Phagocytes

The phagocytic process is initiated by contact and adhesion of an invading cell with a phagocyte cell membrane. Adhesion triggers a process whereby the phagocytic cell extrudes pseudopodia that surround the adhering microbe. As this process progresses, the microbe is actually surrounded by the phagocyte cell membrane. Then, invagination of the membrane fully engulfs the particle, and the membrane is

Scheme 5.1 • Lineages of blood cells. All blood cells derive from a pluripotent stem cell. Various cytokines direct the cells into their specific populations.

resealed with the particle encased inside an intracellular vacuolar body called a phagosome. Lysosomes in the cytoplasm then fuse with the phagosome to form phagolysosomes. The antimicrobial compounds in the phagosomes and lysosomes kill the engulfed pathogen and enzymatically cleave its remains into smaller pieces.

Eosinophils5

Eosinophils are granulocytes that can function as phagocytes, but much less efficiently than neutrophils can. They are present as 2% to 4% of blood leukocytes. Their name derives from the intense staining reaction of their intracellu-lar granules with the dye eosin. Eosinophil granules contain inflammatory mediators such as histamine and leukotrienes, so it makes sense that these cells are associated with the allergic response. Clues to the functions of eosinophils come from their behavior in certain disease states. Eosinophil counts are elevated above normal in the tissues in many different diseases, but they are recognized primarily for their diagnostic role in parasitic infections and in allergies. Eosinophils have a unique mode of action that lends to their extreme importance. Unlike neutrophils, eosinophils need not phagocytose a parasite to kill it. Indeed, some parasites are too large to allow phagocytosis. Eosinophils can physically surround a large parasite, forming a cell coat around the invader. Eosinophil granules release oxidative substances capable of destroying even large, multicellular parasites. Hence, even when phagocytosis fails, a mechanism exists to destroy large parasites.

Mast Cells and Basophils

Mast cells and basophils also release the inflammatory mediators commonly associated with allergy. Mast cells are especially prevalent in the skin, lungs, and nasal mucosa; their granules contain histamine. Basophils, present at only 0.2% of the leukocyte fraction in the blood, also contain histamine granules, but basophils are found circulating in the blood and not isolated in connective tissue. Both mast cells and basophils have high-affinity immunoglobulin E (IgE) receptors. Complexes of antigen molecules with IgE receptors on the cell surface lead to cross-linking of IgE and distortion of the cell membrane. The distortion causes the mast cell to degranulate, releasing mediators of the allergic response. Because of its association with hypersensitivity, IgE has been called "reagin" in the allergy literature. Diagnostically, IgE levels are elevated in allergy, systemic lupus erythe-matosus, and rheumatoid arthritis. Cromolyn sodium is a drug that prevents mast cell degranulation and thus blocks the allergic response. Cromolyn is used in asthma.

Macrophages and Monocytes4,5

Macrophages and monocytes are mononuclear cells that are capable of phagocytosis. In addition to their phagocytic capabilities, they biosynthesize and release soluble factors (complement, monokines) that govern the acquired immune response. The half-life of monocytes in the bloodstream is about 10 hours, during which time they migrate into tissues and differentiate into macrophages. A macrophage is a terminally differentiated monocyte. Macrophages possess a true anatomical distribution because they develop in the tissues to have specialized functions. Special macrophages are found in tissues such as the liver, lungs, spleen, gastrointestinal (GI) tract, lymph nodes, and brain. These specific macrophages are called either histiocytes (generic term) or by certain specialized names (Kupffer cells in liver, Langerhans cells in skin, alveolar macrophages in lung) (Table 5.1). The entire macrophage network is called the reticuloendothelial system. Other macrophages exist free in the tissues, where they carry out more nonspecific functions. Macrophages kill more slowly than neutrophils but have a much broader spectrum. It has been estimated that more than 100 soluble inflammatory substances are produced by macrophages. These substances account for macrophages' prolific abilities to direct, modulate, stimulate, and retard the immune response.

TABLE 5.1 The Reticuloendothelial System

Tissue

Cell

Tissue

Cell

Liver

Kupffer cells

Lung

Alveolar macrophages (dust cells)

Peritoneum

Peritoneal macrophages

Spleen

Dendritic cells

Skin

Langerhans cells

Brain

Microglial cells

Macrophages possess a very specialized function; they act as APCs (Fig. 5.1). APCs are responsible for the preprocessing of antigens, amplifying the numbers of antigenic determinant units, and presenting these determinant structures to the programming cells of the immune system. APCs in ternalize an organism or particle and digest it into small fragments still recognizable as antigen. The fragments are conjugated with molecules of the major histocompatibility complex 2 (MHC-II). These complexes are responsible for self or nonself cell recognition and ascertain that cells being processed are not self. MHCs also direct the binding of the antigenic determinant with immunoreactive cells. Once the antigen-MHC-II complex forms, it undergoes transcytosis to the macrophage's cell surface, where B lymphocytes and T-helper cells recognize the antigen via the B surface Ab and T-cell receptors. It is this step that transfers specificity and memory information from the determinant into the immune system through the modulation of B-cell differentiation. Under the regulatory influence of the T-helper cells, B cells are stimulated to differentiate into plasma cells that produce Ab. The T-helper cells accelerate and retard the

Macrophage Antigen Presentation
Figure 5.1 • Antigen capture and presentation by a macrophage lead to clones of Ab-producing plasma cells and memory B cells.

process as necessary. Thus, unlike the granulocytes, which have only destructive functions, monocytes and macrophages regulate and program the immune response.

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Responses

  • luka
    Do eosinophils carry out phagocytosis?
    2 years ago

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