title: Tolerance, loss of tolerance and regaining tolerance to self by immune-mediated events.
abstract: Autoimmunity has both beneficial and harmful aspects. Beneficial aspects include: (1) removal of released intracytoplasmic antigens (ags) (cells at the end of their life span or damaged by outside agents) by specific nonpathogenic IgM autoantibodies and mononuclear cells and (2) recognition and elimination of cancerous cells. In contrast, harmful aspects include: (1) mounting a pathogenic autoimmune response against a tissue-derived ag, a 'modified self,' resulting in autoimmune disease and (2) inability to recognize and eliminate a cancerous clone. The immune system continuously faces internal and external influences; however, even when it is compromised or overwhelmed, it will still endeavor to regain and maintain tolerance to self. To promote this, we developed a 'modified vaccination technique' (MVT) (described as the third vaccination method after active and passive immunizations). It has two components: purified exogenous/endogenous ag (i.e., target ag) and a high-titer-specific antibody (ab) against the target ag made into an immune complex (IC) with predetermined immune-inducing components. The MVT works by ab information transfer (production of same class of immunoglobulin with the same specificity against the target ag that is present in the vaccine), thereby re-establishing tolerance to self (caused by exogenous/endogenous ags) following repeated administration of appropriate ICs. This vaccination technique can be used both prophylactically and therapeutically, and it mimics the immune system's natural abilities to respond to corrective information specifically, rapidly, safely and with minimal side effects and makes this approach a novel solution for many disorders that are difficult or impossible to cure or manage.
authors.affiliation: Department of Surgery, 2808 Health Sciences Centre, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1, Canada. barabas@ucalgary.ca.
authors.forename: Arpad Zsigmond
authors.initials: AZ
authors.lastname: Barabas
authors.affiliation: Department of Neurosurgery, University of Utah, Salt Lake City, UT, USA.
authors.forename: Chad Douglas
authors.initials: CD
authors.lastname: Cole
authors.affiliation: Department of Pharmacology, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Richard Milton
authors.initials: RM
authors.lastname: Graeff
authors.affiliation: Department of Surgery, 2808 Health Sciences Centre, University of Calgary, 3330 Hospital Dr. NW, Calgary, AB, T2N 4N1, Canada.
authors.forename: Rene
authors.initials: R
authors.lastname: Lafreniere
authors.affiliation: University of Edinburgh Medical School, Edinburgh, Scotland, UK.
authors.forename: Donald Mackay
authors.initials: DM
authors.lastname: Weir
mesh_terms: D000818:Animals; D000941:Antigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D006801:Humans; D007108:Immune Tolerance; D014611:Vaccination
chemical_list: D000941:Antigens
keywords: Autoantibody; Immune complex; Modified vaccination technique; Tolerance