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The thymus gland is a small organ behind the breastbone that plays an important function both in the immune system and endocrine system. Though the thymus begins to atrophy (decay) during puberty, its effect in "training" T lymphocytes to fight infections and even cancer lasts for a lifetime.
Learn more about the role of the thymus in immunity, autoimmunity, and aging, as well as how several disorders may affect this important organ.
Anatomy
The thymus gland lies in the chest, directly behind the breastbone (sternum), and in front of the heart in the area between the lungs called the anterior mediastinum.
Sometimes, however, the thymus gland is found in another (ectopic) location, such as in the neck, the thyroid gland, or on the surface of the lungs (the pleura) near the area where the blood vessels and bronchi enter the lungs.
It is named the thymus due to its shape being similar to that of a thyme leaf—pyramid-shaped with two lobes. The two lobes of the thymus are broken down into lobules. These lobules have an outer cortex occupied by immature T lymphocytes, and an inner medulla occupied by mature T lymphocytes.
The thymus is considered a lymphoid organ (an organ of the immune system) similar to the tonsils, adenoids, and spleen.
Cells of the Thymus
A number of different cell types are present within the thymus gland.
- Epithelial cells:cells that line body surfaces and cavities
- Kulchitsky cells: cells that are the hormone-producing cells of the thymus or neuroendocrine cells
- Thymocytes:cells that become mature T lymphocytes
The thymus gland is also home to some macrophages. Macrophages are known as the "garbage trucks" of the immune system because they eat foreign matter.
Dendritic cells and a few B lymphocytes (the types of lymphocytes that produce antibodies) also reside in the thymus. Interestingly, the thymus gland also contains some myoid (muscle-like) cells.
Changes With Age
The thymus gland is large in infants, but after infancy, it grows and reaches its maximum size during puberty.
After puberty, the thymus gland shrinks and becomes largely replaced with fat.
The gland is very small in elderly people, but can sometimes atrophy prematurely in response to severe stress. The term used to describe the atrophy of the thymus gland with age is "thymic involution."
Function
The thymus gland is very active from before birth until puberty, and it functions as both a lymphatic organ and an endocrine organ (an organ of the endocrine system that produces hormones). In order to understand the role the thymus gland plays in immunity, it's helpful to first distinguish between T lymphocytes and B lymphocytes.
T Cells vs. B Cells
T cells (also known as T lymphocytes or thymus-derived lymphocytes) mature in the thymus gland and play a central role in cell-mediated immunity, meaning that the cells themselves are active in fighting off foreign invaders such as bacteria, viruses, cancer cells, and more.
In contrast, B lymphocytes are part of the humoral immune system and produce antibodies directed at specific invaders.
T Cell Training Ground
As part of the adaptive immune system, the thymus can be thought of as the training ground for T lymphocytes. During childhood, immature T cells (called progenitor cells) that originate in the bone marrow travel via the bloodstream to the thymus gland where they mature and differentiate into specialized T cells.
Types of T Cells
T cells in the thymus differentiate into three primary types:
- Cytotoxic T cells: The word cytotoxic means "to kill." These cells are responsible for directly killing infected cells.
- Helper T cells: These cells are responsible for both causing production of antibodies by B cells and activating other types of T cells to address a foreign invader.
- Regulatory T cells:These cells function as "police." They suppress both B cells and other T cells.
Positive and Negative Selection
The immature T cells that leave the bone marrow enter the thymus in the cortex (known as the classroom of the thymus). During "training," these cells are taught to recognize antigens associated with foreign cells and matter in a process called positive selection. Cells are positively selected for usefulness.
Once the T cells have learned to recognize specific pathogens, they travel to the medulla to undergo "negative selection." In the medulla, the mature T cells are introduced to the body's own antigens. Since T cells that would react with the body's antigens could attack a person's own cells, these cells are eliminated.
T cells are negatively selected for autoimmunity, and these self-attacking cells either die or are turned into regulatory cells.
Not all T cells make it through the selection process—only around 2% eventually make it through positive and negative selection.
The survivors are then exposed to hormones produced by the thymus gland to complete their maturation before being released to do their job (circulating in the bloodstream or waiting in the lymph nodes for foreign invaders).
Roles of Mature T Cells
The mature T cells derived have a few major roles.
Immunity
T cells are part of the adaptive immune system, in which each T cell has been trained to recognize a particular antigen. When exposed to a foreign cell, cytotoxic T cells lock onto the cell and kill it with assistance from helper and regulatory T cells.
This is also referred to as cell-mediated immunity, as it involves the use of immune cells to fight infections.
Autoimmunity
In general, T cells are barricaded in the cortex of the thymus so they do not become sensitized to the body's own cells. However, the process of negative selection in the medulla is used to get rid of cells that accidentally have become sensitized to "self."
This function helps prevent the development of autoimmune disorders, which are medical conditions in which the body attacks its own tissues rather than foreign invaders. If the thymus gland is removed early in life, a person has an increased risk of developing one of these disorders.
Aging
In recent years it's been determined that aging isn't simply a process in which the body wears out, but is actually an active process.
In other words, we are designed to age, and the involution of the thymus gland may be a form of programmed aging, with the involution (beginning around age 60) being the trigger for the deterioration of the immune system with age.
This decrease in immunity as a result of thymus involution can increase the risk of infections and reduce the response to vaccines.
A number of studies have looked at methods to delay the atrophy of the thymus with hopes of slowing the aging process. Early studies suggest that calorie restriction may slow the atrophy, but the research is still in its infancy.
Hormone Production
The thymus gland produces several hormones including:
- • Thymopoietin and thymulin: Hormones that assist in the process where T cells differentiate into different types
- • Thymosin: Accentuates the immune response as well as stimulating pituitary hormones such as growth hormone
- • Thymic humoral factor: Acts similarly to thymosin, but increases the immune response to viruses in particular
The thymus gland may produce small amounts of some hormones produced in other areas of the body, such as melatonin and insulin. Cells in the thymus gland (such as epithelial cells) also have receptors through which other hormones can regulate its function.
Associated Conditions
There are a number of diseases and disorders that can affect the thymus gland, ranging from genetic disorders that are evident at birth, to cancers that are most common in older adults. These disorders can lead to problems with immunity and autoimmunity, such as myasthenia gravis and hypogammaglobulinemia.
Hypoplasia/Aplasia of the Thymus
The developmental disorder called DiGeorge syndrome is an uncommon condition marked by a significant reduction or absence of thymus function. Caused by a gene mutation, children with the condition have severe immunodeficiency and a high risk of infections, as well as hypoparathyroidism.
Thymic Follicular Hyperplasia
Enlargement (hyperplasia) of lymphoid follicles in the thymus gland is often seen in autoimmune diseases such as myasthenia gravis, Graves' disease, and lupus.
Thymic Cysts
On their own, thymic cysts are often an incidental finding, but they can be important in that they sometimes hide cancer (thymoma or lymphoma).
Tumors of the Thymus Gland
Thymomas are tumors that arise in thymic epithelial cells of the thymus gland and may be benign (usually harmless) or malignant (cancerous). They may occur in the usual location of the thymus gland in the mediastinum, but also in other regions where the thymus gland is sometimes located such as the neck, thyroid gland, or on the lungs.
Other tumors that may occur in the thymus include thymic lymphomas, germ cell tumors, and carcinoids.
Symptoms of thymomas may be related to the location of the tumor in the chest (such as shortness of breath), but these tumors may also be discovered due to paraneoplastic syndromes associated with the tumor. There are several of these types of conditions:
- Myasthenia gravis (MG): The autoimmune condition myasthenia gravis occurs in roughly 25% of people with thymomas, but may also occur with thymic hyperplasia. MG is an autoimmune neuromuscular disease caused by problems in communication between nerves and muscles. It is characterized by profound weakness of muscles (both in the extremities and respiratory muscles—this can lead to breathing problems).
- Pure red cell aplasia: This condition is a rare autoimmune disorder in which T cells are directed against the precursors of red blood cells, leading to severe anemia. It occurs in roughly 5% of people with thymomas.
- Hypogammaglobulinemia: Hypogammaglobulinemia (low levels of antibodies) occurs in roughly 10% of people with thymomas.
Thymomas may also cause a condition referred to as thymoma-associated multiorgan autoimmunity. This condition is similar to the rejection seen in some people who have had organ transplants (graft vs. host disease). In this case, the thymic tumor produces T cells that attack a person's body.
Thymectomy
Surgery to remove the thymus gland may be done for a number of reasons. One is for congenital heart surgery. A congenital heart condition is a birth defect of the heart. Due to the location of the thymus gland, it must be removed for surgeons to gain access to the heart in infants.
Another common reason for this surgery is for a person with thymic cancer. In addition, myasthenia gravis (MG) is another condition treated with a thymectomy. When the thymus gland is removed, roughly 60% of people with myasthenia gravis achieved remission.
However, it can take months to years for these effects to be apparent with myasthenia gravis. When used for MG, surgery is usually done between puberty and middle age to avoid the potential consequences of removing the thymus gland earlier in life.
Consequences of Thymus Removal
The thymus gland provides a critical role in cell-mediated immunity, but fortunately, a significant part of this benefit occurs before birth (the T cells formed during development in the uterus are long-lasting). However, there are potential consequences of removal early in life, such as when the thymus is removed during heart surgery in infants.
It appears that early removal may increase the risk of developing infections, the development of autoimmune diseases (such as autoimmune thyroid disease), the risk of atopic disease (allergies, asthma, and eczema), and possibly the risk of cancer, as T cells perform a vital role in preventing cancer.
There is also some evidence that thymus removal may be associated with premature aging of the immune system.