Phagocytosis is the main mechanism of the immune system. Blood cells capable of phagocytosis Cells that carry out phagocytosis
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 the form of soluble - 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 the 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 using 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.
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.
This is how the particle is captured by the phagocyte.
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.
dependent and oxygen-independent mechanisms of bactericidal activity. Opsonins. Methods
study of phagocytic activity of cells.
Phagocytosis is a process in which specially designed blood cells and
body tissues (phagocytes) capture and digest solid particles.
Carried out by two types of cells: circulating in the blood granular
leukocytes (granulocytes) and tissue macrophages.
Stages of phagocytosis:
1. Chemotaxis. In the phagocytosis reaction, a more important role belongs to the positive
chemotaxis. The secreted products act as chemoattractants.
microorganisms and activated cells in the focus of inflammation (cytokines, leukotriene
B4, histamine), as well as cleavage products of complement components (C3a, C5a),
proteolytic fragments of blood clotting factors and fibrinolysis (thrombin,
fibrin), neuropeptides, fragments of immunoglobulins, etc. However, "professional"
chemotaxins are cytokines of the chemokine group. Earlier than other cells in the focus of inflammation
neutrophils migrate, macrophages arrive much later. Speed
chemotactic movement for neutrophils and macrophages is comparable, differences in
the time of arrival is probably associated with different rates of their activation.
2. Adhesion phagocytes to the object. Caused by the presence of phagocytes on the surface
receptors for molecules presented on the surface of an object (own or
contacted him). Phagocytosis of bacteria or old host cells
recognition of terminal saccharide groups - glucose, galactose, fucose,
mannose, etc., which are presented on the surface of phagocytosed cells.
Recognition is carried out by lectin-like receptors of the corresponding
specificity, primarily mannose-binding protein and selectins,
present on the surface of phagocytes. In cases where the objects of phagocytosis
are not living cells, but pieces of coal, asbestos, glass, metal, etc., phagocytes
preliminarily make the object of absorption acceptable for the reaction,
enveloping it with its own products, including components of the intercellular
matrix they produce. Although phagocytes are able to absorb various kinds of
"unprepared" objects, the phagocytic process reaches the greatest intensity
during opsonization, i.e., fixation on the surface of objects of opsonins to which phagocytes
there are specific receptors - to the Fc fragment of antibodies, components of the system
complement, fibronectin, etc.
3. Activation membranes. At this stage, the object is prepared for immersion.
There is an activation of protein kinase C, the release of calcium ions from intracellular depots.
Of great importance are the sol-gel transitions in the system of cellular colloids and actino-
myosin rearrangements.
4. Immersion. The object is wrapped.
5. Phagosome formation. Closing the membrane, immersing an object with a part of the membrane
phagocyte inside the cell.
6. Formation of a phagolysosome. Fusion of phagosome with lysosome
optimal conditions are formed for bacteriolysis and splitting of the killed cell.
The mechanisms of convergence of phagosomes and lysosomes are unclear, probably there is an active
movement of lysosomes to phagosomes.
7. Killing and splitting. The role of the cell wall of the digested cell is great. Main
substances involved in bacteriolysis: hydrogen peroxide, products of nitrogen metabolism,
lysozyme, etc. The process of destruction of bacterial cells is completed due to the activity
proteases, nucleases, lipases and other enzymes whose activity is optimal at low
pH values.
8. Release of degradation products.
Phagocytosis can be:
Completed (killing and digestion were successful);
Incomplete (for a number of pathogens, phagocytosis is a necessary step in their life cycle, for example, in mycobacteria and gonococci).
Oxygen-dependent microbicidal activity is realized through the formation of a significant amount of products with toxic effects that damage microorganisms and surrounding structures. NLDF oxidase (flavoprotedo-cytochrome reductase) of the plasma membrane and cytochrome b are responsible for their formation; in the presence of quinones, this complex transforms 02 into the superoxide anion (02-). The latter exhibits a pronounced damaging effect, and also quickly transforms into hydrogen peroxide according to the scheme: 202 + H20 = H2O2 + O2 (process
catalyzed by the enzyme superoxide dismutase).
Opsonins - proteins that enhance phagocytosis: IgG, acute phase proteins (C-reactive protein,
mannan-binding lectin); lipopolysaccharide-binding protein, complement components - C3b, C4b; surfactant proteins of the lungs SP-A, SP-D.
Methods for studying the phagocytic activity of cells.
To assess the phagocytic activity of peripheral blood leukocytes, 0.25 ml of a microbial culture suspension with a concentration of 2 billion microbes in 1 ml is added to citrate blood taken from a finger in a volume of 0.2 ml.
The mixture is incubated for 30 min at 37°C, centrifuged at 1500 rpm for 5-6 min, the supernatant is removed. A thin silvery layer of leukocytes is carefully aspirated, smears are prepared, dried, fixed, stained with Romanovsky-Giemsa paint. The preparations are dried and microscopically.
The count of absorbed microbes is carried out in 200 neutrophils (50 monocytes). The intensity of the reaction is evaluated by the following indicators:
1. Phagocytic index (phagocytic activity) - the percentage of phagocytes from the number of cells counted.
2. Phagocytic number (phagocytic index) - the average number of microbes absorbed by one active phagocyte.
To determine the digestive capacity of peripheral blood leukocytes, a mixture of taken blood and a suspension of a microorganism is prepared and kept in a thermostat at 37°C for 2 hours. The preparation of smears is similar. At microscopy of the preparation, viable microbial cells are enlarged in size, while digested ones are less intensely stained, smaller. To assess the digestive function, the indicator of phagocytosis completion is used - the ratio of the number of digested microbes to the total number of absorbed microbes, expressed as a percentage.
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So, phagocytosis - what is it? Let's try to understand the definition of this term. The word "phagocytosis" comes from two Greek morphemes - phagos (devouring) and kytos (cell). The international medical term phagokytosis, unlike the Russified one, has the ending osis, which is translated from Greek as "process" or "phenomenon".
Thus, literally, this definition means the process of recognition by specific cells of a foreign agent, purposeful movement towards it, capture and absorption, followed by splitting. In this article we will talk about what the essence of phagocytosis is. We will also talk about what phagocytes are, consider the stages and find the difference between completed and incomplete phagocytosis.
The history of the discovery of special mobile cells
An outstanding Russian naturalist - I. I. Mechnikov in 1882 - 1883. conducted experiments on intracellular digestion, studying the transparent larvae of starfish. The scientist was interested in whether the ability to capture food by isolated cells remained. And also digest it the way the simplest unicellular organisms, such as amoeba, do. II Mechnikov conducted an experiment: he injected carmine powder into the bodies of larvae and observed how a wall of cells grew around these small blood-red grains. They grabbed and swallowed paint. Then the scientist came up with a hypothesis that in any organism there must be special protective cells that can absorb and digest other particles that harm the body. To confirm his hypothesis, the scientist used pink spikes, which he introduced into the body of the larvae. Some time later, the scientist saw that the cells surrounded the spikes, trying to resist the "pests" and push them out. These specific protective particles found in the body of the larva, the scientist called phagocytes. Thanks to this experience, II Mechnikov revealed phagocytosis. In 1883, he reported on his discovery at the Seventh Congress of Russian Naturalists. In the future, the scientist continued to work in this direction, created a comparative pathology of inflammation, as well as a phagocytic theory of immunity. In 1908, together with the scientist P. Ehrlich, he received the Nobel Prize for his most important biological research.
The phenomenon of phagocytosis - what is it?
II Mechnikov traced and found out the role of phagocytosis in the protective reactions of the human body and higher animals. The scientist found that this process plays a significant role in the healing of various wounds. The biological encyclopedic dictionary gives the following definition.
Phagocytosis is the active capture and absorption of foreign objects such as bacteria, microfungi and cell fragments by unicellular organisms or specific cells (phagocytes) present in any multicellular organism. What is the meaning of phagocytosis? It is believed that it represents the oldest form of defense of a multicellular organism. Phagocytosis also plays an important role in the functioning of the human immune system. It is the first reaction to the introduction of various viruses, bacteria and other foreign agents. Phagocytes constantly circulate throughout the body, looking for "pests". When a foreign agent is recognized, it binds with the help of receptors. After that, the phagocyte absorbs the pest and destroys it.
Two main groups of motile cells - "defenders"
Phagocytes are constantly in an active state and are ready at any time to fight the source of infection. They have a certain autonomy, since they can perform their functions not only inside, but also outside the body: on the surface of mucous membranes and in areas of damaged tissue. Human phagocytes, in terms of their effectiveness, scientists divide into two groups - "professional" and "non-professional". The first includes monocytes, neutrophils, macrophages, mast cells and tissue
The most important mobile phagocytes are white blood cells - leukocytes. They emigrate to the focus of inflammation and implement protective functions. Phagocytosis of leukocytes involves the detection, absorption and destruction of foreign objects, as well as their own dead or damaged cells. After performing their functions, part of the leukocytes moves into the vascular bed and continues to circulate in the blood, while the other undergoes apoptosis or dystrophic changes. The "unprofessional" group consists of fibroblasts, reticular and endothelial cells, which have low phagocytic activity.
The process of phagocytosis: the first stage
Consider how the process of combating harmful organisms takes place. Scientists distinguish four stages of phagocytosis. The first is approach: the phagocyte approaches a foreign object. This occurs either as a result of a random collision, or as a result of active directed movement - chemotaxis. There are two types of chemotaxis - positive (movement towards the phagocyte) and negative (movement away from the phagocyte). As a rule, positive chemotaxis is carried out to the site of tissue damage, and is also caused by microbes and their products.
Adherence of phagocytes to a foreign agent
After the "protector" cell approaches the harmful particle, the second stage begins. It is about sticking. The phagocyte reaches the object, touches it and attaches itself. For example, leukocytes that have arrived at the site of inflammation and adhered to the vessel wall do not leave it even despite the high blood flow velocity. The adhesion mechanism is due to the surface charge of the phagocyte. As a rule, it is negative, and the surface of phagocyte objects is positively charged. In this case, the best adhesion is observed. Negatively charged particles, for example, tumor particles, are captured by phagocytes much worse. Nevertheless, adhesion to such particles also exists. It is carried out due to the action of mucopolysaccharides present on the surface of phagocyte membranes, as well as by reducing the viscosity of the cytoplasm and enveloping the foreign agent with serum proteins.
Third stage of phagocytosis
After sticking to a foreign object, the phagocyte proceeds to absorb it, which can occur in two ways. At the point of contact, the shell of the foreign object, and then the object itself, is drawn into the cell. At the same time, the free edges of the membrane close over the object, and as a result, a separate vacuole is formed containing a harmful particle inside. The second way of absorption is the appearance of pseudopodia, enveloping foreign particles and closing on them. As a result, they are enclosed in vacuoles inside the cells. As a rule, with the help of pseudopodia, phagocytes absorb microfungi. Retraction or enveloping of a harmful object becomes possible due to the fact that the phagocyte membrane is endowed with contractile properties.
Intracellular cleavage of the "pest"
The fourth stage of phagocytosis involves intracellular digestion. It happens in the following way. The vacuole containing the foreign particle includes lysosomes that have a complex of digestive enzymes that are activated and poured out. In this case, an environment is formed in which the splitting of biological macromolecules of ribonuclease, amylase, protease and lipase easily occurs. Thanks to the activated enzymes, destruction and digestion occur, and then the release of decay products from the vacuole. Now you know what all four stages of phagocytosis are. The protection of the body is carried out in stages: first, the phagocyte and the object come together, then attraction, that is, the location of the harmful particle on the surface of the "defender", and then the pest is absorbed and digested.
Incomplete and completed phagocytosis. What are their differences?
Depending on what will be the result of intracellular digestion of foreign particles, two types are distinguished - complete and incomplete phagocytosis. The first one ends with the complete destruction of the object and the release of decay products into the environment. Incomplete phagocytosis - what is it? The term means that foreign cells engulfed by phagocytes remain viable. They can destroy the vacuole or use it as "soil" for reproduction. An example of incomplete phagocytosis is the absorption of gonococci in an organism that does not have immunity to them. With the incomplete process of phagocytosis, pathogens remain inside the phagocytes, and are also spread throughout the body. So, in place, phagocytosis becomes a conductor of the disease, helping pests to spread and multiply.
Causes of violation of the process of intracellular digestion
Violation of phagocytosis occurs due to defects in the formation of phagocytes, as well as the suppression of the activity of motile "defender" cells. In addition, a negative change in intracellular digestion is possible due to hereditary diseases such as Alder's and Chedyak-Higashi's diseases. Violation of the formation of phagocytes, including the regeneration of leukocytes, often occurs with radioactive exposure or due to hereditary neutropenia. Suppression of phagocyte activity can occur due to a deficiency of certain hormones, electrolytes and vitamins. Also, glycolytic poisons and microbial toxins adversely affect the functioning of phagocytes. We hope that thanks to our article, you can easily answer the question: "Phagocytosis - what is it?". Good luck!
The protective role of mobile blood cells and tissues was first discovered by I. I. Mechnikov in 1883. He called these cells phagocytes and formulated the main provisions of the phagocytic theory of immunity. Phagocytosis- absorption by the phagocyte of large macromolecular complexes or corpuscles, bacteria. Phagocyte cells: neutrophils and monocytes/macrophages. Eosinophils can also phagocytose (most effective in anthelmintic immunity). The process of phagocytosis is enhanced by opsonins that envelop the object of phagocytosis. Monocytes make up 5-10%, and neutrophils 60-70% of blood leukocytes. Entering the tissue, monocytes form a population of tissue macrophages: Kupffer cells (or stellate reticuloendothelial cells of the liver), CNS microglia, osteoclasts of bone tissue, alveolar and interstitial macrophages).
The process of phagocytosis. The phagocytes move in a direction towards the object of phagocytosis, reacting to chemoattractants: microbial substances, activated complement components (C5a, C3a) and cytokines.
The plasmalemma of the phagocyte embraces bacteria or other corpuscles and its own damaged cells. Then the object of phagocytosis is surrounded by the plasmalemma and the membrane vesicle (phagosome) is immersed in the cytoplasm of the phagocyte. The phagosome membrane fuses with the lysosome and the phagocytosed microbe is destroyed, the pH acidifies to 4.5; lysosome enzymes are activated. The phagocytosed microbe is destroyed by the action of lysosome enzymes, cationic defensin proteins, cathepsin G, lysozyme, and other factors. During the oxidative (respiratory) explosion, toxic antimicrobial forms of oxygen are formed in the phagocyte - hydrogen peroxide H 2 O 2, superoxide O 2 - , hydroxyl radical OH - , singlet oxygen. In addition, nitric oxide and the NO - radical have an antimicrobial effect.
Macrophages perform a protective function even before interacting with other immunocompetent cells (nonspecific resistance). Macrophage activation occurs after the destruction of the phagocytized microbe, its processing (processing) and presentation (representation) of the antigen to T-lymphocytes. In the final stage of the immune response, T-lymphocytes secrete cytokines that activate macrophages (acquired immunity). Activated macrophages, together with antibodies and activated complement (C3b), perform more efficient phagocytosis (immune phagocytosis), destroying phagocytosed microbes.
Phagocytosis can be complete, ending with the death of the captured microbe, and incomplete, in which microbes do not die. An example of incomplete phagocytosis is the phagocytosis of gonococci, tubercle bacilli and leishmania.
All phagocytic cells of the body, according to I. I. Mechnikov, are divided into macrophages and microphages. Microphages include polymorphonuclear blood granulocytes: neutrophils, eosinophils and basophils. Macrophages of various tissues of the body (connective tissue, liver, lungs, etc.), together with blood monocytes and their bone marrow precursors (promonocytes and monoblasts), are combined into a special system of mononuclear phagocytes (MPS). The SMF is phylogenetically older than the immune system. It is formed quite early in ontogeny and has certain age characteristics.
Microphages and macrophages have a common myeloid origin - from a pluripotent stem cell, which is a single precursor of granulo- and monocytopoiesis. The peripheral blood contains more granulocytes (from 60 to 70% of all blood leukocytes) than monocytes (from 1 to 6%). At the same time, the duration of circulation of monocytes in the blood is much longer (half-period 22 hours) than that of short-lived granulocytes (half-period 6.5 hours). Unlike blood granulocytes, which are mature cells, monocytes, leaving the bloodstream, in the appropriate microenvironment, mature into tissue macrophages. The extravascular pool of mononuclear phagocytes is tens of times greater than their number in the blood. The liver, spleen, and lungs are especially rich in them.
All phagocytic cells are characterized by a commonality of basic functions, similarity of structures and metabolic processes. The outer plasma membrane of all phagocytes is an actively functioning structure. It is characterized by pronounced folding and carries many specific receptors and antigenic markers that are constantly updated. Phagocytes are equipped with a highly developed lysosomal apparatus, which contains a rich arsenal of enzymes. The active participation of lysosomes in the functions of phagocytes is ensured by the ability of their membranes to fuse with the membranes of phagosomes or with the outer membrane. In the latter case, cell degranulation and concomitant secretion of lysosomal enzymes into the extracellular space occurs.
Phagocytes have three functions:
1 - protective, associated with cleaning the body of infectious agents, tissue decay products, etc .;
2 - representing, consisting in the presentation of antigenic epitopes on the phagocyte membrane;
3 - secretory, associated with the secretion of lysosomal enzymes and other biologically active substances- monokines, which play an important role in immunogenesis.
Fig 1. Macrophage functions.
In accordance with the listed functions, the following consecutive stages of phagocytosis are distinguished.
1. Chemotaxis - targeted movement of phagocytes in the direction of the chemical gradient of chemoattractants in the environment. The ability to chemotaxis is associated with the presence on the membrane of specific receptors for chemoattractants, which can be bacterial components, degradation products of body tissues, activated fractions of the complement system - C5a, C3a, lymphocyte products - lymphokines.
2. Adhesion (attachment) is also mediated by the corresponding receptors, but can proceed in accordance with the laws of nonspecific physicochemical interaction. Adhesion immediately precedes endocytosis (capture).
3. Endocytosis is the main physiological function of the so-called professional phagocytes. There are phagocytosis - in relation to particles with a diameter of at least 0.1 microns and pinocytosis - in relation to smaller particles and molecules. Phagocytic cells are able to capture inert particles of coal, carmine, latex by flowing around them with pseudopodia without the participation of specific receptors. At the same time, phagocytosis of many bacteria, yeast-like fungi of the genus Candida, and other microorganisms is mediated by special phagocyte mannose-fucose receptors that recognize the carbohydrate components of the surface structures of microorganisms. The most effective is phagocytosis mediated by receptors for the Fc fragment of immunoglobulins and for the C3 fraction of complement. Such phagocytosis is called immune, since it proceeds with the participation of specific antibodies and an activated complement system that opsonize the microorganism. This makes the cell highly sensitive to capture by phagocytes and leads to subsequent intracellular death and degradation. As a result of endocytosis, a phagocytic vacuole is formed - phagosome. It should be emphasized that the endocytosis of microorganisms to a large extent depends on their pathogenicity. Only avirulent or low virulent bacteria (capsular strains of pneumococcus, strains of streptococcus lacking hyaluronic acid and M-protein) are directly phagocytosed. Most bacteria endowed with aggressiveness factors (staphylococcus-A-protein, Escherichia coli-expressed capsular antigen, Salmonella-Vi-antigen, etc.) are phagocytosed only after they are opsonized by complement or (and) antibodies.
The presenting, or representing, function of macrophages is to fix antigenic epitopes of microorganisms on the outer membrane. In this form, they are presented by macrophages for their specific recognition by cells of the immune system - T-lymphocytes.
The secretory function consists in the secretion of biologically active substances - monokines by mononuclear phagocytes. These include substances that have a regulatory effect on the proliferation, differentiation and function of phagocytes, lymphocytes, fibroblasts and other cells. A special place among them is occupied by interleukin-1 (IL-1), which is secreted by macrophages. It activates many functions of T-lymphocytes, including the production of lymphokine - interleukin-2 (IL-2). IL-1 and IL-2 are cellular mediators involved in the regulation of immunogenesis and various forms of the immune response. At the same time, IL-1 has the properties of an endogenous pyrogen, since it induces fever by acting on the nuclei of the anterior hypothalamus. Macrophages produce and secrete such important regulatory factors as prostaglandins, leukotrienes, cyclic nucleotides with a wide range of biological activity.
Along with this, phagocytes synthesize and secrete a number of products with predominantly effector activity: antibacterial, antiviral, and cytotoxic. These include oxygen radicals (O 2 , H 2 O 2), complement components, lysozyme and other lysosomal enzymes, interferon. Due to these factors, phagocytes can kill bacteria not only in phagolysosomes, but also outside the cells, in the immediate microenvironment. These secretory products can also mediate the cytotoxic effect of phagocytes on various target cells in cell-mediated immune responses, for example, in delayed-type hypersensitivity reactions (DTH), in homograft rejection, and in antitumor immunity.
The considered functions of phagocytic cells ensure their active participation in maintaining the homeostasis of the body, in the processes of inflammation and regeneration, in nonspecific anti-infective protection, as well as in immunogenesis and reactions of specific cellular immunity (SIT). The early involvement of phagocytic cells (first, granulocytes, then macrophages) in response to any infection or any damage is explained by the fact that microorganisms, their components, tissue necrosis products, blood serum proteins, substances secreted by other cells, are chemoattractants for phagocytes. In the focus of inflammation, the functions of phagocytes are activated. Macrophages are replacing microphages. In those cases when the inflammatory reaction involving phagocytes is not enough to cleanse the body of pathogens, then the secretory products of macrophages ensure the involvement of lymphocytes and the induction of a specific immune response.
complement system. The complement system is a multicomponent self-assembling system of blood serum proteins that plays an important role in maintaining homeostasis. It is able to be activated in the process of self-assembly, i.e., sequential attachment to the resulting complex of individual proteins, which are called components, or complement fractions. There are nine such factions. They are produced by liver cells, mononuclear phagocytes and are contained in the blood serum in an inactive state. The process of complement activation can be triggered (initiated) in two different ways, called classical and alternative.
When complement is activated, the classic initiating factor is the antigen-antibody complex (immune complex). Moreover, antibodies of only two classes IgG and IgM in the composition of immune complexes can initiate complement activation due to the presence in the structure of their Fc fragments of sites that bind the C1 fraction of complement. When C1 is attached to the antigen-antibody complex, an enzyme (C1-esterase) is formed, under the action of which an enzymatically active complex (C4b, C2a), called C3-convertase, is formed. This enzyme cleaves C3 into C3 and C3b. When the C3b subfraction interacts with C4 and C2, a peptidase is formed that acts on C5. If the initiating immune complex is associated with the cell membrane, then the self-assembling complex C1, C4, C2, C3 ensures the fixation of the activated C5 fraction on it, and then C6 and C7. The last three components together contribute to the fixation of C8 and C9. At the same time, two sets of complement fractions - C5a, C6, C7, C8 and C9 - constitute the membrane attack complex, after which the cell is lysed after its attachment to the cell membrane due to irreversible damage to the structure of its membrane. In the event that complement activation along the classical pathway occurs with the participation of the erythrocyte-antierythrocyte Ig immune complex, erythrocyte hemolysis occurs; if the immune complex consists of a bacterium and an antibacterial Ig, bacterial lysis occurs (bacteriolysis).
Thus, during complement activation in the classical way, the key components are C1 and C3, the cleavage product of which C3b activates the terminal components of the membrane attack complex (C5 - C9).
There is a possibility of C3 activation with the formation of C3b with the participation of the alternative pathway C3 convertase, i.e. bypassing the first three components: C1, C4 and C2. A feature of the alternative pathway of complement activation is that initiation can occur without the participation of the antigen-antibody complex due to polysaccharides of bacterial origin - lipopolysaccharide (LPS) of the cell wall of gram-negative bacteria, surface structures of viruses, immune complexes, including IgA and IgE.