Two mathematical approaches to a study of T cell motion and activation in the lymph node

T cells are part of the immune system and as such play a very important role in keeping us healthy. One crucial step in the complex process which is the immune response to pathogens is T cell activation. The general goal of my thesis is to mathematically describe the migration patterns followed by T cells while waiting to be activated in the lymph node. Insight into these migration patterns could lead to better knowledge of the strategies T cells take to make activation such an efficient process. In order to fulfill my goal I have used two different approaches: one mainly computational and the other mainly theoretical. On the computational side, I analyzed three-dimensional microscopic movies of mice lymph nodes inside of which labelled T cells are moving. From the movies I extracted the trajectories of the cells. I studied movies from two experimental frameworks, exogenous and endogenous. On the former, more frequent type of experiment, T cells are labelled outside the mouse and then transferred in. The endogenous experiments, on the contrary, involve genetically modified mice whose T cells are born labelled. I concluded that there is a significant difference in labelled T cell motion between the two experimental frameworks. This suggests that previous results from exogenous experiments should be treated with caution due to possible errors introduced by the methods specific to that type of experiment. On the theoretical side I studied the time it takes for a model T cell to be activated under different scenarios regarding the characteristics of the lymph node as well as of the other cells in it. Since T cells become activated after establishing contact with a specific cell among many similar ones which also move within the lymph node, what I effectively computed was the mean first passage time for a model T cell to reach a defined target within the model lymph node.Science, Faculty ofMathematics, Department ofGraduat