Front Cover -- The Autoimmune Diseases -- Copyright Page -- Contents -- List of Contributors -- Preface -- Present at the Beginning -- 1 Immunologic Basis of Autoimmunity -- 1 Autoimmune Disease: The Consequence of Disturbed Homeostasis -- Evolution of the Autoimmune Response -- A Phylogenetic Perspective -- The Innate Immune System -- The Adaptive Immune System -- Self and Non-Self, and the Nature of Autoantigens -- Autoimmunity and Autoimmune Disease -- The Common Threads -- The "Proper Study…" -- Towards the Future -- The Last Word -- References -- 2 Autoimmunity: A History of the Early Struggle for Recognition -- The Search for Autoantibodies -- Horror Autotoxicus -- The Nature of Ehrlich's "Contrivances" -- Challenges to the Thesis -- Lens Autoantibodies -- Paroxysmal Cold Hemoglobinuria -- Sympathetic Ophthalmia -- The Wassermann Antibody -- The Shift to Immunochemistry -- The Return of Immunobiology -- Concluding Remarks -- References -- 3 General Features of Autoimmune Disease -- Innate Immune Activation -- Cells of the Adaptive Immune System -- Defining Autoimmune Disease -- Prevalence of Autoimmunity -- Genetics of Autoimmunity -- Association of Single Gene Defects with Autoimmunity -- Genome-wide Association Studies (GWAS) Identify Multiple Gene Loci that are Associated with Autoimmunity -- MHC Associations with Autoimmunity -- Other Genes Identified by GWAS Studies -- GWAS Studies Identify Common Pathways for Autoimmmunity -- Application of Data from GWAS Studies to Clinical Practice -- Epigenetic Alterations Associated with Autoimmunity -- Hormones and Autoimmunity -- Autoimmunity and Central Tolerance -- Autoimmunity and Peripheral Tolerance -- Triggers of Autommunity -- Activation of the Immune System -- Role of Antigen as a Driver of Autoimmunity -- Defective Downregulation of an Immune Response -- Regulatory Lymphocytes.

The Role of the Gut Microbiota in Autoimmunity -- Mechanisms of Tissue Damage -- Flares and Remissions During Disease -- Therapeutic Advances -- Goals for the Future -- Concluding Remarks -- Acknowledgments -- References -- 4 The Concept of Autoinflammatory Diseases -- Historical Perspective -- Definition -- Spectrum from Autoimmune to Autoinflammatory Disease -- Mechanisms in Autoinflammation -- Classical Hereditary Autoinflammatory Disorders -- Common Phenotype -- Cryopyrin-Associated Periodic Syndrome -- Familial Mediterranean Fever -- TNF Receptor-Associated Periodic Syndrome -- HIDS (also Known as Mevalonate Kinase Deficiency) -- Polygenic or Acquired Autoinflammatory Disorders -- Autoinflammatory Mechanisms of Disease in Common Disorders -- Type 2 Diabetes Mellitus -- Atherosclerosis -- Newest Developments: Rare Hereditary Disorders with Autoinflammatory Aspects -- Proteasome Defects -- PLCγ2 Deficiency -- Heme-Oxidized IRP2 Ubiquitin Ligase -- Conclusion -- References -- 2 Immune Cells and Immune Responses -- 5 Innate and Adaptive Systems of Immunity -- Introduction -- The Innate and Adaptive Responses -- Innate Responses -- Cellular Components -- Soluble Mediators -- Adaptive Immune Responses -- T Cell Development -- Functional Activities of T Cells -- B Cell Development and Functions -- Antibodies -- Secondary Lymphoid Tissues -- Resolution of the Immune Response -- References -- 6 T Cells and their Subsets in Autoimmunity -- Introduction -- TH1 Cells -- TH17 Cells -- Discovery and Differentiation -- Function -- Reciprocal Relationship with Tregs -- The Role of IL-23 in the Generation of Th17 Cells -- Th17 Pathogenicity and Plasticity -- Th17 Regulation in the Intestine -- Regulatory CD4+ T Cells -- Tr1 Cells -- TFH Cells -- Th2 Cells -- Th9 Cells -- Concluding Remarks -- References -- 7 Immunological Tolerance-T Cells.

Early Studies Supporting the Induction of Tolerance -- Thymic Tolerance -- Brief Overview of Thymocyte Development -- Mechanisms of Thymic Tolerance -- Clonal Deletion -- Anergy as a Mechanism for Self-Tolerance -- Thymic Development of Regulatory T Cells Maintain Tolerance -- Expression of Tissue-Restricted Antigens in the Thymus -- Peripheral Tolerance -- Impact of Dendritic Cells -- Dendritic Cells: Directors of Peripheral Immune Tolerance -- Molecular Programming of Resting DCs is Critical for Preventing Autoimmunity -- Mechanisms of Peripheral Tolerance -- Clonal Deletion -- Anergy as a Mechanism of Peripheral Tolerance -- Ignorance -- Induced Regulatory T Cells and the Maintenance of Peripheral Tolerance -- Negative Regulatory Mechanisms that Impact Tolerance -- Expression of Tissue-Specific Antigens by Lymph Node Stromal Cells -- Concluding Remarks -- Acknowledgments -- References -- 8 The Role of Invariant Natural Killer T Cells in Autoimmune Diseases -- The Curious Case of iNKT Cells -- The Many Names of NKT Cells -- The Many Faces of iNKT Cells -- Phenotype -- Distribution -- The Many Effector Functions of iNKT Cells -- Activation -- Cytokine Production -- Downstream Effects -- The Many Kinds of iNKT Cells -- Technical Problems and the Species Divide -- The Species Divide -- The Janus-Like Character of iNKT Cells in Autoimmunity -- Too Much of a Good Thing: Detrimental Roles of iNKT Cells -- Atherosclerosis -- Asthma -- IBD/Colitis -- Primary Biliary Cirrhosis (PBC) -- Rheumatoid Arthritis -- Skin Disorders -- Missed so Sadly: Beneficial Roles of iNKT Cells -- Diabetes -- IBD/Crohn's Disease -- Multiple Sclerosis/EAE -- Systemic Lupus Erythematosus (SLE) -- Good or Bad Performers? -- The Far End of the Question? -- What Activates iNKT Cells During Autoimmune Responses?.

Which iNKT Cell Effector Functions Orchestrate the Development of Autoimmune Responses? -- Conclusion -- Acknowledgments -- Abbreviations -- References -- 9 B Cell Development: How to Become One of the Chosen Ones -- Introduction-What has to be Generated in B Cell Development to Make it to Maturity? -- Follicular B Cells -- Intraepithelial B Cells -- Two Types of Memory B Cells -- B Lymphopoiesis Before Ig Repertoire Generation-Development of Progenitor and Precursor Cells -- Development in Waves During Ontogeny, and in Niches Throughout Life -- Cellular Environments of the First Phase of Early, Antigen-Independent B Cell Development -- Early Commitments to Antigen-Independent B Cell Development -- The Second, Eventually Autoantigen-Sensitive, Phase of B Cell Development to sIgM+ Immature B Cells -- The First Checkpoint for the Emerging B Cell Repertoire-Probing the Fitness for a Good BCR -- Expression of IgL Chains -- The Second Checkpoint: Sites and Mechanisms of Selection of Newly Generated sIgM+ B Cells -- Future Approaches to Understanding Central B Cell Tolerance -- Acknowledgments -- References -- 10 B Cell Activation and B Cell Tolerance -- B Cell Activation -- Antigen-Triggered Activation -- Secondary Signals for B Cell Activation -- The Immediate Consequences of B Cell Activation -- B Cell Activation Requires Interaction with Helper T cells -- Cell Surface Molecules Involved in B Cell-T Cell Interactions -- Cytokines Involved in B Cell-T Cell Interactions -- Activation and Maturation of B Cells Occurs in Lymphoid Organs -- Where Do B Cells become Antigen Activated? -- Antigen Activation of B Cells Leads to the Selection of High Affinity Class-Switched Antibody -- The Germinal Center -- T Cell-Independent Antibody Responses -- B Cell Tolerance: A Traditional and New Concept.

B Cell Tolerance is Acquired by at Least Three Different Processes -- Receptor Editing and Clonal Deletion -- Defective Receptor Editing Can Promote Autoimmunity -- Anergy -- Characteristics of Anergic B Cells -- Survival Factors and Tonic Signals Modulate B Cell Tolerance -- Tonic Signaling in B Cell Development -- Tonic Signaling and Autoimmunity -- BAFF and Autoimmunity -- Regulatory T cells -- Antibody-Independent Activity of B cells in Tolerance -- Cytokine Production by B Cells -- Regulatory B Cells -- Future Directions -- References -- 3 Non-Antigen-Specific Recognition -- 11 Role of Macrophages in Autoimmunity -- Introduction -- Origin and Distribution of Monocytes and Macrophages -- Recognition, Sensing, and Responses -- Phagocytosis, Antigen Presentation, and Secretion -- Activation and Downregulation: Interactions with T and B Lymphocytes -- Role of Macrophages in Adaptive Immunity and Tolerance -- Role of Macrophages in Autoimmune Models and Diseases -- Generation of Autoantigens -- Modulation of Macrophage Activation -- Conclusions and Questions -- Acknowledgments -- References -- 12 Dendritic Cells in Autoimmune Disease -- Antigen Processing by Dendritic Cells -- Pattern Recognition Receptors -- Dendritic Cell Activation -- Dendritic Cell Subsets -- Mouse Dendritic Cells -- Dendritic Cells in the Mouse Thymus -- Dendritic Cell Subsets and Tolerance -- Human Dendritic Cell Subsets in Steady State -- Dendritic Cell Subsets in Human Skin: Epidermal Langerhans Cells and dermal Dendritic Cells -- Dendritic Cells and Autoimmune Disease -- Systemic Lupus Erythematosus -- IBD-Crohn's Disease and Ulcerative Colitis -- Dendritic Cell Immunotherapy as a Treatment for Autoimmune Diseases -- Targeting of Dendritic Cells in Autoimmune Disease -- Conclusions and Future Prospects -- References -- 13 Natural Killer Cells -- Introduction to NK Cells.

NK Cell Development and Differentiation.