MadSci Network: Immunology |
A special tip of the hat to Mr. Gurler's query as he is from my place of birth (Ankara, Turkey) and also since his question pertains to autoimmune diseases, the ultimate focus of many current projects in T cell function. Basically, despite having evolved to protect the body, the immune system will sometimes attack its own tissues due to a variety of genetic and environmental factors, causing diverse diseases such as lupus, multiple sclerosis, Behçet disease, or indeed Hashimoto's thyroiditis, depending on which organs or tissues are targeted for self-destruction. Towards the end of this response I will speculate a bit on why people get these types of diseases at all, but first let's rewind a century to review the historical context of the discovery of Hashimoto's thyroiditis. Hakaru Hashimoto (1881-1934), a physician from Kyushu, Japan first published the description of this condition in the medical literature in 1912, referring to it as a "lymphomatous goiter". meaning a swollen neck due to increased numbers of white blood cells accumulating in the area. A curious coincidence that may be of particular interest to Mr. Gurler is that Dr. Hashimoto was born in the same year as Ataturk and likewise died an untimely death 4 years prior to the founder of Turkey. modernizing the country, including its medical system. To put this connection in the context of another autoimmune disease, Istanbul University was established in place of the Ottoman Dar-ul Fünun in 1933, where Dr. Hulusi Behçet established the Department of Dermatology. Several years later, he would submit the first description of Behçet disease, another autoimmune condition involving inflammation of the blood vessels. Clearly, this decade was a busy time for medical research and in particular the discovery of many autoimmune disorders, until the onset of WW2 caused the shift in medical focus away from research to treating battlefield injuries. In Hashimoto's disease, lymphocytes (including T cells specific for self-antigens) invade the thyroid gland (located midway in the neck, i.e.. below the Adam's apple) and destroy the follicles which produce thyroid hormones such as thyroxine, calcitonin, and triiodothyronine, leading to "hypothyroidism" (insufficient levels of thyroid hormones). These molecules regulate key processes in the body such as metabolic rate, protein synthesis, calcium levels and sensitivity to other hormones. Thus, not having enough can lead to drastic consequences. Curiously, in the initial stages of disease there can be marked "hyperthyroidism", possibly due to antibodies to the hormones cross-linking these messengers and temporarily increasing their potency. Symptoms may include behavioral maladies such as depression, fatigue and mania, as well as physiological signs such as weight gain and elevated heart rate. Hypothyroidism can be treated by taking hormone supplements, but barring future solutions involving regenerative medicine (e.g. using stem cells), the patient will have to continue treatment indefinitely. Why do people get autoimmune diseases such as Hashimoto's, where healthy tissues are attacked by the immune system? One theory is that certain individuals are genetically predisposed to having higher levels of auto-reactivity, due to their ancestors having survived epidemics by having more potent immune responses encoded as variations in their genomes. This is passed on to their progeny in the form of genetic variation, and maintained in the population in general if it confers an advantage in surviving childhood infections, for example. Indeed, certain immune-related genetic factors such as the presence of HLA-DR5 (a class II MHC variant) and decreased CTLA-4 function expression occur more frequently in Hashimoto's patients than the overall population. Autoimmune diseases are also more prevalent in women then men (including Hashimoto's). This is thought to be due to the fact that females have more potent immune systems, thus increasing the risk that reactivity to microbes may spill over into targeting otherwise healthy tissues. The immune system is indeed a double-edged sword, and one drawback of keeping such dangerous cells in the body is that they can sometimes turn against their own.
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