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A change !! Since Jon Timmis just had a baby, he will not be able to
come. The opening talk will be given by Leandro Nunes de Castro.
Monday 4/9 Morning: Registration and invited speakers
- 8h-9h Registration
- 9h-10h
Leandro Nunes de Castro: "Artificial Immune Systems: The
Past, The Present. And the Future?"
Abstract: The field of artificial immune systems (AIS) emerged in
the early 1990s by extracting simple metaphors from the vertebrate
immune system and theoretical immunology in order to design computational
tools for problem-solving. After a decade of research, the early immune
algorithms have been applied to a wide number and variety of problems
in many different domains. It is felt by most of the AIS community
that the time has come to a change in approach. And a question that
remains to be answered is that of what this new trend should be. This
talk will start by presenting an introduction to the past and present
of the AIS field, and will be concluded by listing some of the possible
avenues that the field may follow in the years to come.
- 10h-10h30 Coffee Break
- 10h30-13h: The "real" immunologists
enter in scene and debate
- 10h30-11h20: Melvin Cohn : "A default Model of the Decision Processes of the Immune
System"
Abstract: A conceptual framework describing the behavior of the 'adaptive'
immune system is an important prerequisite to any analysis leading
to its manipulation. In order to bring to the forefront all competing
positions. I will develop the view that two distinct decision processes
are mandated. Decision 1, the sorting of the repertoire followed by
Decision 2, the regulation of effector class. The default rules for
a Self-Nonself discrimination (Decision 1) and for choice and regulation
of class (Decision 2) will be analyzed. If we can arrive at a coherent
structure, theoretical immunology would have a meaningful impact on
the direction of the field.
- 11h20-11h50: Zvi Grossman: "The immune system: cells
with specialized functions that are subject to general physiological
rules of regulation"
Abstract : The generation of appropriate immune responses and of their
immunological memory is shaped in part by antigen-driven clonal selection
and genetically hard-wired mechanisms that influence the selection
of a response from the available repertoire. But homeostatic regulation
and fine tuning of these responses appear to depend on dynamic interactions,
involving feedback loops, dynamically defined thresholds, ongoing
selection and adaptation processes and real-time “learning from
experience”. Indeed, it is becoming increasingly evident that
the molecular and cellular elements of the immune system are in a
state of a dynamically regulated flux.
The following is a non-exhaustive list of principles of operation
that have been proposed:
1. The immune system and its cellular components explosively respond
to strong perturbations in a threshold-dependent way.
2. The system and individual cells actively adapt in response to recurrent,
sub-threshold perturbations. The thresholds themselves are subject
to adaptation.
3. Self-nonself discrimination can be explained in terms of the above.
4. Pathogen-host co-adaptation is a common strategy that can facilitate
a stable, non-lethal coexistence.
5. Subthreshold interactions among lymphocytes and between lymphocytes
and other cells likely contribute to a broad range of physiological
functions.
6. The capacity of a cell to self-renew and expand depends on its
differentiation state within a hierarchical organization.
7. Effector cells limit their own production both by promoting differentiation
and by inhibiting self-renewal of their precursors.
8. T-cell activation and homeostasis are concomitantly regulated at
large by a) selective, regulated incorporation of recent thymic emigrants
into the naïve T-cell population; b) selective, regulated incorporation
of naïve T-cells into the memory T-cell pool; and c) structured
death and replacement of memory T-cells.
9. Coordinated activity of several lymphocyte and accessory-cell populations
is required for the immune system to properly function and respond.
Prolonged and excessive stimulation may result in “organization
failure”, leading to irreversible loss of the system’s
regenerative capacity and to immune deficiency.
- 11h50-12h20: Antonio
Coutinho : "Purposeless diversity and degeneracy of molecular
“recognition” are the solution to the unknown: each individual
immune system is a fractal of evolution"
Abstract: The adaptive immune system of vertebrates
deals with the general problem of the co-evolution of species with
greatly divergent life cycles, thus displaying enormous differences
in the relative potential for genetic variation. Microorganisms duplicate
in minutes, while vertebrates take months or years, as required by
the developmental time it takes for reaching their typical size and
structural complexity. Faced with the uselessness of keeping in germ-line
complementary molecules with specificity towards the ever-changing
microbial structures, any viable “solution” had to anticipate
the future and “cover” all possibilities, that is, it
had to provide for the “completeness” of immune repertoires
endowed with some degree of “specificity”. Being anticipatory,
immune “specificity” is necessarily based on “degeneracy”
(lack of bi-univocity between ligands and immune molecules) and cooperative
(specificity to a given ligand owes to the common characteristic of
a population of molecules, each of which interacts with a variety
of other ligands). Sheer numbers of potential molecular “shapes”,
however, exclude germ-line solutions, such that the astonishing evolutionary
novelty consisted in transferring “variation and selection”
to the somatic time of every individual. This involved a few convergent
“strategies”: keep in germ-line molecular mechanisms that
“invent” novel DNA sequences of Variable-region molecules
(VRMs), and are essentially irreversible in each cell where they operate;
evolve a “post-mitotic resting state” for the cells expressing
such VRMs, but endow them with further capacity of amplification (dynamics);
impose on such cells (lymphocytes) a program for “cell death
by default” that can only be rescued by the cellular “utilization”
of VRMs; include a developmental program for the continuous production
of new lymphocytes (and VRMs) from uncommitted precursors throughout
life (metadynamics). In summary, these strategies result in unique
possibilities: a life-long source of an open-ended diversity of VRMs
in “potential repertoires”; the selection into the “available
repertoires” of cells with VRMs that “make sense”
in that individual; the selection for amplification in the “actual
repertoires”, of those VRMs that neutralize (are complementary)
to novel molecular shapes appearing in the organism; the continued
“adjustment” of all repertoires to the individual’s
history of molecular contacts (memory). To be effective in antimicrobial
defense, this evolutionarily novel VRM system had to be deployed together
with pre-existing “ridding mechanisms”, simultaneously
creating the problem of “self-nonself discrimination”
and immunity versus tolerance. The respective solution owes to at
least two “strategies”: on the one hand, to the coupling
of lymphocyte activation/amplification to cellular receptors for invariant
microbial products (the “biological correlates” of infection);
on the other hand, to the “positive selection” of self-reactive
lymphocytes endowed with “regulatory” functions and capable
of suppressing anti-self responses. While the evolutionary pressures
tinkering the adaptive immune system may be related to the unique
protection it affords upon secondary contacts with eminently transmissible
microbes, it is clear that an open-ended source of molecular diversity,
if coupled to the extraordinary dynamics of VRM amplification, also
provides a mechanism for general molecular homeostasis. We have designated
this aspect of the adaptive immune system’s operation as “immunosomatics”
and argued that it may well have been where it all started.
- 12h20-12h50: Irun Cohen - "The Immune Homunculus"
Abstract: The immune system is one of the most studied
of biological systems and its component parts and processes are known
in great detail. Strangely, however, professional immunologists still
do not agree in naming the task the system has evolved to perform
or on the strategy that guides immune system behavior. Is the task
of the immune system a) to distinguish between self and not-self;
b) to defend against pathogens; c) to respond to "danger";
or d) to manage the process called inflammation? Is the immune system
a) ignorant of the body, or b) is it obsessed with the body? Is immune
specificity a) clonal (inherent in its antigen receptors), or b) systemic
(antigen receptors are so degenerate that immune specificity must
be generated down-stream of the antigen receptors)? Is the repertoire
fashioned a) exclusively by foreign antigens (clonal selection), or
b) by learning sets of self-antigens (the immunological homunculus)?
Can the immune system be best understood by a) simple logic, or b)
by complex system design? I shall discuss why I favor the latter options
of each of these issues.
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