The thymus gland is an important part of the immune system. It is located in the chest behind the sternum and between the lungs. The thymus plays a vital role in the development and maturation of T lymphocytes, which are critical cells that help the body fight infection. However, there are several diseases and disorders that can affect the thymus gland and impair its function.
Anatomy and Function of the Thymus Gland
The thymus gland reaches maximum weight during puberty and begins to slowly atrophy after adolescence. It is made up of two lobes and contains two main cell types:
- Epithelial cells – form the structure of the thymus.
- Lymphocytes – immature white blood cells.
The main functions of the thymus gland are:
- Maturation of T lymphocytes – the thymus provides an environment for immature T lymphocyte cells, known as thymocytes, to develop into mature, immune competent T cells.
- T cell selection – self-reactive T cells that may cause autoimmune disease are eliminated in the thymus.
- Hormone production – thymus hormones influence T cell development.
Therefore, diseases affecting the thymus can impair immune function by reducing T lymphocyte numbers and activity.
Primary Immunodeficiencies Affecting the Thymus
Primary immunodeficiencies are genetic disorders that impair the immune system. Some types specifically affect T lymphocyte development and thymic function:
Severe Combined Immunodeficiency
Severe combined immunodeficiency (SCID) is caused by genetic defects leading to impaired development and function of T cells and other immune cells. Patients have increased infections.
DiGeorge Syndrome
DiGeorge syndrome is caused by a deletion in chromosome 22, leading to poor development of the thymus and parathyroid glands. Affected infants have very low T cell levels.
Wiskott-Aldrich Syndrome
This X-linked primary immunodeficiency affects T and B cell function. The thymus is small in size. Recurrent infections are common.
Ataxia Telangiectasia
This autosomal recessive disorder causes progressive cerebellar degeneration. It impairs thymic development, leading to reduced naive T cells.
CHARGE Syndrome
CHARGE syndrome is a genetic condition causing colobomas, heart defects, atresia of the nasal choanae, retardation of growth/development, genital abnormalities, and ear abnormalities. Many patients have thymic hypoplasia.
Secondary Immunodeficiencies Affecting the Thymus
In secondary immunodeficiencies, an acquired factor leads to impaired immune function. Some examples affecting the thymus are:
HIV/AIDS
HIV infection leads to severe loss of CD4 T cells. It also causes damage to the thymus, depleting thymic progenitors needed to produce new T cells.
Chemotherapy
Some chemotherapy agents used to treat cancers can cause thymic toxicity. This impairs the ability to replenish T cell populations.
Corticosteroids
Long-term corticosteroid therapy causes thymus atrophy. This reduces naive T cell output.
Aging
As humans age, the thymus undergoes fatty infiltration and progressively diminishes in size and activity. This age-related thymic involution leads to reduced naive T cell production.
Malnutrition
Protein-calorie malnutrition causes atrophy of lymphoid tissues including the thymus gland. Thymic function improves with nutritional rehabilitation.
Autoimmune Disorders Affecting the Thymus
Some autoimmune diseases target and damage the thymus gland itself:
Myasthenia Gravis
Myasthenia gravis is caused by autoantibodies against acetylcholine receptors on muscle cells. In early-onset cases, patients make antibodies against proteins in thymic epithelial cells. This leads to thymus inflammation or thymoma formation.
Thymoma
Thymomas are rare tumors derived from thymic epithelial cells. About 30% are associated with autoimmune diseases like myasthenia gravis, red cell aplasia, or hypogammaglobulinemia.
Graves Disease
Graves disease is an autoimmune thyroid disorder. It can be associated with thymic hyperplasia, where the thymus enlarges due to increased lymphocyte proliferation.
Infections Affecting the Thymus
Infections can sometimes directly infect the thymus gland:
Cytomegalovirus
Cytomegalovirus (CMV) is a common herpesvirus. CMV infection of the thymus impairs T cell development and causes thymic atrophy.
HIV
As described earlier, HIV infects and destroys thymocytes and disrupts normal T cell maturation in the thymus.
Fungal Infections
Invasive fungal infections such as candidiasis can affect immunocompromised patients. Disseminated disease can infect the thymus.
Congenital Syphilis
Congenital syphilis can cause inflammation of the thymus and other lymphoreticular organs in infected infants.
Thymic Neoplasms
Abnormal growths can arise from cells within the thymus:
Thymoma
Thymomas are the most common tumor of the anterior mediastinum. They originate from thymic epithelial cells and may compress nearby structures.
Thymic Carcinoma
Thymic carcinomas are more aggressive cancers arising in the thymus, and account for about a third of anterior mediastinal tumors.
Thymic Cancer Metastasis
Cancers from other sites like the lung, breast, or lymphoma may metastasize to the thymus gland.
Thymic Cysts
Cystic lesions may develop from remnants of the thymopharyngeal duct. Most are benign thymic cysts.
Other Disorders Affecting Thymic Structure or Function
Some other conditions can impair normal thymus gland structure or activity:
Radiation Therapy
Radiation to treat mediastinal cancers can cause fibrotic damage to the thymus.
Burns
Thermal injury from burns results in rapid loss of thymic mass and affects T cell function.
Congenital Heart Disease
Some infants with certain congenital heart defects have underdeveloped thymus glands. This may contribute to their increased risk of infections.
Chromosome 22q11.2 Deletion
This genetic deletion syndrome is associated with thymic hypoplasia and impaired T cell function.
Trisomy 21
Down syndrome (trisomy 21) is associated with abnormalities in thymus development, morphology, and involution.
Conclusion
The thymus plays an essential role in immune function, and a wide range of diseases and disorders can affect its anatomy and physiology. These include primary and secondary immunodeficiencies, autoimmunity, infections, cancers, congenital abnormalities, and therapy effects. Further research on the thymus gland may provide insight into preserving thymic function and improving immune competence. Maintaining a healthy thymus is key for robust T cell-mediated immunity.
References
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