The mucosal immune system encompasses a wide array of interactions that work in concert to protect an individual from harmful agents while retaining tolerance to molecules, microbes, and self-antigens that present no danger. The upheaval in the regulation-response balance is a critical aspect in both infectious and immune-mediated disease. To understand this balance and methods of its restoration, iterative and integrative modeling cycles on the pathogenesis of disease are necessary. In this thesis, I present three studies highlighting phases of a systems immunology cycle. Firstly, the thesis provides a description of the construction of a computational ordinary differential equation based model on the host-pathogen-microbiota interactions during Clostridium difficile infection and the use of this model for the development of the hypothesis that host-antimicrobial peptide production may correlate with increased disease severity and promote increased recurrence. Secondly, it provides insight into the necessity of trans-disciplinary analysis for the understanding of novel molecular targets in disease through the immunometabolic regulation of CD4+ T cell by NLRX1 in inflammatory bowel disease. Third, it provides the assessment of novel therapeutics in disease through the evaluation of LANCL2 activation in influenza virus infection. In total, the computational and experimental strategies used in this dissertation are critical foundational pieces in the framework of precision medicine initiatives that can assist in the diagnosis, understanding, and treatment of disease. / Ph. D. / Many diseases are a result of altered patterns of interaction between the body, bacteria, viruses or nutrients. When these patterns are altered, inflammation occurs. If not controlled, the inflammation can cause pain, damage to the affected area, and other specific symptoms depending on the type of disease. This dissertation details the use of alternative methods of treating disease and analyzing disease in the context of Clostridium difficile infection, inflammatory bowel disease and influenza infection. It provides insight into the development of computational models with equations to capture the response patterns. It assesses the connections between immunology and metabolism that can lead to inflammation. And, it identifies a new therapeutic target for influenza infection. Together, these three phases are important pieces toward a future with improved understanding of disease and treatments that can be specific and customized for every individual.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/78233 |
| Date | 20 June 2017 |
| Creators | Leber, Andrew James |
| Contributors | Animal and Poultry Sciences, Bassaganya-Riera, Josep, Abedi, Vida, Bevan, David R., Hontecillas-Magarzo, Raquel |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Dissertation |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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