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Immunosurveillance
- 1. IMMUNOSURVEILLANCE KAVYA G MSC BIOTECHNOLOGY 2ND SEM 18LS301010
- 2. INTRODUCTION • Increased incidence of cancer due to inefficiency of immunosurveillance that result due to Ageing Congenital immunodeficiency Acquired immunodeficiency • The immune response to cancer can be broadly divided into innate and acquired components • Innate immunity serves as a first line defense against cancer, as germ line encoded pattern recognition receptors rapidly detect infected or stressed cells, there by triggering potent effector mechanism aimed at tumor containment.
- 3. Cont… • In contrast, adaptive immunity reflecting the requirement for activation and expansion of rare tumor-associated antigen-specific lymphocytes harboring somatically rearranged immunoglobulin or T- cell receptors. • NKT cells and γδT cells function at the interface of innate and adaptive immunity. • The interplay of tumor cells and endogenous immunity is increasingly recognized to play a decisive role throughout the multiple stages of carcinogensis.
- 4. INNATE ANTI-TUMOR RESPONSES • The innate immune system functions as an extrinsic surveillance mechanism for genotoxic injury. • These innate immunity responses may contribute to tumor suppression, their aberrant activation may also prove deleterious when normal tissues are perturbed as during auto-immunity or chronic inflammation. • When NKG2D ligands are expressed on the surface of stressed cells triggers NKG2D dependent activation of NK, NKT, and γδ T-cells which inhibit tumor growth through cytotoxicity and IFN-γ production.
- 5. Cont…. • Additionally, some heat shock proteins-70, uric acid, HMGB1 are produced which activates macrophages and dentritic cells. • In microenvironment of tumor cells have been demonstrated to cleave NKG2D ligands from their surface via the isomerase ERp5 ADAM metalloprotienases, which further fuel the immune suppression.
- 6. 1. NK CELLS 2. NKT CELLS
- 7. 3. MACROPHAGE 4. IKDC
- 8. ADAPTIVE ANTI-TUMOR RESPONSES • Adaptive antitumor responses is typically by dendritic cells which capture dying tumor cells, process the antigenic cargo for MHC class I and II presentation, migrate draining lymph nodes and stimulate antigenic- specific T and B lymphocytes . • In tumor microenvironment the dentritic cell may activated by danger signals released from stressed or necrotic tumor cells, there by triggering a maturation program that includes expansion of multiple co-stimulatory molecules and cytokines that result in effector T-cell responses. • CD4+ T cell CD40 ligand expression may trigger CD40 signaling on dentritic cell resulting in enhanced IL-12 productions and the differentiation of IFN-γ and cytotoxic T lymphocytes.
- 9. MECHANISM OF ESCAPE • Elimination—Immune cells mount the initial antitumor response. • Equilibrium—Insufficient elimination enables developing tumor to acquire tumor evasive mechanisms • Escape—Tumor cell evasion results in cancer progression.
- 10. • Certain tumor cells may shed or stop expressing the surface antigen thus making the tumour cell immunologically invisible Modulation Of Surface Antigen • Some cancer produce a mucoprotein called sialomucin. It bind to the surface of the tumour cell. Since sialomucin is a normal component, the tumour cell are not recognised by immune system Masking Tumour Antigens • Certain tumour cell evokes immune system to produce blocking antibodies, which can not fix and activate complement, resulting in prevention of tumor cell lysis. Production Of Blocking Antibody
- 14. • Due to the fast rate of proliferation of malignant cells tumor may be able to sneak through before the development of an effective immune response and once they reach a certain mass, the tumour may be too great for the host immune system to control Fast Rate Of Proliferate Of Malignant Cell • Some tumour may form cytokine like Tranforming Growth Factor β (TGF-β) which suppressed CMI Suppression Of Cell Mediated Immunity (CMI)