Thymus

 Thymus

PKGhatak, MD

In adults the Thymus gland exists only in name; from the newborn to childhood till the onset of puberty the thymus, sitting in front of the heart, dominates. The thymus in children is the largest gland in the chest. The Greeks thought it was the center of anger and named it thymus. The thymus name was derived from thumos meaning anger. Galen was the first physician who correctly described the evolution of the thymus in childhood and greatly reduced in size in adults. In adults, the thymus produces only a few mature   T-cells throughout life.

The thymus grows from the third and fourth pharyngeal pouches, one on each side. As the two lobes of the thymus grow, the cavities in the stalk are closed off and only a vestige remains. The developing thymus lobes descend in the thorax and move close together towards the center and finally join together as one thymus gland.

Several genes encode the development and maturation of the thymus. Deletion of chromosome 22 results in absence of the thymus and clinically the condition is known as DiGeorge syndrome. This syndrome is incompatible with life beyond a few weeks after birth.

Unlike the pancreas and liver, the thymus is just one gland - an endocrine gland. It secretes Thymosin and other hormones. The task of the thymus is to train the immature lymphocytes to become super sleuths like FBI agents. That task has two aspects - a Positive Selection - is the ability to detect any antigen that is foreign to the human body, and the other is a Negative Selection that quality is not to a mistake and call normal body antigens as foreign agents. The positive section is delineated by the presence of specific receptors on T cells surface that have the ability to recognize MHC immune antigen. MHC stands for major histocompatibility complex. Once the lymphocytes are trained properly, they are released into circulation with an official T-Cell designation. T- cells (thymic lymphocytes) take residence in lymph nodes, and spleen and move around the body in the blood. T-cells are further differentiated in CD (cluster differentiation) grouping based on the presence of cell surface proteins. Out of this classification, the CD4 and CD8 T- cells are well known since HIV/AIDs became prevalent. This acquired quality is called the Adaptive Immune System as opposed to Innate immunity, as for example- the macrophages engulf bacteria.

There is a complex relationship between Testosterone and gut bacterial antigen in the development of Positive and Negative Senses. Testosterone modifies gut bacterial antigen that elevates negative sense, whereas, Estrogen suppresses negative sense. XX chromosome in females and the master gene AIRE gene (Autoimmune regulator) regulate gene expression that codes autoimmunity are active participants in this process.

 Structure of Thymus.

Each thymus gland has an outer zone of densely packed cells called the cortex and a loose collection of cells in the inner zone called the medulla. Each lobe is made up of several lobules.

The cells of the cortex are mostly thymocytes - newly arrived lymphocytes from the bone marrow waiting to be turned into T-cells. The epithelial cells in the cortex are arranged as a fine network of cells supporting the thymocytes. In the cortex, the thymocytes acquire positive selection.

The medulla has a rough distribution of epithelial cells and fewer thymocytes and collections of whorls of epithelial cell remnants from the stock of the third pouch. These whorls are distinct microscopic features of the thymus and are known as Hassall's corpuscles. In the medulla, the thymocytes acquire negative selection.

 Hormones and Cytokines of Thymus:

Thymosin, Thymulin and Thymopoietin are three secretory hormones of the thymus. The first two are involved in T-cells transformation and the thymopoietin helps to keep the mature T-cells to keep up the acquired adaptive immune property. The cytokines are interleukin class IL1, IL 6, GM-CSF, zinc- thymulin complex and other polypeptides.

 Diseases associated with Thymus gland disorder:

Myasthenia gravis. In thymoma or hyperplasia of the thymus the T- cell functions are derailed. The body develops antibodies to Acetylcholine receptors. Lack of action of acetylcholine is felt as facial muscle weakness, weakness of legs and fatigue.

 DiGeorge syndrome: Deletion of chromosome 22 results in a congenital abnormality of the heart, hair lip and cleft palate, esophageal tracheal fistula, absence of Thymus gland and total failure of adaptive immunity of T-cells. If the condition is recognized early in infants Thymus gland transplant is indicated.

SCID: Severe combined immunodeficiency disease. This results from the deficient maturation of hemopoietic progenitor cells. T-cells, B-cells, NK (natural killer) cells are deficient.

Autoimmune endocrine syndrome: In this syndrome, T-cells fail to acquire the Negative Selection knowledge while developing in the medulla of the thymus. Thyroid, Parathyroid, and Adrenal cortex are destroyed due to autoantibodies and hormones from these endocrine glands become deficient. Candida infection of the mouth and GI tract is also a common feature of this entity.

Thymoma is associated with multiorgan autoimmunity. In this disorder, thymus growth disturbs the normal development of T-cells. The disease resembles Graft vs Host Disease.

The thymus gland is damaged by radiation of the chest and chemotherapy for cancer. Regeneration of the thymus is possible, shown recently in experimental animals. The CCL11 cells of the damaged thymus stroma initiate the recruitment of peripheral Eosinophils. The natural killer cells and Th2 cells inter-react with eosinophils and restoration of structure and functions resume.

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