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25 Cards in this Set
- Front
- Back
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Types of Grafts
1) autologous 2) syngeneic 3) allogeneic 4) xenogeneic |
a) from self
b) from identical twin c) from another human other than identical twin d) one species to another |
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Alloantigen Recognition
Name the genes important for recognition of MHC a) Class I b) Class II How are these genes expressed? |
a) HLA A, B, and C for CD8 T-cells
b) HLA DP, DQ, and DR for CD4 T-cells These are codominantly expressed |
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Describe:
a) Direct presentation b) Indirect presentation |
a) Donor APC presents unprocessed allogeneic MHC
b) Host APC presents processed peptide of allogeneic MHC |
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From which progenitor class are dendritic cells derived? Myeloid progenitor or lymphoid progenitor?
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Trick question! Dendritic cells can be derived from either progenitor cell.
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Direct presentation of alloantigen can lead to both CD8 response and CD4 response while indirect cannot. Why is this?
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Because host cells do not have the alloantigen intracellularly and therefore can only express the alloMHC via cross presentation, MHC Class II presentation dominates
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Indirect and Direct MHCII presentation leads to what two responses?
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1) Alloantibodies
2) Delayed type hypersensitivity reaction potential |
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Describe the action and effects of CTLA-4 and CTLA-4 Ig
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CTLA-4 expression on the T-cell, or CTLA-4 Ig (administered) compete with CD28 for binding of B7 on the APC. CTLA-4 thus prevents the coactivation signal of B7:CD28 necessary for IL-2 secretion by the T-cell and T-cell proliferation, survival, and maturation. CTLA-4 WHEN BOUND TO T-CELL ALSO INHIBITS T-CELL AND CONTRIBUTES TO TOLERANCE
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Describe the effects of Anti-CD154
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Anti-CD154 bind CD154(aka CD40L) on the T-cell preventing its interaction with CD40 on APC. Again, blockade of IL-2 and T cell proliferation.
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MLR: Mixed Lympocyte Reaction
1) What is this used for? 2) How is the reaction set up? |
1) To measure the T-cell proliferative response to, ie T-cell regulation of allogeneic MHC
2) Donor irradiated (no longer mitotic mononuclear cells and recipient mitotic mononuclear cells. Mix these together in a dish and measure proliferation of T-cells via measurement of thymidine incorporation. |
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What is the actual Primary Mixed Lymphocyte Reaction in MLR?
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Simply the donor irradiated mononuclear cell presenting alloantigen via MHC Class I and II to recipient CD8 and CD4 recipient T-cells respectively.
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Hyperacute Solid Organ Rejection
1) Time frame 2) Mechanism 3) Result 4) Common risk factors |
1) Min-hrs.
2) IgG preexisting to blood group Ag, ABO incompatibility 3) Intravascular thrombosis, complement endothelial dammage, inflammation 4) Hx of blood transfusions, multiple pregnancies, transplantation |
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Acute Solid Organ Rejection
1) Time frame 2) Mechanism and key players 3) Result |
1) Days-weeks
2) CD4 CD8 T cells launch humoral Ab response 3) Parenchymal damage and inflammation |
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Chronic Solid Organ Rejection
1) Time Frame 2) Key Mediators 3) Result |
1) 8 months-year
2) CD4, CD8 T-cells, and macrophages 3) Chronic fibrosis, accelerated arteriosclerosis via chronic DTH (delayed type hypersensitivity) reaction in intima (ie action of macrophages, CTLs, and NKs)--> smooth muscle migration and proliferation. |
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Bone Marrow/PBSC Primary Graft Failure
1) Time frame 2) Mediators 3) Result |
1) 10-30 days
2) Host NK cells 3) Lysis of donor stem cells |
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Bone Marrow/PBSC Secondary Graft Failure
1) Time frame 2) Mediators 3) Effect 4) Risk factor |
1) 30 days - 6months
2) Autologous T-cells CD4 and CD8 replacing donor T-cells 3) Lysis of donor stem cells 4) This is often infection induced |
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What two things must be matched to prevent rejection?
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ABO blood group compatibility and MHC
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Alright back to Pharm: Drugs used to prevent/treat rejection. Name the five classes and drugs involved.
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1) Inducers/reactors: Antithymocyte Ig,OKT3, Daclizimab, Basiliximab
2) Calcineurin inhibitors: Cyclosporins (Sandimmune, Neoral) Tacrolimus (prograf) 3) Antimetabolits: MMF (Cell Cept), Imuran 4) mTor inhibitors: Rapamycin 5) Corticosteroids: Prednisone, Solumedrol |
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Infliximab
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An antiinflammatory (antiTNFalpha) drug used to help treat and prevent rejection
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Role of Tregs in graft rejection
Also, 1) What gene is normally turned on in Tregs? 2) What cytokine induces naive T cells to become Tregs? |
Tregs decrease graft rejection because they inhibit T-cell maturation to Th1, Th2, and Th17 cells.
1) FoxP3 2) TGF-beta |
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NK Cells
1) CD56 Dim function 2) CD56 Bright function |
1) Cytotoxic effector cell, ADCC, LAK, low cytokine secretion
2) Cytokine producing (Only account for 10% NKs and considered to be less mature than Dim cells) |
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Do DCs cause proNK to mature into NKs or do NKs cause immature DCs to become mature DCs?
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both
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What two signals to NK cells need to be free to kill
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It's inhibitory receptor must not be bound the MHC Class I molecule because they a either missing to mutated and its activating receptor must also be engaged.
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3 Essential Components Required for GVHD
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1) Immuno-incompetent host
2) Infusion of competent donor T-cells 3) HLA disparity between host and donor |
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Acute GVHD
1) Time Frame 2) Symptoms |
1) Day 7-100
2) a) Dermal: macropapular rash on palms and soles, pruritic, cheeks/ears/neck/trunk necrosis/bullae b) Hepatic: hyperbilirubinemia, transaminemia c) GI: diarrhea, abdominal pain, vomiting, nausea |
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Chonic GVHD
1) Time Frame 2) Symptoms |
1) After 100 days
2) Dermal: Rash, allopecia, Joints: althralgia, arthritis, contractures Hepatic: same as acute plus cirrhosis GI: Dysphagia, pain, vomiting, diarrhea Pulmonary: Bronchiolitis Obliterans Hematologic: Cytopenias Pericardial and pleural serositis |
