IMMUNOLOGY - Roitt I. - Mir 2000

Chapter 3. The Lymphoid System

PRIMARY LYMPHOID ORGANS

The Thymus is the site of T-Cell proliferation and maturation. In mammals, the thymus is a bilobed organ situated in the thoracic cavity, superior to The Heart and large Blood Vessels. Each lobe is divided into lobules separated by Connective Tissue septa. Within each lobule, lymphoid Cells (thymocytes) form an outer cortical zone (cortex) and an inner medullary zone (medulla) (Fig. 3.2). The densely packed cortical zone is dominated by relatively immature, proliferating thymocytes, whereas the medullary zone contains more mature forms, displaying a gradient of cellular differentiation from the cortex to the medulla. Mature medullary thymocytes express the CD44 marker, which is absent on cortical thymocytes. This marker acts as a receptor binding hyaluronan and other Extracellular matrix components of connective tissue; it is detected on all circulating lymphocytes, but not on sessile ones. The structural framework of the thymic lobules is formed by a network of epithelial cells that play a crucial role in the differentiation of Bone Marrow-derived thymocyte precursors into mature T lymphocytes.

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Fig. 3.2. Lobular architecture of the thymus (histological section). The section clearly shows the two main zones of a lobule: the outer cortical zone (C), containing immature cells, and the inner medullary zone (M), containing more mature cells. Hassall's corpuscles (H) are also visible in the medulla. Hematoxylin and eosin staining. ×25. (Micrograph kindly provided by Dr A. Stevens and Prof. J. Lowe.)

Three types of epithelial cells are distinguished within the thymic lobules. Based on their spatial arrangement, Structure, function, and surface marker phenotype, at least three types of thymic epithelial cells can be identified. The framework of the cortex is formed by a network of cortical epithelial cells, along with nurse epithelial cells; in the medulla, epithelial cells are mainly aggregated into dense clusters (see Ch. 12). In addition to these cells, the corticomedullary junction harbors branched cells with intertwined processes—dendritic interdigitating cells (IDCs)—as well as macrophages (both of bone marrow origin). Cells enter and leave the thymus via high endothelial venules (HEVs). All epithelial cells, IDCs, and macrophages express MHC molecules on their surface, which are essential for T-cell development and Selection.

The medullary zone of the thymic lobules contains Hassall's corpuscles (thymic corpuscles). Their exact function remains unknown; they have been shown to consist of degenerating epithelial cells rich in high-molecular-weight Keratins.

The mammalian thymus undergoes involution as the Organism matures and ages (Fig. 3.3). In humans, this process begins around Puberty and continues throughout life. Age-related involution primarily affects the cortical zone of the lobules, eventually leading to its complete disappearance, while the medullary zone is preserved. The Atrophy of the cortex is driven by the high sensitivity of cortical thymocytes to adrenal corticosteroid Hormones. Consequently, any condition associated with elevated steroid secretion, such as Pregnancy and stress, induces thymic atrophy. Nevertheless, T-cell generation in the thymus can still occur in adults, albeit at a low rate.

Fig. 3.3. Age-related thymic atrophy. Involution of the lymphoid tissue with replacement by adipose tissue (AT). The cortical zone (C) has largely disappeared, whereas the diminished medullary zone (M) is still discernible. (Micrograph kindly provided by Dr A. Stevens and Prof. J. Lowe.)

Sites of B-cell proliferation and maturation

B-cell development occurs in the fetal Liver and subsequently in the bone marrow. B cells originate from stem cells within hematopoietic tissue islands in the fetal liver and bone marrow, as well as in postnatal bone marrow (Fig. 3.4). In addition to developing B cells, postnatal bone marrow contains mature plasma cells and T cells. Consequently, in humans, the bone marrow also Functions as an important secondary lymphoid organ.

Fig. 3.4. Cytology/practical/86.html">Red bone marrow. In the biopsy sample, hematopoietic tissue (HT) is visible between the bony trabeculae (T). Certain spaces are also occupied by adipocytes (fat cells) (FC). (Micrograph kindly provided by Dr A. Stevens and Prof. J. Lowe.)

In birds, B-Cell Differentiation takes place in the bursa of Fabricius, the folds of which contain lymphoid follicles with distinct cortical and medullary zones.