Thymus

The thymus is the primary lymphoid organ responsible for the maturation and selection of T lymphocytes (T cells), which are central to adaptive immunity. Immature T cell precursors migrate from the bone marrow to the thymus, where they undergo a two-stage selection process: positive selection ensures T cells can recognize self-MHC molecules, while negative selection eliminates autoreactive T cells that might attack the body's own tissues. Mature, immunocompetent T cells then exit the thymus and circulate throughout the body.

The thymus undergoes progressive age-related involution (shrinkage and replacement by fat) beginning around puberty. By middle age, most of the thymic tissue has been replaced by adipose tissue, and T cell production declines significantly. This gradual loss of thymic function contributes to immunosenescence—the age-related decline in immune function—which explains why older adults have reduced responses to new antigens, vaccines, and are more susceptible to infections and cancers.

Myasthenia gravis is an autoimmune neuromuscular disorder in which the body produces antibodies against acetylcholine receptors at the neuromuscular junction, causing muscle weakness and fatigue. Approximately 75% of patients with myasthenia gravis have thymic abnormalities—either thymic hyperplasia (enlarged, overactive thymus) in younger patients or thymoma (a thymic tumor) in older patients. Thymectomy (surgical removal of the thymus) often results in significant improvement or remission of symptoms.

DiGeorge syndrome (22q11.2 deletion syndrome) is a congenital condition caused by deletion of a region on chromosome 22, resulting in failure of the third and fourth pharyngeal pouches to develop properly. Because the thymus derives from these pouches, affected individuals are born with thymic aplasia (absent or severely underdeveloped thymus), causing profound T cell immunodeficiency. Patients are highly susceptible to viral, fungal, and opportunistic infections and may also have heart defects and hypocalcemia.

The thymus is located in the anterior superior mediastinum, behind the sternum and in front of the heart and great vessels. It is largest relative to body size during fetal development and continues to grow until puberty, at which point it weighs approximately 30-40 grams. After puberty, it involutes progressively, and by old age, it is largely replaced by fat, though small remnants of functional thymic tissue persist.