The thymus is an essential component of our immune systems. In simple terms, it is a primary lymphoid organ that functions as the initial site of T cell immune maturation development. T cells gain their name as they mature in the thymus and B cells are so named, as they mature in the bone marrow. This article will look at the anatomy of the thymus including the blood supply and innervation, as well as some histological anatomy and embryological development. We will also discuss function and clinical relevance.
- Clinical points
The thymus gland has dual embryonic origin. Thymic epithelium develops during the sixth week of gestation, from the ventral diverticular epithelium of the third pharyngeal pouch along with the thyroid and parathyroid gland. It extends posterolaterally into the surrounding mesoderm as two flask like structures. The cells that line these flask like structures give rise to further proliferation, and are eventually surrounded and invaded by the mesoderm. It shares it origin with the thyroid and parathyroid glands. During the 8th week of gestation the thymus descends and takes up its final position in the anterosuperior mediastinum. It fuses with its counterpart from the opposite side. Late in development, the hematopoietic bone marrow precursor cells (mesenchymal origin) migrate into the thymus, and this is how the thymocytes come into contact with the thymus gland, and the lymphoid tissue becomes unified with the epithelial cell framework of the thymus. The growth and development of thymus continues until puberty. There are two distinct cell types within the thymus i.e. the lymphoid cells (thymocytes) and the reticular epithelial cells.
In children, T cells densely populate the cortex of the thymus. As the T cells develop they pass to the medulla, before they are released into the circulation. By the age of adolescence, the thymus gland begins to atrophy. Many factors play their role in involution process, the level of circulating hormones in the blood i.e. sex hormones also cause the gland to atrophy and is replaced by fat.
The thymus gland is a soft bilobed organ which is encapsulated. It lies in the superior mediastinum and in the anterior part of the inferior mediastinum, close to the pericardium, anterior to the great vessels of the heart, and deep to the sternum. It extends from the level of the inferior poles thyroid gland above, to the fourth costal cartilage. Parallel to the gland on its left and right side are the phrenic nerves (which go on to supply the diaphragm). The two distinct lobes of the thymus are connected in the midline by an isthmus.
There are numerous thymic arteries that follow the course of the interlobular septae, and are able to enter the substance of the organ. In the cortex of the thymus, the arteries form a series of complex arcades and in association with the reticular endothelial cells and white blood cells (lymphocytes and macrophages) form the blood thymus barrier. Thymic capillaries have non fenestrated endothelium and thick basal lamina making it impermeable to proteins. Blood then drains into the medullary veins. Blood supply to the thymus comes from the internal thoracic artery as well as the superior and inferior thyroid arteries. Drainage is to the left innominate vein as well as the superior, middle and inferior thyroid veins.
The thymus has no afferent lymphatics. The lymph drains to the thymic lymph nodes located near the gland i.e. the internal mammary-parasternal, tracheobronchial-hilar, and mediastinal-brachiocephalic.
Thymus is covered by a connective tissue capsule, the septa of which penetrate into the tissue and divides it into incomplete lobules. Each lobule has a peripheral dark zone called cortex and middle lighter zone called medulla.The capsule is made up of inner and outer layers of collagen and reticular fibres, the lymphocytes are found in between.
This is the outer portion of the thymus gland and contains a large number of small densely packed precursors of T lymphocytes (thymocytes). It also contains epithelial reticular cells and macrophages. The blood vessels of the thymus also lie within this network of epithelial reticular cells. The cortex is where the very early stages of thymocyte development take place, and where the rearrangement of the genes for the receptors on the surface of T cells takes place.
This had numerous blood vessels, has little connective tissue and mature T lymphocytes. B cells and dendritic cells are also found here. Type IV epithelial reticular cells are also present here.
This is the central portion, and is where the network of reticular endothelial cells is denser and where the lymphoid cells are fewer. There are also a number of concentric bodies known as Hassall’s corpuscles. They are flattened epithelial reticular cells concentrically arranged and filled with keratin filaments. Also Within these corpuscles is a central mass of a few granular cells. Some thymocyte development, at latter stage, also occurs in the medulla. The thymocytes located here have passed through the cortex and undergone receptor gene rearrangement and positive selection, with a small amount of negative selection. The medulla is therefore the site at which the vast majority of negative selection takes place.
The thymus is the location where the haemopoietic precursor cells mature into T cells. Pro-thymocytes will migrate from the bone marrow, and enter the thymus gland at the corticomedullary junction. Once the maturation process has been completed, these T cells enter the circulation, and form the basis for the adaptive immune system. The T cells have receptors that are generated from the random shuffling of gene segment.s Initially, a process known as positive selection (which occurs in the cortex) functions, which checks if the developing T cell is able to recognise self MHC proteins (major histocompatibility complex; a set of proteins on the own cell surfaces of a person (that are essential for the adaptive immune system to recognise pathogens), and hence able to recognise the person’s own cells from foreign cells. Cells that do not perform this reaction, or perform it too weakly, are prevented from entering further development.
The next stage is negative selection, where the T cells undergo the process of interaction with thymic dendritic cells. Those cells with a high level of autoreactivity are eliminated, to reduce the likelihood of autoimmune reactions. As a result of this process, there is a large amount of T cells built up over early life, so that by adulthood the organ is largely obsolete and is degraded. The gland does continue to have endocrine function.
T cells are divided into T-helper cells and T-killer cells (cytotoxic cells). Cytotoxic T cells have CD8+ proteins on their surface, and attach to infected cells and destroy them directly. Helper T cells receive information about the pathogen from the antigen presenting cells (B cells and macrophages), and therefore coordinate the immune response (release cytokines which cause further white blood cell division, drive the production of memory B cells for future infections from that pathogen etc.).
This is an uncommon tumour arising from the epithelial cells of the thymus gland. It has an association with myasthenia gravis in 20% of patients. Other risk factors include advanced age and Asian ethnicity. Symptoms are caused by the expanding tumour compressing surrounding structures, e.g. vena cava compression, dysphagia, cough, chest pain etc. Diagnosis is made by a CT scan, and treatment is surgery with additional chemotherapy and radiotherapy in some cases.
This is an autoimmune condition characterized by worsening tiredness as the day goes on, and muscles are used. The symptoms result from autoimmune destruction of the acetylcholine receptors found in postsynaptic neuromuscular junctions due to autoantibodies.
Diagnosis is made with the tensilon test (edrophonium; a short acting acetylcholinesterase inhibitor is given to the patient) that temporarily improves symptoms. Treatment is with long acting acetylcholinesterase inhibitors, as well as immunosuppressant drugs. Surgery to remove the thymus gland (and hence reduce the number of autoantibodies) is also a treatment option.
Prognosis of the condition is generally good. If the medication is well adhered, the quality of life is also good. Patients require monitoring over the first few years as many patients have a myasthenia crisis within this time.
Di George syndrome (22q deletion)
In this syndrome there is an aplasia of the thymus that causes profound detrimental effect on T-cell development and causes immunodeficiency and hence susceptibility to infections. No other white blood cells are affected. The other features of this syndrome are the cardiac abnormality, cleft palate and hypoparathyroidism.