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Immunological Tolerance. Part I of a Report of a Workshop on Foundational Concepts of Immune Regulation
Author(s) -
Anderson C. C.,
Bretscher P.,
Corthay A.,
Dembic Z.,
Havele C.,
Nagy Z. A.,
Øynebråten I.
Publication year - 2017
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12500
Subject(s) - context (archaeology) , immune system , immunology , antigen , cognitive science , neuroscience , biology , epistemology , microbiology and biotechnology , psychology , philosophy , paleontology
This report, the first of two, arose from a one‐week workshop directed at discussing concepts of immune regulation, and focuses on immunological tolerance. We first outline the major ideas we thought sufficiently plausible to provide a context for discussing more controversial issues around tolerance. We then report on our discussion of different experiments that appear paradoxical in terms of the different, contemporary models of CD 4 T cell inactivation/activation, and how such observations might be resolved in terms of insights provided by these contemporary models. These discussions bear on the plausibility of the Pathogen‐Associated Molecular Pattern ( PAMP ), Danger and Two Step, Two Signal Models for the activation of naïve CD 4 T cells. Some of the observations considered appear paradoxical in terms of the PAMP and Danger Models, but not with the Two Step, Two Signal Model. For example, genetically immunodeficient mice have been given foreign, sterile ectopic grafts, and the immune system allowed to develop once these grafts were well‐healed in, and so in the absence of PAMP s or danger. The grafts were rejected, unexpected on the PAMP or Danger Models. We also discussed considerations and observations bearing on the widely held idea that antigen must crosslink the membrane Ig receptors of a B cell to initiate the generation of signal 1, or the alternative possibility that monovalent binding by antigen can do so. We favored the latter possibility, and discussed a particular model, “the Elbow Model,” for how this might be achieved.