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Immune System Disorders_pathology, SLE-failure of self-tolerance mechs -many autoABs -ANA-antinuclear ABs, and RBC ABs -anti-dsDNA-rim of nuc -anti-Smith -if both->diagnostic of SLE -anti-histone, chrom-diffuse in nuc -anti-b2 glycoprotein also binds cardiolipin ->false-positive syphilis test -some delay clotting->lupus anticoagulant -more common in 20-40yoF -more common/severe in black F Clinical Actually PROcoagulant state ->thromboses Recurrent miscarriages False-(+) for syphilis Can have autoABs w/out Sx -twins w/ same autoABs T cell driving force ->Type III HS Necrotizing Vasculitis anywhere Glomerulonephritis (mesan, focal, diffuse, membranous) ->hematuria, proteinuria, HTN -largest factor in morbidity Butterfly rash - worse w/ sunlight Necrosis, imm complexes at dermoepidermal jcn ALL OVER Nonerosive synovitis, little deform. Arthritis in small joints Pericarditis, atherosclerosis -Libman-Sacks endocarditis Pleuritis, pleural effusions FEVER, Immune System Disorders Autoimmune Dzs Scleroderma -overproduction of coll, ECM -due to more fibroblasts -dec T cells, NL #, hyperactive B -inc. T cells cytokines->coll Women 25-50 no clear FH, HLA 96% w/ chrom defects -environmental? ->dysphagia, pulmonary HTN ->malignant HTN (renal aa. fibrosis) -leading cause of death -anti-SCI-70 (topoisomerase) AB -anti-centromere, nucleolar Ag ABs, Immune System Disorders Hypersensitivity Rxns See Hypersensitivity Map, SLE-failure of self-tolerance mechs -many autoABs -ANA-antinuclear ABs, and RBC ABs -anti-dsDNA-rim of nuc -anti-Smith -if both->diagnostic of SLE -anti-histone, chrom-diffuse in nuc -anti-b2 glycoprotein also binds cardiolipin ->false-positive syphilis test -some delay clotting->lupus anticoagulant -more common in 20-40yoF -more common/severe in black F Chronic Discoid Lupus Worse skin problems, scarring -deposition of C3, Ig at DE jcn -only in involved skin Systemic problems rare rarely have anti-dsDNA ABs -but (+) ANA test -10% may develop SLE, Immune System Disorders HLA & Dz 1. Inflam. Dzs HLA-B27->predisposes to ankylosing spondylitis (by 90x) HLA-DR1, 4->Rheum. Arth HLA-DR3,4->IDDM (via HLA-DQb) 2. Inherited errors of metabolism 21-hydroxylase activity 3. Autoimmune Dzs, Immune System Disorders Immunologic Deficiency Syndromes See Imm. Def. map, Immune System Disorders Autoimmune Dzs Rheumatic Fever -arthritis in many areas -Erythema marginatum-pale center rounded margin rash -Painless, freely-movable SC nodules -Chorea-Sydenham's-20%pts, Immune System Disorders Autoimmune Dzs Calcinosis (calc of subcut tissues) Raynaud's Phenomenon-temp vasospasm ->cyanosis in finger tips due to cold/emo Esophageal Dysmotility Sclerodactyly-scleroderma of fingers Telangiectasias-localized dilation of blood vv. -anti-centromere, Immune System Disorders Autoimmune Dzs Polymyositis/Dermatomyositis -CT dz-->proximal mm. weakness DM-weakness, rash on face, neck, shoulders PM/DM-bilateral, symmetric, slow onset -elevated CPK-MM, aldolase -no ocular involvment -Jo-1 AB skin like SLE, but no deposition -BUT, periorbital discoloration, edema -Grotton's lesions (scaly, on joints) 2:! female, HLA-DR3, B8 Cellular/humoral involvement -IC deposit in mm., as do CD4+, NK Toxoplasma, influenza, coxackie 75% of men w/ visceral CA w/in 1 year, Immune System Disorders Autoimmune Dzs Sjogren Syndrome -inflam of salivary, lacrimal glands ->keratoconjunctivitis sicca (dry eyes) ->xerostomia (dry mouth) Primary and Secondary forms 2ndary-occurs w/ SLE, RA, SD, PM Primary-HLA-B8, DR3, DRW52 -can involve lung, thyroid, kidney -AB to ANA, 90% w/ SS-A(Ro), SS-B(La) Rheum factor in 75% -40x inc. risk of lymphoma Lymphocytes in glands, CD4+ T cells, acini atrophy/fibrosis Lip biopsy for Dx Arthritis