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49 Cards in this Set
- Front
- Back
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What are 4 components that define tumor immunology?
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1. Antigenic property of transformed cells
2. Host response to tumor 3. Use of immune cells, molecules, and genes to fight cancer --> Abs, cells, cytokines 4. Cancers of lymphoid cells |
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What are 2 mechanisms by which normal cells are transformed to cancerous?
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1. Genetically transmitted or random mutations/translocations that increase with age --> usually cells that control cell growth, repair DNA, regulate cell cycle
2. Transformation by viruses, environmental insults |
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What are 3 causes of induced mutations?
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1. Chemical carcinogenesis
2. Physical carcinogenesis 3. Viruses |
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Cancer - Heterogenicity?
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Cells mutate to 'outsmart' host
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Cancer - Lack of antigenicity?
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Cells are "self"; impairs immune system recognition
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Cancer - Self-sustaining?
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Cells no longer respond to normal growth regulation, often make own growth factors
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What is metastatic disease?
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Tumor cells that travel to new environment, may grow and stimulate angiogenesis
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Cancer - dormancy?
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Long-term remission followed by relapse?
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What are 4 Immune system responses to cancer?
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1. T cells - recognize via MHC I, stimulate CD8 T cells
2. B cells and Ab - ADCC 3. NKcells - kill tumors that downregulate MHC I, ADCC 4. Macrophage - ADCC |
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What are 3 possible outcomes from normal cell mutation to tumor cell?
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1. Elimination via immunoediting (innate and adaptive immunity)
2. Equilibrium - genetic instability/immune selection 3. Tumor cell escape - no longer recognized by immune system |
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What are oncofetal tumor antigens?
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Antigens that are normally expressed during embryogenesis and then disappear from adult tissues; re-expressed in tumor
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What is carcinoembryonic antigen (CEA)?
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Oncofetal antigen that is expressed in inflammatory or cancerous lesions of the colon and pancreas
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What is Alpha-fetoprotein?
When is it increased? (3) |
An oncofetal a-globulin secreted by fetal liver and yolk sac, present in patients with liver and germ cell tumors
Increased in... 1. hapatitis, other inflammatory disease 2. pregnancy 3. hepatoma, teratoma |
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What does B72.3 antibody recognize?
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Recognizes tumor-associated glycoprotein (TAG-72), mucin-like
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What are 2 examples of carbohydrate tumor antigens?
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1. Gangliosides = normal molecule showing enhanced expression in melanoma and colon cancer
2. Mucin - under-glycosylated mucin, does not require MHC-restriction for T cell activation |
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What are 4 examples of antigens expressed by cancer cells that can be potentially recognized by T lymphocytes?
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1. Cervical carcinoma (HPV)
2. Nasopharyngeal carcinoma (EBV) 3. Hodgkin's Disease (HD) 4. Liver Cancer (HCV) |
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What might tumors do to growth factor receptors?
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Upregulate growth factor receptors in tumors that use receptors in an autocrine loop
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How does Burkitt's Lymphoma come about?
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Translocation of C-myc gene on chromosome 8 to chromosome 14 (beside IgH gene)
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What are 2 tumor-related mechanisms by which a tumor might escape immunologic destruction?
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1. Failure of tumor to induce an effective immune response
2. Failure of the tumor to provide a suitable target |
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What are 3 mechanisms by which a tumor could fail to induce an effective immune response --> tumor escape?
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1. Production of inhibitory substances by tumor
2. Shedding of tumor antigen and tolerance induction 3. Induction of T cell signaling defects |
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What are 3 mechanisms by which a tumor could fail to provide a suitable target for the immune system?
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1. Lack antigenic epitope
2. Lack of MHC class I (may downreg.) 3. Resistance of tumor cell to tumoricidal effector pathway |
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What are 5 mechanisms by which a host can fail to respond to an antigenic tumor?
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1. Immune suppression or signaling defects
2. Deficient presentation of antigens by APCs 3. Failure of host effectors to reach tumor 4. Failure to kill variant tumor cells 5. Dysregulation of Tregs |
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What happens when Fas binds FasL on a tumor cell?
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The T cell expressing Fas dies
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What causes T-Acute Lymphblastic Leukemia?
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Mutation in Pre-T cell
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What causes Pre-B Acute Lymphblastic Leukemia?
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Mutation in Pre-B cell
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What causes T-lymphoblastic lymphoma?
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Mutation in thymocyte
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What do mutations in T lymphocytes cause? (3)
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Cutaneous lymphoma
T-CLL T-lymphoma |
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What causes Mantle cell lymphoma?
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Mutation in resting naive B cell
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What causes Chronic lymphocytic leukemia?
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Activated or memory B cell
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What causes follicular center cell lymphoma?
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Mature memory B cell
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What causes Burkitt's Lymphoma?
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Mutations in cells that resemble germinal center B cells
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What causes Hodgkin's Lymphoma?
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Germinal Center B cell mutation
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What causes Waldenstrom's macroglobulinemia?
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Mutation in Plasma cell --> IgM secreting
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What causes multiple myeloma?
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Mutation in plasma cell --> IgA, IgA, etc. secreting
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IL-2
a. Tumor b. Possible pathophysiology |
a. T lymphoma
b. Septic shock, cytokine storm |
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IL-4
a. Tumor b. Possible pathophysiology |
a. B lymphoma, mastocytoma, T lymphoma
b. Increased IgE --> mast cell activation, Increased IgG4 |
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IL-5
a. Tumor b. Possible pathophysiology |
a. T lymphoma, B lymphoma, Carcinoma
b. Eosinophilia |
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IL-6
a. Tumor b. Possible pathophysiology |
a. B lymphoma, Myeloma, Ovarian carcinoma
b. cachexia, shock, fever, bone absorption |
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IFN-gamma
a. Tumor b. Possible pathophysiology |
a. T lymphoma
b. Increased IgG1, Fever, myalgias |
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TNF/LT
a. Tumor b. Possible pathophysiology |
a. Hodgkin's lymphoma, AML, Myeloma
b. Cachexia, shock |
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IL-10
a. Tumor b. Possible pathophysiology |
a. B lymphoma, T lymphoma
b. Immunosuppression |
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TGF-B super family
a. Tumor b. Possible pathophysiology |
a. Epithelial tumors (breast, prostate, colon), T lymphoma
b. Cachexia and loss of appetite |
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What can be tested (6) using radioimmunoassay, Immunoelectrophoresis, or ELISA on secretions/serum/urine?
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1. Myeloma Ig spike
2. CEA 3. a-feroprotein 4. Alkaline phosphatase - prostate and liver cancer 5. Prostate specific Ag - diagnosis of carcinoma of prostate 6. TAG-7.2-all carcinomas |
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What are 3 methods of immunodiagnosis?
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1. RIA/IEP/ELISA
2. Imaging with antibodies 3. Detection of minimal disaease |
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What are 3 methods of detection of minimal disease?
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1. PCR
2. Circulating tumor cells - flow cytometry 3. Elevations of cytokines, tumor antigens |
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What are 3 methods of conventional immunotherapy?
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Surgery, radiotherapy, chemotherapy
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What are 5 methods of passive immunotherapy?
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1. Monoclonal Abs used to target tumor cells and mediate effector function
2. Kill by ADCC or CDC 3. Kill by signaling apoptosis or preventing cell growth 4. Kill by preventing angiogenesis 5. Kill by preventing homotypic cell adhesion |
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What are 4 ways immunoconjugates that can be used to deliver therapeutic agents to tumors?
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1. Ab-drug
2. Ab-immunotoxin (must internalize) 3. Ab-enzyme (activated when bound to tumor) 4. Ab-radionuclide |
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What are bispecific antibodies?
How can they use to fight tumors? |
Biochemically or genetically splicing of two different Ab combining sites onto a single Fc
One arm binds tumor, other binds T cells or NK |
