General structural plan and embryogenesis
The thymus is covered by a capsule of dense fibrous connective tissue. Septa extend from it inward, dividing the organ into lobules. Each lobule consists of a dark cortex (cortex) at the periphery and a light medulla (medulla) in the center.
During development, the organ is formed from two sources:
- Stromal component: formed from the epithelium of the anterior part of the primary gut. This is a unique feature of the thymus, as the stroma here is epithelial rather than connective tissue.
- Hemal component: represented by T-cell precursors that migrate from the red bone marrow.
Cortex: where lymphocytes mature
The cortex is densely populated with cells. A complex process of T-lymphocytopoiesis takes place here, lasting about 20 days.
Large T-lymphoblasts actively divide in the subcapsular zone. Then they migrate deeper into the cortex, turning into maturing T-lymphocytes. At this time, gene rearrangement occurs to create a unique receptor (TCR).
A crucial stage is selection. At the border with the medulla, T-cells are checked for autoaggression (reaction against the body's own antigens). Cells that fail the test die via apoptosis. Macrophages, dendritic, and interdigitating cells actively participate in this process.
The stroma of the cortex is formed by reticuloepithelial cells, which are divided into:
- Supporting cells (create the framework and the blood-thymus barrier).
- Secretory cells (produce the hormones thymosin and thymopoietin).
- Nurse cells (provide trophic support to developing lymphocytes).
Blood-thymus barrier
To prevent maturing T-lymphocytes from accidentally encountering foreign antigens from the blood (otherwise they would mistake them for "self," leading to immunological tolerance), a powerful barrier exists in the cortex.
Layers of the barrier (from blood to tissue):
- Capillary endothelium with basement membrane.
- Perivascular space.
- Supporting epithelioreticulocytes with their basement membrane.
In addition, afferent lymphatic vessels are absent in the thymus, which prevents antigens from entering with the lymph flow.
Medulla and involution
The medulla appears light due to a smaller number of lymphocytes. It mainly contains mature, recirculating T-lymphocytes. The blood-thymus barrier is absent in this zone, but there are postcapillary venules with high endothelium through which cells freely migrate into the blood and back.
A specific marker of the medulla is Hassall's corpuscles (stratified epithelial corpuscles) formed by concentric layers of keratinizing epithelioreticulocytes.
The thymus undergoes involution (regressive development):
- Age-related: gradual decrease in mass after 20 years.
- Accidental (rapid): sharp reaction to stress under the influence of high doses of glucocorticoids.
Briefly: answers to topical questions
What stages of CD marker expression (CD4, CD8) do T-lymphocytes undergo during maturation in the cortex?
During maturation in the thymus, T-lymphocytes go through three consecutive stages of changing CD4 and CD8 marker expression.
- Double-negative cells ($CD4^-CD8^-$) — the initial stage of differentiation, at which coreceptor molecules are completely absent.
- Double-positive cells ($CD4^+CD8^+$) — the stage when both markers are simultaneously expressed on the cell.
- Single positive cells — formed at the exit from the organ, dividing into T-helper cells ($CD4^+CD8^-$) and cytotoxic T-lymphocytes ($CD4^-CD8^+$).
How is the efferent lymphatic vessel system of the thymus structured?
The lymphatic system of the thymus is represented only by efferent lymphatic vessels.
Afferent lymphatic vessels are absent in the thymus. In the cortex and medulla, lymphatic vessels are indicated as efferent only. This structure prevents antigens from entering the thymus with the lymph flow and maintains the isolation of the organ.
Class and exam questions
What is the main difference between the stroma of the thymus and other hematopoietic organs?
The thymus stroma is of epithelial origin and does not contain reticular fibers. It is formed by reticuloepithelial cells.
Where is the blood-thymus barrier located and why is it needed?
The barrier is located only in the cortex. It protects maturing T-lymphocytes from contact with blood antigens, preventing the development of immunological tolerance to infections.
How to distinguish the cortex from the medulla in a specimen?
The cortex is dark due to high lymphocyte density. The medulla is light, and characteristic layered Hassall's corpuscles are present in it.
What is accidental involution?
This is a rapid decrease in thymus mass in response to severe stress. The process is triggered by high doses of adrenal cortex hormones (glucocorticoids).
What else to study on this topic
- Detailed structure of Hassall's corpuscles and their possible functions
- Mechanisms of positive and negative selection of T-lymphocytes
- Thymic hormones (thymosin, thymopoietin) and their effect on the peripheral immune system
- Structural features of high endothelial venules
- Differences between thymic nurse cells and bone marrow macrophages
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