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Download Thyroid Autoimmune Diseases
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Thyroid Autoimmune Diseases Mechanisms of development of Autoimmune endocrine disease: Two factors could be involved in development of human autoimmune disorders: • Expression of Class II MHC (HLA: human leukocyte antigens) on the surface of the target endocrine cells. • The antigen Cross-reactivity Expression of Class II HLA on The Target Cells Infectious agent (or self-antigen) Inflammatory cells chemotaxis & production of INFγ Expression of HLA genes (MHC class II) Presentation of own cellular proteins Reactive T and B cell response. The antigen cross-reactivity: Infectious agents or external organic material epitopes show antigenic cross- reactivity with self tissues. formation of auto-reactive antibodies. Humoral immune response against self tissues Tissue destruction. Chronic Lymphocytic Thyroiditis: (Hashimoto’s Thyroiditis): • The first disease recognized as autoimmune disease by the Japanese specialist (Hakaru Hashimoto) in Germany in 1912. • The thyroid gland is attacked by cell- and antibody-mediated immune processes. • Hypothyroidism, large and lobulated thyroid gland due to lymphocytic infiltration and fibrosis. General considerations: • Family history of thyroid disease. • HLA gene polymorphism (DR3,DR4, DR5). • CTLA-4 *gene polymorphism (cytotoxic Tlymphocyte associated protein) result in reduced negative regulation of T-cells. • Most common in middle-aged, starts in adulthood. • Woman to men ratio is 5-10: 1. • Associated with other autoimmune diseases such as: SLE, dermatitis, and scleroderma. Other risk factors: • Chromosomal disorders: Turner, Klinefelter’s and Down’s Syndrome. • Tobacco smoking. Immunological features: • Lymphocytic infiltration of the thyroid gland • Presence of antibodies against thyroid antigens. • Cellular sensitization to thyroid antigens. n Pathogenesis of chronic thyroiditis: •Expression of MHC class II-self epitope complex on the thyroid cell surface. • Thyroid cell-CD4+ Lymphocyte interaction. • Chemotaxis of CTL and macrophages. • Loss of T lymphocyte suppressor function due to CTLA gene A mutation: CTL-thyroid cell interaction and killing of target cells by apoptosis. n • Engulfment of cellular peptides by macrophages; antigen presentation. • Activation of B lymphocytes and production of anti- thyroid peroxidase and anti-thyroglobulin antibodies • ADCC of cuboidal cells lining the thyroid follicles by CD8 and N.K cells. Stages & Clinical Features of Chronic Thyroiditis: • Primary stage: Transient hyperthyroidism due to inflammatory breakdown of thyroid follicles (silent painless inflammation). Release of thyroid hormones. • Late stage: Hypothyroidism due to progressive destruction of thyroid tissue and cellular malfunction. • The last outcome of Hashimoto’s disease is hypothyroidism. • A consistent physical sign in Hashimoto’s disease is enlarged thyroid gland (Goiter). • Enlarged surrounding lymph nodes. • Weight gain, muscle weakness, cold intolerance, depression, fatigue, constipation, periorbital edema , hoarse voice and dry skin. • Rarely, symptoms of urticaria and nephritis can be seen due to presence of circulating immune complexes. Diagnosis of Chronic Thyroiditis: o The disease is diagnosed by the presence of autoantibodies: ▫ Anti-thyroglobulin* antibodies. ▫ Anti-thyroid peroxidase antibodies. o These antibodies can be detected by: ▫ Immunofluorescence assay , ELISA or agglutination assay. o In seronegative patients, autoantibodies are localized intrathyroidal. o Histopathology N • Germinal center formation within thyroid tissues: reactive lymphocyte infiltrate. • Pink: dying thyroid cell • Immunohistochemistry for P63. Positive in Germinal center (not found in normal glands). Before After Graves’ Disease: • It is an autoimmune disease where the thyroid is activated by anti-TSH receptor autoantibodies to produce excessive amount of thyroid hormones. • The most common cause of hyperthyroidism (60-90%), affects up to 2% of the female. • 5-10 more common in females than in males. • It has a powerful hereditary component General Considerations: • Hyperthyroidism and thyrotoxicosis with a diffuse goiter. • About 30-50% of people with Graves' disease will also suffer from Graves' ophthalmopathy caused by inflammation of the eye muscles by attacking autoantibodies. • Exophthalmos: upper eyelid retraction, edema, erythema, and conjunctivitis. Graves’ Goiter and Exophthalmos • Specific cross-reactivity between some microbes (viruses; Coxsackieviruses, and bacteria; Yersinia enterocolitica) and TSHreceptors on thyroid follicular cells. • Strong association with DR3, DQα , and DQβ genotype of MHC II haplotypes • Family History: increased risk if other family members are affected. • Associated with different types of autoimmune diseases; such as Hashimoto’s disease and antibodies to gastric intrinsic factors.* Clinical presentation: o Goiter, exophthalmos (30-50%), muscle weakness, weight loss, diarrhea and frequent defecation, hyperactivity, tachycardia, hair loss, and oligomenorrhea. o Immunologic features of Graves’ disease: • Antibodies against TSH receptor; that stimulate thyroid cell function. • Class II HLA expression on the surface of thyroid cells. • Associated autoimmune ophthalmopathy. N Autoantibodies present against TSHreceptor: • Thyroid-stimulating immunoglobulins (TSI): Activate TSH-receptor; increase thyroid hormones levels. • Thyroid growth immunoglobulins (TGI): Growth of thyroid follicles. • Thyrotrophin binding-inhibiting immunoglobulins (TBII): Inhibits TSH binding. • Colloid suspension show lymphocytic infiltration: CD4, CD8, and B lymphocytes. • No cellular immune response; Histology shows no destruction of thyroid tissues. Pathogenesis mechanism of Graves’ disease: N N n Diagnosis of Graves’ disease: o Clinically: Signs and symptoms. o Radiologically: Increased uptake of radioactive iodine. o Serology: ▫ Elevated total and free T4, and T3. ▫ Identification of anti-thyroid antibodies in patient’s sera: • Thyroid stimulating Immunoglobulin (TSI). • Thyroid growth stimulating immunoglobulins • Thyroid binding-inhibiting immunoglobulins Anti-thyroid antibodies can be detected by: • ELISA Test: Microtiter plate wells should be coated by recombinant human TSH-receptors. • Tissue culture(Fisher Rat thyroid cell line) measure the presence and activity of antithyroid antibodies (IgG) in patient's sera. ▫ Serum specimens are incubated with rat thyroid cell line culture; then the incorporation of radioactive thymidine (pyrimidine) are measured. (action of N