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27 Cards in this Set
- Front
- Back
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Gain of function is due to..
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increased expression of...
growth factors (sis), growth factor receptors (HER2), signal transducers (ras, Abl), programmed cell death regulators (bcl-2) |
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Loss of function is due to...
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suppression of...
cell division control (Rb1), Cell suicide genes (p53) |
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Oncogene
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Any gene of viral or cellular origin that contributes to malignant transformation of cells when mutated or abnormally expressed.
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Protooncogene
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any oncogene normally found int he mammallian genome; unaltered form
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Knudsen 2-hit hypothesis
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1st hit- inherited one allele of Rb1 mutated supressor gene
2nd hit- random mutation in the other Rb allele |
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Required cellular traits for malignant transformation
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-self-sufficiency in growth signals
-insensitivity to loss of function (inhibitory signals) -evade apoptosis -defect in DNA repair -limitless replication potential -ability to invade and metastasize |
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Immune Surveillance
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concept that the immune system routinely monitors 'self' for aberrant cells
-looking at MHC-I antigens (viral proteins, fusion proteins) -NK T-cells attack cells lacking MHC-I |
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Support for Effectiveness of Immune Surveillance
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-spontaneous tumor regression
-lymphoid infiltrates many tumors -tumors come from the immunosuppressed -paraneoplastic syndromes (antibody mediated) -cancer more common in old age |
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Why does the immune system fail?
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1. LACK OF ANTIGENICITY
2. tumor-induced immunosuppression 3. loss of tumor MHC antigens 4. immune system is 'evolutionary pressure' (kills what it can, what it cant will survive) |
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Describe MHC-I presentation; MHC-I cytotoxic T-cell mediated
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A tumor antigen cell is ingested by an APC. The MHC-I is transferred to the APC. In the lymph node, the APC meets a CD4+ helper cell, releases cytokines that stimulates CD8+ cell, massive CD8+ proliferation to recognize the tumor and kill it.
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Problem with tumor cells
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the antigen being presented to the CD8+ T cell has got to be unique.
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Fusion Proteins
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All native, but the only thing different is the junction between the two proteins. It's the only part that's seen as a unique protein.
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MHC-II CD4+ T-helper (1 and 2)
B cell-antibody mediated |
on the surface of professional APCs only (dendritic cells, macrophages, B-cells)
antigen comes in, is broken up, put on the surface of the APC with MHC-II, activates CD4+ T cell which activates a B cell that turns into a plasma cell and makes antibodies |
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Tumor Antigen must be....
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UNIQUE!
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What do Natural Killer T-cells kill?
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Tumor cells LACKING MHC-I
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What are Tumor-Specific Antigens?
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TSA
-ANY production = positive for cancer ex PLAC1 for breast cancer |
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What are Tumor-Associated Antigens?
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TAA
-OVER-production = positive expressed at low levels/constant, but if you get too much, like PSA (prostate-specific antigen) or Alpha-fetoprotein (AFP) in liver cancer |
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What do monoclonal antibodies do?
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Cancer immunotherapy.attack the tumor directly, or if they can't kill it, they can target drugs to it. They can also stimulate the immune system, such as with anti-CTLA4
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Why have most attempts for adoptive cellular therapy failed?
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When you pull out dendritic cells, you don't know which they are specific for, and when you inject them back in, they weren't successful in the first place, so why should they be successful now.
*basically creating a neoplasm with possible mutations **may have contaminants that cause cell immortalization |
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Limitations for Antibody Immunotherapy
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1. Inadequate penetration into tumor if tumor is target ( better for free-floating tumors like lymphomas)
2. Inappropriate binding to normal cells 3. Immunogenicity of the antibody |
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What are HUMANIZED antibodies?
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Most of the antibody is from human except for the epitope binding portion, which is mouse.
they're invisible to the immune system except for the epitope. way to control the antibody response. most anti-tumor Abs are humanized. |
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Name 3 neoplasms of the Immune System
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Plasma Cell Myeloma- a B-cell overproliferation
Acute Myelogenous Leukemia Acute Lymphoblastic Leukemia |
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Multiple Myeloma (aka Plasma Cell Myeloma)
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Ab-producing tumor
-bone marrow is going away -decreased RBC and WBC count -severely elevated immunoglobulins |
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Isotype vs idiotype Abs
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idiotype- for the epitope binding region of the Ab
Isotype antibodies- are against the heavy chain of the Ab *electrophoresis for the Isotypes of the Abs |
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Whats flow cytometry good for
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Differentiating lymphocytes in the blood; helps to see CD4 cells in HIV
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Acute Myelogenous Leukemia (AML), you are...
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CD-33 positive as an early marker, and CD34 as an early hematopoietic cell marker found in the bone marrow cells
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Chronic Lymphocytic Leukemia (CLL), you are...
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CD-5/CD19 double positive
expresses both T cell and B cell on the surface CD5 is T cell CD19 is B cell |
