The Danger Model: A Renewed Sense of Self

  title={The Danger Model: A Renewed Sense of Self},
  author={Polly Matzinger},
  pages={301 - 305}
For over 50 years immunologists have based their thoughts, experiments, and clinical treatments on the idea that the immune system functions by making a distinction between self and nonself. Although this paradigm has often served us well, years of detailed examination have revealed a number of inherent problems. This Viewpoint outlines a model of immunity based on the idea that the immune system is more concerned with entities that do damage than with those that are foreign. 

The danger theory: 20 years later

The danger theory vis-à-vis recent experimental data on innate immunity, transplantation, cancers and tolerance to foreign entities, and try to elucidate more clearly whether danger is well defined.

The Natural Autoimmunity : Self-Recognition , Self-Interaction , and Self-Maintenance

Within the last 20-30 years, the field of clinical immunology has been subject to some paradoxes that contradict the positions adopted by most physicians. The puzzle of natural autoimmunity is an

Immune Balance: The Development of the Idea and Its Applications

Advances in mucosal immunology confirm that instead of distinguishing between self and foreign the immune system reacts to microbial, chemical and self-induced alterations to produce responses that counterbalance effects of these changes.

The danger model in deciphering autoimmunity.

Adapting the paradigm of Matzinger-the 'danger model', a case can be made for a perspective that appreciates the fundamental role of the tissues in controlling immune response, favouring a shift of focus in studies on the initiation of autoimmunity.

The Immune Self , the Sign , and the Testes

The immune self is one of the main organizing concepts in immunology. However, it is not quite clear what the immune self is and heated debates are taken place among immunologists concerning the

The danger model: questioning an unconvincing theory

Direct and indirect evidence is reviewed that contradict the widely accepted danger theory, and it is suggested that it may be false.

[On the way to understand the mechanism of immune tolerance].

The problems of "immunological self" and "non-self", the importance of the roles of AIRE gene products, as well as the role of dendritic cells and regulatory T-cells (T-reg cells) in immune tolerance and autoimmunity are discussed.

The danger model: questioning an unconvincing theory

Direct and indirect evidence is reviewed that contradict the widely accepted danger theory, and it is suggested that it may be false.

Autoimmunity under the umbrella of “Danger Model”: new insights into tolerance, rejection and autoimmune therapeutics -

The importance and relevance of Matzinger’s danger model in understanding, investigating and designing new therapies for autoimmune disorders is highlighted.



Essay 1: The Danger Model in Its Historical Context

The Danger model suggests that an evolutionarily useful immune system should concentrate on those things that are dangerous, rather than on those that are simply foreign.

Decoding the Patterns of Self and Nonself by the Innate Immune System

The innate immune system evolved several strategies of self/nonself discrimination that are based on the recognition of molecular patterns demarcating infectious nonself, as well as normal and

A new analysis of allogeneic interactions.

A model of cell interaction is produced which will account for reactivity is much higher between different strains within a species than between species, in spite of the much greater antigenic disparity in the second case, and a very high proportion of cells may respond to allogeneic stimuli.

The evolution and genetics of innate immunity

Studies in fruitflies and in mammals reveal that the defensive strategies of invertebrates and vertebrates are highly conserved at the molecular level, which raises the exciting prospects of an increased understanding of innate immunity.

‘Actively Acquired Tolerance’ of Foreign Cells

The experiments to be described in this article provide a solution—at present only a ‘laboratory’ solution—of the problem of how to make tissue homografts immunologically acceptable to hosts which

Toll-like receptors in the induction of the innate immune response

A group of proteins that comprise the Toll or Toll-like family of receptors perform this role in vertebrate and invertebrate organisms and it is therefore not surprising that studies of the mechanism by which they act has revealed new and important insights into host defence.

A Theory of Self-Nonself Discrimination

The foregoing requirements provide an explanation for self-nonself discrimination, which involves a specific deletion in the activity of both the humoral- and the carrier-antigen-sensitive cells.

T cell mediated neuroprotection is a physiological response to central nervous system insults

It appears that trauma, at least in the central nervous system, evokes a stress signal that activates a T cell dependent response directed against self antigens, and that this response is physiological in nature, beneficial in intent, and amenable to boosting by active or passive immunization.