated rejection take longer than the direct pathway?
Antigens need to be processed
Thrombocytic occlusion happens as a result of hyperacute rejection. What happens as a result of acute rejection?
Parenchymal cell damage
Interstitial inflammation
Endothelialitis
What happens in chronic graft rejection? When does this happen?
Six months after transplant, cytokine secretion results in occlusion of blood vessels due to proliferation of smooth muscle cells
Describe what happens in the indirect pathway.
Recipients APC cells take up donor proteins and present it to CD4 T cells, which activate B cells to mature into plasma cells that secrete antibodies to HLA-I and HLA-II from donor and attack the endothelium in the donated organ
When a bone marrow transplant is indicated, what is done to make sure that the recipient does not have an immune response against the donor's bone marrow?
Recipient is irradiated and treated with cytotoxic drugs to kill off the T cells that would cause this reaction.

Also, donor's bone marrow is treated with anti-CD2 (CD2 is in T cells and NK cells) so that any of the donor's T or NK cells in the marrow are killed ---- this is because the donor's T and NK cells could react against the recipient's cells once transplanted into the recipient (this is graft vs. host disease)
What happens in chronic graft vs. host disease?
T and NK cells react against minor histocompatibility complex
How is matching mainly done for transplantation?
Use PCR to match MHC molecules (can also do lymphoproliferation where you do not want to see proliferation if is a match)
What drugs are used to suppress the immune system of the recipient to prepare for transplantation (anti-inflammatory effect)?

What pathway is being blocked?
Corticosteroids (e.g. prednisone) bc is anti-inflammatory

NFkB pathway (by inducing transcription of IkBa which binds to NFkB so it cannot export to the nucleus)
What are three cytotoxic drugs used to kill proliferating cells so that lymphocytes are killed and immune system response against transplant is minimized?
Azathioprine (kills non-lymphocytes too like hair and liver cells)
Cyclosphosphamide (is oncogenic)
Methotrexate
How do cyclosporin and tacrolimus block T cell activation in order to avoid transplant rejection?
They block activation of calcineurin which blocks activation of NFAT so IL-2 and IL-2R are not transcribed.

Without IL-2, T cell is not activated
How does rapamycin block T cell activation?
Blocks activation (signal transduction) of IL-2R, which is essential for binding IL-2 and activation of T cells
How are NK cells involved in rejection of transplants?
NK cells patrol for non-self cells and so when they find an HLA-C that is "self", an inhibitory receptor prevents the NK cell from killing it. When a transplant happens the HLA-C might have a different AA and so will not be recognized as self, preventing the inhibitory receptor from binding to the NK cells, so the NK cell will go ahead and kill the cell.

-this is not efficient, minor histocompatibility complex
What is a natural defense against "graft vs. host" disease that is being explored as a way to help decrease transplant rejection?
Anti-infalmmatory TH2 response using Treg cells are present in a fetus so that the fetus' immune system does not fight mothers cells and lasts for up until 17 years, and may be an option if we can figure out how this works and induce it in people getting transplants.