The symposium Theory in Immunology has taken place with the co-sponsorship of the Volkswagen Foundation, in the context of a project aiming at an interdisciplinary collaboration of several groups active in the study of complexity in various fields. The collaboration will develop during an entire research year at ZiF, beginning in the fall of the year 2000 (The Sciences of Complexity: From Mathematics to Technology to a Sustainable World).
Immunology has been selected for this symposium as representative of approaches to complexity in biological systems. It is the field where modeling has been most imaginative and most fruitful. In fact, the immune system is as complex as biological systems come, and the high rate of growth of scientific knowledge adds to the complexity, as it provides – each time – more alternatives than certainties. This is a situation where modeling is useful, and perhaps indispensable.
The aim of the meeting was to define a series of concrete questions that deserve future interdisciplinary research. These questions were chosen on the basis of two different pre requisites. First, they had to reflect completely the present state of the art from the point of view of the research in immunology. At the same time, they had to present a sufficient surface of quantitative (and even parametrical) design to be approached by methods that are usually wanting in this field as, for instance, those used in non-linear dynamics and related studies of collective behaviour. A last but not less important prerequisite was that a sufficiently large amount of modeling work has been completed on any selected topic, so as to allow questions on the role of modeling to be leveled both from the point of view of the biologists / immunologists, and of the mathematicians / theorists. The three days of the meeting were organized – in an apparent deviation from the Physiology-Pathology sequence – to present, first, the Immune System in its failure, then, the basic machineries and functions of the immune defences at work, and lastly, the situations where the immune system needs external help in order to perform successfully.
In the first session, Rodney Philips, from Oxford, discussed AIDS from clinical and immunological points of view, while Avidan Neumann (Ramat Gan), Rob De Boer (Utrecht) and Oliver Clay (Naples) illustrated their simulations of the cellular and viral dynamics. Interestingly, the model-born hypothesis that a short interruption of the anti-viral therapy may favour a decisive immune response is being tested clinically by Neumann’s co-workers in Jerusalem and Paris.
The second day displayed for discussion several variants of cellular automata as working models of the immune system. The bench-immunologists were represented by the legendary Avrion Mitchison (London), while Franco Celada (Genoa and New York) presented the IMMSIM model, a “hypercellular automaton” (Bandini) capable of performing both cell-mediated and humoral responses against viruses with different combinations of features. Steven Kleinstein (Princeton) simulated the dynamics of T cells and B cell hypermutation in Germinal centres and Philip Seiden (New York) applied IMMSIM to the still unsolved problem of what determines the isotype switch during the antibody response.
The “Helps” to the immune system discussed during the third day were desensitization in controlling allergy (described by Gerhard Metzner (Leipzig) and modelled by Ulrich Behn (Leipzig)), and vaccination against viruses, which were tackled in quite different ways. Young Brynja Kohler (New York) performed a systematic study in IMMSIM indicating that depending on the characteristics (speed of growth, size of burst, infectivity) of the virus, the vaccine to be successful should sometimes “correct” the balance between humoral and cellular responses. Derek Smith (Santa Fe) showed that in a model of bidimensional antigenic space shape, periodic repetition of anti-influenza vaccination may be detrimental, and began verifying this prediction on WHO bank data, and came out with suggestions about the choice of vaccines for the future.
From the all round discussion of the last day where immunologists and modellists clashed and corroborated each others’ views, the role of models in biological research gained strength, in the opinion of the sixty participants, not only as simulations (imitations) of what happens, but also, and most importantly as generators of hypotheses and stimuli to the imagination.
Giancarlo Andrighetto (Verona), Stefania Bandini (Mailand), Ulrich Behn (Leipzig), Claudia Bergmann (Garching), Michele Bezzi (Triest), Philippe Blanchard (Bielefeld), Rob de Boer (Utrecht), José A. M. Borghans (Utrecht), Markus Brede (Leipzig), Rui P. Ribeiro Ferreira do Carvalho (Lissabon), Filippo Castiglione (Köln), John W. Clark (St. Louis, MO), Oliver K. Clay (Naples), Germinal Cocho (Mexico), Paulo José da Costa Branco (Lissabon), Gianaurelio Cuniberti (Dresden), Joaquim Antonio Fraga Goncalves Dente (Lissabon), Andreas Deutsch (Dresden), José Faro (Salamanca), Mirta B. Gordon (Grenoble), Geoffrey Haughton (Chapel Hill, NC), Ivo Hofacker (Wien), Marcelle Kaufman (Brüssel), Eva Klein (Stockholm), Steven Kleinstein (Princeton, NJ), M Knoflacher (Seibersdorf), Brynja Kohler (New York, NY), Tyll Krüger (Bielefeld), Vipin Kumar (San Diego, CA), Fabio Luciani (Bologna), Rachel Mannion (Dublin), Gerhard Metzner (Leipzig), Avrion Mitchison (London), Avidan U. Neumann (Ramat Gan), Giuseppe Nicosia (Catania), Rodney Phillips (Oxford), Michal Or-Guil (Dresden), Ras P. Pandey (Hattiesburg, MS), Roberto Puzone (Genua), Rino Rappuoli (Siena), Stefan Reimann (St. Augustin), Jan Richter (Leipzig), Stefano Ruffo (Florence), Heather Ruskin (Dublin), Derek Smith (Los Alamos, NM), Raymond Spier (Guildford), Peter F. Stadler (Wien), Dietrich Stauffer (Köln), Ludwig Streit (Bielefeld), Silvana Valensin (Bologna), Luis Vásquez (Madrid), Rui Vilela Mendes (Lisboa)