Silica and the immune system.

This article collects the evidence that shows that the biological reactions to Silica are due to the stimulation of the Immune System. Both Innate and Adaptive Immunity are involved. The following sets of events take place sequentially: (1) Silica is recognized as a PAMP (pathogen-associated molecular pattern) by the Receptors of Innate Immunity; (2) This causes the stimulation first and then the death of the key cells of Innate Immunity (the macrophages); (3) While stimulated, macrophages produce cytokines (IL-1 and TNF) that stimulate fibroblasts; (4) The same and possibly other cytokines produced by silica- activated macrophages induce the maturation of dendritic cells, which are the connecting elements between the Innate and the Adaptive (lymphoid) Immune Systems; (5) It follows a polyclonal activation of the Adaptive Immunity; (6) The end result is the formation of fibro-hyaline tissue.

Interaction of baboon anti-alpha-galactosyl antibody with pig tissues.

As barriers to xenotransplantation are surmounted, such as suppression of hyperacute rejection allowing improved graft survival, it becomes important to define longer-term host-xenograft interactions. To this end we have prepared in baboons high titer anti-alpha-Galactosyl (alphaGal) and anti-porcine aortic endothelial cell antibodies, similar to human natural xenoantibodies and reactive with epitopes of thyroglobulin, laminin, and heparan sulfate proteoglycans. When injected into pigs with a protocol similar to that used in the rat to show the nephritogenic potential of heterologous anti-laminin and anti-heparan sulfate proteoglycan antibodies, baboon immunoglobulins bound first to renal vascular endothelium, and later to interstitial cells, especially fibroblasts and macrophages, and to antigens in basement membranes and extracellular matrix, where they colocalized with laminin- and heparan sulfate proteoglycan-antibodies, and with bound Griffonia simplicifolia B4.

Alpha-galactosyl antibody redistributes alpha-galactosyl at the surface of pig blood and endothelial cells.

The interaction of antibodies with cell surface antigens may induce redistribution of immune complexes, followed by antigen depletion, with increased resistance to injurious effect of antibody and complement (antigenic modulation). Human natural antibodies to Gal alpha 1,3Gal beta 1,4GlcNAc-R (alpha Gal) epitopes expressed at the surface of pig cells are a major obstacle to xenotransplantation. Recent studies have shown that these antibodies do not modulate alpha Gal, but the morphological consequences of the antigen-antibody interaction are unknown.

Staphylococcal enterotoxin B-induced T-cell anergy is mediated by regulatory T cells.

Naive T cells mount a vigorous proliferative response to superantigen (SAg) stimulation in vivo. The proliferative response is followed by a partial deletion of responder T cells. Part of the deletion process has recently been attributed to the action of regulatory cytotoxic T cells that recognize major histocompatibility complex (MHC) class I-associated antigen receptor determinants on the target cell surface.