免疫化学と免疫病理学

Autoimmune Diseases of the Innate and Adaptive Immune System including Atopic Dermatitis, Psoriasis, Chronic Arthritis, Lyme Disease, and Alzheimers Disease

Abstract

Herbert B Allen, Christine M Shaver, Chloe A Etzler and Suresh G Joshi

In atopic dermatitis, we have recently shown the innate immune system is activated by biofilm-forming staphylococci that occlude sweat ducts. Toll-like receptor 2 (TLR 2) is activated and moves from its epidermal control location in the basal zone to the proximal stratum corneum (surrounding the occluded duct). There it likely initiates the MyD88 and the PAR 2 pathways in an effort to inactivate the staphylococci; these efforts are fruitless because of the biofilms and lead to the prime pathological finding of spongiosis and to the prime symptom of pruritus which leads to the disease. If the pruritus is intense enough to cause excoriations severe enough to disrupt the epidermis, the involvement of the dermis likely causes the activation of the adaptive immune system leading to the documented appearance of IL 31, another even more potent pruritogen.
We have also shown that the innate system is involved in psoriasis, again with TLR 2. This time it was present in the dilated upper dermal capillaries; TLR 2 has been shown to lead to TNFa, IL 12/23, and IL 17 which have all been shown to be involved in the production of psoriatic lesions. In this instance, the streptococcus is most likely the organism involved; it is not recoverable because it internalizes or makes biofilms, so TLR 2 instead of combating the bacterium attacks host cells. Anti-streptococcal IgG is markedly elevated in plaque psoriasis in one half the patients; it is of interest to postulate these patients were those who would develop the systemic findings of arthritis, uveitis, and the metabolic syndrome which develop in 40% of patients.
In chronic arthritis, Lyme disease, and Alzheimer’s disease where the disease has been shown to be caused by Borrelia and dental spirochetes, TLR 2 is activated because of the presence of the microbes and their biofilms and leads to the chronic course noted in osteoarthritis, Lyme neuroborreliosis and Alzheimer’s disease. When the adaptive immune system is involved, as in rheumatoid arthritis and after a stroke, it is curious that the disease occurs more rapidly and is much more destructive.