Autoimmunity, PDF

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

10 AUTOIMMUNITY AUTOIMMUNITY Disorders in which immune responses are targeted toward self-antigens and results in damage to organs and Can be due to tissues in the body. 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 Anti-RBC Lupus Multiple Anti-PLT Erythematos cells Anti-lymphocyte us (SLE) Anti-ribosomal complement Anti-endothelium Rheumatoid 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 and Clinical Signs systems - including your joints, Symptoms skin, kidneys, blood cells, brain, heart and Nonspecific lungs. like fatigue, weight loss, malaise, fever, and anorexia. Symmetrical arthritis Erythematous rash Other systemic effects involving the 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 Thrombocytop count enia ESR Increased CRP Normal to Low Complem Low ent Antinuclear antibodies (ANAs) Heterogenous group of antibodies that have different antigen specificities. AutoAb Immunofluorescent Disease pattern Association Anti-dsDNA Peripheral or SLE homogenous Anti-ssDNA Not detected on SLE routine screen Antihistone Homogenous Drug-induced SLE SLE Anti-DNP Homogenous Drug-induced SLE Anti-Sm Coarse speckled Diagnostic for  AutoAb Immunofluorescent Disease pattern Association Anti-SS-A Finely speckled SLE (Ro) Sjögren's Anti-SS-B Finely speckled syndrome (La) Prominent staining Antinucleola nucleoli (smooth, of SLE r Systemic clumpy, or speckled) sclerosis Systemic Anti-Scl-70 Atypical speckled sclerosis Scleroderma Anti-Jo-1 Fine cytoplasmic Polymyositis speckling Anti- Discrete speckled CREST centromere 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 Antihistone luciliae. 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 Speckled specific for SLE) 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 inCentromere Scleroderma. 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 Hashimoto's thyroiditis Target Glands: Thyroid Target Glands: Thyroid gland gland Autoantibodies: Autoantibodies: ⚬ Thyroid stimulating ⚬ Antithyroglobulin hormone receptor ⚬ Antithyroid antibodies (TRAbs) peroxidase (TPO) ⚬ Antithyroglobulin ⚬ Antithyroid peroxidase (TPO) Organ-Specific Autoimmune Diseases 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 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