**7. Conclusion**

580 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

Barabas et al., 2009a), and the development of our understanding of autoimmune disease etiology and pathogenesis, in particular the role of non-pathogenic and pathogenic aabs (Figure 1) in both disease development and in its prevention and cure (Barabas et al., 2004b;

The concept of autoimmunity is presently understood as pathogenic immune response

Autoimmune anomalies cannot be specifically prevented or treated by any of the

The concept of autoimmunity, according to our definition, encompasses four possible

The vaccination method we have developed – which is essentially the third vaccination rubric to have arisen, coming as it has after the conventional active and passive immunization techniques – promises to be able to deal with chronic ailments that are presently only treatable with drugs. Called MVT, it is so named because every time a vaccine is produced it must be formulated of components that are tailor-made to induce a specific corrective immune response. In order to achieve specificity – and to avoid collateral damage to normal body constituents – the production of absolutely pure and specific target ags and their abs is required. This can be done by present techniques, and soon more

 For application in an autoimmune disease: ag prepared *ex vivo* that is identical in molecular composition to, and therefore the specific equivalent of, the host's target ag

For application in a chronic infection: ag derived from the causative organism, prepared

 For application in an autoimmune disease: homologous non-pathogenic IgM ab directed against the target ag(s), prepared *ex vivo* by monoclonal ab technology; For application in a chronic infection: homologous pathogenic neutralizing IgG ab

The modified vaccine is composed of an IC mixture made up of the target ag and ab against the target ag in slight ag excess. E.g. in an experimental autoimmune kidney disease (Barabas et al., 2003; Barabas et al., 2004b; Barabas et al., 2006c; Barabas et al., 2006b) it was

 immunization with suitable IC (rat kidney fraction 3 X rat anti-rat kidney fraction 3 IgM ab) at slight ag excess prior and subsequent to disease-inducing inoculation prevented

against target ags on the surface of infectious agents, prepared *ex vivo*.

 The harmful aspects of autoimmunity manifest in autoimmune diseases and cancer. The immune system's natural ability can be utilized to bring about corrective immune responses which can cure/terminate chronic ailments by proper presentation of the target ag. In other words, the ag that causes or contributes to the disease can also terminate it, provided the antigenic information is presented to the cells of the immune system in the

Barabas et al., 2006c; Barabas et al., 2006b) (e.g. in autoimmune disease).

immune responses against self: two beneficial and two harmful ones.

against self, causing autoimmune disease.

presently available vaccination techniques.

sophisticated methodologies will be available.

**6. Components of the modified vaccine and how it works 6.1 Target ag against which the desired ab response is required** 

(native aag) (Kerjaschki, 2000a; Kerjaschki & Farquhar, 1982);

**6.2 Ab against the disease causing/contributing target ag** 

NOTE:

proper format.

*ex vivo*.

observed that:

There are several reasons why up to now chronic disorders have been mainly treated with drugs and not by immune intervention. Perhaps the most important reason was that we were unable to present the offending ag(s) (i.e., the antigenic information) to the cells of the immune system in a suitable form to elicit corrective immune response outcomes. However, we have learned how to prepare and present exogenous ags such as bacterial/viral products to the body in attenuated or inactivated forms – usually in adjuvants – to elicit protective immune responses.

We have developed a new vaccination methodology called MVT that is able to downregulate immunopathological events in an experimental autoimmune kidney disease in animals and is also able to upregulate immune responses against an exogenous ag. This method, which is the third method of vaccination to be developed, has the potential not only to prevent but with equal effectiveness cure certain autoimmune diseases and chronic infections in humans.

Autoimmunity encompasses four possible immunological events against self, two beneficial and two harmful aspects (Figure 2). The two beneficial aspects of autoimmunity function throughout life to preserve the internal integrity of the organism by maintaining tolerance to normal self while preventing corrupted self from taking hold. The maintenance of antigenic homeostasis is the most important function of the autoimmune system.

The autoimmune system achieves its aim on one hand (the first beneficial aspect of autoimmunity) by degrading cellular debris – from cells damaged by various agents (e.g. chemicals, drugs, smoke, toxins, etc.) and from cells which have come to the end of their lifespan – into reusable small MW peptides. The efficient clearance of cellular waste is assisted by non-pathogenic IgM aabs prior to their degradation by phagocytic cells. These specific IgM aabs are the main agents of the maintenance of tolerance to self, and fulfill a

Four Aspects of Autoimmunity and How to Regain Tolerance to Self

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continuous physiological role throughout life. In a physiological sense, we are not *per se* tolerant to normal self components within cells.

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 them from the system.

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 events leading to functional disturbance of the affected cells, tissues and organs.

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, morphological and functional changes.

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 target ag, as was present in the IC (ab information transfer).

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 infections will be prevented and cured as well.
