The virus-induced HSPs regulate the apoptosis of operatus APCs that result in autoimmunity, not in homeostasis.
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.
Institute of Endocrinology and Diabetes, The Children's Hospital at Westmead, Sydney, NSW, Australia, temajo@grapevine.net.au.
Norbert O
NO
Temajo
Neville
N
Howard
D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism*; D017209:Apoptosis / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology; D015551:Autoimmunity; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D014777:Virus Diseases / Q000150:complications / Q000276:immunology; D014780:Viruses / Q000276:immunology*
D006360:Heat-Shock Proteins