@ARTICLE{two-zone-journal,
   AUTHOR       = {E.D. Sontag},
   JOURNAL      = {Cell Systems},
   TITLE        = {A dynamical model of immune responses to antigen 
      presentation predicts different regions of tumor or pathogen 
      elimination},
   YEAR         = {2017},
   OPTMONTH     = {},
   OPTNOTE      = {},
   OPTNUMBER    = {},
   PAGES        = {231-241},
   VOLUME       = {4},
   KEYWORDS     = {scale invariance, fold change detection, T cells, 
      incoherent feedforward loops, immunology, cancer, 
      internal model principle},
   PDF          = {../../FTPDIR/sontag_cell_systems2017_dynamical_model_immune.pdf},
   ABSTRACT     = {Since the early 1990s, many authors have independently 
      suggested that self/nonself recognition by the immune system might be 
      modulated by the rates of change of antigen challenges. This paper 
      introduces an extremely simple and purely conceptual mathematical 
      model that allows dynamic discrimination of immune challenges. The 
      main component of the model is a motif which is ubiquitous in systems 
      biology, the incoherent feedforward loop, which endows the system 
      with the capability to estimate exponential growth exponents, a 
      prediction which is consistent with experimental work showing that 
      exponentially increasing antigen stimulation is a determinant of 
      immune reactivity. Combined with a bistable system and a simple 
      feedback repression mechanism, an interesting phenomenon emerges as a 
      tumor growth rate increases: elimination, tolerance (tumor growth), 
      again elimination, and finally a second zone of tolerance (tumor 
      escape). This prediction from our model is analogous to the 
      ``two-zone tumor tolerance'' phenomenon experimentally validated 
      since the mid 1970s. Moreover, we provide a plausible biological 
      instantiation of our circuit using combinations of regulatory and 
      effector T cells. }
}

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