Information Technology Reference
In-Depth Information
suppress the activation of the other in order to maintain tolerance. It is then possible
to establish several types of effector functions that introduce negative feedback and
stabilize the system in its homeostatic equilibrium (Fig.7). A similar frustrated
dynamics could also take place at sites of inflammation. However in this case the
mechanism should be confined, e.g. to environments where the several T cells are
present in such a way that frustration is sustained. Otherwise disruptive selection
could take place and lead to autoimmune disease. Hence, we propose that the cellular
frustration mechanism could take place first in the thymus (during the selection of the
system) and then in lymph nodes for the activation of T and B lymphocytes.
5 Conclusions
This work presents a conceptually new approach to the problem of modelling cellular
interactions in the adaptive immune system. As in previous models, it assumes that
kinetic proofreading mechanisms take place when a cell scans the ligands on another
cell [11] to build specific ILs. To establish strong discrimination between self and
nonself in our model, we assumed that the cells of the immune system were
frustrated. In this system of frustrated interactions, immune responses can be triggered
because the introduction of pathogenic cells leads to a disruptive cellular selection.
This is achieved with high sensitivity as a result of a generalized kinetic proofreading
mechanism, that is, a kinetic proofreading mechanism that takes place at the level of
cells. In this framework
all
cells are surveilled and susceptible to immune responses.
Consequently, the system is also intrinsically capable of maintaining homeostasis. In
our framework, the self is defined as the set of cells that can keep short lived
intercellular contacts, without ever mounting an immune reaction. In this manner,
discrimination of self and nonself emerges as a property of the whole system.
Acknowledgments.
FVA greatly benefited from discussions with Brigitte Askonas.
FVA also acknowledges encouragement by Douglas Young. FVA thanks FCT for the
grant SFRH/BSAB/531. CRDA thanks FCT for the grant SFRH/BD/10587/2002.
References
1.
Casal, A., Sumen, C., Reddy, T.E., Alber, M.S., Lee P.P.: Agent-based modeling of the
context dependency in T cell recognition. Journal of Theoretical Biology (2005)
236
(4):
376-391
2.
Leon, K., Lage, A., Carneiro, J..: Tolerance and immunity in a mathematical model of T-
cell mediated suppression. Journal of Theoretical Biology (2003)
225
(1): 107-126
3.
Chan, C., Stark, J., George, A.J.T.: The impact of multiple T cell-APC encounters and the
role of anergy. J. Comp. App. Mathematics (2005)
184
(1): 101-120
4.
Leon, K., Perez, R., Lage, A.,
Carneiro, J.: Three-cell interactions in T cell-mediated
suppression? A mathematical analysis of its quantitative implications. Journal of
Immunology (2001)
166
(9): 5356-5365
5.
Leon, K., Perez, R., Lage, A., Carneiro, J.: Modelling T-cell-mediated suppression
dependent on interactions in multicellular conjugates. Journal of Theoretical Biology
(2000)
207
(2): 231-254
