Introduction

A. Background

The thymus gland and various polypeptide hormones produced by thymus cells play a critical role in the functioning of the immune system. A few major polypeptide hormones elaborated by thymus cells are needed for growth and immunoglobulin production by antibody-producing cells. Here, the object will be to describe these hormones and their actions. Although the thymus epithelial cell is a rich source of thymus hormones, some of these substances are found in other cells of the body, so that the thymus is not always the exclusive source.

In addition to the central role of the thymus in the immune mechanism, the gland may produce components that regulate the secretion of hormones by other glands, for example, the release of prolactin from lacto-trophs of the anterior pituitary. Thymus hormones also regulate the secretion of certain releasing hormones from the hypothalamus. However, if the thymus produces hormones that regulate the secretion of anterior pituitary hormones, then it is possible that feedback regulation could exist, which, in the case of prolactin, might lead to a partial explanation for its pronounced increase in stress (see Chapter 10). Regulation of hypothalamic secretions is important in the development of the sex organs because thymosin, a thymus hormone, is required at birth for the full release of GnRH, which, in turn, triggers the release of the gonadal hormones. Although this process often is not considered until puberty, the availability of GnRH released through the action of thymosin may have a role in the development of the sexual organs. Thus, babies with no thymus present at birth fail to develop normal gonads owing to the lack of thymosin from the thymus gland.

Peripheral T cells originate in the thymus. T cells are continually released that are fully mature and competent to function in antigen recognition. The precursor of the thymus during fetal and embryonic life develops functionally by immigration of precursor cells from bone marrow into the thymus, generation of T lineage-specific surface molecules, expression of the T-cell receptor, and finally diversification into CD4+ or CD8+ classes with effector functions. Some categories of T cells will express T-cell receptor (TCR) with a/fH-subunits or TCR-yS, the CD3 complex, and the CD4

immune complex

inflammation

FIGURE 17-1 Sequence of events in a prototypic immune response. See text for explanation. Reproduced from Stites, D. P., Terr, A. I., and Parslow, T. G. (1994). "Basic and Clinical Immunology," 8th ed., p. 43. Appleton & Lange, Norwalk, CT.

and CD8 molecules. Immature cells are localized within the cortex of the thymus. The more mature cells are located in the medulla, and they leave the thymus to become peripheral T cells.

In the development of the thymus gland, involution occurs. Babies are born with a large thymus, which gradually becomes smaller in proportion to the development of the adrenal gland and the increasing secretion of Cortisol. Involution occurs in cortex cells that are programmed for cell death initiated by glucocorticoids by a process of apoptosis (see Chapter 10), in which the dying cells are altered on their surface so as to be engulfed by macrophages without the development of inflammation. Early on, the large thymus in newborns was considered to be an anomaly since adults had a much smaller organ resulting from the maturation process regulated by Cortisol. By the early 1900s it became recognized that tumors of the thymus gland were linked to the disease myasthenia gravis, and later removal of the tumor-bearing thymus became a successful therapy for this disease.

Because the thymus is the sole source of T lymphocytes, it plays a central role in the development of the immune system. Thymus cells produce hormones that function to activate and proliferate peripheral cells of the immune system, ensuring a surveillance function in the prevention of disease. Degeneration or loss of this system places the organism at risk for the development of cancers and infectious processes common in senescence, which seem to align with lowered functioning of the thymus. Thus, the size of the thymus is largest during the development of the immune system in early childhood. Thymus hormones that maintain a functioning immune system are being examined for use in therapy in diseases where thymus function is decreased.

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