BBSRC MATSYB network  I2M: Immunology, Imaging and Modelling

British Society for Immunology

Mathematical modelling affinity group meeting

Monday 30 November 2009

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Registration from 08:30

Information

Registration from 08:30

Speakers

  • 9:00-10:00

    Cellular dynamics within the lymph node: from dynamical imaging to modelling and back again

    Stan Maree
    John Innes Centre, Norwich, BBSRC

    During the last years rapid developments in live imaging techniques have modified our picture of a lymph node from that of a rather well-organised tissue into being a highly dynamic and complex multi-cellular whirlpool. To analyse the significance of the complex cell migration patterns for the functioning of the lymph node, we have developed spatially explicit models of T cell and DC migration within lymph nodes. While two-photon microscopy (2PM) imaging by itself typically only presents a small fraction of the involved cells, we show that it gives sufficient information to reconstruct, through the modelling, a complete picture of the dynamics. The modelling indicates that the dynamical properties of T cells could in fact be a consequence of the densely packed lymph node environment itself. These insights were used to design new imaging experiments in order to test and confirm the modelling predictions. Importantly, it was essential to develop spatially explicit models with a very direct mapping to the experimental data to allow for a modelling cycle, in which the modelling is able to capture, compare and contrast experimentally observed dynamics, while the experimental questions and imaging setup are inspired and guided by the model. While building up the close mapping between the experiments and modelling, it became clear that imaging experiments are associated with various artifacts. In the final part of my talk I will describe how potential artifacts could affect the interpretation of data sets, and propose how these errors can be recognised and circumvented, and how to avoid that the data analysis itself leads to biased results.
  • 10:00-11:00

    Enrichment for multivalent TCR complexes as a mechanism for increasing T cell sensitivity

    Hisse van Santen
    CBMSO, CSIC, Madrid, Spain

    The acquired immune system provides its host with ''antigenic memory'' which allows the host to respond faster and stronger to a reencounter with specific pathogens. This is on the one hand caused by an increased precursor frequency of memory T cells and by a more vigorous response of these cells upon activation, as compared to naive T cells. However, memory T cells are also more sensitive to antigen stimulation per se. We previously showed that the TCR on the surface of T cell lines and primary T cells is expressed as a combination of monovalent and multivalent TCR complexes (Schamel et al., 2005, J. Exp. Med. 202: 493). These multivalent TCR complexes are preferentially activated under conditions of weak antigenic stimulation, suggesting an important role in providing T cells with sensitivity. We will present our recent data, showing that previously activated and memory T cells are enriched in multivalent TCR complexes at the cell surface as compared to their na´ve counterparts, and that this increased percentage of multivalent complexes coincides with increased antigen sensitivity. Using a point mutant of the TCR-associated CD3γ chain which impairs multivalent TCR complex formation we have found both in vitro and vivo that such multivalent TCR complexes are directly involved in increasing sensitivity of T cells. Finally, we show evidence that the MHC ligands can form multivalent complexes on professional antigen presenting cells, suggesting the existence of a cooperative binding mechanism of TCR complexes and MHC ligands. Together these data indicate that reorganization of TCR complexes into multivalent structures provides T cells with a mechanism to increase their sensitivity to antigen.
    coffee
  • 11:30-12:30

    Imaging and modelling the development and function of lymphoid tissues

    Mark Coles
    University of York

    Imaging technologies have for the first time allowed us to visualize the 4- Dimensional development and function of lymphoid tissues. In the first part of the talk will focus on the role of stromal cells and vasculature in modulating adaptive immune responses. Utilizing Streptococcus pneumoniae as a prototypic pathogen infection in the lung we have imaged the role of vascular remodelling in HEVs during the infection and determined the cellular and molecular basis for this process. We show that this remodelling process leads to rapid lymph node hypertrophy effectively stimulating the adaptive immune response. We have developed agent based simulation models of the HEV network in lymph nodes during infections to analyse the role of vascular remodelling in hypertrophy and utilised results from the model as the basis for further experimentation. In the second part of the talk will focus on the imaging the development of lymphoid tissues, focusing on the early steps of lymph node and Peyer's patch formation and subsequent organisation. We have utilised these data sets to develop simulation models of Peyer's patch development that have allowed us to test the potential role of geometric constraints on lymphoid tissue development. We will discuss the potential role of these constraints on our understanding of lymphoid tissue formation. By combining modelling with imaging and experimental models has allowed us to develop and test novel hypothesis on lymph node development and function.
    lunch
  • 13:30-14:30

    Imaging Immune Cells in Atherosclerosis and Stroke

    Pasquale Maffia
    University of Glasgow

    T lymphocytes are one of the main cells controlling the immune response and they are present in both atherosclerotic vessels and ischemic brain, but their role in vascular injury and stroke remains to be clarified. In vivo analysis of these lymphocytes in the induction and progression of vascular pathologies is the most instructive way to clarify these processes and will be critical for the development of therapies which might target lymphocytes. We are now focusing to better elucidate multiphoton microscopy potentialities in cardiovascular medicine, combining our experience of tracking lymphocytes in vivo with the use of well established animal models of atherosclerosis and stroke, visualising directly in real time, the cellular interactions underlying development and progression of these pathologies.

List of participants

Kieran Alden University of York
Yang Liu University of York
Oliver Tearne Veterinary Laboratories Agency
Roger Leigh University of York
Pallavi Jain University of Essex
Jessica Borger University of Edinburgh
Louise Hurst Sheffield Hallam University
Ruta Furmonaviciene De Montfort University
Nicola Woodroofe Sheffield Hallam University
Elizabeth Jury University College London
Sayma Rahman Karolinska Institute
Ann Gardinerá University of Aberdeen
Graeme Shaw University of Hull
Colin Gray University of Sheffield
Ramneek Johal University of Nottingham
Lesley Walton Liverpool John Moores University
Natalie Carter UCL
Fabian Flores-Borja UCL
Ed Long UCL
Sarah Haywood-Small University of Sheffield
GDL Last revised:
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