Question
Thymus
Answer
The thymus is a bilobed lymphoid organ situated in the anterior mediastinum, serving as the primary (central) lymphoid organ for T-lymphocyte maturation — the site where T cells acquire their antigen-specific receptor repertoire and are screened for self-tolerance before entering the peripheral circulation.
Structure: each lobe is divided into an outer cortex, densely packed with immature, rapidly proliferating thymocytes, and an inner medulla, containing more mature thymocytes and characteristic Hassall’s corpuscles (concentric whorls of degenerating epithelial cells, of uncertain but possibly regulatory function).
Function — T-cell education:
- Positive selection (in the cortex) — thymocytes whose T-cell receptor can recognize self-MHC molecules (with appropriate low-to-moderate affinity) are selected to survive; those unable to interact with self-MHC undergo apoptosis (a form of “death by neglect”) — ensures MHC restriction of the resulting T-cell repertoire.
- Negative selection (mainly at the cortico-medullary junction and medulla) — thymocytes whose receptor binds self-peptide-MHC complexes with high affinity are eliminated by apoptosis (clonal deletion) — the central mechanism generating self-tolerance in T cells. The AIRE (autoimmune regulator) gene promotes expression of a wide range of tissue-specific self-antigens in the medulla, allowing this screening against antigens that would otherwise only be found in peripheral organs.
- Thymocytes that survive both selection steps differentiate into mature single-positive CD4+ or CD8+ T cells and are exported to the periphery.
Involution: the thymus is largest and most active in early childhood and undergoes progressive age-related involution (replacement by fat) after puberty, though it retains some function throughout life; this underlies the reduced capacity for generating new T-cell diversity in older individuals.
Clinical significance: DiGeorge syndrome (thymic aplasia/hypoplasia due to a 22q11 deletion) results in severe T-cell immunodeficiency; thymectomy or thymic pathology (e.g., thymoma) is relevant in autoimmune conditions such as myasthenia gravis.