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Results are presented concerning our attempts to create a suitable model system for studying the connection between microbial antigen (micAg), autoimmunity and autoimmune disease on the basis of hyper-immunization and application ofmicAg in different contexts. Our researchwas focused on tetanus toxoid (TTd) as amodel micAg.Non-pretreated and complete Freund's adjuvant pretreated BALB/c mice were immunized with high doses of TTd mixed with glycerol or aluminum hydroxide as adjuvants. The main aims of the experiments were to evaluate the properties of induced humoral immune responses, evaluate the pathological potential of induced immune responses and determine possible correlations between the properties of a humoral immune response and its pathological potential. The production of TTd-specific and self-reactive β2-glycoprotein I (β2-GP I)-specific antibodies (Abs) was detected in all groups but with specific, context-related properties. Analysis of pregnancy-related pathology (anti-β2-GP I Abs-associated) showed differences in the pathological potential of the induced immune response. It was demonstrated that severity of pathology is positively correlated to the abundance of IgG that recognizes β2-GP I adsorbed onto phosphatidylserine, and to IgG affinity. Furthermore, it was demonstrated that molecular mimicry, which results in generation of anti-β2-GP I Abs upon TTd immunization, is necessary but not sufficient for the development of pregnancy-related pathology. ©2008 The Societies and Blackwell Publishing Asia Pty Ltd.
Stojanović, M., Živković, I., Inić-Kanada, A., Petrušić, V., Mićić, M., & Dimitrijević, L. (2009). The context of tetanus toxoid application influences the outcome of antigen-specific and self-directed humoral immune response. Microbiology and Immunology, 53(2), 89–100. https://doi.org/10.1111/j.1348-0421.2008.00094.x