In 1882-1883. the famous Russian zoologist I. I. Mechnikov conducted his research in Italy, on the shores of the Strait of Messina. The scientist was interested in whether individual cells of multicellular organisms retained the ability to capture and digest food, as unicellular organisms, such as amoeba, do. Indeed, as a rule, in multicellular organisms, food is digested in the alimentary canal and the cells absorb ready-made nutrient solutions. Mechnikov observed starfish larvae. They are transparent and their contents are clearly visible. These larvae do not have circulating blood, but have cells wandering throughout the larva. They captured particles of red carmine paint introduced into the larva. But if these cells absorb paint, then maybe they capture any foreign particles? Indeed, the rose thorns inserted into the larva turned out to be surrounded by cells stained with carmine.

The cells were able to capture and digest any foreign particles, including pathogenic microbes. Mechnikov called wandering cells phagocytes (from the Greek words phagos - eater and kytos - receptacle, here - cell). And the very process of capturing and digesting different particles by them is phagocytosis. Later, Mechnikov observed phagocytosis in crustaceans, frogs, turtles, lizards, and also in mammals - guinea pigs, rabbits, rats and humans.

Phagocytes are special cells. Digestion of captured particles is not necessary for them to feed, like amoebas and other unicellular organisms, but to protect the body. In starfish larvae, phagocytes wander throughout the body, while in higher animals and humans they circulate in the vessels. This is one of the types of white blood cells, or leukocytes, - neutrophils. It is they, attracted by the toxic substances of microbes, that move to the site of infection (see Taxis). Having left the vessels, such leukocytes have outgrowths - pseudopodia, or pseudopodia, with the help of which they move in the same way as amoeba and wandering cells of starfish larvae. Mechnikov called such phagocytic leukocytes microphages.

However, not only constantly moving leukocytes, but also some sedentary cells can become phagocytes (now they are all combined into a single system of phagocytic mononuclear cells). Some of them rush to dangerous areas, for example, to the site of inflammation, while others remain in their usual places. Both of them are united by the ability to phagocytosis. These tissue cells (histocytes, monocytes, reticular and endothelial cells) are almost twice as large as microphages - their diameter is 12-20 microns. Therefore, Mechnikov called them macrophages. Especially a lot of them in the spleen, liver, lymph nodes, bone marrow and in the walls of blood vessels.

Microphages and wandering macrophages themselves actively attack the “enemies”, while immobile macrophages wait for the “enemy” to swim past them in the blood or lymph flow. Phagocytes “hunt” for microbes in the body. It happens that in an unequal struggle with them they are defeated. Pus is the accumulation of dead phagocytes. Other phagocytes will approach it and begin to deal with its elimination, as they do with all sorts of foreign particles.

Phagocytes clean tissues from constantly dying cells and are involved in various restructuring of the body. For example, during the transformation of a tadpole into a frog, when, along with other changes, the tail gradually disappears, whole hordes of phagocytes destroy the tissues of the tadpole's tail.

How do particles get inside the phagocyte? It turns out that with the help of pseudopodia, which capture them, like an excavator bucket. Gradually, the pseudopodia lengthen and then close over the foreign body. Sometimes it seems to be pressed into the phagocyte.

Mechnikov suggested that phagocytes should contain special substances that digest the microbes and other particles captured by them. Indeed, such particles - lysosdma were discovered 70 years after the discovery of phagocytosis. They contain enzymes that can break down large organic molecules.

It has now been clarified that, in addition to phagocytosis, antibodies are predominantly involved in the neutralization of foreign substances (see Antigen and antibody). But for the process of their production to begin, the participation of macrophages is necessary. They capture foreign proteins (antigens), cut them into pieces and expose their pieces (the so-called antigenic determinants) on their surface. Here, those lymphocytes that are able to produce antibodies (immunoglobulin proteins) that bind these determinants come into contact with them. After that, such lymphocytes multiply and secrete many antibodies into the blood, which inactivate (bind) foreign proteins - antigens (see Immunity). The science of immunology deals with these issues, one of the founders of which was I. I. Mechnikov.

Mechnikov observed starfish larvae. They are transparent and their contents are clearly visible. These larvae do not have circulating blood, but have cells wandering throughout the larva. They captured particles of red carmine paint introduced into the larva. But if these cells absorb paint, then maybe they capture any foreign particles? Indeed, the rose thorns inserted into the larva turned out to be surrounded by cells stained with carmine.

This is how the particle is captured by the phagocyte.

He conducted his research in Italy, on the coast of the Strait of Messina. The scientist was interested in whether individual multicellular organisms retained the ability to capture and digest food, as unicellular organisms, such as amoeba, do. Indeed, as a rule, in multicellular organisms, food is digested in the alimentary canal and ready-made nutrient solutions are absorbed. observed starfish larvae. They are transparent and their contents are clearly visible. These larvae do not have a circulating, but wandering larva throughout the larva. They captured particles of red carmine paint introduced into the larva. But if these absorb paint, then maybe they capture any foreign particles? Indeed, the rose thorns inserted into the larva turned out to be surrounded by carmine-colored ones.

They were able to capture and digest any foreign particles, including pathogenic microbes. called wandering phagocytes (from the Greek words phages - devourer and kytos - receptacle, here -). And the very process of capturing and digesting different particles by them is phagocytosis. Later he observed phagocytosis in crustaceans, frogs, turtles, lizards, as well as in mammals - guinea pigs, rabbits, rats and in humans.

Phagocytes are special. Digestion of captured particles is not necessary for them to feed, like amoebas and other unicellular organisms, but to protect the body. In starfish larvae, phagocytes wander throughout the body, while in higher animals and humans they circulate in the vessels. This is one of the types of white blood cells, or leukocytes - neutrophils. It is they who, attracted by the toxic substances of microbes, move to the site of infection (see). Having left the vessels, such leukocytes have outgrowths - pseudopodia, or pseudopodia, with the help of which they move in the same way as an amoeba and wandering starfish larvae. Such leukocytes capable of phagocytosis are called microphages.

However, not only constantly moving leukocytes, but also some sedentary ones can become phagocytes (now they are all combined into a single system of phagocytic mononuclear cells). Some of them rush to dangerous areas, for example, to the site of inflammation, while others remain in their usual places. Both of them are united by the ability to phagocytosis. These tissue (histocytes, monocytes, reticular and endothelial) are almost twice as large as microphages - their diameter is 12-20 microns. Therefore, they called them macrophages. Especially a lot of them in the spleen, liver, lymph nodes, bone marrow and in the walls of blood vessels.

Microphages and wandering macrophages themselves actively attack the “enemies”, while immobile macrophages wait for the “enemy” to swim past them in the current or lymph. Phagocytes “hunt” for microbes in the body. It happens that in an unequal struggle with them they are defeated. Pus is the accumulation of dead phagocytes. Other phagocytes will approach it and begin to deal with its elimination, as they do with all sorts of foreign particles.

Phagocytes are cleansed of constantly dying and are involved in various restructuring of the body. For example, during the transformation of a tadpole into a frog, when, along with other changes, the tail gradually disappears, whole hordes of phagocytes destroy the tadpole's tail.

He suggested that phagocytes should contain special substances that digest the microbes and other particles captured by them. Indeed, such particles were discovered 70 years after the discovery of phagocytosis. They contain capable of breaking down large organic molecules.

Now it has been found out that, in addition to phagocytosis, they are predominantly involved in the neutralization of foreign substances (see). But for the process of their production to begin, the participation of macrophages is necessary. They capture foreign

Actually, evolution went along the path so that one single-celled one ate another. Who will eat who faster. Single-celled organisms united in organized groups - as a result, this led to the formation of multicellular organisms. It was safer that way. Each cell of such an organism acquired its own specialization. When multicellular organisms appeared, the concept of “who will eat whom faster” did not lose its relevance. Among the organization of cells, those from which the primitive immune system was subsequently formed stood out. More advanced multicellular organisms developed specialized immune cells.
Some of the most important in the composition of the immune defense are cells capable of phagocytosis. One cell devours another. To destroy it, eat up, or thus obtain information (“count” the pathogen and warn the others).

In general, the mechanism of phagocytosis is one of the most ancient mechanisms of the immune response. Phagocytosis was observed by Ilya Ilyich Mechnikov when he pricked a starfish larva with a rose thorn (invertebrates, the first fossil invertebrates lived 485 million years ago).
In the future, the immune system is supplemented by an "antibody" mechanism. When specific proteins (antibodies) are produced and the pathogen is inactivated.

Besides being one of the funniest words in biology, the process of phagocytosis is pretty spectacular and cool. Remember the old Pac-Man game? A round yellow ball with a big mouth runs around the maze, dodging enemies, and eating small yellow dots.

I decided to write the article before the subsequent ones dedicated to. It is staphylococcal infection that is dominant in purulent surgery. And what is pus? This is all that remains after the battle of the cells of the immune system and microorganisms ... Phagocytosis in the fight against staphylococcus plays a key role.

What is phagocytosis?

In biology there is a term "endocytosis". The process of absorption by a cell of a particle, molecule, another cell or bacterium. If a large and solid particle is absorbed, then endocytosis is called phagocytosis.

Macrophage vs microbe. What is a macrophage?

The world we live in is a pretty dirty place. Since everything in nature tends to chaos, so in our life everything tends to become littered. We need to constantly ensure that everything in our house is always clean and things are in their place.
A similar situation occurs in our body. The birth and death of new cells is constantly happening, every day and hour in our body a genetic failure occurs in one of the cells - it becomes cancerous. Bacteria live in the intestines, constantly penetrating the liver through the portal vein. Viruses, bacteria, protozoa, trying to turn our body into a nutrient medium ...
Our immune system works constantly, constantly maintaining order. An integral part of this system is the macrophage.

It is an amoeba-like organism (like the slime-like good man in Ghostbusters). The task of a macrophage is to cleanse the body of microscopic debris and bacteria. The homeland of macrophages is the bone marrow, the precursor is a white blood cell - a monocyte.
Macrophages live for about one and a half months, during this time they patrol the body (in the blood test, we look at segmented neutrophils, getting into tissues, they become macrophages).

The tissue macrophage communicates with the helper lymphocyte. Pseudopodia (protrusions of the cytoplasm), he "probes" the external environment.

Stages of phagocytosis

Consider this process using the example of leukocytes (neutrophils are the most numerous of them), as cells of the immune system that absorb a harmful bacterium. Well, firstly, the leukocyte must clearly understand that it is a foreign organism. The recognition process is rather complicated.
The immune cell detects the molecules released by the bacterium as a signal to act. Then the leukocyte must catch on, stick to the bacteria. To do this, there are special receptors on its surface, with the help of which adherence to a foreign cell occurs (it can be not only a bacterium, but also its own cell that does not respond to commands - for example, a cancerous one).

After sticking, the membrane swells outward and envelops the bacterial cell, as it were. As a result, the uninvited guest appears as if in a soap bubble - a phagosome.
Inside the phagosome, the phagocyte cell secretes enzymes that decompose the bacterial cell wall, destroying it.

Let's consider in order.
1. Chemotaxis. And the scent is like that of a dog ... How does a macrophage find a foreign object? Is it really necessary to “touch” all cells (like a person around the room, at night, by touch) with receptors?
No. Chemotaxis is a directed movement relative to an object, depending on the chemicals that this very object releases. It was written about negative hemotaxis in a zoology textbook: a salt crystal was thrown into the water and the amoeba tried to crawl away from such a neighborhood. With macrophages, chemotaxis is positive. Crawls in response to chemicals released by alien organisms. Substances are also attracted - cytokines secreted by their own cells: they call for help. Tuberculosis bacillus, for example, does not emit toxins (“does not smell”), so the immune system does not immediately detect them.

Neutrophils from the blood are the first to migrate to the focus of inflammation, and the “big eater” arrives much later. By the rate of chemotaxis, these cells are identical, but macrophages are activated noticeably later.

2. Adhesion of macrophages to the object. Or "sticking". On the surface of both healthy and pathological cells and microbes, there is a certain set of chemical molecules that signal to the macrophage: “eat me” or “don’t eat me”.
Recognition is carried out by special receptors. And although macrophages are able to phagocytize non-living cells (pieces of coal, asbestos, glass), the phagocytic process is activated after the command of other cells - T-helpers.
It is T-helpers (a type of lymphocyte) that “illuminate” what you need to eat: specific proteins, opsonins, stick to an “unprepared” object. The macrophage goes to the "smell" of opsonins.

3. In the place where contact with the microbe occurred, the cell membrane is activated. She kind of leans in.

4. Formation of the phagosome. The phagosome is the cavity in which the object of absorption is located. A kind of "stomach", in which, under the action of enzymes, a splitting of a foreign organism occurs.
Hydrogen peroxide is involved in lysis (splitting) (stop constantly pouring peroxide on the wound, healthy cells are also damaged in this way!), Nitrous oxide, lysozyme. Various kinds of enzymes - proteases, lipases.
The most impactful enzyme of lysosomes is elastase.

5. Ejection of digestible residues.

Profit! Go to step №1!

This is in ideal conditions. In reality, everything happens much more interesting. The very mechanism of the immune response of a macroorganism (you and me) and a microorganism (everything that can be seen through a microscope) is the result of an arms race that has been going on for millions of years.
A truce in this confrontation is not planned and no one will sign an arms limitation treaty. Who will outsmart whom.
The task of a microbe is to infiltrate, multiply and spread. And evolution tried to have something to implement these plans. Therefore, a rich arsenal of adaptations has accumulated both on the part of the micro- and the macroorganism.
There are pathogens (such as Mycobacterium tuberculosis or gonococcus) for which being ingested by a macrophage is an essential stage of development.
And where is the best place to hide from the immune system? Of course, inside the representative of this immune system!

When not everything is so simple: incomplete phagocytosis

There are microorganisms for which the attack of macrophages on them is not a problem. On the contrary, it is an important stage in their development. As already mentioned, the macrophage absorbs the microbe, forming a phagosome. And this is where the failure occurs. Enzymes involved in the breakdown of everything that the macrophage has absorbed are concentrated in another "soap bubble" - the lysosome.

Normally, the lysosome fuses with the phagosome. An acidic environment is created in the phagosome, the pH decreases. In an acidic environment, enzymes that break down bacteria begin to act.
But Listeria, for example, secretes substances that prevent the attachment of a liposome (containing enzymes) to the phagosome. Blockade of phagosomal-lysosomal fusion is also characteristic of the influenza virus and toxoplasma. The macrophage cannot "digest" the causative agent of gonococcal infection. Gonococcus (staphylococcus, by the way, too) is quite resistant to lysosomal enzymes. And rickettsia destroy the phagosome and can freely swim with the cytoplasm of the phagocyte.

How can you cope with something that cannot be digested and destroyed?

Before continuing the story, it is worth talking about how the mechanism of phagocytosis itself was studied. More precisely, thanks to whom. Dictiostellium.
It is this microorganism that plays the most important role in the study of phagocytosis. Cell slime mold. I wanted to write that this is a unicellular organism, but this is not entirely true ... But not a multicellular one either.
This amoeba-like organism was described in 1935. Due to the fact that it is very easy to grow in the laboratory, it has become the most studied microorganism. The mechanism of phagocytosis is very ancient, in the slime mold and in our macrophages it is very similar. It lives in wet leaf litter, and feeds on bacteria. Another unique feature is that dictyostelium has three “sexes”, and two of the three in any combination are enough for sexual reproduction. For most of its life, dictyostelium lives in the form of solitary amoebas, feeding on leaf litter bacteria.

And now the most interesting. Remember the movie about transformers, when several robots were assembled into one huge one?
So these amoebae, when there is a shortage of food, form cellular aggregates, and the dimensions of such a cellular formation for the microworld are huge - up to 1 cm. This macroorganism is able to crawl and subsequently forms a “fruiting body”.

"Fruiting body" of dictyostelium, capable of moving

Slime molds, before forming a multicellular organism (pseudoplasmodium), absorb bacteria, but do not digest them. Moreover, in a new place, these bacteria are allowed to multiply. Such are the unicellular gardeners.

Macrophages of our body are also capable of creating such a multicellular formation. This "monster" is called the Pirogov-Langhans cell. Previously, these multinucleated cells were identified as an immune response to the introduction of tubercle bacillus.

When a patient with a long-lasting cough is recommended to take a sputum test, the conclusion is written "AFB not detected." AFB are acid-fast mycobacteria. Tuberculosis bacillus cells of our immune system cannot fully phagocytize.
When a macroorganism comes into contact with Mycobacterium tuberculosis, neutrophils are the first to enter the fight. And everyone dies. Mycobacteria is too tough for them. Then the "big brother" - the macrophage - goes into battle. A macrophage absorbs bacteria one by one, but cannot fully digest them. The bacterium is resistant to the acidic environment of the phagosome, and it also affects phagosomal-lysosomal fusion.

Macrophages will do this more efficiently when taught to do so by T-helpers, or helpers. Each subsequent generation of macrophages becomes "more trained". By the way, about the primary contact with a tubercle bacillus. Everyone remembers Mantoux's reaction at school? With this test, it is determined whether our immune system is familiar with the tubercle bacillus or not. The turn of the tuberculin test is just the first contact with mycobacterium.

It is extremely difficult for the immune system to fight the causative agent of tuberculosis (why the clinic largely depends on the number of bacteria that have entered the body). To limit the spread of the infection, the macrophages "gorged" with mycobacteria begin to unite into a large multicellular structure - the Pirogov-Langhans cell. At first, such a microscopic finding was attributed to inflammation in tuberculosis, but then other diseases (for example, actinomycosis) were also revealed.

Huge multinucleated Pirogov-Langhans cell

That's about such an inflammatory process and they say: specific. Well, what should the body do with the tubercle bacillus, which does not want to die in any way? A kind of sarcophagus is formed around the zone of specific inflammation. At first it consists of a fibrous protein - fibrin, then it calcifies. Gon's focus in the lungs is a common finding on fluorography. It is impossible to completely recover from tuberculosis. The person remains permanently infected (but clinically absolutely healthy).
BCG is a vaccine against tuberculosis. Contains killed bacteria to familiarize immune cells with pathogen antigens. The vaccine cannot guarantee protection (it is clear why), but the effectiveness of the immune response increases. Again, it all depends on the number of bacteria and the condition of the body.

Gon's focus is most often detected subpleurally and in the upper lobes of the better ventilated lungs: mycobacteria feel good in an oxygen environment

Some recent research on phagocytosis.

How sleep affects phagocytic activity

One sleepless night is certainly not good, but in most cases it does not cause any consequences.
Another thing - countless sleepless nights. One study published in the journal Neuroscience evaluated the biological effects of sleep deprivation in laboratory mice. It was found that the brain causes damage to itself with a prolonged lack of sleep. Laboratory animals were divided into four groups. One group was “well-rested”, the mice of the second group were periodically awakened, in the third group the animals did not sleep for several days. After that, scientists studied the brain activity of each group. In mice deprived of sleep for a long time, an increase in the activity of phagocytosis was revealed. Phagocytes are the cleaner cells the brain needs to clear the by-products of neural activity throughout the day.
After a long period of sleep deprivation, the brain goes into overdrive, which can be very harmful. Don't panic if your sleep-wake schedule isn't in perfect shape, but try to get enough sleep.

Phagocytosis and hyperglycemia

Why do surgeons often prescribe a blood test with the determination of glucose levels in purulent-inflammatory processes?
Why are infectious diseases more severe in diabetic patients? One of the factors: fast carbohydrates affect the activity of macrophages.
People were given 100-gram portions of carbohydrates from glucose, fructose, sucrose, honey. Then venous blood was taken 1,2,3 and 5 hours after a meal. A suspension containing (Staphylococcus epidermidis) was added to the blood.
Subsequently, the activity of macrophages was studied. It has been established that rapidly digestible carbohydrates inhibit the phagocytic activity of macrophages.
So it is very important to monitor the level of glucose, especially in patients with diabetes mellitus undergoing treatment for purulent-inflammatory processes.

Finally

And although phagocytosis is the most ancient way to protect against foreign organisms, it has not lost its significance. This mechanism is key in the fight against staphylococcal infection.

Palamarchuk Vyacheslav

If you find a typo in the text, please let me know. Highlight a piece of text and click Ctrl+Enter.

Phagocytosis is the absorption of foreign particles or cells and their further destruction.

Phagocytosis is inherent in neutrophils, eosinophils, monocytes and macrophages, which have an extremely wide range of functions directed against infection of the body, to maintain a high level of immunity and remove denatured proteins, remnants of dead cells, tissues and various products from foci of inflammation or infection. In addition, all phagocytes in the process of activation produce a significant set of biologically active compounds that play an important role in the regulation of the physiological functions of the body both under normal and pathological conditions.

Stages of phagocytosis:

1) the approach of a phagocyte to a phagocytosed object or ligand;

2) contact of the ligand with the phagocyte membrane;

3) absorption of the ligand;

4) digestion or destruction of the phagocytosed object.

Movement of the phagocyte towards the ligand

All phagocytes are characterized by amoeboid mobility. The adhesion to the substrate along which the leukocyte moves is called adhesion. Only fixed or adherent leukocytes are capable of phagocytosis.

Phagocyte can pick up distant signals (chemotaxis) and migrate in their direction (chemokinesis). Although hundreds of products affect the mobility of leukocytes, their effect is manifested only in the presence of specific compounds - chemoattractants, or chemokines, which in total is a little more than sixty. The most active phagocyte stimulators are opsonized microorganisms, individual complement components, immune complexes, N-formylmethionyl peptides secreted by some bacteria, bioactive products of lipid metabolism, PAF, leukotrienes (LTB 4), lipopolysaccharides, bacterial endotoxins, fibrin, Hageman factor, plasmin, Ifg , IL-8, IL-16, TNFa, GM-CSF, acute phase proteins, etc.

It is necessary to dwell on one more mechanism that contributes to the attraction of phagocytes to the site of injury. It is known that under physiological conditions, free-radical reactions occur in all cells and membrane structures. lipid peroxidation (LPO), restrained by fat-soluble antioxidants. An important role in the inhibition of lipid peroxidation belongs to the structural organization of the membrane. At the same time, any damage to the cell structure leads to an increase in lipid peroxidation. Consequently, LPO activation is a universal response of cells and tissues to any damage, which serves as a trigger for phagocytosis.

The primary products of lipid peroxidation in membranes are hydroperoxides. However, in the future, as a result of the deepening of LPO processes, biologically active aldehydes are formed - 2-alkenal and 4-hydroxyalkenal. So, during the oxidation of arachidonic and linoleic acids, which are part of the membranes of all cells without exception, aldehyde is formed. 4-hydroxynonenal, which has an extremely high chemotactic activity against granulocytes. At the same time, at a very high concentration of this aldehyde, the movement of neutrophils towards the site of damage is almost completely blocked, which is extremely unfavorable for the development of protective phagocytic reactions.

Thanks to chemotaxis, the phagocyte purposefully moves towards the damaging agent. The higher the concentration of the chemoattractant, the greater the number of phagocytes rushes into the damage zone, and the faster they move. Chemoattractants have specific glycoprotein formations - receptors; their number per neutrophil ranges from 2´103 to 2´105. The movement is carried out by the interaction of actin and myosin. In this case, the pseudopodia is advanced, which serves as a fulcrum for the movement of the phagocyte. Adhering to the substrate, the pseudopodium pulls the phagocyte to a new location. Microtubules play an important role in the movement of the phagocyte. They not only ensure the rigidity of the structure, but also allow the phagocyte to orient itself in the direction of movement. The tubules begin to function only after they receive information through specific cellular mediators, which include cyclic nucleotides - adenosine monophosphate (cAMP) and guanosine monophosphate (cGMP). An increase in the concentration of cAMP leads to a decrease in the functional activity of the phagocyte, an increase in the level of cGMP leads to its increase. Apparently, the phagocyte receptors include adenylate cyclase and guanylate cyclase, the enzymes responsible for the synthesis of cyclic nucleotides.

The leukocyte, moving, is able to overcome obstacles and, in particular, to pass through the endothelium of the capillary. Adhering to the vessel wall with the help of adhesive molecules, it releases a pseudopodia that penetrates the vessel wall. The body of the leukocyte gradually overflows into this protrusion. Further, the leukocyte is separated from the vessel wall and can move in the tissues.

The deployment of neutrophils in infected tissues is a complex multi-step process. First of all, there must be a reaction between the neutrophil and endothelial cells, which is carried out by means of adhesive molecules. Neutrophils moving with the blood flow must stop, pass between the endothelial cells of the vessels, after which they are able to move to the site of damage (inflammation). The process of movement of lymphocytes differs little from the movement of neutrophils, but it is always specific and directed to target organs.

Contact between phagocyte and ligand

To bind microbes on the membrane of phagocytes, there are special receptors for the Fc fragment of immunoglobulins and fragments of the C3 component of complement. When microbes enter the human body, antibodies (Abs) are formed - immunoglobulins of classes M and G (IgM, IgG), which are sorbed on the surface of the microbe. In the case of IgM sorption, the C3b complement fragment is additionally attached to them. Consequently, the phagocyte does not bind the microbe, but the “microbe + IgG antibody” or “microbe + IgM antibody + C3” complex through the listed receptors. Thus, At act here as opsonins factors that facilitate phagocytosis.

A similar mechanism operates during phagocytosis not only of microorganisms, but also of other objects - old and cancer cells and other particles.

The properties of opsonins are cleavage products of IgG proteases. So, a tetrapeptide can be cleaved from IgG (the name itself suggests that it consists of 4 amino acids), which received the name tuftsin. This compound in extremely small doses sharply enhances the phagocytic activity of leukocytes.

A glycoprotein often acts as an opsonin. fibronectin(molecular weight 440,000 Da), which has a significant stickiness, which facilitates the interaction between the phagocyte and the ligand. Fibronectin is found in an insoluble form in connective tissue and in a soluble form in the a2-globulin fraction of plasma. In addition, a protein similar in structure to fibronectin takes part in the interaction of the phagocyte and the phagocytosed object. laminin, as well as ions Ca++ and Mg++.

Ligand uptake

As soon as the ligand binds to the receptor according to the described mechanism, the conformation of the latter changes and the signal is transmitted to the enzyme combined with the receptor into a single complex, due to which the phagocytosed object is absorbed.

There are 5 main mechanisms of absorption, or 5 main types of phagocytosis: 1. retraction or introduction; 2. wrap around; 3. environment; 4. invagination and 5. volvulus. All mechanisms of phagocytosis come down to the fact that the ligand is enclosed in the phagocyte membrane and, at the same time, phagosome. In its formation, an important role is played by the contractile proteins of the phagocyte. As already noted, their properties resemble actin and myosin in muscles. However, unlike muscles in a phagocyte, actin does not activate the ATPase associated with myosin, but can only do so in the presence of a special protein, a cofactor. In addition, in the cytoplasm of the phagocyte there is a special protein that binds actin filaments into bundles and is called actin-binding protein. Actin in the cytoplasm of the phagocyte turns into a gel, after which myosin and the cofactor enter into the reaction, which, in the presence of Mg 2+ ions and ATP, reduce the actin gel, turning it into compact aggregates.

The resulting actin gel is attached to the plasma membrane from the inside and when it contracts against the object of phagocytosis, a depression is formed. In this case, the object itself is surrounded by protrusions of the cytoplasm, which captures it like claws. So it appears phagosome, which breaks away from the membrane and moves to the center of the cell, where it merges with lysosomes, resulting in phagolysosome. In the latter, the phagocytosed object dies. This so-called completed phagocytosis. But it often occurs incomplete phagocytosis, then the phagocytosed object can live and develop in the phagocyte. A similar phenomenon is observed in some infectious diseases - tuberculosis, gonorrhea, meningococcal and viral infections.

Destruction of the ligand

The last stage of phagocytosis is the destruction of the ligand. The main weapons of phagocytes are products of partial oxygen reduction - hydrogen peroxide and the so-called free radicals. They cause peroxidation of lipids, proteins and nucleic acids, due to which the cell membrane is damaged.

The activation of phagocytes is associated with significant changes in cell function. It occurs already at the contact of the phagocyte and the phagocytosed complex. In this case, a number of morphological and biochemical processes occur, the most striking of which are increased metabolism, migration, adhesion and degranulation.

As a result of the interaction of the phagocyte and the stimulator, the consumption of glucose by cells, the activation of individual enzymes, the formation of reactive oxygen species and other pro-oxidants, the appearance of activation products of cyclo- and lipoxygenases sharply increase. These reactions develop suddenly and with extreme speed, which gave rise to the name of this phenomenon "oxygen" or "respiratory explosion". It has been established that after stimulation of polymorphonuclear leukocytes (PMN) oxygen consumption increases by 50-100 times.

A common sign of phagocyte activation is an increase in Ca 2+ content in the cytosol. This reaction is the fastest response to stimulation and is carried out with the help of a chain of rather complex biochemical transformations, accompanied by a change in the phospholipid composition of the membrane, the appearance of prostaglandins and leukotrienes, etc. Ca 2+ ions enter the cytosol from the environment and from the so-called intracellular depots.

An increase in the content of Ca 2+ in the cytosol of leukocytes triggers calcium-dependent processes leading to priming cells, which is expressed in an increase in its functional activity, an increase in the synthesis of biologically active compounds, such as NO, superoxide anion radical, hypochloride anion, H 2 O 2, etc. The products of oxygen metabolism have a bactericidal effect, while nitric oxide has an effect on blood microcirculation, because it relaxes blood vessels. The latter leads to vasodilation and improved microcirculation. In leukocytes, inducible NO synthase is responsible for the synthesis of NO, the appearance of which occurs under the influence of a number of stimuli, including lipopolysaccharides (LPS), cytokines, fragments of the complement system, etc. In vivo, inducible NO synthase is formed in phagocytes located in pathologically altered tissues especially in the focus of inflammation.

The most striking manifestation of phagocyte stimulation is "oxygen explosion" due to activation NADP. H 2 -dependent oxidase.