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Innate and adaptive immunity: specificities and signaling hierarchies revisited

  • An Erratum to this article was published on 01 February 2005


The conventional classification of known immune responses by specificity may need re-evaluation. The immune system can be classified into two subsystems: the innate and adaptive immune systems. In general, innate immunity is considered a nonspecific response, whereas the adaptive immune system is thought of as being very specific. In addition, the antigen receptors of the adaptive immune response are commonly viewed as 'master sensors' whose engagement dictates lymphocyte function. Here we propose that these ideas do not genuinely reflect the organization of immune responses and that they bias our view of immunity as well as our teaching of immunology. Indeed, the level of specificity and mode of signaling integration used by the main cellular participants in the adaptive and innate immune systems are more similar than previously appreciated.

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We thank S. Ugolini and J. Ewbank for review of the manuscript and C. Beziers-Lafosse for graphic art. Supported by the European Union (ALLOSTEM, E.V.; MUGEN and EPI-PEP-VAC, B.M.), Ligue Nationale contre le Cancer (Equipe labellisée La Ligue, E.V.), Association pour la Recherche contre le Cancer (B.M.), Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique and Ministère de l'Enseignement Supérieur et de la Recherche.

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Figure 1: Strategies of immune recognition.
Figure 2: Degeneracy of the TCR antigen-binding site.
Figure 3: Is a 'two-signal' model of T cell activation still tenable? Signals emanating from the TCR (or the BCR) and the optional signals originating from a vast array of cell surface context detectors converge on intracytoplasmic coincident detectors.
Figure 4: Cross-talk between ITAM- and TLR-dependent pathways.