Fish are macrophages. Characteristics, development, location and role of macrophages. Signaling function of phagocytes
Good afternoon, dear readers!
Last time I told you about a very important group of blood cells - which are the real front line fighters of the immune defense. But they are not the only participants in operations to capture and destroy "enemy agents" in our body. They have helpers. And today I want to continue my story and explore functions
leukocytes - agranulocytes.
This group also includes lymphocytes, in the cytoplasm of which there is no granularity.
Monocyte is the largest representative of leukocytes. Its cell diameter is 10-15 microns, the cytoplasm is filled with a large bean-shaped nucleus. There are few of them in the blood, only 2 - 6%. But in the bone marrow, they are formed in large quantities and mature in the same microcolonies as neutrophils. But when they enter the bloodstream, their paths diverge. Neutrophils travel through the vessels and are always ready #1. And monocytes quickly settle in the organs and there they turn into macrophages. Half of them go to the liver, and the rest are settled in the spleen, intestines, lungs, etc.
Macrophages- these are sedentary, finally ripened. Like neutrophils, they are capable of phagocytosis, but, in addition, they have their own sphere of influence and other specific tasks. Under a microscope, a macrophage is a very prominent cell with impressive dimensions up to 40-50 microns in diameter. This is a real mobile factory for the synthesis of special proteins for its own needs and for neighboring cells. It turns out that a macrophage can synthesize and secrete up to 80 per day! various chemical compounds. You ask: what active substances are secreted by macrophages? It depends on where macrophages live and what functions they perform.
Functions of leukocytes:
Let's start with the bone marrow. There are two types of macrophages involved in the process of bone renewal - osteoclasts and osteoblasts. Osteoclasts constantly circulate through the bone tissue, look for old cells and destroy them, leaving behind free space for the future bone marrow, and osteoblasts form new tissue. Macrophages perform this work by synthesizing and secreting special stimulating proteins, enzymes and hormones. For example, they synthesize collagenase and phosphatase to destroy bone, and erythropoietin to grow red blood cells.
There are also cells - "nurses" and cells - "orderlies", which ensure the rapid reproduction and normal maturation of blood cells in the bone marrow. Hematopoiesis in the bones goes in islands - in the middle of such a colony there is a macrophage, and red cells of different ages crowd around. Performing the function of a nursing mother, a macrophage supplies growing cells with nutrition - amino acids, carbohydrates, fatty acids.
They play a special role in the liver. There they are called Kupffer cells. Actively working in the liver, macrophages absorb various harmful substances and particles coming from the intestines. Together with liver cells, they are involved in the processing of fatty acids, cholesterol and lipids. Thus, they unexpectedly turn out to be involved in the formation of cholesterol plaques on the walls of blood vessels and the occurrence of atherosclerosis.
It is not yet entirely clear where the atherosclerotic process begins. Perhaps, an erroneous reaction to “their” lipoproteins in the blood is triggered here, and macrophages, like vigilant immune cells, begin to capture them. It turns out that the voracity of macrophages has both positive and negative sides. Capturing and destroying microbes is, of course, a good thing. But excessive absorption of fatty substances by macrophages is bad and probably leads to a pathology that is dangerous for human health and life.
But it’s hard for macrophages to separate what’s good and bad, so our task is to alleviate the fate of macrophages and take care of our own health and the health of the liver ourselves: monitor nutrition, reduce the consumption of foods containing a large amount of fats and cholesterol, and twice a year remove toxins and toxins.
Now let's talk about macrophages, working in the lungs.
Inhaled air and blood in the pulmonary vessels are separated by the thinnest border. You understand how important it is in these conditions to ensure the sterility of the airways! That's right, here this function is also performed by macrophages wandering through the connective tissue of the lungs.
They are always filled with the remnants of dead lung cells and microbes inhaled from the surrounding air. Lung macrophages multiply right there in the zone of their activity, and their number increases sharply in chronic respiratory diseases.
To the attention of smokers! Dust particles and tar in tobacco smoke are highly irritating to the upper respiratory
way, damage the mucous cells of the bronchi and alveoli. Lung macrophages, of course, capture and detoxify these harmful chemicals. Smokers dramatically increase the activity, number and even size of macrophages. But after 15 - 20 years the limit of their reliability is depleted. The delicate cellular barriers separating air and blood are broken, the infection breaks into the depths of the lung tissue and inflammation begins. Macrophages are no longer able to fully work as microbial filters and give way to granulocytes. So, long-term smoking leads to chronic bronchitis and a decrease in the respiratory surface of the lungs. Too active macrophages corrode the elastic fibers of the lung tissue, which leads to difficulty breathing and hypoxia.
The saddest thing is that, working for wear and tear, macrophages cease to perform very important functions - this is the ability to fight malignant cells. Therefore, chronic hepatitis is fraught with the development of liver tumors, and chronic pneumonia - with lung cancer.
Macrophages spleen.
In the spleen, macrophages act as "killers" by destroying aging red blood cells. On the shells of red blood cells, treacherous proteins are exposed, which are a signal for elimination. By the way, the destruction of old erythrocytes takes place both in the liver and in the bone marrow itself - wherever there are macrophages. In the spleen, this process is most evident.
Thus, macrophages are great workers and the most important orderlies of our body, while performing several key roles at once:
- involved in phagocytosis
- preservation and processing of important nutrients for the needs of the body,
- the release of several dozen proteins and other biologically active substances, which regulates the growth of blood cells and other tissues.
Well, we know functions of leukocytes - monocytes and macrophages.
And again, there was no time left for lymphocytes. About them, the smallest defenders of our body, we will talk next time.
In the meantime, let's get healthier and strengthen the immune system by listening to the healing music of Mozart - Symphony of the Heart:
I wish you good health and prosperity!
MACROPHAGES MACROPHAGES
(from macro... and... phage), cells of mesenchymal origin in the animal body, capable of actively capturing and digesting bacteria, the remains of dead cells, and other foreign and toxic particles for the body. The term "M." introduced by I. I. Mechnikov (1892). They are large cells of variable shape, with pseudopodia, contain many lysosomes. M. are present in the blood (monocytes), connect, tissues (histocytes), hematopoietic organs, liver (Kupffer cells), the wall of the lung alveoli (pulmonary M.), abdominal and pleural cavities (peritoneal and pleural M.). In mammals, M. are formed in the red bone marrow from a hematopoietic stem cell, passing through the stages of monoblast, promonocyte, and monocyte. All these varieties of M. are combined into a system of single-nuclear phagocytes. (see PHAGOCYTOSIS, RETICULOENDOTHELIAL SYSTEM).
.(Source: "Biological Encyclopedic Dictionary." Chief editor M. S. Gilyarov; Editorial board: A. A. Babaev, G. G. Vinberg, G. A. Zavarzin and others - 2nd ed., corrected . - M .: Sov. Encyclopedia, 1986.)
macrophagesCells in the animal body that are capable of actively capturing and digesting bacteria, the remains of dead cells and other foreign and toxic particles for the body. They are found in the blood, connective tissue, liver, bronchi, lungs, and abdominal cavity. The term was introduced by I.I. Mechnikov who discovered the phenomenon phagocytosis.
.(Source: "Biology. Modern Illustrated Encyclopedia." Editor-in-Chief A.P. Gorkin; M.: Rosmen, 2006.)
See what "MACROPHAGES" are in other dictionaries:
- ... Wikipedia
MACROPHAGES- (from the Greek. makros: big and phago eat), vulture. megalophages, macrophagocytes, large phagocytes. The term M. was proposed by Mechnikov, who divided all cells capable of phagocytosis into small phagocytes, microphages (see), and large phagocytes, macrophages. Under… … Big Medical Encyclopedia
- (from macro ... and ... phage) (polyblasts) cells of mesenchymal origin in animals and humans, capable of actively capturing and digesting bacteria, cell debris, and other foreign or toxic particles for the body (see Phagocytosis). For macrophages... Big Encyclopedic Dictionary
The main cell type of the mononuclear phagocyte system. These are large (10-24 microns) long-lived cells with a well-developed lysosomal and membrane apparatus. On their surface there are receptors for the Fc fragment of IgGl and IgG3, C3b fragment C, receptors B ... Dictionary of microbiology
MACROPHAGES- [from macro... and phage (s)], organisms that devour large prey. Wed Microphages. Ecological encyclopedic dictionary. Chisinau: Main edition of the Moldavian Soviet Encyclopedia. I.I. Grandpa. 1989... Ecological dictionary
macrophages- A type of lymphocytes that provide nonspecific protection through phagocytosis and are involved in the development of the immune response as antigen presenting cells. [English Russian glossary of basic terms on vaccinology and ... ... Technical Translator's Handbook
Monocytes (macrophages) are a type of white blood cell involved in fighting infections. Monocytes, along with neutrophils, are the two main types of blood cells that engulf and destroy various microorganisms. When monocytes leave... ... medical terms
- (from macro ... and ... phage) (polyblasts), cells of mesenchymal origin in animals and humans, capable of actively capturing and digesting bacteria, cell debris and other foreign or toxic particles for the body (see Phagocytosis). ... … encyclopedic Dictionary
- (see macro ... + ... phage) cells of the connective tissue of animals and humans, capable of capturing and digesting various particles foreign to the body (including microbes); and. and. Mechnikov called these cells macrophages, in contrast to ... ... Dictionary of foreign words of the Russian language
macrophages- iv, pl. (one macroph/g, a, h). Cells of healthy tissues of living organisms, building scoping and over-etching of bacteria, lattices of dead cells and other foreign or toxic particles for the body. Placenta / pH macrophages / hy macrophages that ... ... Ukrainian glossy dictionary
Books
- placental macrophages. Morphofunctional characteristics and role in the gestational process, Pavlov Oleg Vladimirovich, Selkov Sergey Alekseevich. For the first time in the world literature, the monograph collects and systematizes modern information on a little-studied group of human placental cells - placental macrophages. Described in detail...
Mechnikov classified microphages as granular polymorphonuclear blood leukocytes, which, emigrating from blood vessels, exhibit vigorous phagocytosis mainly in relation to bacteria, and to a much lesser extent (in contrast to macrophages) to various products of tissue decay.
The phagocytic activity of microphages is especially well manifested in pus containing bacteria.
Microphages differ from macrophages in that they do not perceive vital coloring.
Macrophages contain enzymes for the digestion of phagocytosed substances. These enzymes are contained in vacuoles (vesicles) called lysosomes and are able to break down proteins, fats, carbohydrates and nucleic acids.
Macrophages cleanse the human body of particles of inorganic origin, as well as bacteria, viral particles, dying cells, toxins - toxic substances formed during the decay of cells or produced by bacteria. In addition, macrophages secrete some humoral and secretory substances into the blood: complement elements C2, C3, C4, lysozyme, interferon, interleukin-1, prostaglandins, o^-macroglobulin, monokines that regulate the immune response, cytotoxins are poisonous for substance cells.
Macrophages have a subtle mechanism for recognizing foreign particles of an antigenic nature. They distinguish and quickly absorb old and newborn erythrocytes without touching normal erythrocytes. For a long time, the role of “cleaners” was assigned to macrophages, but they are also the first link in a specialized defense system. Macrophages, including the antigen in the cytoplasm, recognize it with the help of enzymes. Substances are released from lysosomes that dissolve the antigen within approximately 30 minutes, after which it is excreted from the body.
The antigen is expressed and recognized by macrophages, after which it passes to lymphocytes. Neutrophil granulocytes (neutrophils, or microphages) are also formed in the bone marrow, from where they enter the bloodstream, where they circulate for 6-24 hours.
Unlike macrophages, mature microphages receive energy not from respiration, but from glycolysis, like prokaryotes, that is, they become anaerobes, and can carry out their activities in oxygen-free zones, for example, in exudates during inflammation, supplementing the activity of macrophages. Macrophages and microphages on their surface carry receptors for immunoglobulin JgJ and complement element C3, which help the phagocyte in recognizing and attaching the antigen to the surface of its cell. Violation of the activity of phagocytes quite often manifests itself in the form of recurrent purulent-septic diseases, such as chronic pneumonia, pyoderma, osteomyelitis, etc.
In a number of infections, various acquisitions of phagocytosis occur. Thus, tuberculosis mycobacteria are not destroyed by phagocytosis. Staphylococcus inhibits its absorption by the phagocyte. Violation of the activity of phagocytes also leads to the development of chronic inflammation and diseases associated with the fact that the material accumulated by macrophages from the decomposition of phagocytized substances cannot be removed from the body due to the deficiency of certain phagocyte enzymes. The pathology of phagocytosis may be associated with impaired interaction of phagocytes with other systems of cellular and humoral immunity.
Phagocytosis is facilitated by normal antibodies and immunoglobulins, complement, lysozyme, leukins, interferon, and a number of other enzymes and blood secretions that pre-process the antigen, making it more accessible for capture and digestion by the phagocyte.
In the 1970s, the mononuclear phagocyte system was hypothesized, according to which macrophages represent the final stage in the differentiation of blood monocytes, which in turn are derived from multipotent blood stem cells in the bone marrow. However, studies conducted in 2008-2013 showed that macrophages in adult mice tissues are represented by two populations that differ in their origin, the mechanism for maintaining numbers, and functions. The first population is tissue, or resident macrophages. They originate from erythromyeloid progenitors (not related to blood stem cells) of the yolk sac and embryonic liver and colonize tissues at various stages of embryogenesis. Resident macrophages acquire tissue-specific characteristics and maintain their numbers through in situ proliferation without any involvement of monocytes. Long-lived tissue macrophages include Kupffer cells of the liver, microglia of the central nervous system, alveolar macrophages of the lungs, peritoneal macrophages of the abdominal cavity, Langerhans cells of the skin, macrophages of the red pulp of the spleen.
The second population is represented by relatively short-lived macrophages of monocytic (bone marrow) origin. The relative content of such cells in a tissue depends on its type and the age of the organism. Thus, macrophages of bone marrow origin make up less than 5% of all macrophages of the brain, liver and epidermis, a small proportion of macrophages of the lungs, heart and spleen (however, this proportion increases with the age of the body) and most of the macrophages of the lamina propria of the intestinal mucosa. The number of macrophages of monocytic origin increases sharply during inflammation and normalizes after it ends.
Macrophage activation
In vitro, under the influence of exogenous stimuli, macrophages can be activated. Activation is accompanied by a significant change in the gene expression profile and the formation of a cell phenotype specific for each type of stimulus. Historically, two largely opposite types of activated macrophages were the first to be discovered, which, by analogy with Th1/Th2, were named M1 and M2. Type M1 macrophages differentiate ex vivo upon stimulation of precursors with interferon γ with the participation of the transcription factor STAT1. M2 type macrophages differentiate ex vivo upon stimulation with interleukin 4 (via STAT6).
For a long time, M1 and M2 were the only known types of activated macrophages, which made it possible to formulate a hypothesis about their polarization. However, by 2014, evidence had accumulated indicating the existence of a whole range of activated states of macrophages that correspond neither to the M1 nor the M2 type. At present, there is no conclusive evidence that the activated states of macrophages observed in vitro correspond to what occurs in vivo, and whether these states are permanent or temporary.
Tumor-associated macrophages
Malignant tumors affect their tissue microenvironment, including macrophages. Blood monocytes infiltrate the tumor and, under the influence of signaling molecules secreted by the tumor (M-CSF, GM-CSF, IL4, IL10, TGF-β), differentiate into macrophages with an "anti-inflammatory" phenotype and, by suppressing antitumor immunity and stimulating the formation of new blood vessels, promote tumor growth and metastasis.
Macrophages (monocytes, von Kupffer cells, Langerhans cells, histiophages, alveolocytes, etc.) are able to effectively capture and destroy various microbes and damaged structures intracellularly.
Microphages (granulocytes: neutrophils, eosinophils, basophils, platelets, endotheliocytes, microglial cells, etc.) to a lesser extent, but are also able to capture and damage microbes.
In phagocytes, during all stages of phagocytosis of microbes, both oxygen-dependent and oxygen-independent microbicidal systems are activated.
The main components of the oxygen-consuming microbicidal system of phagocytes are myeloperoxidase, catalase and reactive oxygen species (singlet oxygen - 02, superoxide radical - 02, hydroxyl radical - OH, hydrogen peroxide - H202).
The main components of the oxygen-independent microbicidal system of phagocytes are lysozyme (muramidase), lactoferrin, cationic proteins, H + ions (acidosis), lysosome hydrolases.
3. Humoral bactericidal and bacteriostatic factors:
Lysozyme, destroying the muramic acid of the peptidoglycans of the wall of gram-positive bacteria, leads to their osmotic lysis;
Lactoferrin, changing the metabolism of iron in microbes, disrupts their life cycle and often leads to their death;
- (3-lysines are bactericidal for most Gram-positive bacteria;
Complement factors, having an opsonizing effect, activate the phagocytosis of microbes;
The interferon system (especially a and y) exhibits a distinct nonspecific antiviral activity;
The activity of both microvilli and glandular cells of the mucous membrane of the airways, as well as sweat and sebaceous glands of the skin, which secrete the corresponding secrets (sputum, sweat and fat), contributes to the removal of a certain number of various microorganisms from the body.
Phagocytosis, the process of active capture and absorption of living and non-living particles by unicellular organisms or special cells (phagocytes) of multicellular animal organisms. Phenomenon F. was discovered by I. I. Mechnikov, who traced its evolution and clarified the role of this process in the protective reactions of the body of higher animals and humans, mainly during inflammation and immunity. F. plays an important role in wound healing. The ability to capture and digest particles underlies the nutrition of primitive organisms. In the process of evolution, this ability gradually passed to individual specialized cells, first digestive, and then to special cells of the connective tissue. In humans and mammals, active phagocytes are neutrophils (microphages, or special leukocytes) of the blood and cells of the reticuloendothelial system that can turn into active macrophages. Neutrophils phagocytize small particles (bacteria, etc.), macrophages are able to absorb larger particles (dead cells, their nuclei or fragments, etc.). Macrophages are also able to accumulate negatively charged particles of dyes and colloidal substances. The absorption of small colloidal particles is called ultraphagocytosis, or colloidopexy.
Phagocytosis requires energy and is associated primarily with the activity of the cell membrane and intracellular organelles - lysosomes, containing a large number of hydrolytic enzymes. During F. several stages are distinguished. First, the phagocytosed particle attaches to the cell membrane, which then envelops it and forms an intracellular body, the phagosome. From the surrounding lysosomes, hydrolytic enzymes enter the phagosome, digesting the phagocytosed particle. Depending on the physicochemical properties of the latter, digestion may be complete or incomplete. In the latter case, a residual body is formed, which can remain in the cell for a long time.
Complement - (obsolete alexin), a protein complex found in fresh blood serum; an important factor in natural immunity in animals and humans. The term was introduced in 1899 by the German scientists P. Ehrlich and J. Morgenrot. K. consists of 9 components, which are designated from C "1 to C" 9, and the first component includes three subunits. All 11 proteins that make up K. can be separated by immunochemical and physicochemical methods. To. is easily destroyed when serum is heated, during its long-term storage, exposure to light. To. takes part in a number of immunological reactions: joining the antigen complex (See Antigens) with an antibody (See Antibodies) on the surface of the cell membrane, it causes lysis of bacteria, erythrocytes, and other cells treated with the corresponding antibodies. For membrane destruction and subsequent cell lysis, the participation of all 9 components is required. Some components of K. have enzymatic activity, and the component that has previously joined the antigen-antibody complex catalyzes the addition of the next one. In the body, K. also participates in antigen-antibody reactions that do not cause cell lysis. The resistance of the organism to pathogenic microbes, the release of histamine during allergic reactions of the immediate type, and autoimmune processes are associated with the action of K.. In medicine, preserved K. preparations are used in the serological diagnosis of a number of infectious diseases, for the detection of antigens and antibodies.
INTERFERONS - a group of low molecular weight glycoproteins produced by human or animal cells in response to a viral infection or under the action of various inducers (for example, double-stranded RNA, inactivated viruses, etc.) and have an antiviral effect.
Interferons are represented by three classes:
alpha-leukocyte, produced by nuclear blood cells (granulocytes, lymphocytes, monocytes, poorly differentiated cells);
beta-fibroblast - synthesized by cells of the skin-muscle, connective and lymphoid tissues:
gamma-immune - produced by T-lymphocytes in cooperation with macrophages, natural killers.
The antiviral action does not occur directly during the interaction of interferons with the virus, but indirectly through cellular reactions. Enzymes and inhibitors, the synthesis of which is induced by interferon, block the start of translation of foreign genetic information, destroy messenger RNA molecules. Interacting with the cells of the immune system, they stimulate phagocytosis, the activity of natural killers, the expression of the major histocompatibility complex. By directly acting on B cells, interferon regulates the process of antibody formation.
ANTIGEN - Chemical molecules that are found in (or embedded in) the cell membrane and are capable of eliciting an immune response are called antigens. They are divided into differentiated and deterministic. Differentiated antigens include CD antigens. The major histocompatibility complex is HLA (hyman lencocyte antigen).
Antigens are divided into:
toxins;
isoantigens;
Heterophilic antigens;
Home antigens;
Gantens;
Immunogens;
Adjuvants;
hidden antigens.
Toxins are waste products of bacteria. Toxins can be chemically converted into toxoids, in which the toxic properties disappear, but the antigenic properties remain. This feature is used to prepare a number of vaccines.
A- and B-isoantigens are mucopolysaccharide antigens, against which the body always has antibodies (aplotinins).
By antibodies to A- and B-isoantigens, 4 blood groups are determined.
Heterophilic antigens are present in the tissue cells of many animals; they are absent in human blood.
Household antigens are self-antigens, most of which are tolerated by the immune system.
Ganthens are substances that specifically react with antibodies, but do not contribute to their formation. Ganthens are formed during allergic reactions to drugs.
Immunogens (viruses and bacteria) are stronger than soluble antigens.
Adjuvants are substances that, when administered with an antigen, enhance the immune response.
The latent antigen may be semen, which in some cases acts as a foreign protein in traumatic testicular injuries or changes caused by mumps.
Antigens are also divided into:
Antigens that are components of cells;
External antigens that are not components of cells;
Autoantigens (hidden), not penetrating to immunocompetent cells.
Antigens are classified according to other criteria:
By the type of inducing an immune response - immunogens, allergens, tolerogens, transplantation);
By foreignness - on hetero- and autoantigens;
By connection with the thymus gland - T-dependent and T-independent;
By localization in the body - O-antigens (zero), thermostable, highly active, etc.);
By specificity for the carrier microorganism - species, type, variant, group, stage.
The interaction of the body with antigens can occur in different ways. The antigen can penetrate the macrophage and be eliminated in it.
In another variant, it can be connected to receptors on the surface of the macrophage. The antigen is able to react with the antibody on the macrophage outgrowth and come into contact with the lymphocyte.
In addition, the antigen can bypass the macrophage and react with the antibody receptor on the surface of the lymphocyte or enter the cell.
Specific reactions under the action of antigens proceed in different ways:
With the formation of humoral antibodies (during the transformation of the immunoblast into a plasma cell);
The sensitized lymphocyte turns into a memory cell, which leads to the formation of humoral antibodies;
The lymphocyte acquires the properties of a killer lymphocyte;
A lymphocyte can become a non-reactive cell if all of its receptors are bound to an antigen.
Antigens give cells the ability to synthesize antibodies, which depends on their form, dosage and route of entry into the body.
Types of Immunity
There are two types of immunity: specific and nonspecific.
Specific immunity is individual in nature and is formed throughout a person's life as a result of contact of his immune system with various microbes and antigens. Specific immunity preserves the memory of the infection and prevents its recurrence.
Nonspecific immunity is species-specific in nature, that is, it is almost the same for all representatives of the same species. Nonspecific immunity ensures the fight against infection in the early stages of its development, when specific immunity has not yet been formed. The state of nonspecific immunity determines a person's predisposition to various banal infections, the causative agents of which are conditionally pathogenic microbes. Immunity can be species or innate (for example, a person to the causative agent of canine distemper) and acquired.
Natural passive immunity. Abs from the mother are transmitted to the child through the placenta, with breast milk. It provides short-term protection against infection, as antibodies are consumed and their number decreases, but provides protection until the formation of one's own immunity.
Natural active immunity. The production of own antibodies upon contact with the antigen. Immunological memory cells provide the most stable, sometimes lifelong immunity.
Acquired passive immunity. It is created artificially by introducing ready-made antibodies (serum) from immune organisms (serum against diphtheria, tetanus, snake venom). Immunity of this type is also short-lived.
Acquired active immunity. A small amount of antigens is injected into the body in the form of a vaccine. This process is called vaccination. A killed or attenuated antigen is used. The body does not get sick, but produces AT. Repeated administration is often made and stimulates faster and more sustained formation of antibodies that provide long-term protection.
Specificity of antibodies. Each antibody is specific for a particular antigen; this is due to the unique structural organization of amino acids in the variable regions of its light and heavy chains. The amino acid organization has a different spatial configuration for each antigen specificity, so when the antigen comes into contact with the antibody, the numerous prosthetic groups of the antigen mirror the same groups of the antibody, due to which fast and tight binding occurs between the antibody and antigen. If the antibody is highly specific and there are many binding sites, there is a strong bond between the antibody and antigen through: (1) hydrophobic bonds; (2) hydrogen bonds; (3) ion attraction; (4) van der Waals forces. The antigen-antibody complex also obeys the thermodynamic law of mass action.
Structure and functions of the immune system.
Structure of the immune system. The immune system is represented by lymphoid tissue. This is a specialized, anatomically isolated tissue, scattered throughout the body in the form of various lymphoid formations. Lymphoid tissue includes the thymus, or goiter, gland, bone marrow, spleen, lymph nodes (group lymph follicles, or Peyer's patches, tonsils, axillary, inguinal and other lymphatic formations scattered throughout the body), as well as lymphocytes circulating in the blood. Lymphoid tissue consists of reticular cells that make up the backbone of the tissue, and lymphocytes located between these cells. The main functional cells of the immune system are lymphocytes, subdivided into T- and B-lymphocytes and their subpopulations. The total number of lymphocytes in the human body reaches 1012, and the total mass of lymphoid tissue is approximately 1-2% of body weight.
Lymphoid organs are divided into central (primary) and peripheral (secondary).
Functions of the immune system. The immune system performs the function of specific protection against antigens, which is a lymphoid tissue capable of neutralizing, neutralizing, removing, destroying a genetically alien antigen that has entered the body from outside or formed in the body itself.
The specific function of the immune system in the neutralization of antigens is complemented by a complex of mechanisms and reactions of a non-specific nature aimed at ensuring the body's resistance to the effects of any foreign substances, including antigens.
Serological reactions
In vitro reactions between antigens and antibodies or serological reactions are widely used in microbiological and serological (immunological) laboratories for a wide variety of purposes:
serodiagnostics of bacterial, viral, less often other infectious diseases,
seroidentification of isolated bacterial, viral and other cultures of various microorganisms
Serodiagnosis is carried out using a set of specific antigens produced by commercial firms. According to the results of serodiagnostic reactions, the dynamics of antibody accumulation in the course of the disease, the intensity of post-infectious or post-vaccination immunity are judged.
Seroidentification of microbial cultures is carried out to determine their type, serovar using sets of specific antisera, also produced by commercial firms.
Each serological reaction is characterized by specificity and sensitivity. Specificity is understood as the ability of antigens or antibodies to react only with homologous antibodies contained in the blood serum, or with homologous antigens, respectively. The higher the specificity, the fewer false positives and false negatives.
Serological reactions involve antibodies belonging mainly to the immunoglobulins of the IgG and IgM classes.
The agglutination reaction is a process of agglutination and precipitation of a corpuscular antigen (agglutinogen) under the influence of specific antibodies (agglutinins) in an electrolyte solution in the form of lumps of agglutinate.
Our body is surrounded by a huge number of negative and damaging environmental factors: ionizing and magnetic radiation, sharp temperature fluctuations, various pathogenic bacteria and viruses. To resist their negative influence and maintain homeostasis at a constant level, a powerful protective complex is built into the biocomputer of the human body. It unites organs such as the thymus, spleen, liver and lymph nodes. In this article, we will study the functions of macrophages that are part of the mononuclear phagocytic system, and also find out their role in the formation of the immune status of the human body.
general characteristics
Macrophages are "big eaters", this is the translation of the name of these protective cells, proposed by I.I. Mechnikov. They are capable of amoeboid movement, rapid capture and splitting of pathogenic bacteria and their metabolic products. These properties are explained by the presence in the cytoplasm of a powerful lysosomal apparatus, the enzymes of which easily destroy the complex membranes of bacteria. Histiocytes quickly recognize antigens and transmit information about them to lymphocytes.
The characteristic of macrophages as cells produced by the organs of the immune system indicates that they can be found in all vital structures of the body: in the kidneys, in the heart and lungs, in the blood and lymphatic channels. They have oncoprotective and signaling properties. The membrane contains receptors that recognize antigens, the signal of which is transmitted to active lymphocytes that produce interleukins.
Currently, histologists and immunologists believe that macrophages are cells formed from multipotent stem structures of the red bone marrow. They are heterogeneous in structure and function, differ in location in the body, degree of maturation and activity in relation to antigens. Let's consider them further.
Types of protective cells
The largest group is represented by phagocytes circulating in connective tissues: lymph, blood, osteoclasts and membranes of internal organs. In the serous cavities of the stomach and intestines, in the pleura and pulmonary vesicles, there are both free and fixed macrophages. This provides protection and detoxification of both the cells themselves and their blood supply elements - the capillaries of the pulmonary alveoli, the small and large intestines, as well as the digestive glands. The liver, as one of the most important organs, has an additional protective system of mononuclear phagocytic structures - Kupffer cells. Let us dwell on their structure and mechanism of action in more detail.
How the main biochemical laboratory of the body is protected
In the systemic circulation, there is an autonomous system of blood supply to the liver, called the portal vein circuit. Due to its functioning, from all organs of the abdominal cavity, blood immediately enters not into the inferior vena cava, but into a separate blood vessel - the portal vein. Further, it sends venous blood saturated with carbon dioxide and decay products to the liver, where hepatocytes and protective cells formed by the peripheral organs of the immune system break down, digest and neutralize toxic substances and pathogens that have entered the venous blood from the gastrointestinal tract. Protective cells have chemotaxis, therefore they accumulate in the foci of inflammation and phagocytize pathogenic compounds that have entered the liver. Now consider Kupffer cells, which play a special role in protecting the digestive gland.
Phagocytic properties of the reticuloendothelial system
The functions of liver macrophages - Kupffer cells - are to capture and process hepatocytes that have lost their functions. At the same time, both the protein part of the blood pigment and the heme itself are cleaved. This is accompanied by the release of iron ions and bilirubin. At the same time, bacteria are lysed, primarily E. coli, that have entered the bloodstream from the large intestine. Protective cells come into contact with microbes in the sinusoidal capillaries of the liver, then capture pathogenic particles and digest them using their own lysosomal apparatus.
Signaling function of phagocytes
Macrophages are not only protective structures that provide cellular immunity. They can identify foreign particles that have entered the cells of the body, since there are receptors on the phagocyte membrane that recognize molecules of antigens or biologically active substances. Most of these compounds cannot directly contact lymphocytes and trigger a defensive response. It is phagocytes that deliver antigenic groups to the membrane, which serve as beacons for B-lymphocytes and T-lymphocytes. Macrophage cells obviously perform the most important function of transmitting a signal about the presence of a damaging agent to the most active and rapidly acting immune complexes. Those, in turn, are able to react with lightning speed to pathogenic particles in the human body and destroy them.
Specific properties
The functions of the elements of the immune system are not limited to protecting the body from foreign environmental components. For example, phagocytes are capable of exchanging iron ions in the red bone marrow and spleen. Participating in erythrophagocytosis, protective cells digest and break down old red blood cells. Alveolar macrophages accumulate iron ions in the form of ferritin and hemosiderin molecules. They can be found in the sputum of patients suffering from heart failure with stagnation of blood in the pulmonary circulation and various forms of heart disease, as well as in patients who have had a heart attack aggravated by pulmonary embolism. The presence of a large number of immune cells in various types of clinical studies, for example, in vaginal swabs, in urine or semen, may indicate inflammatory processes, infectious or oncological diseases occurring in a person.
Peripheral organs of the immune system
Given the critical role of phagocytes, leukocytes and lymphocytes in maintaining the health and genetic uniqueness of the body, as a result of evolution, two lines of defense were created and improved: the central and peripheral organs of the immune system. They produce various types of cells involved in the fight against foreign and pathogenic agents.
These are primarily T-lymphocytes, B-lymphocytes and phagocytes. The spleen, lymph nodes, and follicles of the digestive tract are also capable of producing macrophages. This enables the tissues and organs of the human body to quickly recognize antigens and mobilize humoral and cellular immunity factors to effectively fight infection.
Macrophage many-sided and ubiquitous
One hundred and thirty years ago, the remarkable Russian researcher I.I. Mechnikov, in experiments on starfish larvae from the Strait of Messina, made an amazing discovery that drastically changed not only the life of the future Nobel laureate himself, but also turned the then ideas about the immune system upside down.
Sticking a pink spike into the transparent body of the larva, the scientist discovered that large amoeboid cells surround and attack the splinter. And if the alien body was small, these wandering cells, which Mechnikov called phagocytes (from the Greek. Devourer), could completely absorb the alien.
For many years it was believed that phagocytes perform the functions of "rapid reaction troops" in the body. However, recent studies have shown that, due to their enormous functional plasticity, these cells also "determine the weather" of many metabolic, immunological and inflammatory processes, both in normal and pathological conditions. This makes phagocytes a promising target when developing a strategy for the treatment of a number of serious human diseases.
Depending on their microenvironment, tissue macrophages can perform various specialized functions. For example, macrophages of bone tissue - osteoclasts, are also involved in the removal of calcium hydroxyapatite from the bone. With the insufficiency of this function, marble disease develops - the bone becomes excessively compacted and at the same time fragile.
But perhaps the most surprising property of macrophages was their enormous plasticity, i.e., the ability to change their transcriptional program (“switching on” of certain genes) and their appearance (phenotype). The consequence of this feature is the high heterogeneity of the cellular population of macrophages, among which there are not only "aggressive" cells that come to the defense of the host organism; but also cells with a "polar" function, responsible for the processes of "peaceful" restoration of damaged tissues.
Lipid "antennas"
Macrophage owes its potential "diversity" to the unusual organization of genetic material - the so-called open chromatin. This not fully understood version of the structure of the cellular genome provides a rapid change in the level of expression (activity) of genes in response to various stimuli.
The performance of a particular function by a macrophage depends on the nature of the stimuli it receives. If the stimulus is recognized as "alien", then the activation of those genes (and, accordingly, functions) of the macrophage that are aimed at destroying the "alien" occurs. However, the macrophage can also activate signal molecules of the organism itself, which induce this immune cell to participate in the organization and regulation of metabolism. So, in the conditions of "peacetime", i.e. in the absence of a pathogen and the inflammatory process caused by it, macrophages are involved in the regulation of the expression of genes responsible for the metabolism of lipids and glucose, the differentiation of adipose tissue cells.
Integration between the mutually exclusive "peaceful" and "military" areas of macrophage work is carried out by changing the activity of cell nucleus receptors, which are a special group of regulatory proteins.
Among these nuclear receptors, the so-called lipid sensors, i.e., proteins capable of interacting with lipids (for example, oxidized fatty acids or cholesterol derivatives) should be highlighted (Smirnov, 2009). Disruption of these lipid-sensitive regulatory proteins in macrophages may be the cause of systemic metabolic disorders. For example, deficiency in macrophages of one of these nuclear receptors, referred to as PPAR-gamma, leads to the development of type 2 diabetes and an imbalance in lipid and carbohydrate metabolism throughout the body.
Cellular metamorphoses
In a heterogeneous community of macrophages, based on the basic characteristics that determine their principal functions, three main cell subpopulations are distinguished: M1, M2, and Mox macrophages, which are involved, respectively, in the processes of inflammation, repair of damaged tissues, and protection of the body from oxidative stress.
The “classic” M1 macrophage is formed from a progenitor cell (monocyte) under the action of a cascade of intracellular signals that are triggered after recognition of an infectious agent using special receptors located on the cell surface.
The formation of the "eater" M1 occurs as a result of a powerful activation of the genome, accompanied by activation of the synthesis of more than a hundred proteins - the so-called inflammation factors. These include enzymes that promote the generation of free oxygen radicals; proteins that attract other cells of the immune system to the focus of inflammation, as well as proteins that can destroy the bacterial membrane; inflammatory cytokines - substances that have the ability to activate immune cells and have a toxic effect on the rest of the cellular environment. Phagocytosis is activated in the cell, and the macrophage begins to actively destroy and digest everything that comes in its path (Shvarts and Svistelnik, 2012). So there is a focus of inflammation.
However, already at the initial stages of the inflammatory process, M1 macrophage begins to actively secrete anti-inflammatory substances - low molecular weight lipid molecules. These signals of the "second echelon" begin to activate the aforementioned lipid sensors in new "recruits" - monocytes arriving at the site of inflammation. Inside the cell, a chain of events is triggered, as a result of which the activating signal arrives at certain regulatory regions of DNA, increasing the expression of genes responsible for the harmonization of metabolism and simultaneously suppressing the activity of “pro-inflammatory” (i.e., provoking inflammation) genes (Dushkin, 2012).
So, as a result of alternative activation, M2 macrophages are formed, which complete the inflammatory process and promote tissue repair. The population of M2 macrophages can, in turn, be divided into groups depending on their specialization: scavengers of dead cells; cells involved in the acquired immunity reaction, as well as macrophages that secrete factors that contribute to the replacement of dead tissues with connective tissue.
Another group of macrophages, Mox, is formed under conditions of the so-called oxidative stress, when the risk of damage by free radicals increases in tissues. For example, Mohs make up about a third of all macrophages in atherosclerotic plaque. These immune cells are not only resistant to damaging factors themselves, but also participate in the body's antioxidant defense (Gui et al., 2012).
Foamy kamikaze
One of the most intriguing macrophage metamorphoses is its transformation into the so-called foam cell. Such cells were found in atherosclerotic plaques, and got their name because of their specific appearance: under a microscope, they resembled soap suds. In fact, the foam cell is the same M1 macrophage, but full of fatty inclusions, mainly consisting of water-insoluble compounds of cholesterol and fatty acids.
It was hypothesized, which has become generally accepted, that foam cells form in the wall of atherosclerotic vessels as a result of uncontrolled absorption by macrophages of low-density lipoproteins that carry "bad" cholesterol. However, later it was found that the accumulation of lipids and a dramatic (tens of times!) increase in the rate of synthesis of a number of lipids in macrophages can be provoked in the experiment by inflammation alone, without any participation of low density lipoproteins (Dushkin, 2012).
This assumption was confirmed by clinical observations: it turned out that the transformation of macrophages into a foam cell occurs in various diseases of an inflammatory nature: in the joints - with rheumatoid arthritis, in adipose tissue - with diabetes, in the kidneys - with acute and chronic insufficiency, in brain tissue - with encephalitis . However, it took about twenty years of research to understand how and why a macrophage turns into a cell stuffed with lipids during inflammation.
It turned out that the activation of pro-inflammatory signaling pathways in M1 macrophages leads to the “switching off” of the same lipid sensors that control and normalize lipid metabolism under normal conditions (Dushkin, 2012). When they are “turned off”, the cell begins to accumulate lipids. At the same time, the resulting lipid inclusions are not at all passive fat reservoirs: the lipids that make up them have the ability to enhance inflammatory signaling cascades. The main goal of all these dramatic changes is to activate and strengthen the protective function of the macrophage, aimed at the destruction of “aliens” by any means (Melo and Drorak, 2012).
However, the high content of cholesterol and fatty acids is costly for the foam cell - they stimulate its death through apoptosis, programmed cell death. Phosphatidylserine, a phospholipid normally located inside the cell, is found on the outer surface of the membrane of such "doomed" cells: its appearance outside is a kind of "death knell". This is the “eat me” signal, which is perceived by M2 macrophages. Absorbing apoptotic foam cells, they begin to actively secrete mediators of the final, restorative stage of inflammation.
Pharmacological target
Inflammation as a typical pathological process and the key participation of macrophages in it is, to one degree or another, an important component primarily of infectious diseases caused by various pathological agents, from protozoa and bacteria to viruses: chlamydial infections, tuberculosis, leishmaniasis, trypanosomiasis, etc. At the same time, macrophages, as mentioned above, play an important, if not leading, role in the development of so-called metabolic diseases: atherosclerosis (the main culprit of cardiovascular diseases), diabetes, neurodegenerative diseases of the brain (Alzheimer's and Parkinson's disease, consequences of strokes and craniocerebral brain injury), rheumatoid arthritis, and cancer.
Modern knowledge of the role of lipid sensors in the formation of various macrophage phenotypes has made it possible to develop a strategy for controlling these cells in various diseases.
Thus, it turned out that in the process of evolution, chlamydia and tubercle bacilli learned to use lipid sensors of macrophages in order to stimulate an alternative (in M2) activation of macrophages that is not dangerous for them. Due to this, the tuberculosis bacterium absorbed by the macrophage can, swimming like cheese in oil in lipid inclusions, calmly wait for its release, and after the death of the macrophage, multiply using the contents of the dead cells as food (Melo and Drorak, 2012).
If in this case synthetic activators of lipid sensors are used, which prevent the formation of fatty inclusions and, accordingly, prevent the "foamy" transformation of the macrophage, then it is possible to suppress the growth and reduce the viability of infectious pathogens. At least in experiments on animals, it has already been possible to significantly reduce the contamination of the lungs of mice with tuberculosis bacilli, using a stimulator of one of the lipid sensors or an inhibitor of fatty acid synthesis (Lugo-Villarino et al., 2012).
Another example is diseases such as myocardial infarction, stroke and gangrene of the lower extremities, the most dangerous complications of atherosclerosis, which are caused by the rupture of so-called unstable atherosclerotic plaques, accompanied by the instant formation of a blood clot and blockage of a blood vessel.
The formation of such unstable atherosclerotic plaques is facilitated by the M1 macrophage/foam cell, which produces enzymes that dissolve the collagen coating of the plaque. In this case, the most effective treatment strategy is to transform an unstable plaque into a stable, collagen-rich one, which requires the transformation of an “aggressive” M1 macrophage into a “pacified” M2.
Experimental data indicate that such a macrophage modification can be achieved by suppressing the production of pro-inflammatory factors in it. Such properties are possessed by a number of synthetic activators of lipid sensors, as well as natural substances, for example, curcumin, a bioflavonoid that is part of the turmeric root, a well-known Indian spice.
It should be added that such a transformation of macrophages is relevant in obesity and type 2 diabetes (most macrophages in adipose tissue have an M1 phenotype), as well as in the treatment of neurodegenerative diseases of the brain. In the latter case, the "classic" activation of macrophages occurs in the brain tissues, which leads to damage to neurons and the accumulation of toxic substances. The transformation of M1 aggressors into peaceful M2 and Mox janitors, destroying biological "garbage", may soon become the leading strategy for the treatment of these diseases (Walace, 2012).
Inflammation is inextricably linked with cancerous degeneration of cells: for example, there is every reason to believe that 90% of tumors in the human liver arise as a result of infectious and toxic hepatitis. Therefore, in order to prevent cancer, it is necessary to control the population of M1 macrophages.
However, not all so simple. Thus, in an already formed tumor, macrophages predominantly acquire signs of the M2 status, which promotes the survival, reproduction, and spread of the cancer cells themselves. Moreover, such macrophages begin to suppress the anti-cancer immune response of lymphocytes. Therefore, for the treatment of already formed tumors, another strategy is being developed based on stimulating the signs of classical M1 activation in macrophages (Solinas et al., 2009).
An example of this approach is the technology developed at the Novosibirsk Institute of Clinical Immunology of the Siberian Branch of the Russian Academy of Medical Sciences, in which macrophages obtained from the blood of cancer patients are cultivated in the presence of the stimulant zymosan, which accumulates in cells. The macrophages are then injected into the tumor, where zymosan is released and begins to stimulate the classical activation of "tumor" macrophages.
Today it is becoming more and more obvious that compounds that cause metamorphosis of macrophages have a pronounced atheroprotective, antidiabetic, neuroprotective effect, and also protect tissues in autoimmune diseases and rheumatoid arthritis. However, such drugs, which are currently in the arsenal of a practicing physician, are fibrates and thiazolidone derivatives, although they reduce mortality in these serious diseases, but at the same time they have pronounced severe side effects.
These circumstances stimulate chemists and pharmacologists to create safe and effective analogues. Abroad, in the USA, China, Switzerland and Israel, costly clinical trials of such compounds of synthetic and natural origin are already being carried out. Despite financial difficulties, Russian researchers, including those from Novosibirsk, are also making their own contribution to solving this problem.
Thus, a safe compound TS-13 was obtained at the Department of Chemistry of Novosibirsk State University, which stimulates the formation of Mox phagocytes, which has a pronounced anti-inflammatory effect and has a neuroprotective effect in an experimental model of Parkinson's disease (Dyubchenko et al., 2006; Zenkov et al., 2009) .
at the Novosibirsk Institute of Organic Chemistry. N. N. Vorozhtsov SB RAS created safe anti-diabetic and anti-atherosclerotic drugs that act on several factors at once, due to which the “aggressive” macrophage M1 turns into a “peaceful” M2 (Dikalov et al., 2011). Of great interest are herbal preparations obtained from grapes, blueberries, and other plants using the mechanochemical technology developed at the Institute of Solid State Chemistry and Mechanochemistry, Siberian Branch, Russian Academy of Sciences (Dushkin, 2010).
With the help of state financial support, it is possible in the very near future to create domestic means for pharmacological and genetic manipulations with macrophages, thanks to which there will be a real opportunity to turn these immune cells from aggressive enemies into friends that help the body maintain or restore health.
Literature
Dushkin M. I. Macrophage/foam cell as an attribute of inflammation: formation mechanisms and functional role // Biochemistry, 2012. V. 77. C. 419-432.
Smirnov A. N. Lipid signaling in the context of atherogenesis // Biochemistry. 2010. V. 75. S. 899-919.
Shvarts Ya. Sh., Svistelnik A. V. Functional phenotypes of macrophages and the concept of M1-M2 polarization. Part 1 Pro-inflammatory phenotype. // Biochemistry. 2012. V. 77. S. 312-329.
