Antigenic Complementarity in the Origins of Autoimmunity A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura英文文献资料.docVIP

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Antigenic Complementarity in the Origins of Autoimmunity A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura英文文献资料.doc

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Antigenic Complementarity in the Origins of Autoimmunity A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura英文文献资料

ClinicalDevelopmentalImmunology,March2006;13(1):49–65 Antigeniccomplementarityintheoriginsofautoimmunity:Ageneral theoryillustratedwithacasestudyofidiopathicthrombocytopenia purpura ROBERTROOT-BERNSTEINJACOBCOUTURIER DepartmentofPhysiology,MichiganStateUniversity,EastLansing,MI,USA Abstract We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP). Pairs of stereochemically complementaryantigensinducecomplementaryimmuneresponses(antibodyorT-cell)thatcreatelossofregulationandcivil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cellscreatingperivascularcuf?ng.Thisimmunologicalcivilwarabrogatestheself–nonselfdistinction.Ifatleastoneof thecomplementaryantigensmimicsaselfantigen,thenthisunregulatedimmuneresponsewilltargethosttissuesaswell. Datademonstratingthatcomplementaryantigensarefoundinsomeanimalmodelsofautoimmunityandmaybepresentin various human diseases, especially ITP, are reviewed. Speci?c mechanisms for preventing autoimmunity or suppressing existingautoimmunityarederivedfromthetheory,andcriticaltestsproposed.Finally,wearguethatKoch’spostulatesare inadequateforestablishingdiseasecausationformultiple-antigendiseasesanddiscussthepossibilitythatcurrentresearchhas failedtoelucidatethecausesofhumanautoimmunediseasesbecauseweareusingthewrongcriteria. Keywords: Circulatingimmunecomplexes,complementaryantigens,idiotype–antiidiotype,ITP,Koch’spostulates,theoryof autoimmunity Introduction observations exists, nor have any of the current theories led to the development of autoimmune disease models in animals that reproduce naturally occurringprocessesofautoimmunityinduction.This paper attempts to provide an integrated, testable theoryofautoimmunediseaseinductionthatprovides strategiesforidentifyinginfectiousagentsinvolvedin disease induction. W