MECHANISMS OF AUTOIMMUNITY I. Exogenous A Molecular mimicry B. Superantigenic stimulation C Microbial adjuvanticity ll Endogenous A. Altered antigen presentation 1. Loss of immunologic privilege 2. Presentation of novel or crytic epitopes(epitope spreading 3. Alteration of self-antigen 4. Enhanced function of antigen-presenting cells a. Costimulatory molecule expression b. Cytokine production B. Increased T cell help 1. Cytokine production 2. Co-stimulatory molecules C. Increased B cell function D. Apoptotic defects E. Cytokine imbalance F. Altered immunoregulation
MECHANISMS OF TISSUE DAMAGE IN AUTOIMMUNE DISEASE EFFECTOR MECHANISM TARGET DISEASE Autoantibody Blocking or a(Chain of the nicotinic Myasthenia gravis inactivation acetylcholine receptor Phospholipid-B2-glycoprotein Antiphospholipid 1 complex Insulin receptor Insulin-resistant diabetes mellitus Intrinsic factor Pernicious anemia Stimulation TSH receptor (LATS) Graves disease Proteinase-3 (ANCA) Wegener's granulomatosis Epidermal cadherin, Pemphigus vulgaris Desmoglein 3 Complement activation a Chain of collagen IV Goodpasture's syndrome Immune-complex formation Double-strand DNA Systemic lupus erythematosus lg Rheumatoid arthritis opsonization Platelet Gpllb: la Autoimmune thrombocytopenic purpura Rh antigens, I antigen Autoimmune hemolytic anemia Antibody-dependent Thyroid peroxidase Hashimoto's thyroiditis cellular cytotoxicity thyroglobulin T cells Cytokine production Rheumatoid arthritis, multiple sclerosis, Type 1 diabetes mellitus Cellular cytotoxicity Type 1 diabetes mellitus