General Structure and Tissue Organization
Externally, the organ is surrounded by a connective tissue capsule, from which septa—trabeculae—extend inward, dividing it into lobules.
Each lobule is divided into two main zones:
- Cortex: densely populated with developing T-lymphocytes (thymocytes) and cortical epithelial cells.
- Medulla: contains medullary epithelial cells, macrophages, dendritic cells, and unique layered structures—Hassall's corpuscles.
The border between the cortex and medulla is called the corticomedullary junction.
The main volume of the organ is occupied by the parenchyma, which is a three-dimensional epithelial reticulum—a framework made of epithelial cells. All stages of T-lymphocyte development unfold precisely within this network. The proportion of connective tissue stroma is extremely small.
Cellular composition
Thymus cells have various embryonic origins, which ensures their specific functions.
Cells of bone marrow origin:
- Thymocytes: the most numerous, but transient population (they leave the thymus as they mature).
- Macrophages and dendritic cells: participate in thymocyte selection and cytokine production.
Thymic epithelial cells (TECs): play a key role in supporting lymphocyte maturation by forming the microenvironment. Cortical and medullary TECs are distinguished. They carry out selection through the expression of MHC-I and MHC-II molecules, and also secrete crucial cytokines (e.g., IL-7).
Stages of Thymocyte Development
T-lymphocyte maturation is inextricably linked to their migration through the zones of the thymus and changes in their phenotype (expression of CD4 and CD8 markers):
- Double-negative thymocytes (DN): CD4⁻CD8⁻. Localized in the subcapsular zone. Intensive proliferation and rearrangement of T-cell receptor (TCR) genes occur here. The primary antigen-recognizing repertoire is formed.
- Double-positive thymocytes (DP): CD4⁺CD8⁺. Occupy the cortex, making up to 75% of all lymphoid cells. At this stage, thymocytes undergo positive selection (with the participation of cortical TECs). Cells that fail selection die via apoptosis.
- Transition to single-positive (SP): CD4⁺CD8⁻ or CD4⁻CD8⁺. Occurs in the corticomedullary and medullary zones. Here, negative selection takes place (involving medullary TECs and dendritic cells), eliminating self-reactive clones. Mature SP cells leave the thymus.
Blood-Thymus Barrier
The thymus is protected from the accidental ingress of external cells by the blood-thymus barrier. It is localized in the cortex (absent in the medulla) and consists of three structures that migrating precursors must overcome:
- Endothelium of postcapillary venules: precursor cells use adhesion molecules (selectins, integrins, CD44) to recognize ligands on the endothelium.
- Perivascular space: migrating cells are protected from macrophages by sialic acid and secrete enzymes (hyaluronidase, collagenase) to advance through the matrix.
- Basement membrane of the thymic epithelium: the final barrier before entering the epithelial space, overcome with the help of metalloproteinases.
Briefly: answers to topical questions
What hormones does the thymus secrete?
The thymus secretes peptide hormones (neuropeptides), which include thymulin, thymosins, and thymopoietins.
- Thymulin (Zn-binding nonapeptide)—exhibits activity only in a complex with zinc ions, produced exclusively in the thymus.
- Thymosins (primarily thymosin alpha-1)—polypeptide factors inducing the expression of mature T-lymphocyte markers.
- Thymopoietins—produced by the same secretory cells of the thymic epithelium.
Sources also mention the thymic humoral factor (FTS), which is a historical name for thymulin.
What histological layers make up the blood-thymus barrier?
The blood-thymus barrier, located exclusively in the cortical substance of the thymus, consists of five histological layers.
- Capillary endothelium (of postcapillary venules)—the vascular wall that migrating cells overcome using adhesion molecules.
- Capillary basement membrane.
- Pericapillary space (extraepithelial)—contains connective tissue fibers and macrophages.
- Basement membrane of epithelial reticular cells—the final barrier before contact with the thymic epithelium.
- Cytoplasm of epithelial reticular cells—includes desmosomes.
What is the detailed topography (holotopy, skeletotopy, syntopy) of the thymus?
The thymus is located in the thoracic cavity, occupying the anterior part of the superior mediastinum and extending into the anterior mediastinum.
- Holotopy: thoracic cavity, superior and anterior mediastinum.
- Skeletotopy: the upper parts lie posterior to the manubrium and the upper part of the body of the sternum, the lower border reaches the level of the cartilage of the 3rd rib.
- Syntopy: anteriorly, it is adjacent to the posterior surface of the sternum and the attachment site of the sternothyroid muscles; posteriorly, it abuts the trachea, the anterior surface of the pericardium, and large vessels (superior vena cava, brachiocephalic veins, aortic arch); laterally, it borders the mediastinal pleura and overlaps the anterior edges of the lungs.
Which arteries supply blood to the thymus?
Blood supply to the thymus is provided by thymic branches (rr. thymici), which branch off from several major vessels of the neck and thoracic cavity. According to available data, the main sources of arterial blood supply are:
- Internal thoracic artery (a. thoracica interna).
- Inferior thyroid artery (a. thyroidea inferior).
Venous drainage from the thymus occurs, in particular, via the unpaired thyroid plexus (plexus thyroideus impar), which collects blood and empties into the brachiocephalic veins.
From which embryonic primordia does the thymus develop?
The thymus develops primarily from the endoderm of the pharyngeal pouches with the participation of neural crest mesenchyme.
- Endoderm of the 3rd–4th pharyngeal (branchial) pouches—serves as the primary source for the development of epithelial cells (stromal epithelium) of the thymus.
- Neural crest mesenchyme—cells migrate into the organ primordium, serve as a source of epithelium differentiation inducers, and presumably give rise to cells producing neurohormones.
The concept of a mixed endodermal-ectodermal origin of the organ is currently rejected.
Class and exam questions
What are Hassall's corpuscles?
Peculiar multilayered structures in the thymic medulla formed by epithelial cells. They secrete the TSLP cytokine, which is important for the differentiation of regulatory T cells.
How do cortical epithelial cells functionally differ from medullary epithelial cells?
Cortical epithelial cells are responsible for positive selection of thymocytes, while medullary cells are responsible for negative selection.
What is the essence of the blood-thymus barrier?
It selectively allows only T-lymphocyte precursor cells from the blood to enter the thymic cortex, isolating maturing thymocytes from antigens and other cells. At the same time, the barrier is absent in the medulla.
What else to study on this topic
- Genetic control of thymus development (role of Hoxa3, Pax9, Foxn1)
- Molecular signals of precursor migration (chemokines CXCL12, CCL25)
- Interaction of integrins and adhesion molecules during barrier crossing
- Humoral function of thymic epithelial cells and the organ's minor cytokine network
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