Immune and inflammatory system of the body. Inflammation. What is inflammation? The concept of immune deficiency. AIDS. amyloidosis

Inflammatory processes today account for 90-95% of all human pathology. According to the latest data presented at the Immunological Congress in Stockholm in 2001, even atherosclerosis is one of them. Therefore, deciphering the mechanisms of inflammation is a fundamental general biological problem of great practical importance.

Each of us has repeatedly suffered from certain inflammatory ailments, for example, a common cold, cholecystitis, gastritis, and those who are not lucky, and such severe forms like pneumonia. However, it is not easy to define this process. Modern pathophysiology and general pathology state: "Inflammation is a typical phase-developing pathological process, formed in the course of evolution and arising in response to local tissue damage."

Today in the world, inflammatory processes are being studied at the cellular-molecular level, which requires a "clarification of the relationship" between inflammation and immunity - two forms of the body's defense against any foreign agent that has invaded it. What is immunity? According to the definition of Academician R.V. Petrov, this is "a way to protect the body from living bodies and substances that bear signs of genetically alien information." That is, inflammation is a local, and immunity is a global (of the whole organism) method of protection.

In addition, the immune system constantly monitors the reliability of individual "citizens of the state", ruthlessly destroying infected, mutated and tumor cells, thereby maintaining the genetic and phenotypic homeostasis of the body.

central cell immune system are lymphocytes. Their main feature is the ability to recognize a strictly defined molecular determinant, the total number of which exceeds 10 14 and, as a rule, is localized in the structure of various proteins.

There are two main subpopulations of lymphocytes: B-lymphocytes responsible for the production of antibodies, or immunoglobulins (Ig) that bind antigens and T-lymphocytes - CTLs and T-helpers (the latter specialize in performing regulatory functions, producing a wide range of hormone-like substances of protein nature upon activation - cytokines, predominantly controlling the development of inflammation and the immune response).

How are inflammation and immunity related? The first to formulate this problem in 1871 was the great Russian scientist I. I. Mechnikov (later an honorary member of the St. Petersburg Academy of Sciences, Nobel laureate). In experiments, he discovered that leukocytes, like amoeba, digest various invading bodies, most often microbial agents. At that time, it was believed that the accumulation of leukocytes at the site of tissue damage was only an indicator of some kind of pathology in the body, and not its reaction to damage. But Mechnikov decided: such an army of cells is not needed just to testify to the pathology in the body. And on the basis of experiments, he came to an idea that contemporaries compared with Hippocratic: leukocytes carry out a protective reaction of the body. Later, he established that not single cells are responsible for it, but a whole system designed to protect the body from an invading agent. Mechnikov called them "devourer cells".

In the course of further work, the scientist came to the conclusion: as living organisms become more complex (starting from amoeba and ending with humans), the process of "devouring" is being improved. But if in the former the protective reaction coincides with digestion (whatever gets inside the body, everything is digested), then in more complexly organized animals (having a developed circulatory system and many specialized tissues) these two processes are separated, as a result of which they respond more quickly to the introduction of a foreign agent. So, in a starfish larva, a response must be expected for at least 12 hours, while in a person it occurs in a few minutes.

In 1891, Mechnikov gave the name phagocytes to "devouring cells" (from the Greek "phagos" - "I devour"). Subsequently, the phagocytic concept put forward by him was called the "cellular theory of immunity." It has retained its relevance to this day, although, of course, the scientist did not foresee the whole variety of what was happening. Therefore, let us dwell on what has been accumulated in biological science, especially in immunology, after II Mechnikov.

INFLAMMATORY PROCESS AND IMMUNE REACTIVITY

Inflammation, as we have already said, is a universal, genetically programmed reaction of the body to damage. different nature. Its essence lies in the concentration of phagocytes and other protective factors in the area of ​​damage and the elimination of biologically aggressive material there, as well as in restoring the structure and functions of the affected tissue.

However, in order for phagocytes to perform their functions in relation to microbes, they themselves need help from soluble opsonins (protein stimulators of phagocytosis), as well as regulatory support from T-helpers. Even before contact with a phagocyte - more precisely, with a macrophage (MF) - the pathogen is covered with individual protein factors of the complement system (a set of immune proteins), acting with low selectivity in relation to many types of microbes, as well as antigen-specific antibodies of class G and M (IgG and IgM ). However, the former can attack the microbe directly - through the formation of a membrane attack complex (MAC), which damages the walls of bacteria.

But the main action of the complement is the activation of phagocytes and their "guidance" to the objects of phagocytosis. For this, phagocytes have complement-fixing receptors CR. In turn, the antibodies fixed on the surface of the microbe also "mark" the microbes, since the phagocyte has the so-called Fc receptors (FcR), which bind the Fc fragments of antibodies that are oriented outward, nonspecific to antigens. In addition to complement, other antigen-specific humoral protective factors, such as C-reactive protein, may also be involved in this process.

Unlike non-specific factors, the production of antigen-specific effector lymphocytes (one of the forms of leukocytes) and antibodies requires prior contact of the lymphoid tissue with antigens and time (several days) for clonal proliferation (growth) of cells. In this case, at first, the antigen in the lymphoid organs is presented to T-lymphocytes by antigen-presenting cells (A-cells), which are most often macrophages or dendritic cells of the stromal microenvironment (performing the function of supporting structures) of the lymphocyte microenvironment close to them in origin. In the process of the immune response, memory cells are formed that do not immediately enter into a "fight" with the antigen, but they can exist for a long time even after the disappearance of the antigen from the body. These cells enhance the severity of the reaction of the immune system with a multiple reduction in the time of its development in the conditions of repeated entry of the antigen into the body. This phenomenon is used by physicians during preventive vaccinations.

Damage factors, including those of antigenic nature, are very diverse. Therefore, the reaction of the body should not be stereotyped. Thus, a number of cells with functional features are involved in the development of inflammation and immune reactivity, which determines various options for the development of immune and inflammatory reactivity. However, this is largely dictated by the presence of T-helper differentiation, starting from their poorly differentiated predecessors. First, T-helpers-0 are formed from the latter, which can then be differentiated in two alternative directions - Tx1 or 2. Each of them is capable of secreting strictly defined cytokine spectra on a competitive basis. And they have a different effect on the production of certain isotypes of antibodies with different functions by B-lymphocytes, affect different types cells upon activation of Tx directly in the focus of inflammation. As a rule, inflammation develops locally, but almost all body systems, primarily immune and neuroendocrine, are involved in its implementation (of course, to varying degrees).

Microvessels (especially postcapillary venules, stromal cells) of the injured organ, leukocytes migrating to the focus of inflammation, as well as complement system factors and many other plasma proteins, are integral participants in inflammation.

Inflammation includes a number of well-known external signs and microstructural changes. The former include edema, pain, hyperemia, local or systemic fever, dynamic changes in the structure and function of the damaged organ. To the second - exudative-vascular reaction, migration of leukocytes to the inflammation site with the formation of cellular infiltrates, and at the final stage - fibroblasts and other cells involved in the process of post-inflammatory repair or sclerosis of damaged tissues.

According to the dynamics of the development of acute inflammation uncomplicated by the development of infection, several successive stages can be distinguished, which are clearly recorded in experiments on animals. The first of these is tissue alteration, or damage. It initiates the reaction of the endothelium of postcapillary venules and the hemostasis system, which provokes the development of an exudative-vascular reaction within a few minutes. In the second stage, exposure to microbial antigen promotes the migration and subsequent activation of polymorphonuclear leukocytes, mainly neutrophils: onset - after 25-40 minutes, maximum - after 3-6 hours. This occurs when the complement system, immunoglobulins, many acute-phase proteins and some other serum factors. The action of these mechanisms is aimed at the elimination of the antigen. At the peak of the neutrophil-dependent phase, the migration of mononuclear cells begins - monocytes (one of the forms of leukocytes) and lymphocytes. The former differentiate into macrophages in the focus of inflammation, and after about a day, mononuclear cells become the dominant cellular elements of the infiltrate. This stage ends with the final sterilization of the focus of inflammation, its purification from tissue decay products. At the same time, reparative (liquidation) processes develop, acquiring dominant significance at the final stage.

Migration of fibroblasts to the focus of inflammation begins in 1-3 days from the moment of alteration, after another 2-3 days, they actively form collagen fibers and other components of the extracellular matrix. All these processes ultimately lead to complete regeneration or scarring of the damaged tissue.

Duration and severity of individual phases inflammatory process depends on the nature of the damage and its accompanying conditions, including the development of immunodeficiency.

Despite the universality of the underlying mechanisms of inflammation in each case, the process is unique in its manifestations. The individual features of inflammation depend on its localization in various organs, the nature of the etiological factor, the phenotypic and genetic properties of the invading macroorganism, the ratio of the duration and severity of individual phases and the particular mechanisms underlying it.

According to the degree of involvement in the process of various anti-inflammatory mechanisms, it can be divided into two alternative options: exudative-destructive, or purulent inflammation, and productive, or proliferative-cellular. The determining influence in the first case is exerted by neutrophils with a pronounced phlogogenic (inflammatory-damaging) potential, as well as the complement system and immunoglobulins functionally associated with them (especially class G, more precisely, their main subclass IgGI). In the second case, the purulent reaction is much less pronounced, and the predominant cellular element of the infiltrate is mononuclear cells (monocytes-macrophages and lymphocytes), in some cases (for example, when the tissue reacts to helminths or their larvae) - eosinophils.

The development of exudative-destructive inflammation, as a rule, is associated with the aggression of rapidly multiplying pyogenic bacteria in the extracellular environment. In turn, to obligate (constantly occurring) infection with intracellular pathogens, the usually protective and dominant form of response is the development of productive or proliferative cell inflammation with the predominant involvement of "inflammatory" macrophages and functionally cooperating with them T-lymphocytes and normal killer cells. At the same time, the latter are able to attack modified cells without a preliminary immune response. Involvement in the process of inflammation of many types of cells, sub cellular elements and organ systems determines the formation complex mechanisms regulation of inflammatory and immune reactivity both at the local and organismal levels.

The duration of the inflammatory process is acute (up to one month), subacute (three to six months) and chronic. In the latter case, the alteration mechanism is preserved, say, in the form of a prolonged infection of the damaged tissue. In turn, chronic inflammation can have a relapsing, torpid (sluggish form) or progressive (constantly progressive) course.

With the prolongation of the inflammatory process, the transformation of its various manifestations in time and layer-by-layer localization often occurs. So, with an exacerbation of a sluggish, productive inflammation, development proceeds in an exudative-destructive direction, and a number of layers with dissimilar morphological and functional characteristics are distinguished in the structure of the formed abscess.

The classical variants of inflammation, in essence, are local processes, biological entity which is reduced to the concentration of vital resources and protective factors of the body in the area of ​​tissue damage. This function is implemented by the "launch" of the stress program by the neuroendocrine system, as well as changes in the regenerative potencies of the bone marrow and lymphoid organs, the synthesis of acute phase proteins in the liver, etc.

The systemic reaction in case of local damage provides not only the priority supply of the necessary cellular and humoral factors to the inflammation focus, but also contributes to the neutralization of infections (infected objects), toxic tissue decay products, and various biologically aggressive factors protective in the inflammation focus in the bloodstream.

As already mentioned, the immune system is responsible for maintaining the body's genetic homeostasis. According to the concept formulated by academician R. V. Petrov, the immune system, like the sense organs, is a kind of scanner of information entering the body - it checks biological objects inside the body for the presence of foreignness. In case of detection of "foreign" antigens, it remembers them, analyzes them and responds to their impact by entering antigen-specific Ig- and T-lymphocytes into the focus of inflammation.

Thus, the immune system, along with the central nervous system, is another mechanism that complements (on the basis of acquired experience) the genetically determined program of the organism's behavior. However, the analytical activity of the immune system takes place outside the framework of our consciousness.

In case of damage, both systems work cooperatively, contributing to the development of an adaptation process that mobilizes the body's resources to eliminate the damaging factor itself and the consequences of its impact. At the same time, like the central nervous system, the immune system forms a morphological and functional dominant, the core of which is antigen-specific clones of T- and B-lymphocytes.

The objects of the regulatory effects of the immune system are all the most important organs, but it has the closest and most multifaceted contact with the neuroendocrine system. With the latter, it integrates into a single immunoneuroendocrine supersystem, in which, during a pronounced inflammatory process, some long-range acting cytokines (for example, IL-1 or IL-6), tumor necrosis factor, etc. serve as the main connecting element of various regulatory systems.

The influence of immunocytes on the nervous system is carried out not only through cytokines, but also through a number of hormones (including most tropic hormones of the pituitary gland), endorphins, neurotransmitters, and others. To some extent, almost all hormones and many neurotransmitters secreted by peripheral nerves have immunotropic effects. In small amounts, a number of pro-inflammatory cytokines are produced by neurons and macroglial and microglial cells directly in the central nervous system. The impetus for their "production" can be not only significant tissue damage, but also severe psychogenic trauma.

EVOLUTIONARY ASPECTS OF THE FORMATION OF THE IMMUNE SYSTEM

The immune system is the main anti-inflammatory mechanism and the most vulnerable system in conditions of immunodeficiency. It should be noted that in mammals it is the end result of a long evolutionary process. Already in primitive invertebrates, specialized phagocytes are found - amoeboid cells that recognize objects of phagocytosis using contact receptors. These cells, with the participation of opsonins (protein stimulators of phagocytosis), are able to simultaneously bind to a phagocyte, on the one hand, and a microbe, on the other.

The basic mechanisms of the inflammatory process are, first of all, factors of the paleoimmunity system: phagocytes of blood and tissues, endothelium of postcapillary venules, complement and hemostasis systems, acute-phase and antibiotic-like proteins, and other non-antigen-specific protective organisms.

In invertebrates, such mechanisms are able to effectively carry out the immune defense of the body. The system of paleoimmunity in animals with a much more complex organization is not able to independently solve this problem. First of all, it concerns the counteraction of rapidly evolving pathogenic microflora. Therefore, the appearance of an antigen-specific system of neoimmunity in vertebrates can be considered as a product of the crisis in the relationship between macro- and micro-organisms during the Cambrian evolutionary explosion (about 350 million years ago). The formation of lymphoid organs was an adequate response to this challenge, which ensured the survival of highly organized organisms.

The introduction of viral recombinases into the genome of macroorganisms made it possible to “shuffle” the genetic segments of the variable genes of the Ig- and T-cell receptor, and thereby form and clonally fix a huge variety of variants of these genes that were not initially encoded in the zygote. As established recently, the theoretically possible number of antigen-specific clones of lymphocytes is approximately 10 18 variants. This essentially allows the immune system to recognize virtually any antigen.

The neoimmunity system can be considered as a superstructure on the paleoimmunity system. This can be done, firstly, because antibodies and immunocompetent effector cells were formed as a result of evolutionary metamorphoses of various paleoimmunity factors and, secondly, they always act as an amplification link in the focus of inflammation in cooperation with the basic mechanisms dependent on them. paleoimmunity. In the process of development, cooperation of antigen-specific and antigen-nonspecific mechanisms took place.

As a result, the regulatory mechanisms that ensure the relationship between the immune and other, primarily neuroendocrine, systems of the body have become much more complicated. At the same time, the formation of a single immunoneuroendocrine regulatory complex has become the pinnacle of the development of bioinformation systems

In humans, the effectiveness of the elimination of the inflammatory process depends on the degree of cooperative interconnectedness of antigen-specific factors of neoimmunity and evolutionarily older, but less specific mechanisms of paleoimmunity both in the focus of inflammation and the whole organism.

Academician V.A. CHERESHNEV, Director of the Institute of Ecology and Genetics of Microorganisms, Perm Scientific Center, Ural Branch of the Russian Academy of Sciences

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The most important role of cellular elements in the development of acute and chronic inflammation deserves special consideration.

Neutrophils

Because in rheumatic diseases such as rheumatoid arthritis or SLE, there is a chronic hyperproduction of phagocytosed material - immune complexes and products of inflammatory tissue destruction, the role of neutrophils in aggravating and further maintaining chronic inflammation is especially great.

The process of phagocytosis begins with the binding of the phagocytosed substance to the surface receptors of the neutrophil, resulting in hyperpolarization of the cell membrane and local loss of calcium ions. This is followed by the production of previously little-known reactive oxygen derivatives by neutrophils, including the superoxide anion of oxygen (O) and especially hydroxyl radical (OH).

These products are toxic to microbes, which explains the biological feasibility of their production in the process of phagocytosis. However, with increased production, they can also cause damage to surrounding tissues of the body. The next step is the release of arachidonic acid from the phospholipids of the cell membrane (under the action of the phospholipase enzyme), which, under the influence of cyclooxygenase, is oxidized into prostaglandins and other substances chemically similar to them.

At the same time, phagocytosis itself takes place, which can be observed under a microscope: protrusions are formed in the neutrophil, covering the phagocytosed material and immersing it in the cytoplasm, due to which it lies intracellularly - in a cavity called the phagosome.

At the same time, changes occur in the so-called cytoskeletal system (the "micromusculature" of the cell). The microfilaments of actin and myosin located in the neutrophil interact with the actin-binding protein located under the plasmolemma, after which they condense and contact the microtubular system of the cell. Only after this, specific and azurophilic granules permanently located in the cytoplasm of neutrophils merge with the phagosome, and the destructive enzymes contained in them come into contact with the phagocytosed substance and its intracellular "digestion" begins.

All the described processes occur very quickly. In particular, the release of enzymes from azurophilic granules into the phagosome can occur within a few seconds after interaction with a substance undergoing phagocytosis.

Thus, neutrophils produce 3 groups of active inflammatory mediators:

1. Toxic oxygen derivatives that actively interact with body tissues.

2. Arachidonic acid derivatives, among which the most active are endoperoxides (unstable prostaglandins Ga and H2), thromboxane A2, prostacyclin and hydroxyheptadecatrienoic acid. These substances, which are chemically unstable and therefore highly active, are capable of inducing many of the cardinal signs of inflammation, including the accumulation of new neutrophils (due to their inherent chemotactic properties).

The accumulation of neutrophils again leads to the production of unstable prostaglandins, due to which a kind of vicious circle can occur, leading to chronic inflammation. The production of unstable prostaglandins is also accompanied by the additional formation of free oxygen radicals from oxygen molecules, which contributes to tissue destruction, and thereby maintaining the inflammatory process. At the same time, stable prostaglandins (E2 and F, thromboxane B3), into which their unstable precursors are rapidly converted, contrary to previous opinion, are not the primary mediators of inflammation.

W. Samuelsson et al. (1979) described a new class of inflammation, which are also metabolites of arachidonic acid, the so-called leukotrienes. One of them (leukotriene C) appears to be chemically identical to the previously described slow active ingredient anaphylaxis.

3. Destructive enzymes contained in neutrophil granules and entering in the process of phagocytosis not only into the phagosome, but also extracellularly. Perhaps their damaging effect and body tissues. These enzymes include neutral proteases contained in azurophilic granules, myeloperoxidase, as well as lysosomal enzymes proper - acid hydrolases, which are especially characteristic of a damaging effect on tissues. Enzymes characteristic of specific neutrophil granules include lysozyme and lactoferrin.

The abundance of inflammatory mediators in neutrophils and their mutually reinforcing effect largely explain the crucial role of these cells in most inflammatory processes, including those in patients with rheumatic diseases. It is no coincidence that G. Weissmanr (1979) called neutrophils the secretory organs of rheumatoid inflammation.

In the body, there are antagonists of some of the considered mediators, with the help of which, apparently, the possible damaged effect of phagocytosis on the surrounding tissues is limited. Thus, the activity of proteases is inhibited by azmacroglobulin and a1-antitrypsin, and the activity of free oxygen radicals is inhibited by the copper-containing protein ceruloplasmin and the enzyme superoxide dismutase, which is especially widespread in the body, destroys free superoxide oxygen anions and thereby prevents the formation of an even more toxic hydroxyl radical.

When evaluating the role of neutrophils in the development of inflammation, one should keep in mind their high content in the peripheral blood, from where they can quickly and in large quantities enter the inflammation zone. These cells are short-lived - they disintegrate after a few hours.

macrophages

The latter are extremely important in the implementation of adaptive reactions of the body - immune, inflammatory and reparative. Participation in such reactions is facilitated by such biological properties of macrophages as the ability to migrate to inflammatory foci, the possibility of a rapid and persistent increase in bone marrow cell production, active phagocytosis of foreign material with rapid splitting of the latter, activation under the influence of foreign stimuli, secretion of a number of biologically active substances, the ability to " process” the antigen that has entered the body, followed by the induction of the immune process.

It is also fundamentally important that macrophages are long-lived cells capable of long-term functioning in inflamed tissues. It is essential that they are able to proliferate in the foci of inflammation; at the same time, the transformation of macrophages into epithelioid and giant multinucleated cells is possible.

Lacking immunological specificity (like T- and B-lymphocytes), the macrophage acts as a non-specific auxiliary cell with the unique ability not only to capture the antigen, but also to process it so that the subsequent recognition of this antigen by lymphocytes is greatly facilitated.

This stage is especially necessary for the activation of T-lymphocytes (for the development of delayed-type immune responses and for the production of antibodies to thymus-dependent antigens). In addition to participating in immune reactions due to antigen pretreatment and its subsequent “presentation” to lymphocytes, macrophages also perform protective functions more directly, destroying some microorganisms, fungi, and tumor cells.

Thus, in rheumatic diseases, cellular reactions of immune inflammation involve not only specifically immunized lymphocytes, but also monocytes and macrophages that do not have immunological specificity.

These cells are attracted by monocytic chemotactic substances produced in the foci of inflammation. These include C5a, partially denatured proteins, kallikrein, plasminogen activator, basic proteins from neutrophil lysosomes. T-lymphocytes produce a similar factor upon contact with its specific antigen, B-lymphocytes - with immune complexes.

In addition, lymphocytes also produce factors that inhibit the migration of macrophages (i.e., fixing them in the focus of inflammation) and activating their function. In inflammatory foci, in contrast to normal conditions, mitoses of macrophages are observed and thus the number of these cells also increases due to local proliferation.

The importance of macrophages in maintaining the inflammatory process is determined by the following anti-inflammatory agents released from these cells:

1. Prostaglandins.

2. Lysosomal enzymes (in particular, during phagocytosis of antigen-antibody complexes, and the cell is not destroyed during their isolation).

3. Neutral proteases (plasminogen activator, collagenase, elastase). Normally, their number is negligible, but with foreign stimulation (during phagocytosis), the production of these enzymes is induced and they are released in significant quantities. The production of neutral proteases is inhibited by inhibitors of protein synthesis, including glucocorticosteroids. The production of plasminogen activator and collagenase is also stimulated by factors secreted by activated lymphocytes.

4. Phospholipase A3, which releases arachidonic acid from more complex complexes - the main precursor of prostaglandins. The activity of this enzyme is inhibited by glucocorticosteroids.

5. A factor that stimulates the release from the bones of both mineral salts and the organic basis of the bone matrix. This factor exerts its influence on bone tissue through direct action without requiring the presence of osteoclasts.

6. A number of complement components that are actively synthesized and released by macrophages: C3, C4, C2 and, apparently, also C1 and factor B, which is necessary for an alternative pathway of complement activation. The synthesis of these components increases upon activation of macrophages and is inhibited by inhibitors of protein synthesis.

7. Interleukin-1, which is a typical representative of cytokines - biologically active substances of a polypeptide nature, produced by cells (primarily cells of the immune system). Depending on the sources of production of these substances (lymphocytes or monocytes), the terms "lymphokines" and "monokines" are often used. The name "interleukin" with an appropriate number is used to refer to specific cytokines - especially those that mediate cellular interaction. It is not yet clear whether interleukin-1, which is the most important monokine, represents a single substance or a family of polypeptides with very similar properties.

These properties include the following:

• stimulation of B cells, accelerating their transformation into plasma cells;
• stimulation of the activity of fibroblasts and synoviocytes with their increased production of prostaglandins and collagenase;
• pyrogenic influence, which is realized in the development of fever;
• activation of the synthesis in the liver of acute phase proteins, in particular the serum amyloid precursor (this effect may be indirect - due to stimulation of the production of interleukin-6).

8. Interleukin-6, which also activates B cells, stimulates hepatocytes to produce acute phase proteins and has the properties of b-interferon.

9. Colony-stimulating factors that promote the formation of granulocytes and monocytes in the bone marrow.

10. Tumor necrosis factor (TNF), which is not only really capable of causing tumor necrosis, but also plays a significant role in the development of inflammation. This polypeptide, consisting of 157 amino acids, in the early phase of the inflammatory response promotes the adherence of neutrophils to the endothelium and thereby contributes to their penetration into the inflammation site. It also serves as a powerful signal for the production of toxic oxygen radicals and is a stimulator of B-cells, fibroblasts and endothelium (the last two types of cells produce colony-stimulating factors).

It is clinically important that TNF, as well as interleukin-1 and interferon, inhibit the activity of lipoprotein lipase, which ensures the deposition of fat in the body. That is why when inflammatory diseases often there is a pronounced weight loss that does not correspond to high-calorie nutrition and preserved appetite. Hence the second name of the tumor necrosis factor is cachectin.

Activation of macrophages, which is manifested by an increase in their size, a high content of enzymes, an increase in the ability to phagocytosis and the destruction of microbes and tumor cells, can also be non-specific: due to stimulation by other (not related to the existing pathological process) microorganisms, mineral oil, lymphokines produced by T- lymphocytes, to a lesser extent - B-lymphocytes.

Macrophages are actively involved in bone and cartilage resorption. Electron microscopic examination at the border of pannus and articular cartilage revealed macrophages closely associated with particles of digested collagen fibers. The same phenomenon was noted in the contact of macrophages with resorbed bone.

Thus, macrophages play an important role in the development of the inflammatory process, its maintenance and chronicity, and already a priori can be considered as one of the main "targets" of antirheumatic therapy.

fibroblasts

fibroblasts- essential cells connective tissue, the main source of collagen, elastin, glycosaminoglycans and glycoproteins, i.e. the main biochemical structures that make up this tissue. In chronic inflammation (including immune-mediated inflammation), fibroblasts actively multiply and, together with the connective tissue components produced by them (fibers and ground substance) and newly formed capillary loops, form granulation tissue, which in some diseases can play a significant role in the development of the underlying pathological process and its outcomes. .

In particular, in rheumatoid arthritis, granulation tissue in the joint cavity (pannus) can actively destroy cartilage and bone. This destruction, in addition to pannus cells as such, also involves macrophages entering through the newly formed vessels of the granulation tissue. It is noteworthy that macrophages are not only able to activate fibroblast division and collagen synthesis, but also secrete collagenase that interacts with collagen produced by fibroblasts. On the other hand, the newly formed collagen has chemotactic properties in relation to macrophages.

In this regard, macrophages and fibroblasts can be considered as a friendly cellular system that functions in case of damage and structural restoration of the connective tissue. When chronic inflammation subsides, including under the influence of targeted treatment, granulation tissue becomes less vascularized, the number of cells and the amount of the main substance in it decrease, and the amount of mature collagen increases. This process ends with the formation of scar tissue.

Fibroblasts, apparently, can also take part in the generation of inflammatory reactions. They are characterized by weak phagocytic properties (there are receptors for solid particles on the surface), when stimulated, they are able to secrete lysosomal enzymes and neutral proteases (plasminogen activator and collagenase) into the extracellular space, but in much smaller quantities compared to macrophages.

It has also been established that fibroblasts can produce interleukins 1 and 6, Rinterferon, and factors that stimulate stem cell differentiation into mature neutrophil and monocyte colonies (similar to colony-stimulating factors produced by macrophages).

Thus, fibroblasts are important at different stages of the inflammatory process. It is also clear from the foregoing that an adequate inhibitory effect on fibroblasts can be manifested by a decrease in the severity of chronic inflammation and sclerosis processes.

General reactions in inflammation

They are secondary to inflammation, and this is their fundamental difference from the biological reactions inherent in the systems of inflammation generation considered earlier. Among such nonspecific reactions, the most obvious is fever, the main mediator of which is considered to be interleukin-1, produced by macrophages in the foci of inflammation and interacting with the centers of thermoregulation in the hypothalamus.

An increase in body temperature during inflammation has a clear biological feasibility, since it increases phagocytic activity and thereby facilitates the destruction of microorganisms and tissue repair. Thus, a local process causes a general reaction, which in turn purposefully influences this local process. In addition, using the example of fever, it is easy to see that a biologically expedient reaction can be individually (clinically) unfavorable, since an increase in body temperature in itself can cause serious harm to the body.

The characteristic systemic manifestations of an acute inflammatory reaction are left-shift neutrophilic leukocytosis and (less known) thrombocytosis. In addition to interleukin-1, colony-stimulating factors produced by macrophages and fibroblasts can be mediators of these manifestations. Weight loss, muscle atrophy and weakness that often develop in inflammatory diseases are most likely the result of the influence of tumor necrosis factor (a product of macrophages).

In addition, interleukin-1 is also able to induce skeletal muscle proteolysis. The general adaptation syndrome discovered by N. Selye in the 1950s, the leading feature of which is the increased production of cortisol, also appears to be a systemic reaction during inflammation in its early stages. It should be borne in mind that the effect of this corticosteroid is manifested, in particular, in a moderate increase in the number of leukocytes and platelets.

The characteristic laboratory symptoms of inflammation are the so-called acute phase proteins synthesized in the liver, which are determined in the blood. Some of them have a "negative" meaning, since in inflammatory diseases their content in plasma decreases (due to increased catabolism or inhibition of their synthesis due to switching of the biosynthetic activity of the cell to other metabolic pathways). These include albumin, prealbumin, and transferrin, of which only the former is of real clinical value.

Much more attention is paid to those acute phase proteins, the concentration of which increases with the development of inflammation. Their increased production by the liver apparently reflects the biological expediency of these substances fixed in phylogenesis, which regulate the severity of the inflammatory process in the reflection of external harmful influences. They include proteins of different nature, performing a variety of functions.

In particular, it is necessary to note the increase in a number of coagulation factors- fibrinogen, prothrombin, factor VIII and plasminogen. This is most likely due to the fact that evolutionary inflammation in higher mammals was very often the result of trauma and was accompanied by bleeding. In addition, coagulation in the area of ​​penetration of the damaging factor (including microbes) contributes to the localization of pathological changes.

The quantitatively increasing acute phase proteins also include complement components and its inhibitors (as well as inhibitors of other proteolytic enzymes - a1-antitrypsin and a2-antichymotrypsin). An increase in the level of haptoglobin, ferritin and hemopexin possibly reflects an increased use of iron from decaying hemoglobin, ceruloplasmin - the binding of free oxygen radicals, C-reactive protein - non-specific opsonization, facilitating the subsequent influence of immune mechanisms (in connection with which C-reactive protein is called "primitive antibody").

There are also acute phase proteins whose function is unknown: orosomucoid (a1-acid mucoprotein), serum amyloid component (SAA), CD globulin. The degree of growth of the considered substances is different. Thus, the content of ceruloplasmin and the 3rd complement component (C3) more often increases 1.2-1.5 times, fibrinogen - 2-3 times, C-reactive protein and SAA - hundreds of times.

Despite the non-specificity of the production of acute phase proteins (their level increases with inflammation of any origin), there are isolated exceptions in this regard. In particular, in systemic lupus erythematosus, despite the generalized inflammatory process, a noticeable increase in the level of C-reactive protein often does not occur.

Sigidin Ya.A., Guseva N.G., Ivanova M.M.

Phagocytosis.

Phagocytosis - consists in the absorption and digestion of bacteria, products of cell damage and decay. Phagocytic activity is shown primarily by neutrophilic leukocytes and macrophages. There are 4 stages of phagocytosis: the 1st stage is the approach of the phagocyte to a foreign object, the 2nd stage is the adhesion of the phagocyte to the object. It is preceded by coating of the phagocyte with immunoglobulins M and J and complement fragments (opsonization). 3rd stage - absorption of the object by invagination of the phagocyte and the formation of a vacuole - phagosome. Before the formation of a phagosome, oxidase is activated in the phagocyte, which ensures the synthesis of hydrogen peroxide. Hydrogen peroxide under the influence of peroxidases forms active oxygen molecules, which destroys cell membranes by peroxidation. The destruction of membranes is also facilitated by lysosomal enzymes and bactericidal proteins released during degranulation of leukocytes. This occurs in the 4th stage - intracellular cleavage and digestion of phagocytosed microbes and remnants of damaged cells. In this case, the phagocytes themselves die. The products of their destruction stimulate the processes of proliferation.

Proliferation.

Elements of proliferation take place from the very beginning of inflammation, but it becomes predominant as the exudation subsides. At the stage of proliferation, destructive processes gradually stop and are replaced by creative ones. There is an active repayment of the inflammatory process. In this regard, the protein α 2 -macroglobulin plays an active role. He a wide range actions, in particular, inhibits kinins. In the inactivation of inflammatory cells, in addition to local factors, common factors such as endocrine. Cortisol inhibits the synthesis of vasoactive substances, causes eosinophilopenia, lymphopenia and basophilopenia. Then the defect is replaced with healthy tissue. This is done by multiplying the remaining living cells (resident cells), as well as new cells from neighboring zones (emigrant cells). Stem cells of vascular tissue - polyblasts and lymphoid cells multiply, new capillaries appear. Granulation tissue is formed. Growth stimulants are: thrombocytic fibroblast growth factor (platelets); similar factors are formed in lymphocytes and monocytes. In some organs, substances stimulating proliferation are formed. For example, in the pituitary gland, fibroblast growth factor, in the liver, somatomedin, which also stimulates proliferation. There are also proliferation inhibitors - kalons, the hormone cortisone.

At the end of inflammation, when it is completed, two cells, fibroblast and endotheliocyte, play a decisive role. There is a settlement of the zone of inflammation with fibroblasts and neoangiogenesis. Fibroblasts synthesize collagen. Endotheliocytes contribute to the formation of blood vessels.

At little damage tissues, with wounds healing by primary intention, the inflammatory process ends with a complete recovery. When a large number of cells die, the defect is replaced by connective tissue with the formation of a scar. There may be excess scar tissue formation.

Pathogenesis clinical signs inflammation.

Redness is due to the development of arterial hyperemia, an increase in blood flow with a high oxygen content, an increase in the number of functioning capillaries.

"Swelling" is explained by arterial and venous hyperemia, exudation, and migration of leukocytes.

Fever is due to an increase in metabolism early stages inflammation, blood flow with more high temperature, dissociation of the processes of biological oxidation and phosphorylation.

Fever develops under the influence of pyrogenic factors coming from the focus of inflammation, such as lipopolysaccharides, cationic proteins, interleukin-1, etc.

Pain is caused by irritation of receptors in the focus of inflammation by mediators, especially serotonin, kinins, prostaglandins, a shift in the reaction of the environment to the acid side, the occurrence of dysionia, an increase in osmotic pressure, and mechanical stretching or compression of tissues.

Violation of the function of the inflamed organ is associated with a disorder of its neuroendocrine regulation, the development of pain, and structural disorders.

Leukocytosis is due to the activation of leukopoiesis and the redistribution of leukocytes in the bloodstream. Among the main reasons for its development are: stimulation of the sympathetic-adrenal system, exposure to certain bacterial toxins, tissue decay products, as well as a number of inflammatory mediators (interleukin-1).

The change in the protein "profile" of the blood is expressed in the fact that during an acute process, the so-called "acute phase proteins" of inflammation - C-reactive protein, etc. accumulate in the blood. globulins.

An increase in ESR occurs due to a decrease in the negative charge of erythrocytes, agglomeration of erythrocytes, changes in the protein spectrum of the blood, in particular, an increase in fibrinogen content, and a rise in temperature.

Immunity and inflammation.

Changes in the immune system during inflammation are expressed in an increase in antibody titer, the appearance of sensitized lymphocytes in the blood. In the development of immunity during inflammation, such nonspecific factors as phagocytosis and complement should be noted. The place of phagocytosis carried out by PNL and monocytic phagocyte (macrophage) in the immune system is determined by the fact that despite the non-specificity of the act of phagocytosis itself, macrophages take part in their processing into an immunogenic form. The complement system is involved in specific reactions, attaching its components to antibody molecules, which ensures the lysis of antigenic substances against which antibodies have been developed, it activates immune complexes. Thus, the activation of the immune response during inflammation is provided by two cellular systems of nonspecific defense - the system of PMNs and macrophages, as well as plasmas. system - the complement system.

The relationship of local and general changes in inflammation.

In the focus of inflammation, complex processes occur that cannot proceed autonomously. They are a signal for inclusion in the inflammatory response of various body systems. The material substrate of these signals is the accumulation and circulation of biologically active substances, complement components, interferon, etc. in the blood. Of the factors that determine the relationship between local and general changes during inflammation, the so-called acute phase reactants are of great importance. These substances are not specific for inflammation. They appear 4-6 hours after various injuries, including after damage during inflammation. Highest value of which they have: C-reactive protein, interleukin-1, T-kininogen, transferrin, apoferritin, etc. Most of the acute phase reactants are synthesized by macrophages, hepatocytes. Interleukin-1 affects the function of the cells of the inflammatory focus, including lymphocytes, activates PNL, stimulates the synthesis of prostaglandins and prostacyclins in endotheliocytes, and promotes a hemostatic reaction in the lesion. The concentration of C-reactive protein increases during inflammation by 100-1000 times. This protein activates the cytolytic activity of killer T-lymphocytes and inhibits platelet aggregation.

T-kininogen is a precursor of kinins and a proteinase inhibitor. Inflammation induces the synthesis of apoferritin in the liver, which stimulates the production of PNL. The acute phase reactants determine the nonspecific response of the body, creating conditions for the development of a local inflammatory reaction. At the same time, they stimulate the inclusion of other body systems in the process, contributing to the interaction of local and general during inflammation.

The size, prevalence of the focus of inflammation, as well as the characteristics of the damaging agent have a pronounced effect on the relationship between local and general changes in inflammation. Starting from some critical size of this focus, the development of inflammation is combined with a number of homeostasis disorders caused both by products of tissue damage and mediators, and by stress (pain, emotional).

Inflammation and reactivity of the body.

The occurrence, development, course and outcome of inflammation depend on the reactivity of the organism. Reactivity depends primarily on the state of higher regulatory systems: nervous, endocrine, immune.

The use of anesthetic substances that can turn off receptor formations significantly weakens the course of the inflammatory process. The creation of a stable focus of excitation in the central nervous system sharply weakens the course and intensity of inflammation. Deep anesthesia markedly weakens the formation of infiltrates. The endocrine system has a significant influence on the development of inflammation. In relation to inflammation, hormones can be divided into pro- and anti-inflammatory. The former include somatotropin, mineralocorticoids, thyroid hormones, insulin, the latter - corticotropin, glucocorticoids. Anti-inflammatory hormones: 1. Reduce vascular permeability. 2. Stabilize lysosomal membranes. 3. Enhance the action of catecholamines. 4. Weaken the synthesis and

action of biologically active substances (histamine, serotonin). 5. Reduce emigration

leukocytes, weaken phagocytosis.

The development of inflammation significantly depends on age. In newborn children, the exudative component of inflammation is almost not expressed, since the vascular reactions are imperfect. They are imperfect because they are not sufficiently formed as peripheral nerve endings sympathetic and vagus nerves, as well as their centers. The sympathetic nervous system retains its dominant influence on vascular tone after birth, leading to vasospasm. Inflammation in the neonatal period takes on an alternative character. The proliferative component of inflammation is delayed. Most often at this age, inflammation of the skin occurs, since the epidermal layer is very poorly developed.

Skin and mucous membranes of children infancy not able to provide antimicrobial protection. The phagocytic activity of leukocytes is very low. Moreover, phagocytes are able to absorb microbes, but they cannot lyse them, because. activity of hydrolytic enzymes is low (not completed phagocytosis). The phagosomes of such leukocytes turn into "repositories" of viable microbes, causing generalization of the infection.

In children, starting from the age of 5 months, inflammation of the small and large intestines (enteritis, colitis) often occurs.

In old age, inflammatory processes of the gastrointestinal tract occur more often, because. the acidity of gastric juice decreases, which is a protective factor when bacteria enter the stomach. As a result of inhibition of the activity of the cilia of the epithelium respiratory tract pneumonia often occurs.

Types of inflammation.

Depending on the nature of the dominant local process (alteration, exudation, proliferation), 3 types of inflammation are distinguished. In alternative inflammation, damage, dystrophy, and necrosis predominate. It is observed most often in parenchymal organs in infectious diseases that occur with severe intoxication (cheesy decay of the lungs in tuberculosis).

Exudative inflammation is characterized by severe circulatory disorders with symptoms of exudation and emigration of leukocytes.

comrade By the nature of the exudate, serous, purulent, hemorrhagic, fibrinous, putrefactive, mixed inflammation are distinguished.

Proliferative or productive inflammation is characterized by the fact that it is dominated by the reproduction of cells of hematogenous and histiogenic origin. Cellular infiltrates appear in the inflamed area. During inflammation, cells undergo transformation and differentiation, resulting in the formation of young connective tissue. It goes through all stages of maturation, as a result of which the organ or part of it is penetrated by connective tissue strands.

According to the nature of the course, inflammation can be acute, subacute and chronic. Acute inflammation lasts from several days to several weeks. It is characterized by: a pronounced intensity of the inflammatory reaction and the predominance of either alternative or vascular-exudative phenomena. The role of the main effectors in its pathogenesis is played by PNL. Chronic inflammation is a sluggish, long-term ongoing process. It is dominated by dystrophic and proliferative phenomena. The main role in chronic inflammation belongs to macrophages and lymphocytes. Subacute inflammation occupies an intermediate position.

outcomes of inflammation.

1. Complete restoration of the damaged organ. This takes place if neither the action of the phlogogenic factor nor the development of the inflammatory process leads to the death of a significant amount of tissue. 2. If, as a result of the action of a phlogogenic factor or as a result of secondary alteration, a significant amount of tissue is lost, then the tissue defect is eliminated by the formation of a scar or diffuse germination of connective tissue. The presence of a scar sometimes does not cause a significant violation of the function of the organ, but in some cases it can lead to serious consequences. For example, scarring in the wall of the esophagus (after burning it) can cause narrowing of the esophagus, which will make it difficult to feed the body. 3. Inflammation can be detrimental to the body. This is due to the fact that in the case of extensive alteration, the tissue of a vital organ may die, or as a result of exudation, organs such as

brain, heart, lungs, which can so disrupt their function,

that it will become incompatible with life.

Chronic inflammation (Ado 1994, pp. 171-173).

Chronic inflammation begins with the accumulation of a large number of

la irritated (activated) macrophages in one place. Persistent irritation of macrophages is caused by different ways: 1. Macrophage defect. In this case, macrophages absorb the foreign factor, but cannot destroy it. There is an incomplete phagocytosis. Therefore, macrophages are constantly in an active state. 2. A number of microorganisms are absorbed by macrophages, but due to their characteristics, they do not die in phagosomes and get the opportunity to live and multiply for a long time. These forms include pathogens of tuberculosis, leprosy, toxoplasmosis and many others. infectious diseases. 3. Macrophages cannot absorb a foreign agent. They surround it, become excited and begin to attract new macrophages, forming granulation tissue.

The attraction of new macrophages, monocytes, lymphocytes to the localization zone of activated macrophages is associated with substances that cause positive chemotaxis. These substances are secreted by the irritated macrophages themselves. These include leukotrienes C and D, prostaglandins of the E 2 group. The influx of macrophages into the focus of inflammation is facilitated by an increase in vascular permeability. Leukotrienes, FAT, collagenase increase the permeability of microvessels. These substances either loosen the basement membrane of the capillaries or contract endothelial cells and widen the interendothelial gaps. Thus, mononuclear cells - monocytes, macrophages, lymphocytes - accumulate in the focus of chronic inflammation. The accumulation of such cells is called "granuloma".

Activated macrophages secrete biooxidants that trigger lipid peroxidation in the cell membranes of the infiltration zone. Macrophages also secrete lysosomal enzymes. Monocytes secrete their biologically active substances especially fibronectin. Thanks to fibronectin, monocytes are firmly bound to the granuloma and immobilized.

Lymphocytes secrete various lymphokines, including those that activate macrophages and sharply increase their effector

functions in the focus of chronic inflammation. Macrophages, in turn, secrete interleukin-1, which enhances the growth of lymphocytes and increases their activity.

Thus, chronic inflammation differs significantly from acute inflammation. Acute inflammation begins with alteration and impaired microcirculation, chronic with activation of macrophages. The leading cell of acute inflammation is the neutrophil, chronic - an active macrophage. Acute inflammation ends quickly, chronic inflammation flows for a long time, sometimes throughout life. Chronic inflammation flows for a long time because macrophages in the focus of inflammation have a long life cycle. They need a lot of time to go into an irritated state, in addition, new cells constantly enter the granuloma, which also slowly turn into an active state. Exacerbation in chronic inflammation is associated with the influx of fresh macrophages with high pro-inflammatory activity into the inflammation focus. Chronic inflammation often ends with sclerosis with partial or complete shutdown of organ functions.

The biological significance of inflammation.

Like any pathological process, inflammation is inherently a contradictory process. It combines both the mobilization of the body's defenses and the phenomena of damage. The body is protected from the effects of alien and harmful factors by delimiting the inflammatory focus from the whole organism. This action prevents the spread and generalization of the inflammatory process, focusing the fight against a harmful agent in one place. The inflammatory focus captures everything that is in it, absorbs toxic substances circulating in the blood. This is explained by the fact that a kind of barrier with one-sided permeability is formed around the focus. Initially, it is created due to blockage of the outgoing vessels and due to the blockade of extravascular tissue transport. Further, this barrier is finally formed due to the size. connective tissue cells between normal and diseased tissue. In the focus of inflammation, unfavorable conditions for the life of microorganisms are created. In this regard, the main role is played by phagocytes and specific antibodies, enzymes. Positive side inflammation is especially manifested in the stage of proliferation and regeneration. Inflammation is one of the ways in which immunity is formed. Second opposite side inflammation always carries elements of destruction. The fight against the damaging agent in the zone of inflammation is inevitably combined with the death of one's own cells. In some cases, alteration begins to predominate, which leads to the death of a tissue or organ. Exudation can lead to malnutrition of the tissue, its enzymatic melting, hypoxia and general intoxication. Resorption from the inflammatory focus of various toxins. substances cause intoxication. The transfer of phagocytosed bacteria by leukocytes during incomplete phagocytosis can cause the development of foci of inflammation in other parts of the body.

Principles of pathogenetic therapy for inflammation:

I. Impact on the damaging factor in order to prevent or stop primary alteration (antibiotics, immune responses)

collars, etc.)

II Pro-inflammatory therapy.

1. Local stimulating effect on the focus of inflammation (hot baths, heating pads, etc.)

2. General effect on the body (vaccine therapy, lactotherapy, autohemotherapy).

III. Anti-inflammatory therapy:

1. The use of drugs that prevent the formation and release of permeability mediators:

a) blockade of the release of lysosomal enzymes, stabilization of lysosomal membranes.

b) Suppression of glycolysis as a source of energy for the release of permeability factors.

2. The use of antagonists and inhibitors of biologically active substances.

a) kinin inhibitors.

b) Prostaglandin inhibitors.

c) Antiprotease drugs.

3. Local application vasoconstrictor drugs.

4. Local effects on many parts of the inflammatory process (cold).

5. General effect on the body ( balanced diet, healthy lifestyle life).

Pathology of the immune system. Immune tissue damage. Autoimmune diseases.

The immune system has evolved in humans as a defense mechanism against microbial infections. It provides two forms of immunity: specific And non-specific.

Nonspecific immune response provided by the following mechanisms: 1. Mechanical protection- the skin and mucous membranes form a barrier to the invasion of pathogenic pathogens.

2. Humoral defense mechanisms- fluids produced by body tissues (sweat, blood, lacrimal fluid, saliva, intestinal secretions, gastric juice, pancreatic enzymes) contain antibacterial substrates (lysozyme, polyamines, C-reactive protein, interferons).

3. Cellular defense mechanisms. Many types of cells are involved in the mechanisms of nonspecific immunity: polymorphonuclear leukocytes (neutrophilic, basophilic and eosinophilic), mononuclear phagocytes, mast cells and natural killer cells (NK).

Cells of the mononuclear phagocyte system are widely distributed in tissues. Depending on the organ affiliation, they have different names:

in the connective tissue and lymphoid system - histiocytes, in the liver Kupffer cells, in the lungs alveolar macrophages, in the brain - microglial cells, in the renal glomeruli mesangiocytes, in other tissues macrophages.

Leukocytes and macrophages are able to absorb and destroy pathogens. NK cells form a subpopulation of lymphocytes. With the help of non-specific mechanisms, they are able to destroy the cells of the host organism infected with any pathogen.

specific immune response - is manifested in the fact that an infection caused by a pathogen leads to the development of protection only against this pathogen or a closely related agent.

This immunological memory against a particular pathogen can persist throughout life and protect the body from re-infection (the basis of natural and artificial immunization).

In addition to immunological memory, an important mechanism of a specific immune response is the recognition of “self” and “foreign”. During the intrauterine development of the fetus, a stable specific immunity to its tissues occurs - this condition is called immunological tolerance.

Specific immune responses are triggered antigens. These responses appear in form of humoral and cellular reactions.

Humoral immune response expressed in synthesis antibodies that neutralize the antigen. Antibodies belong to a group of proteins referred to as immunoglobulins. Antibodies are produced by B-lymphocytes.

During immune differentiation, B-lymphocytes are transformed into plasma cells, which will be detected during the humoral immune response in the bone marrow, in the spleen, in the lymph nodes, in the foci of inflammation.

Cellular immune response does not depend on the production of antibodies and are implemented using T-lymphocytes.

Pathology of the immune system. Distinguish four main types pathological conditions immune system:

1. hypersensitivity reactions, which are mechanisms of immunological tissue damage in a number of diseases; 2. autoimmune diseases, which are immune reactions against one's own body;

3. immune deficiency syndromes, arising from a congenital or acquired defect in the normal immune response; 4. amyloidosis.

Hypersensitivity reactions (immune tissue damage). The contact of the body with the antigen leads not only to the development of a protective immune response, but also to the appearance of reactions that damage tissues.

Hypersensitivity diseases are classified on the basis of the immunological mechanisms that cause them. There are 4 types of hypersensitivity reactions:

For type I hypersensitivity reactions(anaphylactic type) the immune response is accompanied by the release of vasoactive and spasmodic substances that act on blood vessels and smooth muscles, disrupting their functions.

Itype of reactions hypersensitivity may develop locally and be systemic. Systemic reaction develops in response to intravenous administration of an antigen to which the host organism is previously sensitized.

Local reactions depend on the site of penetration of the antigen and have the character of skin edema (skin allergy, urticaria), hay fever, bronchial asthma or allergic gastroenteritis (food allergy), nasal and conjunctival discharge (allergic rhinitis and conjunctivitis). For example, with allergic rhinitis, fibro-edematous polyps form in the nasal cavity.

Type I hypersensitivity reactions go through two phases with their development. Initial response phase develops in 5-30 minutes. after contact with an allergen and is characterized by vasodilatation, an increase in their permeability, as well as spasm of smooth muscles or secretion of glands.

late phase observed after 2-8 hours without additional contact with the antigen and lasts for several days. It is characterized by intense infiltration by eosinophils, neutrophils, basophils and monocytes, as well as damage to epithelial cells of the mucous membranes.

IItype humoral antibodies are directly involved in cell damage, making them susceptible to phagocytosis or lysis.

Antibodies appear in the body that are directed against antigens located on the surface of cells or other tissue components. In this case, the antibody, reacting with the antigen, activates:

A) a membrane attack complex that “perforates” the lipid layer of cell membranes. In this variant of type II hypersensitivity, blood cells are most often damaged (blood transfusion of an incompatible donor, fetal erythroblastosis, autoimmune hemolytic anemia, thrombocytopenia, agranulocytosis).

B) causes cooperation of leukocytes and NK, lysis of target cells occurs without phagocytosis (graft rejection reaction). C) causes a violation of only the function of cells without damage, without the development of inflammation (myasthenia gravis).

For hypersensitivity reactionsIIItype(immunocomplex diseases) humoral antibodies bind antigens and activate complement. Complement fractions then attract neutrophils, which cause tissue damage.

Diseases caused by immune complexes can be generalized if immune complexes form in the blood and settle in many organs (acute serum sickness) or local associated with individual organs, such as the kidneys (glomerulonephritis), joints (arthritis), small vessels of the skin (local Arthus reaction).

For hypersensitivity reactionsIVtype tissue damage occurs, the cause of which is the pathogenic effect of sensitized lymphocytes.

1. Granulomatous inflammation(DTH reaction). With the persistence of the antigen in the areas of damage, an accumulation of sensitized lymphocytes, monocytes, macrophages, epithelioid cells occurs - a granuloma is formed.

2. Cytotoxic damage sensitized T-lymphocytes of target cells that are antigen carriers (viral infections).

transplant rejection. The graft rejection reaction is associated with the recognition by the host of the transplanted tissue as foreign. Graft rejection is a complex process during which both cellular immunity and circulating antibodies play a role.

The target of antigenic and antibody rejection are graft microvessels, which develop inflammation (vasculitis), thrombi, which leads to ischemia, necrosis, and graft rejection. Rejection reaction of a human kidney transplant - a picture of inflammation in the blood vessels (vasculitis) is visible in the kidney tissue.

Autoimmune diseases - This is a group of diseases, which are based on the development of an immune response to the body's own tissues. There are autoimmune diseases in which the action of antibodies is directed to a single organ (for example, the thyroid gland) or against cell structures and tissues of many organs (for example, against the nuclei of various cells in lupus erythematosus).

Mechanism of autoimmune diseases . A normal immune response is necessary for the recognition of self-histocompatibility antigens.

When lost immunological tolerance arises autoimmunization, that is, a pathological process, which is based on the development of immune reactions to antigens of the body's own tissues.

Distinguish three groups of autoimmune diseases:1. Organ-specific autoimmune diseases (multiple sclerosis, thyroiditis, aplastic anemia). In these diseases, the immune system produces autoantibodies and sensitized lymphocytes on unchanged antigens organs with organ specificity.

2. Non-organ-specific autoimmune diseases (systemic lupus erythematosus, systemic scleroderma, rheumatoid arthritis). In these diseases, autoimmunization develops in relation to the antigens of many organs and tissues that do not have organ specificity. 3. Intermediate autoimmune diseases (myasthenia gravis, autoimmune gastritis type A).

Characteristics of some autoimmune diseases . Hashimoto's thyroiditis(lymphomatous struma) is an autoimmune organ-specific disease caused by several autoantibodies (to thyroglobulin and to microsomes of the follicular epithelium).

Hashimoto's thyroiditis is a chronic disease that is characterized by a gradual slow enlargement of the thyroid gland with the development of hypothyroidism.

Microscopic picture- dense lymphocytic infiltration with the formation of lymphoid follicles is determined in the gland. The epithelial follicles of the gland itself are displaced, atrophy, followed by growth of connective tissue in the gland. .

scleroderma(progressive systemic sclerosis) is an organ-nonspecific disease. In this disease, the skin is most often affected, in which there is an excessive formation of collagen. The skin becomes dense and inactive. A mask-like face appears, a "pouch" around the mouth, fusion and deformation of the fingers.

Microscopically in the skin there is: atrophy of the epidermis, atrophy of the sweat and sebaceous glands, compaction and gluing of collagen fibers, cellular infiltrate of lymphocytes, plasma cells and macrophages around small sclerotic vessels and remnants of the glands.

myasthenia gravis – autoimmune disease intermediate type, in which antibodies react with acetylcholine receptors in the motor end plates of skeletal muscles, disrupting neuromuscular transmission and thus causing muscle weakness. In these patients, tumor-like hyperplasia of the thymus occurs, the lymphocytes of which are producers of autoantibodies. .

The concept of immune deficiency. AIDS. Amyloidosis.

Immune deficiency syndromes. All immunodeficiencies are divided into 1) primary, which are almost always genetically determined, and 2) secondary, associated with complications of infectious diseases, malabsorption, aging, side effects of immunosuppression, radiation, cancer chemotherapy and other autoimmune diseases.

Most immunodeficiencies are rare, and some, such as IgA deficiency, are quite common, especially in children. Typically, primary immunodeficiencies appear in children between 6 months and 2 years of age with increased susceptibility to recurrent infectious diseases.

Bruton's agammaglobulinemia associated with the X chromosome, one of the most common primary immunodeficiencies and is characterized by the absence of serum immunoglobulins. Severe recurrent infections begin at 8–9 months of age when the child stops receiving maternal immunoglobulins.

Most often, pyogenic microorganisms (staphylococci) are detected, patients suffer from recurrent conjunctivitis, pharyngitis, otitis media, bronchitis, pneumonia and skin infections. Autoimmune lesions often develop, diseases such as rheumatoid arthritis occur, as well as systemic lupus erythematosus, dermatomyositis and other autoimmune diseases.

Lymph nodes and spleen do not have reproduction centers. IN lymph nodes, spleen, bone marrow and connective tissue lack plasma cells. The palatine tonsils are particularly poorly developed or vestigial.

common variable immunodeficiency is a heterogeneous group of diseases. May be congenital or acquired. A common feature of all patients is hypogammaglobulinemia.

Clinically, the disease is manifested by recurrent infections. Histologically, hyperplasia of B-cell areas of lymphoid tissue (lymphoid follicles in the lymph nodes, spleen and intestines) is observed.

In addition to bacterial infections, these patients suffer from severe enterovirus infections, recurrent herpes, and persistent diarrhea. The frequency of autoimmune diseases is high (about 20%), including rheumatoid arthritis, pernicious and hemolytic anemia.

Isolated IgA deficiency very common. Patients suffer from sino-pulmonary infections (a combination of sinusitis and pneumonia) and diarrhea, a high frequency of respiratory tract allergies and various autoimmune diseases, especially systemic lupus erythematosus and rheumatoid arthritis.

DiGeorge Syndrome (thymus hypoplasia). Patients completely lack a cellular immune response (due to hypoplasia or absence of the thymus), develop tetany (lack of parathyroid glands) and congenital defects of the heart and large vessels.

Severe combined immunodeficiency diseases are characterized by a combined B- and T-lymphocytic defect. Sick children suffer from severe recurrent infections. Among the pathogens should be distinguished: Candida albicans, Pneumocystis carinii, Pseudomonas, as well as cytomegalovirus, varicella-zoster virus and others. Without a bone marrow transplant, death occurs in the first years of life.

Immunodeficiency with thrombocytopenia and eczema (Wiskott-Aldrich syndrome) is an X-linked disorder characterized by thrombocytopenia, eczema, susceptibility to recurrent infection, and early death. Patients often develop malignant lymphomas.

Genetic deficiency of the complement system causes increased susceptibility to infection by pathogenic bacteria. Patients develop congenital angioedema, characterized by local swelling of the affected skin and mucous membranes, recurrent neisserial (gonococcal, meningococcal) infections.

HIV INFECTION

HIV infection - long-term infectious disease caused by the human immunodeficiency virus (HIV), which has a polymorphic clinical picture with the development in the final of acquired immunodeficiency syndrome (AIDS) with total suppression of the immune system, accompanied by the development of opportunistic infections and tumors (Kaposi's sarcoma, lymphomas). The disease is always fatal.

Epidemiology. The name "AIDS" is reserved only for the final stage of the disease. The spread of HIV infection has become a pandemic. Among the sick, people aged 20-50 years predominate (the peak of the disease occurs at the age of 30-40 years). Children often get sick.

Source of infection are a sick person and a virus carrier. The highest concentration of the virus is found in blood, semen, cerebrospinal fluid, in smaller amounts the virus is found in tears, saliva, cervical and vaginal secretions of patients.

Currently proven three ways of transmission of the virus: 1) sexual (with homosexual and heterosexual contacts); 2) by parenteral administration of the virus with blood products or infected instruments; 3) from mother to child (transplacental, with milk).

HIV is unstable in the external environment, quickly inactivated by ethyl alcohol, acetone, ether, relatively resistant to ionizing radiation and ultraviolet radiation.

The pathogenesis of HIV infection. All those infected with HIV will develop the disease sooner or later. HIV infection develops over a long period (from 1 to 15 years), progresses slowly, passing through several periods (stages) that have a certain clinical and morphological expression.

1. Incubation period depends on the ways and nature of infection, the magnitude of the infectious dose, as well as on the initial state of the immune system and can last from several weeks to 10-15 years (average - 28 weeks). Antigens are determined in the blood or anti-HIV antibodies from the 6-8th week of the disease. The period of appearance of anti-HIV antibodies is called seroconversion.

During the seroconversion period, there may be a syndrome called acute HIV infection, which is manifested by symptoms varying degrees gravity. The most common are fever, weakness, headache, sore throat, myalgia, arthralgia, lymphadenopathy and maculopapular rash. The duration of the acute period of infection, as a rule, varies from 1-2 to 6 weeks.

2. Persistent generalized lymphadenopathy. Characterized by persistent (more than 3 months) increase various groups lymph nodes. It is based on follicular hyperplasia - an increase in lymphoid follicles due to a sharp increase in light centers. The duration of the stage is 3-5 years.

3. PreAIDS, or AIDS-associated complex, occurs against the background of moderate immunodeficiency. It is characterized by lymphadenopathy, fever, diarrhea, weight loss (usually up to 10%). In this period, there is a tendency to develop secondary infections - SARS, shingles, pyoderma, etc. This stage also lasts for several years.

4. Acquired immunodeficiency syndrome - AIDS. This is the fourth stage of the disease, which is characterized by the development of a detailed picture of AIDS with its characteristic opportunistic infections and tumors, which on average lasts up to 2 years. During this period, as a rule, the number of anti-HIV antibodies decreases.

Classification. The course of HIV infection, duration of stages, and clinical and morphological manifestations are extremely variable. There are 4 stages: 1. stage of incubation.

2 . Stage of primary manifestations(acute infection, asymptomatic infection, generalized lymphadenopathy).

3. Stage of secondary diseases: A- loss of less than 10% of body weight; fungal, viral, bacterial lesions of the skin and mucous membranes; shingles, repeated pharyngitis, sinusitis;

B- loss of more than 10% of body weight, unexplained diarrhea or fever lasting more than 1 month, hairy leukoplakia, pulmonary tuberculosis, repeated or persistent viral, bacterial, fungal, protozoal lesions of internal organs, recurrent or disseminated herpes zoster, localized Kaposi's sarcoma;

4. Terminal stage.

Pathological anatomy. The morphology of HIV infection consists of: 1) changes in the lymph nodes, 2) characteristic lesions of the CNS (associated with HIV), and 3) the morphology of opportunistic infections and tumors.

In the AIDS stage, follicular hyperplasia of the lymph nodes is replaced by depletion of the lymphoid tissue. The lymph nodes decrease sharply and are difficult to determine.

The specific manifestations of AIDS include HIV - encephalomyelitis with a lesion of predominantly white matter and basal ganglia. Microscopically characteristic is the formation of glial nodules, multinuclear symplasts. There are foci of softening and vacuolization of the white matter, especially the lateral and posterior horns of the spinal cord. Due to demyelination, the white matter acquires a gray tint.

For opportunistic infections AIDS is characterized by a severe relapsing course with generalization of the process and resistance to ongoing therapy.

Can be caused by protozoa (pneumocysts, toxoplasma, cryptosporidium); fungi (Candida genus, cryptococci), viruses (cytomegaloviruses, herpes viruses, some slow viruses); bacteria (Mycobacterium avium intracellulare, legionella, salmonella).

One of the most characteristic opportunistic infections is pneumocystis pneumonia . Occur edema and desquamation of cells of the alveolar epithelium, filling the alveoli with a foamy liquid.

Hypoxia develops, with the rapid progression of the disease, respiratory failure increases with the development of pulmonary edema, plethora and cell infiltration of the interalveolar septa with possible destruction. It can occur as a mixed infection with the addition of other microflora (fungi, cytomegalovirus, cocci, mycobacteria, etc.).

toxoplasma infection, arises toxoplasma encephalitis, it is characterized by foci of necrosis and abscess formation. At cryptosporidiosis the intestines are affected, colitis and enteritis develop, manifested by prolonged profuse diarrhea.

Often noted candidiasis involving the esophagus, trachea, bronchi, lungs, and cryptococcosis , process prone to dissemination.

The most common viral infection cytomegalovirus from the development of retinitis, esophagitis, gastritis, colitis, pneumonitis, hepatitis, encephalitis. Retinitis is characterized by necrotic damage to the retina.

herpetic infection long-term damage to the mucous membranes and skin is characteristic.

The most common bacterial infection mycobacterial infection , which leads to the development of a disseminated process with damage to the lymph nodes and internal organs. Tuberculosis in patients with HIV infection may occur long before the development of opportunistic infections.

Malignant tumors with HIV infection occur in 40% of cases. The most characteristic are Kaposi's sarcoma and malignant lymphomas.

Kaposi's sarcoma (multiple idiopathic hemorrhagic sarcoma) - a rare disease that usually occurs in men over 60 years of age, is characterized by a slow course.

Manifested by purple spots, plaques, nodes, usually located on the skin of the distal extremities. Ulcerations may be observed. Spontaneous involution is possible with the appearance of scars and depigmented spots at the site of the tumor.

Microscopically, the tumor consists of many newly formed chaotically located thin-walled vessels and bundles of spindle-shaped cells. Hemorrhages and accumulations of hemosiderin are often visible, it is characterized by a generalization of the process with damage to the lymph nodes, gastrointestinal tract, lungs and other internal organs.

Malignant lymphomas in HIV infection, predominantly B-cell. Burkitt's lymphoma is common. Primary lymphomas of the central nervous system, gastrointestinal tract (especially the rectoanal zone) are often observed.

Opportunistic infections and malignant tumors are so typical of HIV infection that they are called indicator diseases, or indicators of HIV infection. The presence of these diseases allows suspecting and diagnosing HIV infection.

In Russia, fungal and herpetic lesions, pneumocystis pneumonia, tuberculosis, and toxoplasmosis have been registered among opportunistic infections.

clinical options. The variety of opportunistic infections, often combined with each other, as well as with tumors, makes the clinical picture of HIV infection extremely diverse.

In this regard, some of the most typical clinical variants of HIV infection: 1) pulmonary, 2) syndrome of lesions of the central nervous system, 3) gastrointestinal syndrome, 4) fever of unknown origin.

Pulmonary variant- the most frequent. It is represented by a combination of pneumocystis pneumonia, cytomegalovirus and atypical mycobacterial infection, and Kaposi's sarcoma.

Syndrome of damage to the central nervous system includes HIV encephalitis, lesions associated with toxoplasmosis, cryptococcosis, and cytomegalovirus infection, as well as lymphoma; leads to the development of dementia.

Gastrointestinal syndrome- this is a combination of candidiasis, cytomegalovirus infection, cryptosporidiosis and atypical mycobacterial infection; accompanied by diarrhea and the development of cachexia in the final.

Fever of unknown origin: in some cases, it is possible to detect an atypical mycobacterial infection or malignant lymphoma.

Causes of death. Death occurs more often from opportunistic infections and generalization of tumors. In developed countries, 50% of patients die within 18 months from the date of diagnosis (AIDS) and 80% within 36 months. Mortality in AIDS reaches 100%.

Amyloidosis. Amyloid is a protein that is deposited between cells in various tissues and organs. Its recognition in the clinic depends solely on detection in biopsy specimens.

At light-optical study using traditional stains, amyloid looks like an amorphous, eosinophilic, hyaline-like intercellular substance, as a result of progressive accumulation and pressure of which cell atrophy develops.

To distinguish amyloid from other deposits, a histochemical method is used - painting Congo red.

Chemically, amyloid is heterogeneous. There are two main forms. They are formed with the participation of different pathogenetic mechanisms. Therefore, amyloidosis is a group of diseases, the main feature of which is the deposition of similar substances of a protein structure.

Physical nature of amyloid. On electron microscopy, amyloid consists of non-branching fibrils approximately 7.5-10 nm long. This amyloid structure is the same in all types of amyloidosis. The second component (P-component).

Chemical nature of amyloid. Approximately 95% of amyloid is made up of fibrillar protein , the remaining 5% remain on the share glycoprotein P-component.

There are two main ones: light chain amyloid (AL), which is produced by plasma cells (immunocytes) and contains immunoglobulin light chains; bound amyloid (AA) is a unique non-immunoglobulin protein synthesized by the liver from larger precursors circulating in the blood (serum-bound amyloid). AA protein is formed in secondary amyloidosis.

Scheme 19. Intercellular interaction during inflammation

Scheme 16. Cellular defense systems and kinetics of the inflammatory response

Damage (alteration) is an essential component of inflammation. This is initially what the vascular-mesenchymal reaction occurs, which is the essence of inflammation. Can alteration be considered a phase of inflammation? This issue is not unambiguously resolved. Some modern pathologists do not single out alteration as such, replacing it with microcirculation disorders and blood rheological properties. AM Chernukh in his monograph "Inflammation" (1979) calls the vascular stage the first stage of inflammation, distinguishing two phases in it. D.S. Sarkisov and V.N. Galankin (1988) consider alteration as a non-specific component of inflammation, and not always mandatory (V.N. Galankin) for the development of subsequent exudation and proliferation. In other words, the possibility of developing inflammation without damage is allowed, and the alteration in such a situation is replaced by a functional deficiency of polymorphonuclear leukocytes. This position, even conditionally admitted, excludes the understanding of inflammation as a vascular-mesenchymal reaction to damage.

Many pathologists [Ogrukov AI, 1972; Serov V.V., Spiders B.C., 1995; Cottier H., 1980] advocate the need to identify an alternative phase of inflammation, characterizing the initial processes (dystrophy, necrosis) and the release of mediators. Probably, the pathologist has every reason to preserve this phase, which has a specific morphological and biochemical expression.

■ It should be noted that the preservation of the alternative phase of the inflammatory response does not justify the allocation of an alternative form of inflammation, in which the vascular-mesenchymal reaction to damage is practically absent. Therefore, it is necessary to agree with the majority of modern pathologists that the recognition of alternative inflammation, isolated by the classical pathology of the past, contradicts the essence of the inflammatory reaction in its modern interpretation.

Damage and mediation are inseparable components of the morphogenesis of inflammation, since mediators are "born" in the damage itself (alterations).

It is customary to isolate plasma (circulating) mediators, represented primarily by the kallikrein-kinin system, the complement system and the blood coagulation system, as well as cellular (local) mediators associated with many cells: mastocytes, platelets, basophils, PMNs, macrophages, lymphocytes, fibroblasts and etc. However, both plasma and cellular mediators are closely interrelated and work during inflammation as an autocatalytic system using the principles of " feedback", "duplication", "necessary diversity" and "antagonism".

These principles of the system allow circulating mediators ensure an increase in vascular permeability and activation of PMN chemotaxis for phagocytosis, and intravascular coagulation in the vessels draining from the focus of inflammation to delimit the pathogen and the focus of inflammation itself (barrier function of the focus of inflammation). At the same time, the main stages of the vascular reaction - increased permeability, activation of PMN chemotaxis and the Hageman factor - are duplicated by several mediators. The same system principles in an autocatalytic reaction cellular mediators provide not only an increase in vascular permeability, phagocytosis and secondary destruction, but also the inclusion of an immune response to eliminate the damaging agent and damage products and, finally, tissue repair through cell proliferation and differentiation in the focus of inflammation.

The principle of duplication is most clearly expressed among cells - carriers of vasoactive substances - mast cells, basophils, platelets, and antagonistic principles - between these cells and eosinophilic leukocytes: mediators of mast cells and basophils stimulate the chemotaxis of eosinophils, while the latter are able to inactivate these mediators and phagocytize mast cell granules (Scheme 17 ). Among the cells carrying mediators of vascular permeability, an "antagonistic balance" arises, which determines the peculiarity of the morphology of the vascular phase of inflammation, especially in allergic reactions.

Cellular mediators - leukokines, monokines (interleukin-1), lymphokines (interleukin-2) and fibrokines - are local regulators of cell cooperation in the "field" of inflammation - PMN, macrophage, lymphocyte and fibroblast [Serov VV., Shekhter A.B., 1981]. In other words, cellular mediators determine the sequence and proportion of participation in inflammation of the phagocytic and immune systems, on the one hand, and the connective tissue system- with another.

Macrophage monokines should be considered as the "conductor" of the ensemble of cellular mediators (Scheme 18). Macrophages, supported by mediator autoregulation, are able to control, with the help of monokines, the differentiation of granulocytes and monocytes from stem cells, the proliferation of these cells, i.e. are regulators of phagocytosis. Macrophages not only affect the functional activity of T- and B-lymphocytes, take part in their cooperation, but also secrete the first 6 complement components, i.e. mediates the involvement of the immune system in the inflammatory response. Macrophages induce fibroblast growth and collagen synthesis, i.e. are stimulators of the final phase of the reparative reaction in inflammation. At the same time, macrophages themselves are regularly affected by lymphokines and fibrokines; are closely connected in local cellular regulation with lymphocyte and fibroblast [Serov VV, Shekhter AB, 1981; Mayansky A.N., Mayansky D.N., 1983].

Cell reception plays a huge role in local cellular regulation during inflammation. It is associated with intercellular interaction and attraction of components of immune responses to the focus of inflammation, since all effector cells of inflammation have Fc-receptors of immunoglobulins and C-receptors of complement. Become understandable inextricable connection and unequal in time conjugation of the phagocytic system, the immune system and the connective tissue system in the realization of the ultimate goal of the inflammatory response(Scheme 19).

Variants of this conjugation, depending on the characteristics of both the damaging agent and the organism responding to damage, should most likely determine the development of one or another form of inflammation. Thus, purulent inflammation (a type of exudative inflammation) probably reflects a special form of conjugation of the functionally incompetent PMN system with macrophages. At the same time, macrophages, intensively phagocytizing the decaying PMNs, become resistant to the pathogen. VE Pigarevsky (1978), who studies this special relationship between the two systems of phagocytosis, calls it resorptive cell resistance. As can be seen, it reflects the secondary failure of the phagocytic function of macrophages in the primary failure of PMN phagocytosis.

The primary and selective failure of the system of monocytic phagocytes, its dissociation from the PMN system underlie granulomatous inflammation (a type of productive inflammation). Phagocytic insufficiency of macrophages determines the formation of epithelioid and giant cells from them, which lose their phagocytic functions. Phagocytosis is replaced by delimitation, persistence of the pathogen. Incomplete phagocytosis makes the inflammatory reaction itself incomplete and imperfect. It becomes an expression of a delayed-type hypersensitivity reaction (DTH).

It is also obvious that hereditary defects in each of the defense systems, as well as the system of the connective tissue itself, make the inflammatory reaction defective both in the form of its manifestation and course, and in the possibility of realizing the ultimate goal. It suffices to recall the hereditary insufficiency of the bactericidal systems of PMN and monocytes, which is most clearly represented in chronic granulomatous disease of children, hereditary and congenital immune deficiencies and the fatality of a purulent infection developing with them, congenital insufficiency of the connective tissue and the persistence of chronic inflammation. It is impossible not to say about the hereditary deficiencies of the complement system, especially its C3 and C5 components. These deficiencies are manifested either by recurrent purulent infection or by a lupus-like syndrome. During inflammation, especially caused by various agents, both circulating in the blood and local heterologous immune complexes appear, with chronic course inflammation, they can be autologous. So, with inflammation, immunocomplex reactions occur - the most frequent among immediate-type hypersensitivity reactions (IHT).

The connection between inflammation and immune reactions in a sensitized organism has been known for a long time, since the formation of the very concept of "allergy" by C.F. Pirquet and B. Schick (1905). The same C.F. Pirquet proposed to distinguish among allergic reactions immediate (accelerated) and slow (stretched) forms. However, only after the works of R. Rossle (1914) and AI Abrikosov (1933) did the hyperergic essence of allergic inflammation become clear. They showed that hyperergic inflammation is characterized not only by pronounced exudation, but also by dystrophic and necrotic (fibrinoid necrosis) changes in the connective tissue, microthrombi in the vessels, and hemorrhages.

It took several decades of searches and discoveries of immunology and morphology in order to show that immediate and delayed allergies are based on immunopathological reactions, and the latter are represented by a kind of inflammation, which, not without reason, began to be called immune [Strukov A.I., 1979] . It is important to note that the nature of immune inflammation, i.e. the morphology of hypersensitivity reactions depends entirely on the characteristics of the immunopathological mechanism (for more details, see lecture 17 "Hypersensitivity reactions").