Innate and Adaptive Immunity to Bordetella pertussis and Francisella tularensis

Open Access
- Author:
- Place, David Ezekzel
- Graduate Program:
- Immunology and Infectious Diseases
- Degree:
- Doctor of Philosophy
- Document Type:
- Dissertation
- Date of Defense:
- August 28, 2015
- Committee Members:
- Girish Soorappa Kirimanjeswara, Dissertation Advisor/Co-Advisor
Girish Soorappa Kirimanjeswara, Committee Chair/Co-Chair
Eric Thomas Harvill, Committee Member
Jason Laurence Rasgon, Special Member
Pamela Hankey Giblin, Committee Member
Na Xiong, Committee Member - Keywords:
- Francisella tularensis
Bordetella pertussis
interleukin-1
inflammasome
CD8 T cells
memory cells
vaccination - Abstract:
- Respiratory infections by bacteria are the cause of significant deaths throughout the world. By understanding how different bacteria interact with the innate and adaptive immune systems of the hosts they infect, we can gain insight in how to better treat, vaccinate, and prevent the diseases they cause. In this dissertation the focus will be on two different bacterial pathogens which are often focused on in terms of respiratory infection, Bordetella pertussis and Francisella tularensis. Chapter 2 investigates the role of the inflammasome signaling complex and IL-1 signaling during interactions with B. pertussis and shows that the IL-1 response in the host, while required, does not require signaling through the inflammasome in the mouse model. In Chapter 3 we describe the development of a novel tool for studying CD8 T cell responses to F. tularensis LVS following vaccination by intranasal inhalation. Because Francisella can infect the respiratory tract as well as naturally infect through the intradermal route, which is the route by which humans are vaccinated, Chaper 4 reviews the currently limited immune responses generated locally within the skin. By understanding these various aspects of innate and adaptive immunity to each pathogen, we begin to develop and understanding of how both arms of the immune system interact to protect hosts during both primary and secondary challenges.