- Title
- Investigation of the immune mechanisms in pregnancy and asthma leading to increased susceptibility and disease severity to respiratory virus infections
- Creator
- Vanders, Rebecca Louise
- Relation
- University of Newcastle Research Higher Degree Thesis
- Resource Type
- thesis
- Date
- 2013
- Description
- Research Doctorate - Doctor of Philosphy (PhD)
- Description
- The immune system is an essential component of the human body, providing protection against invading pathogens like the respiratory viruses, human rhinoviruses (HRVs) and influenza virus. Numerous alterations occur in the maternal immune system during pregnancy in order to accommodate the presence of a growing fetus. During pregnancy, there is an increased maternal risk for susceptibility to these respiratory virus infections, as well as increased disease severity following infection. The presence of an underlying inflammatory immune disease, like asthma, may lead to an imbalance in maternal immunity, which may further worsen the outcomes in these women following respiratory virus infections. In order to improve the health of both mother and baby, it is first necessary to understand the underlying changes that occur in maternal immunity following respiratory virus infections, as well as the confounding effect that may result from having asthma. In this study, an in vitro system was utilized, in which peripheral blood mononuclear cells (PBMCs) were isolated from pregnant and nonpregnant women, with and without asthma. PBMCs were cultured with different strains of HRVs and influenza, as well as with positive stimuli, and a range of antiviral and inflammatory factors were then measured. The activity of specific cell types was also assessed following viral infection. This study shows that PBMCs from pregnant women have a significant attenuation in their innate antiviral immune response following infection with both HRV and 2009 pandemic swine flu (H1N1pdm09). Alterations were also identified in the number and activity of key antiviral immune cells during pregnancy following H1N1pdm09 infection. Asthma during pregnancy altered maternal immunity, resulting in impaired innate and adaptive antiviral immune responses and an enhanced inflammatory response. In conclusion, this study identifies significant changes that occur in maternal antiviral immunity, which may explain the increased risk for susceptibility to respiratory virus infections in these women. In addition, altered antiviral and inflammatory immunity in pregnant women with asthma provides a plausible explanation for the high prevalence of respiratory virus-induced asthma exacerbations that occur in these women.
- Subject
- pregnancy; innate immunity; swine flu; Interferons; virus; pDCs; CD8 T cells; IFN-alpha; IFN-lambda; vaccination
- Identifier
- http://hdl.handle.net/1959.13/937514
- Identifier
- uon:12574
- Rights
- Copyright 2013 Rebecca Louise Vanders
- Language
- eng
- Full Text
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| View Details Download | ATTACHMENT02 | Thesis | 6 MB | Adobe Acrobat PDF | View Details Download |