[c]
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 naïve 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 Gardiner | 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 |
|
