Lymphatics: Thymus

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The thymus sits in the superior mediastinum, just behind the sternum. It is the only lymphoid organ with a primary educational role: the thymus is where T lymphocytes are born, tested, and either approved for service or eliminated. No other organ does this. After puberty, the thymus gradually shrinks and its functional tissue is replaced by fat — a normal process called thymic involution. By adulthood, only small islands of active thymic tissue remain.

Overall Architecture: Lobules, Cortex, and Medulla

A connective tissue capsule surrounds the thymus and sends inward partitions called septa that divide the organ into irregular lobules. This lobulated architecture is one of the first things you will notice on a low-power slide.

Each lobule has two distinct zones that are immediately visible because of their contrasting staining:

The cortex is the outer, darker region. It is densely packed with immature T cells called thymocytes, making it one of the most cell-dense tissues in the body. The dark staining reflects this high cellular density.

The medulla is the inner, paler region. It is less densely packed and contains more mature T cells preparing to leave the thymus. The medulla is continuous across lobules — the septa divide the cortex but not the medulla.

Low-power thymus section — identify the capsule, septa, cortex (dark), and medulla (pale) in at least two lobules

The Cortex: Selection and Sacrifice

The thymic cortex is where T cell education — and elimination — takes place. Three cell types share this crowded space:

Thymocytes are the developing T cells. They are tested here for two things. First, positive selection checks whether the thymocyte can recognize self-MHC molecules (the proteins your own cells use to display antigens). Cells that cannot pass are useless and die. Second, negative selection eliminates any thymocyte that reacts too strongly to self-antigens — which would cause autoimmune disease. The result: roughly 98% of thymocytes die in the cortex by apoptosis. The 2% that survive are self-tolerant and MHC-restricted.

Epithelial reticular cells form a structural mesh throughout the cortex, their branching cytoplasmic extensions supporting the architecture. These cells express MHC molecules and provide the molecular signals used during selection.

Macrophages clean up the massive wave of apoptotic thymocytes. On a slide, you can sometimes spot macrophages with engulfed nuclear debris (a “starry sky” appearance in very active cortex).

The Medulla and Hassall’s Corpuscles

T cells that survived selection migrate into the medulla to finish maturation. The medulla is looser, with scattered thymocytes and clusters of epithelial reticular cells.

The medulla’s most important — and most recognizable — histological landmark is the Hassall’s corpuscle (also called a thymic corpuscle). These are concentric whorls of flattened epithelial cells stacked around each other like the rings of an onion. The cells in the center are often degenerated, appearing keratinized, calcified, or completely hyalinized. Hassall’s corpuscles are found only in the thymic medulla. If you see them on a slide, you know exactly what organ you are looking at.

Their precise function is still under investigation, but current evidence suggests they produce signaling molecules that help generate regulatory T cells — a population critical for suppressing autoimmunity.

hymic medulla at higher magnification — identify at least one Hassall’s corpuscle with concentric whorls and degenerated center

The Blood-Thymus Barrier

The cortex has a blood-thymus barrier that keeps antigens in the bloodstream away from the developing thymocytes. If antigens reached the cortex too early, they would interfere with selection, potentially producing T cells that cannot tolerate normal tissue antigens. The barrier consists of three components working together: the continuous endothelium of cortical capillaries (with tight junctions), a thick basement membrane, and surrounding epithelial reticular cells.

This barrier is absent in the medulla — intentionally. T cells in the medulla need exposure to circulating self-antigens for negative selection to be completed before they leave.

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