Theory in Immunology

October 16-19, 1999

ZiF, Bielefeld


Experimentalists made a state of the art picture of the field. Modellers showed and discussed their models. The "meneur de jeu" (a figure akin to playmaker/master of ceremonies/quizmaster) posed questions (What does this model do for immunology? What does it to theory? etc.) to panel 1 (biologists) and panel 2 (physicists). Active panel 1 and 2 were reshuffled each morning. No participant - if asked - could refuse to be a panel member. The meneur de jeu was free to use any means he liked, provided he got the answers.


Friday, 15-Oct-1999

Arrival in Bielefeld


Saturday, 16-Oct-1999

When the Immune System fails, e.g. AIDS
Meneur de jeu: Avrion MITCHISON (London)
09.30 - 10.40 Rodney PHILLIPS (Oxford):
How does the Immune System recognize HIV?
10.40 - 11.00 Discussion
11.00 - 11.30 - Coffee break -
11.30 - 12.00 Avidan NEUMANN (Ramat Gan):
Modelling virus dynamics
12.00 - 12.30 Discussion
12.30 - 14.00 - Lunch -
14.00 - 14.30 Rob de BOER (Utrecht):
Modelling cell dynamics (small variations in multiple parameters account for wide variations in HIV-1 set points)
14.30 - 15.00 Discussion
15.00 - 15.30 - Coffee break -
15.30 - 16.00 Oliver CLAY (Naples):
Virus' eye view of host landscape
16.00 - 16.30 Eva KLEIN (Stockholm):
SH2D1A and SLAM expression in human lymphocytes and derived cell lines
16.30 - 17.00 Discussion
17.00 - 17.30 - Coffee break -
17.30 Discussion


Sunday, 17-Oct-1999

When the Immune System works. The two immune systems.
Meneur de jeu: Rodney PHILLIPS (Oxford)
09.30 - 10.10 Avrion MITCHISON (London):
The Immune System: an extended family
10.10 - 10.40 José BORGHANS (Utrecht):
Interactions between innate and adaptive responses
10.40 - 11.00 Discussion
11.00 - 11.30 - Coffee break -
11.30 - 12.10 Franco CELADA (Genoa and New York):
Cellular-humoral interplay in antivirus response
12.10 - 12.30 Discussion
12.30 - 14.00 - Lunch -
14.00 - 14.30 Stefania BANDINI (Milano):
Hypercellular automata: a shared computational model for widely different applications
14.30 - 15.00 Discussion
15.00 - 15.30 - Coffee break -
15.30 - 16.00 Steven KLEINSTEIN (Princeton):
Cell dynamics of the germinal centre
16.00 - 16.30 Marcelle KAUFMAN (Bruxelles):
The logic of signalling
16.30 - 17.00 Discussion
17.00 - 17.30 - Coffee break -
17.30 - 18.00 Dietrich STAUFFER (Cologne):
Damage spreading simulations for immunological cellular automaton
18.00 Discussion


Monday, 18-Oct-1999

When the Immune System needs help. Vaccines, allergy.
Meneur de jeu: Geoffrey HAUGHTON (Chapel Hill)
09.30 - 10.10 Rino RAPPUOLI (Siena):
Vaccines of the present, vaccines of the future
10.10 - 10.40 Brynja KOHLER (New York):
Vaccine development via IMMSIM
10.40 - 11.00 Discussion
11.00 - 11.30 - Coffee break -
11.30 - 12.00 Derek SMITH (Los Alamos and New York):
Variable efficacy of repeated annual influenza vaccination
12.00 - 12.30 Discussion
12.30 - 14.00 - Lunch -
14.00 - 14.30 Vipin KUMAR (La Jolla):
Receptor vaccination in autoimmune encephalomielytis
14.30 - 15.00 Discussion
15.00 - 15.30 Philip SEIDEN (New York):
Humoral response in an automaton: the isotype switch
15.30 - 16.00 Discussion
16.00 - 16.30 - Coffee break -
16.30 - 17.10 Gerhard METZNER (Leipzig):
Allergy - the disease
17.10 - 17.40 Ulrich BEHN (Leipzig):
A model of desensitization
17.40 - 18.00 Jan RICHTER (Leipzig):
Experimental results
18.00 - 18.30 Discussion
19.00 - Dinner at ZiF -


Tuesday, 19-Oct-1999

Fields for future modelling
Chairman: Rui VILELA MENDES (Lisbon)
09.30 - 10.30 Avrion MITCHISON (London):
Genetics as a probe of mechanism
10.30 - 11.00 Discussion
11.00 - 11.30 - Coffee break -
11.30 - 12.00 John CLARK (St. Louis):
Steps toward a probabilistic theory of neurobiological computation
12.00 - 12.30 Tyll KRÜGER (Berlin):
Self-organized models in biology
12.30 - 13.00 Discussion
13.00 - 14.00 - Lunch -
14.00 - 14.30 Paulo BRANCO (Lisbon):
Technological applications of immunity-based systems: a status report
14.30 - 15.00 Discussion
15.00 - 15.30 - Coffee break -
15.30 General discussion
Insights into the 2000-2001 ZiF Programme
"The Sciences of Complexity: From Mathematics to Technology to a Sustainable World"



The symposium Theory in Immunology has taken place at ZiF, October 16-20, 1999, 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 the representative of approaches to complexity in Biological systems. It is the field where modeling has been most both imaginative and 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 - at any single 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 a future interdisciplinary research. These questions were chosen on the basis of two different pre requisites. First they had to completely reflect the present state of the art from the point of view of the research in immunology. But also 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, the ones used in non linear dynamics and related studies of collective behaviour. A last but not least 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 discussing 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.