Macrophages(from ancient Greek μακρός - large, and φάγος - eater (synonyms: histiocyte-macrophage, histophagocyte, macrophagocyte, megalophage-eater)), polyblasts, cells of mesenchymal nature in the animal body, capable of actively capturing and digesting bacteria, residues dead cells and other particles foreign or toxic to the body. The term “macrophages” was introduced by Mechnikov.

Macrophages include blood monocytes, connective tissue histiocytes, endothelial cells of the capillaries of the hematopoietic organs, Kupffer cells of the liver, cells of the wall of the lung alveoli (pulmonary macrophages) and the peritoneal wall (peritoneal macrophages).

It has been established that in mammals, macrophage precursors are formed in the bone marrow. The cells of the reticular tissue of the hematopoietic organs, which are combined with macrophages into the reticuloendothelial (macrophagic) system, which performs a protective function in the body, also have active phagocytic properties.

Morphology

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 of B and T lymphocytes, complement, other interleukins and histamine.

Tissue macrophages

In fact, a monocyte becomes a macrophage when it leaves the vascular bed and penetrates the tissue.

Depending on the type of tissue, the following types of macrophages are distinguished.

· Histiocytes - macrophages of connective tissue; component of the reticuloendothelial system.

· Kupffer cells - otherwise endothelial stellate cells of the liver.

· Alveolar macrophages - otherwise, dust cells; located in the alveoli.

· Epithelioid cells - components of granulomas.

· Osteoclasts are multinucleated cells involved in bone resorption.

· Microglia are cells of the central nervous system that destroy neurons and absorb infectious agents.

Macrophages of the spleen

Identification of macrophages

macrophages contain numerous cytoplasmic enzymes and can be identified in tissues by histochemical methods that detect these enzymes. Some enzymes, such as muramidase (lysozyme) and chymotrypsin, can be detected by a labeled antibody test (immunohistochemistry), which uses antibodies against the enzyme proteins. Such monoclonal antibodies against various CD antigens are widely used to identify macrophages.

Functions of macrophages

Macrophage functions include phagocytosis, antigen processing, and interaction with cytokines.

Phagocytosis

· Non-immune phagocytosis: macrophages are able to phagocytose foreign particles, microorganisms and the remains of damaged cells directly, without inducing an immune response. However, phagocytosis of microorganisms and their destruction are greatly facilitated by the presence of specific immunoglobulins, complement and lymphokines, which are produced by immunologically activated T lymphocytes.

· Immune phagocytosis: macrophages have surface receptors for the C3b and Fc fragment of immunoglobulins. Any particles that are coated with immunoglobulin or complement (opsonized) are phagocytosed much more easily than “naked” particles.

· “Processing” of antigens: macrophages “process” antigens and present them to B- and T-lymphocytes in the required form; This cellular interaction involves the simultaneous recognition by lymphocytes of MHC molecules and “processed antigens” found on the surface of macrophages.

· Interaction with cytokines: Macrophages interact with cytokines produced by T lymphocytes to protect the body against certain damaging agents. A typical result of such interaction is the formation of granulomas. Macrophages also produce cytokines, including interleukin-1, interferon-β, and T- and B-cell growth factors. Various interactions of lymphocytes and macrophages in tissues manifest themselves morphologically during chronic inflammation.

The role of macrophages is not limited to the secretion of IL-1. These cells synthesize a number of biologically active substances, each of which makes its own contribution to inflammation. These include: esterases, proteases and antiproteases; lysosomal hydrolases - collagenase, alastase, lysozyme, α-macroglobulin; monokines - IL-1, colony-stimulating factor, fibroblast growth-stimulating factor; anti-infective agents - interferon, transferrin, transcobalamin; complement components: C1, C2, C3, C4, C5, C6; Arachidonic acid derivatives: prostaglandin E2, thromboxane A2, leukotrienes.

Macrophages is a heterogeneous specialized cell population of the body's defense system. There are two groups of macrophages - free and fixed. Free macrophages include macrophages of loose connective tissue, or histiocytes; macrophages of serous cavities; macrophages of inflammatory exudates; alveolar macrophages of the lungs. Macrophages are able to move throughout the body. The group of fixed macrophages consists of macrophages of bone marrow and bone tissue, spleen, lymph nodes, intraepidermal macrophages, macrophages of placental villi, and the central nervous system.

The size and shape of macrophages vary depending on their functional state. Typically macrophages have one nucleus. Macrophage nuclei are small, round, bean-shaped or irregular in shape. They contain large clumps of chromatin. The cytoplasm is basophilic, rich in lysosomes, phagosomes and pinocytotic vesicles, contains a moderate amount of mitochondria, granular endoplasmic reticulum, Golgi apparatus, inclusions of glycogen, lipids, etc.

Forms of manifestation of the protective function of macrophages: 1) absorption and further breakdown or isolation of foreign material; 2) neutralizing it upon direct contact; 3) transfer of information about foreign material to immunocompetent cells capable of neutralizing it; 4) providing a stimulating effect on another cell population of the body’s defense system.

The number of macrophages and their activity especially increase during inflammatory processes. Macrophages produce factors that activate the production of immunoglobulins by B lymphocytes and the differentiation of T and B lymphocytes; cytolytic antitumor factors, as well as growth factors that influence the reproduction and differentiation of cells of their own population, stimulate the function of fibroblasts. Macrophages are formed from HSCs, as well as from promonocytes and monocytes. Complete renewal of macrophages and loose fibrous connective tissue in experimental animals occurs approximately 10 times faster than fibroblasts. One type of macrophage is multinucleated giant cells, which were previously called “foreign body giant cells”, as they can form, in particular, in the presence of a foreign body. Multinucleated giant cells are symplasts containing 10-20 nuclei or more, arising either by endomitosis without cytotomy. Multinucleated giant cells contain a developed synthetic and secretory apparatus and an abundance of lysosomes. The cytolemma forms numerous folds.

Concept of the macrophage system. This system includes the totality of all cells that have the ability to capture foreign particles, dying cells, non-cellular structures, bacteria, etc. from the tissue fluid of the body. Phagocytosed material undergoes enzymatic cleavage inside the cell, due to which agents harmful to the body that arise locally or penetrate from the outside are eliminated. I.I. Mechnikov was the first to come to the idea that phagocytosis, which arises in evolution as a form of intracellular digestion and is assigned to many cells, is at the same time an important protective mechanism. He substantiated the feasibility of combining them into one system and proposed calling it macrophage. The macrophage system is a powerful protective apparatus that takes part in both general and local protective reactions of the body. In the whole organism, the macrophage system is regulated both by local mechanisms and by the nervous and endocrine systems.

4. Dense connective tissue. Classification, structural features and differences from loose tissue. Tendon structure. A common feature for PVST is the predominance of the intercellular substance over the cellular component, and in the intercellular substance the fibers predominate over the main amorphous substance and are located very close to each other (densely) - all these structural features are reflected in a compressed form in the name of this tissue. PVST cells are represented overwhelmingly by fibroblasts and fibrocytes; macrophages, mast cells, plasmacytes, poorly differentiated cells, etc. are found in small numbers (mainly in layers of PVST).
Dense fibrous connective tissues are characterized by a relatively large number of densely arranged fibers and a small amount of cellular elements and basic amorphous substance between them. Depending on the location of the fibrous structures, this tissue is divided into dense unformed and dense formed connective tissue. Dense, unformed connective tissue is characterized by a disordered arrangement of fibers. In dense, structured fibrous connective tissue, the arrangement of fibers is strictly ordered and in each case corresponds to the conditions in which the organ functions. Formed fibrous connective tissue is found in tendons and ligaments, in fibrous membranes. Tendon. It consists of thick, densely lying parallel bundles collagen fibers. Between these bundles are located fibrocytes and a small amount of fibroblasts and ground amorphous material. Thin lamellar processes of fibrocytes enter the spaces between the fiber bundles and are in close contact with them. Fibrocytes of tendon bundles are called tendon cells.

Each bundle of collagen fibers, separated from the adjacent layer of fibrocytes, is called first order beam. Several bundles of the first order, surrounded by thin layers of loose fibrous connective tissue, make up second order beams. Layers of loose fibrous connective tissue separating second-order bundles are called endotenonium. From beams of the second order they are composed third order beams, separated by thicker layers of loose connective tissue - peritenonium. Large tendons may also have fourth-order bundles.

The peritenonium and endotenonium contain blood vessels that supply tendons, nerves, and proprioceptive nerve endings. Dense, shaped fibrous connective tissue also includes nuchal ligament.

Fibrous membranes. This type of dense fibrous connective tissue includes fascia, aponeuroses, tendon centers of the diaphragm, capsules of some organs, dura mater, sclera, perichondrium, periosteum, as well as the tunica albuginea of ​​the ovary and testicle, etc. Fibrous membranes are difficult to stretch. In addition to bundles of collagen fibers, fibrous membranes contain elastic fibers. Fibrous structures such as periosteum, sclera, tunica albuginea, joint casulas, etc.

5.Cartilage tissue. General morpho-functional characteristics. Classification. Development and structural features of various cartilaginous tissues. Perichondrium. Growth of cartilage, regeneration capabilities and age-related changes in cartilage tissue.

Cartilage tissue is part of the organs of the respiratory system, joints, intervertebral discs, and consists of cells – chondrocytes and chondroblasts and intercellular substance.Classification: There are three types of cartilage tissue: hyaline, elastic, fibrous.

During the development of cartilage tissue from mesenchyme a cartilaginous differential is formed:
1. Stem cell
2. Semi-stem cell
3. Chondroblast
4. Chondrocyte
Stem and semi-stem cells are poorly differentiated cambial cells, mainly localized around the vessels in the perichondrium. By differentiating they turn into chondroblasts and chondrocytes, i.e. necessary for regeneration.
Chondroblasts are young cells located in the deep layers of the perichondrium singly, without forming isogenic groups. Under a light microscope, blasts are flattened, slightly elongated cells with basophilic cytoplasm. Under an electron microscope, the granular ER, Golgi complex, and mitochondria are well expressed in them, i.e. protein-synthesizing complex of organelles because The main function of x/blasts is the production of the organic part of the intercellular substance: proteins collagen and elastin, glycosaminoglycans (GAG) and proteoglycans (PG). In addition, ch/blasts are capable of reproduction and subsequently turn into chondrocytes. In general, x/blasts provide appositional (superficial) growth of cartilage from the side of the perichondrium.
Chondrocytes are the main cells of cartilage tissue, located in the deeper layers of cartilage in cavities - lacunae. Cells can divide by mitosis, while the daughter cells do not separate, but remain together - so-called isogenic groups are formed. Initially, they lie in one common lacuna, then an intercellular substance is formed between them and each cell of a given isogenic group has its own capsule. X/cytes are oval-round cells with basophilic cytoplasm. Under an electron microscope, the granular ER, Golgi complex, and mitochondria are well defined, i.e. protein synthesizing apparatus, because The main function of cartilage tissue is the production of the organic part of the intercellular substance of cartilage tissue. The growth of cartilage due to the division of cells and their production of intercellular substance is ensured by interstitial (internal) growth of cartilage.
The intercellular substance of cartilage tissue contains collagen, elastic fibers and ground substance. The intercellular substance is highly hydrophilic, the water content reaches 75% of the mass of the cartilage, this determines the high density and turgor of the cartilage. Cartilaginous tissues in the deep layers do not have blood vessels; nutrition is diffuse through the vessels of the perichondrium.

The source of development of cartilage tissue is mesenchyme. In the first stage, in some parts of the body of the embryo, where cartilage is formed, mesenchymal cells lose their processes, multiply vigorously and, tightly adjacent to each other, create a certain tension - turgor. Such areas called chondrogenic primordia, or chondrogenic islets. The stem cells contained in them differentiate into chondroblasts, cells similar to fibroblasts. In the next stage, the formation of primary cartilaginous tissue, the cells of the central region round, increase in size, granular EPS develops in their cytoplasm, with the participation of which the synthesis and secretion of fibrillar proteins occurs. Along the periphery of the cartilaginous anlage, at the border with the mesenchyme, perichondrium
The perichondrium is a layer of connective tissue covering the surface of the cartilage. In the perichondrium, there is an outer fibrous layer (from a dense, unformed SDT with a large number of blood vessels) and an inner cellular layer containing a large number of stem, semi-stem cells and f/blasts. In the process of secreting synthesis products and layering onto existing cartilage along its periphery, the cells themselves are “embedded” in the products of their activity. This is how cartilage grows by applying.
The difference between the 3 types of cartilage. The differences mainly concern the structure of the intercellular substance:
Hyaline cartilage –

Covers all articular surfaces of bones, is contained in the sternal ends of the ribs, in the airways. The main difference between hyaline cartilage and other cartilages is in the structure of the intercellular substance: the intercellular substance of hyaline cartilage in preparations stained with hematoxylin-eosin appears homogeneous and does not contain fibers. In fact, in the intercellular substance there is a large number of collagen fibers, whose refractive index is the same as the refractive index of the main substance, so collagen fibers are not visible under a microscope, i.e. they are camouflaged. The second difference of hyaline cartilage is that there is a clearly defined basophilic zone around the isogenic groups - the so-called territorial matrix. This is due to the fact that x/cytes secrete a large amount of GAG with an acidic reaction, so this area is stained with basic dyes, i.e. basophilic. The weakly oxygenic areas between the territorial matrices are called the interterritorial matrix.
Elastic cartilage

present in the auricle, epiglottis, corniculate and sphenoid cartilages of the larynx. The main difference between elastic cartilage is the intercellular substance except collagen fibers there are a large number of randomly located elastic fibers, which gives elasticity to the cartilage. Elastic cartilage contains less lipids, chondroethinsulfates and glycogen. Elastic cartilage does not calcify.
Fibrous cartilage

located at the attachment points tendons to bones and cartilage, in the symphysis and intervertebral discs. In structure it occupies an intermediate position between densely formed connective and cartilaginous tissue. Difference from other cartilages: in the intercellular substance there are much more collagen fibers, and the fibers are oriented - they form thick bundles, clearly visible under a microscope. X/cytes often lie singly along the fibers, without forming isogenic groups.

Age-related changes.As the body ages, the concentration of proteoglycans and the associated hydrophilicity in cartilage tissue decrease. The processes of reproduction of chondroblasts and young chondrocytes are weakened. After the death of chondrocytes, some of the gaps are filled with an amorphous substance and collagen fibrils. In places, deposits of calcium salts are found in the intercellular substance, as a result of which the cartilage becomes cloudy, opaque, and becomes hard and brittle. Regeneration. Physiological regeneration of cartilage tissue is carried out due to unspecialized cells of the perichondrium and cartilage through reproduction and differentiation prechondroblasts and chondroblasts.Post-traumatic regeneration of cartilage tissue of extra-articular localization is carried out due to the perichondrium.

Good afternoon, dear readers!
Last time I told you about a very important group of blood cells - which are the real fighters of the front line of immune defense. But they are not the only participants in operations to capture and destroy “enemy agents” in our body. They have assistants. And today I want to continue my story and study functions leukocytes - agranulocytes. This group also includes lymphocytes, the cytoplasm of which lacks granularity.
Monocyte is the largest representative of leukocytes. The diameter of its cell 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 blood, their paths diverge. Neutrophils travel through blood vessels and are always in readiness No. 1. And monocytes quickly spread throughout the organs and there turn into macrophages. Half of them go to the liver, and the rest are distributed to the spleen, intestines, lungs, etc.

Macrophages– these are sedentary, finally matured. 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 visible 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 may ask: what active substances do macrophages secrete? 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 tissue renewal - osteoclasts and osteoblasts. Osteoclasts constantly circulate through bone tissue, finding old cells and destroying them, leaving behind free space for future bone marrow, and osteoblasts form new tissue. Macrophages perform this work by synthesizing and secreting special stimulating proteins, enzymes and hormones. For example, to destroy bone they synthesize collagenase and phosphatase, and to grow red blood cells - erythropoietin.
There are also “nurse” cells and “nurse” cells that ensure rapid reproduction and normal maturation of blood cells in the bone marrow. Hematopoiesis in the bones occurs in islands - in the middle of such a colony there is a macrophage, and red cells of different ages are crowded around. Performing the function of a nursing mother, the 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 participate 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 gluttony 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 dangerous to human health and life.

But it is difficult for macrophages to separate what is good and what is bad, so our task is to ease the fate of macrophages and take care of our own health and the health of the liver: monitor nutrition, reduce the consumption of foods containing large amounts of fat and cholesterol, and remove toxins twice a year toxins.

Now let's talk about macrophages, working in the lungs.

The inhaled air and blood in the pulmonary vessels are separated by a thin border. You understand how important it is to ensure sterility of the airways under these conditions! 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 remains of dead lung cells and microbes inhaled from the surrounding air. Macrophages of the lungs multiply immediately in the area of ​​their activity, and their number increases sharply in chronic diseases of the respiratory tract.

Attention smokers! Dust particles and tarry substances from tobacco smoke greatly irritate the upper respiratory tract paths, damage the mucous cells of the bronchi and alveoli. Pulmonary macrophages, of course, capture and neutralize these harmful chemicals. In smokers, the activity, number and even size of macrophages sharply increases. But after 15–20 years, the limit of their reliability is exhausted. 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. Thus, long-term smoking leads to chronic bronchitis and a decrease in the respiratory surface of the lungs. Overly active macrophages corrode the elastic fibers of the lung tissue, which leads to difficulty breathing and hypoxia.

The saddest thing is that when they are worn out, macrophages cease to perform very important functions - 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 perform the function of “killers”, destroying aging red blood cells. On the membranes of red blood cells, treacherous proteins are exposed, which are a signal for elimination. By the way, the destruction of old red blood cells occurs both in the liver and in the bone marrow itself - wherever there are macrophages. In the spleen this process is most obvious.

Thus, macrophages are great workers and the most important orderlies of our body, performing several key roles at once:

1. participation in phagocytosis,
2. preservation and processing of important nutrients for the body's needs,
3. release of several dozen proteins and other biologically active substances that regulate 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. We will talk about them, the smallest defenders of our body, next time.
In the meantime, let's get healthier and strengthen our immune system by listening to the healing music of Mozart - Symphony of the Heart:

I wish you good health and prosperity!

Mechnikov included granular polymorphonuclear blood leukocytes as microphages, which, emigrating from blood vessels, exhibit energetic phagocytosis mainly in relation to bacteria, and to a much lesser extent (as opposed to macrophages) to various products of tissue decay.

The phagocytic activity of microphages is especially evident in pus containing bacteria.

Microphages also differ from macrophages in that they do not perceive vital color.

Macrophages contain enzymes to digest phagocytosed substances. These enzymes are contained in vacuoles (vesicles) called lysosomes and are capable of breaking 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 breakdown of cells or produced by bacteria. In addition, macrophages secrete into the blood some humoral and secretory substances: complement elements C2, C3, C4, lysozyme, interferon, interleukin-1, prostaglandins, o^-macroglobulin, monokines that regulate the immune response, cytoxins - toxic to cell substance.

Macrophages have a subtle mechanism for recognizing foreign particles of an antigenic nature. They distinguish between and quickly absorb old and new red blood cells without affecting normal red blood cells. For a long time, macrophages have been assigned the role of “cleaners,” 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 the lysosomes that dissolve the antigen within approximately 30 minutes, after which it is excreted from the body.

The antigen is manifested and recognized by the macrophage, after which it passes to the 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, i.e., they become anaerobes, and can carry out their activities in oxygen-free zones, for example, in exudates during inflammation, complementing the activity of macrophages. Macrophages and microphages on their surface carry receptors for the immunoglobulin JgJ and the complement element C3, which help the phagocyte in recognizing and attaching the antigen to the surface of its cell. Disruption of phagocyte activity quite often manifests itself in the form of recurring purulent-septic diseases, such as chronic pneumonia, pyoderma, osteomyelitis, etc.

In a number of infections, various acquisitions of phagocytosis occur. Thus, tuberculous mycobacteria are not destroyed during phagocytosis. Staphylococcus inhibits its absorption by the phagocyte. Disturbance in 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 phagocytosed substances cannot be removed from the body due to the deficiency of certain phagocyte enzymes. The pathology of phagocytosis may be associated with a violation of the 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 hypothesis was formulated, according to which macrophages represent the final stage of 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 the tissues of adult mice are represented by two populations that differ in their origin, mechanism of maintaining numbers and functions. The first population is tissue, or resident macrophages. They originate from erythromyeloid precursors (not related to blood stem cells) of the yolk sac and embryonic liver and populate tissues at various stages of embryogenesis. Resident macrophages acquire tissue-specific characteristics and maintain their numbers through proliferation in situ without any participation of monocytes. Long-lived tissue macrophages include liver Kupffer cells, 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 monocyte (bone marrow) origin. The relative content of such cells in a tissue depends on its type and 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 organism) and most of the macrophages of the lamina propria of the intestinal mucosa. The number of macrophages of monocyte origin increases sharply during inflammation and returns to normal 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 cellular phenotype specific to each type of stimulus. Historically, the first to be discovered were two largely opposite types of activated macrophages, which, by analogy with Th1/Th2, were called M1 and M2. M1 macrophages differentiate ex vivo upon stimulation of precursors with interferon γ with the participation of the transcription factor STAT1. M2 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, information had accumulated indicating the existence of a whole spectrum of activated states of macrophages that do not correspond to either type M1 or type M2. At present, there is no convincing evidence that the activated states of macrophages observed in vitro correspond to what occurs in vivo, and whether these states are permanent or transient.

Tumor associated macrophages

Malignant tumors influence 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, 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 intracellularly destroy various microbes and damaged structures.

Microphages (granulocytes: neutrophils, eosinophils, basophils, platelets, endothelial cells, microglial cells, etc.) to a lesser extent, but are also capable of capturing and damaging microbes.

In phagocytes, during all stages of microbial phagocytosis, both oxygen-dependent and oxygen-independent microbicidal systems are activated.

The main components of the oxygen-dependent microbicidal system of phagocytes are myeloperoxidase, catalase and reactive oxygen species (singlet oxygen - O2, superoxide radical - O2, hydroxyl radical - OH, hydrogen peroxide - H2O2).

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 peptidoglycans in the walls of gram-positive bacteria, causes 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 distinct nonspecific antiviral activity;

The activity of both microvilli and glandular cells of the mucous membrane of the airways, as well as the sweat and sebaceous glands of the skin, which secrete corresponding secretions (sputum, sweat and sebum), helps remove a certain number of various microorganisms from the body.

Phagocytosis, the process of active capture and absorption of living and nonliving particles by unicellular organisms or special cells (phagocytes) of multicellular animal organisms. The phenomenon of 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 transferred to individual specialized cells, first digestive, and then to special connective tissue cells. In humans and mammals, active phagocytes are neutrophils (microphages, or special leukocytes) of the blood and cells of the reticuloendothelial system, capable of turning into active macrophages. Neutrophils phagocytose small particles (bacteria, etc.), macrophages are able to absorb larger particles (dead cells, their nuclei or fragments, etc.). Macrophages are also capable of accumulating 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 - a phagosome. From the surrounding lysosomes, hydrolytic enzymes enter the phagosome and digest 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 German scientists P. Ehrlich and J. Morgenroth. K. consists of 9 components, which are designated from C "1 to C" 9, with the first component including three subunits. All 11 proteins that make up K. can be separated by immunochemical and physicochemical methods. K. is easily destroyed when the whey is heated, stored for a long time, or exposed to light. K. takes part in a number of immunological reactions: by joining the complex of an antigen (See Antigens) with an antibody (See Antibodies) on the surface of the cell membrane, it causes the lysis of bacteria, erythrocytes, and other cells treated with appropriate antibodies. The destruction of the membrane and subsequent cell lysis requires the participation of all 9 components. Some components of antigens 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 action of K. is associated with the body's resistance to pathogenic microbes, the release of Histamine in immediate allergic reactions, and autoimmune processes. In medicine, canned K. preparations are used in the serological diagnosis of a number of infectious diseases and for the detection of antigens and antibodies.

INTERFERONS are a group of low molecular weight glycoproteins produced by human or animal cells in response to a viral infection or under the influence 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 musculocutaneous, connective and lymphoid tissue:

gamma immune - produced by T lymphocytes in cooperation with macrophages, natural killers.

The antiviral effect does not occur directly through 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 onset of translation of foreign genetic information and destroy messenger RNA molecules. By interacting with cells of the immune system, they stimulate phagocytosis, natural killer cell activity, and 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 causing an immune response are called antigens. They are divided into differentiated and deterministic. Differentiated antigens include CD antigens. The major histocompatibility complex includes HLA (hyman lencocyte antigen).

Antigens are divided into:

Toxins;

Isoantigens;

Heterophilic antigens;

Household antigens;

Dumbbells;

Immunogens;

Adjuvants;

Hidden antigens.

Toxins are waste products of bacteria. Toxins can be chemically converted into toxoids, which then lose their toxic properties, but retain their antigenic properties. 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).

Antibodies to A- and B-isoantigens determine 4 blood groups.

Heterophilic antigens are present in the tissue cells of many animals; they are absent in human blood.

Household antigens include self-antigens, most of which are tolerant to the immune system.

Gantenas are substances that specifically react with antibodies, but do not contribute to their formation. Gantenas are formed due to allergic reactions to medications.

Immunogens (viruses and bacteria) are more powerful than soluble antigens.

Adjuvants are substances that enhance the immune response when an antigen is introduced.

The hidden antigen may be sperm, which in some cases acts as a foreign protein in cases of traumatic damage to the testicles or changes caused by mumps.

Antigens are also divided into:

Antigens, which are components of cells;

External antigens that are not components of cells;

Autoantigens (hidden) that do not penetrate immunocompetent cells.

Antigens are also classified according to other criteria:

By type of inducing an immune response - immunogens, allergens, tolerogens, transplantation);

By foreignness - 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, typical, variant, group, stage.

The body's interaction with antigens can occur in different ways. The antigen can penetrate into the macrophage and be eliminated within it.

With another option, it is possible to connect with receptors on the surface of the macrophage. The antigen is able to react with the antibody on the macrophage process 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 occur in different ways:

With the formation of humoral antibodies (during the transformation of an 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 turn into a non-responsive cell if all its receptors are associated with 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, that is, it is almost the same in 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 formed. The state of nonspecific immunity determines a person’s predisposition to various common infections, the causative agents of which are opportunistic microbes. Immunity can be specific or congenital (for example, a person to the causative agent of canine distemper) and acquired.

Natural passive immunity. AT 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 they provide protection until their own immunity is formed.

Natural active immunity. Production of own antibodies upon contact with antigen. Immunological memory cells provide the most durable, sometimes lifelong, immunity.

Acquired passive immunity. It is created artificially by introducing ready-made antibodies (serum) from immune organisms (serum against diphtheria, tetanus, snake venoms). This type of immunity also does not last long.

Acquired active immunity. A small amount of antigens is introduced into the body in the form of a vaccine. This process is called vaccination. A killed or weakened antigen is used. The body does not get sick, but produces AT. Repeated administration is frequent and stimulates faster and longer-lasting production of antibodies that provide long-lasting protection.

Specificity of antibodies. Each antibody is specific for a specific 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 an antigen comes into contact with an antibody, the numerous prosthetic groups of the antigen correspond as a mirror image to the same groups of the antibody, due to which rapid and tight binding occurs between the antibody and the antigen. If the antibody is highly specific and there are many binding sites, strong adhesion occurs between the antibody and antigen through: (1) hydrophobic bonds; (2) hydrogen bonds; (3) ionic attraction; (4) van der Waal 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 distinct tissue, scattered throughout the body in the form of various lymphoid formations. Lymphoid tissue includes the thymus, or thymus, 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 skeleton of the tissue, and lymphocytes located between these cells. The main functional cells of the immune system are lymphocytes, divided 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, through a complex of cellular and humoral reactions carried out using a set of immunoreagents, neutralizing, neutralizing, removing, destroying a genetically foreign antigen that has entered the body from the outside or formed in the body itself.

The specific function of the immune system in neutralizing antigens is complemented by a complex of mechanisms and reactions of a nonspecific 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:

serodiagnosis 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 companies. Based on the results of serodiagnostic reactions, the dynamics of antibody accumulation during the disease process and the intensity of post-infectious or post-vaccination immunity are judged.

Seroidentification of microbial cultures is carried out to determine their type and serovar using sets of specific antisera, also produced by commercial companies.

Each serological reaction is characterized by specificity and sensitivity. Specificity refers to the ability of antigens or antibodies to react only with homologous antibodies contained in blood serum or with homologous antigens, respectively. The higher the specificity, the fewer false positive and false negative results.

Serological reactions involve antibodies belonging mainly to immunoglobulins of the IgG and IgM classes.

The agglutination reaction is the process of gluing 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.

№ 1 immunity. Types of immunity.

Immunity is a way of protecting the body from genetically foreign substances - antigens, aimed at maintaining and preserving homeostasis, the structural and functional integrity of the body.

1. Innate immunity is a genetically fixed, inherited immunity of a given species and its individuals to any antigen, developed in the process of phylogenesis, determined by the biological characteristics of the organism itself, the properties of this antigen, as well as the characteristics of their interaction. (example: plague cattle)

innate immunity can be absolute and relative. For example, frogs that are not sensitive to tetanus toxin may respond to its administration by raising their body temperature.

Species-specific immunity can be explained from different positions, primarily by the absence of a particular species of receptor apparatus that provides the first stage of interaction of a given antigen with cells or target molecules that determine the initiation of a pathological process or activation of the immune system. The possibility of rapid destruction of the antigen, for example, by body enzymes, or the absence of conditions for the engraftment and reproduction of microbes (bacteria, viruses) in the body, cannot be excluded. Ultimately, this is due to the genetic characteristics of the species, in particular the absence of immune response genes to this antigen.

2. Acquired immunity is immunity to an antigen of a sensitive human body, animals, etc., acquired in the process of ontogenesis as a result of a natural encounter with this antigen of the body, for example, during vaccination.

An example of natural acquired immunity a person may have immunity to infection that occurs after an illness, the so-called post-infectious

Acquired immunity can be active or passive. Active immunity is due to an active reaction, active involvement of the immune system in the process when it encounters a given antigen (for example, post-vaccination, post-infectious immunity), and passive immunity is formed by introducing ready-made immunoreagents into the body that can provide protection against the antigen. Such immunoreagents include antibodies, i.e. specific immunoglobulins and immune sera, as well as immune lymphocytes. Immunoglobulins are widely used for passive immunization.

distinguish between cellular, humoral, cellular-humoral and humoral-cellular immunity.

An example of cellular immunity can serve as antitumor, as well as transplantation immunity, when the leading role in immunity is played by cytotoxic killer T-lymphocytes; immunity during infections (tetanus, botulism, diphtheria) is mainly due to antibodies; in tuberculosis, the leading role is played by immunocompetent cells (lymphocytes, phagocytes) with the participation of specific antibodies; in some viral infections (smallpox, measles, etc.), specific antibodies, as well as cells of the immune system, play a role in protection.

In infectious and non-infectious pathology and immunology, to clarify the nature of immunity depending on the nature and properties of the antigen, the following terminology is also used: antitoxic, antiviral, antifungal, antibacterial, antiprotozoal, transplantation, antitumor and other types of immunity.

Finally, the immune state, i.e. active immunity, can be maintained or maintained either in the absence or only in the presence of an antigen in the body. In the first case, the antigen plays the role of a triggering factor, and immunity is called sterile. In the second case, immunity is interpreted as non-sterile. An example of sterile immunity is post-vaccination immunity with the introduction of killed vaccines, and non-sterile immunity is immunity in tuberculosis, which persists only in the presence of Mycobacterium tuberculosis in the body.

Immunity (resistance to antigen) can be systemic, i.e. generalized, and local, in which there is a more pronounced resistance of individual organs and tissues, for example, the mucous membranes of the upper respiratory tract (therefore it is sometimes called mucosal).

№2 Antigens..

Antigens are foreign substances or structures that are capable of causing an immune response.

Antigen characteristics:

Immunogenicity- This is the property of an antigen to cause an immune response.

Antigen specificity- this is the ability of an antigen to selectively react with antibodies or sensitized lymphocytes that appear as a result of immunization. Certain parts of its molecule, called determinants (or epitopes), are responsible for the specificity of an antigen. The specificity of an antigen is determined by a set of determinants.

CLASSIFICATION OF ANTIGENS:

Name	Antigens
Corpuscular antigens	Various cells and large particles: bacteria, fungi, protozoa, red blood cells
Soluble antigens	Proteins of varying degrees of complexity, polysaccharides
Transplant antigens	Cell surface antigens controlled by MHC
Xenoantigens (heterologous)	Antigens of tissues and cells that differ from the recipient at the species level (donor and recipient of different species)
Alloantigens (homologous)	Antigens of tissues and cells that differ from the recipient at the intraspecific level (donor and recipient belong to genetically non-identical individuals of the same species)
Syngeneic	The donor and recipient belong to the same inbred line of animals
Isogenic (isologous)	Genetic identity of individuals (eg identical twins)
Autoantigens	Antigens of the body's own cells
Allergens	Antigens of food, dust, plant pollen, insect poisons, causing increased reactivity
Tolerogens	Antigens of cells, proteins that cause unresponsiveness
Synthetic antigens	Artificially synthesized polymers of amino acids, carbohydrates
	Simple chemical compounds mainly of the aromatic series
Thymus - dependent	The full development of a specific immune response to these antigens begins only after the connection of T cells
Thymus - independent	Polysaccharides with repeating structurally identical epitopes stimulate B cells; capable of initiating an immune response in the absence of T helper cells

The main types of bacterial antigens are:

Somatic or O-antigens (in gram-negative bacteria, specificity is determined by deoxysugars of LPS polysaccharides);

Flagellar or H-antigens (protein);

Surface or capsular K antigens.

№3 Antibodies (immunoglobulins.)

Antibodies are serum proteins produced in response to an antigen. They belong to serum globulins and are therefore called immunoglobulins (Ig). Through them, the humoral type of immune response is realized. Antibodies have 2 properties: specificity, i.e. the ability to interact with an antigen similar to the one that induced (caused) their formation; heterogeneity in physical and chemical structure, specificity, genetic determination of formation (by origin). All immunoglobulins are immune, that is, they are formed as a result of immunization and contact with antigens. Nevertheless, based on their origin, they are divided into: normal (anamnestic) antibodies, which are found in any body as a result of household immunization; infectious antibodies that accumulate in the body during an infectious disease; post-infectious antibodies, which are found in the body after an infectious disease; post-vaccination antibodies that arise after artificial immunization.

№4 nonspecific protective factors and their characteristics

1) humoral factors - complement system. Complement is a complex of 26 proteins in the blood serum. Each protein is designated as a fraction in Latin letters: C4, C2, C3, etc. Under normal conditions, the complement system is in an inactive state. When antigens enter, it is activated; the stimulating factor is the antigen-antibody complex. Any infectious inflammation begins with the activation of complement. The complement protein complex is integrated into the cell membrane of the microbe, which leads to cell lysis. Complement is also involved in anaphylaxis and phagocytosis, as it has chemotactic activity. Thus, complement is a component of many immunolytic reactions aimed at freeing the body from microbes and other foreign agents;

2) cellular protection factors.

Phagocytes. Phagocytosis (from the Greek phagos - devour, cytos - cell) was first discovered by I. I. Mechnikov, for this discovery in 1908 he received the Nobel Prize. The mechanism of phagocytosis consists of the absorption, digestion, and inactivation of substances foreign to the body by special phagocyte cells. Mechnikov classified macrophages and microphages as phagocytes. Currently, all phagocytes are united into a single phagocytic system. It includes: promonocytes - produced by bone marrow; macrophages - scattered throughout the body: in the liver they are called “Kupffer cells”, in the lungs - “alveolar macrophages”, in bone tissue - “osteoblasts”, etc. The functions of phagocyte cells are very diverse: they remove dying cells from the body, absorb and inactivate microbes, viruses, fungi; synthesize biologically active substances (lysozyme, complement, interferon); participate in the regulation of the immune system.

The process of phagocytosis, i.e. the absorption of a foreign substance by phagocyte cells, occurs in 4 stages:

1) activation of the phagocyte and its approach to the object (chemotaxis);

2) adhesion stage - adherence of the phagocyte to the object;

3) absorption of an object with the formation of a phagosome;

4) formation of a phagolysosome and digestion of the object using enzymes.

№5 Organs, tissues and cells of the immune system

There are central and peripheral organs of the immune system, in which cells of the immune system develop, mature and differentiate.

The central organs of the immune system are the bone marrow and thymus. In them, from hematopoietic stem cells, lymphocytes differentiate into mature non-immune lymphocytes, the so-called naive lymphocytes (from the English naive), or virgin (from the English virgine).

Hematopoietic bone marrow is the birthplace of all cells of the immune system and the maturation of B lymphocytes (B lymphopoiesis).

The thymus (thymus gland) is responsible for the development of T-lymphocytes: T-lymphopoiesis (rearrangement, i.e. rearrangement of TcR genes, receptor expression, etc.). In the thymus, T-lymphocytes (CD4 and CD8) are selected and cells that are highly avid to self-antigens are destroyed. Thymic hormones complete the functional maturation of T-lymphocytes and increase their secretion of cytokines. The ancestor of all cells of the immune system is the hematopoietic stem cell. From lymphoid stem cells, precursors of T and B cells are formed, which serve as a source of T and B lymphocyte populations. T lymphocytes develop in the thymus under the influence of its humoral mediators (thymosin, thymopoectin, timorin, etc.). Subsequently, thymus-dependent lymphocytes settle in peripheral lymphoid organs and transform. T 1 - cells are localized in the periarterial zones of the spleen, react weakly to the action of radiant energy and are precursors of effectors of cellular immunity, T 2 - cells accumulate in the pericortical zones of the lymph nodes, are highly radiosensitive and are distinguished by antigen reactivity.

Peripheral lymphoid organs and tissues (lymph nodes, lymphoid structures of the pharyngeal ring, lymphatic ducts and spleen) are the territory of interaction of mature non-immune lymphocytes with antigen-presenting cells (APC) and subsequent antigen-dependent differentiation (immunogenesis) of lymphocytes. This group includes: skin-associated lymphoid tissue); lymphoid tissue associated with the mucous membranes of the gastrointestinal, respiratory and genitourinary tracts (solitary follicles, tonsils, Peyer's patches, etc.). Peyer's patches (group lymphatic follicles) are lymphoid formations of the wall of the small intestine. Antigens penetrate from the intestinal lumen into Peyer's patches through epithelial cells (M cells).

№6 T cells of the immune system, their characteristics

T-lymphocytes participate in cellular immunity reactions: delayed-type allergic reactions, transplant rejection reactions and others, and provide antitumor immunity. The T-lymphocyte population is divided into two subpopulations: CD4 lymphocytes - T-helpers and CD8 lymphocytes - cytotoxic T-lymphocytes and T-suppressors. In addition, there are 2 types of T helper cells: Th1 and Th2

T lymphocytes. Characteristics of T-lymphocytes. Types of molecules on the surface of T lymphocytes. The decisive event in the development of T lymphocytes, the formation of the antigen recognition T cell receptor, occurs only in the thymus. To ensure the possibility of recognizing any antigen, millions of antigen recognition receptors with different specificities are needed. The formation of a huge variety of antigen recognition receptors is possible due to gene rearrangement during the proliferation and differentiation of progenitor cells. As T-lymphocytes mature, antigen-recognition receptors and other molecules appear on their surface, mediating their interaction with antigen-presenting cells. Thus, CD4 or CD8 molecules participate in the recognition of self-molecules of the major histocompatibility complex, along with the T-cell receptor. Intercellular contacts are provided by sets of surface adhesion molecules, each of which corresponds to a ligand molecule on the surface of another cell. As a rule, the interaction of a T lymphocyte with an antigen-presenting cell is not limited to recognition of the antigen complex by the T-cell receptor, but is accompanied by the binding of other pairwise complementary surface “costimulatory” molecules. Table 8.2. Types of molecules on the surface of T-lymphocytes Molecules Functions Antigen recognition receptor: T-cell receptor Recognition and binding of the complex: antigenic peptide + own molecule of the major histocompatibility complex Coreceptors: CD4, CD8 Participate in the binding of the molecule of the major histocompatibility complex Adhesion molecules Adhesion of lymphocytes to endothelial cells, to antigen-presenting cells, to elements of the extracellular matrix Costimulatory molecules Participate in the activation of T-lymphocytes after interaction with an antigen Immunoglobulin receptors Bind immune complexes Cytokine receptors Bind cytokines A combination of surface molecules of lymphocytes, which are usually designated by serial numbers of “clusters of differentiation” (CD), is referred to as the “cell surface phenotype,” and individual surface molecules are called “markers” because they serve as markers of specific subpopulations and stages of T lymphocyte differentiation. For example, at the later stages of differentiation, some T lymphocytes lose the CD8 molecule and retain only CD4, while others lose CD4 and retain CD8. Therefore, among mature T-lymphocytes, CD4+ (T-helper cells) and CD8+ (cytotoxic T-lymphocytes) are distinguished. Among T-lymphocytes circulating in the blood, there are approximately twice as many cells with the CD4 marker as there are cells with the CD8 marker. Mature T lymphocytes carry receptors for various cytokines and receptors for immunoglobulins on their surface (Table 8.2). When a T cell receptor recognizes an antigen, T lymphocytes receive activation, proliferation, and differentiation signals toward effector cells, i.e., cells that can directly participate in protective or damaging effects. To achieve this, the number of adhesion and costimulatory molecules, as well as receptors for cytokines, sharply increases on their surface. Activated T lymphocytes begin to produce and secrete cytokines that activate macrophages, other T lymphocytes, and B lymphocytes. After completion of the infection, associated with enhanced production, differentiation and activation of T-effectors of the corresponding clone, within a few days 90% of the effector cells die because they do not receive additional activation signals. Long-lived memory cells remain in the body, carrying receptors corresponding in specificity and capable of responding with proliferation and activation to a repeated encounter with the same antigen.

№7 B cells of the immune system, their characteristics

B lymphocytes constitute about 15-18% of all lymphocytes found in peripheral blood. After recognizing a specific antigen, these cells multiply and differentiate, transforming into plasma cells. Plasma cells produce large amounts of antibodies (immunoglobulins Ig), which are their own receptors for B lymphocytes in dissolved form. The main component of immunoglobulins Ig (monomer) consists of 2 heavy and 2 light chains. The fundamental difference between immunoglobulins is the structure of their heavy chains, which are represented by 5 types (γ, α, μ, δ, ε).

8. Macrophages

Macrophages are large cells formed from monocytes, capable of phagocytosis. In addition to direct phagocytosis,

macrophages take part in the complex processes of the immune response, stimulating lymphocytes and other immune cells.

In fact, a monocyte becomes a macrophage when it leaves the vascular bed and penetrates the tissue.

Depending on the type of tissue, the following types of macrophages are distinguished.

Histiocytes are connective tissue macrophages; component of the reticuloendothelial system.

Kupffer cells - otherwise endothelial stellate cells of the liver.

Alveolar macrophages - otherwise, dust cells; located in the alveoli.

Epithelioid cells are the components of granulomas.

Osteoclasts are multinucleated cells involved in bone resorption.

Microglia are cells of the central nervous system that destroy neurons and absorb infectious agents.

Macrophages of the spleen

Macrophage functions include phagocytosis, antigen processing, and interaction with cytokines.

Non-immune phagocytosis: macrophages are able to phagocytose foreign particles, microorganisms and debris

damaged cells directly, without causing an immune response. “Processing” of antigens:

macrophages “process” antigens and present them to B and T lymphocytes in the required form.

Interaction with cytokines: macrophages interact with cytokines produced by T lymphocytes

to protect the body against certain damaging agents.

9. Cell cooperation in the immune response.

Patrol macrophages, having discovered foreign proteins (cells) in the blood, present them to T-helper cells

(happens processing Ag macrophages). T helper cells transmit antigen information to B lymphocytes,

which begin to blast transform and proliferate, releasing the necessary immunoglobulin.

A minority of T helper cells (inducers) stimulate macrophages and macrophages begin to produce

interleukin I– activator of the main part of T-helpers. Those, getting excited, in turn announce

general mobilization, beginning to vigorously highlight interleukin II (lymphokine), which accelerates proliferation and

T-helpers and T-killers. The latter have a special receptor specifically for those protein determinants

which were presented by patrolling macrophages.

Killer T cells rush to target cells and destroy them. At the same time, interleukin II

promotes the growth and maturation of B lymphocytes, which turn into plasma cells.

The same interleukin II will breathe life into T-suppressors, which close the overall reaction of the immune response,

stopping the synthesis of lymphokines. The proliferation of immune cells stops, but memory lymphocytes remain.

10.Allergies

Specific increased sensitivity of an organism of a pathogenic nature to substances with antigenic properties.

Classification:

1.immediate type hypersensitivity reactions: develop within a few minutes. Antibodies are involved. Therapy with antihistamines. Diseases - atopic bronchial asthma, urticaria, serum sickness

2. delayed-type hypersensitivity reactions: after 4-6 hours, symptoms increase within 1-2 days. There are no antibodies in the serum, but there are lymphocytes that can recognize the antigen with the help of their receptors. Diseases - bacterial allergy, contact dermatitis, transplant rejection reactions.

4 types of reactions for jel and cubes:

Type 1 anaphylactic reactions: they are caused by the interaction of antigens entering the body with antibodies ( IgE), deposited on the surface of mast cells and basophils. These target cells are activated and biologically active substances (histamine, serotonin) are released. This is how anaphylaxis and atopic bronchial asthma develop.

Type 2 cytotoxic: Antibodies circulating in the blood interact with antigens fixed on cell membranes. As a result, the cells are damaged and cytolysis occurs. Autoimmune hemolytic anemia, hemolytic disease of the newborn.

Type 3 reaction of immune complexes: circulating antibodies interact with circulating antigens. The resulting complexes settle on the walls of blood capillaries, damaging the blood vessels. Serum sickness of daily injections

Type 4 cell-mediated immune reactions: they do not depend on the presence of antibodies, but are associated with the reactions of thymus-dependent lymphocytes. T-lymphocytes damage foreign cells. Transplata, bacterial allergy.

Type 5 anti-receptor: antibodies interact with hormone receptors on the cell membrane. This leads to cell activation. Graves' disease (increased thyroid hormones)

11.Immunodeficiencies

Immunodeficiency is a certain degree of insufficiency or loss of the normal function of the body's immune system, as a result of genetic or other types of lesions. Genetic analysis reveals a spectrum of chromosomal abnormalities in immunodeficiencies: from chromosome deletions and point mutations to changes in transcription and translation processes.

Immunodeficiency conditions

accompanied by many pathological processes. There is no single generally accepted classification of immunodeficiencies. Many authors divide immunodeficiencies into “primary” and “secondary”. Congenital forms of immunodeficiency are based on a genetic defect. Abnormalities in chromosomes, primarily the 14th, 18th and 20th, are of primary importance.

Depending on which effector links led to the development of immunodeficiency, one should distinguish between deficits of specific and nonspecific links of the body’s resistance.

Congenital immunodeficiency conditions

A. Immunodeficiencies of a specific link:

T-cell deficiencies:

variable immunodeficiencies.

Selective immunodeficiency for the Ir gene.

B-cell deficiencies:

Combined immunodeficiencies:

Selective Deficiencies:

B. Nonspecific immunodeficiencies

Lysozyme deficiency.

Complement system deficiencies:

Deficiencies in phagocytosis.

Secondary immunodeficiencies

Diseases of the immune system.

Generalized bone marrow disorders.

Infectious diseases.

Metabolic disorders and intoxication.

Exogenous influences.

Immunodeficiencies during aging.

HIV infection. Human immunodeficiency virus (HIV) causes an infectious disease mediated by primary damage to the immune system virus, with pronounced

pronounced secondary immunodeficiency, which causes the development of diseases caused by opportunistic infections.

HIV has an affinity for lymphoid tissue, specifically T-helper cells. The HIV virus in patients is found in the blood, saliva, and seminal fluid. Therefore, infection is possible through transfusion of such blood, sexually, or vertically.

It should be noted that disorders of the cellular and humoral components of the immune response in AIDS are characterized by:

a) a decrease in the total number of T-lymphocytes, due to T-helpers

b) decrease in the function of T-lymphocytes,

c) increasing the functional activity of B-lymphocytes,

d) an increase in the number of immune complexes,

k) decrease in the cytotoxic activity of natural killer cells,

f) decreased chemotaxis, cytotoxicity of macrophages, decreased production of IL-1.

Immunological disorders are accompanied by an increase in alpha interferon, the appearance of antilymphocyte antibodies, suppressive factors, a decrease in thymosin in the blood serum, and an increase in the level of β2-microglobulins.

The causative agent of the disease is human T-lymphocyte virus

Such microorganisms usually live on the skin and mucous membranes, called resident microflora. The disease has a phase character. The period of pronounced clinical manifestations is called acquired immunodeficiency syndrome (AIDS).