The speed of change: towards a discontinuity theory of immunity?

Nat Rev Immunol. 2013 Oct;13(10):764-9. doi: 10.1038/nri3521. Epub 2013 Sep 2.


Immunology - though deeply experimental in everyday practice - is also a theoretical discipline. Recent advances in the understanding of innate immunity, how it is triggered and how it shares features that have previously been uniquely ascribed to the adaptive immune system, can contribute to the refinement of the theoretical framework of immunology. In particular, natural killer cells and macrophages are activated by transient modifications, but adapt to long-lasting modifications that occur in the surrounding tissue environment. This process facilitates the maintenance of self-tolerance while permitting efficient immune responses. In this Essay we extend this idea to other components of the immune system and we propose some general principles that lay the foundations for a unifying theory of immunity - the discontinuity theory. According to this theoretical framework, effector immune responses (namely, activated responses that lead to the potential elimination of the target antigen) are induced by an antigenic discontinuity; that is, by the sudden modification of molecular motifs with which immune cells interact.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology*
  • Antigens, Viral / genetics
  • Antigens, Viral / immunology*
  • Autoantigens / genetics
  • Autoantigens / immunology*
  • Gene Expression
  • Humans
  • Immunity, Innate*
  • Killer Cells, Natural / cytology
  • Killer Cells, Natural / immunology*
  • Macrophages / cytology
  • Macrophages / immunology*
  • Models, Immunological*
  • Self Tolerance
  • Time Factors


  • Antigens, Bacterial
  • Antigens, Viral
  • Autoantigens