Analysis and modelling of immune cell behaviour in lymph nodes based on multi-photon imaging

This thesis presents quantitative studies of T cell and dendritic cell (DC) behaviour in mouse lymph nodes (LNs) in the naive state and following immunisation. These processes are of importance and interest in basic immunology, and better understanding could improve both diagnostic capacity and therapeutic manipulations, potentially helping in producing more effective vaccines or developing treatments for autoimmune diseases. The problem is also interesting conceptually as it is relevant to other fields where 3D movement of objects is tracked with a discrete scanning interval. A general immunology introduction is presented in chapter 1. In chapter 2, I apply quantitative methods to multi-photon imaging data to measure how T cells and DCs are spatially arranged in LNs. This has been previously studied to describe differences between the naive and immunised state and as an indicator of the magnitude of the immune response in LNs, but previous analyses have been generally descriptive. The quantitative analysis shows that some of the previous conclusions may have been premature. In chapter 3, I use Bayesian state-space models to test some hypotheses about the mode of T cell search for DCs. A two-state mode of movement where T cells can be classified as either interacting to a DC or freely migrating is supported over a model where T cells would home in on DCs at distance through for example the action of chemokines. In chapter 4, I study whether T cell migration is linked to the geometric structure of the fibroblast reticular network (FRC). I find support for the hypothesis that the movement is constrained to the fibroblast reticular cell (FRC) network over an alternative 'random walk with persistence time' model where cells would move randomly, with a short-term persistence driven by a hypothetical T cell intrinsic 'clock'. I also present unexpected results on the FRC network geometry. Finally, a quantitative method is presented for addressing some measurement biases inherent to multi-photon imaging. In all three chapters, novel findings are made, and the methods developed have the potential for further use to address important problems in the field. In chapter 5, I present a summary and synthesis of results from chapters 3-4 and a more speculative discussion of these results and potential future directions.

Swedish-speaking Finns: a multi-method qualitative study of belonging and identification

The Swedish-speaking minority in Finland, often described as an ‘elite minority’, holds a special position in the country. With linguistic rights protected by the constitution of Finland, Swedish-speakers, as a minority of only 5.3%, are often described in public discourse and in academic and statistical studies as happier, healthier and more well off economically than the Finnish-speaking majority. As such, the minority is a unique example of language minorities in Europe. Knowledge derived from qualitatively grounded studies on the topic is however lacking, meaning that there is a gap in understanding of the nature and complexity of the minority. Drawing on ethnographic research conducted in four different locations in Finland over a period of 12 months, this thesis provides a theoretically grounded and empirically informed rich account of the identifications and sites of belonging of this diverse minority. The thesis makes a contribution to theoretical, methodological and empirical research on the Swedish-speaking minority, debates around identity and belonging, and ethnographic methodological approaches. Making use of novel methodology in studying Swedish-speaking Finns, this thesis moves beyond generalisations and simplifications on its nature and character. Drawing on rich ethnographic empirical material, the thesis interrogates various aspects of the lived experience of Swedish-speaking Finns by combining the concepts of belonging and identification. Some of the issues explored are the way in which belonging can be regionally specific, how Swedish-speakers create Swedish-spaces, how language use is situational and variable and acts as a marker of identity, and finally how identifications and sites of belonging among the minority are extremely varied and complex. The thesis concludes that there are various sites of belonging and identification available to Swedish-speakers, and these need to be studied and considered in order to gain an accurate picture of the lived experience of the minority. It also argues that while identifications are based on collective imagery, this imagery can vary among Swedish-speakers and identifications are multiple and situational. Finally, while language is a key commonality for the minority, the meanings attached to it are not only concerned with ‘Finland Swedishness’, but connected to various other factors, such as the context a person grew up in and the region one lives in. The complex issues affecting the lived experience of Swedish-speaking Finns cannot be understood without the contribution of findings from qualitative research. This thesis therefore points towards a new kind of understanding of Swedish-speaking Finns, moving away from stereotypes and simplifications, shifting our gaze towards a richer perception of the minority.