Niels Bohr Institutet > Kalender - det sker på NBI > 2010 > Master Thesis Defense ...

Master Thesis Defense by Pernille Yde

Inflammatory response and Excitable Media 

During acute inflammation white blood cells are recruited to the site of infection, in order to combat pathogens and clean up after the damage. The white blood cells migrate from the blood vessels and into the tissue, following a signal of chemoattractants, which are secreted from damaged host cells.

This thesis investigates two main questions regarding the recruitment of white blood cells: 1) How is the chemoattractant signal transmitted through the tissue? And 2) how does the white blood cells respond to the signal in order to achieve directed motion?

To answer these questions the mechanisms that regulate immune response have been investigated. In particular the regulatory network of the transcription factor NfkB, has been coupled to the production and regulation of the neutrophil chemoattractant TNF.

A new simple NfkB-TNF model, has been constructed in order to capture the essential mechanisms of the system: Adaptation, amplification, thresholded response and spatial coupling (diffusion). Since the number of variables in the simple model is rather low, it is possible to investigate the phase space of the system. From this analysis I have found that many of the observed phenomena can be explained by shifts in the nullclines.

In order to investigate the system at tissue level, a one dimensional model of spatially coupled cells have been constructed. The spatially coupled system exhibits behavior which is typical for excitable media, and is able to produce single or repetitive waves of high-gradient chemoattractant signal, that propagate through the tissue without loosing amplitude.

In order to address the question of how the white blood cells respond to the chemoattractant signal, previous studies of neutrophil chemotaxis and the social amoeba Dictyostelium discoideum, have inspired us to construct a new chemotaxis model. This model accounts for a mechanism in which the neutrophils can respond to a travelling wave of chemoattractant in order to achieve directed motion towards the source of the waves - and hence towards the site of infection.

In the last part of the thesis the chemotaxis model is combined with the simplified NfkB-TNF model in order to compare chemotaxis in different TNF profiles. I illustrate that the waves of chemoattractant constitute an efficient and long-ranged recruitment of neutrophils.