Immune Regulatory Dysfunction

REGULATORY defect Innate Autoinflammatory syndrome Severe Colitis Adaptive Hemophagocytic Lymphohistiocytosis (HLH) Griscelli syndrome,  Chédiak-Higashi syndrome, and  The Hermansky-Pudlak type II syndrome Adult haemophagocytic syndrome Lancet 2013 ALPS (Autoimmune lymphoproliferative Syndrome) Natural history of autoimmune lymphoproliferative syndrome associated with FAS gene mutations BLood 2014 Revised diagnostic criteria and classification for the autoimmune lymphoproliferative syndrome (ALPS): report from the 2009 NIH International Workshop Blood  Case 27-2013: A 6.5-Month-Old Boy with Fever, Rash, and Cytopenias Autoimmune and inflammatory disease Autoimmunity vs Autoimmune Diseases 3 Mechanism preventing autoimmunity: Harrison's  Principles of IM19 e Mechanism of Autoimmunity: Harrison's Principles of Internal Medicine, 19e Exogenous Molecular mimicry Superantigenic stimulation Microbial and tissue damage–associated adjuvanticity Endogenous Altered antigen presentation Loss of immunologic privilege Presentation of novel or cryptic epitopes (epitope spreading) Alteration of self-antigen Enhanced function of antigen-presenting cells Costimulatory molecule expression Cytokine production Increased T cell help (intense stimulation of T cell leads to bypass of antigen specific helper T cell, and lead to polyclonal autoantibodies; Examples of Diseases  autoimmune hemolytic anemia and  immune complex–mediated glomerulonephritis Increased B cell function B cell activating factor (BAAF) Examples Lupus like syndrome Costimulatory molecules Apoptotic defects or defects in clearance of apoptotic material  Examples of Disease  SLE  Cytokine imbalance Diminished production of  TNF and  IL 10  IBD that mimics Crohn's disease (cured by ASCT) MS (in animal model) Overproduction or therapeutic supplementation of Type 1 IFN Altered immunoregulation Deficiency of IL 10 producing regulatory B cells Human SLE  Endocrine abnormalities Case 1-2016: An 18-Year-Old Man with Fever, Abdominal Pain, and Thrombocytopenia Repressing Immunity in Autoimmune Disease NEJM 2016