White blood cells typically destroy invading microorganisms via phagocytosis (Figure 1). While phagocytic leukocytes possess cell surface receptors against bacterial lipopolysaccharides or peptidoglycans, in most cases they recognize infective pathogens indirectly, by the presence of antibodies or complement factors that have previously adhered to their surface. The process of tagging an invader with protective proteins to facilitate recognition by phagocytic leukocytes is called opsonization.
Fig1. Phagocytosis. This figure depicts the destruction of an opsonized microorganism, shaded in ORANGE, by a neutrophil via phagocytosis. The multilobed nucleus of the neutrophil is shown in purple, secretory granules in green. The presence of an antibody or complement tag is indicated by a yellow triangle, with the corresponding cell surface receptor as a bright orange square. Cellular debris from the microorganism is represented as orange line segments. (A)The neutrophil binds an antigen molecule on the opsonized microbe via a receptor. (B) The neutrophil envelops the microbe. (C) Secretory granules fuse with the newly internalized phagosome, delivering their contents. (D) Granule-derived enzymes and cytotoxins destroy the microorganism. (E)The phagosome then fuses with the cell membrane, expelling any remaining debris.
Pathogen binding triggers dramatic alterations in the shape of the phagocyte, which proceeds to envelop the target cell until it is encased within an internalized membrane vesicle called a phagosome (phagolysosome). The encapsulated invader is then destroyed using a combination of hydrolytic enzymes (eg, lysozyme, proteases), antimicrobial peptides (defensins), and reactive oxygen species. This arsenal of toxins and degradatory enzymes are stored in cytoplasmic vesicles known as granules, which fuse with the phagosome (Table 1). Since these granules can be observed under a microscope, the cells that harbor them are referred to as granulocytes. Eventually, after digestion of the microbial invader and absorption of their component sugars, amino acids, etc., the phagosome migrates to and fuses with the plasma membrane of the white blood cell, expelling any remaining debris.
Table1. Enzymes & Proteins of the Granules of Phagocytic Leukocytes
The components of this debris, which include fragments of proteins, oligosaccharides, lipopolysaccharides, peptidoglycans, and polynucleotides, provide an important source of antigens for stimulating the production of new antibodies. Helper T cells and other leukocytes absorb these materials via endocytosis, then route them to the cell surface in association with a membrane protein called the major histocompatibility complex (MHC). The MHC serves as a scaffold for presenting potential antigens to surrounding lymphocytes in a form likely to stimulate the production of new antibodies.
The three principal classes of phagocytic leukocytes are neutrophils, eosinophils, and macrophages. Neutrophils, which comprise roughly 60% of the white blood cells present in the circulation, phagocytize bacteria and small eukaryotic microorganisms such as fungi. The less numerouseosinophils, which make up 2 to 3% of the leukocytes in the blood, ingest larger eukaryotic microorganisms such as paramecia. Macro phages are derived from monocytes, which comprise about 5% of the leukocytes in the blood. Monocytes migrate from the bloodstream into tissues throughout the body where, on receipt of a stimulus, they differentiate to form macrophages. While macrophages can ingest invading microbes, the signature function of these large phagocytes is to destroy human host cells that have been compromised by infection, malignant transformation, or programmed cell death, also known as apoptosis. These functionally compromised cells are recognized by the appearance of aberrant proteins and oligosaccharides on their surface. Precocious activation of macrophages is associated with the etiology of many degenerative diseases such as osteo porosis, atherosclerosis, arthritis, and cystic fibrosis. They also can facilitate the metastasis of cancer cells.
