Figure 520

Electron micrograph of a small blood vessel. The nucleus at the upper left belongs to the endothelial cell that forms the wall of the vessel. At the right is another cell, a pericyte, that is in intimate relation to the endothelium. Note that the basal lamina (BL) covering the endothelial cell divides (arrows) to surround the pericyte. xl1,000.

TEM studies have shown that pericytes surrounding the smallest venules have cytoplasmic characteristics almost identical with those of the endothelial cells of the same vessel. Pericytes associated with larger venules have characteristics of smooth muscle cells of the tunica media of small veins. In fortuitous sections cut parallel to the long axis of venules, the distal portions and proximal portions of the same pericyte have characteristics of endothelial cells and smooth muscle cells, respectively. These studies suggest that during the development of new vessels, cells with characteristics of pericytes may differentiate into the smooth muscle of the vessel wall.

The fibroblasts and blood vessels within healing wounds develop from undifferentiated mesenchymal cells associated with the tunica adventitia of venules

Autoradiographic studies of wound healing using parabiotic (crossed-circulation) pairs of animals have established that undifferentiated mesenchymal cells located in the tunica adventitia of venules and small veins are the primary source of new cells in healing wounds. In addition, fibroblasts, pericytes, and endothelial cells in portions of the connective tissue adjacent to the wound divide and give rise to additional cells that form new connective tissue and blood vessels.

Lymphocytes, Plasma Cells, and Other Cells of the Immune System

Lymphocytes are principally involved in immune responses

Connective tissue lymphocytes are the smallest of the free cells in the connective tissue (see Fig. 5.18). They have a thin rim of cytoplasm surrounding a deeply staining, het-erochromatic nucleus. Often, the cytoplasm of connective tissue lymphocytes may not be visible. Normally, small numbers of lymphocytes are found in the connective tissue throughout the body. The number increases dramatically, however, at sites of tissue inflammation caused by pathogenic agents. Lymphocytes are most numerous in the lamina propria of the respiratory and gastrointestinal tracts, where they are involved in immunosurveillance against pathogens and foreign substances that enter the body by crossing the epithelial lining of these systems.

Lymphocytes are a heterogeneous population of at least three functional cell types: T cells, B cells, and NK cells

At the molecular level, lymphocytes are characterized by the expression of specific molecules on the plasma membrane known as cluster of differentiation (CD) proteins. CD proteins recognize specific ligands on target cells. Because some CD proteins are present only on specific types of lymphocytes, they are considered specific marker proteins. On the basis of these specific markers, lymphocytes can be classified into three functional cell types:

• T lymphocytes are characterized by the presence of the CD2, CD3, and CD7 marker proteins and the T cell receptors (TCRs). These cells have a long life span and are effectors in cell-mediated immunity.

• B lymphocytes are characterized by the presence of CD9, CD19, CD20, and CD24 proteins and attached immunoglobulins IgM and IgD. These cells recognize antigen, have a variable life span, and are effectors in antibody-mediated (humoral) immunity.

• Natural killer (NK ) lymphocytes are non-T, non-B lymphocytes that express the CD16, CDS6, and CD94 proteins, not found on other lymphocytes. These cells do not produce immunoglobulins, nor do they express TCR on their surface. Thus, NI< lymphocytes are not antigen specific. Similar in action to T lymphocytes, however, they destroy virus-infected cells and some tumor cells by a cytotoxic mechanism.

In response to the presence of antigens, lymphocytes become activated and may divide several times, producing clones of themselves. In addition, clones of B lymphocytes mature into plasma cells. A description of B and T lymphocytes and their functions during immune response reactions is presented in Chapter 13.

Plasma cells are antibody-producing cells derived from B lymphocytes

Plasma cells are a prominent constituent of loose connective tissue where antigens tend to enter the body, e.g., the gastrointestinal and respiratory tracts. They are also a normal component of salivary glands, lymph nodes, and hemopoietic tissue. Once derived from its precursor, the B lymphocyte, a plasma cell has only limited migratory ability and a somewhat short life span of 10 to 30 days.

The plasma cell is a relatively large, ovoid cell (20 ¿am) with a considerable amount of cytoplasm. The cytoplasm displays strong basophilia because of an extensive rER (Fig. 5.21). The Golgi apparatus is usually prominent because of its relatively large size and lack of staining. It appears in light microscope preparations as a clear area, in contrast to the basophilic cytoplasm.

The nucleus is spherical and typically offset or eccentrically positioned. It is small, not much larger than the nucleus of the lymphocyte. It exhibits large clumps of peripheral heterochromatin alternating with clear areas of euchromatin. This arrangement has traditionally been described as resembling a cartwheel or analog clock face, with the heterochromatin resembling the spokes of the wheel or the numbers on a clock. The heterochromatic nucleus of the plasma cell is somewhat surprising, given the cell's function in synthesizing large amounts of protein. However, because the cells produce large amounts of only one type of protein—a specific antibody—only a small segment of the genome is exposed for transcription.

Eosinophils, monocytes, and neutrophils are also observed in connective tissue

As a result of immune responses and tissue injury, certain cells rapidly migrate from the blood to enter the connective tissue, particularly neutrophils and monocytes. Their presence generally indicates an acute inflammatory reaction. In these reactions, neutrophils migrate into the connective tissue in substantial numbers, followed by large numbers of monocytes. As noted, the monocytes

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