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Publications about 'T cells'
Articles in journal or book chapters
  1. E.D. Sontag. A dynamical model of immune responses to antigen presentation predicts different regions of tumor or pathogen elimination. Cell Systems, 4:231-241, 2017. [PDF] Keyword(s): scale invariance, fold change detection, T cells, incoherent feedforward loops, immunology, cancer.
    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.


Conference articles
  1. E.D. Sontag. Some remarks on immune control of infections and tumors. In Proc. IEEE Conf. Decision and Control, Dec. 2016, pages 2476-2480, 2016. Keyword(s): scale invariance, fold change detection, T cells, incoherent feedforward loops, immunology, cancer.


Internal reports
  1. E.D. Sontag. A remark on incoherent feedforward circuits as change detectors and feedback controllers. Technical report, arXiv:1602.00162, 2016. [PDF] Keyword(s): scale invariance, fold change detection, T cells, incoherent feedforward loops, immunology.
    Abstract:
    This note analyzes incoherent feedforward loops in signal processing and control. It studies the response properties of IFFL's to exponentially growing inputs, both for a standard version of the IFFL and for a variation in which the output variable has a positive self-feedback term. It also considers a negative feedback configuration, using such a device as a controller. It uncovers a somewhat surprising phenomenon in which stabilization is only possible in disconnected regions of parameter space, as the controlled system's growth rate is varied.


  2. E.D. Sontag. Two-zone tumor tolerance can arise from a simple immunological feedforward motif that estimates tumor growth rates. Technical report, bioRxiv https://doi.org/10.1101/095455, 2016. [PDF] Keyword(s): scale invariance, fold change detection, T cells, incoherent feedforward loops, immunology, cancer.
    Abstract:
    Preprint version of "A dynamical model of immune responses to antigen presentation predicts different regions of tumor or pathogen elimination", to appear in Cell Systems 2017. However, the journal version does not include Section 9 on degradation-based IFFL's from this preprint.


  3. E.D. Sontag. Incoherent feedforward motifs as immune change detectors. Technical report, bioRxiv http://dx.doi.org/10.1101/035600, December 2015. [PDF] Keyword(s): scale invariance, fcd, fold change detection, T cells, incoherent feedforward loops, immunology.
    Abstract:
    We speculate that incoherent feedforward loops may be phenomenologically involved in self/nonself discrimination in immune-infection and immune-tumor interactions, acting as "change detectors". In turn, this may result in logarithmic sensing (Weber phenomenon) and even scale invariance (fold-change detection).



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Last modified: Thu Nov 23 10:40:57 2017
Author: sontag.


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