The thymus is situated in the upper anterior thorax, just above the heart. It consists of numerous lobules, each clearly differentiated into an outer cortical region—the thymic cortex—and an inner medulla (Fig. 8.16). In young individuals, the thymus contains large numbers of developing T-cell precursors embedded in a network of epithelia known as the thymic stroma. This provides a unique microenvironment for T-cell development analogous to that provided for B cells by the stromal cells of the bone marrow.
Fig. 8.15 T cells undergo development in the thymus and migrate to the peripheral lymphoid organs, where they are activated by foreign antigens. T-cell precursors migrate from the bone marrow to the thymus, where they commit to the T-cell lineage following Notch receptor signaling. In the thymus, T-cell receptor genes are rearranged (top first panel); α:β T-cell receptors that are compatible with self MHC molecules transmit a survival signal on interacting with thymic epithelium, leading to positive selection of the cells that bear them. Self-reactive receptors transmit a signal that leads to cell death, and cells bearing them are removed from the repertoire in a process of negative selection (top second panel). T cells that survive selection mature and leave the thymus to circulate in the periphery; they repeatedly leave the blood to migrate through the peripheral lymphoid organs, where they may encounter their specific foreign antigen and become activated (top third panel). Activation leads to clonal expansion and differentiation into effector T cells. Some of these are attracted to sites of infection, where they can kill infected cells or activate macrophages (top fourth panel); others are attracted into B-cell areas, where they help to activate an antibody response (not shown).
Precursors commit to the T-cell lineage following Notch signaling and initiate T-cell receptor gene rearrangements Activated T cells proliferate and eliminate infection Mature T cells encounter foreign antigens in the peripheral lymphoid organs and are activated Immature T cells that recognize self MHC receive signals for survival. Those that interact strongly with self antigen are removed from the repertoire T-cell precursor mature T cell dendritic cell macrophage Notch thymic stromal cell thymus lymph node spleen self MHC activates kills gastro-intestinal tract
T-cell progenitors develop in the bone marrow and migrate to the thymus where the cells complete their development by rearranging their antigenreceptor genes and undergoing repertoire selection Mature T cells migrate to the peripheral lymphoid organs Activated T cells migrate to sites of infection
Fig. 8.16The cellular organization of the human thymus. The thymus, which lies in the midline of the body, above the heart, is made up of several lobules, each of which contains discrete cortical (outer) and medullary (central) regions. As shown in the diagram on the left, the cortex consists of immature thymocytes (dark blue); branched cortical epithelial cells (pale blue), with which the immature cortical thymocytes are closely associated; and scattered macrophages (yellow), which are involved in clearing apoptotic thymocytes. The medulla consists of mature thymocytes (dark blue) and medullary epithelial cells (orange), along with macrophages (yellow) and dendritic cells (yellow) of bone marrow origin. Hassall’s corpuscles are probably also sites of cell degradation. The thymocytes in the outer cortical cell layer are proliferating immature cells, whereas the deeper cortical thymocytes are mainly immature T cells undergoing thymic selection. The photograph shows the equivalent section of a human thymus, stained with hematoxylin and eosin. The cortex is darkly stained, whereas the medulla is lightly stained. The large body in the medulla is a Hassall’s corpuscle. Photograph courtesy of C.J. Howe.