Term
commonly transplanted organs from un-related donors? |
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Definition
heart, pancreas, kidney, lungs, bone marrow, cornea, skin (although this is autologous usually), liver |
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Term
autograft isograft allograft xenograft |
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Definition
self ident. twin unrelated donor animal |
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Term
first set rejection
second set rejection |
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Definition
1-2 weeks, primary immune response
when more tissue from same donor is transplanted a second time, memory response, 5-6 days |
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Term
what helps prevent graft rejection? |
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Definition
block cd4 and cd8>block cd4>block cd8=no treatment |
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Term
helper t cells carry initiate the rejection process, but who carries it out? |
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Definition
Th1(DTH) cells CTL-mediated lyses ADCC |
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Term
during rejection of an organ one sees high levels of which ctyokine? |
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Definition
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Term
What are the stages and char of graft rejection? |
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Definition
sensitization: alloreavtive activation of CD4 and CD8, DCs of graft or host DCs can be APCs
Effector Stage: DTH=inflammation, CTL=cytotoxic respoonse, see production of IL2 (T cell prolif, CTL activation), IFNgamma(macrophage recuirtment, DTH response, increase in MHC I and II), TNFB(directly cytotoxic to graft cells, increase MHC-I)
ADCC is least important effector component |
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Term
What are the three categories of graft rejection? |
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Definition
Acute=differences is classical MHC, 2-4 weeks
Hyperacute=few days, preexisiting antibodies cause ADCC (complement, NKs, etc.), seen in patients with repeated blood transfusions, multi-gravid women, and of course patients with previous graft
Chronic Rejection=slowest/least vigorous, differences in Minor HC, immunosuppresives can help with acute but not chronic |
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Term
How do you ensure graft survival? |
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Definition
MHC II match is more import. than MHC I, blood type match, possible Minor HC loci too |
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Term
Why is it so hard to get a MHC match? |
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Definition
polymorphic, polygenic, co-dominantly expressed |
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Term
Major issue with bone marrow transplants? |
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Definition
Graft vs. Host disease (GvHD)=left over donor T cells attack host tissue and cause problems in skin, liver, and GI tract
Solution=kill all donor T cells |
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Term
What Immunosuppresive therapies are used for organ transplants? |
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Definition
mitotic inhibitors=cyclophosphamide, methotrexate, no B/T cell prolif
General immunosuppresives=corticosteroids
Specific Immunosuppresives:
fungal metabolites=cyclosporin A, FK506, block IL2 and IL2R transcription
Antibodies to treat donor tissue=anti CD3, anti-CD25(IL2R), anti CD20 |
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Term
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Definition
chemical,phyical carcinogens and viruses |
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Term
cancer is heterogeneous becasue? |
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Definition
constant changes mutations) and evasion of host control (often lack antigenicity), metastaic because it can move around |
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Term
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Definition
c-myc in tranlocated in front of IgH gene enhancer |
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Term
immune response best in cancers associated with? |
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Definition
viruses, physical (melanomas), chemical |
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Term
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Definition
tumor specific antigen=found in tumor cells but not normal cells, mutated protein
tumor associated anitgens=in embryonic cells and tumor cells but not mature normal cells or not at as high of a level, also called oncofetal antigens, two examples of these include carcinoembryonic antigen (CEA) and alpha feta protein (AFP) |
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Term
CEA association? AFP assocaition? |
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Definition
colon cancer
liver and germ cell tumors (teratomas) (naturally increased in hepatitis and pregnancy, materanl tolerance to fetus) |
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Term
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Definition
presented on MHC I, oncogenes from virus infected cell, protooncogenes from normal cell counterpart |
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Term
how do tumor cells avoid immune recognition? |
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Definition
1) may not be expressing abnormal proteins
2) have decreased expression of MHC
3)decreased co-stimulatory molecules like B7
4)produce inhibitory cytokines
5)shed antigens leading to tolerance |
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Term
If tumor antigens are present, why no recog? |
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Definition
1) immune suppression 2) defective t--cells 3)deficient antigen processing 4) effector cell unable to reach tumor |
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Term
Radioimmunassay/immunoelectrophoresis for:
B cell tumors? prostate tumors? liver tumors? |
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Definition
myeloma proteins
alkailine phosphatase or prostate specific antigen
alkaline phosphatase |
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Term
other methods for detecting tumors? |
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Definition
immunofluouresnce=flow cytometry or in situ microscopy
detect minimal disease=PCR, circulating tumor cells, changes in cytokine levels |
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Term
passive immunotherapy for cancer? |
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Definition
monoclonal antibodies for TSAs to get ADCC
monoclonal antibodies to singal apoptoisis and prevent angiogenesis |
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Term
active immunotherapy for cancer? |
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Definition
1)isolate tumor infiltrating lymphocytes, stimulate with IL2 and inject back in patient
2)dendritic cells pulsed with tumor antigens
3)bone marrow transplant for lymphomas
4)cytokines given
5) vaccination against tumor causing virus HPV 16 and 18 |
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Term
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Definition
kidney cancer melanoma
enhances tumor antigen presentation, for hairy cell leukemia, and kaposi sarcoma |
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