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Hashimoto´s Thyroiditis, Grave´s Disease and Neonatal Thyrotoxicus

by Peter Delves, PhD
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    00:01 There are a number of thyroid autoimmune diseases.

    00:04 But by far the most common are the two that are shown here - Hashimoto’s disease and Grave’s disease.

    00:14 In Hashimoto’s disease, there are autoantibodies against the enzyme thyroid peroxidase and against the molecule thyroglobulin, which is a molecule upon which the thyroid hormones are generated.

    00:30 Autoantibodies will bind to the thyroid epithelial cells and there will also be lymphocytic infiltration of the thyroid with subsequent destruction of the thyroid tissue by cytotoxic T-lymphocytes, releasing perforin and granzyme which will destroy the thyroid epithelial cells.

    00:55 The autoantibodies that are bound to the thyroid epithelial cells can activate the classical pathway of complement, leading to the generation of the membrane attack complex which can also contribute to the damage.

    01:11 The result of the destruction of the thyroid tissue is hypothyroidism - an underactive thyroid with reduced production of thyroid hormone.

    01:24 In contrast, in Grave’s disease there are autoantibodies that bind to the TSH receptor, the thyroid stimulating hormone receptor.

    01:38 Crucially, these autoantibodies act as agonists to the receptor, they mimic the effect of TSH.

    01:46 And therefore they are stimulatory autoantibodies.

    01:50 Following binding to the TSH receptor, there is stimulation of the thyroid epithelial cells, just like thyroid stimulating hormone would stimulate the thyroid epithelial cells.

    02:02 Here we have an autoantibody that is doing the same thing.

    02:06 And this results in hyperthyroidism.

    02:09 Now normally, once we’ve made enough thyroid hormone, there’s a feedback mechanism that stops the production of more thyroid hormone, reduces the level of TSH and everything will settle back to produce the needed level of thyroid hormone. Here you have plasma cells that are constantly pumping out these stimulatory autoantibodies. So there is no negative feedback on the autoantibody, so a constant stimulation of the thyroid leading to hyperthyroidism.

    02:39 There is a very interesting condition that is associated with a small number of autoimmune diseases.

    02:49 And in these particular types of autoimmune disease, there is a syndrome that is seen in the newborn where the newborn baby has symptoms that are very similar to the mother due to an autoimmune condition.

    03:06 One of the best described examples of this is neonatal thyrotoxicosis.

    03:12 In the mother, she is producing IgG antibodies against the TSH receptor.

    03:18 So this lady has Grave’s disease.

    03:22 But during pregnancy, IgG antibodies are passed across the placenta.

    03:27 Now most of those will be good IgG against common pathogens.

    03:32 But if amongst those IgG antibodies that are against pathogens, there are also autoantibodies of the IgG class.

    03:40 They can also go across the placenta.

    03:42 So the maternal IgG crosses the placenta.

    03:46 And this includes the anti-TSH receptor stimulatory autoantibodies.

    03:51 So this causes a condition that is very similar to Grave’s disease in the neonate.

    03:57 And this is referred to as neonatal thyrotoxicosis.

    04:02 In type I diabetes, the patient’s serum contains IgG that has bound to cells in the pancreatic islet that we can see here on this immunoflurescence tissue section of the pancreas.

    04:18 We can see that the patient’s serum is only staining one particular area of the pancreas.

    04:25 The exocrine pancreas is not stained.

    04:30 What is being stained here is the beta cells in the islets of Langerhans, because it is the beta cells in the pancreas that produce insulin.

    04:40 And the autoimmune attack is directed specifically towards the beta cells.

    04:49 The autoantibodies that are present in type I diabetes include autoantibodies to insulin, to the enzyme glutamic acid decarboxylase, to insulinoma antigen-2 (IA-2) and to the zinc transporter 8.

    05:08 These autoantibodies will bind to the surface of the beta cells.

    05:11 There is also lymphocytic infiltration of the pancreas with cytotoxic T-lymphocytes recognizing pancreas specific or beta cell specific peptides shown to the T-cell receptor on the cytotoxic T-lymphocyte.

    05:27 And the result is the destruction of the beta cells in the islets of Langerhans leading to hyperglycemia.

    05:34 Again the autoantibodies activating complement causing the generation of the membrane attack complex and the cytotoxic T-cells releasing perforin and granzymes causing apopototic cell death in the beta cells.


    About the Lecture

    The lecture Hashimoto´s Thyroiditis, Grave´s Disease and Neonatal Thyrotoxicus by Peter Delves, PhD is from the course Hypersensitivity and Autoimmune Disease. It contains the following chapters:

    • Goodpasture's Syndrome
    • Hashimoto’s Disease
    • Graves’ Disease
    • Type I Diabetes

    Included Quiz Questions

    1. Glutamic acid decarboxylase
    2. GPIb-IX
    3. H⁺K⁺ ATPase
    4. Citrullinated proteins
    5. Type IV collagen
    1. Thyroid peroxidase
    2. TSH receptor
    3. Type IV collagen
    4. Thyroid epithelial cells
    5. Fcγ
    1. Anti-TSH receptor IgG autoantibodies transferred across the placenta from mother
    2. Genetic defect causing proliferation of Anti-TSH receptor IgG autoantibodies
    3. Anti-thyroid peroxidase IgG autoantibodies transferred across the placenta from mother
    4. Genetic defect causing proliferation of anti-thyroid peroxidase IgM autoantibodies
    5. Anti-TSH receptor IgM autoantibodies transferred across the placenta from mother
    1. Destruction of beta cells in the islets of Langerhans
    2. Anti-RBC autoantibodies
    3. Destruction of basement membrane of pancrease
    4. Anti-beta cell autoantibodies that cause a stimulatory effect
    5. Deposition of citruliinated proteins in pancreatic islets of Langerhans

    Author of lecture Hashimoto´s Thyroiditis, Grave´s Disease and Neonatal Thyrotoxicus

     Peter Delves, PhD

    Peter Delves, PhD


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