Cells and Tissues of the Immune Response(진행중)
On the first two chapters, we have made reference to T and B lymphocytes, to macrophages and neutrophils, and to lymph nodes, thymus, and bone marrow. It is now time to examine in more detail these and other cells and tissues whose actions and products result in the elimination of foreign entities and the preservation of our good health.
A. Cells of the Immune System
I. TYPES OF HEMATOPOIETIC CELLS
As noted in Chapter 1, mammalian blood is made up of a plasma fluid phase containing oxygen-carrying erythrocytes (red blood cells) and infection-fighting leukocytes (white blood cells). These cells are known as hematopoietic cells. All hematopoietic cells are derived in the bone marrow from a common precursor called the hematopoietic stem cell (HSC), in a process called hematopoiesis (“the generation of blood”), which is described later in this chapter. Hematopoietic cells are categorized as being of either the myeloid or lymphoid lineage. Myeloid cells include erythrocytes and nonlymphocyte leukocytes such as neutrophils, monocyte/macrophages, eosinophils, basophils, and megakaryocytes. Cells considered to be of the lymphoid lineage include T and B lymphocytes, natural killer (NK) cells, and natural killer T (NKT) cells. Dendritic cells (DCs) can arise from either myeloid or lymphoid lineage cells (see Ch.11). The physical characteristics of these cell types are illustrated in Figure 3-1. Different hematopoietic cell types tend to reside and function in different compartments of the body (Fig. 3-2). Hematopoietic stem cells and early hematopoietic progenitors are generated and remain primarily in the bone marrow. Lymphocytes can be found in both the blood and the peripheral tissues. Other hematopoietic cell types tend to concentrate in either the blood or the tissues, but may move between these compartments when infection or injury occurs. We will first explore the features and functions of myeloid cells, followed by those of lymphoid cells. We then move to a discussion of how these cells are generated in the first place, and how and why they die. The second section of this chapter focuses on lymphoid tissues, which are the regions of the body where adaptive immune responses are initiated.
II. CELLS OF THE MYELOID LINEAGE
i) Introducing Myeloid Cells
Among the largest blood cells in the circulation are the monocytes, phagocytes that possess a regularly shaped nucleus. The principal functional features of these cells are their cytoplasmic lysosomes, which contain hydrolytic enzymes, and their abundance of organelles, which are required for the synthesis of secreted and membrane-bound proteins. Monocytes circulate in the blood at low density (3–5% of all blood leukocytes) for approximately 1 day before entering the tissues and serous cavities and maturing further to become macrophages. Macrophages (from the Greek, “big eaters”) are large, powerful phagocytes that function primarily in the tissues, tirelessly engulfing and digesting not only foreign entities, but also spent host cells and cellular debris: they are the “garbage collectors” of our tissues. In addition to their function in innate immunity as key phagocytes during inflammation, macrophages are also important antigenpresenting cells (APCs) for the T cells of the adaptive immune response. The functions of macrophages are discussed later in this chapter in more detail. Neutrophils, basophils, and eosinophils are all considered to be granulocytes, which are myeloid leukocytes that harbor large intracellular granules containing microbe-destroying hydrolytic enzymes. Neutrophils are the most common white cells in the body and respond immediately in great numbers to tissue injury. In addition to being granulocytes, neutrophils are phagocytes capable of engulfing macromolecules and particles. Neutrophils were originally called polymorphonuclear (PMN) leukocytes because of the appearance under the light microscope of their irregularly shaped, multilobed nuclei. The term “neutrophil” arose when it was observed that the cytoplasm and cytoplasmic granules of these cells stained neutrally with certain dyes. Neutrophil functions are discussed in more detail later in this chapter. Eosinophils and basophils acquired their names from the colors taken on by their cytoplasmic granules (as viewed under the microscope) when these cells were originally stained and examined in blood smears. Eosinophils are leukocytes with bilobed nuclei and large cytoplasmic granules that stain reddish with certain acidic dyes (such as eosin). These granules are filled with highly basic proteins and enzymes that are effective in the killing of large parasites. The eosinophil’s primary function is the removal of such pathogens, although it can also carry out phagocytosis. The vast majority (99%) of mature eosinophils reside in the connective tissues and so constitute less than 4% of all leukocytes in the blood. Eosinophils also have a role in allergy, and will be discussed in that context in Chapter 28. Basophils are circulating leukocytes with irregularly shaped nuclei and cytoplasmic granules that react with basic dyes (such as hematoxylin), thus staining a dark blue color. Basophils are important for inflammation, since their granules contain heparin and vasoactive amines, as well as many enzymes. Basophils are present in the body in very low numbers, residing primarily in the blood until they move into the tissues during an inflammatory response (see Ch.4). Mast cells (from the German word “mast,” meaning “food” or “feed”) were named by Paul Ehrlich, who found this cell type to be increased in the tissues of fattened animals. This observation is consistent with the role of mast cells in countering attacks by worms and other parasites. The cytoplasmic granules of mast cells stain in a way similar to the staining of basophilic granules, and also contain heparin and histamines. However, mast cells are derived from a separate cell lineage, mast cell nuclei are not lobed, and mast cell granules tend to be more numerous and of a smaller size compared to those of basophils. Unlike basophils, mast cells are rarely found in the blood, preferring to reside in the connective tissues and, in some cases, the gastrointestinal mucosa. The degranulation (release of granule contents) of mast cells is rapidly triggered by tissue injury, causing the release of histamine and dozens of cytokines and growth factors that initiate the inflammatory response and, occasionally, hypersensitivity and allergy (see Ch.28). Megakaryocytes are multinucleate cells (containing up to 20 nuclei) from which platelets are derived. Platelets are small, colorless, irregularly shaped nonnucleated cells. The primary role of platelets is to mediate blood clotting, but activated platelets also secrete cytokines that influence the functions and migration of other leukocytes during an inflammatory response. These cytokines are produced from preformed messenger RNAs (mRNAs) that are translated upon platelet activation. Erythrocytes are myeloid cells that are very important physiologically; however, they contribute minimally to the immune response and we will not discuss them further here.