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This dissertation, A Complementary Activation of Peripheral NK Cell Immunity in EBV Related Nasopharyngeal Carcinoma by Ying, Zheng, 鄭盈, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract Abstract of thesis entitled A COMPLEMENTARY ACTIVATION OF PERIPHERAL NK CELL IMMUNITY IN EBV RELATED NASOPHARYNGEAL CARCINOMA Submitted by Zheng Ying For the degree of Master of Philosophy At the University of Hong Kong in October 2005 NK cells, αβ- and γδ-cytotoxic T lymphocytes (CTLs) are important players in cellular immunity against tumors. NK cells and γδ-CTLs are believed to play a more dominant role in early innate immunity due to their non-MHC-restricted cytotoxicity whereas αβ-CTLs, with their MHC-restricted cytolytic effect, are more frequently associated with the adaptive immunity. Nasopharyngeal carcinoma (NPC) has a high incidence in several areas in Southern China, especially in the Cantonese region around Guangzhou. Similar to other EBV-related diseases, the immunity to NPC is mainly T cell mediated. Previous studies have demonstrated that NPC patients with active disease exhibit quantitative and qualitative deficits in γδT cells and EBV-specific αβT cells. However, NK cells, the direct killers of cancers, are rarely mentioned in NPC studies. I In this study, further observations of a complementary activation of peripheral NK cells in NPC patients were reported. The NK cells in these patients, compared to those of healthy subjects and NPC survivors, were preferentially activated in response to the stimulation of myeloma cell line XG-7 and expanded in the presence of exogenous IL-2. The production of IFN-γ was lowest in the patient group, whereas IL-12, IL-15 and TNF-α were produced higher levels in patients than the donors and survivors. The cytolytic effect of the NK cells against NPC cells in the patient group was higher than that of the healthy donors and NPC survivors. Furthermore, the patients at later stages of NPC exhibited lower γδ-CTLs activity but higher NK cytotoxicity towards NPC targets, accompanied with higher production of IL-12, IL-15 and TNF-α but lower production of IFN-γ, than patients at earlier stages. This repertoire from NK cells may be part of a compensatory re-activation of the innate immunity triggered, which is believed through various cytokines and chemokines, when adaptive T cell immunity is breached. Our study results have suggested complementary roles of innate and adaptive immune response in tumor immunity where NK cells, γδ- and αβ-CTLs compensate for the deficits of one another at different stages of tumor invasion. II DOI: 10.5353/th_b3460516 Subjects: Nasopharynx - Cancer - Immunological aspectsKiller cellsT cells

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