The Thymus

Anatomy > Gray's Anatomy of the Human Body > XI. Splanchnology > 4c. The Thymus

Henry Gray (1821–1865). Anatomy of the Human Body. 1918.

The Thymus

The thymus (Fig. 1178) is a temporary organ, attaining its largest size at the time of puberty (Hammar), when it ceases to grow, gradually dwindles, and almost disappears. If examined when its growth is most active, it will be found to consist of two lateral lobes placed in close contact along the middle line, situated partly in the thorax, partly in the neck, and extending from the fourth costal cartilage upward, as high as the lower border of the thyroid gland.

It is covered by the sternum, and by the origins of the Sternohyoidei and Sternothyreoidei. Below, it rests upon the pericardium, being separated from the aortic arch and great vessels by a layer of [fascia]]. In the neck it lies on the front and sides of the trachea, behind the Sternohyoidei and Sternothyreoidei. The two lobes generally differ in size; they are occasionally united, so as to form a single mass; and sometimes separated by an intermediate lobe. The thymus is of a pinkish-gray color, soft, and lobulated on its surfaces. It is about 5 cm. in length, 4 cm. in breadth below, and about 6 mm. in thickness. At birth it weighs about 15 grams, at puberty it weighs about 35 grams; after this it gradually decreases to 25 grams at twentyfive years, less than 15 grams at sixty, and about 6 grams at seventy years.

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FIG. 1178– The thymus of a full-time fetus, exposed in situ (Picture From the Classic Gray's Anatomy)

Development

The thymus appears in the form of two flask-shaped entodermal diverticula, which arise, one on either side, from the third branchial pouch (Fig. 1175), and extend lateralward and backward into the surrounding mesoderm in front of the ventral aortae. Here they meet and become joined to one another by connective tissue, but there is never any fusion of the thymus tissue proper.

The pharyngeal opening of each diverticulum is soon obliterated, but the neck of the flask persists for some time as a cellular cord. By further proliferation of the cells lining the flask, buds of cells are formed, which become surrounded and isolated by the invading mesoderm. In the latter, numerous lymphoid cells make their appearance, and are agregated to form lymphoid follicles. These lymphoid cells are probably derivatives of the entodermal cells which lined the original diverticula and their subdivisions. Additional portions of thymus tissue are sometimes developed from the fourth branchial pouches. Thymus continues to grow until the time of puberty and then begins to atrophy.

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FIG. 1179– Minute structure of thymus. Follicle of injected thymus from calf, four days old, slightly diagrammatic, magnified about 50 diameters. The large vessels are disposed in two rings, one of which surrounds the follicle, the other lies just within the margin of the medulla. (Watney.) 'a' and 'b' From thymus of camel, examined without addition of any reagent. Magnified about 400 diameters. 'a' Large colorless cell, containing small oval masses of hemoglobin. Similar cells are found in the lymph glands, spleen, and medulla of bone. 'b' Colored blood corpuscles. (Picture From the Classic Gray's Anatomy)

Structure

Each lateral lobe is composed of numerous lobules held together by delicate areolar tissue; the entire gland being enclosed in an investing capsule of a similar but denser structure. The primary lobules vary in size from that of a pin’s head to that of a small pea, and are made up of a number of small nodules or follicles, which are irregular in shape and are more or less fused together, especially toward the interior of the gland. Each follicle is from 1 to 2 mm. in diameter and consists of a medullary and a cortical portion, and these differ in many essential particulars from each other.

The cortical portion is mainly composed of lymphoid cells, supported by a network of finely branched cells, which is continuous with a similar network in the medullary portion. This network forms an adventitia to the bloodvessels. In the medullary portion the reticulum is coarser than in the cortex, the lymphoid cells are relatively fewer in number, and there are found peculiar nest-like bodies, the concentric corpuscles of Hassall. These concentric corpuscles are composed of a central mass, consisting of one or more granular cells, and of a capsule which is formed of epithelioid cells (Fig. 1179). They are the remains of the epithelial tubes which grow out from the third branchial pouches of the embryo to form the thymus.

Each follicle is surrounded by a vascular plexus, from which vessels pass into the interior, and radiate from the periphery toward the center, forming a second zone just within the margin of the medullary portion. In the center of the medullary portion there are very few vessels, and they are of minute size. Watney has made the important observation that hemoglobin is found in the thymus, either in cysts or in cells situated near to, or forming part of, the concentric corpuscles. This hemo globin occurs as granules or as circular masses exactly resembling colored blood corpuscles. He has also discovered, in the lymph issuing from the thymus, similar cells to those found in the gland, and, like them, containing hemoglobin in the form of either granules or masses. From these facts he arrives at the conclusion that the gland is one source of the colored blood corpuscles. More recently Schaffer has observed actual nucleated red-blood corpuscles in the thymus. The function of the thymus is obscure. It seems to furnish during the period of growth an internal secretion concerned with some phases of body metabolism, especially that of the sexual glands.

Vessels and Nerves

The arteries supplying the thymus are derived from the internal mammary, and from the superior and inferior thyroids.

The veins end in the left innominate vein, and in the thyroid veins.

The lymphatics are described on page 698. The nerves are exceedingly minute; they are derived from the vagi and sympathetic. Branches from the descendens hypoglossi and phrenic reach the investing capsule, but do not penetrate into the substance of the gland.

Function

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T cell maturation

The thymus facilitates the maturation of T cells, an important part of the immune system providing cell-mediated immunity. T cells begin as hematopoietic precursors from the bone-marrow, and migrate to the thymus, where they are referred to as thymocytes. In the thymus they undergo a process of maturation, which involves ensuring the cells react against antigens ("positive selection"), but that they do not react against antigens found on body tissue ("negative selection"). Once mature, T cells emigrate from the thymus to provide vital functions in the immune system.

Each T cell has a distinct T cell receptor, suited to a specific substance, called an antigen. Most T cell receptors bind to the major histocompatibility complex on cells of the body. The MHC presents an antigen to the T cell receptor, which becomes active if this matches the specific T cell receptor. In order to be properly functional, a mature T cell needs to be able to bind to the MHC molecule ("positive selection"), and not to react against antigens that are actually from the tissues of body ("negative selection"). Positive selection occurs in the cortex and negative selection occurs in the medulla of the thymus. After this process T cells that have survived leave the thymus, regulated by sphingosine-1-phosphate. Further maturation occurs in the peripheral circulation. Some of this is because of hormones and cytokines secreted by cells within the thymus, including thymulin, thymopoietin, and thymosins.

Positive selection

T cells have distinct T cell receptors. These distinct receptors are formed by process of V(D)J recombination gene rearrangement stimulated by RAG1 and RAG2 genes. This process is error-prone, and some thymocytes fail to make functional T-cell receptors, whereas other thymocytes make T-cell receptors that are autoreactive. If a functional T cell receptor is formed, the thymocyte will begin to express simultaneously the cell surface proteins CD4 and CD8.

The survival and nature of the T cell then depends on its interaction with surrounding thymic epithelial cells. Here, the T cell receptor interacts with the MHC molecules on the surface of epithelial cells. A T cell with a receptor that doesn't react, or reacts weakly will die by apoptosis. A T cell that does react will survive and proliferate. A mature T cell expresses only CD4 or CD8, but not both. This depends on the strength of binding between the TCR and MHC class 1 or class 2. A T cell receptor that binds mostly to MHC class I tends to produce a mature "cytotoxic" CD8 positive T cell; a T cell receptor that binds mostly to MHC class II tends to produces a CD4 positive T cell.

Negative selection

T cells that attack the body's own proteins are eliminated in the thymus, called "negative selection". Epithelial cells in the medulla and dendritic cells in the thymus express major proteins from elsewhere in the body. The gene that stimulates this is AIRE. Thymocytes that react strongly to self antigens do not survive, and die by apoptosis. Some CD4 positive T cells exposed to self antigens persist as T regulatory cells.

Additional images

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  Thymus of a fetus

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  On chest X-ray, the thymus appears as a radiodense (brighter in this image) mass by the upper lobe of the child's right (left in image) lung.

External links

• T cell development in the thymus. Video by Janice Yau, describing stromal signaling and tolerance. Department of Immunology and Biomedical Communications, University of Toronto. Masters Research Project, Master of Science in Biomedical Communications. 2011.

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