BBSRC MATSYB network  I2M: Immunology, Imaging and Modelling

British Society for Immunology, Mathematical modelling affinity group

Experimental and theoretical immunology in the real world

University of Leeds, 10 Jan 2011

Registration: free for BSI members, 10 pounds for others.
To register, please email i2m



  • 9:30-10:15
    Mats Kvarnström (Fraunhofer-Chalmers, Sweden)

    Quantitative image analysis in microscopy

    The amount of recorded data from modern microscopes is huge and seemingly constantly increasing. Furthermore, questions raised in biology are getting more complex from bulk behavior of cells at a specific time instant to single cell behavior and sometimes even interaction between cells over time as the surrounding environment changes. Due to the shear amount and complexity of data, quantitative and automated methods are needed in order to carry out a thorough analysis and to be able to draw viable conclusions from data.
    In this talk I will present image analysis methods and algorithms for recognition and tracking and subsequent extraction of data in time-lapse light and fluorescence microscopy Examples will mainly be drawn from yeast cell and hepatocyte bile canaliculi analysis but most methods are generic in that the general methodology applies to a variety of applications.
  • 10:15-11:00
    José Faro (University of Vigo, Spain)

    How many selecting ligands are involved in thymocyte selection?

    The TCR repertoire of a normal animal is shaped in the thymus by ligand-specific positive- and negative-selection events. These processes are believed to be determined at the single-cell level primarily by the affinity of the TCR-ligand interactions. The relationships among all the variables involved are still unknown due to the complexity of the interactions and the lack of quantitative analysis of those parameters. We have developed a quantitative model of thymic selection that provides estimates of the fractions of positively and negatively selected thymocytes in the cortex and in the medulla, as well as upper-bound ranges for the number of selecting ligands required for the generation of a normal diverse TCR repertoire.
  • 11:00-11:30 coffee
  • 11:30-12:15
    Mark Arnold (Veterinary Laboratories Agency)

    Modelling the spread of H1N1 through the pig industry in Great Britain

    The 2009 H1N1 swine influenza pandemic raised serious concerns about the potential for pig-human transmission of the virus. While several swine influenza viruses had become endemic in Great Britain (GB), the potential for transmission of the pandemic 2009 H1N1 strain was very uncertain and thus the potential for transmission from pigs to agricultural workers was unknown. The objectives of this study were to (i) explore the potential for transmission of 2009 pandemic H1N1 swine influenza between pig holdings in GB and thus determine the likelihood that this new strain of swine influenza would become endemic in the GB pig population and (ii) provide estimates of the likely prevalence of H1N1 swine influenza infected pig holdings over time, for input into a human risk assessment. While the routes of transmission of swine influenza between pig holdings was uncertain, it was expected that the movement of infected pigs was the most likely route. Therefore a network model of the pig industry was built, where the nodes of the network were pig holdings and the links between holdings represented the movements of infected pigs. Data on actual pig movements between 2002-2006 were obtained from official movement records, used in the network model, which replayed the movements of pigs between pig holdings from a random initial seed. This was coupled with a simple model of within-holding transmission dynamics, to simulate the within-holding prevalence. In addition to looking at the likely holding-level prevalence, the model was also used to explore the potential impact of vaccination on the propagation of H1N1 through the pig industry.
  • 12:15-13:30 lunch
  • 13:30-14:15
    Charlotte Cook (Veterinary Laboratories Agency)

    Modelling the breeding for genetic resistance to scrapie in the Cypriot goat population

    Scrapie is a member of the family of transmissible spongiform encephalopathy prion diseases that also include BSE in cattle and vCJD in humans. Although no direct link to human vCJD has been proven there remains concern that the disease may have impacts on human health, particularly in goats. Due to this potential risk, disease eradication measures are taken in scrapie-infected flocks of sheep and goats. These actions involve the removal of animals that are susceptible to the disease and encouraging breeding with animals that are genetically resistant to clinical scrapie infection. Cyprus is currently experiencing a large outbreak of scrapie in the sheep and goat population. Whilst the genetics of resistance to scrapie in sheep are well characterised and have been used as a disease management tool for a number of years, the resistant genotypes within goats have only recently been identified proposed. As part of the actions for scrapie eradication and limitation in Cyprus, a breeding for resistance program has been proposed. The aims of this project were to simulate different breeding strategies and the impact of them on the long-term goal of a wholly scrapie resistant goat population. Data on the existing goat population structure was produced from a government genetic resistance sampling programme. Currently of the 300,000 animals 100,000 have been testing for genetic resistance to scrapie. A simulation model was built in R using Mendelian inheritance patterns for resistance markers and artificial breeding practices (AI). The model was used to investigate the effects of difference selection techniques for breeding programs and selective removal. The impact of different techniques is measured through the proportion of scrapie resistance and susceptible animals in the population, whilst maintaining desirable qualities such a goat breed and age structure.
  • 14:15-15:00
    Alan Bennet (Adaptimmune, Oxford)

    High affinity TCRs for T cell Adoptive Therapy of HIV and Cancer

    Therapeutic cancer vaccination often produces good T cell responses but this response generally fails to produce even a modest clinical benefit. Adoptive T cell therapy where cancer-specific T cell receptors (TCRs) are transfected into the patient's killer and helper T cells shows great promise. Unfortunately, most cancer-specific T cells have a relatively low avidity for target antigen and their ''wildtype'' TCRs are poorly-suited for cancer therapy. At Adaptimmune and our sister company Immunocore we have successfully used semi-randomly mutated TCR bacteriophage libraries to isolate TCRs with greatly-enhanced antigen binding properties. I will describe how mutant TCR bacteriophage libraries are generated and how affinity-enhanced TCRs are identified by molecular evolution. The TCR molecule is a heterodimer of two chains and high affinity mutants are found in three main areas in each chain. These mutants can be combined to make ultra-high affinity TCRs for antibody-like cancer cell targeting (Immunocore) or can be partially back-mutated to produce more physiological affinity-enhanced TCRs suitable for T cell adoptive therapy. The anti- cancer cell activity of TCR-transfected T cell lines and the relationships of target recognition and antigen specificities to TCR affinity and antigen binding half-lives will be presented and discussed.
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