On Sunday I travelled to the Max Planck Institute for the Physics of Complex Systems in Dresden to attend a conference on modelling the immune system. Before coming here I knew almost none of the participants personally although quite a few of them were known to me by name and by their papers. It seems to me that this conference is bringing together a lot of the leading figures in the area of mathematical immunology. I find the atmosphere at the conference very pleasant and friendly. There is a high percentage of the participants who have changed fields.
In what follows I will summarize some of the most interesting things I heard. There is so much information to absorb that many deserving topics will get left out. In his talk Antonio Freitas presented experimental evidence for how the number of B cells in a mouse is controlled by a quorum sensing mechanism. In particular this involved the technique of parabiosis which I mentioned in a previous post. In fact he went further than standard parabiosis and joined three mice together rather than just two. According to the picture he presented the number of B cells is not determined by production rate but by something else, a soluble substance. Through a series of experiments this substance was identified as IgG antibody. More specifically, there is more than one population of B cells present and it is a population of cells secreting IgM which is held in check by the concentration of IgG. The IgG binds to a receptor on the B cells causing a repression. Mice where this mechanism fails suffer from a lupus-like syndrome.
Robin Callard talked about T cell homeostasis. He works at the Institute of Child Health and in his presentation the development of the immune system in children played an important role. With age the thymic production of T cells decreases but the number of T cells remains relatively constant. Due to the volume change of the body it is not the same thing to look at the number of T cells as to look at their density. He mentioned the concept of TRECs (T cell receptor excision circles) which may be used as an indicator that T cells have recently come from the thymus. The origin of these is as follows. During the development of the T cell receptor DNA rearrangement takes place and some pieces of DNA which have been excised survive as closed loops in the cell. Due to other processes going on it is rather hard to interpret the significance of measurements of TRECs for T cell dynamics. Callard and his collaborators have produced a mathematical model in order to provide better insights into this question (J. Immunology, 183, 4329). In the last part of his talk Callard explained some ideas (which he described as speculation) about the dynamics of the long asymptomatic phase in HIV infection. The main idea was that HIV slowly damages the lymph nodes (or other lymphatic tissues). This proposed process is irreversible, which means that interrupting therapy in HIV (for instance in children) could have lasting negative effects.
Andreas Radbruch gave a talk about the ways in which modelling and experiment can be combined to obtain a better understanding of the immune system. He discussed three examples. The cytokine IL2 is responsible for the proliferation of T cells. In situations where certain T cells should not proliferate their growth must be held in check by other factors. The first example in the talk concerned a system responsible for this control which was only recently discovered. Key players are the transcription factor Foxo1 and the microRNA miR-182. The original work is in Nature Immunology 11, 1057. The second example concerned work on the way in which a T cell which has differentiated in the direction of Th1 then becomes committed to that state. The underlying work has already been mentioned in a previous post and since I had already studied this paper in some detail this was rather familiar ground for me. The third example was about memory B cells. There is a class of cells of this type which reside in the bone marrow with each one being attached to its own stromal cell. I did not understand the details of this story and had the impression that it was not so easy to follow for even some of the expert members of the audience.
I have just finished writing about the talks from yesterday and I will stop here for now. I hope to continue with my extracts from the conference in the near future.
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