General Architecture and Embryogenesis
The thymus is covered by a dense connective tissue capsule. Trabeculae extend inward from the capsule, dividing the organ into lobules. Each lobule consists of a dark peripheral cortex (cortex) and a light central medulla (medulla).
During development, the organ forms from two sources:
- Stromal component: Derived from the pharyngeal epithelium of the third pharyngeal pouch. This is a unique feature of the thymus, as its stroma is epithelial rather than connective tissue.
- Hemal component: Represented by T-cell precursors that migrate from the red bone marrow.
Cortex: Site of Lymphocyte Maturation
The cortex is densely populated with cells. T-lymphocytopoiesis occurs here, taking about 20 days.
Large T-lymphoblasts actively divide in the subcapsular zone. They then migrate deeper into the cortex, differentiating into maturing T-lymphocytes. During this time, gene rearrangement occurs to create a unique T-cell receptor (TCR).
A critical step is selection. At the corticosomedullary junction, T-cells are tested for self-tolerance (reactivity against the body's own antigens). Cells that fail this screening undergo apoptosis. Macrophages, dendritic cells, and interdigitating cells actively participate in this process.
The cortical stroma is formed by reticuloepithelial cells, which are divided into:
- Supporting cells (form the structural framework and the blood-thymus barrier).
- Secretory cells (produce hormones such as thymosin and thymopoietin).
- Nurse cells (provide trophic support to developing lymphocytes).
Blood-Thymus Barrier
To prevent maturing T-lymphocytes from prematurely encountering circulating foreign antigens (which could lead to inappropriate tolerance), a robust barrier exists in the cortex.
Layers of the barrier (from blood to tissue):
- Capillary endothelium with a thick basement membrane.
- Perivascular space containing macrophages.
- Supporting reticuloepithelial cells with their basement membrane.
Additionally, the thymus lacks afferent lymphatic vessels, which prevents antigens from entering via the lymph flow.
Medulla and Involution
The medulla appears lighter due to a lower density of lymphocytes. It mainly contains mature, recirculating T-lymphocytes. The blood-thymus barrier is absent in this zone, but high endothelial venules (HEVs) are present, allowing cells to freely migrate into and out of the bloodstream.
A specific histological marker of the medulla is Hassall's corpuscles (concentric thymic corpuscles) formed by layered, keratinizing reticuloepithelial cells.
The thymus undergoes involution (regression):
- Age-related: Gradual reduction in mass and replacement by adipose tissue after puberty.
- Accidental: Rapid reduction in response to stress mediated by high levels of glucocorticoids.