| الوصف: |
The innate immune system detects pathogens and initiates adaptive immune responses. Inflammasomes are central components of the innate immune system, but whether inflammasomes provide sufficient signals to activate adaptive immunity is unclear. In this dissertation, I present the work I have done using a genetic mouse model system that allowed me to simultaneously express the model antigen ovalbumin (Ova) and activate the NAIP–NLRC4 inflammasome in specific cells throughout the mouse. Chapter One begins with an introduction to innate and adaptive immunity. I then provide an overview of inflammasome activation, followed by a discussion of what is currently known about how inflammasomes influence adaptive immunity. This section discusses the roles inflammasome-driven lytic cell death (termed pyroptosis) might play in antigen release, evidence for inflammasome activation driving CD4+ and CD8+ T cell responses, and instances where inflammasome activation appears to inhibit adaptive immunity. This chapter closes with evidence for inflammasomes influencing adaptive immunity in vaccines, anti-tumor immunity, and autoimmunity. Overall, Chapter One provides a foundation for appreciating why we need better understanding of the role inflammasome activation plays in driving adaptive immune responses. In Chapter Two, I present my early doctoral work, where I began to explore what role(s) NAIP–NLRC4 inflammasome activation might have on adaptive T cell immunity. Here I introduce the OvaFla mouse model previously, which was described by the Vance lab. These mice use the Cre-Lox system to inducibly express a fusion protein containing Ova antigen and the 166 amino acid C-terminal of flagellin, which will activate NAIP–NLRC4 but not an alternative flagellin sensor called TLR5. For experiments in this chapter, I crossed these “OvaFla” mice with mice containing a tamoxifen-inducible Cre driver, Cre-ERT2, that results in systemic OvaFla expression following tamoxifen administration. I found that systemic OvaFla can drive cross ... |
