Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Marburg virus disease wikipedia , lookup
Sarcocystis wikipedia , lookup
Herpes simplex virus wikipedia , lookup
Hepatitis C wikipedia , lookup
Onchocerciasis wikipedia , lookup
African trypanosomiasis wikipedia , lookup
Hospital-acquired infection wikipedia , lookup
Neonatal infection wikipedia , lookup
Oesophagostomum wikipedia , lookup
Schistosomiasis wikipedia , lookup
Human cytomegalovirus wikipedia , lookup
Visceral leishmaniasis wikipedia , lookup
ImmunoPathology II Autoimmune Diseases R. Pat Bucy, MD, PhD Professor of Pathology, Microbiology, and Medicine Organ Specific and Non-Organ Specific Autoimmune Diseases Organ Specific Localized to Antigen given organ Non-Organ Specific Widespread throughout the body Antigen in organ Immune Complex Lesions is target of deposition in many tissues immune attack – skin, joints, kidney With other organ With other non-organ Overlap specific diseases specific diseases Breaking Tolerance Experimental Induction of anti-self responses • Conjugation of self epitopes to immunogenic determinants • Localization with another vigorous immune response • Exposure of "Hidden" self antigens • Genetic patterns of responsiveness General Scheme Induction of Organ Specific Autoimmune Disease • Induction of local immune response – Infection, Drug Rx, Trauma, etc • Malfunction of immune regulation – Genetic predisposition • Progressive immune response to tissue Ag – Epitope Spreading • Tissue destruction and loss of function Organ Specific Autoimmune Diseases • Endocrine – Thyroiditis/Grave's Disease – Insulin Dependent Diabetes – Atrophic Gastritis/Pernicious Anemia – Idiopathic Addison's Disease – Idiopathic Hypoparathyroidism – Idiopathic Hypogonadism – Idiopathic Hypophysitis • Neuromuscular system – Multiple Sclerosis – Guillian-Barre (Idiopathic Polyneuritis) – Myasthenia Gravis • Gastrointestinal – – – – Crohn's Disease Ulcerative colitis Primary Biliary Cirrhosis Chronic Active Hepatitis • Miscellaneous – – – – – – Sjögren's Syndrome Idiopathic myocarditis Interstitial pneumonitis Idiopathic Interstitial Nephritis Lichen Planus Bullous Skin Diseases • Iatrogenic • Joints – Rheumatoid arthritis – Relapsing Polychrondritis – Allo-Transplant rejection Multiple Sclerosis • • • • Immune Destruction of CNS Myelin Histopathology - Depends on stage of lesion Viral infection as Antecedent Animal Models - EAE Experimental autoimmune encephalomelitis (EAE) Insulin Dependent Diabetes Mellitus Immune mediated destruction of Islet b cells • Histopathology • Epidemiology – Viral Antecedent – MHC linkage • Animal Models – BB rat – NOD mouse – low dose streptozoticin Islets of Langerhans Normal mouse NOD mouse with acute “insulitis” Autoimmune Thyroiditis • Lymphocytic (Hasimoto’s) Thyoiditis – Chronic inflammatory lesion that results in destruction of follicles and ultimately hypothyriodism • Grave’s Disease – Antibody to TSH Receptor that stimulates receptor function and results in hyperthyroidism Graves’ Disease Myasthenia Gravis • Muscle weakness due to autoantibody to acetylcholine receptor of neuromuscular junction • Symptoms can be transferred with antibody to AchR • Relationship to the Thymus Myasthenia Gravis (Blocking auto-antibodies) Inflammatory Bowel Disease Two clinical entities with substantial overlap • Crohn's Disease (Regional Enteritis) – Transmural inflammation – Occurs throughout GI tract, terminal ileum most common – "Skip lesions" and granulomas common – Several new animal models • Ulcerative Colitis – inflammation restricted to mucosa – involves contiguous areas in colon (may extend into ileum) Rheumatoid Arthritis • Chronic inflammatory disease of joint synovium • Presence of Rheumatoid factor – antibody to Fc of IgG usually of IgM class – form immune complexes but rarely result in glomerulonephritis • Erosive lesions of cartilage and bone result from inflammatory “pannus” • Can involve other organs besides joints • Occasionally associated with other autoimmune syndromes Rheumatoid Arthritis Rheumatoid Nodule Plasma cells in Rheumatoid synovitis Rheumatoid Arthritis Rheumatoid Arthritis Synovial erosions Systemic Lupus Erythematosis • Classic “Systemic” Autoimmune Disease • Mediated by immune complex injury – DNA/anti-DNA immune complexes often implicated in tissue injury • Animals models - genetic predisposition to immune complex formation and nephritis • Variant forms of Lupus Lupus Nephritis A B C D E Focal Proliferative GN Diffuse Proliferative GN “wire loop” lesions Subendothelial IC “Granular” pattern of IgG Lupus skin Lesion “butterfly” rash General Scheme Induction of Organ Specific Autoimmune Disease • Induction of local immune response – Infection, Drug Rx, Trauma, etc • Malfunction of immune regulation – Genetic predisposition • Progressive immune response to tissue Ag – Epitope Spreading • Tissue destruction and loss of function Infection and Hypersensitivity anti-viral immune response Activity Tissue Injury (auto-antigens) Viral infection ? Potential Hypersensitivity auto-Ag T cells Memory Time (days) Infection and Hypersensitivity anti-viral immune response Activity Tissue Injury (auto-antigens) Viral infection auto-Ag T cells Time (days) auto-Ag Regulatory T Infection and Hypersensitivity anti-viral immune response Activity Tissue Injury (auto-antigens) Viral infection ? Potential Hypersensitivity auto-Ag T cells Time (days) Infection and Hypersensitivity anti-viral immune response Activity Tissue Injury (auto-antigens) Viral infection auto-Ag T cells Time (days) Autoimmune Disease Infection and Hypersensitivity anti-viral immune response Activity Tissue Injury (auto-antigens) Viral infection ? Potential Hypersensitivity auto-Ag T cells Time (days) Infection and Hypersensitivity anti-viral immune response Activity Tissue Injury (auto-antigens) Viral infection auto-Ag T cells Time (days) Infection and Hypersensitivity anti-viral immune response Activity Tissue Injury (auto-antigens) Viral infection Contributors to control auto-Ag • T cells • • • Time (days) Dynamics of infectious organism Frequencies and function of autoreactive T cells Cytokine milieu - TGFb + IL-10 versus IL-6, TNFa, IFNg Amount and kinetic course of auto-Ag Overview of ImmunoPathology • Immune mechanisms that result in tissue injury • Classification by mechanism vs antigen source • Exogenous antigens – Infectious Agents – Environmental Agents • Iatrogenic – Solid organ transplants – Bone marrow transplants • Neoplastic cells • Autoantigens ImmunoPathology Lab Discussion http://peir.path.uab.edu/iplab/