Amanda Griffin

E-mail: kiek0015@umn.edu

Thesis Advisor: Stephen McSorley

Year entered: 2005

Degree received:
B.A., Biology, St. Olaf College, Northfield, MN 2003

Honors and awards:

• Immunology Training Grant 2008-2010
• MICaB student representative 2008-2009

Thesis research:
My thesis project examines acquired immunity to typhoid, a disease caused by oral infection with Salmonella typhi. Every year 16 million cases of typhoid occur worldwide and approximately 200,000 of these patients die. Furthermore, in 1984 Salmonella was used intentionally by a cult in Oregon causing the largest documented bio-terrorist attack on US soil. Therefore, understanding immunity to Salmonella infection could aid vaccine development that is relevant to global and US healthcare.

As virulent Salmonella kill inbred mice, previous studies of mouse typhoid have examined the robust immune response following immunization with live vaccine strains (LVS) of Salmonella. However, patients in endemic areas are known to suffer from multiple, sequential cases of typhoid, suggesting that acquired immunity is less robust than mouse models predict. The goal of my thesis project is to generate a model to examine natural acquired immunity to typhoid. First, we identified an antibiotic (AB), enrofloxacin, that allowed mice to recover from primary typhoid. Interestingly, after clearance of bacteria, these mice developed a weak protective response to secondary typhoid. Thus, our AB-treatment model differs substantially from LVS-immunization and is more relevant to immunity in typhoid endemic areas. We have examined the basis of acquired immunity in the AB-treatment model and demonstrated that antibody, CD4 T cells, and IFN-gamma are all required. Furthermore, we have examined the maturation of Th1 cells in both models. In the AB-treatment model, Th1 cells develop rapidly but are lost over time. In contrast, Th1 cells develop slowly following LVS-Salmonella. Our data suggest sustained CD4 stimulation is required for optimal generation of Th1 responses and protective memory. In the coming year we will examine whether antigen persistence is sufficient for protective immunity to Salmonella, or whether there is another factor, such as a Salmonella virulence gene, that is needed in addition to antigen persistence.

Publications:

• Salazar-Gonzalez, R.M., A. Srinivasan, A. Griffin, G. Muralimohan, J.M. Ertelt, A.T. Vella, and S.J. McSorley. 2007. Salmonella flagellin induces bystander activation of splenic dendritic cells and hinders bacterial replication in vivo. J. Immunol. 179:6169-75.
• Griffin, A., D. Baraho-Hussain, and S.J. McSorley. 2009. Successful treatment of bacterial infection hinders development of acquired immunity. J. Immunol. (In press)
• Srinivasan, A., M. Nanton, A. Griffin, and S.J. McSorley. 2009. Culling of activated CD4 T cells during typhoid is driven by Salmonella virulence genes. J. Immunol. (In press)