Week 10 Autoimmunity PDF

10 AUTOIMMUNITY AUTOIMMUNITY Disorders in which immune responses are targeted toward self-antigens and results in damage to organs and tissues in the body. Can be due to autoimmune antibodies or T-cell mediated immune response. Etiology of autoimmune disease: Self-tolerance Abi...

10 AUTOIMMUNITY AUTOIMMUNITY Disorders in which immune responses are targeted toward self-antigens and results in damage to organs and tissues in the body. Can be due to autoimmune antibodies or T-cell mediated immune response. Etiology of autoimmune disease: Self-tolerance Ability of the immune system to accept self-antigens and not initiate a response against them. Autoimmune disease is thought to result from LOSS of self-tolerance. Etiology of autoimmune disease: genetics There is an association between HLA and risk of developing a particular autoimmune disorder. The strongest link found is between the HLA-B27 allele and the development of ankylosing spondylitis Etiology of autoimmune disease: Hormonal influence Women are 2.7 times more likely to acquire and autoimmune disease than men. The stimulatory effect of female hormones may place women at a greater risk for developing autoimmune disease. Etiology of autoimmune disease: Tissue trauma and release of cryptic antigen Inflammation or tissue trauma could cause cryptic or hidden antigen to be released and to suddenly be accessible to the uneducated lymphocytes, triggering immune response. Etiology of autoimmune disease: Microbial infections Microbes can trigger autoimmunity via molecular mimicry (bacterial and viral agents contain antigens that closely, resemble self-antigens.) Systemic Autoimmune Diseases Disease Target cells Autoantibodies Anti-dsDNA Anti-Sm Phospholipid antibodies Systemic Lupus Anti-RBC Erythematosus (SLE) Multiple cells Anti-PLT Anti-lymphocyte Anti-ribosomal complement Anti-endothelium Rheumatoid factor (RA) Systemic Lupus Erythematosus Occurs when your body's immune system attacks your own tissues and organs (autoimmune disease). Inflammation caused by lupus can affect many different body systems - including your joints, skin, kidneys, blood cells, brain, heart and lungs. Clinical Signs and Symptoms Nonspecific like fatigue, weight loss, malaise, fever, and anorexia. Symmetrical arthritis Erythematous rash Other systemic effects involving the heart, nervous system, and the blood. drug induced lupus Most common implicated drugs are procainamide, hydralazine, chlorpromazine, isoniazid, quinidine, anticonvulsant such as methyldopa, and possible oral contraceptives. Symptoms disappear once drug is discontinued.  laboratory tests CBC Leukopenia, Anemia Platelet count Thrombocytopenia ESR Increased CRP Normal to Low Complement Low Antinuclear antibodies (ANAs) Heterogenous group of antibodies that have different antigen specificities. AutoAb Immunofluorescent Disease pattern Association Anti-dsDNA Peripheral or homogenous SLE Anti-ssDNA Not detected on routine screen SLE Antihistone Homogenous Drug-induced SLE Anti-DNP Homogenous SLE Drug-induced SLE Anti-Sm Coarse speckled Diagnostic for SLE Anti-RNP Coarse speckled SLE, MCTD  AutoAb Immunofluorescent Disease pattern Association Anti-SS-A (Ro) Finely speckled SLE Anti-SS-B (La) Finely speckled Sjögren's syndrome Antinucleolar Prominent staining of nucleoli SLE (smooth, clumpy, or speckled) Systemic sclerosis Anti-Scl-70 Atypical speckled Systemic sclerosis Scleroderma Anti-Jo-1 Fine cytoplasmic speckling Polymyositis Anti-centromere Discrete speckled CREST syndrome  Double-stranded DNA (dsDNA) antibodies Most specific antibody for SLE. Produces peripheral (rim) or homogenous pattern. One particularly sensitive assay for dsDNA is an IF test using a hemoflagellate organism called Crithidia luciliae. Antihistone antibodies Supports the diagnosis of drug-induced SLE.  Extractable nuclear antigens (ENAs) Named because they were isolated in saline extracts of mammalian tissues. Examples: ribonucleoproteins (RNP), Smith (Sm) antigen, SS-A (Ro), SS-B (La), Scl-70, Jo-1, and PM-1. Indirect immunofluorescent assay Most widely used and accepted test for ANAs because it is highly sensitive, detects wide range of antibodies, and is inexpensive and easy to perform. Hep-2, is the standard substrate for clinical laboratories worldwide.  homogenous Characterized by uniform staining of the entire nucleus. Associated autoantibodies: Anti-dsDNA Anti-histones Anti-DNP Found in SLE, drug-induced SLE and other AIDs.  Peripheral Greater staining intensity around the outer circle surrounding the nucleus Seen when anti-dsDNA is present (most specific for SLE) Speckled Characterized by discrete, fluorescent specks throughout the nuclei. Characteristic of anti-ENAs.  Nucleolar Prominent staining of the nucleoli within the nuclei. Due to antibodies to RNA and RNP Mainly seen in Scleroderma. Centromere Numerous discrete speckles (most cells have 46 speckles) Seen in CREST patients: Calcinosis - cachin De ranirien Raynaud's phenomenon Esophageal dysmotility Sclerodactyly Telangiectasias Rheumatoid arthritis Chronic, symmetric, and erosive arthritis of the peripheral joints that can also affect multiple organs such as the heart and the lungs. Strongest environmental risk: Cigarette SMOKING Autoantibodies: Rheumatoid factor (RF) Antibodies to CCP  Rheumatoid factor An antibody of the lgM class produced by the patients with rheumatoid arthritis that is directed toward the Fc region of IgG. Anti-CCP Anti-cyclic citrullinated proteins. Specifically associated with RA. Organ-Specific Autoimmune Diseases Addison's disease Target Glands: Adrenal glands Antibody to adrenals Autoimmune hemolytic anemia Target Glands: RBCs Antibody to RBCs Organ-Specific Autoimmune Diseases Autoimmune hepatitis Target Glands: Liver Autoantibodies: Smooth muscle antibodies (AIH-1) Anti-liver kidney microsomal antibody (anti-LKM-1) ; AIH-2 Anti-liver cytosol type 1 antibody (anti-LC-1); AIH-2 Organ-Specific Autoimmune Diseases Autoimmune thrombocytopenic purpura Target Glands: Platelets Autoantibodies Antiplatelet antibody Celiac disease Target Glands: Small intestines Autoantibodies Anti-transglutaminase(tTG) Antibodies to deaminated gliadin peptides (DGPs) Endomysial antibodies Organ-Specific Autoimmune Diseases Goodpasture's syndrome Target Glands: Kidneys and Lungs Autoantibodies: Antiglomerular basement membrane of the lungs and kidneys Organ-Specific Autoimmune Diseases grave’s disease Target Glands: Thyroid gland Autoantibodies: Thyroid stimulating hormone receptor antibodies (TRAbs) Antithyroglobulin Antithyroid peroxidase (TPO) Organ-Specific Autoimmune Diseases Hashimoto's thyroiditis Target Glands: Thyroid gland Autoantibodies: Antithyroglobulin Antithyroid peroxidase (TPO) Multiple sclerosis Target Glands: Myelin sheath of nerves Autoantibodies: Antibodies to myelin basic protein Organ-Specific Autoimmune Diseases Myasthenia gravis Target Glands: Nerve-muscle synapse Autoantibodies: Antibodies to acetylcholine receptors (AChR) Anti-muscle-specific kinase Antibody to the lipoprotein (LRP4) Organ-Specific Autoimmune Diseases pernicious anemia Target Glands: Stomach Autoantibodies: Parietal cell antibody Anti-intrinsic factor Poststreptococcal glomerulonephritis Target Glands: Kidneys Autoantibodies: Streptococcal antibodies that cross-react with kidney tissue Organ-Specific Autoimmune Diseases Primary biliary cirrhosis Target Glands: Intrahepatic bile ducts Autoantibodies: Antimitochondrial antibodies (AMA) Rheumatic fever Target Glands: Heart Autoantibodies: Streptococcal antibodies that cross-react with cardiac tissue Organ-Specific Autoimmune Diseases Scleroderma Target Glands: Connective tissues Autoantibodies: Antinuclear antibodies Anti-Scl-70 Anticentromere antibody Organ-Specific Autoimmune Diseases Sjogren's syndrome Target Glands: Eyes, mouth Autoantibodies: Antinuclear antibodies Rheumatoid factor Anti-salivary duct antibodies Anti-lacrimal gland antibodies Organ-Specific Autoimmune Diseases Type 1 Diabetes mellitus Target Glands: Pancreas Autoantibodies: Anti-insulin Islet cell antibodies Anti-IA-2 and anti-IA-2ßA Antibody to glutamic acid phosphatase