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39 Cards in this Set
- Front
- Back
Types of Tumor Antigens
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• Products of mutated genes
• Abnormal expression of normal genes • Oncogenic virus genes • Oncofetal antigens • Altered glycolipid and glycoprotein antigens • Tissue-specific differentiation antigens |
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Products of Mutated Genes
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• The amino acid sequence determines what peptides are bound to what MHC molecules
• A change in the sequence will change what peptides can be presented. |
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Altered Glycolipid and glycoprotein antigens
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• Most human tumors express increased levels or abnormal forms or cell surface glycoproteins and glycolipids
o Gangliosides (GM2, GD2, GD3), blood group antigens, mucins |
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Tissue Specific Differentiation Antigens
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• Cell surface markers or intracellular proteins/receptors that are found only on/in specific lineages of cells.
o CD10 or CD20 on B cell derived lymphomas, Tyrosinase in melanomas, CD4 on T cell derived leukemias |
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List the Innate Immune Responders
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- NK cells
- NK Receptors - Macrophages |
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What is NK Cells Mechanism of Recognition?
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Altered cell surface glycoproteins, Loss of class I MHC, Bound antibodies
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What is the Mechanism of Killing for NK Cells?
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Release of cytotoxic granules
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What are NK Receptors?
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Some of the NK cell receptors are heterodimer of two different protein families
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What are the two types of NK Receptors?
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- NKG2 family (6 members)
- Ly49 family (? Family): |
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What is NKG2 family inhibitory and activating?
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A and B are inhibitory,
C and D are activating |
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What are Ly49 family inhibitory and activating?
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A and G are inhibitory
D and H are activating |
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What is the Mechanism of Recognition for Macrophages?
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Bound antibodies, receptor interactions (Can express NKG2D receptors)
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What is the mechanism of killing for Macrophages?
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Phagocytosis, NO production
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What are Adaptive Immune Response types?
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- CD8 + Cytolytic T cells
- B lymphocytes |
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What is the Mechanism of Recognition for CD8 + Cytolytic T cells?
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Tumor antigens presented in Class I MHC
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What is the Mechanism of Killing for CD8 + Cytolytic T cells?
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Release of cytotoxic granules
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What is the Mechanism of Recognition types for B lymphocytes?
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Cell surface tumor antigen, T cell help
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What is the Mechanism of Killing for B lymphocytes?
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ADCC, antibody dependent cell mediated cytoxcity, complement activation?
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How Tumors evade recognition and destruction?
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• Tolerance
• Regulatory T cells • Loss of class I MHC • Loss of tumor antigens • Suppressive secretions by tumor cells |
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List a Regulatory T cell
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CD4 CD25+ autoreactive T cells
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What is the role of CD4 CD25+ autoreactive T cells?
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Role is to inhibit the activation of other autoreactive T cells.
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What happens when there is a loss of Class I MHC?
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• Tumors often lose expression from non-vital genes due to rapid mutations and selection by the immune system
• Loss of Class I MHC is positively selected for by protecting the cell from CTL killing • With lost of Class I MHC: CTL Killing goes down, NK cell killing goes up |
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What happens when there is a loss of tumor antigen?
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• Tumors often lose expression from non-vital genes due to rapid mutations
• Loss of any protein is positively selected for if it is not essential for growth and is being responded to by the immune system |
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Secretion of Suppressive COmpounds by tumor cells-- list mechanisms by which tumors escape immune recognition
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- Low immunogenicity
- Antigenic modulation - Tumor-induced immune suppression |
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What happans in Low immunogenicity?
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- No peptide MHC ligand
- No adhesion molecules - No co stomulatory molecules |
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What happens to Antigenic modulation?
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- Anti body against tumor cell- surface antigens can induce endocytosis and degradation of the antigen.
- immune selection of antigen loss variants |
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What happens to Tumor indued immune suppression?
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- factors (e.g. TGF-B) secreted by tumor cells inhbit T cells directly
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For Chronic Inflammation, What does Macrophage released factors cause?
(role of Immune system in promoting tumor growth) |
Promote angiogenesis (make new blood vessels) and tissue remodeling, promote DNA damage (oxygen free radicals).
Ex: hep B infection, H. Pylori infection |
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List the Immune Therapy for Tumors
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• Tumor Vaccination
• Augmenation of tumor responses • Blocking inhibitory pathways • Non-specific stimulation • Passive Immunotherapy: Adoptive cell culture, Graft vs. Leukemia Reaction, Anti-tumor Ab Therapy • Problems with chemotherapy |
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For Tumor Vaccination What are the steps?
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1. Dendritic cells from patient are removed and “loaded” with tumor antigens, then returned
2. A plasmid that will express a tumor antigen is used as a vaccine. • Dendritic cells from a patient are transfected with the same plasmid before return. |
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What happens in Augmentation of Tumor responses?
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• Tumor cells are removed and forced to express immune modulating genes, then returned.
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What happens in Blocking Inhibitory Pathways?
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• Normal pathways that are used to inhibit or down-regulate an immune response include CD152/CTLA-4
• Antibodies are injected to block this receptor, allowing the immune system to respond to the tumor (self) • The immune system is full of self regulating networks meant to prevent unnecessary activation or prolongation of an immune response. • CD152 is upregulated with activation and binds the same targets (CD80/CD86) as CD28, but slightly better. |
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what happens in Non Specific Stimulation?
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• Antigen non specific stimulators of the immune system are injected in the tumor: Cytokines, BCG, Anti-CD3 antibodies
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List Pasttive Immunotherapy
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- Adoptive Cell Culture
- Gradft vs. Leukemia Reaction - Anti-tumor Antobodies |
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what is Adoptive Cell Culture?
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: Lymphocytes are removed, activated by tumor antigens, and expanded in vitro, then returned to patient.
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What is Graft vs. Leukemia Reaction?
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Alloreactive T cells are administered along with stem transplants
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What is Anti-Tumor Antibodies?
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Antibodies to tumor cell markers are injected t induce humoral immunity
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What are the problems with Chemotherapy?
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- Chemotherapeutic agents typically cause apoptotic cell death
- More cells than just tumor cells need to divide in the body normally - Cells dying from necrossi promote inflammation - Cells dying from apoptosis inhit inflammation |
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In problems with chemotherapy, what type of dying cells promote phagocytosis?
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- Cells dying from necrossi promote inflammation
- Cells dying from apoptosis inhit inflammation |