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Tumor immunology by nidhi
- 1. Report On SeminarTopic Entitles “Tumor Immunology”. Submitted in partial fulfilment of M.Sc. II Semester III to the Post Graduate Department of Zoology, Hislop College, RTM Nagpur University By Nidhi Lilhare Under the supervision of Dr. R. J. Andrew Dr. Payal Verma Dr. Nilesh Thaokar Mrs. Reena Agrawal Post Graduate Department of Zoology Hislop College Nagpur 2019-20
- 2. Contents What isimmunology? What is tumor? Tumor origin Types of tumor Classification of malignant tumor Malignant transformation of cell Tumor antigen Immune response to tumor RIA ELISA
- 3. What is immunology? Immunology has its origins in the study of how the body protects itself against foreign invasion in body that is harmful to our body. Our immunity decides our resistance and susceptibility to foreign harmful invasions. These foreign invaders can be any microorganisms, such as bacteria, viruses, protozoa, and fungi, and also parasitic organisms, such as helminth worms.
- 4. What is Tumor? A tumor is defined as a swelling or morbid enlargement that results from an overabundance of cell growth and division; normally cells grow and divide to produce new cells in a controlled and orderly manner. Tumor cells are self cells that have escaped normal growth regulating mechanisms.
- 5. Types of tumor There are two types tumors. These are: Benign Tumor: A tumor that is encapsulated and does not invade the healthy surrounding tissue is benign. Malignant tumor: A Tumor that grows uncontrolled invasive, progressive, destructive and that exhibit metastasis is malignant. These tumors are called cancer.
- 6. Classification of Malignanttumors. Malignant tumors are classified according to embryonic origin of the tissue from which the tumor is derived. Carcinomas: These arise from the endodermal or ectodermal origin. Sarcomas: Arise from mesodermal connective tissue. Leukemia, Lymphoma and myeloma are malignant tumors of hematopoietic cells of the bone marrow.
- 7. Malignant transformation ofcells Treatment of normal cultured cells with chemical carcinogens, irradiations, and certain viruses can alter their morphology and growth properties. In some cases this process is called as transformation, makes the cells able to produce tumors when injected into animals. Such cells are said to undergone malignant transformation, and they often exhibit properties in vitro similar to those of cancer cells. For example, they have decreased requirement for growth factors and serum, and are no longer anchorage dependent, and grow in density- independent fashion.
- 8. General features ofTumor immunity Tumor express antigens that are recognized as foreign by the immune system of the tumor bearing host. Though tumor cells are derived from host cell they are capable of elicit immune response. The first experimental demonstration that tumor can induce protective immune response came from studies of transplanted tumors in 1959s. Immune responses frequently fail to prevent the growth of tumors. Experimental demonstration of tumor immunity
- 9. Tumor antigens Twotypes of tumor antigens have been identified on the surface of tumor cells: Tumor specific transplantation antigens (TSTAs) Tumor associated transplantation antigen (TATAs)
- 10. Tumor specific antigen Tumor-specific antigen have been identified on tumor induced with chemical or physical carcinogens and on virally induced tumors. Demonstrating the presence of tumor specific antigens on spontaneously occurring tumors is particularly difficult because the immune response to such tumors eliminates all of the tumor cells bearing sufficient numbers of the antigens and in this way selects for cells bearing low levels of the antigens. Methylcholanthrene and ultraviolet light are two carcinogens that have been used extensively to generate lines of tumor cells.
- 11. Tumor associated antigens These antigens may be present in the normal cells. Oncofetal tumor antigens: As the name implies, are found not only on cancerous cells but also on normal fetal cells. These antigens appear early in embryonic development, before the immune system acquires immunocompetence, if these cells appear later on cancer cells, they are recognized as non- self and induce immunological response. Two well-studied oncofetal antigens are alpha-fetoprotein(AFP) and carcinoembryonic antigen (CEF). Oncogene proteins as tumor antigen: These proteins are also present in normal cells encoded by corresponding proto oncogene. In many cases, there is no qualitative difference between oncogene and proto oncogene products, instead increased level of oncogene product can be recognized by immune system.
- 12. Types of tumorantigens
- 13. Immune response totumor CTLs perform a surveillance function by recognizing and killing potentially malignant cells that express peptides derived from mutant cellular proteins or oncogenic viral proteins. The principal mechanism of tumor immunity is killing of tumor cells by CD8+ CTLs. CD8+ T-cells responses specific for tumor antigens may require cross presentation of the tumor antigen by professional APCs, such as dendritic cells. Tumor bearing hosts may produce antibodies against various tumor antigens. NK cells kill many types of tumor cells specially cells that have reduced class-I MHC expression and can escape killing by CTLs. The role of macrophages in anti-tumor immunity is largely inferred from the demonstration that in vitro, activated macrophages can kill many tumor cells more efficiently then they can kill normal cells.
- 14. Induction of T-cellresponse to tumor
- 15. Evasion of immuneresponse by tumor Many malignant tumor possess mechanism that enable them to evade or resist host immune responses. The process of evasion, often called as tumor escape, maybe a result of several mechanism. Class-I MHC expression may be downregulated on tumor cells so that they cannot be recognized by CTLs. Tumor lose expression of antigen that elicit immune responses. Tumors may fail to induce CTLs because most tumor cells do not express co-stimulators or class-II MHC molecules. The product of tumor cell may supress anti-tumor immune responses. Tumor antigens may induce specific immunologic tolerance.
- 17. Cancer Immunosurveillance versus Immunoediting Cancer immunoediting process is envisaged to consist of three phases: elimination, equilibrium, and escape . Elimination phase corresponds to the original concept of cancer immunosurveillance, whereby nascent tumor cells are successfully recognized and eliminated by the immune system, thus returning the tissues to their normal state of function. tumor cells that elude the immunosurveillance phase will progress to the immune editing phase, called the equilibrium phase of advanced oncogenesis, where tumor expansion and metastasis are minimal (tumor dormancy) and usually occur without symptoms. In the equilibrium phase, the immune system may eventually eliminate all tumor cells leading to an outcome similar to the elimination phase. In a second scenario, the constant interaction of the immune system with tumor over a long period of time may actually “edit” or sculpt the phenotype of the developing tumor, resulting in the immunoselection of a tumor that has been shaped into a less-immunogenic state. tumor that are no longer susceptible to immune attack then progress into the immunoediting process, termed “escape.” The emergence of clinical symptoms of cancer generally correlates with the escape stage. tumor subverts the immune system, either directly through its nonimmunogenic phenotype, or indirectly through a variety of immunosuppressive mechanisms.
- 18. Immunotechniques Two immunetechniques will be discussed here: Radioimmunoassay (RIA) Enzyme linked immunosorbent assay(ELISA)
- 19. RIA Radioimmunoassay (RIA)is an in vitro assay that measures the presence of an antigen with very high sensitivity. Basically any biological substance for which a specific antibody exists can be measured, even in minute concentrations. Radioimmunoassay (RIA) method: The target antigen is labeled radioactively and bound to its specific antibodies (a limited and known amount of the specific antibody has to be added). A sample, for example a blood-serum, is then added in order to initiate a competitive reaction of the labeled antigens from the preparation, and the unlabeled antigens from the serum-sample, with the specific antibodies. The competition for the antibodies will release a certain amount of labeled antigen. This amount is proportional to the ratio of labeled to unlabeled antigen. A binding curve can then be generated which allows the amount of antigen in the patient's serum to be derived.
- 20. Cont…. That meansthat as the concentration of unlabeled antigen is increased, more of it binds to the antibody, displacing the labeled variant. The bound antigens are then separated from the unbound ones, and the radioactivity of the free antigens remaining in the supernatant is measured. A binding curve can be generated using a known standard, which allows the amount of antigens in the patient's serum to be derived. Radioimmunoassay is an old assay technique but it is still a widely used assay and continues to offer distinct advantages in terms of simplicity and sensitivity.
- 21. ELISA ELISA (enzyme-linkedimmunosorbent assay) is a plate-based assay technique designed for detecting and quantifying peptides, proteins, antibodies and hormones. In an ELISA, an antigen must be immobilized to a solid surface and then complexed with an antibody that is linked to an enzyme. Detection is accomplished by assessing the conjugated enzyme activity via incubation with a substrate to produce a measurable product. The most crucial element of the detection strategy is a highly specific antibody-antigen interaction. In ELISA, various antigen-antibody combinations are used, always including an enzyme-labeled antigen or antibody, and enzyme activity is measured colorimetric ally. The enzyme activity is measured using a substrate that changes color when modified by the enzyme. Light absorption of the product formed after substrate addition is measured and converted to numeric values. Depending on the antigen-antibody combination, the assay is called a direct ELISA, indirect ELISA, sandwich ELISA, competitive ELISA etc.
- 22. Direct ELISA Atarget protein (or a target antibody) is immobilized on the surface of microplate wells and incubated with an enzyme- labeled antibody to the target protein (or a specific antigen to the target antibody). After washing, the activity of the microplate well-bound enzyme is measured.
- 23. Indirect ELISA Atarget protein is immobilized on the surface of microplate wells and incubated with an antibody to the target protein (the primary antibody), followed by a secondary antibody against the primary antibody. After washing, the activity of the microplate well-bound enzyme is measured. Although indirect ELISA requires more steps than direct ELISA, labeled secondary antibodies are commercially available, eliminating the need to label the primary antibody.
- 24. Sandwich ELISA Anantibody to a target protein is immobilized on the surface of microplate wells and incubated first with the target protein and then with another target protein-specific antibody, which is labeled with an enzyme. After washing, the activity of the microplate well-bound enzyme is measured. The immobilized antibody (orange) and the enzyme- labeled antibody (green) must recognize different epitopes of the target protein.
- 25. Summary Tumor cellsare self cells that have escaped normal growth regulating mechanisms. There are two types of tumor benign tumor and malignant tumor. Malignant tumor are also referred to as cancer. There are two types of tumor antigens: tumor associated transplantation antigen Tumor specific transplantation antigen Basic response to tumor by immune system is immunosurveillance. We discussed two types of immunotechniques: RIA & ELISA
- 26. References R. Goldsby,T. Kindt & B. Osborne, Kuby immunology, fourth edition, Page No. 540-553 A. Abbas & A. Lichtman, Cellular and Molecular Immunology, Page No. 401-403 https://www.verywellhealth.com/what-does-malignant-and-benign- mean-514240 https://www.immunopaedia.org.za/immunology/special-focus-area/2- cancer-tumors/immune-responses-to-cancer/ https://www.antibodies- online.com/resources/17/1215/radioimmunoassay-ria/ http://ruo.mbl.co.jp/bio/e/support/method/elisa.html https://openi.nlm.nih.gov/detailedresult?img=PMC5354689_oncotarge t-08-10650-g001&req=4
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