Conference on modelling the immune system in Dresden, part 2

Here I continue with my presentation of themes from the conference. On Tuesday there was a talk by Thomas Höfer. One of the main themes was the stochastic variability of the behaviour of cells. For instance the production of IL-4 by Th2 cells is subject to considerable variation among cells. Modelling was used to try to understand if individual cells change their secretion rates with time. Might they cycle between states of higher and lower production? This appears not to be the case – they probably only change their behaviour once. I had a chance to talk about this subject in some more detail with Michael Flossdorf at the poster session on Monday. Another case is that of the production of interferon \beta by cells infected by a virus. There is a large variability and it seems that this has little to do with the details of the behaviour of the virus. Instead it is intrinsic to the cells producing the interferon.

Rob de Boer talked about experiments to study the dynamics of lymphocyte populations by labelling. In one type of experiments volunteers were given deuterated water for a certain period and during and after that period the amount of deuterium in the DNA of lymphocytes was measured. The only way in deuterium can be built into the cells is by being incorporated into DNA during cell division. Thus it is a signature of division. Interpreting the results required quite a bit of mathematical modelling. A useful comparison is provided by labelling using BrdU (bromodeoxyuridine). Deuterium has the advantage that it is not toxic.

Ramit Mehr talked about natural killer cells. These have been studied a lot less than their relatives, the T and B cells. NK cells cannot specifically recognize antigens like the other cells and so the question immediately arises how they know which cells to kill. An answer to this question which was at first controversial but now seems to be generally accepted is the ‘missing self hypothesis’ of Klas Kärre. The idea is that the MHC type I molecules on the surface of host cells can repress the activity of NK cells. If the MHC molecules are not there, and thus ‘self’ is missing, the NK cell attacks. When a virus affects a cells it may be in its interest to suppress MHCI molecules to avoid attracting the attention of cytotoxic T cells. Then it may just get out of the CD8 frying pan into the NK fire. Not so much is known about where and how NK cells develop. It seems that although NK cells do not undergo selection like T cells they nevertheless need to go through a period of education in order to do their job optimally.

Gregoire Altan-Bonnet discussed the influence of Treg cells on effector T cells. IL-2 stimulates T cells to proliferate. Treg cells can rapidly bind IL-2 and internalize it. Under certain circumstances this can deplete the amount of IL-2 and thus limit the proliferation of effector T cells. A mathematical model of this process has been studied by a group of people including several participants of this conference. (See Busse et. al. PNAS 107, 3058). As explained by Altan-Bonnet, it has been argued due to experiments with cells kept in separate wells that cell contact was necessary for the action of Tregs but this argument is not conclusive. The wells can simply act as a hindrance to diffusion of the IL-2.

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One Response to “Conference on modelling the immune system in Dresden, part 2”

  1. Conference on systems biology of T cells in Baeza « Hydrobates Says:

    [...] on a similar subject by de Boer before at a conference in Dresden and I wrote about it briefly in a previous post. I liked that earlier talk but I liked the talk today much more. This was probably less due to the [...]

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