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continuous physiological role throughout life. In a physiological sense, we are not *per se*

On the other hand (the second beneficial aspect of autoimmunity) the autoimmune system works to eliminate abnormal cell lines that emerge as a result of external (e.g. drugs, radiation, smoking, etc.) and internal (e.g. genetic) influences. Emerging cancer cells are recognized and eliminated by NK cells. In addition, cancer specific ags can stimulate a pathogenic lytic IgG aab response, particularly when presented to the system with an adjuvant. These aabs may lyse cancer cells in the presence of complement and eliminate

The two harmful aspects of autoimmunity, i.e., autoimmune disease and cancer, will manifest only if external (e.g. carcinogens, chemicals, infectious agents, UV irradiation, drugs, smoking) or internal (e.g. genetic) influences cause changes in the structural makeup of cells or cell products containing native ags. Such changes could result in harmful immune

Taking advantage of recent insight into the workings of the immune system, our MVT has proved itself to be effective in preventing the development of an experimental autoimmune kidney disease, and when the disease was in its progressive phase, in terminating it altogether, by halting immunopathological events that were causing the symptomatic,

The immune system has a natural ability to correct immunological mishaps and restore the body to normalcy, provided the right information is presented to it for processing. The MVT is a way of presenting that information, in the form of specific ICs, and triggering or enhancing the body's own ability to counteract autoimmune disease, cancer, and chronic infection. We have observed that by injecting ICs – made up of a given endogenous or exogenous ag and a specific ab against it at slight ag excess – into experimental animals, the recipient's immune system produced the same ab, with the same specificity against the

We have shown in experimental situations that corrective immune responses can be induced by the application of the MVT. We remain convinced that by the proper application of the MVT in humans, chronic diseases such as cancer, autoimmune disease, and chronic

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**29** 

*Japan* 

Yoshio Osada

**Parasitic Helminths as Potential Therapeutic** 

In developed countries, the prevalence of both allergic disease (asthma) and autoimmune disorders such as Crohn's disease (CD), multiple sclerosis (MS), and type 1 diabetes (T1D) is increasing. This trend seems to be inversely correlated to prominent decreases in infectious diseases such as measles, tuberculosis, and hepatitis A (Bach, 2002). Based on such epidemiological observations, the "hygiene hypothesis", that exposure to infectious agents; i.e. bacteria, viruses, and parasites, especially in childhood, lowers the risk of later onset of immunological disorders, has attracted much attention. According to the hypothesis, a reduced exposure to infectious agents due to improved hygienic conditions in developed countries, urbanized areas, and/or a westernized lifestyle is responsible for the higher incidence of autoimmunity and allergies in modern society. A number of epidemiological and experimental studies have demonstrated the plausibility of this hypothesis. However, there is also considerable evidence that does not support or contradicts the hypothesis. In

Most studies trying to elucidate the mechanisms involved have been conducted using rodent models. In various models of autoimmune or allergic diseases, effects of bacterial, viral or parasitic infections were tested. Consequently, in many cases, preventive or ameliorating effects of infectious agents have been confirmed. In the main part of this chapter, the influence of parasitic helminths on autoimmune disorders will be introduced. Although the mechanisms underlying the amelioration and/or prevention of immunological disorders by infectious agents have been studied extensively, they are not yet fully understood. As both Th1-polarizing (bacteria and viruses) and Th2-polarizing (parasitic helminths) infectious agents have anti-autoimmune/anti-allergic activities (Zaccone & Cooke, 2011), the "Th1/Th2 paradigm" is not enough to explain the mechanisms involved. Additionally, some autoimmune diseases have been shown to be dependent on a pathogenic T helper subset (Th17), and not on the Th1 subset. The suppressive mechanisms of infectious agents have been attributed to various regulatory/suppressive cell populations, such as Treg cells, Breg cells, NKT cells and alternatively activated macrophages (AA MΦs). In addition, the involvement of suppressive cytokines (e.g. IL-4, IL-10 or TGF-β) has been studied and demonstrated. Focusing on helminth infections, the

Some autoimmune diseases are being treated successfully with recently developed biological products (mainly humanized monoclonal antibodies against pro-inflammatory

this chapter, conflicting reports are introduced and discussed.

possible involvement of regulatory cells and cytokines is discussed.

**1. Introduction** 

**Agents Against Autoimmune Disorders** 

*University of Occupational and Environmental Health, Japan* 

