Cell and Vascular Response to Infection and Injury 5
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Chapter 5 Cell and Vascular Response 5 to Infection and Injury Activation of the defense systems gives rise to inflam- small numbers (1–6%). Their life span is somewhat mation which, if microbes are involved, is called in- longer than that of the neutrophils. Under normal fection. The reactions may be acute or chronic and condition they migrate into the tissues and are found involve different types of inflammatory cells together scattered everywhere, but especially in the mucosa with lymphatics and blood vessels. of the gastrointestinal tract. In hypersensitivity reac- tions a high number of eosinophils may be present in tissues as well as in the circulating blood. Mostly 5.1 the nucleus has no more than two segments and the Inflammatory Cells cytoplasm carries large, bright, eosinophilic granules, The types, number and proportion of inflammatory which differentiate them from old neutrophils with cells taking part in an inflammatory reaction depend eosinophilic cytoplasm. Eosinophilic granules contain on the type of inflammation/infection. cationic (positively charged) proteins, three of which are major basic protein (MBP), eosinophilic cationic protein (ECP), and eosinophilic derived neurotoxin 5.1.1 (EDN) (Peters et al. 1986). These positively charged Neutrophils proteins make eosinophils able to bind to negatively Neutrophils or granulocytes (i.e., white blood cells charged molecules on other cells and make them toxic with discreet granules in the cytoplasm) are continu- for worms and other large parasites. ously produced in the bone marrow and make up the main part of the white blood cells that normally circu- late in the blood (40–75%). At need more neutrophils 5.1.3 are recruited, which is followed by an increased num- Lymphocytes ber in the circulation. Neutrophils are end cells and As already mentioned, B cells originate in the bone thus cannot divide. Their life span is short (3–4 days). marrow and T cells in the thymus. Together they make The nucleus of the cell is divided into two to five seg- up 20–45% of the white cells circulating in the periph- ments depending on the age of the cell (Fig. 12.1b). eral blood. Mature lymphocytes are small and have a The cytoplasm carries two types of fine, inconspicuous, round, compact and dark nucleus, and sparse cyto- and enzyme-containing granules. Neutrophils engulf plasm (Fig. 15.1). In routinely stained sections, B and (phagocytose) microbes and kill them by means of the T cells look alike. However, it is possible to differenti- enzymes stored in the cytoplasm. When released into ate between them and also between their subgroups by the tissue these enzymes also have the ability to de- means of immunohistochemical staining techniques grade dead cells and tissue fragments. Neutrophils do using monoclonal antibodies directed against their not reside in the tissues under normal condition, but surface antigens. are called upon at need, and thus are the dominating Stimulated lymphocytes are larger than mature lym- cells in acute inflammation. In old multisegmented phocytes. In routinely prepared sections stimulated B neutrophils the cytoplasm becomes eosinophilic and cells are easily identified in the fully developed germi- the cells may be mistaken for eosinophils. nal center of a lymphocytoma. They have large, light, and somewhat irregular nuclei, which contain one or two nucleoli (Fig. 18.2c). However, stimulated T cells, 5.1.2 usually components of a mixed lymphocytic infiltrate, Eosinophils stand out because they have a slightly irregular form Like neutrophils, eosinophils are end cells, produced and are larger and seem more compact than the sur- in the bone marrow. They circulate in the blood in rounding normal lymphocytes (Fig. 20.5c). The latter 22 5 Cell and Vascular Response to Infection and Injury Fig. 5.1 Mast cells. a ACA. Between three dilated venules there ter (arrow); H&E, ×1000. c ACA. A small mast cell with hazy are two large mast cells (large arrows) and two small heav- cytoplasm (arrow). The vessel is an arteriole; H&E, ×1000. ily charged with granules (small arrows); toluidine blue, ×400. d Mastocytoma. Arrows binuclear cells; H&E, ×400 b ACA. A large mast cell stuffed with large granules in the cen- is an artifact probably due to too much stain and/or blood, but are present in connective tissue through- thick sections. The reason for this proposition is that out the body. Morphologically there are two variants in smears (Fig. 26.3c) and in sections, slightly faded of mast cells, a larger and a smaller. The large cells are after demonstration using a carbon arc lamp projec- also called connective tissue mast cells, and the small tor, these cells also reveal large nuclei containing one cells mucosal mast cells. In spite of this, both variants or two nucleoli and many mitotic figures (Fig. 26.3f). may be present together in the skin as well as in the In routinely stained sections, stimulated T cells are mucous membranes. The large mast cell is triangular, impossible to differentiate from T cell lymphoma cells has a round nucleus and a rich cytoplasm stuffed with (Sect. 26.3.4). large granules. The small mast cell is round or slightly oval. It has a round nucleus and because of densely packed small granules the cytoplasm is hazy. Among 5.1.4 other substances the granules contain histamine. In Plasma Cells normal skin, mast cells are located around vessels in Plasma cells, the effector cells of B cells, are larger than the papillary dermis and close to nerves and append- lymphocytes. They are oval and have a round and ec- ages. centrically located nucleus. In the cytoplasm close to A greatly increased number of mast cells are found the nucleus there is a typical crescent-like light area. in urticaria pigmentosa, mastocytoma, and related In longstanding lesions binuclear plasma cells may be conditions. However, the number of mast cells is also present (Figs. 18.1 and 18.4b). Plasma cells are com- increased in lesions of common dermatoses such as mon in chronic inflammation and are often numer- chronic dermatitis, psoriasis, and lichen planus (Tharp ous in infections caused by spirochetes and Leishma- 2001). According to the experience of the author there nia protozoa. They develop and mature in the lymph is also an increase in mast cells in infectious diseases nodes and migrate to the skin. such as acrodermatitis chronica atrophicans (ACA), a kind of borreliosis, and secondary syphilis, and in amalgam tattoo. In acute inflammation/infection to- 5.1.5 gether with basophils they release histamine (Sect. Mast Cells 5.2.1). Mast cells originate from the bone marrow and are Once recognized in H&E-stained sections, mast able to divide. They do not normally circulate in the cells are not difficult to identify, but they are better 5.2 Acute Inflammation 23 Fig. 5.2 Phagocytosis. Smear from a subepidermal vesicle. with a newly engulfed neutrophil. In the middle there is a group There are two old neutrophils with a multisegmented nucleus of macrophages which contain the remains of neutrophils in (arrowheads) and several macrophages. Arrow, top left macro- various stages of processing in the cytoplasm. In the macro- phage in close contact with a neutrophil containing a disinte- phage in the top right corner the remains of a nucleus are lying grating, swollen neutrophil; arrow, bottom right macrophage in a vacuole (arrow). Mayer staining, ×1000 displayed by means of special stains such as toluidine of phagocytosis are often, as in this book, called his- blue or Giemsa stains, which accentuate the granules tiocytes. Macrophages (histiocytes) are a common (Figs. 5.1 and 29.7b). In sections stained with tolu- component of inflammatory cell infiltrates in chronic idine and Giemsa, granules become blue and with infections and in the healing stage of acute infections May-Grünwald Giemsa metachromatically red. (Fig. 5.2). 5.1.6 5.2 Basophils Acute Inflammation Basophils are bone marrow-derived granulocytes The histologic hallmarks of acute inflammation are which circulate in the blood in small numbers (0–1%). exudation of plasma and migration of inflammatory They have a segmented nucleus and like mast cells cells, predominantly neutrophils, from postcapillary carry basophilic granules containing histamine in the venules into the perivascular tissue. cytoplasm. They are not precursors of mast cells. 5.2.1 5.1.7 Active Phase Monocytes/Macrophages In response to injury or bacterial infection, histamine Monocytes have an abundant cytoplasm and a large and serotonin, short-lived vasoactive chemical media- bean-shaped nucleus. They originate from the bone tors stored in the tissue (histamine in mast cells and marrow and circulate in the blood (2–10%). However, basophils and serotonin in platelets) are released and after a short time in the circulation they migrate into start the inflammatory process. Histamine and sero- connective tissue where they become larger, acquire tonin cause dilatation of arterioles, which increases the capacity to phagocytose and when doing so be- the blood flow and capillary pressure. Closed capillar- come activated. Like neutrophils, macrophages rec- ies open up and become filled with blood. Due to the ognize bacteria by surface receptors that are specific increased capillary flow and pressure, postcapillary for bacterial products. On activation they become venules become distended and gaps appear between even larger, and their ability to phagocytose and kill the endothelial cells, through which plasma leaks out bacteria increases. Tissue macrophages without signs into the surrounding tissue. The gaps are the result of 24 5 Cell and Vascular Response to Infection and Injury contraction of two adjacent endothelial cells brought but then they suddenly stop and stick to the intima about by the influence of the vasoactive mediators. before they sneak through the wall using the gaps be- Contracted cells bulge into the vascular lumen and tween the epithelial cells.