Phagocytosis




Several types of cells in the immune system engulf microorganisms via phagocytosis.

Sequence of Events

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:


Release of Regulatory Molecules

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.

The release of cytokines by macrophages is especially important. Two important examples are TNF-alpha and IL-1. These help coordinate an immune response. But they are especially important as potent imflammatory paracrines. Also, you are going to find that TNF-alpha can be released in serious infections in such quantity that it is life-threatening or even fatal.


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.

OK, see if you remember: What is the difference between lysosome and lysozyme?

Answer


While you are at it: What is a paracrine?

Answer




Difficult Pathogens

But, as mentioned above, sometimes phagocytes have a difficult time with certain pathogens. For example, Listeria monocytogenes can escape from the phagosome into the cytosol. This food-borne illness is less common than salmonella, but more likely to cause fatalies. It tends to be spread by various raw foods, such as soft-ripened cheeses. One outbreak caused some fatalities in Colorado due to cantaloupes. It is especially a problem in pregnant women because it can have serious effects on the baby. As with viruses, once listeria is inside a cell, the problem can no longer be solved by the potent immune mechanisms acting in the extracellular fluid, and thus the whole cell must be destroyed in order to get rid of the infection.

Tuberculosis is an especially important example. A macrophage can usually engulf the tuberculosis bacterium, but then the bacterium has a means for preventing the lysosomes from fusing with the phagosome. If the macrophage is not "activated" by paracrines from a specific immune response, the bacteria may remain alive for long periods within the macrophage. In this circumstance, other macrophages surround and wall off the infected macrophages, forming a type of chronic inflammation called a granuloma. Leprosy is another bacterium that is difficult for macrophages to destroy. Again, more on this later.

Some pathogenic bacteria are surrounded by a capsule that make phagocytosis difficult. Anthrax is one example. Anthrax spores entering the body from the lungs or a cut in the skin make their way first to lymph nodes, where they change to their "vegetative form" and begin dividing. But because they are difficult to destroy, they quickly become quite numerous and accumulate in the blood, causing sepsis. Not only do the bacteria release toxins, but also, as is the case in certain other dangerous infections, macrophages respond to the crisis by releasing enough IL-1 and TNF-alpha to cause inflammation systemically, that is, throughout the body. Indeed, this hyperinflammation by itself can quickly be fatal. It can include, for example, widespread formation of small blood clots, which is termed disseminated intravascular coagulation.



Quick Quiz

Fill in Answer Correct False Correct Answer
What type of membrane-bounded vesicle fuses with a phagosome to begin the process of destroying the microorganism?
What is produced by the oxidase enzyme found in the membrane of a lysosome?
What is is the general name of an enzyme that digests proteins?
What type of phagocytic white blood cell quickly enters the tissues during an acute infection?
What type of cell forms granulomas by surrounding and walling of tuberculosis bacteria.
What is the term for a molecule that binds to a microorganism and thereby speeds phagocytosis.

(Spelling must be correct)
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