Skip to Main Content
 

Global Search Box

 
 
 
 

Files

File List


6703.pdf (2.58 MB)

ETD Abstract Container

Abstract Header

Autoimmune Mechanisms in Cigarette Smoke-Induced Inflammation and Pathology

Eppert, Bryan L
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1382950967

Abstract Details

2013, PhD, University of Cincinnati, Medicine: Toxicology (Environmental Health).
Cigarette smoking is the leading cause of preventable death in the United States. The global prevalence of cigarette smoking continues to rise despite considerable efforts to prevent the use of cigarettes. The most common causes of mortality attributable to cigarette smoking are cardiovascular disease, chronic obstructive pulmonary disease, and lung cancer. The effects of cigarette smoking on the immune system are important contributors to the mechanism of cigarette smoke associated diseases. Cigarette smoking is also a significant risk factor for a variety of autoimmune diseases including rheumatoid arthritis, multiple sclerosis, and systemic lupus erythematosus. Increasingly, research into the inflammatory processes underlying chronic obstructive pulmonary disease has identified an important role for the adaptive immune system in disease progression. Some of the effects of cigarette smoking on the cells of the adaptive immune system in patients with chronic obstructive pulmonary disease are consistent with an autoimmune response. Definitively attributing a causative role to cigarette smoke in the development of an autoimmune process in patients with chronic obstructive pulmonary disease is prevented by the confounding effects of concurrent infections or cancer. This dissertation tests the hypothesis that chronic cigarette smoking is sufficient to trigger an autoimmune response that results in pulmonary pathology in mice. In Chapter 2 I demonstrate that chronic cigarette smoke (CS) leads to the generation of T cells that cause antigen-dependent lung pathology. I also explore the mechanism whereby CS leads to aberrant T cell activation by testing the hypothesis that chronic CS exposure leads to a defect in the ability of regulatory T cells to suppress T cell activation. Finally, I characterize the functional effects of chronic CS exposure on CD4+ and CD8+ T cells. In Chapter 3 I observe that plasma from mice chronically exposed to CS is sufficient to cause alveolar destruction in CS-naive recipient mice. I also investigate potential mechanisms responsible for the development of pulmonary pathology in recipients of plasma from CS exposed mice. This dissertation presents strong evidence that chronic CS exposure is sufficient to initiate both cell-mediated and humoral autoimmunity in mice. This provides proof-of-concept that autoimmunity may play a role in some CS-associated diseases such as chronic obstructive pulmonary disease and supports a causative role for CS in the development of CS-associated autoimmune diseases. The goal of this research is to provide better understanding of the development of CS-associated diseases in the hopes of informing new therapies when efforts to prevent cigarette smoking fail.
Michael Borchers, Ph.D. (Committee Chair)
Divaker Choubey, Ph.D. (Committee Member)
Ralph Panos, M.D. (Committee Member)
William Ridgway, Ph.D. (Committee Member)
Glendon Michael Zinser, Ph.D. (Committee Member)
102 p.
Toxicology
Lung; Autoimmunity; Immunology; Cigarette smoking; Chronic obstructive pulmonary disease; Animal models

Recommended Citations

Citations

  • Eppert, B. L. (2013). Autoimmune Mechanisms in Cigarette Smoke-Induced Inflammation and Pathology [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1382950967

    APA Style (7th edition)

  • Eppert, Bryan. Autoimmune Mechanisms in Cigarette Smoke-Induced Inflammation and Pathology. 2013. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1382950967.

    MLA Style (8th edition)

  • Eppert, Bryan. "Autoimmune Mechanisms in Cigarette Smoke-Induced Inflammation and Pathology." Doctoral dissertation, University of Cincinnati, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1382950967

    Chicago Manual of Style (17th edition)

ucin1382950967
446
© 2013, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.