Phagocytosis is one of the most basic and, at the same time, the most effective defense mechanisms of the human body. The proper functioning of the phagocytosis process is an essential component of a proper immune response. Find out what exactly phagocytosis is, how phagocytosis works, why phagocytosis is needed and what effects phagocytosis disorders can have?

Phagocytosisis the ingestion of pathogens, dead cell fragments, and tiny particles by specialized cells called phagocytes. Phagocytosis can be compared to "cleaning up" at the cellular level - it allows cells to get rid of unnecessary or dangerous elements.

Contents:

  1. What is phagocytosis?
  2. The role of phagocytosis in the body
  3. Which cells are capable of phagocytosis?
  4. Phagocytosis - types
    • spontaneous (native) phagocytosis
    • facilitated phagocytosis
  5. Phagocytosis - stages
  6. Phagocytosis - and what next?
  7. Ways to avoid phagocytosis by microorganisms
  8. Phagocytosis disorders
    • Chronic Granulomatous Disease
    • Chediak team- Higashi

What is phagocytosis?

Phagocytosis is a biological process in which a cell absorbs foreign particles. The phenomenon of phagocytosis is common in many living organisms - the most primitive ones (e.g. protozoa) use phagocytosis as a way of taking food from the external environment.

In humans, the ability to phagocytose is primarily used by the cells of the immune system.

Phagocytosis belongs to the mechanisms of innate, i.e. non-specific immunity. The process of phagocytosis is therefore one of the first and basic defense lines of our body. In addition to its role in the immune system, phagocytosis is of great importance in maintaining tissue homeostasis (or equilibrium).

Phagocytosis allows the removal of dead and damaged cells of the body's own body, which in turn enables efficient regeneration and reconstruction of all tissues.

Phagocytosis is one of the types of endocytosis, i.e. the transfer of molecules from the external environmentinside the cell. In phagocytosis, solid particles are absorbed: the phagocytic cell first surrounds them with a fragment of its own cell membrane and then draws it inside. This creates a vesicle containing the absorbed particle, called a phagosome.

The content of the phagosome is then digested with a variety of chemicals and enzymes. The whole process resembles the "eating" of the particle by the cell, which is also reflected in the term phagocytosis.

The name comes from the Greek phagein meaning "to eat, to devour".

Phagocytosis takes place in our body constantly - billions of phagocytes constantly "eat" dangerous microorganisms, fragments of dead cells or unnecessary particles. It is a common, albeit extremely complicated process.

Correct target recognition by the phagocytic cell and the correct interaction between the phagocyte and the target of "attack" requires the continuous collaboration of various proteins, signaling molecules, antibodies and helper cells.

The role of phagocytosis in the body

It is not difficult to guess that the basic application of the phagocytosis process is the defense of our body against pathogens. The penetration of an infectious agent into the body starts a cascade of signals to "call" phagocytic cells to the site of infection.

Acute inflammation begins, the role of which is to neutralize the pathogen. Phagocytes flow to the lesion with the blood, constituting one of the most important mechanisms of the primary immune response. At the site of inflammation, phagocytes "eat" both pathogens and damaged cells.

In the course of infection, we are dealing with another, very important type of phagocytosis. It is the so-called eferocytosis.

The process of eferocytosis involves swallowing dying cells as the inflammation subsides. Once the phagocytes have fulfilled their function and eliminated pathogens, they become unnecessary.

Then they die naturally, followed by eferocytosis, means "cleaning up the battlefield". This type of phagocytosis reduces inflammation and allows the body to return to the state it was before the infection.

At this point it is worth emphasizing that the dying of cells in our body is a continuous process, not only as a result of infection. Each cell has a specific life span, after which it dies and is replaced by a new one. The process of programmed cell death is called apoptosis.

Apoptosis is a natural phenomenon that allows our tissues to renew constantly. That dying cellscould be replaced with their new counterparts, they must first be cleaned up. As you can easily guess, this is also the task of phagocytes.

Apoptotic (dying) cells emit special signals on the surface of their cell membranes, allowing them to be recognized and neutralized by phagocytes.

In this case, phagocytosis occurs without inflammation. So we see that phagocytosis is not only a method of defense against foreign microorganisms, but also a process that enables the development, remodeling and renewal of all tissues.

Which cells are capable of phagocytosis?

Cells capable of carrying out phagocytosis are called phagocytes. Depending on the efficiency and effectiveness of phagocytosis, we distinguish the so-called professional and non-professional phagocytes.

Non-professional phagocytes deal with phagocytosis "on a regular basis" - this process is not their main task. Sometimes, however, there are particles / fragments of dead cells in the vicinity of these cells that require cleaning.

Then they show some phagocytic activity, although compared to professional phagocytes, it is significantly limited and less effective. Many types of cells are classified as non-professional phagocytes, incl. epithelial cells, some connective tissue cells, and also the vascular endothelium.

Professional phagocytes are the main cells responsible for phagocytosis in our body. Among them, we distinguish mainly neutrophils, monocytes and macrophages. These cells belong to the family of leukocytes, or white blood cells, which mainly perform immune functions. All three types of professional phagocytes specialize in phagocytosis, although each carries it out slightly differently.

Neutrophils are the main cells responsible for the formation of acute inflammation. Normally, neutrophils circulate with the blood throughout the body. When an infection begins, these cells immediately cluster in the disease focus. Phagocytosis by neutrophils is rapid and intense: these cells have a wide range of ways to inactivate absorbed pathogens.

Monocytes, like neutrophils, circulate in the bloodstream, but can leave the bloodstream and colonize various tissues. The mature monocytes then transform into tissue macrophages. Macrophage-mediated phagocytosis is less rapid and much slower. Macrophages are the main pool of cells found in sites of chronic inflammation.

Phagocytosis - types

Phagocytosis is a complicated process that depends onthe type of phagocytic cell, the phagocytic object, and many intermediary molecules. There are two basic phagocytosis pathways:

  • spontaneous (native) phagocytosis

This is a relatively slow-occurring phagocytosis that is rarely involved in the antimicrobial response. The role of spontaneous phagocytosis is to remove dead cells and "clean up" unnecessary elements within the tissues. In order to initiate spontaneous phagocytosis, it is necessary to stimulate the so-called "scavenger receptors" primarily present on macrophages. This type of phagocytosis is anti-inflammatory in nature.

  • facilitated phagocytosis

Facilitated phagocytosis is much faster and more efficient than spontaneous phagocytosis. Thanks to this, it is highly effective in destroying pathogens. In order for the phagocytosis process to take place so intensively, it is necessary - as the name suggests - some facilities.

How can phagocytes facilitate their activity? One of the most common methods is special "marking" of objects that should be disposed of. This process is called opsonization.

The essence of opsonization is the attachment of certain molecules to the surface of the microorganism. This "marked" pathogen is quickly targeted and destroyed by the food cells. The molecules that enable opsonization are called opsonins. These are mainly antibodies and components of the so-called complement system.

Opsonins efficiently recognize pathogens, mark them and thus significantly facilitate the course of the phagocytosis process.

Phagocytosis - stages

We already know which cells, when and why, deal with phagocytosis. So let's try to closely follow the course of this process:1. Activation and influx of phagocytes to the site of infectionThe penetration of the microorganism into the body causes the immediate stimulation of the immune system. Cells in the gate of infection begin to send a signal of an existing threat.

The messenger molecules (mainly the so-called pro-inflammatory cytokines) are spread throughout the bloodstream. In this way, phagocytes "find out" that they have become infected and are activated.

The activated phagocytes reach the site of infection with the blood. The efficient influx of phagocytes to the correct location is possible thanks to the so-called chemotaxis. It is the process of directed cell movement under the influence of chemical signals.

Active phagocytes also have the ability to pass through the walls of blood vessels, creating an inflammatory infiltrate at the site of theinfections.

2. Pathogen diagnosis

When phagocytes reach the site of infection, they begin to recognize pathogens. This process is often facilitated by other molecules (see section 4 for facilitated phagocytosis). Each phagocyte has on the surface of its cell membrane the so-called receptors, or proteins that enable the recognition of various molecules.

When the receptors responsible for recognizing microorganisms are stimulated, the phagocyte binds closely to the target of its attack.

3. Absorption of the pathogen

The phagocyte "stuck" to the pathogen starts the process of its absorption. The phagocyte cell membrane begins to surround the pathogen, "climbing" its edges. This creates a vesicle containing the microorganism. This vesicle, called the phagosome, is now inside the phagocytic cell. In order to fully neutralize the microorganism, it is necessary to destroy the content of the phagosome.

Digestion of phagosome contents

In order for the contents of the phagosome to be digested, it is necessary to deliver digestive enzymes to its interior. Such enzymes are stored in special vesicles called lysosomes.

The last stage of phagocytosis therefore requires combining the content of lysosomes with the content of the phagosome - this is how the so-called phagolysosome.

The enzymes in the lysosomes can break down most complex chemicals, resulting in the destruction of the microorganism. The elimination of the pathogen with the participation of digestive enzymes is called oxygen-independent.

As you can easily guess, there is also an oxygen dependent elimination. It is much more rapid and effective, but only some phagocytes can do it. Oxygen-dependent elimination occurs only in cells with the ability to generate the so-called "oxygen explosion".

An oxygen explosion is a sudden release of very active oxygen species (e.g. hydrogen peroxide), which has a strong antimicrobial effect. An oxygen explosion begins a series of chemical reactions leading to the rapid elimination of pathogens. Oxygen-dependent microbial destruction is characteristic primarily of neutrophils.

Phagocytosis - and what next?

The phagocytosis process ends with the digestion of the phagosome inside the cell. What happens next to the debris from the destroyed particles? The phagocytic cell gets rid of most of the unnecessary products by simply "throwing" them outside. However, some of the material left over after digestion can be very useful.

Some phagocytes also play other roles in the immune system. A good examplethere are macrophages that, in addition to phagocytosis, also deal with the so-called presentation of antigens. Antigen presentation consists in showing other immune cells fragments of destroyed microorganisms.

The macrophage, after phagocytosis of the pathogen is completed, exposes a part of the phagocytic material on its surface, and then "travels" with it throughout the body.

Every cell of the immune system that he encounters "learns" thanks to this, how to recognize a given pathogen. This phenomenon is extremely important in building efficient mechanisms of antimicrobial defense.

It is also worth knowing that the phagocytosis process does not always end with the final destruction of the microorganism. There are pathogens that can survive inside phagosomes thanks to specially developed defense mechanisms. A good example is the tuberculosis bacilli, which can survive inside macrophages for many years.

Ways to avoid phagocytosis by microorganisms

Phagocytosis as a way to eliminate "biological opponents" is a very old mechanism. For this reason, some microorganisms have managed to evolve ways to avoid or survive phagocytosis. Here are their examples:

  • killing phagocytes

The easiest way to avoid phagocytosis seems to be to neutralize the cell that causes it. Some microorganisms have the ability to produce substances that irreversibly damage phagocytes. An example of such a pathogen is staphylococcus aureus (LatinStaphylococcus aureus ), which produces toxins which, by destroying the cell membrane of phagocytes, cause their death.

  • extinction of the inflammatory response

Inflammation in the gate of infection facilitates the transmission of an infection signal. Thanks to it, activation and arrival of phagocytes to the correct location is possible. There are pathogens that can mask themselves in such a way as not to be recognized by the host's immune system and to avoid causing inflammation.

  • avoiding opsonization

Opsonization, or special "labeling" of pathogens, is one of the most effective ways to facilitate phagocytosis. No wonder microbes try to avoid it. Some strains of staphylococci can destroy opsonins or hide them on their surface.

  • avoiding phagocyte recognition

In order for the phagocytosis to begin, it is necessary to recognize the harmfulness of a given microorganism by the phagocyte. Some pathogens, such as spirochetesTreponema pallidumcausingSyphilis can attach antigens similar to the host cells to their surface. The immune system then recognizes them as its own, which allows pathogens to avoid phagocytosis.

  • blockage of phagosome production

One of the key stages of phagocytosis is surrounding the attacked microorganism with a vesicle, which is then absorbed into the cell. In nature, however, there are many ways to avoid it. Some microbes produce substances that break down the phagosome wall. A different mechanism is used by the blue oil stick ( Pseudomonas aeruginosa ). This bacterium produces a slippery coating (biofilm) around itself, preventing the formation of this bubble.

  • survival inside the phagocyte

Phagolysosome becomes the final habitat of pathogens during phagocytosis. Its environment is extremely hostile; it is full of enzymes and killer substances. However, microorganisms can develop mechanisms that enable them to survive even in such difficult conditions. One example is the tuberculosis ( Mycobacterium tuberculosis ). This bacterium has developed a special cell membrane with a very high lipid content that is not affected by standard digestive enzymes.

  • escape from the phagosome

As incredible as it sounds to escape the phagosome, there are indeed microbes that have developed such a clever defense mechanism. Listeria monocytogenes produces substances capable of destroying the phagosome wall. What's more, this pathogen, after escaping from the phagosome, can multiply inside the phagocyte, and also get further beyond its limits.

Phagocytosis disorders

Properly running phagocytosis is of fundamental importance for the smooth functioning of the immune system. Disturbances in some stages of phagocytosis underlie immunodeficiency diseases. Examples of such diseases are:

  • Chronic Granulomatous Disease

The cause of chronic granulomatous disease is a disorder of phagocytosis at the stage of generating an oxygen burst. The lack of an appropriate enzyme (the so-called NADPH oxidase) prevents the formation of reactive oxygen species, which, in turn, does not allow for a quick and effective elimination of microorganisms.

Damage to the enzyme has a genetic background, so there is no causal treatment of the disease yet. In the course of chronic granulomatous disease, frequent infections, abscesses and granulomas develop due to the inadequate intracellular elimination system.pathogens.

  • Chediak- Higashi Team

In the Chediak-Higashi syndrome, there is a defect in phagocytosis at the stage of phagosome-lysosome connection. A genetic mutation of one of the proteins prevents the transfer of digestive enzymes to the vesicle containing the pathogen, thus preventing its elimination.

In addition to a significant impairment of immunity, albinism and disturbances in the functioning of the nervous system are also characteristic for the Chediak-Higashi syndrome.

About the authorKrzysztof BialaziteA medical student at Collegium Medicum in Krakow, slowly entering the world of constant challenges of the doctor's work. She is particularly interested in gynecology and obstetrics, paediatrics and lifestyle medicine. A lover of foreign languages, travel and mountain hiking.

Read more articles by this author

Category:

Immune system