Phagocyte

Yet another enzyme in the neutrophil's membrane makes __ __, which is a powerful inducer of __.

Yet another enzyme in the neutrophil's membrane makes nitric oxide, which is a powerful inducer of inflammation.

Phagosome Maturation and Microbial Killing A membranous organelle called a __ adds digestive chemicals to the maturing __, which is now called a __. Phagolysosomes contain __ substances, such as highly __, toxic forms of __, in an environment with a pH of about __ due to active pumping of __ from the __ into the __. These substances, along with __ or so different enzymes, such as l__, proteases, and n__, destroy the engulfed microbes .

A membranous organelle called a lysosome adds digestive chemicals to the maturing phagosome, which is now called a phagolysosome (fag-ō-lī'sō-sōm) . Phagolysosomes contain antimicrobial substances, such as highly reactive, toxic forms of oxygen, in an environment with a pH of about 5.5 due to active pumping of H+ from the cytosol into the phagolysosome. These substances, along with 30 or so different enzymes, such as lipases, proteases, and nucleases, destroy the engulfed microbes .

After arriving at the site of an infection, phagocytes __ to microorganisms through the binding of complementary __, such as __, found on the __ of cells . This process is called __ or __. Some bacteria have virulence factors, such as slippery __, which hinder adhesion by __.

After arriving at the site of an infection, phagocytes attach to microorganisms through the binding of complementary chemicals, such as glycoproteins, found on the membranes of cells . This process is called adhesion or attachment. Some bacteria have virulence factors, such as slippery capsules, which hinder adhesion by phagocytes.

Adhesions All pathogens are more readily __ if they are first covered with __ proteins, such as __ proteins (discussed later) or specific antimicrobial proteins of adaptive immunity called __ . This coating process is called __ , and the proteins are called __. Generally, __ increase the number and kinds of __ sites on a microbe's surface.

All pathogens are more readily phagocytized if they are first covered with antimicrobial proteins, such as complement proteins (discussed later) or specific antimicrobial proteins of adaptive immunity called antibodies (discussed in Chapter 16). This coating process is called opsonization10 (op'sŭ-nī-za'shun), and the proteins are called opsonins. Generally, opsonins increase the number and kinds of binding sites on a microbe's surface.

As discussed earlier, __ can phagocytize; however, this is not their usual mode of __. Instead, eosinophils secrete __ chemicals against __ that are too __ to ingest. They attack parasitic __ (__) by adhering to the __'s surface, where they secrete __ onto the surface of the worms. These toxins __ the helminth and may even __ it.

As discussed earlier, eosinophils can phagocytize; however, this is not their usual mode of attack. Instead, eosinophils secrete antimicrobial chemicals against pathogens that are too large to ingest. They attack parasitic helminths (worms) by adhering to the worm's surface, where they secrete toxins onto the surface of the worms. These toxins weaken the helminth and may even kill it.

Besides their attacks against parasitic __, __ have recently been discovered to use a never-before-seen tactic against bacteria: __ from Gram-__ bacterial cell walls triggers __ to rapidly eject their __ DNA, which combines with previously extruded __ proteins to form a __ barrier. This extracellular structure binds to and then kills the bacteria. This is the first evidence that __ can have __ activity, and scientists are investigating exactly how __ DNA might act as an __ agent.

Besides their attacks against parasitic helminths, eosinophils have recently been discovered to use a never-before-seen tactic against bacteria: Lipopolysaccharide from Gram-negative bacterial cell walls triggers eosinophils to rapidly eject their mitochondrial DNA, which combines with previously extruded eosinophil proteins to form a physical barrier. This extracellular structure binds to and then kills the bacteria. This is the first evidence that DNA can have antimicrobial activity, and scientists are investigating exactly how mitochondrial DNA might act as an antibacterial agent.

Chemicals that attract phagocytic __ include microbial __, parts of microbial __, components of damaged __ and __ blood cells, and __ factors. Chemotactic factors include __, __ derived from complement , and chemicals called __, which are released by __ already at the site of infection.

Chemicals that attract phagocytic leukocytes include microbial secretions, parts of microbial cells, components of damaged tissues and white blood cells, and chemotactic factors. Chemotactic factors include defensins, peptides derived from complement , and chemicals called chemokines, which are released by leukocytes already at the site of infection.

Chemotaxis is movement of a cell either toward a __ stimulus (__ chemotaxis) or __ from a chemical stimulus (__ chemotaxis). In the case of phagocytes, positive chemotaxis involves the use of __ to __ toward microorganisms at a site of an infection .

Chemotaxis is movement of a cell either toward a chemical stimulus (positive chemotaxis) or away from a chemical stimulus (negative chemotaxis). In the case of phagocytes, positive chemotaxis involves the use of pseudopods (soo'dō-podz) to crawl toward microorganisms at a site of an infection .

Elimination Digestion is not always __, and phagocytes eliminate remnants of microorganisms via __, a process that is essentially the reverse of __ . Some microbial components are specially __ and remain attached to the __ __ of some phagocytes, particularly __ cells, a phenomenon that plays a role in the __ immune response.

Elimination Digestion is not always complete, and phagocytes eliminate remnants of microorganisms via exocytosis, a process that is essentially the reverse of ingestion . Some microbial components are specially processed and remain attached to the cytoplasmic membrane of some phagocytes, particularly dendritic cells, a phenomenon that plays a role in the adaptive immune response (discussed in Chapter 16).

Neutrophils can also destroy nearby microbial cells without phagocytosis, though phagocytosis is more common. They do this in several ways: Enzymes in a __'s cytoplasmic membrane add __ to oxygen, creating highly reactive __ radical __ and __ __ (__). Another enzyme converts these into __, the active __ ingredient in household __. These chemicals can __ nearby invaders.

Enzymes in a neutrophil's cytoplasmic membrane add electrons to oxygen, creating highly reactive superoxide radical O−2 and hydrogen peroxide (H2O2). Another enzyme converts these into hypochlorite, the active antimicrobial ingredient in household bleach. These chemicals can kill nearby invaders.

__, an abnormally __ number of __ in the blood, is often indicative of __ infestation, though it is also commonly seen in patients with __.

Eosinophilia (ē-ō-sin'ō-fil-e-ă), an abnormally high number of eosinophils in the blood, is often indicative of helminth infestation, though it is also commonly seen in patients with allergies.

For improved understanding, we will consider the process of phagocytosis in six steps: __, __, __, __, __, and __ (FIGURE 15.6). However, the process is actually __ and doesn't proceed in a discrete step-wise manner.

For improved understanding, we will consider the process of phagocytosis in six steps: chemotaxis, adhesion, ingestion, maturation, killing, and elimination (FIGURE 15.6). However, the process is actually continuous and doesn't proceed in a discrete step-wise manner.

Ingestion After phagocytes adhere to pathogens, they extend __ to surround the microbe . The encompassed microbe is internalized as the pseudopods __ to form a food __ called a __.

Ingestion After phagocytes adhere to pathogens, they extend pseudopods to surround the microbe . The encompassed microbe is internalized as the pseudopods fuse to form a food vesicle called a phagosome.

Phagosome Maturation and Microbial Killing Most pathogens are dead within __ minutes of the __'s formation, though some bacteria contain __ __ (such as waxy __ __) that resist a __'s action. In the end, a phagolysosome is known as a __ __.

Most pathogens are dead within 30 minutes of the phagolysosome's formation, though some bacteria contain virulence factors (such as waxy cell walls) that resist a lysosome's action. In the end, a phagolysosome is known as a residual body.

__ __ __ (__ cells) are another type of defensive __ of __ immunity that works by secreting __ onto the surfaces of __ infected cells and __ (__). __ cells identify and spare __ body cells because the latter express __ proteins similar to those on the __ cells. The name natural killer comes from the fact that NK cells are programmed to kill other cells unless they receive an __ signal.

Natural killer lymphocytes (NK cells) are another type of defensive leukocyte of innate immunity that works by secreting toxins onto the surfaces of virally infected cells and neoplasms (tumors). NK cells identify and spare normal body cells because the latter express membrane proteins similar to those on the NK cells. The name natural killer comes from the fact that NK cells are programmed to kill other cells unless they receive an inhibitory signal.

Neutrophils also generate webs of extracellular fibers nicknamed __s, for __ __ __. Neutrophils synthesize NETs via a unique form of cellular __ involving the __ of their __. As the nuclear __ breaks down, __ and __ are released into the __, and the mixing of nuclear components with membranes and proteins derived from cytoplasmic granules combine to form NET __.

Neutrophils also generate webs of extracellular fibers nicknamed NETs, for neutrophil extracellular traps. Neutrophils synthesize NETs via a unique form of cellular suicide involving the disintegration of their nuclei. As the nuclear envelope breaks down, DNA and histones are released into the cytosol, and the mixing of nuclear components with membranes and proteins derived from cytoplasmic granules combine to form NET fibers.

Neutrophils can also destroy nearby microbial cells without ___, though __ is more common. They do this in several ways:

Neutrophils can also destroy nearby microbial cells without phagocytosis, though phagocytosis is more common. They do this in several ways:

Nonphagocytic Killing Phagocytosis involves __ a pathogen once it has been ingested—that is, once it is inside the phagocyte. In contrast, __, __ __ cells, and __ can accomplish killing without __.

Phagocytosis involves killing a pathogen once it has been ingested—that is, once it is inside the phagocyte. In contrast, eosinophils, natural killer cells, and neutrophils can accomplish killing without phagocytosis.

Phagocytosis, which means "__ by a __," is a way that some microbes obtain __ (see Chapter 3), but phagocytes —phagocytic defense cells of the body—use phagocytosis to rid the body of __ that have evaded the body's __ line of defense.

Phagocytosis, which means "eating by a cell," is a way that some microbes obtain nutrients (see Chapter 3), but phagocytes (fag'ō-sītz)—phagocytic defense cells of the body—use phagocytosis to rid the body of pathogens that have evaded the body's first line of defense.

How is it that phagocytes destroy invading pathogens and leave the body's own healthy cells unharmed? At least two mechanisms are responsible for this: Some phagocytes have __ __ receptors for various microbial surface __ lacking on the body's cells, such as microbial __ __ components or __ proteins. __ such as certain __ proteins and __ molecules called __ provide a signal to the __.

Some phagocytes have cytoplasmic membrane receptors for various microbial surface components lacking on the body's cells, such as microbial cell wall components or flagellar proteins. Opsonins such as certain blood proteins and immune molecules called antibodies provide a signal to the phagocyte.

The neutrophil then kills itself using __ and __. The dying cell releases the __ as its cytoplasmic __ ruptures. NETs trap both Gram-__ and Gram-__ bacteria, immobilizing them and sequestering them along with antimicrobial __, which kill the __. Thus even in their dying moments, neutrophils fulfill their role as __ cells.

The neutrophil then kills itself using superoxide and peroxide. The dying cell releases the NETs as its cytoplasmic membrane ruptures. NETs trap both Gram-positive and Gram-negative bacteria, immobilizing them and sequestering them along with antimicrobial peptides, which kill the bacteria. Thus even in their dying moments, neutrophils fulfill their role as defensive cells.