The immune system is a fascinating complex system taking decisions on how to respond to a wide variety of stimuli, varying from lethal pathogens to harmless proteins in the food. Decisions are remembered for life in the form of immunological memory. Most of the research in immunology is of a qualitative nature, describing novel cell types, molecules, and genes. The proper understanding of such a complex systems also requires a more quantitative approach describing the various population sizes, the turnover rates of the cells within each population, their migration rates, and the rates at which cells form contacts with other cells.
A major part of our work is to develop a more quantitative immunology by describing the population dynamics of its major populations using a variety of labeling techniques and mathematical modeling to analyze the data. Using deuterium labeling we estimate the expected life span of naïve and memory T cells in volunteers and HIV infected patients, finding that long-lived immunological memory is maintained by short-lived cells, and that HIV infecting increases cellular turnover rates. We aim to quantify the daily number of target cells that one cytotoxic T cell can kill per day.
Using a variety of modeling techniques we analyze 2-photon microscopy data to quantify the migration of T cells in lymphoid tissue and within the skin of mice. We estimate the true long contact times required to stimulated naïve T cells from short videos, and find evidence for directed migration of cytotoxic T cells in peripheral tissues.
Pathogens are also fascinating complex systems that by their faster evolution manage to exploit properties of the immune system to elicit inappropriate immune reactions. We study host-pathogen evolution by in silico evolution models. We study the evolution of polymorphism in the antigen presentation pathway and of the KIR molecules on natural killer cells. Recently we started to study the evolution and epidemiology of pathogens that are adapting each unique immune system of their massively heterogeneous hosts.
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