Autoimmunity

  1. Pathogenesis of Autoimmunity
    1. Genetic Factors
      1. HLA Associations
        1. HLA Class I Disease Associations
          1. HLA-B27 and Spondyloarthropathies
            1. HLA-A3 and Hemochromatosis
            2. HLA Class II Disease Associations
              1. HLA-DR3 and Type 1 Diabetes
                1. HLA-DR4 and Rheumatoid Arthritis
                  1. HLA-DQ2/DQ8 and Celiac Disease
                  2. Mechanisms of HLA-Disease Association
                    1. Molecular Mimicry
                      1. Altered Peptide Presentation
                        1. Linkage Disequilibrium
                      2. Non-HLA Genetic Factors
                        1. CTLA-4 Polymorphisms
                          1. Regulatory T Cell Function
                            1. Costimulation Regulation
                            2. PTPN22 Variants
                              1. T Cell Receptor Signaling
                                1. B Cell Receptor Signaling
                                2. FOXP3 Mutations
                                  1. Regulatory T Cell Development
                                    1. IPEX Syndrome
                                    2. Complement Deficiencies
                                      1. C1q Deficiency
                                        1. C4 Deficiency
                                          1. Immune Complex Clearance
                                          2. Fas/FasL Mutations
                                            1. Autoimmune Lymphoproliferative Syndrome
                                              1. Apoptosis Defects
                                            2. Familial Clustering
                                              1. Twin Studies
                                                1. Family Aggregation
                                                  1. Shared Environmental Factors
                                                2. Environmental Triggers
                                                  1. Infectious Agents
                                                    1. Molecular Mimicry
                                                      1. Cross-Reactive Epitopes
                                                        1. Examples in Specific Diseases
                                                          1. Rheumatic Fever
                                                            1. Guillain-Barré Syndrome
                                                              1. Multiple Sclerosis
                                                            2. Bystander Activation
                                                              1. Inflammatory Cytokine Release
                                                                1. Adjuvant Effects
                                                                  1. Tissue Damage and Antigen Release
                                                                  2. Epitope Spreading
                                                                    1. Primary Epitope Recognition
                                                                      1. Secondary Epitope Development
                                                                      2. Superantigen Effects
                                                                        1. Polyclonal T Cell Activation
                                                                          1. Cytokine Storm
                                                                        2. Chemical and Drug Exposures
                                                                          1. Drug-Induced Autoimmunity
                                                                            1. Hydralazine-Induced Lupus
                                                                              1. Procainamide-Induced Lupus
                                                                                1. Anti-TNF-Induced Autoimmunity
                                                                                2. Occupational Exposures
                                                                                  1. Silica and Autoimmunity
                                                                                    1. Organic Solvents
                                                                                    2. Heavy Metal Exposure
                                                                                      1. Mercury
                                                                                        1. Lead
                                                                                      2. Physical Factors
                                                                                        1. Ultraviolet Radiation
                                                                                          1. DNA Damage
                                                                                            1. Apoptosis Induction
                                                                                              1. Lupus Flares
                                                                                              2. Trauma and Tissue Damage
                                                                                                1. Sympathetic Ophthalmia
                                                                                                  1. Post-Cardiac Injury Syndrome
                                                                                                2. Hormonal Influences
                                                                                                  1. Sex Hormone Effects
                                                                                                    1. Estrogen and Autoimmunity
                                                                                                      1. Testosterone and Protection
                                                                                                      2. Pregnancy Effects
                                                                                                        1. Immune System Modulation
                                                                                                          1. Postpartum Flares
                                                                                                          2. Stress Hormones
                                                                                                            1. Cortisol Effects
                                                                                                              1. HPA Axis Dysfunction
                                                                                                            2. Microbiome Alterations
                                                                                                              1. Dysbiosis
                                                                                                                1. Reduced Microbial Diversity
                                                                                                                  1. Pathogenic Bacterial Overgrowth
                                                                                                                  2. Molecular Mimicry with Microbes
                                                                                                                    1. Short-Chain Fatty Acid Production
                                                                                                                      1. Barrier Function Disruption
                                                                                                                    2. Mechanisms of Tolerance Breakdown
                                                                                                                      1. Central Tolerance Failure
                                                                                                                        1. Thymic Dysfunction
                                                                                                                          1. AIRE Gene Defects
                                                                                                                            1. Incomplete Negative Selection
                                                                                                                            2. Peripheral Tolerance Failure
                                                                                                                              1. Regulatory T Cell Defects
                                                                                                                                1. Reduced Numbers
                                                                                                                                  1. Functional Impairment
                                                                                                                                    1. Resistance to Suppression
                                                                                                                                    2. Costimulatory Dysregulation
                                                                                                                                      1. Inappropriate Costimulation
                                                                                                                                        1. Checkpoint Inhibitor Effects
                                                                                                                                        2. Cytokine Imbalance
                                                                                                                                          1. Pro-inflammatory Dominance
                                                                                                                                            1. Anti-inflammatory Deficiency
                                                                                                                                        3. Tissue Damage Mechanisms
                                                                                                                                          1. Antibody-Mediated Damage
                                                                                                                                            1. Type II Hypersensitivity
                                                                                                                                              1. Complement-Mediated Lysis
                                                                                                                                                1. Antibody-Dependent Cellular Cytotoxicity
                                                                                                                                                  1. Opsonization and Phagocytosis
                                                                                                                                                  2. Type III Hypersensitivity
                                                                                                                                                    1. Immune Complex Formation
                                                                                                                                                      1. Complement Activation
                                                                                                                                                        1. Neutrophil Recruitment
                                                                                                                                                          1. Tissue Deposition Sites
                                                                                                                                                          2. Functional Interference
                                                                                                                                                            1. Receptor Blocking
                                                                                                                                                              1. Receptor Stimulation
                                                                                                                                                                1. Enzyme Inhibition
                                                                                                                                                              2. T Cell-Mediated Damage
                                                                                                                                                                1. Type IV Hypersensitivity
                                                                                                                                                                  1. Delayed-Type Hypersensitivity
                                                                                                                                                                    1. Cytotoxic T Cell Killing
                                                                                                                                                                      1. Inflammatory Cytokine Production
                                                                                                                                                                      2. Th1-Mediated Inflammation
                                                                                                                                                                        1. Macrophage Activation
                                                                                                                                                                          1. Granuloma Formation
                                                                                                                                                                          2. Th17-Mediated Inflammation
                                                                                                                                                                            1. Neutrophil Recruitment
                                                                                                                                                                              1. Tissue Destruction
                                                                                                                                                                            2. Innate Immune Activation
                                                                                                                                                                              1. Complement System Activation
                                                                                                                                                                                1. Neutrophil Extracellular Traps
                                                                                                                                                                                  1. Macrophage Activation
                                                                                                                                                                                    1. Dendritic Cell Maturation

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                                                                                                                                                                                2. Immunological Tolerance

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                                                                                                                                                                                4. Spectrum of Autoimmune Diseases