Figure 131

Overview of the structures constituting the lymphatic system. Because lymphatic tissue is the main component of some organs, they are regarded as organs of the lymphatic system (spleen, thymus, lymph nodes). Lymphatic tissue is present as part of other organs, such as red bone marrow, lymphatic nodules of the alimentary canal (tonsils, vermiform appendix, gut-associated lymphatic tissue [GALT]) and of the respiratory system (bronchus-associated lymphatic tissue IBALT]), and, not shown in the illustration, diffuse lymphatic tissue of mucous membranes (mucus-associated lymphatic tissue [MALTl). The lymph nodes are interspersed along the superficial lymphatic vessels (associated with the skin and superficial fascia) and deep lymphatic vessels (associated with main arteries); ultimately, the lymphatic vessels empty into the bloodstream by joining the large veins at the base of the neck. The thoracic duct is the largest lymphatic vessel.

v lymphatic cells Overview

Cells of the immune system include lymphocytes and various supporting cells

Lymphocytes and a variety of supporting cells make up the cells of the immune system. Three types of lymphocytes are recognized: B cells, T cells, and natural killer (NK) cells. Sup-

porting cells include reticular cells, macrophages, follicular dendritic cells, Langerhans' cells, and epithelioreticular cells.

Supporting cells in the lymphatic organs are organized into loose meshworks

In lymph nodules, lymph nodes, and the spleen, reticular cells and the reticular fibers produced by these cells form elaborate meshworks. Lymphocytes, macrophages, follicular dendritic cells and other cells of the immune system reside in these meshworks and in the loose connective tissue of the body; Langerhans' cells are found only in the middle layers of epidermis. At these sites, they carry out their mission of surveillance and defense. In the thymus, epithelioreticular cells form the structural meshwork within the tissue. Despite their name, these cells neither produce nor are related to reticular fibers.

Different types of cells in lymphatic tissue are identified by specific cluster of differentiation (CD) markers on their surface

Different lymphatic and hematopoietic tissue cells possess unique cell surface molecules. These specific markers, called cluster of differentiation (CD) molecules, are designated by numbers according to an international system that relates them to antigens expressed at different stages of their differentiation. CD molecules can be visualized by im-munohistochemical methods using monoclonal antibodies and are useful in identifying specific subtypes of lymphatic or hematopoietic cells. Some CD markers are expressed by a cell line throughout its entire life; others are expressed only during one phase of differentiation or during cell activation. Table 13.1 lists the most clinically useful markers.

Lymphocytes

Circulating lymphocytes are the chief cellular constituent of lymphatic tissue

To understand the function of lymphocytes, one must realize that most lymphocytes (approximately 70%) in blood or lymph represent a circulating pool of immunocompetent cells. These cells participate in a cycle during which they exit the systemic circulation to enter the lymphatic tissue. While there, they are responsible for immunologic surveillance of surrounding tissues. The cells then return to the systemic circulation. This population of cells is represented mainly by long-lived, mature lymphocytes (mainly T cells). Mature lymphocytes have developed the capacity to recognize and respond to foreign antigens and are in transit from one site of lymphatic tissue to another.

The remaining 30% of lymphocytes in the blood vessels do not circulate between the lymphatic tissues and the systemic circulation. This population comprises mainly shortlived, immature cells or activated cells destined for a specific tissue. These cells leave the capillaries and migrate directly to the tissues, especially into the connective tissue that underlies the lining epithelium of the respiratory, gastrointestinal, and urogenital tracts as well as into the intercellular spaces of these epithelia.

Functionally, three types of lymphocytes are present in the body: T lymphocytes, B lymphocytes, and NK cells

The functional classification of lymphocytes is independent of their morphologic (size) characteristics. Functionally, three types of lymphocytes are recognized:

• T lymphocytes (T cells) are named for the thymus, where they differentiate. They have a long lifespan and are involved in cell-mediated immunity. They account for 60 to 80% of circulating lymphocytes. T cells express CD2, CD3, and CD7 markers; however, they are subclassified according to the presence or absence of two other important surface markers, CD4 and CDS. T cells that also express CD4 markers are called helper CD4+ T lymphocytes. T cells that also express CDS markers are called cytotoxic CD8+ T lymphocytes.

• B lymphocytes (B cells) are so named because they were first recognized as a separate population in the bursa of Fabricius in birds (page 361) or bursa-equivalent organs such as bone marrow and GALT in mammals. They have variable lifespans and are involved in the production and secretion of the various circulating antibodies, also called immunoglobulins, the immune proteins associated with humoral immunity (Fig. 13.2 and Table 13.2). B cells account for 20 to 30% of the circulating lymphocytes. In addition to secreting circulating immunoglobulins, B cells express immunoglobulin M (IgM) and immunoglobulin D (IgD) as well as the major histocompatibility complex II (MHC II) molecules on the cell surface. Their CD markers are CD9, CD19, CD20, and CD24.

• NK cells, which develop from the same precursor cell as B and T cells, are named for their ability to kill certain types of transformed cells. They constitute about 5 to 10% of circulating lymphocytes. During their development, they are genetically programmed to recognize transformed cells (i.e., cells infected with a virus or tumor cells). Following recognition of a transformed cell, they release perforins and fragmentins, substances that create channels in the cell's plasma membrane and cytoplasm, which induces them to self-destruct (a process known as apoptosis) and lyse. Their specific markers include GDI 6, CD56, and CD94.

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