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Moving in for the Kill: Natural Killer Cell Localization in Regulation of Humoral Immunity

Moran, Michael
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460446618

Abstract Details

2016, MS, University of Cincinnati, Medicine: Immunology.
Modern medicine has advanced tremendously over the past century to develop vaccines that have successfully reduced the spread of, or eradicated, many infectious diseases including measles, smallpox and polio. While this progression has dramatically improved global health, the development of vaccination strategies for protection against deadly pathogens, such as human immunodeficiency virus (HIV) and hepatitis C virus, have been elusive. Further investigation of immune-regulatory mechanisms that are influential in the development of protective humoral immunity must be pursued for the generation of robust vaccinations to continue. Here, we present our findings on a regulatory role for natural killer (NK) cells in the generation of the humoral immune response to viral infection. Specifically, we have determined that in mice infected with the acute strain of lymphocytic choriomeningitis virus (LCMV), NK cells impair the development of T follicular helper cells and the germinal center response. We have determined that this suppressive function is carried out in a perforin-dependent manner at an early stage of infection. Importantly, during this early time frame, an anatomic redistribution of NK cells occurs in the spleen to areas involved in generation of the germinal center responses, including the B cell follicle and T/B border of the white pulp. Mechanistically, we have identified a subset of these NK cells expressing the B-cell follicle homing receptor CXCR5 that are present in the spleen at these same early time points of infection. Taken together, these data support out hypothesis that this subset of white pulp localizing NK cells traffics to this region early in infection to facilitate direct contact with cells involved in the generation of T follicular helper cell and germinal center responses. While in contact with these precursors, we suspect NK cells carry out perforin-dependent cytolysis of target cells to ultimately suppress the generation of humoral immune responses. These NK cells may represent an immunoregulatory subset and a possible new target of interventions to facilitate the generation of robust and protective vaccine strategies against pathogens.
Stephen Noel Waggoner, Ph.D. (Committee Chair)
Leah Claire Kottyan, Ph.D. (Committee Member)
J, Matthew Kofron, Ph.D. (Committee Member)
Jonathan Katz, Ph.D. (Committee Member)
46 p.
Immunology
Natural killer cells; localization; viral infection; LCMV; humoral immunity

Recommended Citations

Citations

  • Moran, M. (2016). Moving in for the Kill: Natural Killer Cell Localization in Regulation of Humoral Immunity [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460446618

    APA Style (7th edition)

  • Moran, Michael. Moving in for the Kill: Natural Killer Cell Localization in Regulation of Humoral Immunity. 2016. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460446618.

    MLA Style (8th edition)

  • Moran, Michael. "Moving in for the Kill: Natural Killer Cell Localization in Regulation of Humoral Immunity." Master's thesis, University of Cincinnati, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1460446618

    Chicago Manual of Style (17th edition)

ucin1460446618
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© 2016, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.
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