Tolerance and autoimmunity.

@article{Kamradt2001ToleranceAA,
  title={Tolerance and autoimmunity.},
  author={Thomas Kamradt and Neil Mitchison},
  journal={The New England journal of medicine},
  year={2001},
  volume={344 9},
  pages={
          655-64
        }
}
The immunologic specificity of the antigen receptors of T cells and B cells is the result of random shuffling of the many genes that form the DNA code for the antigen-binding site of these receptors.1–3 Theoretically, this process could generate 109 different T-cell receptors, including some that can bind to autoantigens (these cells are often called self-reactive T cells). Tolerance is the process that eliminates or neutralizes such autoreactive cells, and a breakdown in the working of this… 

Figures and Tables from this paper

Cross-reactivity of T lymphocytes in infection and autoimmunity
TLDR
Recent data are reviewed that show a previously unexpected degeneracy of antigen recognition by T cells, suggesting that the idea that cross-reactivity per se would cause autoimmune disease is most likely too simple.
Advances in Immunology
HE immunologic specificity of the antigen receptors of T cells and B cells is the result of random shuffling of the many genes that form the DNA code for the antigen-binding site of these receptors.
Antigen-presenting cells and tolerance induction.
T cell tolerance induction to foreign and self-antigens has occupied research since the beginning of the understanding of the immune system. Much controversy still exists on this question even though
T Lymphocytes and Autoimmunity.
Autoimmunity: A Multi Factor Associated Complex Immune Imbalance
TLDR
Questions remain with respect to the exact nature of the inciting antigen, the regulatory mechanisms that govern the onset and extent of the autoimmune response and the mechanisms by which spontaneous remissions and flare-ups occur.
The continuous discovery of autoantigens in endocrine organ-specific autoimmunity: do they help us to understand pathogenesis?
TLDR
This review focuses on how scientists, over the years, have directed their strategies to investigating the pathogenesis of organ-specific autoimmunity, by searching, for example, for novel autoantigens and/or antigens related to environmental factors, and comment on the relevance of their findings aimed at the gradual acquisition of the disease process.
What is Autoimmunity: Basic Mechanisms and Concepts
TLDR
The development of autoimmune diseases proved that deletion of autoreactive clones was not absolute but that the remaining clones must be silenced or anergized to self-antigens, and that none of these mechanisms is foolproof for all individuals.
Molecular mechanisms of T-cell anergy
  • E. Kuklina
  • Biology, Medicine
    Biochemistry (Moscow)
  • 2013
Anergy is a long-term stable state of T-lymphocyte unresponsiveness to antigenic stimulation associated with the blockade of IL-2 production and proliferation. Anergy is a pathway of peripheral
Tolerogenic dendritic cells.
TLDR
It is suggested that several clinical situations, including autoimmunity and certain infectious diseases, can be influenced by the antigen-specific tolerogenic role of DCs.
Modulation of the dendritic cell-T-cell synapse to promote pathogen immunity and prevent autoimmunity.
TLDR
Recent work relative to the molecular mechanisms controlling DC-T-cell synapse and their implications on immunoregulation to control autoimmunity and potentiate pathogen immunity are discussed.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 157 REFERENCES
T cell-independent rescue of B lymphocytes from peripheral immune tolerance.
TLDR
It is shown that challenge with self-mimicking foreign antigen rescues B cells from peripheral tolerance independent of T cell help, resulting in the accumulation of self-reactive cells in the lymph nodes and secretion of immunoglobulins that bind to a liver-expressed self-antigen.
B cells in autoimmunity.
  • N. Mitchison, L. Wedderburn
  • Medicine, Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 2000
TLDR
Therapy aimed specifically at T cells has proved disappointing, but this disappointment has been made up for by the impressive success of clinical trials in rheumatoid arthritis of inhibitors of tumor necrosis factor.
Regulatory T cells in autoimmmunity*.
  • E. Shevach
  • Biology, Medicine
    Annual review of immunology
  • 2000
Clonal deletion of autoreactive T cells in the thymus is not the sole mechanism for the induction of tolerance to self-antigens since partial depletion of peripheral CD4(+) T cells from neonatal and
Molecular mimicry and autoimmunity.
TLDR
Molecular mimicry is one mechanism by which infectious agents (or other exogenous substances) may trigger an immune response against autoantigens, and a susceptible host acquires an infection with an agent that has antigens that are immunologically similar to the host antIGens but differ sufficiently to induce an immune Response.
Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme.
TLDR
In this study, the target of both the initiating T cells and pathogenic immunoglobulins was identified as glucose-6-phosphate isomerase, a glycolytic enzyme.
Self-reactive B Cells Are Not Eliminated or Inactivated by Autoantigen Expressed on Thyroid Epithelial Cells
TLDR
Transgenic mice were generated selectively expressing membrane-bound hen egg lysozyme on thyroid epithelium, providing evidence that tolerance is not actively acquired to organ-specific antigens in the preimmune B cell repertoire, underscoring the importance of maintaining tolerance to such antigen by other mechanisms.
Cross-reactivity of myelin basic protein-specific T cells with multiple microbial peptides: experimental autoimmune encephalomyelitis induction in TCR transgenic mice.
TLDR
The definition of a supertope by global amino acid substitution can identify multiple microbial mimic peptides that activate an encephalitogenic TCR.
Shaping of the autoreactive T-cell repertoire by a splice variant of self protein expressed in thymic epithelial cells
TLDR
The role of T-cell tolerance to proteolipid protein (PLP) in susceptibility to experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis, is analyzed and lack of tolerance to this epitope offers an explanation for the exquisite susceptibility of SJL/J mice to EAE.
Levels of peripheral T cell tolerance induced by different doses of tolerogen.
TLDR
A liver-specific inducible promoter was used to drive the expression of the major histocompatibility complex antigen Kb in transgenic mice, which induced tolerance by partial down-regulation of the T cell receptor (TCR) on the self-reactive CD8+ cells.
...
1
2
3
4
5
...