05免疫疾病

nullChapter 5：Diseases of the Immune SystemChapter 5：Diseases of the Immune SystemDepartment of Pathology Peking Union Medical College Lu ZhaohuiImmunity and DiseaseImmunity and DiseaseThe normal immune response is best understood in the context of defense against infectious pathogens, the classical definition of immunity. Innate immunity Adaptive immunity AUTOIMMUNE DISEASES AUTOIMMUNE DISEASES Immune reactions against self-antigens-autoimmunity result in the damage to tissues and single or mutiple organsMechanismMechanismImmunological tolerance is the phenomenon of unresponsiveness to an antigen as a result of exposure of lymphocytes to that antigen. Self-tolerance refers to lack of responsiveness to an individual's own antigens, and it underlies our ability to live in harmony with our cells and tissues. Lose of Immunological Tolerance Lose of Immunological Tolerance Central Tolerance peripheral tolerancenullnullRole of genetic factors Role of Infections Role of EstrogenTypes of Autoimmune DiseasesTypes of Autoimmune DiseasesOrgan / Cell specific AD Hashimoto thyroiditis autoimmune hemolytic anemia autoimmune atrophic gastritis of pernicious anemia autoimmune encephalomyelitis autoimmune orchitis Goodpasture syndrome autoimmune thrombocytopenia Type Ⅰ diabetes mellitus myasthenia gravis Graves disease primary biliary cirrhosis autoimmune hepatitis ulcerative colitis membranous glomerulonephritis Types of Autoimmune DiseasesTypes of Autoimmune DiseasesSystemic or multiple organs systemic lupus erythematosus rheumatoid arthritis Sjögren syndrome Reiter syndrome imflammatory myopathy systemic sclerosis polyarteritis nodosaSystemic Lupus Erythematosus, SLE Systemic Lupus Erythematosus, SLE nullSLE is the prototype of a multisystem disease of autoimmune origin, characterized by a vast array of autoantibodies, particularly antinuclear antibodies (ANAs). Acute or insidious in its onset, it is a chronic, remitting and relapsing, often febrile illness characterized principally by injury to the skin, joints, kidney, and serosal membranes. Etiology and Pathogenesis of SLE Etiology and Pathogenesis of SLE Genetic Factors Immunological Factors Environmental Factors OthersMechanisms of Tissue Injury Mechanisms of Tissue Injury SLE is a complex disorder of multifactorial origin resulting from interactions among genetic, immunological, and environmental factors that act in concert to cause activation of helper T cells and B cells and result in the production of several species of pathogenic autoantibodies. mesangial proliferative (class II) mesangial proliferative (class II) Morphology Morphology Kidney minimal mesangial (class I); mesangial proliferative (class II); focal proliferative (class III); diffuse proliferative (class IV); membranous (class V). None of these patterns is specific for lupus. MorphologyMorphologySkin. Joints Central Nervous System. Pericarditis and Other Serosal Cavity Involvement Cardiovascular system Spleen Lung Other Organs and Tissues. Rheumatoid Arthritis, RA Rheumatoid Arthritis, RA nullRheumatoid arthritis is a chronic systemic inflammatory disorder that may affect many tissues and organs-skin, blood vessels, heart, lungs, and muscles-but principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis that often progresses to destruction of the articular cartilage and ankylosis of the joints Etiology and PathogenesisEtiology and PathogenesisGenetic susceptibility Environmental arthritogen Autoimmunity MorphologyMorphologyJoints infiltration of synovial stroma by a dense perivascular inflammatory infiltrate increased vascularity aggregation of organizing fibrin accumulation of neutrophils osteoclastic activity in underlying bone pannus Skin. Rheumatoid nodules Blood Vessels. Rheumatoid nodules of Skin Rheumatoid nodules of Skin SJÖGREN SYNDROME SJÖGREN SYNDROME nullSjögren syndrome is a chronic disease characterized by dry eyes (keratoconjunctivitis sicca) and dry mouth (xerostomia) resulting from immunologically mediated destruction of the lacrimal and salivary glands.Etiology and PathogenesisEtiology and Pathogenesislymphocytic infiltration and fibrosis of the lacrimal and salivary glands Autoimmune factors RF: 75% ANAs: 50%-80% RNP,SS-A,SS-B: 90% Genetic factors HLA-B8,HLA-B3,DRW52,HLA-DQA1,HLA-DQB1 MorphologyMorphologyLacrimal and salivary periductal and perivascular lymphocytic infiltration. The ductal lining epithelial cells may show hyperplasia atrophy of the acini fibrosis, and hyalinization Kidney Lung Skin Central Nervous System Involvement of salivary gland Involvement of salivary gland INFLAMMATORY MYOPATHIES INFLAMMATORY MYOPATHIES nulldermatomyositis, polymyositis, and inclusion-body myositis probably immunologically mediated SYSTEMIC SCLEROSIS SYSTEMIC SCLEROSIS nullchronic inflammation thought to be the result of autoimmunity widespread damage to small blood vessels progressive interstitial and perivascular fibrosis in the skin and multiple organs Etiology and Pathogenesis Etiology and Pathogenesis progressive fibrosis Microvascular disease MorphologyMorphologySkin Alimentary Tract Musculoskeletal System Kidneys Lungs Heart extensive subcutaneous fibrosis extensive subcutaneous fibrosis Vasculitis Vasculitis GIANT-CELL ARTERITIS GIANT-CELL ARTERITIS Giant-cell (temporal) arteritis is the most common form of vasculitis among elderly chronic, typically granulomatous inflammation of large to small-sized arteries principally the temporal arteries MorphologyMorphology nodular intimal thickening granulomatous inflammation elastic lamina fragmentationGIANT-CELL ARTERITISGIANT-CELL ARTERITISPOLYARTERITIS NODOSA POLYARTERITIS NODOSA Polyarteritis nodosa (PAN) is a systemic vasculitis of small or medium-sized muscular arteries typically involving renal and visceral vesselsMorphology. Morphology. segmental transmural necrotizing inflammation of small to medium-sized arteries weakens the arterial wall Impaired perfusion transmural inflammation fibrinoid necrosis thickening of the vessel wall POLYARTERITIS NODOSAPOLYARTERITIS NODOSATHROMBOANGIITIS OBLITERANS THROMBOANGIITIS OBLITERANS Thromboangiitis obliterans (Buerger disease) is a distinctive disease that often leads to vascular insufficiency segmental, thrombosing, acute and chronic inflammation of medium-sized and small arteries tibial and radial arteries PathogenesisPathogenesisThe strong relationship to cigarette smokingMorphology Morphology sharply segmental acute and chronic vasculitis of medium-sized and small arteries microabscesses WEGENER GRANULOMATOSIS WEGENER GRANULOMATOSIS Acute necrotizing granulomas of the upper respiratory tract Necrotizing or granulomatous vasculitis affecting small to medium-sized vessels Renal diseaseMorphology. Morphology. Upper respiratory tract lesions granulomas with geographic patterns of central necrosis vasculitis renal lesions Rejection of Tissue Transplants Rejection of Tissue Transplants Mechanisms of Recognition and Rejection of Allografts Mechanisms of Recognition and Rejection of Allografts T Cell-Mediated Reactions Antibody-Mediated Reactions Rejection of Solid organ transplantation (Kidney)Rejection of Solid organ transplantation (Kidney)Hyperacute Rejection. Acute Rejection. Acute cellular rejection Acute humoral rejection (rejection vasculitis) Chronic Rejection. Acute rejection of liver transplantationAcute rejection of liver transplantationTransplantation of Hematopoietic Cells Transplantation of Hematopoietic Cells GVH disease occurs in any situation in which immunologically competent cells or their precursors are transplanted into immunologically crippled recipients, and the transferred cells recognize alloantigens in the host Acute GVH disease Chronic GVH disease Immunodeficiency Syndromes Immunodeficiency Syndromes nullprimary immunodeficiency disorders, always genetically determined secondary immunodeficiency states, which may arise as complications of various diseases , ect. Infection of virus primary immunodeficiency Very rareACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) ACQUIRED IMMUNODEFICIENCY SYNDROME (AIDS) Caused by the retrovirus human immunodeficiency virus (HIV) Profound immunosuppression Opportunistic infections Secondary neoplasms Neurologic manifestations. Epidemiology Epidemiology Homosexual or bisexual men Intravenous drug abusers Hemophiliacs Recipients of blood and blood components Heterosexual contacts Parenteral transmission 5% can not be determinedEtiology:Etiology:Structure of HIV Pathogenesis of HIV Infection and AIDS Pathogenesis of HIV Infection and AIDS Clinical FeatureClinical FeatureDeletion of CD4+ lmyphocytes Opportunistic Infections pneumonia Pneumocystis jiroveci Candidiasis Cytomegalovirus atypical mycobacteria M. tuberculosis Cryptococcosis Infection of TB in an AIDS lymph nodeInfection of TB in an AIDS lymph nodeTumors Tumors Kaposi Sarcoma AIDS-related lymphomas Central Nervous System Disease Clinical Course and Drug therapy of AIDSClinical Course and Drug therapy of AIDShighly active antiretroviral therapy combination antiretroviral therapy Acute stage Chronic stage Risky stage