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24 Cards in this Set
- Front
- Back
- 3rd side (hint)
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Immunological surveillance
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detection of transformed cells by the immune system --could be induced at later stage to limiting of tumor development.
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immune system reacts against tumors
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rejection of tumor-transplant that pre-exposed that tumor (Mem B cell) --- immunodeficient can cause increase cancer
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Immune Recognition 1 Virus
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Tumor (self) make surface Ag (different structure) to be recognized by Imm Sys (Virus infected cell present viral protein)
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Immune Recognition 2 Silent genes (Oncofetal antigens)
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1) fetoprotein (AFP) in hepatic cancer -- 2) carcinoembryonic Ag (CEA) in intestinal cancers
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Immune Recognition 3 mutations
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point mutations; e.g. p53
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Immune Recognition 4 carbohydrates
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Abnormal surface carbohydrates with new antigenic activity
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Immune Recognition 5 surface of cycling cells
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1) Cancer cells are faster dividing than normal cells -- 2) Important: 95 kDa glycoprotein, F19 in sarcomas & several carcinoma
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Immune Recognition 6 CALLA
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is an antigen associated with childhood leukemia
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CALLA (CD10)
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Common Acute Lymphoblastic Leukemia Antigen normally expressed only on B-cell progenitors (lymphoblast)
They make up < 1% of normal bone marrow cells CALLA becomes more abundant in the commonest childhood leukemia |
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Immune Responses
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1) T Lymphocytes: (CD8+ CTLs --rejection) 2) MHC I (recognition & killing) 3) Tumor-infiltrating lymphocytes (TILs) use CTLs for lysing the tumor --> most imp 4) CD4+ helper provide cytokines ( tumor necrosis factor (TNF) & interferon-g (IFN-g) -- act marcrophage
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Specificity of tumor immunity or Tc specificity
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Subclone tumor (modified by ratiation - make it different so spleen Tc can recog and kill by only ONE aa)
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Immune Responses _ NK
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Natural Killer Cells: -- lysis viral infected cells & hematopoietic tumors in vitro (wt NO Th and MHC) -- Low IgG affinity Fc-receptors (use Fc to bind and release granzyme) -- Cytokines (IFNs, TNF, IL-2, IL-12) increase the tumoricidal capacity of NK cells --- IL-2 activated NK cells are called lymphokine-activated killer (LAK) cells
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Immune Responses _ Macrophage
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use lysosomal enz -- reactive O2 metabolize -- NO -- TNF (cachectin) modulate adipocyte metabolism (lyse cell) and induce hermorrhagic necrosis (cut off blood supply)
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Immune Responses _ Antibody
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some evidence but less important
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NK's role in immunosurveillance:
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Nude (no Th) mice low incidence of spontaneous tumors due to NK
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lymphokine-activated killer (LAK) cells
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IL-2 activated NK cells increase the tumoricidal capacity of NK cells --> Cytokines (IFNs, TNF, IL-2, IL-12)
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Tumor escape msm
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1) Down reg MCH1 (Tc can't see) 2) MCH2 (Th can't act Macr) 3) lack Costi (B7) less Tc activation 4) Use tumor products to suppress anti-tumor response 5) Host tolerance (neonatal expose-in tolerigenic form) 6) mutant wo MHC 7) Antigenic modulation (endocytosis or shedding Ab-Ag comple) --> Macro can't see 8) Hiding by glycocalyx -- fibrin cocoon 9) sneaking thru -- kinetic resistant
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3 ways Tumor Ag presentation
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1) no costi (B7) --> anergy 2) wt costi--> Tc act 3) wt costi and APC --> act both Tc and Th (macro)
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Cancer Immunotherapy _Vaccine
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1) Active immunization (oncogenic viral proteins vaccine)
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Cancer Immunotherapy _CLL
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immunization wt chronic lymphocytic leukemia (CLL) cells idiotype fused with GM-CSF
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Cancer Immunotherapy _Transfection
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adding costi (B7) and cytokine (INF gam- IL-2-4-7)
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Cancer Immunotherapy _Monoclonal Ab
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magic bullet -- conjugate wt toxin or radionuclides on tumor or Ag on fibrorlblast
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Cancer Immunotherapy _Innate immune msm
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LAK treat renal cancer -- IFN-gam and al treat Tc (hairy leukemia-mycosis fungoides less eff on Kaposi sarcoma --- need combining therapy
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Strategies for enhancing antitumor immune responses
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Vaccine wt dendritic cell having Ag -- plasmid wt Ag code -- tumor cell wit B7 or IL2
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