Chapter 21. Novel Mechanisms of Autoantibody Induction and Pathogenesis in Experimental Autoimmunity

Summary

This chapter contains sections titled:

• Introduction

• The Autoimmune Ovarian Disease (AOD) Models

  • The ZP3 Model

  • The Day-3 Thymectomy AOD Model

  • The Neonatal AOD Model

• Mechanism of Induction and Antigen Specificity of Autoantibodies

  • T-cell Peptide of a Self-protein Elicits Autoantibodies to Distant Sites of the Protein Antigen

  • Mechanism of the Amplified Autoantibody Response

  • Amplified Autoantibody Response Also Occurs in Response to a Foreign T-cell Epitope That Mimics a Self T-cell Epitope

  • Autoantibody Production in AOD of Day-3 Thymectomized Mice Is Suppressed by the CD4⁺CD25⁺ T Cells from Normal Mice

• Pathogenic Mechanisms of Autoantibodies in Autoimmune Disease

  • Studying Autoantibody Response Without Concomitant Autoreactive T-cell Response Based on Chimeric Peptide

  • ZP Antibodies Cause Organ Failure by Retargeting T Cellinduced Inflammation to the Functional Target

  • Autoantibodies that are Non-pathogenic in Adults can be Pathogenic in Neonatal Mice (nAOD)

  • Mechanism of nAOD I: Autoantibody Induction of de novo Neonatal Pathogenic T-cell Response by Formation of the Autoantigen-Antibody Complex

  • Mechanism of nAOD II: Disease Induction Is Influenced by the B-cell Epitope Specificity of the Autoantibody

  • Mechanism of nAOD III: Neonatal Time Window of Disease Susceptibility That Is Partially Influenced by the CD4⁺CD25⁺ Regulatory T Cells

  • Mechanism of nAOD IV: Requirement of NK Cells, FcR, and Proinflammatory Cytokines in Disease Pathogenesis