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have a low avidity for the pathogenic cell before infection, but which has increased
the most after infection. In other words, recognition in this system results from
changes relative to the remaining population of interacting cells and not on the
absolute values of the affinities between ligands and receptors.
Towards modeling the physiological immune system, we next generalized our
approach to include different cell types (or classes), such that ILs are structured
according to (1), with respect to interactions between cells of different cell types. This
means that cells belonging to class A would first have all cells belonging to class B,
then those of class C and at last the remaining cells of their own type, on their IL. The
way cells of a same type are organized in the appropriate region of the IL, can also be
structured, but in the next example they were randomly distributed. This arrangement
of ILs allows defining a new system that still preserves a frustrated dynamics, as
shown in Fig.6, and where it is again possible to detect pathogens as described above.
Long-Lived
Conjugate
Effector Function
T
1
cell activation/
T
1
cell proliferation
APC-T
1
T
2
proliferation/
T
1
cell apoptosis, inhibition or
anergy
T
1
-T
2
T
2
apoptosis, inhibition or
anergy
T
2
-APC
Fig. 7.
The mechanism of recognition in lymph nodes may result from a frustrated dynamics
involving APCs and T cells of at least two types.
(Left)
Given a chance, T
1
cells conjugated to
APCs and detecting a T
2
cell, should promote interactions with T
2
cells and terminate previous
interactions with the APC. A similar analysis would apply to the other possible interactions in
the system.
(Right)
If long-lived interactions emerge, immune reactions take place that allow a
negative feedback loop to stabilize the system. For instance, if a long-lived APC-T
1
cell
conjugate emerges (resulting for example from the presentation of a foreign peptide or from the
uncontrolled proliferation of self cells), then convenient effector function that leads to negative
feedback consists in T
1
cell activation (which will reduce the presentation of this peptide in the
future) or/and T
1
cell proliferation (to increase the attack of pathogens).
Interestingly, as cells belonging to the same type can interact and possibly react
with each other, the system is able to respond to significant changes in the number of
cells in each class. Hence, if one cell type expands considerably relatively to its
numbers in the frustrated dynamical equilibrium , it would be possible to detect and
react against this growth. This is an interesting homeostatic property of the system
useful to fight virus infected cells or tumor growth. Here again we observed that the
long-lived interactions were formed involving cells belonging to the cell type that
grew and those cells for which these cells have bigger avidity (in the example of
Fig.6, long-lived interactions involve cells of type A and B). This happens because
there are cells of type A that became highly ranked in the ILs of some cells of type B,
in comparison to the stable configuration situation.
This example is the simplest that could describe interactions between T cells and
APCs in lymphoid organs. It can describe a scenario where one T cell type could
