How do phagocytes fight pathogenic microbes?

Phagocytosis begins with the neutrophil or macrophage flowing around the pathogen and engulfing it so that it winds up enclosed in a phagosome (phagocytic vesicle). But this is only the first step, because the more challenging task of destroying the microorganisms remains. Indeed, some pathogens have special, effective mechanisms for frustrating this destruction step.

The next step is the fusion of lysosomes with the phagosome. The result is called a phagolysosome. Lysosome are derived from the Golgi apparatus, much like secretion vesicles, but their contents are focused on destroying microorganisms.

Destruction of the Microbes

The following are important factors that help destroy microorganisms within a phagolysosome:

Oxygen Radicals. A complex of proteins called phagocyte oxidase in the membrane of a phagolysosome generates oxygen radicals in the phagosome. A single electron is taken from NADPH and added to oxygen, partially reducing it. The resulting highly reactive molecules react with proteins, lipids and other biological molecules. See the next webpage for details.

Nitric Oxide. Nitric oxide synthase synthesizes nitric oxide, a reactive substance that reacts with superoxide to create further molecules that damage various biological molecules. (But nitric oxide is also, remarkably enough, an important regulatory molecule elsewhere. More on this later this quarter.)

Anti-Microbial Proteins. Lysosomes contain several proteases, including a broad spectrum enzyme,elastase, which is important or even essential for killing various bacteria. Another anti-microbial protein is lysozyme, which attacks the cell walls of certain (gram positive) bacteria.

Anti-Microbial Peptides.Defensins and certain other peptides attack bacterial cell membranes. Similar molecules are found throughout much of the animal kingdom.

Binding Proteins.Lactoferrin binds iron ions, which are necessary for growth of bacteria. Another protein binds vitamin B12.

Hydrogen Ion Transport. Transporters for hydrogen ions (a second role of the oxidase) acidify the phagolysosome, which kills various microorganisms and is important for the action of the proteases described above.

In addition to destroying the microorganism, phagocytes also release molecules that diffuse to other cells and help coordinate the overall response to an infection.

Regulatory molecules that regulate an immune response are called cytokines. Most are small proteins and are mainly released by white blood cells and their relatives, such as macrophages.

Cytokines for the most part act as paracrines, which are regulatory molecules that are released by one cell and diffuse locally to neighboring cells. (Locally in this context means over millimeters or perhaps a few centimeters). But occasionally cytokines act more widely. For example, certain cytokines diffuse from a site of infection and cause fever.

Identification of Pathogen

We will go into this topic in more detail later. But here are a few points for now. Neutrophils and macrophages have some ability on their own to recognize microorganisms and begin phagocytosis. We will use the term innate receptors for the molecules on such cells that available immediately to bind foreign molecules. These can act as soon as a microbe enters the body. They are naturally found on the surface of phagocytes and do not require a specific immune response to be made. Innate receptors are possible because microorganisms have various molecules on their surfaces that much different than those found in a human.

But phagocytosis is far more effective if microorganisms are labelled by special molecules that bind to their surface. Any molecule that binds to a microorganism and thereby speeds phagocytosis is called an opsonin. Most important here are antibodies(such as IgG), which specifically identify molecules at the surface of specific microorganisms. With this attached to the surface of the microorganisms, phagocytosis is much more effective and rapid.

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