What cells are involved in phagocytosis? Phagocytic cells of the body
Phagocytosis performs the most important function of granulocytic blood cells - protection from foreign xenoagents attempting to invade the internal environment of the body (preventing or slowing down this invasion, as well as “digesting” the latter, if they were able to penetrate).
Neutrophils release various substances into the environment and, therefore, perform a secretory function.
Phagocytosis = endocytosis is the essence of the process of absorption of a xenosubstance by the part of the cytoplasmic membrane (cytoplasm) enveloping it, as a result of which the foreign body is included in the cell. In turn, endocytosis is divided into pinocytosis (“cell drinking”) and phagocytosis (“cell nutrition”).
Phagocytosis is very clearly visible already at the light-optical level (in contrast to pinocytosis, which is associated with the digestion of microparticles, including macromolecules, and therefore it can only be studied using electron microscopy). Both processes are ensured by the mechanism of invagination of the cell membrane, as a result of which phagosomes of various sizes are formed in the cytoplasm. Most cells are capable of pinocytosis, while only neutrophils, monocytes, macrophages and, to a lesser extent, basophils and eosinophils are capable of phagocytosis.
Once at the site of inflammation, neutrophils come into contact with foreign agents, absorb them and expose them to digestive enzymes (this sequence was first described by Ilya Mechnikov in the 80s of the 19th century). While absorbing a variety of xenoagents, neutrophils rarely digest autologous cells.
The destruction of bacteria by leukocytes is carried out as a result of the combined effect of proteases of digestive vacuoles (bassoon), as well as the destructive effect of toxic forms of oxygen 0 2 and hydrogen peroxide H 2 0 2, which are also released into the phagosome.
The importance of the role played by phagocytic cells in protecting the body was not specifically emphasized until the 40s. last century - until Wood and Iron proved that the outcome of an infection is decided long before the appearance of specific antibodies in the serum.
About phagocytosis
Phagocytosis is equally successful both in an atmosphere of pure nitrogen and in an atmosphere of pure oxygen; it is not inhibited by cyanides and dinitrophenol; however, it is inhibited by glycolysis inhibitors.
To date, the effectiveness of the combined effect of the fusion of phagosomes and lysosomes has been clarified: many years of controversy ended with the conclusion that the simultaneous effect of serum and phagocytosis on xenoagents is very important. Neutrophils, eosinophils, basophils and mononuclear phagocytes are capable of directional movement under the influence of chemotactic agents, but such migration also requires a concentration gradient.
How phagocytes distinguish various particles and damaged autologous cells from normal ones is still not clear. However, this ability of theirs is perhaps the essence of the phagocytic function, the general principle of which is: particles to be absorbed must first be attached (adhered) to the surface of the phagocyte with the assistance of Ca ++ or Mg ++ ions and cations (otherwise weakly attached particles ( bacteria) can be washed away from the phagocytic cell). They enhance phagocytosis and opsonins, as well as a number of serum factors (for example, lysozyme), but directly affecting not phagocytes, but particles to be absorbed.
In some cases, immunoglobulins facilitate contact between particles and phagocytes, and certain substances in normal serum may play a role in the maintenance of phagocytes in the absence of specific antibodies. Neutorophils appear to be unable to ingest non-opsonized particles; at the same time, macrophages are capable of neutrophil phagocytosis.
Neutrophils
In addition to the known fact that the contents of neutrophils are released passively as a result of spontaneous cell lysis, a number of substances are probably activated by leukocytes, released from granules (ribonuclease, deoxyribonuclease, beta-glucuronidase, hyaluronidase, phagocytin, lysozyme, histamine, vitamin B 12). The contents of specific granules are released before the contents of the primary ones.
Some clarifications are given regarding the morphofunctional characteristics of neutrophils: transformations of their nuclei determine the degree of their maturity. So, for example:
– band neutrophils are characterized by further condensation of their nuclear chromatin and its transformation into a sausage-shaped or rod-shaped shape with a relatively equal diameter of the latter along the entire length;
– subsequently, a narrowing is observed in some place, as a result of which it is divided into lobes connected by thin bridges of heterochromatin. Such cells are already interpreted as polymorphonuclear granulocytes;
– determination of the lobes of the nucleus and its segmentation is often necessary for diagnostic purposes: early folio deficiency states are characterized by an earlier release of young forms of cells into the blood from the bone marrow;
– at the polymorphonuclear stage, the nucleus, stained by Wright, has a deep purple color and contains condensed chromatin, the lobes of which are connected by very thin bridges. In this case, the cytoplasm containing small granules appears pale pink.
The lack of consensus on the transformations of neutorophils nevertheless suggests that their deformations facilitate their passage through the vascular wall to the site of inflammation.
Arnet (1904) believed that division of the nucleus into lobes continues in mature cells and that granulocytes with three to four nuclear segments are more mature than those with bisegments. “Old” polymorphonuclear leukocytes are not able to perceive neutral color.
Thanks to advances in immunology, new facts have become known confirming the heterogeneity of neutrophils, the immunological phenotypes of which correlate with the morphological stages of their development. It is very important that by determining the function of various agents and the factors that control their expression, it is possible to understand the sequence of changes accompanying cell maturation and differentiation that occurs at the molecular level.
Eosinophils are characterized by the content of enzymes found in neutrophils; however, only one type of granule crystalloids is formed in their cytoplasm. Gradually, the granules acquire an angular shape, characteristic of mature polymophnonuclear cells.
Condensation of nuclear chromatin, reduction in size and final disappearance of nucleoli, reduction of the Golgi apparatus and double segmentation of the nucleus - all these changes are characteristic of mature eosinophils, which - like neutrophils - are just as mobile.
Eosinophils
In humans, the normal concentration of eosinophils in the blood (as calculated by a leukocyte counter) is less than 0.7-0.8 x 10 9 cells/l. Their numbers tend to increase at night. Physical activity reduces their number. The production of eosinophils (as well as neutrophils) in a healthy person occurs in the bone marrow.
The basophil series (Ehrlich, 1891) are the smallest leukocytes, but their function and kinetics have not been sufficiently studied.
Basophils
Basophils and mast cells are morphologically very similar, but they differ significantly in the acidic content of their granules containing histamine and heparin. Basophils are significantly inferior to mast cells both in size and in the number of granules. Mast cells, unlike basophil cells, contain hydrolytic enzymes, serotonin and 5-hydroxytryptamine.
Basophil cells differentiate and mature in the bone marrow and, like other granulocytes, circulate in the bloodstream without being normally found in connective tissue. Mast cells, on the other hand, are associated with connective tissue surrounding blood and lymph vessels, nerves, lung tissue, the gastrointestinal tract, and skin.
Mast cells have the ability to free themselves from granules, throwing them out (“exoplasmosis”). After phagocytosis, basophils undergo internal diffuse degranulation, but they are not capable of “exoplasmosis”.
Primary basophilic granules form very early; they are bounded by a membrane 75 A wide, identical to the outer membrane and the vesicular membrane. They contain large amounts of heparin and histamine, slow reacting substance of anaphylaxis, kallekrein, eosinophil chemotactic factor and platelet activating factor.
Secondary - smaller - granules also have a membrane environment; they are classified as peroxidase-negative. Segmented basophils and eosinophils are characterized by large and numerous mitochondria, as well as a small amount of glycogen.
Histamine is the main component of basophilic granules of mast cells. Metachromatic staining of basophils and mast cells explains their proteoglycan content. Mast cell granules contain predominantly heparin, proteases and a number of enzymes.
In women, the number of basophils varies depending on the menstrual cycle: with the greatest number at the beginning of bleeding and a decrease towards the end of the cycle.
In persons prone to allergic reactions, the number of basophils changes, along with IgG, throughout the flowering period of plants. A parallel decrease in the number of basophils and eosinophils in the blood is observed when using steroid hormones; The general influence of the pituitary-adrenal system on both of these cell lines has also been established.
The paucity of basophils and mast cells in the circulation makes it difficult to determine both the distribution and duration of residence of these pools in the bloodstream. Blood basophils are capable of slow movements, which allows them to migrate through the skin or peritoneum after the introduction of a foreign protein.
The ability to phagocytose remains unclear for both basophils and mast cells. Most likely, their main function is exocytosis (throwing out the contents of histamine-rich granules, especially in mast cells).
So, phagocytosis - what is it? Let's try to understand the definition of this term. The word "phagocytosis" arose 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, targeted 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 types of phagocytes there are, consider the stages and find the difference between completed and incomplete phagocytosis.
The history of the discovery of special motile cells
Outstanding Russian naturalist - I. I. Mechnikov in 1882 - 1883. conducted experiments on intracellular digestion, studying transparent starfish larvae. The scientist was interested in whether the isolated cells still had the ability to capture food. And also digest it in the same way as simple single-celled organisms, such as amoebas, do. I. I. Mechnikov conducted an experiment: he injected carmine powder into the bodies of the larvae and observed how a wall of cells grew around these small blood-red grains. They grabbed and swallowed the paint. Then the scientist had a hypothesis that any organism must have 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 larva. Some time later, the scientist saw that the cells were surrounded by spikes, trying to counteract the “pests” and push them out. The scientist called these specific protective particles found in the body of the larvae phagocytes. Thanks to this experience, I. I. Mechnikov discovered phagocytosis. In 1883, he reported on his discovery at the Seventh Congress of Russian Naturalists. Subsequently, the scientist continued work in this direction, creating 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?
I. I. Mechnikov traced and clarified 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 ingestion of foreign objects such as bacteria, microfungi and cell fragments by single-celled organisms or specific cells (phagocytes) found in any multicellular organism. What is the essence of phagocytosis? It is believed to represent the oldest form of defense for a multicellular organism. Phagocytosis also plays a critical 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 using receptors. After which 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. From the point of view of their effectiveness, scientists divide human phagocytes 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 site 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, some of the leukocytes move into the vascular bed and continue to circulate in the blood, while the other undergoes apoptosis or dystrophic changes. The "non-professional" group consists of fibroblasts, reticular and endothelial cells, which have low phagocytic activity.
Phagocytosis process: first stage
Let's consider how the process of combating harmful organisms occurs. Scientists distinguish four stages of phagocytosis. The first represents 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.
Adhesion of phagocytes to a foreign agent
After the “protector” cell approaches the harmful particle, the second stage begins. It's about sticking. The phagocyte reaches the object, touches it and attaches. For example, leukocytes that arrive at the site of inflammation and adhere to the wall of the vessel do not come off it even despite the high speed of blood flow. The adhesion mechanism is carried out 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 less well. Nevertheless, there is adhesion to such particles. It is carried out due to the action of mucopolysaccharides present on the surface of the membranes of phagocytes, as well as by reducing the viscosity of the cytoplasm and enveloping the foreign agent with serum proteins.
Third stage of phagocytosis
After adhering to a foreign object, the phagocyte begins 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. In this case, 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. They end up trapped in vacuoles inside cells. As a rule, phagocytes consume microfungi with the help of pseudopodia. Retracting or enveloping a harmful object becomes possible due to the fact that the phagocyte membrane is endowed with contractile properties.
Intracellular breakdown of the "pest"
The fourth stage of phagocytosis involves intracellular digestion. This happens as follows. The vacuole containing the foreign particle contains lysosomes containing a complex of digestive enzymes that are activated and released. This creates an environment in which the biological macromolecules ribonuclease, amylase, protease and lipase are easily broken down. Thanks to the activated enzymes, destruction and digestion occurs, and then the release of decay products from the vacuole. Now you know what all four stages of phagocytosis are. The body’s defense 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 absorption and digestion of the pest.
Incomplete and completed phagocytosis. What are their differences?
Depending on the result of intracellular digestion of foreign particles, two types are distinguished - completed and incomplete phagocytosis. The first 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. When the process of phagocytosis is not completed, pathogenic microorganisms are stored inside phagocytes and are also distributed throughout the body. Thus, in place, phagocytosis becomes a vehicle for the disease, helping pests to spread and multiply.
Causes of disruption of the intracellular digestion process
Impaired phagocytosis occurs due to defects in the process of formation of phagocytes, as well as when the activity of motile “defender” cells is suppressed. In addition, a negative change in intracellular digestion is possible due to hereditary diseases such as Alder and Chedyak-Higashi diseases. Impaired phagocyte formation, including leukocyte regeneration, often occurs due to radiation 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 negatively affect the functioning of phagocytes. We hope, 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 basic principles of the phagocytic theory of immunity. Phagocytosis- absorption of large macromolecular complexes or corpuscles and bacteria by the phagocyte. Phagocyte cells: neutrophils and monocytes/macrophages. Eosinophils can also phagocytose (they are 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 reticuloendotheliocytes of the liver), microglia of the central nervous system, osteoclasts of bone tissue, alveolar and interstitial macrophages).
Process of phagocytosis. Phagocytes move directionally to the object of phagocytosis, reacting to chemoattractants: microbial substances, activated complement components (C5a, C3a) and cytokines.
The phagocyte plasmalemma envelops 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 merges with the lysosome and the phagocytosed microbe is destroyed, the pH acidifies to 4.5; Lysosome enzymes are activated. The phagocytosed microbe is destroyed under the action of lysosome enzymes, cationic defensin proteins, cathepsin G, lysozyme and other factors. During an oxidative (respiratory) explosion, toxic antimicrobial forms of oxygen are formed in the phagocyte - hydrogen peroxide H 2 O 2, superoxidation 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 phagocytosed microbe, its processing (processing) and presentation (presentation) of the antigen to T-lymphocytes. In the final stage of the immune response, T lymphocytes release cytokines that activate macrophages (acquired immunity). Activated macrophages, together with antibodies and activated complement (C3b), carry out more effective phagocytosis (immune phagocytosis), destroying phagocytosed microbes.
Phagocytosis can be complete, ending with the death of the captured microbe, and incomplete, in which the 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 (MPF). The SMF is phylogenetically more ancient than the immune system. It is formed quite early in ontogenesis and has certain age-related characteristics.
Microphages and macrophages have a common myeloid origin - from a pluripotent stem cell, which is a single precursor of granulo- and monocytopoiesis. Peripheral blood contains more granulocytes (60 to 70% of all blood leukocytes) than monocytes (1 to 6%). At the same time, the duration of circulation of monocytes in the blood is much longer (half-life 22 hours) than that of short-lived granulocytes (half-life 6.5 hours). Unlike blood granulocytes, which are mature cells, monocytes, leaving the bloodstream, mature into tissue macrophages in the appropriate microenvironment. 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 common 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, which 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 merge with the membranes of phagosomes or with the outer membrane. In the latter case, cell degranulation occurs and concomitant secretion of lysosomal enzymes into the extracellular space.
Phagocytes have three functions:
1 - protective, associated with cleansing the body of infectious agents, tissue decay products, etc.;
2 - presenting, 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. Functions of a macrophage.
In accordance with the listed functions, the following sequential stages of phagocytosis are distinguished.
1. Chemotaxis - targeted movement of phagocytes in the direction of a chemical gradient of chemoattractants in the environment. The ability for chemotaxis is associated with the presence on the membrane of specific receptors for chemoattractants, which can be bacterial components, products of degradation of body tissues, activated fractions of the complement system - C5a, C3a, products of lymphocytes - 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 (uptake).
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 capable of capturing inert particles of coal, carmine, latex, 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 mannose fucose receptors of phagocytes, which recognize the carbohydrate components of the surface structures of microorganisms. The most effective is receptor-mediated phagocytosis for the Fc fragment of immunoglobulins and for the C3 fraction of complement. This phagocytosis is called immune, since it occurs with the participation of specific antibodies and the activated complement system, which opsonize the microorganism. This makes the cell highly susceptible to engulfment by phagocytes and leads to subsequent intracellular death and degradation. As a result of endocytosis, a phagocytic vacuole is formed - a phagosome. It should be emphasized that the endocytosis of microorganisms largely depends on their pathogenicity. Only avirulent or low-virulent bacteria (non-capsular strains of pneumococcus, strains of streptococcus lacking hyaluronic acid and M-protein) are directly phagocytosed. Most bacteria endowed with aggressive factors (staphylococci - A-protein, E. coli - expressed capsular antigen, salmonella - Vi-antigen, etc.) are phagocytosed only after they are opsonized by complement and/or antibodies.
The presentation, 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 of the secretion of biologically active substances - monokines - by mononuclear phagocytes. These include substances that have a regulating effect on the proliferation, differentiation and functions 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 the lymphokine interleukin-2 (IL-2). IL-1 and IL-2 are cellular mediators involved in the regulation of immunogenesis and various forms of 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 spectrum 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 cells, in the immediate microenvironment. These secretory products can also mediate the cytotoxic effect of phagocytes on various target cells in cell-mediated immune reactions, for example, in a delayed-type hypersensitivity reaction (DTH), in homograft rejection, and in antitumor immunity.
The considered functions of phagocytic cells ensure their active participation in maintaining homeostasis of the body, in the processes of inflammation and regeneration, in nonspecific anti-infective defense, as well as in immunogenesis and reactions of specific cellular immunity (SCT). The early involvement of phagocytic cells (first granulocytes, then macrophages) in the 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. At the site of inflammation, the functions of phagocytes are activated. Macrophages replace microphages. In cases where the inflammatory reaction with the participation of 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-assembled system of serum proteins that plays an important role in maintaining homeostasis. It is capable of being activated during the process of self-assembly, i.e., the sequential attachment of individual proteins, which are called components or complement fractions, to the resulting complex. Nine such factions are known. 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 in the classical way, the 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 joins the antigen-antibody complex, an enzyme (C1-esterase) is formed, under the action of which an enzymatically active complex (C4b, C2a) is formed, called C3-convertase. This enzyme breaks down S3 into S3 and S3b. When subfraction C3b 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 fraction C5, and then C6 and C7, on it. The last three components jointly promote the fixation of C8 and C9. In this case, two sets of complement fractions - C5a, C6, C7, C8 and C9 - constitute a membrane attack complex, after which it attaches to the cell membrane, the cell is lysed 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, hemolysis of erythrocytes occurs; if the immune complex consists of a bacterium and an antibacterial Ig, lysis of the bacteria occurs (bacteriolysis).
Thus, when activating complement 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 activation of S3 with the formation of S3b with the participation of S3 convertase of the alternative pathway, i.e., bypassing the first three components: C1, C4 and C2. The peculiarity 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.
dependent and oxygen-independent mechanisms of bactericidal activity. Opsonins. Methods
studying the phagocytic activity of cells.
Phagocytosis is a process in which blood cells specially designed for this purpose and
body tissues (phagocytes) capture and digest solid particles.
Carried out by two types of cells: granular cells circulating in the blood
leukocytes (granulocytes) and tissue macrophages.
Stages of phagocytosis:
1. Chemotaxis. In the phagocytosis reaction, a more important role belongs to the positive
chemotaxis. Products secreted act as chemoattractants
microorganisms and activated cells at the site of inflammation (cytokines, leukotriene
B4, histamine), as well as breakdown products of complement components (C3a, C5a),
proteolytic fragments of blood coagulation and fibrinolysis factors (thrombin,
fibrin), neuropeptides, fragments of immunoglobulins, etc. However, “professional”
Chemotaxins are cytokines from the chemokine group. Before other cells reach the site of inflammation
Neutrophils migrate, macrophages arrive much later. Speed
chemotactic movement for neutrophils and macrophages is comparable, differences in
arrival times are probably associated with different rates of activation.
2. Adhesion phagocytes to the object. Caused by the presence of phagocytes on the surface
receptors for molecules present on the surface of an object (its own or
contacted him). During phagocytosis of bacteria or old cells of the host body
recognition of terminal saccharide groups occurs - 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
first make the absorption object acceptable for the reaction,
enveloping it with its own products, including components of the intercellular
matrix they produce. Although phagocytes are capable of absorbing various types of
“unprepared” objects, the phagocytic process reaches its greatest intensity
during opsonization, i.e. fixation on the surface of objects of opsonins to which phagocytes
there are specific receptors - for the Fc fragment of antibodies, components of the system
complement, fibronectin, etc.
3. Activation membranes. At this stage, the object is prepared for immersion.
Protein kinase C is activated and calcium ions are released from intracellular stores.
Sol-gel transitions in the system of cellular colloids and actino-
myosin rearrangements.
4. Dive. The object is enveloped.
5. Phagosome formation. Closing the membrane, immersing an object with part of the membrane
phagocyte inside the cell.
6. Phagolysosome formation. Fusion of the phagosome with lysosomes, resulting in
optimal conditions are formed for bacteriolysis and breakdown of the killed cell.
The mechanisms of bringing the phagosome and lysosomes closer together are unclear; there is probably an active
movement of lysosomes to phagosomes.
7. Killing and splitting. The role of the cell wall of the cell being digested is great. Basic
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. NLDP 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 is also quickly transformed into hydrogen peroxide according to the scheme: 202 + H20 = H202 + O2 (process
catalyzes the enzyme superoxide dismutase).
Opsonins are 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 citrated blood taken from a finger in a volume of 0.2 ml.
The mixture is incubated for 30 minutes at 37°C, centrifuged at 1500 rpm for 5-6 minutes, and the supernatant is removed. A thin silvery layer of leukocytes is carefully sucked out, smears are prepared, dried, fixed, and painted with Romanovsky-Giemsa paint. The preparations are dried and microscopically examined.
The count of absorbed microbes is carried out in 200 neutrophils (50 monocytes). The intensity of the reaction is assessed using the following indicators:
1. Phagocytic indicator (phagocytic activity) - the percentage of phagocytes from the number of counted cells.
2. Phagocytic number (phagocytic index) - the average number of microbes absorbed by one active phagocyte.
To determine the digestive ability of peripheral blood leukocytes, a mixture of the taken blood and a suspension of the microorganism is prepared and kept in a thermostat at 37°C for 2 hours. Preparation of smears is similar. During microscopy of the preparation, viable microbial cells are increased in size, while digested ones are less intensely colored and smaller in size. 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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Most often, we learn from adults raised by various TV shows that immunity lives in the intestines. It is important to wash everything, boil it, eat right, saturate the body with beneficial bacteria and everything like that.
But this is not the only thing that matters for immunity. In 1908, Russian scientist I.I. Mechnikov received the Nobel Prize in physiology, telling (and proving) to the whole world about the presence in general and the importance in particular of phagocytosis in work
Phagocytosis
Our body's defense against harmful viruses and bacteria occurs in the blood. The general principle of operation is this: there are marker cells, they see the enemy and mark him, and rescue cells use the marks to find the stranger and destroy him.
Phagocytosis is the process of destruction, that is, the absorption of harmful living cells and non-living particles by other organisms or special cells - phagocytes. There are 5 types of them. And the process itself takes about 3 hours and includes 8 stages.
Stages of phagocytosis
Let's take a closer look at what phagocytosis is. This process is very orderly and systematic:
First, the phagocyte notices the object of influence and moves towards it - this stage is called chemotaxis;
Having caught up with the object, the cell firmly sticks, attaches to it, i.e., adheres;
Then it begins to activate its shell - the outer membrane;
Now the phenomenon itself begins, marked by the formation of pseudopodia around the object;
Gradually, the phagocyte encloses the harmful cell inside itself, under its membrane, so a phagosome is formed;
At this stage, the fusion of phagosomes and lysosomes occurs;
Now you can digest everything - destroy it;
At the final stage, all that remains is to throw away the digestion products.
All! The process of destroying the harmful organism is completed; it died under the influence of the strong digestive enzymes of the phagocyte or as a result of a respiratory explosion. Ours won!
Jokes aside, phagocytosis is a very important mechanism of the body’s defense system, which is inherent in humans and animals, moreover, in vertebrate and invertebrate organisms.
Characters
Not only the phagocytes themselves participate in phagocytosis. Despite the fact that these active cells are always ready to fight, they would be completely useless without cytokines. After all, the phagocyte, so to speak, is blind. He himself does not distinguish between friends and strangers, or rather, he simply does not see anything.
Cytokines are signaling, a kind of guide for phagocytes. They just have excellent “sight”, they are well versed in who is who. Having noticed a virus or bacteria, they glue a marker on it, by which, like smell, the phagocyte will find it.
The most important cytokines are the so-called transfer factor molecules. With their help, phagocytes not only find out where the enemy is, but also communicate with each other, call for help, and awaken leukocytes.
By receiving a vaccination, we train cytokines, teach them to recognize a new enemy.
Types of phagocytes
Cells capable of phagocytosis are divided into professional and non-professional phagocytes. Professionals are:
monocytes - belong to leukocytes, have the nickname “janitors”, which they received for their unique ability to absorb (so to speak, they have a very good appetite);
Macrophages are large eaters that consume dead and damaged cells and promote the formation of antibodies;
Neutrophils are always the first to arrive at the site of infection. They are the most numerous, they neutralize enemies well, but they themselves also die in the process (a kind of kamikaze). By the way, pus is dead neutrophils;
Dendrites - specialize in pathogens and work in contact with the environment,
Mast cells are the progenitors of cytokines and also scavengers of gram-negative bacteria.
