Antitoxic serum. Antitoxic and antibacterial serums

Anti-diphtheria serum is an effective anti-diphtheria drug that is obtained from horse blood (these animals are first immunized with diphtheria toxoid). After the whey is isolated by enzymatic hydrolysis, it is purified and concentrated.

Compound

As mentioned above, anti-diphtheria serum contains (specific immunoglobulins) extracted from equine blood serum (the animals are previously hyperimmunized with diphtheria toxoid), concentrated and purified by salt fractionation and peptic digestion.

This product is transparent, slightly opalescent, yellowish or clear liquid, without sediment.

In addition to the main ingredient, the product contains 0.1% chloroform as a preservative.

Immunobiological properties

1 ml of anti-diphtheria serum contains at least 1500 IU (international antitoxic unit of activity), which neutralizes the diphtheria bacterial toxin. The dosage of the drug depends on the form of the disease, general condition the patient and his age.

Indications

The use of antitoxic anti-diphtheria serum is justified and highly effective in the development of various forms of diphtheria in adults or children.

Release forms

Concentrated anti-diphtheria serum is packaged in 10 ml ampoules; in addition, the kit includes 1 ml ampoules that are used for intradermal tests (the serum in them is diluted 1:100). The package contains 10 ampoules.

The label of each ampoule contains the following information:

• amount of IU;
• expiration dates;
• bottle and series numbers;
• name of the drug;
• name of the institute and manufacturing plant (and their location);
• OBK number.

The same information must be applied to the packaging; in addition, it must contain information about the manufacturer (full name, address and the ministry that controls it), the name of the product in Latin, methods of use, as well as storage conditions.

Store the serum in a dark, dry place at a temperature of 3-10 degrees. A drug that has been frozen and subsequently thawed without changing physical properties, is considered suitable.

In case of turbidity, formation of sediment or foreign inclusions (fibers, flakes) that do not break up when shaken, the serum should not be used. In addition, you cannot use the product if there is no label on it or if the ampoules are damaged in any way.

Rules of application

Administration of anti-diphtheria serum is possible both subcutaneously and intramuscularly into the buttock (outer upper quadrant) or into the thigh (upper third of its anterior surface).

Before use, the serum ampoule should be carefully checked. The injection is usually carried out by a doctor, but can also be performed by nursing staff, but exclusively under the supervision of a doctor.

Administration of anti-diphtheria serum using the Bezredko method

Before using the serum, the patient’s sensitivity to horse (heterogeneous) protein should be determined, which is done using an intradermal test with serum at a dilution of 1 to 100, which comes with the main drug. This test is carried out with a syringe that has a division of 0.1 ml and a thin needle. Moreover, for each such sample, an individual needle and a separate syringe are used.

The test is performed as follows: diluted anti-diphtheria serum according to the Bezredko method (0.1 ml) is injected into the forearm (into its flexor surface) intradermally, after which the reaction is monitored for 20 minutes. A test is called negative if the diameter of the emerging papule is less than 0.9 cm and there is slight redness around it. A test is considered positive if the papule is larger than 1 cm and there is significant redness around it.

In case of a negative intradermal test, undiluted serum (0.1 ml) is injected under the skin, and if there is no reaction to it, all the required serum is used for 30 (up to 60) minutes. therapeutic dose.

If diluted serum is not available, then 0.1 ml of undiluted serum is injected under the skin of the forearm (into its flexor surface) and the reaction to it is assessed 30 minutes after the injection.

If there is no reaction, an additional volume of serum in the amount of 0.2 ml is injected under the skin and observed again, but for 1-1.5 hours. In case of a successful outcome (no reaction), the entire therapeutic dose of anti-diphtheria serum is administered.

If the intradermal test is positive or the appearance of serum is observed, therapy is used only in extreme cases (the presence of absolute indications), very carefully, with the personal participation and supervision of a doctor. In this case, use diluted serum (which is used for intradermal tests): first 0.5, then 2, and then 5 ml (the interval between injections is 20 minutes).

If a positive reaction does not occur, undiluted serum in a volume of 0.1 ml is injected subcutaneously and the patient’s condition is observed for half an hour. If there is no reaction, then an injection is performed in the amount of the entire required therapeutic dose.

If it is impossible to use anti-diphtheria serum due to the occurrence of positive reactions to any of the doses described above, a therapeutic dose of serum should be administered under anesthesia, having previously prepared syringes with 5% Ephedrine or Adrenaline (1 to 1000).

In case of development anaphylactic shock due to the administration of diphtheria serum, urgent adequate therapy: use of ephedrine or adrenaline, analeptics, glucocorticosteroids, cardiac glycosides, calcium chloride, novocaine.

Application of serum

The effectiveness of diphtheria serum directly depends on the correctly selected first and course dosage and the earliest possible use this tool after confirmation of the diagnosis.

• In the case of island localized diphtheria of the pharynx (oral segment of the pharynx), the initial dosage is 10-15 thousand IU, and the course dosage is 10-20 thousand IU.
• In the case of the filmy form: from 15 to 30 thousand (first dose), and course - up to 40 thousand IU.
• For widespread diphtheria of the pharynx, the 1st dose of serum is 30-40 thousand IU, and the course dose, respectively, is 50-60 thousand IU.
• In the case of a subtoxic form that has developed in the oral segment of the pharynx, the dosage is 40-50 thousand, and the course dose is 60-80 thousand IU.

Anti-diphtheria serum: administration algorithm for a toxic form of pathology

• 1st degree - initial dosage 50-70 thousand IU, course dosage 80-120 thousand IU;
• 2nd degree - initial dosage 60-80 thousand IU, course dosage 150-200 thousand IU;
• 3rd degree - initial (first) dose 100-200 thousand IU, course dose 250-350 thousand IU.

At toxic form The serum should be used every 12 hours for 2-3 days, and then the dose and frequency of administration are adjusted in accordance with the dynamics of the disease. Moreover, in the first few days the patient is administered 2/3 of the course dosage.

• In the case of hypertoxic diphtheria of the oral segment of the pharynx, maximum dosages of the drug are prescribed. So, 1 dose is 100-150 thousand IU, and a course dose is no more than 450 thousand IU.
• In cases of localized croup: 1 dose - 30-40 thousand IU, and a course dose of 60-80 thousand IU.
• In cases of diphtheria localized in the nasal segment of the pharynx, doses are 15-20 thousand and 20-40 thousand IU (first and course dosages, respectively).

Therapy for localized diphtheria

• In case of eye damage. The primary dosage is 10-15 thousand IU, course dosage - 15-30 thousand IU.
• Diphtheria lesions of the genital organs - 10-15 thousand IU, course - 15-30 thousand IU.
• Skin lesions: initial dose - 10 thousand IU, course dose - 10 thousand IU.
• Nasal lesions: the first dose is 10-15 thousand IU, and the course dose is 20-30 thousand IU.
• Navel lesions: the initial dose is 10 thousand IU, and the course dose is also 10 thousand IU.

The number of injections with anti-diphtheria serum is prescribed depending on the clinical form of the pathology. For example, a single administration is prescribed to patients who have localized or widespread forms of diphtheria of the oropharynx or nose.

If the plaque does not disappear within 24 hours after the serum is prescribed, then the drug is reapplied 24 hours later.

The serum is discontinued after a significant improvement in the patient’s condition (disappearance of swelling of the cervical tissue, pharynx (oral part), plaque and reduction of intoxication).

Side effects

Can be:

• immediate (appears immediately after applying the serum);
• early (4-6 days after using the drug);
• long-term (two or more weeks after injection).

The following side effects may occur: hyperthermia ( elevated temperature), skin rash, chills, disturbances in functioning of cardio-vascular system, convulsions and so on. Ongoing similar phenomena no more than a few days. Collapse is rarely possible. If such adverse effects occur, it is necessary to prescribe timely and adequate symptomatic therapy.

Antitoxic serums are obtained by immunizing horses with increasing doses of toxoids, and then with the corresponding toxins. The sera are subjected to purification and concentration using the “Diaferm-3” method, control for harmlessness and pyrogen-freeness, then titrated, i.e., the content of antitoxins in 1 ml of the drug is determined. The specific activity of sera or the amount of antibodies is measured using special methods based on the ability of sera in vitro and in vivo to neutralize the corresponding toxins and is expressed in international antitoxic units (ME) adopted by WHO. 1 ME is taken to be the minimum amount of serum that is capable of neutralizing a certain dose of toxin, expressed in standard units designated as lethal, necrotic or reactive doses, depending on the type of toxin and the titration method.

Titration of antitoxic serums can be carried out by three methods - the Ehrlich, Roemer, and Rayon methods. Titration of serums according to the Rayon method is carried out using a flocculation reaction against a known toxoid or toxin, one Lf (Limes flocculationis - flocculation threshold) of which is neutralized by one unit of diphtheria antitoxin. The primary or initial flocculation reaction occurs when the number of antigenic units of the toxoid corresponds to the number of antitoxins in the test serum. Based on the results of the primary flocculation reaction, the antitoxic units in 1 ml of the test serum are calculated. However, Ramon's method is only indicative.

Ehrlich's method. Before titrating serums using the Ehrlich method, a conditional lethal (test) dose of the toxin Lt (Limes tod) is determined. Lt is determined using a standard antitoxic serum, to a certain amount of which various volumes of toxin are added and, after keeping the mixture at room temperature (for 45 minutes), it is administered to white mice or guinea pigs. Then the animals are observed for four days. The experimental dose of toxin (Lt) is taken to be the amount of toxin that, when mixed with 1 IU of standard serum, causes the death of 50% of the experimental animals.

At the second stage of titration, a test dose of toxin is added to various dilutions of the test serum, the mixture is also kept and administered to animals. Based on the results obtained, the titer of the tested antitoxic serum is calculated.

Roemer's method. Titration of antitoxic serums according to Roemer's method is also carried out in two stages, but is more economical, since the experiment is carried out on one animal. An experimental necrotic dose of toxin - Ln (limes necrosis) is preliminarily determined by intradermal injection guinea pig varying amounts of toxin with standard serum. The necrotic dose of the toxin is taken to be the smallest amount that, when administered intradermally to a guinea pig mixed with 1/50 IU of standard anti-diphtheria serum, causes necrosis at the injection site on the 4-5th day. Then, various volumes of the test serum mixed with titrated A necrotic dose of toxin is injected intradermally into a guinea pig and based on the results, the serum titer is calculated. Anti-diphtheria serum is titrated using Roemer's method.

The following antitoxic serums are currently produced and used.

1. Anti-diphtheria serum is produced by hyperimmunizing horses with diphtheria toxoid and is used mainly for therapeutic purposes.

1 ME of standard anti-diphtheria serum is taken to be the minimum amount that neutralizes 100 Dim of standard toxin for a guinea pig weighing 250 g. 1 ml of serum must contain at least 2006 ME. The dose of administered serum depends on the severity of the disease: 5000-15000 IU for mild forms and from 30000-50000 IU for toxic ones. The serum is administered subcutaneously or intramuscularly.

2. Tetanus serum is a preparation obtained from the blood serum of horses hyperimmunized with tetanus toxoid or toxin.

For 1 ME antitetanus serum the amount of serum that neutralizes 1000 Dim of standard toxin for a guinea pig weighing 350 g is taken.

1 ml of antitetanus serum should contain at least 1500 IU.

One prophylactic dose equal to 3000 IU of tetanus antitoxin is administered subcutaneously. WITH therapeutic purpose serum is administered in significantly larger doses (100,000-200,000 IU) intramuscularly, intravenously or into the spinal canal, depending on the severity of the disease.

3. Anti-gangrenous mono- and polyvalent serums are obtained by hyperimmunizing horses with toxoids or toxins of gas gangrene pathogens (Cl. perfringens, C1.oedematiens, Cl. septicum). The dose of each type of antitoxin is 10,000 IU in 1 ml of serum.

Antigangrenous serums are used for the treatment and prevention of gas gangrene. For prophylactic purposes, the serum is administered intramuscularly, for therapeutic purposes - intravenously, very slowly, by drip.

Before establishing a bacteriological diagnosis, it is necessary to administer a mixture of monovalent serums or polyvalent serum. After determining the type of pathogen that caused gas gangrene, serum of the appropriate type is injected.

4. Antibotulinum antitoxic serums A, B, E is obtained from horses hyperimmunized with toxoids of the corresponding types, and is released in the form of monovalent sera, including 1 ampoule of each type of serum, or in the form of a polyvalent serum containing antibodies to all 3 types of clostridial botulinum toxins in an ampoule.

I ME of anti-botulinum serum is taken to be the smallest amount of it that has the ability to neutralize 10,000 Dim of toxin for mice weighing 18-20 g.

One therapeutic dose of antitoxin type A is 10,000 IU, type B is 5000 IU and type E is 10,000 IU. Antitoxins types C and F are currently not included in polyvalent serum, since diseases caused by pathogens of these types are rare.

At the first signs of the disease, the patient is administered polyvalent serum (intramuscularly or intravenously).

After establishing the type of toxin, the appropriate monovalent serum is prescribed.

For prophylactic purposes, serums are administered to people who have consumed foods that caused poisoning.

Antibacterial and antiviral serums

Antibacterial serums are obtained by hyperimmunizing horses with the corresponding killed bacteria or antigens and contain antibodies with agglutinating, lytic and opsonizing properties.

They have not found widespread use due to their low efficiency.

Antibacterial serums are non-titrated drugs, since the generally accepted unit of measurement for them is healing power re exists. Therefore, antibacterial medicinal serums are dosed in volumetric units, directly at the patient’s bedside, based on the severity of the disease.

For the purification and concentration of antibacterial sera and some antiviral sera, a method is used based on the separation of protein fractions of native sera and the isolation of active immunoglobulins ethyl alcohol at low temperatures (cold hydroalcoholic deposition method).

Among antibacterial serums (immunoglobulins), the following drugs are used:

1. Anti-anthrax globulin - contains |3 and - globulins extracted from the sera of horses hyperimmunized with anthrax bacilli. They are used for prophylaxis for people who have had contact with infected material, and for treatment immediately after diagnosis. Globulin is administered intramuscularly.

2. Antileptospirosis gamma globulin is obtained from the blood serum of oxen hyperimmunized with Leptospira pathogens for humans (L. icterohaemorrhaqia, L. qrippotyphosa, L. pomona, L. canicola, L. tarassovi).

The activity of the drug is determined in the agglutination reaction; the agglutination titer must be at least 1: 8000.

Gamma globulins are used to treat leptospirosis. The drug is dosed in volumetric units depending on the severity of the disease and is administered intramuscularly. Before administering gamma globulin, it is necessary to check the patient's sensitivity to heterogeneous bovine protein.

Antiviral sera are also obtained from the blood serum of animals immunized with vaccine strains of viruses or corresponding viruses. They produce antiviral serums purified by alcohol fractionation at low temperatures.

The following drugs are used:

1. Gamma globulin against tick-borne encephalitis contains gamma-globulin and partially beta-globulin (5-30%) fractions extracted from the serum of horses hyperimmunized with tick-borne encephalitis virus.

Gamma globulin is used for the treatment and prevention of tick-borne encephalitis, Omsk hemorrhagic fever and two-wave meningoencephalitis, administered intramuscularly.

2. Antirabies gamma globulin (heterogeneous immunoglobulin) is extracted from the blood serum of horses hyperimmunized with the fixe virus. Gammaglobulin activity should be at least 800 IU/ml.

The more correct name for the drugs is “immunoglobulins”, but for many produced serums the old name “gamma globulins” is still preserved.

Immunoglobulins (homologous)

Immunoglobulins obtained from human blood are prepared in two types - anti-measles (or normal) and targeted immunoglobulins. The advantage of these immunoglobulins over heterogeneous ones is that they are practically non-reactogenic and circulate in the body for a longer time, for 30-40 days.

Immunoglobulins are extracted from human blood serum by fractionation (according to the Cohn method) with ethyl alcohol at temperatures below zero.

Measles (or normal) immunoglobulin is obtained from donor, placental or abortion blood. Contains antibodies against the measles virus, as well as against influenza viruses, hepatitis, polio, whooping cough pathogens and some other viral and bacterial infections.

The drug is used to prevent measles, infectious hepatitis, whooping cough, poliomyelitis, meningococcal infection, etc.

To prevent measles, immunoglobulins are administered to all children over 3 months of age who have been in contact with a sick person and who have not been vaccinated with measles vaccine. Immunoglobulins are administered for prophylactic purposes to all children under 6 years of age who have been in contact with a patient with whooping cough and have not been vaccinated against this infection.

Prevention of hepatitis A with immunoglobulin is carried out in the pre-epidemic period and in epidemic foci. The drug in some cases has a protective effect or more often mitigates the clinical course of the disease. It is very important to correctly adhere to the dosage of immunoglobulin (0.02 ml per 1 kg of weight). The duration of the preventive effect of the drug is 3-6 months.

Targeted immunoglobulins are prepared from the blood serum of human volunteers who have undergone special immunization against a specific infection. Such drugs contain increased concentrations of specific antibodies and are used for medicinal purposes. Currently, immunoglobulins directed against influenza, rabies, smallpox, tick-borne encephalitis, tetanus and staphylococcal infections are being produced.

Anti-influenza gamma globulin is prepared from the blood serum of donors immunized with live influenza vaccine types A and B.

The drug is used for the treatment and prevention of influenza and is administered intramuscularly in certain doses depending on age.

2. Anti-rabies gamma globulin (immunoglobulin) is extracted from the serum of people immunized with a vaccine strain of the rabies virus. This drug is administered to people who have been bitten by rabid animals and who cannot receive heterogeneous rabies gamma globulin due to high sensitivity to equine protein. The drug is also used in the treatment of complications caused by rabies vaccinations.

3. Anti-smallpox donor immunoglobulin contains the gamma globulin fraction of the blood of donors specially revaccinated against smallpox. Blood for the preparation of immunoglobulin is taken starting from the 14-21st day after revaccination at the maximum content of virus-neutralizing antibodies (not lower than 1:4000).

The drug is used to treat complications after smallpox vaccinations and to treat the disease.

4. Human tetanus immunoglobulin is obtained from the blood serum of human donors revaccinated with tetanus toxoid.

Tetanus immunoglobulin is used for emergency prevention tetanus in unvaccinated children and adults and, if necessary, in the treatment of tetanus.

The drug can be administered alone or in combination with toxoid. Indications for emergency prophylaxis of tetanus are injuries, burns and frostbite of the second and third degrees and in a number of other cases associated with damage to the integrity of the mucous membranes and skin.

Emergency active-passive prophylaxis of tetanus for injuries has been introduced in the USSR since 1960.

5. Human anti-staphylococcal immunoglobulin is a gamma globulin fraction of the blood serum of human donors (immunized with staphylococcal toxoid) and from placental blood.

1 ml of the drug should contain 50 IU of donor immunoglobulin and 20 IU of placental immunoglobulin.

Anti-staphylococcal immunoglobulin is used to treat children and adults with various staphylococcal infections, especially in septic diseases.

Anti-staphylococcal plasma, which is the liquid part of the blood of human volunteers immunized with staphylococcal toxoid, is also used for the same purpose.

Antitoxic serums are obtained by immunizing horses with increasing doses of toxoids. In the practice of producing antitoxic serums, they widely use calcium chloride, potassium alum, Freud-type adjuvants, tapioca. Antitoxic serums are produced with a certain content of antitoxins, measured in international units (IU) adopted by WHO. 1 IU is the minimum amount of serum that can neutralize a certain dose of the toxin. The action of serums is reduced to neutralizing toxins produced by the pathogen. Titration of antitoxic serums can be carried out by three methods - Ehrlich, Roemer, Ramon. Therapeutic effect serum is the formation of a non-toxic toxin-antibody complex through direct contact between botulinum toxin freely circulating in the patient's blood and serum antibodies.

Treatment with antitoxic serum

For the prevention and treatment of botulism, anti-botulinum therapeutic and prophylactic antitoxic serums are used, produced in the form of a set of monovalent or polyvalent serums. The serum is used after mandatory determination of the patient’s sensitivity to horse protein using an intradermal test. At positive reaction serum is administered according to absolute indications under the supervision of a doctor special precautions. Sick people and all persons who consumed the product that caused poisoning are prescribed antitoxic polyvalent serum.

Active immunization is carried out with purified sorbed pentaanatoxin, which provides protection against botulinum toxins types A, B, C, O, E, and sextaanatoxin. The drugs are intended for immunization of a limited population. One therapeutic dose for antitoxins type A, C, E is 10,000 IU, type B is 5,000 IU.

At mild form- on the first day - two doses, the next day one dose, each three types serums A, B, C. A total of 2-3 doses per course of treatment. The serum is administered intravenously or intramuscularly after preliminary desensitization (Bezredko method). When administering serum intravenously, it is necessary to mix it with 250 ml of physiological solution heated to 37 ° C.

At average severe form-- on the first day, 4 doses of each type of serum are administered intramuscularly with an interval of 12 hours, thereafter - according to indications. The course of treatment is 10 doses.

In severe cases, 6 doses on the first day, 4-5 doses on the second. The course of treatment is 12-15 doses. Administered intramuscularly at intervals of 6-8 hours.

A test for sensitivity to a foreign protein is required, since the antitoxic serum is heterogeneous. If the test is positive, then preliminary desensitization is carried out (in the presence of a doctor), then the required dose of serum is administered under the cover of corticosteroids. Serum may cause various complications, the most dangerous of them is anaphylactic shock. Serum sickness may develop in the second week of the disease. There is an alternative to antitoxic serum - native homologous plasma (250 ml administered 1-2 times a day).

Native immune sera contain unnecessary proteins (albumin), from these sera specific proteins - immunoglobulins - are isolated and purified. Cleaning methods: precipitation with alcohol, acetone in the cold, treatment with enzymes.

Immune serums create passive specific immunity immediately after administration. Used for therapeutic and prophylactic purposes. For the treatment of toxinemic infections (tetanus, botulism, diphtheria, gas gangrene), as well as for the treatment of bacterial and viral infections (measles, rubella, plague, anthrax). For therapeutic purposes, serum preparations IM. Prophylactically: intramuscularly to persons who have had contact with the patient to create passive immunity.

No. 96 Antitoxic serums. Preparation, purification, titration. Application. Complications during use and their prevention.

Antitoxic heterogeneous serums are obtained by hyperimmunization of various animals. They are called heterogeneous because they contain whey proteins foreign to humans. More preferable is the use of homologous antitoxic serums, for the production of which the serum of people who have recovered (measles, parotid), or specially immunized donors (antitetanus, antibotulinum), serum from placental and abortive blood is used, containing antibodies to a number of pathogens of infectious diseases due to vaccination or transferred disease.

To purify and concentrate antitoxic serums, methods are used: precipitation with alcohol or acetone in the cold, enzyme treatment, affinity chromatography, ultrafiltration.

The activity of immune antitoxic serums is expressed in antitoxic units, i.e. the smallest number of antibodies that causes a visible or registered reaction with a certain number of specific antigen. The activity of antitoxic tetanus serum and the corresponding Ig is expressed in antitoxic units.

Antitoxic serums are used to treat toxinemic infections (tetanus, botulism, diphtheria, gas gangrene).

After the administration of antitoxic serums, complications in the form of anaphylactic shock and serum sickness are possible, therefore, before administering the drugs, an allergy test is performed to determine the patient’s sensitivity to them, and they are administered in fractions, according to Bezredka.

No. 97 Immunoglobulin preparations. Preparation, purification, indications for use.

Native immune sera contain unnecessary proteins (albumin), from these sera specific proteins - immunoglobulins - are isolated and purified.

Immunoglobulins and immune sera are divided into:

1. Antitoxic - sera against diphtheria, tetanus, botulism, gas gangrene, i.e. sera containing antitoxins as antibodies that neutralize specific toxins.

2. Antibacterial - sera containing agglutinins, precipitins, complement-fixing antibodies to pathogens typhoid fever, dysentery, plague, whooping cough.

3. Antiviral serums (measles, influenza, anti-rabies) contain virus-neutralizing, complement-fixing antiviral antibodies.

Purification methods: precipitation with alcohol, acetone in the cold, enzyme treatment, affinity chromatography, ultrafiltration.

The activity of immunoglobulins is expressed in antitoxic units, in titers of virus-neutralizing, hemagglutinating, agglutinating activity, i.e., the smallest amount of antibodies that causes a visible reaction with a certain amount of a specific antigen.

Immunoglobulins create passive specific immunity immediately after administration. Used for therapeutic and prophylactic purposes. For the treatment of toxinemic infections (tetanus, botulism, diphtheria, gas gangrene), as well as for the treatment of bacterial and viral infections (measles, rubella, plague, anthrax). For therapeutic purposes, serum preparations IM. Prophylactically: intramuscularly to persons who have had contact with the patient to create passive immunity.

If it is necessary to urgently create immunity, immunoglobulins containing ready-made antibodies are used to treat a developing infection.

No. 98 The concept of immunomodulators. Operating principle. Application.

Immunomodulators are substances that affect the function of the immune system, changing the activity of the immune system towards increasing (immunostimulants) or decreasing (immunosuppressants) its activity.

Exogenous immunomodulators include a large group of substances of different chemical nature and origin that have a nonspecific activating or suppressive effect on the immune system, but are foreign to the body. Antibiotics, levamisole, polysaccharides, LPS, adjuvants.

Endogenous immunomodulators are a fairly large group of oligopeptides synthesized by the body itself, its immunocompetent cells, and capable of activating the immune system by enhancing the function of immunocompetent cells. These include regulatory peptides: interleukins, interferons, thymus hormones.

Use of immunomodulators: for primary and secondary immunodeficiencies of various origins, for oncological diseases, for organ and tissue transplantation, for the treatment of immunopathological and allergic diseases, in immunoprophylaxis and treatment of infectious diseases.

Drugs have been created that have an immunomodulatory effect: interferon, leukoferon, viferon.

No. 99 Interferons. Nature, methods of production. Application.

Interferons- glycoproteins produced by cells in response to viral infection and other stimuli. They block the reproduction of the virus in other cells and participate in the interaction of cells of the immune system. There are two serological groups of interferons: type I - IFN-α and IFN-β; Type II - IFN-.γ Type I interferons have antiviral and antitumor effects, while type II interferon regulates the specific immune response and nonspecific resistance.

α-interferon (leukocyte) is produced by leukocytes treated with viruses and other agents. β-interferon (fibroblast) is produced by fibroblasts treated with viruses.

Type I IFN, binding to healthy cells, protects them from viruses. The antiviral effect of type I IFN may also be due to the fact that it is able to inhibit cell proliferation by interfering with the synthesis of amino acids.

IFN-γ is produced by T lymphocytes and NK cells. Stimulates the activity of T - and B-lymphocytes, monocytes/macrophages and neutrophils. Induces apoptosis of activated macrophages, keratinocytes, hepatocytes, cells bone marrow, endothelial cells and suppresses apoptosis of peripheral monocytes and herpes-infected neurons.

Genetically engineered leukocyte interferon is produced in prokaryotic systems (Escherichia coli). Biotechnology for producing leukocyte interferon includes the following steps: 1) treatment of leukocyte mass with interferon inducers; 2) isolation of a mixture of mRNA from the treated cells; 3) obtaining total complementary DNA using reverse transcriptase; 4) insertion of cDNA into the E. coli plasmid and its cloning; 5) selection of clones containing interferon genes; 6) inclusion of a strong promoter in the plasmid for successful transcription of the gene; 7) interferon gene expression, i.e. synthesis of the corresponding protein; 8) destruction of prokaryotic cells and purification of interferon using affinity chromatography.

Interferons apply for the prevention and treatment of a number of viral infections. Their effect is determined by the dose of the drug, however high doses interferon have toxic effect. Interferons are widely used for influenza and other acute respiratory diseases. The drug is effective on early stages diseases, applied topically. Interferons have therapeutic effect for hepatitis B, herpes, and also for malignant neoplasms.

No. 000 Immunotherapy and immunoprophylaxis of infectious diseases.

Immunoprophylaxis and immunotherapy are branches of immunology that study and develop methods and methods for specific prevention, treatment and diagnosis of infectious and non-infectious diseases using immunobiological preparations, affecting the function of the immune system, or whose action is based on immunological principles.

Immunoprophylaxis is aimed at creating active or passive immunity to the causative agent of an infectious disease, its antigen in order to prevent a possible disease by creating immunity to them in the body.

Immunotherapy is aimed at treating an already developed disease, which is based on a dysfunction of the immune system.

Immunoprophylaxis and immunotherapy are used when necessary:

a) form, create specific immunity, activate the activity of the immune system;

b) suppress the activity of parts of the immune system;

c) normalize the functioning of the immune system.

Immunoprophylaxis and immunotherapy are used in the prevention and treatment of infectious diseases, allergies, immunopathological conditions, in oncology, transplantology, and for primary and secondary immunodeficiencies.

In the treatment of toxinemic infections (botulism, tetanus), serotherapy, i.e., the use of antitoxic serums, and immunoglobulin is important.

Immunocytokines are used in the treatment of oncological diseases.

For all this - immunobiological drugs.

No. 000 Methods for microbiological diagnosis of infectious diseases

Microbiological (bacteriological, mycological, virological) methods are based on the isolation of a pure culture of the pathogen and its subsequent identification based on morphological, cultural, biochemical, antigenic (serological) and other characteristics. Having a pure culture of bacteria, it is possible to determine their genus and species, pathogenicity factors, as well as sensitivity to antibiotics and chemotherapeutic drugs.

Mycological studies are carried out less frequently than bacteriological studies, since microscopic diagnosis of mycoses is quite reliable. Mycological studies are carried out in the diagnosis of candidiasis by determining the increase in the number of cells of yeast-like fungi of the genus Candida, as well as deep mycoses.

The virological method is the most reliable in diagnosing viral infections. However, its labor intensity associated with the preparation of cell culture, processing of the studied material, as well as the relatively frequent obtaining negative results, limit the use of this method. In addition, it requires a relatively large investment of time, especially when conducting “blind” passages. In many cases, the virological method is used for retrospective diagnosis of viral infections.

All microbiological methods are of decisive importance in laboratory diagnostics; they are the most informative and reliable, especially if they are confirmed by additional serological data.

No. 000 Pathogens of typhoid fever and paratyphoid fever. Taxonomy and characteristics. Microbiological diagnostics. Specific prevention and treatment.

Typhoid fever and paratyphoid fever A and B - acute intestinal infections, characterized by damage to the intestinal lymphatic system and severe intoxication. Their causative agents are respectively Salmonella typhi, Salmonella paratyphiA And Salmonella schottmuelleri.

Taxonomic position. Causative agents of typhoid fever and paratyphoid fever A And IN belong to the department Gracilicutes, family Enterobacteriaceae, family Salmonella.

. Salmonella are small gram-negative rods with rounded ends. They are located randomly in the smears. They do not form spores, have a microcapsule, and are peritrichous.

Cultural properties. Salmonella are facultative anaerobes. The optimal temperature for growth is 37C. They grow on simple nutrient media. The selective medium for Salmonella is bile broth.

Biochemical activity salmonella is quite high, but they do not ferment lactose. S. typhi less active than paratyphoid pathogens.

Antigenic properties and classification. Salmonella have O - and H-antigens, consisting of a number of fractions. Each species has a certain set antigens. All species of Salmonella that have a common so-called group fraction of 0-antigen are combined into one group. There are currently about 65 such groups. S. typhi and some other Salmonella have Vi- antigen (a type of K-antigen), the virulence of bacteria and their resistance to phagocytosis are associated with this antigen.

Pathogenicity factors. Salmonella produces endotoxin, which has enterotropic, neurotropic and pyrogenic effects. Adhesive properties are associated with outer membrane proteins; the presence of a microcapsule determines resistance to phagocytosis.

Resistance. Salmonella is quite resistant to low temperatures. Very sensitive to disinfectants high temperature, ultraviolet rays. IN food products(meat, milk) salmonella can not only persist for a long time, but also multiply.

Epidemiology. Typhoid and paratyphoid fever A- anthroponotic infections; The source of the disease is sick people and bacteria carriers. Source of paratyphoid IN there may also be farm animals. The mechanism of infection is fecal-oral. The predominant mode of transmission is water.

Pathogenesis. Pathogens enter the body through the mouth and reach small intestine, where they multiply in its lymphatic formations and then enter the blood (bacteremia stage). With the bloodstream, they spread throughout the body, penetrating into parenchymal organs (spleen, liver, kidneys, bone marrow). When bacteria die, endotoxin is released, causing intoxication. From the gallbladder, where S. can persist for a long time, they again enter the same lymphatic formations of the small intestine. As a result of repeated intake of S., an allergic reaction may develop, manifested in the form of inflammation and then necrosis lymphatic formations. Salmonella is excreted from the body in urine and feces.

Clinic. Clinically, typhoid fever and paratyphoid fever are indistinguishable. Incubation period is 12 days. The disease begins acutely: with an increase in body temperature, the appearance of weakness, fatigue; sleep and appetite are disturbed. Typhoid fever is characterized by clouding of consciousness, delirium, hallucinations, and rash. Very serious complications are perforation of the intestinal wall, peritonitis, intestinal bleeding resulting from necrosis of the lymphatic formations of the small intestine.

Immunity. After an illness, immunity is strong and long-lasting.

The main diagnostic method is bacteriological: inoculation and isolation of S. typhi from blood (hemoculture), feces (coproculture), urine (urine culture), bile, bone marrow. RIF for detection of pathogen antigen in biological fluids. Serological method detection of 0- and H-antibodies in RPGA. Bacteria carriers are identified by the detection of Vi-antibodies in the blood serum using RPHA and positive result bacteriological; excretion of the pathogen. Phagotyping is used for intraspecific identification.

Treatment. Antibiotics. Immunoantibiotic therapy.

Prevention. Sanitary and hygienic measures. Vaccination - typhoid chemical and typhoid alcohol vaccine enriched with Vi-antigen. For emergency prevention - typhoid bacteriophage.

No. 000 Pathogens of Escherichiosis. Taxonomy. Characteristic. The role of Escherichia coli in normal and pathological conditions. Microbiological diagnosis of escherichiosis.

Escherichiosis- infectious diseases caused by Escherichia coli.

There are enteral (intestinal) and parenteral escherichiosis. Enteral escherichiosis is an acute infectious disease characterized by primary damage to the gastrointestinal tract. They occur in the form of outbreaks; the causative agents are diarrheagenic strains of E. coli. Parenteral escherichiosis is a disease caused by opportunistic strains of E. coli - representatives normal microflora colon. With these diseases, damage to any organs is possible.

Taxonomic position. The causative agent - Escherichia coli - is the main representative of the genus Escherichia, family Enterobacteriaceae, belonging to the department Gracilicutes.

Morphological and tinctorial properties. E. coli are small gram-negative rods with rounded ends. In smears they are arranged randomly, do not form spores, peritrichous. Some strains have a microcapsule, pili.

Cultural properties. Escherichia coli is a facultative anaerobe, optimal. pace. for height - 37C. E. coli It is not demanding on nutrient media and grows well on simple media, giving diffuse turbidity on liquid media and forming colonies on solid media. To diagnose escherichiosis, differential diagnostic media with lactose are used - Endo, Levin.

Enzyme activity. E. coli has a large set of different enzymes. Most hallmark E. coli is its ability to ferment lactose.

Antigenic structure. Escherichia coli has somatic ABOUT-, flagellar H and surface K antigens. O-antigen has more than 170 variants, K-antigen - more than 100, H-antigen - more than 50. The structure of O-antigen determines its serogroup. Strains E. coli, having their own set of antigens (antigenic formula) are called serological variants (serovars).

According to antigenic, toxigenic properties, two biological variants are distinguished E. coli: 1) opportunistic coli; 2) “certainly” pathogenic, diarrheagenic.

Pathogenicity factors. Forms endotoxin, which has enterotropic, neurotropic and pyrogenic effects. Diarrheagenic Escherichia produces an exotoxin that causes significant damage water-salt metabolism. In addition, some strains, like the causative agents of dysentery, contain an invasive factor that promotes the penetration of bacteria into cells. The pathogenicity of diarrheagenic Escherichia is in the occurrence of hemorrhage and nephrotoxic action. To pathogenicity factors of all strains E. coli include pili and outer membrane proteins that promote adhesion, as well as a microcapsule that prevents phagocytosis.

Resistance. E. coli is characterized by higher resistance to various environmental factors; it is sensitive to disinfectants and quickly dies when boiled.

RoleE . coli . Escherichia coli is a representative of the normal microflora of the colon. It is an antagonist of pathogenic intestinal bacteria, putrefactive bacteria and fungi of the genus Candida. In addition, it is involved in the synthesis of vitamins B, E And TO, partially breaks down fiber.

Strains that live in the large intestine and are opportunistic can get beyond the gastrointestinal tract and, with a decrease in immunity and their accumulation, become the cause of various nonspecific purulent-inflammatory diseases (cystitis, cholecystitis) - parenteral escherichiosis.

Epidemiology. The source of enteric escherichiosis is sick people. Mechanism of infection - fecal-oral, transmission routes - alimentary, contact and household.

Pathogenesis. Oral cavity. It enters the small intestine and is adsorbed in epithelial cells with the help of pili and outer membrane proteins. Bacteria multiply and die, releasing endotoxin, which increases intestinal motility, causes diarrhea, fever and other symptoms of general intoxication. Produces exotoxin - severe diarrhea, vomiting and significant disruption of water-salt metabolism.

Clinic. The incubation period is 4 days. The disease begins acutely, with fever, abdominal pain, diarrhea, and vomiting. There are disturbances in sleep and appetite, headache. At hemorrhagic form Blood is found in the stool.

Immunity. After an illness, immunity is fragile and short-lived.

Microbiological diagnostics . Basic method - bacteriological. The type of pure culture is determined (gram-negative bacilli, oxidase-negative, fermenting glucose and lactose to acid and gas, forming indole, not forming hydrogen sulfide) and belonging to the serogroup, which makes it possible to distinguish opportunistic E. coli from diarrheagenic ones. Intraspecific identification, which has epidemiological significance, consists of determining the serovar using diagnostic adsorbed immune sera.

No. 000 Pathogens of intestinal yersiniosis. Taxonomy. Characteristic. Microbiological diagnostics. Treatment.

Intestinal yersiniosis- an acute infectious disease characterized by damage to the gastrointestinal tract and a tendency to generalize from various organs and systems.

The causative agent of intestinal yersiniosis is Yersinia enterocolitica.

Taxonomy. Y. xdu Yersinia.

Morphological and tinctorial properties. The pathogen is polymorphic: it can be either rod-shaped with rounded ends or ovoid with bipolar staining. Has no spores, sometimes forms a capsule. There is peritrichus. Some strains have pili. Gram-negative.

Cultural properties. Y. enterocolitica is a facultative anaerobe. Naib. favorable temp. 25C. The pathogen is unpretentious and grows on simple nutrient media.

Biochemical activity. The biochemical activity of the pathogen is high. Within the species, according to the spectrum of biological activity: indole formation, esculin utilization, Voges–Proskauer reaction, they are divided into 5 chemovars.

Main agricultural characteristics: breakdown of urea, fermentation of sucrose, absence of fermentation of rhamnose, production of ornithine decarboxylase.

Antigenic structure. O - and H-antigens, in some strains K-antigen was found. Based on the 0-antigen, more than 30 serogroups are distinguished, of which representatives of serogroups 03, 09, 05 are most often isolated from patients.

Pathogenicity factors. Forms heat-stable endotoxin. Some strains secrete a substance corresponding to an exotoxin and having an enteric and cytotoxic effect. An invasive protein and proteins that interfere with phagocytosis were also found in Yersinia. The adhesive activity of Yersinia is associated with pili and outer membrane proteins.

Resistance. Sensitive to high temperatures, sunlight, disinfectants, but very resistant to low temperatures: tolerates temperatures of -20 ° C.

Epidemiology. Sources of disease for humans are rats, mice, animals and birds. The mechanism of infection with yersiniosis is fecal-oral, the main route of transmission is nutritional: the disease can occur when consuming fruits, vegetables, milk, and meat. But contact (when people come into contact with sick animals) and water transmission routes are also possible.

Pathogenesis. The pathogen enters the body through the mouth, in lower parts small intestine attaches to the epithelium of the mucous membrane, penetrates into epithelial cells, causing inflammation. Under the influence of toxins, intestinal motility increases and diarrhea occurs. Sometimes in pathological process The appendix is ​​involved and appendicitis develops. Incomplete phagocytosis contributes to the generalization of the process. People with reduced immunity may develop sepsis with the formation of secondary purulent foci in the brain, liver and spleen.

Clinic. There are gastroenterocolitic, appendicular and septic forms. The incubation period ranges from 1 to 4 days. The disease begins acutely with an increase in body temperature to 39C, general intoxication, vomiting, abdominal pain, and diarrhea. The course is long.

Microbiological diagnostics. Bacteriological and serological research methods are used. The purpose of the bacteriological method is to identify the pathogen, determine the antibiogram, intraspecific identification (identification of serovar, biochemical variant, phagovar). The material for the bacteriological method of research is feces, cerebrospinal fluid, blood, urine, and sometimes the appendix. The material to be tested is placed in phosphate buffer and subjected to cold enrichment. Serological diagnosis carried out by staging RNGA, with a diagnostic titer of 1:160. Monitoring the increase in antibody titer over time is of important diagnostic importance.

Treatment. Etiotropic antibiotic therapy.

No. 000 Pathogens of shigellosis. Taxonomy. Characteristic. Microbiological diagnostics. Specific prevention and treatment.

Genus Shigella includes 4 types: S. dysenteriae - 12 serovars, S. flexneri- 9 serovars, S. boydii- 18 serovars, S. sonnei - 1 serovar.

Morphology. Shigella is represented by fixed rods. They do not form spores or capsules.

Cultural properties. They grow well on simple nutrient media. On dense media they form small, smooth, shiny, translucent colonies; on liquids - diffuse turbidity. The liquid enrichment medium is selenite broth. U S. sonnei S R dissociation was observed during growth on dense media.

Biochemical activity: weak; no gas formation during glucose fermentation, no hydrogen sulfide production, no lactose fermentation.

Resistance. Most unstable during external environment view S. dysenteriae. Shigella tolerates drying and low temperatures and quickly dies when heated. S. sonnei in milk they can not only survive for a long time, but also reproduce. U S. dysenteriae a transition to an uncultivated form was noted.

Antigenic structure. Somatic O-antigen, depending on the structure of which they are divided into serovars, a S. flexneri within serovars it is divided into subserovars. S. sonnei has a phase 1 antigen, which is the K antigen.

Pathogenicity factors. The ability to cause invasion with subsequent intercellular spread and reproduction in the epithelium of the large intestinal mucosa. Functioning of a large invasion plasmid, which is present in all 4 Shigella species. The invasion plasmid determines the synthesis of proteins that make up the outer membrane, which ensure the process of mucosal invasion. They produce Shiga and Shiga-like protein toxins. Endotoxin protects Shigella from the effects of low pH and bile.

Epidemiology: Diseases - shigellosis, anthroponoses with a fecal-oral transmission mechanism. Disease caused by S. dysenteriae, has a contact-household transmission route. S. flexneri- aquatic, a S. sonnei- nutritional.

Pathogenesis and clinic: Infectious diseases characterized by damage to the large intestine, with the development of colitis and intoxication.

Shigella interacts with the epithelium of the colon mucosa. By attaching to M cells with invasins, Shigella is absorbed by macrophages. The interaction of Shigella with macrophages leads to their death, resulting in the release of IL-1, which initiates inflammation in the submucosa. When Shigella dies, Shiga toxins are released, the action of which leads to the appearance of blood in the feces.

Immunity. Secretory IgA, preventing adhesion, and cytotoxic antibody-dependent activity of lymphocytes.

Microbiological diagnostics.

B actoriological: material for research - feces. For culture, purulent-blood formations are selected from the feces, which, when diagnosing the disease, are sown on lactose-containing differential nutrient solid media. If bacteria carriers are detected, stool is inoculated into selenite broth with the pathogen isolated on solid lactose-containing differential nutrient media. Lactose-negative colonies are selected from those grown on these media and identified to species and serovar, and the isolated cultures S. flexneri- to subserovars, S. sonnei - to chemovars. Used as an auxiliary serological method with the formulation of RNGA.

Treatment and prevention: For treatment - oral bacteriophage, antibiotics after determining the antibiogram; in case of dysbiosis, probiotic preparations to correct the microflora. Not specific prevention.

No. 000 Salmonella pathogens. Taxonomy. Characteristics. Microbiological diagnosis of salmonellosis. Treatment.

An acute intestinal zoonotic infection caused by Salmonella serovars, characterized by damage to the gastrointestinal tract.

Morphological properties: movable, gram “-” sticks, no capsules. They grow well on simple nutrient and bile-containing media. On dense ones - they form colonies in R- and S-forms, on liquid ones - turbidity. On lactose-containing media they form colorless colonies.

Biochemical activity: glk fermentation to acid and gas, no lactose fermentation, hydrogen sulfide production, no indole formation.

Antigenic structure: somatic O-antigen, flagellar H-antigen, Some - K-antigen. Genus Salmonella consists of two types - type S. enterica, which includes all Salmonella that are pathogens of humans and warm-blooded animals, and the species S. bongori, which is divided into 10 serovars.

View S. enterica divided into 6 subspecies, which are subdivided into serovars. Some Salmonella serovars, in particular S. Typhi, have a polysaccharide Vi antigen, which is a type of K antigen.

Epidemiology. The causative agents of salmonellosis are a large group of Salmonella, included in the subspecies enterica. The most common causative agents of salmonellosis in humans are the serovars S. Typhimurium, S. Dublin, and S. Choleraesuis. The main transmission factors are meat, milk, eggs, water.

Pathogenesis and clinic. The disease occurs in the local form of gastroenteritis, the leading syndrome is diarrhea. Having invaded the mucous membrane of the small intestine through M-cells and penetrated the submucosa, Salmonella are captured by macrophages, transported by them to Peyer's patches, where they form the primary focus of infection. In this case, endotoxin and protein enterotoxin are released. Enterotoxin activates the entry of large amounts of liquid, K, and Na into the intestinal lumen. Diarrhea, vomiting.

Immunity: Unstrained, serovar-specific, mediated by secretory IgA, which prevents the process of penetration of Salmonella into the small intestinal mucosa. Antibodies can be detected in the blood.

Microbiological diagnostics. Vomit, gastric lavage, feces, bile, urine, and blood are subjected to bacteriological examination. When identifying isolated cultures, a wide range of diagnostic O - and H - sera is required.

For serological testing, RNGA and ELISA are used. Important diagnostic value has an increase in antibody titer over the course of the disease.

Treatment. Pathogenetic therapy is used aimed at normalizing water-salt metabolism. For generalized forms - etiotropic antibiotic therapy.

Salmonella group, adsorbed O- and H-agglutinating sera. They are used to identify Salmonella serogroups and serovars in an agglutination reaction.

Salmonella O- and H-monodiagnosticums They are suspensions of salmonella killed by heating (O-diagnosticums) or treatment with formaldehyde (H-diagnosticums). Used for serodiagnosis of typhoid fever.

Prevention. Specific prevention of salmonellosis in agricultural animals and birds. Nonspecific prevention - carrying out veterinary and sanitary measures.

No. 000 Pathogens of cholera. Taxonomy. Characteristic. Microbiological diagnostics. Specific prevention and treatment.

The causative agent is Vibrio cholerae, serogroups O1 and O139, characterized by toxic damage small intestine, violation of water-salt balance.

Morphological and cultural properties. The vibrio has one polarly located flagellum. Under the influence of penicillin, L-forms are formed. Gram negative, do not form spores. Facultative anaerobe. Not picky about nutrient media. Temperature optimum 37C.

On dense media, vibrios form small, round, transparent S-colonies with smooth edges. A yellowish coating forms on the slanted agar. In opaque R-colonies, bacteria become resistant to the action of bacteriophages and antibiotics and are not agglutinated by O-sera.

Biochemical properties. Active: ferment glucose, maltose, sucrose, mannitol, lactose, starch to acid. All vibrios are divided into six groups in relation to three sugars (mannose, sucrose, arabinose). The first group, which includes the true causative agents of cholera, consists of vibrios, which decompose mannose and sucrose and do not decompose arabinose: they decompose proteins to ammonia and indole. H2S is not formed.

Antigenic structure. Thermostable O-antigen and thermolabile H-antigen. N-AGs are common to a large group of Vibrios.

The causative agents of classical cholera and El Tor cholera are combined into serogroup 01. Antigens of serogroup 01 include A-, B- and C-subunits in various combinations. The combination of AB subunits is called serovar Ogawa, the combination AC is called serovar Inaba, and the combination ABC is called Gikoshima. R-form colonies lose O-AG.

Resistance. Vibrios do not tolerate drying well. They remain in water bodies and food products for a long time. El-Tor biovar is more stable in environment than classical vibrio.

Epidemiology. Acute intestinal infection with a fecal-oral transmission mechanism. The route of transmission is water, food. The source of infection is a sick person or a vibration carrier.

Pathogenicity factors. Peel adhesion ; mucinase enzyme, which thins mucus and provides access to the epithelium. Epithelial cells secrete an alkaline secretion, which, in combination with bile, is an excellent nutrient medium for the proliferation of vibrios. Toxin formation of vibrios that produce endo- and exotoxins. Exotoxin (enterotoxin) cholerogens- thermolabile protein, sensitive to proteolytic enzymes. Cholerogen contains 2 subunits: A and B. A activates intracellular adenylate cyclase, which increases the release of fluid into the intestinal lumen. Diarrhea, vomiting. Neuraminidase enzyme enhances the binding of cholera exotoxin to the epithelium of the intestinal mucosa. Endotoxin starts a cascade arachidonic acid, which triggers the synthesis of prostaglandins (E, F). They cause contraction of the smooth muscles of the small intestine and suppress the immune response, which causes diarrhea.

Therapeutic serums are obtained from the blood of animals (most often horses) that have been subjected to prolonged immunization with various microbes and their products - toxins and toxoids.

Depending on the type of immunization, sera are divided into antitoxic and antibacterial.

For immunization they choose completely healthy horses. After bloodletting, the serum separated from the clot is kept for 3 months before use.

In cases where the serum is heated at 56° for an hour, it can be consumed 2 months after the bloodletting.

Serums are a yellowish or greenish, sometimes slightly opalescent liquid, odorless or with the smell of a preservative. Serums are preserved with chloroform (no more than 0.5%), quinosol (no more than 0.05%), phenol (no more than 0.5%), tricresol (no more than 0.4%).

Serums preserved with phenol or tricresol are not used for intravenous and spinal injections.

Serums are clear or slightly opalescent at the time of preparation; later, during storage, a light sediment forms. This sediment is not a sign of spoilage; the liquid above the sediment remains clear and retains its effectiveness. The presence of sediment that does not break down when shaken, the formation of unbreakable flakes, threads, general turbidity, discoloration, and the presence of a foul odor are signs of spoilage of the whey.

Sera must be sterile and harmless in animal testing and must not contain bacterial toxins or other bacterial products.

Healing serums can also be used in purified and concentrated form. It is considered proven that serum antitoxins are associated with the pseudoglobulin fraction, and the antibodies of antibacterial serums are mainly associated with the euglobulin fraction of the serum. The method of purification and concentration of serums consists of isolating the indicated fractions (due to which unnecessary protein fractions are purified) and their subsequent dissolution in a smaller volume, thereby increasing the concentration. If salting out followed by dialysis is used to isolate the indicated serum fractions, then such sera are called dialyzed.

The benefits of these serums are: a large number of active units per 1 ml, due to which less foreign and ballast proteins are introduced into the body, causing the so-called serum phenomena. On the label of ampoules containing these serums, in addition to the information required for ordinary serum, there must be an indication that the serum is dialyzed and freed from ballast substances,

Requirements for purified and concentrated serums and to native serums are the same.

All medicinal serums are subject to mandatory state control, according to special instructions

The activity of serums is determined by the content of antitoxic, or protective, units in them.

Determination of serum activity (titration) is carried out according to standards distributed to production institutes by the Central State Scientific and Control Institute.

The minimum permissible serum activity (minimum titer) is determined by a decree of the Ministry of Health.

The serum is poured aseptically into sterilized ampoules, which are sealed.

Each ampoule must be provided with a label containing the following information: 1) the name of the institute that produced the serum; 2) date of manufacture; 3) series number; 4) name of the drug; 5) number of active units; 6) number and date of state control; 7) shelf life of the drug; 8) the amount of content in each ampoule.

Storage. Serums are stored in a place protected from light at temperatures from -2° to +10°. Sera that were subjected to a single freezing and did not change their external properties, usable. Shelf life: 2 years from the date of state control.