Autoimmune Disease: Aetiology and Pathogenesis

Abstract

Unfortunate combinations of genetic susceptibility and exogenous factors (microbial, toxic, stress) lead to full‐blown autoimmune disease

Keywords: hashimoto's thyroiditis; type 1 diabetes; rheumatoid arthritis; environmental factors

Figure 1.

The immunopathogenic events that take place during the development of autoimmunity and ultimately lead to autoimmune glandular failure. In a first afferent phase, antigen‐presenting cells (APCs), probably mostly monocyte derived, accumulate in the putative target gland. The APC influx can be induced by aspecific inflammatory stimuli, such as necrosis of target cells by viruses or toxins. Altered metabolism or growth of the target cells may also be an induction factor for APC accumulation (see text). The accumulated APCs take up relevant autoantigens and leave the tissues to travel to the draining lymph nodes. In a second central phase the APCs seek contact with T and B cells in the draining lymph nodes. Apparently, an aberrant immune response results. Instead of reinforcing tolerance, the APCs generate an autoimmune reaction. The figure lists the various abnormalities found in animal models underlying this aberrant regulation of the autoimmune response. In a final afferent phase the generated autoreactive T cells, B cells and antibodies have their effect on the target cells after having gained access to the target gland (see text for various mechanisms). mo, monocyte; en, endothelial cell; Ag (red triangle), autoantigen; Cy, cytokines; E, endocrine cell; Mϕ, macrophage; ADCC, antibody‐dependent cell‐mediated cytotoxicity; P, plasma cell; TH1, T helper cell type 1; TH2, T helper cell type 2; Tr, T regulator cell; B, B cell; Aabs, autoantibodies; AICD, activation‐induced cell death; IFN, interferon; IL, interleukin; +, stimulation, −, suppression:→, traffic.

Figure 2.

Prevalence of thyroperoxidase (TPO) antibody positivity in the normal population according to age and gender. TPO antibodies determined by Lumitest (Henning, Berlin, Germany). Red bars, females; blue bars, males.

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Rosmalen, JGM, Leenen, PJM, and Drexhage, HA(Jan 2003) Autoimmune Disease: Aetiology and Pathogenesis. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0001277]