Programme
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Location
Room A, Wellcome Trust Building
Transport
How to get to Institute of Child Health
Programme
- 10:00-10:45
Hugo van den Berg
Warwick
Dynamic TCR crossreactivity through coreceptor tuning
The functional sensitivity of a T cell to peptide-MHC ligands is a
dynamic quantity which is continually being adjusted by
immunoregulatory mechanisms. This process is vital in the maintenance
of a diverse repertoire, avoidance of autoimmunity, and the ability to
mount an efficacious immune response against a pathogenic
challenge. There are various modulatory mechanisms which, acting in
concert, alter a T cell's activation threshold through costimulation
and its TCR's affinity and triggering threshold through coreceptor
tuning. Various mechanism have been proposed for the effect of the
coreceptor CD8 on TCR sensitivity. We have studied the quantitative
importance of each mechanism, combining experiments and theoretical
analysis. These studies suggest that the TCR repertoire resolves the
paradox of attaining sufficient functional diversity with a
comparatively modest number of clonotypes, whilst avoiding
autoimmunity, by means of a novel mechanism which we call "focussed
specificity". On this theory, each TCR is potentially crossreactive to
many ligands, but will at any one time have a large functional
sensitivity to only a few of them. Dynamic specifity focussing would
constitute the T cell counterpart to affinity maturation in B cell
immunity.
- 11:00-11:45
Graham Anderson
MRC Centre for Immune Regulation, University of Birmingham, B15 2TT
Regulation of T-cell Development In The Thymus
The development of functionally competent antigen-specific T-cells
occurs within the thymus. Blood-borne immature T-cell progenitors are
recruited to the thymus by a chemotactic process, involving CCR7-
CCL21 and CCR9-CCL25 interactions. Development of T-cell progenitors
within the thymus involves a complex series of steps including
proliferation, antigen receptor gene rearrangement, differentiation,
and selection of T-cell receptor specificities to ensure the
production of a self-tolerant T-cell repertoire. It is clear that all
the appropriate queues that drive T-cell development are provided by
stromal cells that make up the thymic microenvironment. These cells
include cortical and medullary epithelial cells, dendritic cells,
macrophages and mesenchymal fibroblasts. To gain a better
understanding of how thymic stromal cells regulate T-cell
development, we have established in vitro techniques based on the
disaggregation and reaggregation of thymic tissue. This allows us to
form three-dimensional thymic structures in vitro from defined
thymocyte and stromal cell subsets, enabling the analysis of specific
developmental events in a synchronous fashion. Data presented will
summarise our use of this system to study the positive and negative
selection of the T-cell repertoire, as well as the processes driving
thymic epithelial cell development.
- 11:45-12:30 discussion
- 12:30-2:00 lunch
- 2:00-2:45
Rachel Norman
Head of the Mathematics and Statistics Group
Department of Computing Science and Mathematics
University of Stirling
Mathematical Models of Disease Systems: an Applied Example and a Theoretical Approach.
The talk will consist of two parts. In the first I will present work
which has been carried out for a number of years on modelling Louping
ill virus. This is a tick borne infection of sheep and grouse which is
of economic importance in the Scottish Highlands. There are a number
of different hosts involved in this system, some which are simply
hosts for the ticks (e.g. deer) and some which are involved in disease
transmission (e.g. mountain hares). In this part of the talk we will
look how we might control the disease by manipulating the host
densities on different estates. In the second part of the talk I will
introduce a new theoretical approach which I have been working on with
colleagues in Computing Science. We have utilised a technique which
allows us to write down rules of individual behaviour and then to
scale up to behaviour at the population level. I will illustrate this
by looking at transmission in a disease system, but this could easily
be applied to a number of different systems, including immunological
ones.
- 3:00-4:30 discussion
(proposals, FP7, web of network, INI programme, etc.)
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