Immunologic Research

, Volume 60, Issue 2–3, pp 208–218 | Cite as

The virus-induced HSPs regulate the apoptosis of operatus APCs that result in autoimmunity, not in homeostasis

FRONTIERS IN AUTOIMMUNITY
First Online:

Abstract

The viruses stand salient as environmental factors that trigger autoimmunity. The virus realizes its effects through induction of heat-shock proteins (HSPs) as well as by the viral IE-axis-mediated conversion of organ epithelial cells into virgin de novo professional antigen-presenting cells (APCs). The HSP is the accomplished operator in homeostasis by the logic of it being the regulator of apoptosis. By virtue of its regulation of apoptosis, the HSP is also involved in autoimmunity: (1) adornment of viral IE-axis-generated virgin de novo professional APCs with HSP-induced co-stimulatory molecules which transform these otherwise epithelial cells to competent antigen presenters, the operatus APCs, liable to apoptosis that becomes the initiator of organ damages; (2) molecular mimicry mechanism: epitopes on the HSP may be mistaken for viral peptides and be presented by operatus APCs to autoreactive TCRs resulting in the apoptosis of the operatus APCs; (3) regulation of MHC class II DR-mediated apoptosis of operatus APCS which can result in organ-specific autoimmune syndromes. We should remember, however, that Nature’s intended purpose for apoptosis of the professional APCs is benevolence: as a principal regulator of immune homeostasis. But the apoptosis of our postulated operatus APCs can result in autoimmunity. The transformation of virgin de novo professional APCs to operatus APCs mirrors the maturation of DCs through their acquisition of HSP-induced costimulatory molecules. What happens to mature DCs as antigen presenters that end in homeostasis is replicated by what happens to operatus APCs that ends instead in autoimmunity.

Keywords

Viruses Heat-shock proteins (HSPs) Apoptosis Autoimmune diseases (ADs) Immediate early proteins (IE) Antigen-presenting cells (APCs) 
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Notes

Acknowledgments

This investigation was supported by grants from the NSW Health Department. The authors would like to thank Professor Schlink for providing the facilities for the investigation. Dr Temajo is particularly grateful to his wife Julianne Temajo for her enlightening suggestions in their learned and civilized discourse.

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© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Institute of Endocrinology and DiabetesThe Children’s Hospital at WestmeadSydneyAustralia
  2. 2.TurnerAustralia
  3. 3.WestmeadAustralia

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