Tolerance, danger, and the extended family

Annu Rev Immunol. 1994:12:991-1045. doi: 10.1146/annurev.iy.12.040194.005015.


For many years immunologists have been well served by the viewpoint that the immune system's primary goal is to discriminate between self and non-self. I believe that it is time to change viewpoints and, in this essay, I discuss the possibility that the immune system does not care about self and non-self, that its primary driving force is the need to detect and protect against danger, and that it does not do the job alone, but receives positive and negative communications from an extended network of other bodily tissues.

Publication types

  • Review

MeSH terms

  • Animals
  • Antigen-Presenting Cells / immunology
  • Antigens / immunology
  • Autoimmunity / immunology
  • Humans
  • Immune Tolerance / physiology*
  • Major Histocompatibility Complex / immunology*
  • Self Tolerance / physiology
  • T-Lymphocyte Subsets / immunology*


  • Antigens