Summer Intern Project 2010: Lenka Matejovicova

Project: Migration, recirculation and search: a problem in starting immune responses

Supervisors: Prof. Benjamin Chain, Prof. John Shawe-Taylor

Most immunological responses start when specific (CD4 T) lymphocytes meet their antigens (for example a fragment of a pathogen) which are “presented” to them by dendritic cells, which sit within lymph nodes or the “white pulp” area of the spleen. This initial encounter presents some logistic problems. Each specific T cell is present at very low numbers – typically 10-100 cells, out of a total of 100 million in the mouse, for example. The number of dendritic cells carrying the antigen is also very limited – typically probably 100-1000 cells. In order to ensure this process is as efficient as possible, T cells recirculate rapidly moving from one lymph node to another (via the blood) and searching for the “matching” antigen. Optimising this process is a key determinant in delivering new and better vaccines.

In this project, the overall objective was to build a model describing the kinetics of T cell recirculation, and use this to derive probability distributions which describe the distribution of the time required for T cells to run through the lymph node, scanning dendritic cells for matching antigens. Data were obtained from an experiment, where an efferent lymph vessel of a particular lymph node of a sheep and a vein (in neighbourhood of this lymph node) were cannulated, lymphocytes were taken and injected back to the bloodstream when labelled. Samples of blood and leaving lymph were taken in time intervals after the injection and percentages of labelled lymphocytes in blood and lymph samples were determined (using flow cytometry).

Using mathematic software (Matlab), I built several different models of lymphocyte movement through the lymph node, visualised them and evaluated their disadvantages. I learnt to deal with a number of questions which arose after each problem solved, choosing the most relevant ones to tackle next. I also got great practice working in Matlab, a better notion of the way the immune response works and improved my academic skills.

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