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54 Cards in this Set
- Front
- Back
What are oncogene products?
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mutated Ras, Bcr/Abl fusion proteins
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What is a tumor suppressor gene product that gets mutated?
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p53 protein
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what self proteins are sometimes overexpressed in tumors?
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tyrosinase, gp100, cancer/testis antigens
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What are some oncogenic viruses and the protein products they produce?
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HPV E6 and E7 proteins in cervical carcinoma and EBNA proteins in EBV induced lymphomas
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What are the majority of tumor antigens?
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endogenous cytosolic proteins displayed on MHC 1
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All cells display peptides on MHC I. However tumor cells do often express what?
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MHC II
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For CD8 cells to proliferate what has to occur?
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they can become activated by MHC I receptors but they also need the help of CD4 cells which are stimulated by MHC II presentation
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What is cross priming?
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also called cross presentation, it occurs when dendritic cells engulf to tumor cells or antigen and present them to CD8 and CD4 cells
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In order for a CD8 cell to become activated by dendritic cells they need what receptors?
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CD8 cells have CD28 which binds costimulator B7 on dendritic cells
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CD8 cells have to do what in order to kill tumor cells?
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differentiate with CD4 help
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What are 3 ways tumors evade immune response?
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1) do not express antigen (Antigen loss variant)
2) do not express MHC 1 3) produce a CD8 inhibitory ligand |
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Tumors that do not express MHC1 can still be killed via?
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NK cells
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What cytokine do tumors secrete that suppresses immune response?
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TGF-beta
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When treating B cell tumors with an antibody, what is the antibody directed against?
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CD20
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animals that are identical to one another are called what?
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syngeneic
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What does allogeneic mean?
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animals of the same species that are not identical
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What is xenogeneic?
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animals of different species
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antigens of allografts are that are the principal target of rejection are proteins encoded in what?
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MHC
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what is the MHC found in humans called/
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HLA
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How many MHC 1 alleles are there and what are they?
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6, HLA-A, B, C one from each parent
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There are at least 6 MHC II alleles what are they?
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HLA-DQ, DR, DP one from each parent
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All MHC molecules are targets of immune rejection, although 2 alleles are associated with the least immune response. What are they?
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HLA-C and DP
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What elicits one of the strongest immune responses?
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MHC antigens on another individuals cells
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What recognizes MHC molecules?
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TCRs on T cells
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What is an example of an immunologic cross reaction?
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allogeneic MHC molecules because they are recognized by recipient T cells and are also have bound foreign peptide to them (direct recognition)
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What does negative selection in the thymus do?
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eliminate T cells that strongly recognize self MHC
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What is the difference between allgeneic grafts MHC recognition and that of an infected self cell in terms of T cell recognition and response?
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Only a few MHC types on an infected cell will display foreign antigen, whereas all of the MHCs on a graft can be interpreted as foreign
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What are non-MHC antigens on allogeneic grafts called?
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minor histocompatibility antigens which are allelic forms of normal cellular proteins that happen to differ from donor to recipient
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What are examples of minor histocompatibility complex reactions that occur in the body?
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1) blood transfusions
2) bone marrow transplantation |
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recipient APCs can present alloantigens to recipient T cells. Can recipient T cells recognize and interact with donor APCs? What is the process called?
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yes, direct recognition because it is a direct presentation of alloantigens
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what is indirect recognition of alloantigens?
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recipient dendritic cells display alloantigen to recipient T cells that induce the immune response. This is similar to cross presentation in tumor cells
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What is different about the response generated between direct and indirect recognition of grafts?
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in indirect the CTLs are specific for alloantigen displayed by self MHC molecules on host APCs and cannot recognize and kill cells in the graft
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Is a delayed type hypersensivity with graft rejection seen with direct or indirect alloantigen presentation? why?
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indirect because CTLs cannot directly kill donor cells, so CD4 cells move with other APCs to graft and slowly secrete cytokines that destroy the tissue
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Is acute or chronic rejection mediated by direct or indirect recognition?
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acute = direct
chronic = indirect |
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How is hyperacute graft rejection characterized? What is an example?
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occurs within minutes via thrombosis of graft vessels and ischemia
blood donation |
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What is the cause of hyperacute graft rejection?
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preformed antibodies to endothelial cells on grafts. Antibodies may include IgM for blood groups, or allogenic antibodies from past blood transfusion, pregnancy, or prior organ transplant
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The antibodies in both acute and hyperacute rejection do what?
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bind endothelium and activate complement and clotting systems
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How is hyperacute rejection avoided?
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cross matching the blood type
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what reaction occurs with xenotransplantation?
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hyperacute
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When does acute rejection present?
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within days or weeks and is the principal cause of early graft failure
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What occurs in acute rejection?
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mainly a T cell mediated reaction to alloantigens, although antibodies also contribute especially to the vascular damage
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When does chronic rejection occur?
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within months to years leading to a progressive loss of graft function
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What occurs cellularly in chronic graft rejection?
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fibrosis and gradual narrowing of graft blood vessels via T cells stimulating fibroblasts and vascular smooth muscle
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What is the most clinically useful drug in blocking graft rejection?
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cyclosporine because it blocks T cell phosphatase (calcineurin) needed to activate NFAT so cytokine production is inhibited
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What is the problem with drugs other than cyclosporine?
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they are nonspecific immunosuppressants
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Why do the blood group antigens not elicit T cell responses?
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because they are sugars
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princeps, principis
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earliest, first
leader, chief |
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What is the MOA of FK506? What else is it known as?
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same as cyclosporine, blocks release of cytokines from T cells
Tacrolimus |
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What is the MOA of mycophenolate mofetil?
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blocks lymphocyte proliferation by inhibiting guanine nucleotide synthesis... inhibits inosine monophosphate dehydrogenase which is particularly effective at destroying lymphocytes because they lack the alternative salvage pathway
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what is the MOA of rapamycin?
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blocks lymphocyte proliferation by inhibiting IL2
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What is the MOA of corticosteriods?
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reduce inflammation by blocking cytokine release from macrophages
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WHat is the MONA of anti-CD3 monoclonal antibody?
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Depletes T cells by binding CD3 and promoting phagocytosis or complement-mediated lysis (drug is muromonab)
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What is the MOA of anti-IL2 receptor antibody?
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inhibits T cell proliferation by blocking IL2 binding... drug is called daclizumab
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What is the MOA of CTLA4-Ig?
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inhibits T cell activation by blocking B7 costimulator binding to T cell CD28... drug is (abatacept)
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