Immunomodulators are a group of pharmacological drugs that activate the body's immunological defenses at the cellular or humoral level. These drugs stimulate the immune system and increase the body's nonspecific resistance.

major organs of the human immune system

Immunity is a unique system of the human body that can destroy foreign substances and needs proper correction. Normally, immunocompetent cells are produced in response to the introduction of pathogenic biological agents into the body - viruses, microbes and other infectious agents. Immunodeficiency states are characterized by reduced production of these cells and are manifested by frequent morbidity. Immunomodulators are special preparations, united by a common name and a similar mechanism of action, used to prevent various ailments and strengthen the immune system.

Currently, the pharmacological industry produces a huge number of drugs that have immunostimulating, immunomodulating, immunocorrective and immunosuppressive effects. They are freely sold in the pharmacy chain. Most of them have side effects and have a negative effect on the body. Before purchasing such medicines, you should consult with your doctor.

• Immunostimulants strengthen human immunity, ensure more efficient functioning of the immune system and provoke the production of protective cellular links. Immunostimulants are harmless to people who do not have immune system disorders and exacerbations of chronic pathologies.
• Immunomodulators correct the balance of immunocompetent cells in autoimmune diseases and balance all components of the immune system, suppressing or increasing their activity.
• Immunocorrectors affect only certain structures of the immune system, normalizing their activity.
• Immunosuppressants suppress the production of immunity links in cases where its hyperactivity harms the human body.

Self-medication and inadequate intake of drugs can lead to the development of autoimmune pathology, while the body begins to perceive its own cells as foreign and fight them. Immunostimulants should be taken according to strict indications and as prescribed by the attending physician. This is especially true for children, because their immune system is fully formed only by the age of 14.

But in some cases, it is simply impossible to do without taking drugs of this group. In severe diseases with a high risk of developing serious complications, taking immunostimulants is justified even in babies and pregnant women. Most immunomodulators are low-toxic and quite effective.

The use of immunostimulants

Preliminary immunocorrection is aimed at eliminating the underlying pathology without the use of basic therapy drugs. It is prescribed to persons with diseases of the kidneys, digestive system, rheumatism, in preparation for surgical interventions.

Diseases in which immunostimulants are used:

1. congenital immunodeficiency,
2. malignant neoplasms,
3. Inflammation of viral and bacterial etiology,
4. Mycoses and protozooses,
5. Helminthiasis,
6. Renal and hepatic pathology,
7. Endocrine pathology - diabetes mellitus and other metabolic disorders,
8. Immunosuppression against the background of taking certain drugs - cytostatics, glucocorticosteroids, NSAIDs, antibiotics, antidepressants, anticoagulants,
9. Immunodeficiency due to ionizing radiation, excessive alcohol intake, severe stress,
10. Allergy,
11. Conditions after transplantation,
12. Secondary post-traumatic and post-intoxication immunodeficiency states.

The presence of signs of immune deficiency is an absolute indication for the use of immunostimulants in children. The best immunomodulator for children can only be selected by a pediatrician.

People who are most often prescribed immunomodulators:

• Children with weak immunity
• Elderly people with depleted immune systems
• People with busy lifestyles.

Treatment with immunomodulators should be under the supervision of a physician and an immunological blood test.

Classification

The list of modern immunomodulators today is very large. Depending on the origin, immunostimulants are isolated:

Self-administration of immunostimulants is rarely justified. Usually they are used as an adjunct to the main treatment of pathology. The choice of drug is determined by the characteristics of immunological disorders in the patient's body. The effectiveness of drugs is considered maximum during an exacerbation of the pathology. The duration of therapy usually varies from 1 to 9 months. The use of adequate doses of the drug and proper adherence to the treatment regimen allows immunostimulants to fully realize their therapeutic effects.

Some probiotics, cytostatics, hormones, vitamins, antibacterial drugs, immunoglobulins also have an immunomodulatory effect.

Synthetic immunostimulants

Synthetic adaptogens have an immunostimulatory effect on the body and increase its resistance to adverse factors. The main representatives of this group are "Dibazol" and "Bemitil". Due to the pronounced immunostimulating activity, the drugs have an anti-asthenic effect and help the body recover quickly after a long stay in extreme conditions.

With frequent and protracted infections, for prophylactic and therapeutic purposes, Dibazol is combined with Levamisole or Decamevit.

Endogenous immunostimulants

This group includes preparations of thymus, red bone marrow and placenta.

Thymic peptides are produced by thymus cells and regulate the immune system. They change the functions of T-lymphocytes and restore the balance of their subpopulations. After the use of endogenous immunostimulants, the number of cells in the blood is normalized, which indicates their pronounced immunomodulatory effect. Endogenous immunostimulants enhance the production of interferons and increase the activity of immunocompetent cells.

• Timalin has an immunomodulatory effect, activates regeneration and reparation processes. It stimulates cellular immunity and phagocytosis, normalizes the number of lymphocytes, increases the secretion of interferons, and restores immunological reactivity. This drug is used to treat immunodeficiency conditions that have developed against the background of acute and chronic infections, destructive processes.
• "Imunofan"- a drug widely used in cases where the human immune system cannot independently resist the disease and requires pharmacological support. It stimulates the immune system, removes toxins and free radicals from the body, and has a hepatoprotective effect.

Interferons

Interferons increase the nonspecific resistance of the human body and protect it from viral, bacterial or other antigenic attacks. The most effective drugs that have a similar effect are "Cycloferon", "Viferon", "Anaferon", "Arbidol". They contain synthesized proteins that push the body to produce its own interferons.

Natural medicines include leukocyte human interferon.

Long-term use of drugs in this group minimizes their effectiveness, inhibits a person's own immunity, which ceases to function actively. Inadequate and too prolonged use of them has a negative impact on the immunity of adults and children.

In combination with other drugs, interferons are prescribed to patients with viral infections, laryngeal papillomatosis, and cancer. They are used intranasally, orally, intramuscularly and intravenously.

Preparations of microbial origin

Medicines of this group have a direct effect on the monocyte-macrophage system. Activated blood cells begin to produce cytokines that trigger innate and adaptive immune responses. The main task of these drugs is to remove pathogenic microbes from the body.

Herbal adaptogens

Herbal adaptogens include extracts of echinacea, eleutherococcus, ginseng, lemongrass. These are "soft" immunostimulants widely used in clinical practice. Preparations from this group are prescribed to patients with immunodeficiency without a preliminary immunological examination. Adaptogens start the work of enzyme systems and biosynthetic processes, activate the nonspecific resistance of the organism.

The use of plant adaptogens for prophylactic purposes reduces the incidence of acute respiratory viral infections and, resists the development of radiation sickness, weakens the toxic effect of cytostatics.

For the prevention of a number of diseases, as well as for a speedy recovery, patients are recommended to drink ginger tea or cinnamon tea daily, take black peppercorns.

Video: about immunity - School of Dr. Komarovsky

The concept of immunomodulators . The immune system of humans and higher animals performs an important function of maintaining the constancy of the internal environment of the body, carried out by recognizing and eliminating from the body of foreign substances of an antigenic nature, both endogenously occurring (cells modified by viruses, xenobiotics, malignant cells, etc.) and exogenously penetrating (primarily microbes). This function of the immune system is carried out with the help of factors of innate and acquired (or adaptive) immunity. The former include neutrophils, monocytes/macrophages, dendritic cells, NK- and T-NK -lymphocytes; to the second - T- and B-cells, which are responsible for the cellular and humoral immune response, respectively. When the number and functional activity of cells of the immune system are disturbed, immunity diseases develop: immunodeficiencies, allergic, autoimmune and lymphoproliferative processes (the latter are not considered in this chapter), the treatment of which is carried out using a complex of immunotherapy methods, one of which is the use of immunotropic drugs.

Immunotropic drugs are drugs whose therapeutic effect is associated with their predominant (or selective ) effect on the human immune system. There are three main groups of immunotropic drugs: immunomodulators, immunostimulants and immunosuppressants.

Immunomodulators- These are drugs that restore the functions of the immune system in therapeutic doses (effective immune protection). Consequently, the immunological effect of immunomodulators depends on the initial state of the patient's immunity: these drugs reduce elevated and increase reduced immunity. In line with the name immunostimulants- these are drugs that predominantly enhance immunity, bringing low rates to normal values. Immunosuppressants are drugs that suppress the immune response. This section analyzes only those drugs that have the ability to restore immunity (immunomodulators and immunostimulants), an analysis of their classification, pharmacological action and the principles of their clinical use.

Classification of immunomodulators . In 1996, we proposed a classification of immunomodulators, according to which all drugs in this group were divided into three groups: exogenous, endogenous and chemically pure. To a certain extent, this classification coincided with that J. Hadden . Currently, keeping this principle of classification, we distinguish 7 main groups of drugs with immunomodulatory properties (Table 1). To a certain extent, this classification, like the previous one, is based on the basic principles of the functioning of the immune system. The main activators of innate and inductors of acquired immunity in humans and higher animals are the antigens of microbial cells, from which the search, study and creation of immunotropic drugs (exogenous drugs) began. The formation of the immune response occurs under the control of a number of immunoregulatory molecules. Therefore, another direction in the development of immunotropic drugs was the search, isolation and study of the complex of those substances and molecules that are synthesized in the body during the development of the immune response and which regulate it (endogenous drugs).

Immunomodulators of microbial origin can be conditionally divided into three generations. The first drug approved in the early 50s in the United States and European countries for medical use as an immunostimulant was the BCG vaccine, which has a pronounced ability to enhance both innate and acquired immunity factors. At that time, the main task in the use of BCG as an immunostimulant was the activation of antitumor immunity and the treatment of malignant diseases. It was not possible to solve this problem with the help of BCG. An exception is bladder cancer, in which intravesical administration of BCG gives a pronounced clinical effect. The microbial preparations of the first generation can also include such drugs as pyrogenal and prodigiosan, which are polysaccharides of bacterial origin. They have been widely used in clinical practice to stimulate antibacterial immunity. Currently, pyrogenal and prodigiosan are rarely used due to their high pyrogenicity and other side effects.

Microbial preparations of the second generation include lysates (Broncho-Munal*, Broncho-Vaxom*, IRS-19*, Imudon*) and ribosomes (Ribomunil*) of bacteria, which are mainly pathogens of respiratory infections: Kl. pneumoniae, Str. pneumoniae, Str. pyogenes, H. influenzae and others (*hereinafter, imported drugs approved for medical use in Russia). These drugs have a dual purpose: specific (vaccinating) and non-specific (immunostimulating). To enhance the immunostimulatory effect, one of the components of ribomunil is cell wall peptidoglycan Kl. pneumoniae . The use of extracts of bacteria and fungi as immunostimulants is approved for medical use in a number of Western European countries and in Japan: for example, picibanil - extract Str. pyogenes , biostim* - extract from Kl. pneumoniae , christine and lentinan are mushroom polysaccharides.

When studying various cellular components of BCG, it was found that muramyl dipeptide (MDP), the minimum component of the peptidoglycan of the bacterial cell wall, had the greatest immunostimulatory effect. Due to the high pyrogenicity, MDP has not found application in the clinic. But in Russia and abroad, its analogues have been synthesized that retain immunostimulating properties, but do not have pyrogenic activity. Likopid is such a drug, which can be attributed to microbial preparations of the third generation. It consists of a natural disaccharide: glucosaminylmuramyl, and a synthetic dipeptide attached to it: L-alanyl-D -isoglutamine. Such structures are present in the peptidoglycan of all known Gram-positive and Gram-negative bacteria. Muramylpeptide preparations are also being developed in a number of foreign countries. In Japan, romurtide is approved for medical use, which is a MDP to which stearic acid is attached through the amino acid lysine. The main purpose of romurtide is the restoration of leukopoiesis and immunity after radio- and chemotherapy in cancer patients.

Immunomodulators of endogenous origin can be divided into immunoregulatory peptides and cytokines. As is known, the central organs of immunity are the thymus and bone marrow, which regulate the development of the cellular and humoral immune responses, respectively. A group of Russian scientists led by Academician R.V. Petrov used these organs to isolate immunoregulatory peptides in order to create drugs that restore cellular and humoral immunity. The impetus for the creation of such drugs was the discovery of a new class of biologically active compounds - thymic peptide hormones, which include the family of thymosins, thymopoietins and serum thymic factor - thymulin. These peptides, when released into the bloodstream, affect the entire peripheral immune system, stimulating the growth and proliferation of lymphoid cells.

The ancestor of the first generation thymic preparations in Russia is taktivin, which is a complex of peptides extracted from the thymus of cattle. The preparations containing a complex of thymic peptides also include thymalin, timoptin, etc., the preparations representing thymus extracts include thystimulin *, vilozen. The advantage of taktivin is the presence of thymic hormone in it.a1-thymosin. Immunomodulators, which are peptide extracts from the thymus, are approved for medical use in a number of Western European countries: thymomulin, thymomodulin, tim-urovac.

The clinical efficacy of first-generation thymic preparations is not in doubt, but they have one drawback: they are an inseparable mixture of biologically active peptides and are rather difficult to standardize. Progress in the field of drugs of thymic origin went along the line of creating drugs of the 2nd and 3rd generation, which are synthetic analogues of natural thymus hormones: a 1-thymosin and thymopoietin, or fragments of these hormones with biological activity. The last direction turned out to be the most productive, especially in relation to thymopoietin. On the basis of one of the fragments, including the amino acid residues of the active center of thymopoietin, the drug thymopentin, which received permission for medical use in the West, and immunofan, which received permission for medical use in Russia and is a synthetic hexapeptide analog of the 32-36 thymopoietin site, were created.

Another direction in the creation of synthetic thymic preparations was the analysis of the active principles of the complex of peptides and thymus extracts. So, when studying the composition of the drug thymalin, a dipeptide consisting of tryptophan and glutamine was identified. This dipeptide had a pronounced immunotropic activity and it was the basis for the creation of a synthetic drug - thymogen, which is L-glutamyl-L-tryptophan. A synthetic drug resembling thymogen is bestim, which consists of the same amino acids. The difference between bestim and thymogen lies in the presence of the first g-peptide bond and the presence of not L -, but D-glutamine. These changes led to an increase in the specific biological activity of bestim in the test for stimulating the differentiation of bone marrow precursor lymphocytes.

The ancestor of drugs of bone marrow origin is myelopid, which is a complex of bioregulatory peptide mediators - myelopeptides (MP), with a molecular weight of 500-3000 D, produced by pig bone marrow cells. It has now been established that it contains 6 myelopeptides, each of which has a certain biological effect. It was originally assumed that bone marrow preparations would have a predominant effect on the development of humoral immunity. Subsequently, it was found that different MPs have an effect on different parts of the immune system. So, MP-1 increases the functional activity of T-helpers, MP-2 has the ability to suppress the proliferation of malignant cells and significantly reduce the ability of tumor cells to produce toxic substances, MP-3 stimulates the phagocytic activity of leukocytes, MP-4 affects the differentiation of stem cells, contributing to their faster maturation. The amino acid composition of the MP is completely deciphered, which was the basis for the development of new synthetic drugs of bone marrow origin. A drug seramil based on MP-3 with an antibacterial effect and a drug bivalen based on MP-2 with an antitumor effect were created.

The regulation of the developed immune response is carried out by cytokines - a complex complex of endogenous immunoregulatory molecules. These molecules were and are the basis for the creation of a large group of both natural and recombinant immunomodulatory drugs. The first group includes leukinferon and superlymph, the second group includes betaleykin, roncoleukin, molgramostin*. Leukinferon is a complex of cytokines of the 1st phase of the immune response in their natural ratio, which is obtained in vitro by inducing a leukomass of healthy donors with a vaccine strain of the Newcastle disease virus. The drug contains interleukin-1 (IL), IL-6, IL-8, macrophage inhibition factor (MIF), tumor necrosis factor- a(TNF), a complex of interferov- a. Superlymph is also a complex of natural cytokines produced in vitro during the induction of peripheral blood mononuclear cells in pigs with a T-mitogen - phytohemagglutinin. The drug contains IL-1, IL-2, IL-6, IL-8, TNF, MIF, transforming growth factor- b. Superlymph is intended primarily for local use and is practically the first cytokine preparation intended for local immunocorrection. Roncoleukin is a dosage form of recombinant IL-2, which is one of the central regulatory cytokines of the human immune system. The drug is obtained using methods of immune biotechnology from producer cells - a recombinant strain of non-pathogenic baker's yeast, in the genetic apparatus of which the human IL-2 gene is inserted. Betaleukin is a dosage form of recombinant IL-1 b, which plays an important role in the activation of innate immunity factors, the development of inflammation and the first stages of the immune response. The drug is obtained using methods of immune biotechnology from producer cells - a recombinant strain of Escherichia coli, in the genetic apparatus of which the human IL-1 gene is inserted. b.

To activate the activity of bone marrow cells and stimulate leukopoiesis, sodium nucleinate was approved for medical use. This preparation is a sodium salt of a nucleic acid obtained by hydrolysis and further purification from yeast. The drug contains a large number of nucleic acid precursors and promotes the growth and reproduction of almost all dividing cells. Subsequently, it was found that sodium nucleinate has the ability to stimulate factors of both innate and acquired immunity. This is quite natural, since the development of the immune response is associated with the active proliferation of T- and B-lymphocytes. Sodium nucleinate is the first drug in its group to be approved for medical use not only as a leukopoiesis stimulant, but also as an immune stimulant. Derinat, a sodium salt of native DNA isolated from sturgeon milt, polydan, a highly purified mixture of sodium salts of DNA and RNA, also obtained from sturgeon milt, and ridostin, an RNA isolated from baker's yeast, belong to this series of drugs. On the basis of nucleic acids, a number of synthetic preparations have been developed, for example, poludan - a complex of polyadenyl-uridylic acid. Conventionally, this group of drugs includes inosine pranobex * (isoprinosine) - a complex of inosine with acetylamidobenzoic acid, methyluracil and riboxin - a complex compound consisting of hypoxanthine-riboside. Abroad, some synthetic preparations of nucleic acids have permission for medical use as immunostimulants: the previously mentioned inosine pranobex and poly-AU (a double-stranded polynucleotide of adenylic and uridylic acids). All drugs from the group of nucleic acids are pronounced inducers of interferon. At the same time, it should be borne in mind that synthetic and natural preparations of nucleic acids containing precursors for DNA and RNA induce the growth and reproduction of both eukaryotic and prokaryotic cells. So, for sodium nucleinate, the possibility of stimulating the growth and reproduction of bacteria has been shown.

Currently, herbal preparations and, in particular, various derivatives of Echinacea purpurea are widely used abroad to stimulate immunity. Some of these drugs are registered in Russia as immunostimulants: Immunal*, Echinacin Liquidum*, Echinacea compositum C*, Echinacea VILAR. We believe that drugs of this kind are more appropriate to refer to food additives or adaptogens such as ginseng root, eleutoroc, pantocrine, etc. All these compounds have an immunostimulating effect to one degree or another, but they can hardly be attributed to drugs with a selective effect. on the human immune system.

The group of chemically pure immunomodulators can be divided into two subgroups: low molecular weight and high molecular weight. The former include a number of well-known drugs that additionally have immunotropic activity. The ancestor of such drugs is levamisole (decaris) - phenylimidothiazole, a well-known antihelminthic agent, which subsequently revealed pronounced immunostimulating properties. Levamisole, as well as BCG, is one of the first drugs approved for medical use in the United States and Western Europe as an immunostimulant. Close in chemical structure to levamisole is dibazole (an imidazole derivative), which has some immunostimulating properties. This is, apparently, the basis for some researchers to recommend dibazol as a prophylactic for influenza and other respiratory infections. However, the prophylactic use of this drug is unreasonable, since no placebo-controlled studies have been conducted to study the ability of dibazol to reduce the risk of developing respiratory infections. An interesting drug from this subgroup is diucifon, which was originally created as an anti-tuberculosis agent. Derivatives of sulfonic acid, which is the basis of this drug, have pronounced antimycobacterial properties. The addition of methyluracil to this acid did not reduce its antibacterial effect, but led to the appearance of immunostimulating activity in the drug. The creation of drugs that combine antimicrobial and immunostimulating properties is a very promising direction in the study of immunomodulators. Some antibiotics of the latest generation (rovomycin, rulid, etc.) have the ability to stimulate phagocytosis and induce the synthesis of certain cytokines. Another promising drug from the subgroup of low molecular weight immunomodulators is Galavit, a derivative of phthalhydrazide. A feature of this drug is the presence, in addition to immunomodulatory, pronounced anti-inflammatory properties. The subgroup of low molecular weight immunomodulators includes three synthetic oligopeptides: Gepon, Glutoxim and Alloferon. Gepon is an oligopeptide consisting of 14 amino acids: Thr -Glu -Lys -Lys -Arg -Arg -Glu -Thr -Val -Glu -Arg -Glu -Lys -Glu. A feature of this drug is the presence, in addition to immunomodulatory, pronounced antiviral properties.

High-molecular chemically pure immunomodulators obtained by targeted chemical synthesis include the drug polyoxidonium. It is an N-oxidized polyethylenepiperazine derivative with a molecular weight of about 100 kD. According to its chemical structure, polyoxidonium is close to substances of natural origin. N-oxide groups, which are the basis of the drug, are widely found in the human body, since nitrogenous compounds are metabolized through the formation of N-oxides. The drug has a wide range of pharmacological effects on the body: immunomodulatory, detoxifying, antioxidant and membrane-protective.

Drugs with pronounced immunomodulatory properties, no doubt, include interferons and interferon inducers (Table 2). We considered to separate these drugs into a separate section, since their main pharmacological property is the antiviral effect. But interferons, as an integral part of the overall cytokine network of the body, are immunoregulatory molecules that have an effect on all cells of the immune system. For example, interferon a and TNF, synthesized at the first stages of the immune response, are powerful activators of NK cells, which in turn are the main source of production of interferon- g, long before the start of its synthesis by T-lymphocytes. Many other examples of the immunomodulating action of interferons can be cited. Therefore, all interferons and interferon inducers are antiviral and immunomodulatory drugs. As noted above, nucleic acids and their various derivatives, especially poludan and ridostin, are also strong inducers of interferons.

Drugs with immunomodulatory properties include immunoglobulin preparations: human immunoglobulin, intraglobin, octagam, pentaglobin, sandoglobulin, etc. However, their main effect is substitution therapy and they belong to the group of vital drugs.

Pharmacological action of immunomodulators . When analyzing the pharmacological action of immunomodulators, it is necessary to take into account an amazing feature of the functioning of the immune system, namely, this system “works” according to the system of communicating weights, i.e. the presence of a load on one of the cups sets the whole system in motion. Therefore, regardless of the initial orientation, under the influence of an immunomodulator, the functional activity of the entire immune system as a whole eventually changes to one degree or another. An immunomodulator may have a selective effect on the corresponding component of immunity, but the final effect of its effect on the immune system will always be multifaceted. For example, substance X induces the formation of only one IL-2. But this cytokine enhances the proliferation of T-, B- and NK -cells, increases the functional activity of macrophages, NK -cells, T-killers, etc. IL-2 is no exception in this regard. All cytokines are the main regulators of immunity, mediating the action of both specific and nonspecific stimuli on the immune system, and have multiple and varied effects on the immune system. Currently, no cytokines with a strictly specific effect have been identified. Such features of the functioning of the immune system make the existence of an immunomodulator with an absolutely selective final effect on immunity practically impossible. This provision allows us to formulate the following principle:

Any immunomodulator that selectively acts on the corresponding component of immunity (phagocytosis, cellular or humoral immunity), in addition to the effect on this component of immunity, will, to one degree or another, affect all other components of the immune system.

Given this situation, however, it is possible to single out the leading directions of the pharmacological action of the main immunomodulators, which, in accordance with the presented classification, belong to various groups.

Immunomodulator - a special drug of biological, plant or synthetic origin that affects the immune system. Drugs in this category can both stimulate it (immunostimulants) and suppress it (immunosuppressors). Their use in a number of diseases can significantly speed up recovery and minimize adverse effects.

Immunostimulants and immunomodulators: differences

Immunostimulants and immunomodulators These are two groups of drugs that stimulate the immune system. In a broad sense, these drugs are identical, since they perform the same function, but still, they have differences from each other. In order to understand and remember once and for all what are the differences between immunostimulants and immunomodulators, you need to know what each of these terms implies.

Immunomodulators- these are (conditionally) "weakly neutral" drugs that simply affect the body and make their own immunity work more carefully under certain conditions (for example, with ARVI).

Immunostimulants- these are more "powerful" and "strong" drugs that are used only in cases where the human immune system suffers significantly, and its own immunity cannot cope even with minor diseases. In other words, these drugs are mainly used only in immunodeficient conditions (for example, HIV).

Classification of immunomodulators

1. Thymic - increase the number of special cells (T-cells), which largely determine the adequacy of the immune response. The latest generations of thymic preparations are synthetic analogues of thymus hormones, or the human thymus gland.

2. Bone marrow - in their composition, the so-called. myelopeptides, which have both a stimulating effect on T cells and an inhibitory effect on malignant tumor cells.<

3. Microbial. They combine two actions - vaccinating (specific) and nonspecific.

4. Cytokines are endogenous immunoregulatory molecules, the lack of which does not allow the body to adequately respond to a viral threat.

5. Nucleic acids.

6. Chemically pure immunomodulators with a wide spectrum of action - immunity stimulation, antioxidant, antitoxic. They are also capable of exerting a membrane-protective effect.

The action and use of immunomodulators and immunostimulants

Similar drugs are prescribed as part of complex therapy. This is due to the fact that they do not have a direct effect on the pathogen. The immunomodulator corrects and stimulates the body's defense reactions, allowing you to effectively fight infection. But in some cases, the immune system begins to fight against the cells of the body (autoimmune diseases) - in this case, immunosuppressants are shown that suppress the immune system. Suppressors are also used in transplantation to prevent rejection of transplanted donor organs.

The use of immunocorrectors is indicated for a variety of infections (especially chronic, venereal), allergic diseases, neoplasms, HIV. As a separate (independent) drug, they can be used as a prophylactic agent during epidemics (influenza, SARS) - for this purpose, both plant immunomodulators and synthetic complexes can be used. Of the modern and proven immunostimulants, it is worth noting "Timogen" - a unique drug that allows you to use it from the age of 6 months. The dosage of the drug is prescribed by the doctor, in accordance with the age and severity of the condition.

Immunosuppressants. Classification. Characteristics and mechanism of action of drugs. Application. Side effects.

Drugs designed to artificially suppress human immunity are called immunosuppressants, their other name is immunosuppressants. This group of drugs is usually used in organ transplant surgery.

Means that stimulate the processes of immunity (immunostimulants) are used in immunodeficiency states, chronic sluggish infections, and also in some oncological diseases.

Immunodeficiency- this is a violation of the structure and function of any link of the integral immune system, the loss of the body's ability to resist any infections and restore violations of its organs. In addition, with immunodeficiency, the process of body renewal slows down or stops altogether. At the heart of a hereditary immunodeficiency state ( primary immunological deficiency) lie genetically determined defects in the cells of the immune system. At the same time, acquired immunodeficiency ( secondary immunological deficiency) is the result of the influence of environmental factors on the cells of the immune system. The most well-studied factors of acquired immunodeficiency include radiation exposure, pharmacological agents, and acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV).

Classification of immunostimulants.

1. Synthetic: LEVAMIZOL (decaris), DIBAZOL, POLYOXIDONIUM.

2. Endogenous and their synthetic analogues:

• Preparations of thymus, red bone marrow, spleen and their synthetic analogues: TIMALIN, THYMOGEN, TAKTIVIN, IMUNOFAN, MYELOPID, SPLENIN.
• Immunoglobulins: human polyvalent immunoglobulin (INTRAGLOBIN).
• Interferons: human immune interferon-gamma, recombinant gamma interferon (GAMMAFERON, IMUKIN).

3. Preparations of microbial origin and their synthetic analogues: PRODIGIOSAN, RIBOMUNE, IMUDON, LYCOPID.

4. Herbal preparations.

1. Synthetic drugs.

Levamisole is an imidazole derivative used as an antihelminthic and immunomodulating agent. The drug regulates the differentiation of T-lymphocytes. Levamisole increases the response of T-lymphocytes to antigens.

POLYOXIDONIUM is a synthetic water-soluble polymer compound. The drug has an immunostimulating and detoxifying effect, increases the body's immune resistance against local and generalized infections. Polyoxidonium activates all factors of natural resistance: cells of the monocyte-macrophage system, neutrophils and natural killers, increasing their functional activity at initially reduced levels.

DIBAZOL. Immunostimulating activity is associated with the proliferation of mature T - and B-lymphocytes.

2. Polypeptides of endogenous origin and their analogues.

2.1. TIMALIN and TAKTIVIN are a complex of polypeptide fractions from the thymus (thymus gland) of cattle. The drugs restore the number and function of T-lymphocytes, normalize the ratio of T- and B-lymphocytes and cellular immunity reactions, enhance phagocytosis.

Indications for the use of drugs: complex therapy of diseases accompanied by a decrease in cellular immunity - acute and chronic purulent and inflammatory processes, burn disease (a set of dysfunctions of various organs and systems resulting from extensive burns), trophic ulcers, oppression of hematopoiesis and immunity after radiation and chemotherapy .

MYELOPID is obtained from the bone marrow cell culture of mammals (calves, pigs). The mechanism of action of the drug is associated with stimulation of proliferation and functional activity of B - and T-cells. Myelopid is used in the complex therapy of infectious complications after surgical interventions, injuries, osteomyelitis, nonspecific pulmonary diseases, chronic pyoderma.

IMUNOFAN is a synthetic hexapeptide. The drug stimulates the formation of interleukin-2, has a regulatory effect on the production of immune mediators (inflammation) and immunoglobulins. It is used in the treatment of immunodeficiency states.

2.2. Immunoglobulins.

Immunoglobulins are a completely unique class of immune molecules that neutralize most infectious agents and toxins in our body. The principal feature of immunoglobulins is their absolute specificity. This means that in order to neutralize each type of bacteria, viruses and toxins, the body produces its own and unique immunoglobulins in structure. Immunoglobulins (gamma globulins) are purified and concentrated preparations of whey protein fractions containing high antibody titers. An important condition for the effective use of sera and gamma globulins for the treatment and prevention of infectious diseases is their earliest possible appointment from the moment of illness or infection.

2.3. Interferons.

These are species-specific proteins produced by vertebrate cells in response to the action of inducing agents. Interferon preparations are classified according to the type of active ingredient into alpha, beta and gamma, according to the method of preparation into:

a) natural: INTERFERON ALPHA, INTERFERON BETA;

b) recombinant: INTERFERON ALPHA-2a, INTERFERON ALPHA-2b, INTERFERON BETA-lb.

Interferons have antiviral, antitumor and immunomodulatory effects. As antiviral agents, interferon preparations are most active in the treatment of herpetic eye diseases (locally in the form of drops, subconjunctival), herpes simplex with localization on the skin, mucous membranes and genitals, herpes zoster (locally in the form of an ointment), acute and chronic viral hepatitis B and C (parenterally, rectally in suppositories), in the treatment and prevention of influenza and SARS (intranasally in the form of drops).

In HIV infection, recombinant interferon preparations normalize immunological parameters, reduce the severity of the disease in more than 50% of cases.

3 . Preparations of microbial origin and their analogues.

Immunostimulants of microbial origin are:

Purified bacterial lysates (BRONCHOMUNAL, IMUDON);

Bacterial ribosomes and their combinations with membrane fractions (RIBOMUNIL);

Lipopolysaccharide complexes (PRODIGIOSAN);

Bacterial cell membrane fractions (LICOPID).

BRONCHOMUNAL and IMUDON are freeze-dried lysates of bacteria that most commonly cause respiratory tract infections. The drugs stimulate humoral and cellular immunity. Increases the number and activity of T-lymphocytes (T-helpers), natural killers, increases the concentration of IgA, IgG and IgM in the mucous membrane of the respiratory tract. Applied for infectious diseases of the respiratory tract, resistant to antibiotic therapy.

RIBOMUNIL is a complex of the most common pathogens of ENT and respiratory tract infections (Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae). Stimulates cellular and humoral immunity. The ribosomes that make up the drug contain antigens that are identical to the surface antigens of bacteria, and cause the formation of specific antibodies to these pathogens in the body. Ribomunil is used for recurrent infections of the respiratory tract (chronic bronchitis, tracheitis, pneumonia) and ENT organs (otitis media, rhinitis, sinusitis, pharyngitis, tonsillitis, etc.).

PRODIGIOSAN is a high polymer lipopolysaccharide complex isolated from the microorganism Bac. prodigiosum. The drug enhances the nonspecific and specific resistance of the organism, mainly stimulates B-lymphocytes, increasing their proliferation and differentiation into plasma cells that produce antibodies. Activates phagocytosis and killer activity of macrophages. It enhances the production of humoral immunity factors - interferons, lysozyme, especially when administered locally in inhalations. It is used in the complex therapy of diseases accompanied by a decrease in immunological reactivity: in chronic inflammatory processes, in the postoperative period, in the treatment of chronic diseases with antibiotics, in sluggishly healing wounds, and radiation therapy.

LICOPID in chemical structure is an analogue of a product of microbial origin - a semi-synthetic dipeptide - the main structural component of the bacterial cell wall. It has an immunomodulatory effect.

4. Herbal preparations.

IMMUNAL and other drugs ECHINACEI . Immunal is a stimulator of nonspecific immunity. Echinacea purpurea juice, which is part of Immunal, contains active substances of a polysaccharide nature, which stimulate bone marrow hematopoiesis, and also increase the activity of phagocytes. Indications: prevention of colds and flu; weakening of the functional state of the immune system caused by various factors (exposure to ultraviolet rays, chemotherapy drugs); long-term antibiotic therapy; chronic inflammatory diseases. Echinacea tinctures and extracts, juice and syrup are also used.

Side effects of immunostimulants:

Immunomodulators of synthetic origin - allergic reactions, soreness at the injection site (for injectable drugs)

Thymus preparations - allergic reactions; bone marrow preparations - pain at the injection site, dizziness, nausea, fever.

Immunoglobulins - allergic reactions, increase or decrease in blood pressure, fever, nausea, etc. With slow infusion, many patients tolerate these drugs well.

Interferons have different severity and frequency of adverse drug reactions, which may vary depending on the drug. In general, interferons (injectable forms) are not well tolerated by everyone and may be accompanied by a flu-like syndrome, allergic reactions, etc.

Bacterial immunomodulators - allergic reactions, nausea, diarrhea.

Plant immunomodulators - allergic reactions (Quincke's edema), skin rash, bronchospasm, lowering blood pressure.

Contraindications for immunostimulants

Autoimmune diseases such as rheumatoid arthritis;
- blood diseases;
- allergy;
- bronchial asthma;
- pregnancy;
- age up to 12 years.

IV. Consolidation.

1. What is the main function of the human immune system?

2. What is an allergy?

3. What are the types of allergic reactions?

4. How are antiallergic drugs classified?

5. What is the predominant use of drugs of the first generation? 2nd generation? 3rd generation?

6. What drugs are classified as mast cell membrane stabilizers?

7. What are mast cell membrane stabilizers used for?

8. What are the main side effects of antiallergic drugs?

9. What are the measures to help with anaphylactic shock?

10. What drugs are called immunotropic?

11. How are they classified?

12. What are the indications for the use of immunosuppressants?

13. How are immunostimulants classified?

14. What are the indications for the use of representatives of each subgroup?

15. Name the side effects of the use of immunostimulants and contraindications to their use.

V. Summing up.

The teacher makes a generalization of the topic, assesses the activities of students, draws conclusions whether the objectives of the lesson have been achieved.

VI. Homework assignment.

Orenburg State Agrarian University

Department of Microbiology

Abstract on the topic:

"Microbial immunomodulators"

Orenburg, 2010

1. Immunity and immune system.

2. Immunomodulators

1. Immunity and immune system.

Immunity is the protection of the organism from genetically alien agents of exogenous and endogenous origin, aimed at preserving and maintaining the genetic homeostasis of the organism, its structural, functional, biochemical integrity and antigenic individuality. Immunity is one of the most important characteristics for all living organisms created in the process of evolution. The principle of operation of defense mechanisms is the recognition, processing and elimination of foreign structures. Protection is carried out using two systems - nonspecific (innate, natural) and specific (acquired) immunity. These two systems represent two stages of a single process of protecting the body. Nonspecific immunity acts as the first line of defense and as its final stage, and the acquired immunity system performs intermediate functions of specific recognition and memory of a foreign agent and the activation of powerful innate immunity tools at the final stage of the process. The innate immune system operates on the basis of inflammation and phagocytosis, as well as protective proteins (complement, interferons, fibronectin, etc.). This system reacts only to corpuscular agents (microorganisms, foreign cells, etc.) and toxic substances that destroy cells and tissues, or rather , on the corpuscular products of this destruction. The second and most complex system - acquired immunity - is based on the specific functions of lymphocytes, blood cells that recognize foreign macromolecules and react to them either directly or by producing protective protein molecules (antibodies).

In addition to somatic and infectious diseases, which are widespread among people, the human body is adversely affected by social (insufficient and irrational nutrition, housing conditions, occupational hazards), environmental factors, medical measures (surgical interventions, stress, etc.), in which First of all, the immune system suffers, secondary immunodeficiencies occur. Despite the constant improvement of the methods and tactics of the ongoing basic therapy of diseases and the use of deep reserve drugs involving non-drug methods of influence, the effectiveness of treatment remains at a rather low level. Often the cause of these features in the development, course and outcome of diseases is the presence in patients of certain disorders of the immune system. Studies conducted in recent years in many countries around the world have made it possible to develop and introduce into wide clinical practice new integrated approaches to the treatment and prevention of various nosological forms of diseases using targeted immunotropic drugs, taking into account the level and degree of disorders in the immune system. An important aspect in the prevention of relapses and the treatment of diseases, as well as in the prevention of immunodeficiencies, is the combination of basic therapy with rational immunocorrection. Currently, one of the urgent tasks of immunopharmacology is the development of new drugs that combine such important characteristics as efficiency and safety of use.

2. Immunomodulators

Immunomodulators- These are drugs that, when used in therapeutic doses, restore the functions of the immune system (effective immune protection).

Immunomodulators (immunocorrectors) - a group of drugs of biological (drugs from animal organs, plant materials), microbiological and synthetic origin, with the ability to normalize immune responses.

2.1. Clinical application of immunomodulators.

The most reasonable use of immunomodulators seems to be in immunodeficiencies, manifested by increased infectious morbidity. The main target of immunomodulatory drugs are secondary immunodeficiencies, which are manifested by frequent recurrent, difficult-to-treat infectious and inflammatory diseases of all localizations and any etiology. At the heart of each chronic infectious and inflammatory process are changes in the immune system, which are one of the reasons for the persistence of this process. The study of the parameters of the immune system can not always reveal these changes. Therefore, in the presence of a chronic infectious and inflammatory process, immunomodulatory drugs can be prescribed even if the immunodiagnostic study does not reveal significant deviations in the immune status.

As a rule, in such processes, depending on the type of pathogen, the doctor prescribes antibiotics, antifungal, antiviral or other chemotherapy drugs. According to experts, in all cases when antimicrobial agents are used for secondary immunological deficiency, it is advisable to prescribe immunomodulatory drugs.

The main requirements for immunotropic drugs are:

Immunomodulatory properties;
high efficiency;
natural origin;
safety, harmlessness;
no contraindications;
lack of addiction;
no side effects;
no carcinogenic effects;
lack of induction of immunopathological reactions;
do not cause excessive sensitization and do not potentiate it with other medicines;
easily metabolized and excreted from the body;
do not interact with other drugs and
have high compatibility with them;
non-parenteral routes of administration.

At present, the main principles of immunotherapy have been developed and approved:

1. Mandatory determination of the immune status before the start of immunotherapy;
2. Determining the level and degree of damage to the immune system;
3. Monitoring the dynamics of the immune status in the process of immunotherapy;
4. The use of immunomodulators only in the presence of characteristic clinical signs and changes in the parameters of the immune status
5. Appointment of immunomodulators for preventive purposes to maintain the immune status (oncology, surgical interventions, stress, environmental, professional and other impacts)

Currently, 6 main groups of immunomodulators are distinguished by origin:

Microbial immunomodulators;

Thymic immunomodulators;
bone marrow immunomodulators;
cytokines;
nucleic acids;
chemically pure.

3. Immunomodulators of microbial origin

Immunomodulators of microbial origin can be conditionally divided into three generations. The first drug approved for medical use as an immunostimulant was the BCG vaccine, which has a pronounced ability to enhance factors of both innate and acquired immunity.

The microbial preparations of the first generation include such drugs as pyrogenal and prodigiosan, which are polysaccharides of bacterial origin.

Currently, due to pyrogenicity and other side effects, they are rarely used.

Microbial preparations of the second generation include lysates (Bronchomunal, IPC-19, Imudon, a Swiss-made drug Broncho-Vaxom, which has recently appeared on the Russian pharmaceutical market) and ribosomes (Ribomunil) of bacteria, which are mainly among the causative agents of respiratory infections Klebsiella pneumoniae, Streptococcus pneumoniae , Streptococcus pyogenes, Haemophilus influezae, etc. These drugs have a dual purpose specific (vaccinating) and nonspecific (immunostimulating).

Likopid, which can be attributed to microbial preparations of the third generation, consists of a natural disaccharide - glucosaminylmuramil and a synthetic dipeptide attached to it - L-alanyl-D-isoglutamine. In the body, the main target for immunomodulators of microbial origin are phagocytic cells. Under the influence of these drugs, the functional properties of phagocytes are enhanced (phagocytosis and intracellular killing of absorbed bacteria increase), the production of anti-inflammatory cytokines, necessary for the initiation of humoral and cellular immunity, increases. As a result, the production of antibodies may increase, the formation of antigen-specific T-helpers and T-killers may be activated.

3.1. Preparations of microbial origin.

Bifiform, bifidumbacterin, probifor, linex, acipol, kipacid, enterol, bactisubtil, bifikol, gastrofarm, acilact, bronchomunal, BCG, imudon, IRS-19, sodium nucleinate, prodigiosan, ribomunil, ruzam

Table 4The main immunomodulators of microbial origin, approved for use in Russia

A drug	Origin	Clinical indications
Broncho-munal	Bacteria lysate Str. pneumonia, H. influenzae, Klebsiella pneumonia, Kl. ozaenae, Staphylococcus aureus, Str. viridans, Str. pyogenes, M. catarrhalis	Treatment and prevention of recurrent respiratory tract infections
	Bacteria lysate L. lactis, L. acidophilus, L. helveticus, L. fermentatum, St. aureus, Kl. pneumonia, Corynobacterium pseudodiphteriticum, Fusobacterium nucleatum, candida albicans	Gingivitis, periodontitis, alveolar pyorrhea, pericoronitis, periodontal abscesses, glossitis, stomatitis, oral candidiasis
	Lizat Str. pneumonia, St. aureus, Neisseria,Kl. pneumonia, M. cataralis, H. influenzae,Acinetobacter, Enterococcus faecium, E. faecalis	Therapy and prevention of recurrent infections of the upper respiratory tract
sodium nucleinate	Nucleic acid sodium salt derived from yeast	Chronic viral and bacterial infections, leukopenia
pyrognal	Lipopolysaccharide Ps. aerogenosa	Chronic infections, some allergic processes, psoriasis, dermatoses
Prodigiosan	Lipopolysaccharide Ps. prodigisiosum	Chronic infections, non-healing wounds
Ribomunil	Ribosomes Kl. pneumonia, Str. pneumonia,Str. pyogenes, H. influenzae, peptidoglycan Kl. pneumonia	Chronic nonspecific respiratory diseases
	Waste product of thermophilic staphylococcus	Chronic nonspecific lung diseases, bronchial asthma

For more than half a century, the immunomodulatory role of Mycobacterium tuberculosis has been known. The BCG vaccine currently has no independent value as an immunomodulator. The exception is the method of immunotherapy for bladder cancer, using the BCG-Imuron vaccine. The BCG-Imuron vaccine is a live lyophilized bacteria of the BCG-1 vaccine strain. The drug is used as instillations into the bladder.

Live mycobacteria, multiplying intracellularly, lead to nonspecific stimulation of the cellular immune response. BCG-Imuron is intended for the prevention of recurrence of superficial bladder cancer after surgical removal of the tumor, as well as for the treatment of small tumors of the bladder, which cannot be removed.

Study of the mechanism of immunomodulatory action of the BCG vaccine. showed that it is reproduced with the help of the inner layer of the cell wall of Mycobacterium tuberculosis - peptidoglycan, and in the composition of peptidoglycan the active principle is muramyl dipeptide, which is part of the peptidoglycan of the cell wall of almost all known gram-positive and gram-negative bacteria. However, due to high pyrogenicity and other undesirable side effects, muramyl dipeptide itself turned out to be unsuitable for clinical use. Therefore, the search for its structural analogues began.

This is how the drug Licopid (glucosaminylmuramyl dipeptide) appeared, which, along with low pyrogenicity, has a higher immunomodulatory potential.

Licopid has an immunomodulatory effect primarily due to the activation of cells of the phagocytic system of immunity (neutrophils and macrophages). The latter, by phagocytosis, destroy pathogenic microorganisms and, at the same time, secrete mediators of natural immunity - cytokines (interleukin-1, tumor necrosis factor, colony-stimulating factor, gamma interferon), which, acting on a wide range of target cells, cause further development defensive response of the body. Ultimately, Likopid affects all three main links of immunity: phagocytosis, cellular and humoral immunity, stimulates leukopoiesis and regenerative processes.

The main indications for the appointment of licopid: chronic nonspecific lung diseases, both in the stage of exacerbation and remission; acute and chronic purulent-inflammatory processes (postoperative, post-traumatic, wound), trophic ulcers; tuberculosis; acute and chronic viral infections, especially genital and labial herpes, herpetic keratitis and keratouveitis, herpes zoster, cytomegalovirus infection; lesions of the cervix caused by the human papillomavirus; bacterial and candidal vaginitis; urogenital infections.

The advantage of licopide is its ability to be used in pediatrics, including neonatology. Likopid is used in the treatment of bacterial pneumonia in term and premature infants. Licopid is used in the complex treatment of chronic viral hepatitis in children. Since Licopid is able to stimulate the maturation of glucuronyltransferase in the liver of newborns, its effectiveness is being tested in conjugated hyperbilirubinemia in the neonatal period.

Microorganisms from exopolysaccharides of various composition microbial origin, as well as mucin produced ... and teichoic acids, known polyclonal inducers immunomodulators. Study of the anti-infective and immunostimulatory activity of L. ...