Dissertation
Deciphering the MHC class I-unrestricted immune response to Rhodocossus equi
Washington State University
Doctor of Philosophy (PhD), Washington State University
08/2010
DOI:
https://doi.org/10.7273/000006030
Abstract
Rhodococcus equi is an important respiratory pathogen of foals which is ubiquitous in the environment. The bacterium survives within the soil, likely infecting foals within the first few weeks of life. Adult horses are naturally immune due to a protective type I immune response. Foals, however, lack the protective type I immune response during the neonatal period rendering them susceptible to disease. Protective immunity to R. equi is characterized by Th1 CD4+ T-lymphocytes and CD8+ cytotoxic T-lymphocytes (CTL). The CD4+ T-lymphocytes are potent producers of IFN-[gamma], which functions to upregulate phagosomal maturation, while the CTL directly lyse R. equi infected macrophages. Recent characterization of the CTL demonstrated several unique features, namely that they are MHC class I-unrestricted, they are present in all adult horses, and they are absent during the neonatal period and develop as the foal ages. The first part of this project demonstrated that the antigens recognized by MHC class I-unrestricted CTL was a non-protein, and was later shown to be R. equi cell wall lipids. The cell wall lipids were composed of three primary lipid fractions: trehalosemonomycolate (TMM), trehalose-dimycolate (TDM), and cardiolipin (CL). MHC mismatched target cells pulsed with purified TMM and CL, but not TDM were lysed by CTL. Furthermore, all three lipids significantly elevated transcription of the cytokine IFN-[gamma], but not IL-4, supporting the role of lipids as immunogens. Future work will focus on whether the lipid antigen is presented by CD1 molecules. The second part of this project evaluated the protective mechanism behind oral inoculation in neonatal foals with live R. equi. Foals orally inoculated with virulent R. equi had accelerated appearance of CTL, which developed by three weeks of age in comparison to uninoculated controls which developed CTL at five weeks. Unexpectedly, foal PBMC produced adult levels of IFN-[gamma] at 1, 3, and 5 weeks when stimulated by R. equi or extracted cell wall lipids. This data supports CTL as being an important component in protective immunity.
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Details
- Title
- Deciphering the MHC class I-unrestricted immune response to Rhodocossus equi
- Creators
- Seth Paul Harris
- Contributors
- Stephen A. Hines (Chair)Wendy C Brown (Committee Member)Melissa Trogdon Hines (Committee Member)Robert Hamilton Mealey (Committee Member) - Washington State University, Department of Veterinary Clinical SciencesTerry F McElwain (Committee Member) - Washington State University, Paul G. Allen School for Global Animal Health
- Awarding Institution
- Washington State University
- Academic Unit
- College of Veterinary Medicine
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 64
- Identifiers
- 99901055028701842
- Language
- English
- Resource Type
- Dissertation