Tolerance, danger, and the extended family.

@article{Matzinger1994ToleranceDA,
  title={Tolerance, danger, and the extended family.},
  author={Polly Matzinger},
  journal={Annual review of immunology},
  year={1994},
  volume={12},
  pages={
          991-1045
        }
}
  • P. Matzinger
  • Published 1994
  • Psychology
  • Annual review of immunology
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… 
View on PubMed
cs.unm.edu
4,846 Citations
Highly Influential Citations
136
Background Citations
1,770
Methods Citations
73
Results Citations
51

4,846 Citations

Citation Type

Citation Type

The Four Ds of the Danger Model: Distress, Damage, Destruction, and Death
For three quarters of a century, immunologists have based their theories and experiments on the fundamental belief that the primary function of the immune system is to discriminate between self and…
An Innate Sense of Danger
  • P. Matzinger
  • Biology
    Annals of the New York Academy of Sciences
  • 2002
TLDR
The danger model is based on the idea that the driving force for the immune system is the need to recognize danger and, under this model, antigen-presenting cells are activated by alarm signals from stressed or damaged tissues.
Immune system protects integrity of tissues.
There is only one immune system! The view from immunopathology.
TLDR
In every response, whether positive or negative, the factors mobilized and the balance between protection and damage depend upon the quality, quantity, location, and timing of immunogen presentation, as well as upon properties of the host.
Immune Balance: The Development of the Idea and Its Applications
  • B. Swiatczak
  • Psychology
    Journal of the history of biology
  • 2014
TLDR
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.
Discrimination and dialogue in the immune system.
  • I. Cohen
  • Biology
    Seminars in immunology
  • 2000
This paper presents reasons for concluding that the immune system maintains the individual body throughout the vicissitudes of life without the need to make an absolute distinction between self and…
The Influences of Immune Cells on the Success of Pregnancy
TLDR
It is widely held that the immune system evolved for maintaining the health of an individual and many of the ideas associated with self/nonself discrimination have been defined by organ and bone marrow transplantation.
The danger theory: 20 years later
TLDR
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.
Reconceiving autoimmunity: An overview.
  • A. Tauber
  • Biology
    Journal of theoretical biology
  • 2015
Autoimmunity as a special case of immunity: removing threats from within.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 139 REFERENCES
A Theoretical Framework for Self-tolerance and its Relevance to Therapy of Autoimmune Disease
Is immunological tolerance (non-responsiveness) a consequence of interleukin 2 deficit during the recognition of antigen?
Peripheral Tolerance in Transgenic Mice: Tolerance to Class II MHC and non‐MHC Transgene Antigens
Itnmunological toleratice to self is one of the central issues in the study of the immune system, for it is important to understand how a system devised for aggression against foreign antigens can…
Self Tolerance in the B‐Cell Repertoire
TLDR
There are a number of arguments which speak against a callow explanation for B-ce!I tolerance, but at least two situations can be envisaged where a pathogenic autoantibody response could occur as a result of the association of B- cell epitopes with foreign T-cell epitopes.
A walk round the edges of self tolerance.
TLDR
The immunologists of my generation were brought up on Sir Macfarlane Burnet's clonal selection theory, and believed that all that matters in the immune system is the sum of the decisions taken by individual lymphocytes, where engagement of its receptor by antigen suffices to drive a lymphocyte to respond.
The mechanism of immunological paralysis.
Immunological Self‐Tolerance: An Analysis Employing Cytokines or Cytokine Receptors Encoded by Transgenes or a Recombinant Vaccinia Virus
The immune system is an endeavor aimed at the identification and neutralization of foreign, potentially noxious agents within the organisms. By inference, this system must have elaborated strategies…
A Theory of Self-Nonself Discrimination
TLDR
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.
Specialization, tolerance, memory, competition, latency, and strife among T cells.
TLDR
This survey offers an interpretation of regulatory T-cell function in terms of epitope linkage and the need to free B cells of responsibility for self-tolerance, as would be expected for the efficient working of the immune system.
A new analysis of allogeneic interactions.
TLDR
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.
...
1
2
3
4
5
...