Figure 99

Neutrophil phagocytosis, a. Phagocytosis begins with recognition and attachment of foreign material (antigen), mainly by Fc receptors that interact with the Fc region of antibodies bound to the antigen.

b. The antigen is then engulfed by pseudopods of the neutrophil.

c. As the pseudopods come together and fuse, the antigen is internalized. d. Once the phagosome is formed, digestion is initiated by activation of membrane-bounded oxidases of the phagosome, e. Next, both specific and azurophilic granules fuse with the phagosome and exocytosis release their contents, forming a phagolysosome. This fusion and release of granules is called degranulation. f. The enzymatic contents of the granules are responsible for killing and digesting the microorganism. The entire digestive process occurs within the phagolysosome, which protects the cell from self-injury, g. The digested material is either exocytosed into the extracellular space or stored as residual bodies within the neutrophil.

azurophilic ranule

antigen pseudopod

Fc receptor azurophilic ranule pseudopod antigen

Eosinophils and lymphocytes are more commonly found at sites of chronic inflammation.

Eosinophils

Eosinophils are named for the large, eosinophilic, retractile granules in their cytoplasm

Eosinophils are about the same size as neutrophils, and their nuclei are typically bilobed (Fig. 9.10). As in neutrophils, the compact heterochromatin of eosinophils is chiefly adjacent to the nuclear envelope, whereas the eu-chromatin is located in the center of the nucleus. The cytoplasm contains two types of granules: numerous, large, elongated specific granules and azurophilic granules (otherwise, the eosinophil contains only a sparse representation of membranous organelles).

• Specific granules of eosinophils contain a aystalloid body that is readily seen with the TEM, surrounded by a less electron-dense matrix. These crystalloid bodies are responsible for the refractivity of the granules in the light microscope. They contain four major proteins: an arginine-rich protein called major basic protein (MBP) that accounts for the intense acidophilia of the granule, eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), and eosinophil-derived neurotoxin (EDN). MBP is localized in the crystalloid body; the other three proteins are found in the granule matrix. Specific granules also contain histaminase, arylsulfatase, collage-nase, and cathepsins. MBP, ECP, and EPO have a strong cytotoxic effect on protozoans and helminthic parasites; EDN causes nervous system dysfunction in parasitic organisms; histaminase neutralizes the activity of histamine; and arylsulfatase neutralizes slow-reacting substance of anaphylaxis (SRS-A) secreted by basophils (see Chapter 5, page 145).

• Azurophilic granules are lysosomes. They contain a variety of the usual lysosomal acid hydrolases and other hydrolytic enzymes that function in destruction of parasites and hydrolysis of antigen-antibody complexes internalized by the eosinophil.

Eosinophils are associated with allergic reactions, parasitic infections, and chronic inflammation

The release of arylsulfatase and histaminase by eosinophils at sites of allergic reaction moderates the potentially deleterious effects of inflammatory vasoactive agents. The eosinophil also participates in other immunologic responses, and phagocytoses antigen-antibody complexes. Thus, the count of eosinophils in blood samples of individuals with allergies and parasitic infections is usually high. Eosinophils play a major role is host defense against helminthic parasites. They are also found in large numbers in the lamina propria of the intestinal tract and at other sites of potential chronic inflammation.

Basophils

Basophils are the least numerous of the WBCs, accounting for less than 0.5% of the total leukocytes

Often, several hundred WBCs must be examined in a blood smear before one basophil is found. Basophils are about the same size as neutrophils and are so named because the numerous large granules in its cytoplasm stain with basic dyes. The lobed basophil nucleus is usually obscured by the granules in stained blood smears, but its characteristics are evident in electron micrographs (Fig. 9.11). Heterochromatin is chiefly in a peripheral location, and euchromatin is chiefly centrally located; typical cytoplasmic organelles are sparse. The basophil plasma membrane possesses numerous Fc receptors for immunoglobulin E (IgE) antibodies. In addition, a specific 39-kDa protein called CD40L is expressed on the basophil's surface. CD40L interacts with a complementary receptor (CD40) on B lymphocytes, which results in increased synthesis of IgE.

The basophil cytoplasm contains two types of granules: specific granules that are larger than the specific granules of the neutrophil and nonspecific azurophilic granules.

• Specific granules exhibit a grainy texture and myelin figures when viewed with the TEM. These granules contain a variety of substances, namely, heparan sulfate, histamine, and SRS-A. Histamine and the SRS-A are vasoactive agents that, among other actions, cause dilation of small blood vessels. Heparan sulfate is a sulfated gly-cosaminoglycan that is closely related to the heparin found in the granules of tissue mast cells. The amount of sulfate in this molecule accounts for the intense basophilia of the specific granules of the basophil. No role for heparan sulfate in inflammation has yet been elucidated.

• Azurophilic granules are the lysosomes of basophils and contain a variety of the usual lysosomal acid hydrolases similar to those in other leukocytes.

The function of basophils is closely related to that of mast cells

Basophils are functionally related to, but not identical with, mast cells of the connective tissue (see Table 5.6). Both mast cells and basophils bind an antibody secreted by plasma cells, IgE, through Fc receptors expressed on their cell surface. The subsequent exposure to, and reaction with, the antigen specific for IgE triggers the release of vasoactive agents from the basophil and mast cell granules. These substances are responsible for the severe vascular disturbances associated with hypersensitivity and anaphylaxis. Furthermore, both basophils and mast cells are derived from the same hemopoietic stem cell. Precursors of

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