Files and links (1)
PDFOpen Access (License Unspecified), Open Access
Dissertation
Effects of extrinsic and intrinsic factors on age-associated decline in natural killer cell activity during primary influenza infection
Doctor of Philosophy (Ph.D.), Drexel University
Jun 2010
DOI:
https://doi.org/10.17918/etd-3321
Abstract
The fastest growing segment of the U.S. population is the group of individuals over the age of 65 years. Aging is accompanied by numerous changes in immune function and is associated with an increased morbidity as well as mortality to virus infections. Influenza is a major public health concern. Each year seasonal influenza disease occurs with a number of hospitalizations. In addition, influenza and its secondary complications rank as the 4th leading cause of deaths among the elderly. An age-associated decrease and delay in cell-mediated response, a reduction in the proliferative T cell response, and an altered cytokine production in response to influenza vaccination or infection have been reported. These are parameters of adaptive immune response. However, study of innate immune response against primary influenza infection has lacked attention. Natural killer (NK) cells are an integral part of innate immunity and play a key role in controlling viral infections and foreign pathogens. Here we report that NK cells are essential for controlling influenza virus replication early during infection independent of age. Importantly, there is an age-associated impairment in influenza-inducible NK cytotoxicity and a lack of increase in NK cells at the site of infection. In addition, aged mice produced less interleukin (IL)-15 and interferon (IFN)-[gamma] compared to young mice following influenza infection. While enhancement of NK cytotoxicity in response to stimulation with IL-2 or IL-15 in vitro was comparable in young and aged mice, aged mice demonstrated significantly lower enhancement of granzyme B expression in response to IL-2 or IL-15 and of IFN-[gamma] production in response to IL-15. These results demonstrate that age-associated impairment in influenza-inducible NK cytotoxicity may be caused by a combination of extrinsic influences, i.e. limited NK stimulating cytokines in the aged environment, and intrinsic defects, i.e. a limited inability of NK cells of aged mice to respond to cytokines and possibly other stimuli. These findings suggest that NK cells may be therapeutic targets for an intervention to restore or boost inducible NK cell cytotoxicity during primary viral infection.
Metrics
29 File views/ downloads
11 Record Views
Details
- Title
- Effects of extrinsic and intrinsic factors on age-associated decline in natural killer cell activity during primary influenza infection
- Creators
- Shoko Nogusa - DU
- Contributors
- Donna Murasko (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- Biology; College of Arts and Sciences; Drexel University
- Other Identifier
- 3321; 991014632665404721