CorpusHuman Anatomy
Lymphatic & ImmuneLymphoid organ

Thymus

Thymus

Also known as: thymus gland

A bilobed primary lymphoid organ in the anterior superior mediastinum where bone-marrow-derived precursors mature into T lymphocytes and are selected to recognise self-MHC but tolerate self-antigens; it is largest in childhood and involutes after puberty.

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Overview

Weight≈ 15 g at birth; ≈ 30–40 g at puberty; mostly fat in old age
Thymocyte survival≈ 2–5% (95–98% die during selection)
Embryological origin3rd pharyngeal pouch endoderm

The thymus lies behind the manubrium in the superior and anterior mediastinum, in front of the pericardium, aortic arch and left brachiocephalic vein; in infants it is relatively huge and may extend up into the neck towards the thyroid and down over the heart. It consists of two asymmetric lobes joined in the midline by connective tissue. Its absolute weight peaks around puberty (≈ 30–40 g); thereafter it undergoes progressive involution, the functional tissue being replaced by fat, though small islands continue to produce new T cells into old age.

A thin capsule sends septa inwards, dividing each lobe into incomplete lobules, each with a dark-staining cortex packed with immature T cells (thymocytes) and a pale medulla that is continuous between lobules. Unlike lymph nodes, the thymus has no lymphoid follicles and no afferent lymphatics, and its supporting framework is not reticular fibres but a network of thymic epithelial cells (epithelial reticular cells). In the medulla these form Hassall (thymic) corpuscles — concentric whorls of keratinising epithelial cells that are diagnostic of the organ.

T-cell precursors enter at the corticomedullary junction and migrate outwards then inwards: double-negative (CD4⁻CD8⁻) cells in the subcapsular cortex rearrange their TCR genes and become double-positive (CD4⁺CD8⁺) cortical thymocytes; positive selection on cortical epithelial cells keeps only those that can recognise self-MHC (MHC restriction and commitment to CD4 or CD8); negative selection in the medulla, on medullary epithelial cells expressing tissue antigens under the control of AIRE and on dendritic cells, deletes strongly self-reactive cells or diverts them into regulatory T cells. About 95–98% of thymocytes die in the process; the survivors leave as naive single-positive T cells.

Location

Superior and anterior mediastinum, posterior to the manubrium and upper sternal body; in children it may extend into the lower neck.

Parts & subdivisions

  1. Capsule and septa
    Thin connective-tissue capsule (from neural-crest mesenchyme) with septa that carry vessels and create incomplete lobules.
  2. Cortex
    Densely packed double-positive thymocytes, cortical epithelial cells (positive selection) and macrophages that clear dying cells. Protected by the blood–thymus barrier.
  3. Medulla
    Paler zone with fewer, more mature single-positive thymocytes, medullary epithelial cells (AIRE) and dendritic cells — the site of negative selection and Treg generation.
  4. Hassall corpuscles
    Concentric layers of flattened, keratinised epithelial cells in the medulla; secrete TSLP, which conditions dendritic cells to induce regulatory T cells.
  5. Blood–thymus barrier
    In the cortex: continuous non-fenestrated endothelium, thick basal lamina, pericytes, perivascular macrophages and an epithelial-cell sheath, shielding developing thymocytes from blood-borne antigen.
  6. Thymocytes
    Developing T cells; they leave as mature naive CD4⁺ or CD8⁺ T cells.

Anatomy

Innervation

Vagus nerve and sympathetic fibres from the cervicothoracic (stellate) ganglion; the capsule receives phrenic and descendens hypoglossi branches.

Arterial supply

Branches of the internal thoracic and inferior thyroid arteries (anterior intercostal branches contribute).

Venous drainage

Thymic veins to the left brachiocephalic vein, internal thoracic and inferior thyroid veins.

Lymphatic drainage

Efferent lymphatics only (no afferents) to parasternal, brachiocephalic and tracheobronchial nodes.

Relations

Anterior: manubrium, sternohyoid and sternothyroid. Posterior: pericardium, ascending aorta and arch, left brachiocephalic vein, trachea. Lateral: mediastinal pleura and lungs. Superior: may reach the inferior poles of the thyroid gland.

Histology

Lobules with dark basophilic cortex and pale medulla, no follicles, Hassall corpuscles in the medulla; with age, increasing adipose tissue between residual lymphoid islands.

Development

Epithelium from the endoderm of the third pharyngeal pouch (ventral wing), which also forms the inferior parathyroid glands; the two primordia migrate caudally and medially to meet in the anterior mediastinum during weeks 6–8. Mesenchyme of the capsule and septa derives from neural crest; lymphoid precursors arrive from the fetal liver and later the bone marrow. Ectopic thymic tissue (and inferior parathyroids) may be left along the path of descent in the neck.

Function

  • Site of T-lymphocyte maturation (a primary lymphoid organ).
  • Positive selection — establishes MHC restriction and CD4/CD8 lineage commitment.
  • Negative selection and generation of natural regulatory T cells — central tolerance.
  • Produces peptide hormones (thymulin, thymosins, thymopoietin) that support T-cell development.

Clinical significance

Thymic aplasia — DiGeorge syndrome

22q11.2 deletion disrupts the 3rd and 4th pharyngeal pouches: absent or hypoplastic thymus (T-cell deficiency, viral and fungal infections), hypoparathyroidism (hypocalcaemic tetany), conotruncal cardiac anomalies and facial dysmorphism.

Thymoma and myasthenia gravis

About 75% of patients with myasthenia gravis have thymic abnormalities — mostly lymphoid follicular hyperplasia (≈ 65%), with thymoma in ≈ 10–15%; conversely about a third to a half of patients with thymoma develop myasthenia. Thymectomy improves outcomes in many patients. Thymoma is one of the "4 Ts" of anterior mediastinal masses (thymoma, teratoma/germ-cell tumour, retrosternal thyroid, "terrible" lymphoma).

The infant thymus on X-ray

A normal large infant thymus can widen the mediastinum and produce the triangular "sail sign" on a chest radiograph — not to be mistaken for a mass. It may shrink rapidly with stress or corticosteroids (and rebound afterwards).

Mnemonics

Order of selection

"Cortex before Medulla, + before −": positive selection in the cortex (can you see self-MHC at all?), negative selection in the medulla (do you react too strongly to self?).

Test yourself

In the thymus, positive selection of developing T cells…
  1. Deletes thymocytes that bind self-antigen strongly
  2. Occurs in the medulla under the control of AIRE
  3. Allows survival of thymocytes able to recognise self-MHC, establishing MHC restriction
  4. Generates the TCR by somatic hypermutation

Answer: Allows survival of thymocytes able to recognise self-MHC, establishing MHC restriction

Positive selection takes place in the cortex on cortical epithelial cells: double-positive thymocytes whose TCR weakly recognises self-peptide–MHC survive (MHC restriction, CD4/CD8 commitment); the rest die by neglect. Negative selection (medulla, AIRE) removes strongly self-reactive cells.

More lymphatic & immune system questions

Compiled from standard anatomy and physiology references — see the Lymphatic & Immune System sources. For education only; not medical advice.