Granulocytic Cells

The granulocytes are classified as neutrophils, eosinophils, or basophils on the basis of cellular morphology and cytoplasmic staining characteristics (Figure 2-10). The neu-trophil has a multilobed nucleus and a granulated cytoplasm that stains with both acid and basic dyes; it is often called a polymorphonuclear leukocyte (PMN) for its multilobed nucleus. The eosinophil has a bilobed nucleus and a granulated cytoplasm that stains with the acid dye eosin red (hence its name). The basophil has a lobed nucleus and heavily granulated cytoplasm that stains with the basic dye methylene blue. Both neutrophils and eosinophils are phagocytic, whereas basophils are not. Neutrophils, which constitute 50%-70% of the circulating white blood cells, are much more numerous than eosinophils (1%-3%) or basophils (<1%).

NEUTROPHILS

Neutrophils are produced by hematopoiesis in the bone marrow. They are released into the peripheral blood and circulate for 7-10 h before migrating into the tissues, where they have a life span of only a few days. In response to many types of infections, the bone marrow releases more than the usual number of neutrophils and these cells generally are the first to arrive at a site of inflammation. The resulting transient increase in the number of circulating neutrophils, called leukocytosis, is used medically as an indication of infection.

Movement of circulating neutrophils into tissues, called extravasation, takes several steps: the cell first adheres to the vascular endothelium, then penetrates the gap between adjacent endothelial cells lining the vessel wall, and finally penetrates the vascular basement membrane, moving out into the tissue spaces. (This process is described in detail in Chapter 15.) A number of substances generated in an inflammatory reaction serve as chemotactic factors that promote accumulation of neutrophils at an inflammatory site. Among these chemotactic factors are some of the complement

Granulocytic Cell NeutrophilRespiratory Burst

(c) Basophil

Neutrophils also employ both oxygen-dependent and oxygen-independent pathways to generate antimicrobial substances. Neutrophils are in fact much more likely than macrophages to kill ingested microorganisms. Neutrophils exhibit a larger respiratory burst than macrophages and consequently are able to generate more reactive oxygen intermediates and reactive nitrogen intermediates (see Table 2-6). In addition, neutrophils express higher levels of defensins than macrophages do.

EOSINOPHILS

Eosinophils, like neutrophils, are motile phagocytic cells that can migrate from the blood into the tissue spaces. Their phagocytic role is significantly less important than that of neutrophils, and it is thought that they play a role in the defense against parasitic organisms (see Chapter 17). The secreted contents of eosinophilic granules may damage the parasite membrane.

BASOPHILS

Basophils are nonphagocytic granulocytes that function by releasing pharmacologically active substances from their cy-toplasmic granules. These substances play a major role in certain allergic responses.

(c) Basophil

Granulocytic Cell Basophil

Glycogen

Granule

Drawings showing typical morphology of granulocytes. Note differences in the shape of the nucleus and in the number and shape of cytoplasmic granules.

Glycogen

Granule

FIGURE 2-10

Drawings showing typical morphology of granulocytes. Note differences in the shape of the nucleus and in the number and shape of cytoplasmic granules.

components, components of the blood-clotting system, and several cytokines secreted by activated TH cells and macrophages.

Like macrophages, neutrophils are active phagocytic cells. Phagocytosis by neutrophils is similar to that described for macrophages, except that the lytic enzymes and bactericidal substances in neutrophils are contained within primary and secondary granules (see Figure 2-10a). The larger, denser primary granules are a type of lysosome containing peroxidase, lysozyme, and various hydrolytic enzymes. The smaller secondary granules contain collagenase, lactoferrin, and lyso-zyme. Both primary and secondary granules fuse with phagosomes, whose contents are then digested and eliminated much as they are in macrophages.

MAST CELLS

Mast-cell precursors, which are formed in the bone marrow by hematopoiesis, are released into the blood as undifferenti-ated cells; they do not differentiate until they leave the blood and enter the tissues. Mast cells can be found in a wide variety of tissues, including the skin, connective tissues of various organs, and mucosal epithelial tissue of the respiratory, genitourinary, and digestive tracts. Like circulating basophils, these cells have large numbers of cytoplasmic granules that contain histamine and other pharmacologically active substances. Mast cells, together with blood basophils, play an important role in the development of allergies.

DENDRITIC CELLS

The dendritic cell (DC) acquired its name because it is covered with long membrane extensions that resemble the den-drites of nerve cells. Dendritic cells can be difficult to isolate because the conventional procedures for cell isolation tend to damage their long extensions. The development of isolation techniques that employ enzymes and gentler dispersion has facilitated isolation of these cells for study in vitro. There are many types of dendritic cells, although most mature dendritic cells have the same major function, the presentation of antigen to TH cells. Four types of dendritic cells are known: Langerhans cells, interstitial dendritic cells, myeloid cells, and lymphoid dendritic cells. Each arises from hematopoi-etic stem cells via different pathways and in different locations. Figure 2-11 shows that they descend through both the myeloid and lymphoid lineages. Despite their differences,

Hematopoietic stem cell

Hematopoietic stem cell

Common myeloid progenitor

Common lymphoid progenitor

Common myeloid progenitor

Common lymphoid progenitor

Folliculaire Dendritische Cellen

Langerhans cell

FIGURE 2-11

Interstitial dendritic cell

Myeloid dendritic cell

Lymphoid dendritic cell

Langerhans cell

FIGURE 2-11

Interstitial dendritic cell

Myeloid dendritic cell

Lymphoid dendritic cell

Dendritic cells arise from both the myeloid and lymphoid lineages. The myeloid pathway that gives rise to the monocyte/macrophage cell type also gives rise to dendritic cells. Some dendritic cells also arise from the lymphoid lineage. These considerations do not apply to follicular dendritic cells, which are not derived from bone marrow.

they all constitutively express high levels of both class II MHC molecules and members of the co-stimulatory B7 family. For this reason, they are more potent antigen-presenting cells than macrophages and B cells, both of which need to be activated before they can function as antigen-presenting cells (APCs). Immature or precursor forms of each of these types of dendritic cells acquire antigen by phagocytosis or endocy-tosis; the antigen is processed, and mature dendritic cells present it to TH cells. Following microbial invasion or during inflammation, mature and immature forms of Langerhans cells and interstitial dendritic cells migrate into draining lymph nodes, where they make the critical presentation of antigen to TH cells that is required for the initiation of responses by those key cells.

Another type of dendritic cell, the follicular dendritic cell (Figure 2-12), does not arise in bone marrow and has a different function from the antigen-presenting dendritic cells described above. Follicular dendritic cells do not express class II MHC molecules and therefore do not function as antigen-presenting cells for TH-cell activation. These dendritic cells were named for their exclusive location in organized structures of the lymph node called lymph follicles, which are rich in B cells. Although they do not express class II molecules, follicular dendritic cells express high levels of membrane receptors for antibody, which allows the binding of antigen-an tibody complexes. The interaction of B cells with this bound antigen can have important effects on B cell responses.

Coping with Asthma

Coping with Asthma

If you suffer with asthma, you will no doubt be familiar with the uncomfortable sensations as your bronchial tubes begin to narrow and your muscles around them start to tighten. A sticky mucus known as phlegm begins to produce and increase within your bronchial tubes and you begin to wheeze, cough and struggle to breathe.

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