Porth's Essentials of Pathophysiology, 4e

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Hematopoietic Function

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There are three types of lymphocytes: B lympho- cytes, T lymphocytes, and natural killer cells. 1,2 The B lymphocytes are so named because they were first recognized as a separate population in the bursa of Fabricius in birds and bursa-equivalent organs (e.g., bone marrow) in mammals. They differentiate to form antibody-producing plasma cells and are involved in humoral-mediated immunity. The T lymphocytes dif- ferentiate in the thymus. They activate other cells of the immune system (helper T cells) and are involved in cell- mediated immunity (cytotoxic T cells). Natural killer cells participate in innate or natural immunity and their function is to destroy foreign cells. The lymphocytes of the three different subsets have unique surface markers that can be identified and used to define their function and diagnose disease (discussed in Chapter 15). Although all lymphocytes are morphologically simi- lar, they comprise elements that vary in terms of lineage, cell membrane molecules and receptors, function, and response to antigen. These cells are often distinguished by surface proteins that can be identified using panels of monoclonal antibodies. These identified proteins are then correlated with cell functions. The standard nomenclature for these proteins is the “CD” (clusters of differentiation) numeric designation (CD4, CD8), which is used to delineate surface proteins that define a particular cell type or stage of cell differentiation and are recognized by a cluster or group of antibodies. 2 Although this nomenclature was originally developed for lymphocytes, it is now common practice to apply it to blood cells other than lymphocytes. Monocytes/Macrophages. Monocytes are the largest of the white blood cells and constitute approximately 3% to 8% of the total leukocyte count. They are dis- tinguished by a large amount of cytoplasm and a darkly stained kidney-shaped nucleus. Although these cells are considered agranular, they contain small, dense, azuro- philic granules that contain lysosomal enzymes similar to those found in the azurophilic granules of neutro- phils. Monocytes travel from the bone marrow to the body tissues, where they differentiate into various tissue phagocytes including the histiocytes of loose connective tissue, microglial cells of the brain, Kupffer cells of the liver, and tissue macrophages. During inflammation, monocytes leave the blood vessel at the site of inflamma- tion and transform into tissue macrophages that phago- cytose bacteria and tissue debris. Macrophages also play an important role in immune responses by activat- ing lymphocytes and by presenting antigen to T cells (see Chapter 15). Leukocyte Developmental Stages Leukocyte development begins with the myeloid and lym- phoid stem cells in the bone marrow 2–4 (Fig. 11-3). The immature precursor cells for each of the cell lines are called blast cells. The names of the various leukocyte devel- opmental stages are often used in describing blood cell changes that occur in hematopoietic disorders (e.g., acute lymphoblastic leukemia, chronic myelogenous leukemia).

granules. The azurophilic granules stain purple and are lysosomes. The granulocytes are divided into three types— neutrophils, eosinophils, and basophils—according to the staining properties of their specific granules. Neutrophils. The neutrophils, which constitute 60% to 65% of the total white blood cells, have specific gran- ules that are neutral and do not stain with an acidic or a basic dye. 1 Because these white cells have nuclei that are divided into three to five lobes, they are often called polymorphonuclear leukocytes (PMNs). The neutrophils are primarily responsible for main- taining normal host defenses against invading bacteria and fungi, cell debris, and a variety of foreign sub- stances. After release from the marrow, the neutrophils spend only approximately 4 to 8 hours in the circula- tion before moving into the tissues. They survive in the tissues for approximately 4 to 5 days. 1 They die in the tissues by discharging their phagocytic function or from senescence. The pool of circulating neutrophils (i.e., those that appear in the blood count) is in a closely maintained equilibrium with a similar-sized pool of cells marginating along the walls of small blood vessels. These are the neutrophils that respond to chemotactic factors and migrate into the tissues toward the offend- ing agent during an inflammatory reaction. Eosinophils. The specific cytoplasmic granules of the eosinophils stain red with the acidic dye eosin. These leukocytes constitute 1% to 3% of the total white blood cells and increase in number during allergic reactions and parasitic infections. 1 During allergic reactions, they are thought to release enzymes or chemical mediators that detoxify agents associated with the reaction. In parasitic infections, the eosinophils use surface mark- ers to attach themselves to the parasite and then release hydrolytic enzymes that kill it. Basophils. The basophils are the least numerous of the white blood cells, accounting for only 0.3% to 0.5% of the total leukocytes. 1 The specific granules of the baso- phils stain blue with a basic dye. These granules contain heparin, an anticoagulant; histamine, a vasodilator; and other mediators of inflammation. The basophil, which is a blood cell, is related to the connective tissue mast cell that contains similar granules. Both the basophils and mast cells are thought to be involved in allergic and hypersensitivity reactions. Agranulocytes Agranulocytes are leukocytes that lack cytoplasmic gran- ules. They include both the lymphocytes and monocytes/ macrophages. Lymphocytes. Lymphocytes are the most common of the agranulocytes, accounting for approximately 30% of the total blood leukocytes. 1 They originate in the bone marrow from lymphoid stem cells and migrate through the peripheral lymphoid organs, where they recognize antigens and participate in immune responses.