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Cancer Immunology

WVSOM -- Immuno/Micro -- Cancer and Immunology

What is oncogenesis? unconroled cellular expansion
What promotes oncogenesis? mutations thru increase of function or loss of function
What happens to function with uncontrolled cellular expansion increase or gain of function
What is an oncogene? any gene of viral or cellular origin that contributes to malignant transformation of cells when mutated or abnormally expressed
What is a proto-oncogene any oncogene normally found in the mammalian genome
What is sis? growthfactors that stimulate cells to grow. Leads to overproduction of prlatelet-derived growthfactor
What are the 3 growth factor receptors? erb B, erb B-2, HER2/neu
What do mutations in growth factor receptors do? mutations cause them to always be ON.
When is mutations in HER2/neu gene amplicifcation seen? breast CA
where are mutations of erb adn erb B-2 seen? epidermal growth facter and is most common
What do mutations in signal transducers result in? they are turned on. common ones are ras, and Abl
What do mutations in transcription factors result in? they control which genes are active. Mutations result in over activity. Seen in lung CA, leukemia, lymphoma and a number of other cancer types. Myc is most common
What do programmed cell death regulators result in? BCL-2; prevent cell from committing suicide so when abnormal cells don't die
What is the knudsen 2-hit model? first hit is inheriting one allele of Rb1 mutated tumor suppressor gene and the second hit is a random mutation in the other Rb allele. seen in retinoblastoma
What are fusion proteins? joining of 2 ore more genese which originally coded for sepearte proteins. Results in a single polypeptide with functional properties derived form each of the original proteins; Bcr-Abl
What are the requried cellular traits for malignant transformation? self-sufficiency in growth signals; insenstiviity to growth-inhibitory signals; evasion of apoptosis; defects in DNA repair; limitless repliciation potential (telomerase) sustained angogenesis; ability to ivade and metastasize
What is immune surveillance concept that the immune system routinely monitors "self" for aberrant cells
What are danger signals in immune surveillance? hypoxemic stress; physical pressure; virally infected
What antigens are involved in immune survellance? viral proteins; fusion proteins; aberrantly expressed proteins
Why does the immune system fail against cancer? lack of antigenicity of tumor; tumro-induced immunosuppression; loss of tumor MHC antigens; immune system is "evolutionary pressure"
What is the effectiveness of immune surveillance spontaneous regression of soem tumors; lymphoid infiltrates of many tumors; tumors arise due to immunosuppression; new immunotehrapies cause tumor regression; paraneoplastic syndroms; cancer more common in old age
What cells are MHC Class I found? nucleated cells
Where are class II MHC found? macrophages, dendritic cells, B cells (aka APC)
What is the way for a viral infected cell to be recognized? MHC Class I (CD8+ cytotoxic T cell mediated)
what does happens if tumor antigen is not unque? paraneoplastic peripheral neuropthaty
What will inbit NK T-cell killing of tumor cells? MHC Class I receptors on the target cell. It will inhibt NK T-cells
What is TSA? Tumor-specific antigens; any production is productive. can be a target for the immune system (MHC)
What are tumor-associated antigens? A molecule that may be associated with specific tumors– TAAs may elicit cellular and/or humoral immune responses against the tumor, but rarely defend the host against the tumor
What is carcinoembryonic antigen? TAA for colon cancer
What is alpha-fetoprotein? TAA for liver cancer
What si CALLA TAA for leukemmia
What is Prostate specific antigen? TAA for prostate cancer
What is tyrosinase? TAA for melanoma
What is CA-125, HE4 TAA for ovarian cancer
What does monoclonal antibody treatment do? stimulates the immune system to attack tumores (anti-CTLA4, anti-cd20, anti HER2)
What is imunomodulated antigen delivery? (vaccine like) provenge for prostate cancer stimulates a patietn's immune system against prostate cancer
What is adoptive cellular therapy helpign the immune system fight and/or recognize cancer. isolate lymphcytes from blood or tumor infiltrate; expand lymphocytes by culture in IL-2; transfer lymphocytes into patient with or without systemic IL-2; tumor regression
What are the drawbacks of adoptive cellular therapy? very high danger and does not work much. Treatment of last resort
How do dendritic Cell vaccines for cancer immunotherapy work? Autologous Dendritic celsl are loaded with tumor antigens and cytokines. they are then infused into patient ti induce anti-tumor immune response
What are the problems with dendritic cell vaccines? source of teh DC (plasmacytoid or vyeloid) antigen idetnifcation and preparation; route of administration; immune monitoring; side effects
how does monoclonal antibody therapy work? attack tumor OR stimulates immune response (anti-CTLA4)
What are the limitations to antibody immunotherapy inadequate penetration into tumor if tumor is target; inappropriate binding to normal cells; immunogenicity of the antibody;
What is a humanized antibody? type of monoclonal antibody that have been synthesized using recombinant DNA technology to circumvent the clinical problem of immune response to foreign antigens. Fab from the mouse.
Created by: tjamrose