Immunodeficiencies: diagnosis and immunotherapy. Laboratory diagnosis of immunodeficiency diseases
History. A characteristic sign of immunodeficiency states is infection caused by bacteria (especially with hypogammaglobulinemia), viruses and fungi (impaired cellular immunity), and, finally, general (combined immunodeficiencies). Infectious complications can appear already in the first weeks of a child’s life, as well as at an older age. With an autosomal recessive type of inheritance, boys and girls are affected; the parents are often consanguineous. A sex-linked recessive form of immunodeficiency affects boys exclusively. Observations have shown that the disease is transmitted to the child from a clinically healthy mother.
Methods for detecting immunodeficiencies. In each specific case, it should be borne in mind that, in addition to special immunological tests for assessing T- and B-links immune system, determine disorders of phagocytosis and the complement system, which manifest themselves in a number of diseases.
Skin tests are performed primarily with bacterial antigens.
In vitro methods. Quantitative assessment of peripheral blood lymphocytes. In severe combined immunodeficiencies, the content of lymphocytes is usually reduced. However normal indicators do not exclude immunodeficiency.
T-lymphocytes: spontaneous rosette reaction with washed sheep erythrocytes (E-marker) or CD3 test. Identification of the T cell subpopulation using CD4 and CD8 markers, as well as the use of differentiation markers to determine the localization of the cell maturation block. The discrepancy between the presence of a marker and possible lymphocyte dysfunction must be taken into account.
B lymphocytes: detection of Ig, rosette formation reaction with erythrocytes sensitized by Ig and complement.
A-cells: adhesion, phagocytosis.
Functional assessment of the T-link of immunity:
Stimulation of lymphocytes (nonspecific) with mitogens PHA, ConA;
Specific stimulation with antigens of infectious agents and allogeneic antigens in a mixed culture of lymphocytes (unidirectional MLC);
Production of lymphokines (FUM, FUL); It is advisable to compare the data of RBTL and RTML, and if there are indications of circulating inhibitors, to use serum from other individuals in tests.
Assessment of the B-link of immunity. Quantitative and qualitative analysis 1. Conventional electrophoresis is not entirely suitable for detecting immunodeficiency. Immunoelectrophoresis gives only qualitative assessment 1. The most common test is radial immunodiffusion (sensitivity limit - 10 μg/ml, method error 10%). Radioimmunodiffusion (up to 100 ng/ml) and radioimmune test (1-10 ng/ml) are more sensitive.
Determination of the level of natural antibodies, for example isohemagglutinins, heterophilic antibodies to sheep and rabbit erythrocytes (without absorption!), antibodies to E. coli.
Determination of the level of antibodies to antigens of infectious agents: typhoid - paratyphoid (agglutination), Brucella (agglutination), Candida (agglutination), tetanus (hemagglutination), diphtheria (hemagglutination, PAS reaction), influenza, as well as to streptolysin, histoplasmin and blastomycin (RSK) ).
Detection of autoantibodies (antibodies to DNA, rheumatoid factor, incomplete antibodies to the Coombs reaction, antibodies to tissue antigens thyroid gland and gastric mucosa).
Evidence of immunoregulatory dysfunction. Determination of the direct effect of helper cells. Identification of immunoregulatory cells using CD4 and CD8 markers. An indicator of a disorder of the immune system is an imbalance of immunoregulatory cells.
Manifestation of cellular cytotoxicity. If immunodeficiency is suspected, it is advisable to evaluate ADCC and natural killer cell activity.
Diagnostic sensitization. Test with DNCB. 2,4-dinitro-1-chlorobenzene is used to assess cellular immunity, since almost 95% healthy individuals turn out to be sensitized after just a single contact. Antigenic properties appear after covalent binding of the drug (hapten) to the protein of the epidermis. For sensitization, 1-2 mg of DNCB (1-2% solution in acetone) is applied to the surface of the skin with an area of 3 cm2. As a result of the irritation caused, in most cases, erythema and swelling occur within 3-12 hours; after 3-4 days, these phenomena gradually disappear. Sensitization develops within 7-21 days. DNCB at a dose of 50-100 mcg (0.05-1% solution) is applied as an application to another site after 14 days. The results are taken into account after 48 hours. Redness and infiltration are noted at the site of repeated contact, and sometimes a bubble forms. In some cases positive reaction detected only by histological examination. For quantitative assessment, DNCB is applied to different doses(0.1 - 100 μg) and conduct a comparative analysis. A false positive reaction as a result of the toxic effect of the drug should be excluded (an allergic reaction is characterized by a histological picture of lymphoid infiltration). False negative reactions are sometimes noted. For a semi-quantitative assessment of the results of the DNCB test, the following scale is proposed: H-erythema, ++ erythema-4-induration, + ++bladder formation, + + + + ulceration.
Instead of DNCB, you can use 2,4-dinitro-1-fluorobenzene or the drug CCN (snail hemocyanin).
Introduction of bacterial and viral antigens. The use of live vaccines is contraindicated. For sufficiently effective stimulation, 3-4 applications with appropriate antigens should be carried out. The examination program includes the following antigens:
- diphtheria and tetanus, whooping cough: application in standard doses; Antibody levels are determined after 2 weeks (CHIK reaction, passive hemagglutination);
- (killed!) polio vaccine (1 ml IM); threefold administration within 2 weeks; Antibody levels are determined 2 weeks after the last injection (virus neutralization reaction);
Pneumococcal polysaccharide (0.1 mg IM); twice within 1 week; Antibody levels are determined 2 weeks after the last injection (precipitation);
Polyribose phosphate (0.05 mg subcutaneously); Antibody levels are determined after 2 weeks (hemagglutination);
Bacteriophages X174: this is a group of fairly strong antigens. Antigen clearance is determined by comparing the primary and secondary immune responses;
Vi antigen or E. coli (0.1 mg subcutaneously); Antibody levels are determined after 2 weeks (passive hemagglutination). Flagillin (5 μg) or snail hemocyanin are used in a similar manner.
In unvaccinated children, diphtheria, tetanus and polio antigens are primarily used. In vaccinated children, an effect is possible with small doses of these antigens. Children under 1 year of age should not be given antigens containing polysaccharides.
Day 1 - blood test: determination of Ig concentration, level of antibodies to streptococcal antigens, influenza virus, isohemagglutinins; skin tests (streptokinase, candidin, CHIC reaction);
3rd day - recording of skin tests (late reaction), immunization with antigens of typhoid or tetanus pathogens, sensitization with DNCB (with negative intradermal tests);
Day 17 - determination of antibody levels, test with DNCB.
Histological studies. The above immunological methods, as a rule, make it possible to determine the level of immune system disorders in accordance with the generally accepted classification. However, in some cases there is a need for histological analysis. Material for histological studies serve as lymph nodes, bone marrow and mucous membrane.
Lymph nodes: structural analysis of thymus-dependent and thymus-independent zones is carried out 5-7 days after local stimulation with antigen (application of diphtheria and tetanus toxoids on inside hip and groin examination lymph nodes). Lymphoid devastation in the paracortical zone is evidence of T-cell deficiency; the absence of plasma cells and germinal centers indicates a violation of the B-link of the immune system.
Bone marrow: quantitative and functional assessment plasma and lymphoid cells.
Mucosa: the number of Ig-secreting plasma cells (especially IgA) is determined, mainly in conditions associated with insufficient local antibody production.
Metabolism study. If combined immunodeficiency or a defect in the T-link of the immune system is suspected, the activity of ADA and PNF enzymes should be determined. It is advisable to detect fetoprotein when diagnosing ataxia-telangiectasia (46-2200 mg/l in 95% of patients). Transcobalamin deficiency is indicated by symptoms of megaloblastic anemia with normal concentrations B12 and normal ability to absorb B12.
Early diagnosis is of particular importance for timely recognition and taking urgent measures to prevent infectious complications. During the immunological examination of newborns, cases of morbidity in families are taken into account. The Ig level indicator is not informative, since it refers to maternal Ig. The number of lymphocytes may be normal. Diagnostic value has an indicator proliferative activity lymphocytes. The immune system is assessed in accordance with the well-known WHO program. To detect hypogammaglobulinemia, the IgM level is determined. One way prenatal diagnosis Deficiency of ADA and transco-balamin-2 serves to cultivate amnion fibroblasts. Chronic granulomatosis can be detected by fetal blood testing as early as the 20th week of pregnancy.
Immunodeficiencies is a weakened state of the human immune system, which ultimately leads to more frequent illnesses infectious diseases. In immunodeficiency, the infection is more severe than in normal people. This disease in people with immunodeficiency is also more difficult to treat.
According to their origin, immunodeficiencies are divided into primary (that is hereditary ) And secondary (that is acquired ).
The main signs of immunodeficiency of both types are chronic infectious diseases. In such conditions, infections of the upper and lower respiratory tract, skin, ENT organs, etc. occur. The manifestation of diseases, their severity and types are determined depending on what type of immunodeficiency occurs in a person. Sometimes, due to immunodeficiency, a person develops allergic reactions And .
Primary immunodeficiency
Primary immunodeficiency is a disease of the immune system that is hereditary in nature. According to medical statistics, such a defect occurs in one child in ten thousand. Primary immunodeficiency is a disease that is transmitted to children from parents. There are many forms of this condition. Some of them can openly manifest themselves almost immediately after the birth of a child, while other forms of immunodeficiency do not make themselves felt for many years. In approximately 80% of cases, by the time primary immunodeficiency is diagnosed, the patient’s age does not exceed twenty years. About 70% of cases of primary immunodeficiency are diagnosed in males, since most syndromes are directly related to X chromosome .
With primary immunodeficiency genetic defects, are divided into several groups. At humoral immunodeficiencies the body does not produce sufficiently or ; at cellular immunodeficiencies lymphocytic immunodeficiency occurs; at phagocytosis defects bacteria cannot be fully captured ; at complement system defects There is an inferiority of proteins that destroy foreign cells. In addition, there are combined immunodeficiencies , as well as a number of other immunodeficiencies in which there are problems with the main links .
In most cases, primary immunodeficiencies are conditions that persist in a person throughout his life. However, many patients whose disease was diagnosed on time and adequately treated have a normal life expectancy.
Secondary immunodeficiency
Under secondary immunodeficiency the presence of acquired diseases of the immune system should be understood. IN in this case, as with primary immunodeficiencies, we're talking about about too frequent attacks of infectious diseases due to weakened immunity. Most famous example of this type immunodeficiency is , which develops as a result . In addition, secondary immunodeficiencies occur under the influence of medicines, radiation, certain chronic diseases. Secondary immunodeficiency can be observed in patients who consult a doctor with complaints of a variety of ailments.
In general, all actions that, one way or another, weaken a person’s immune system contribute to the development of secondary immunodeficiency.
In addition, this condition occurs with nutritional deficiencies, in which there is protein-calorie malnutrition , as well as the disadvantage vitamins And microelements . In this case, deficiency has a particularly detrimental effect on the human condition. , Selena , zinc . Also at risk of immunodeficiency are people with chronic metabolic disorders resulting from liver and kidney diseases. People who have undergone serious surgery or injury are also somewhat susceptible to developing immunodeficiency.
In secondary immunodeficiencies, it is important to detect bacterial infections as early as possible and take the necessary treatment.
How does immunodeficiency manifest?
The main and in some cases the only sign of immunodeficiency is a person’s predisposition to very frequent manifestations of infectious diseases. The state of immunodeficiency is characterized by the manifestation recurrent respiratory infections . However, in this case, doctors clearly distinguish between the manifestations of immunodeficiency and the so-called sickness of children, who often contract colds from their peers.
A more characteristic sign of immunodeficiency is the manifestation of a severe bacterial infection, which is recurrent. As a rule, with its development, there is a periodic recurrence of sore throat, as well as infection of the upper respiratory tract. As a result, the patient develops chronic sinusitis , , otitis . Also characteristic feature immunodeficiency is the ease of development and subsequent progression of diseases. Thus, in patients with immunodeficiency, bronchitis very easily turns into pneumonia , appears respiratory failure And bronchiectasis .
In addition, such patients often develop infections. skin, mucous membranes of the body. So, most characteristic conditions in this case there are mouth ulcers , periodontitis , , which is resistant to treatment. In addition, patients with immunodeficiency very often develop and baldness .
A typical manifestation of this condition may also be a number of disorders digestive system, For example, , malabsorption .
In more rare cases, hematological disorders are diagnosed in immunodeficiency, e.g. leukopenia , autoimmune hemolytic anemia etc.
In some cases, seizures may also occur neurological nature: convulsions , , , vasculitis . There is evidence of an increased incidence of development stomach cancer in such patients.
Diagnosis of immunodeficiency
In the process of diagnosing an immunodeficiency state, the doctor must pay close attention to the family history. So, it is quite possible that there are frequent autoimmune diseases
, early mortality, early manifestation malignant diseases. A similar diagnosis may also be indicated adverse reaction on vaccination
. Carrying out radiation therapy
certain areas of the body may also be a prerequisite for establishing such a diagnosis.
When examining a patient, the attending physician must pay attention to his appearance. As a rule, such a person looks especially sickly, has very pale skin, and constantly suffers from general malaise. A close examination of the skin is important, since immunodeficiency often causes pyoderma , vesicular rash , eczema .
In addition, the state of immunodeficiency is characterized by other manifestations: the occurrence eye inflammation , chronic diseases ENT organs , swelling of the nostrils , chronic persistent cough .
To establish an accurate analysis, it is necessary to conduct a thorough examination of the patient. At the first stage of research, as a rule, a detailed blood test, screening tests, and determination of blood levels are prescribed. immunoglobulins . Other tests are also ordered to determine what type of infection a person has. If a patient is diagnosed with a recurrent infection, then examinations of such a patient are carried out regularly. If necessary, depending on the clinical situation, smears and subsequent microbiological studies are carried out.
Complications of immunodeficiencies
Serious infectious diseases should, first of all, be noted as frequently occurring complications of both types of immunodeficiencies. This sepsis , pneumonia , etc. In each specific case of manifestation of immunodeficiency, complications are determined individually.
Human immunodeficiency virus
The human immunodeficiency virus is usually classified as a member of the retrovirus family. Today, doctors identify two types of this virus - HIV1 And HIV2 . Their fundamental differences lie in antigenic and structural features.
The human immunodeficiency virus is not resistant to the influence of features external environment. It is destroyed by almost every substance with disinfectant properties. It is believed that this virus can be present in every biological fluid of the human body. But in the absence of blood in such a fluid, the amount of virus is not enough for infection to occur. Therefore, non-hazardous biological fluids considered saliva, sweat, tears, vomit. At the same time, in every liquid that is associated with , contains a virus in large quantities. That is why the risk of HIV transmission through sexual intercourse, as well as during breastfeeding, is very high. Therefore, the most hazardous liquids organism from the point of view of HIV infection are blood , vaginal secretions , lymph , sperm , cerebrospinal , ascitic , pericardial liquids , breast milk .
The human immunodeficiency virus, once in the body, enters target cells, which are regulators in the process of the immune response. Gradually the virus enters other cells, and pathological process happens in different systems and organs.
In the process of death of cells of the immune system, immunodeficiency appears, the symptoms of which are caused by a virus. Under its influence, a person develops diseases that are both infectious and non-infectious in nature.
The severity of the disease and the rate of its progression directly depend on the presence of infections, the genetic characteristics of the human body, his age, etc. Incubation period last from three weeks to three months.
After this, the stage of primary manifestations begins, in which the patient exhibits various clinical symptoms and antibodies are actively produced. This stage is different people may proceed in different ways. It may be asymptomatic, the presence acute infection without secondary diseases, as well as infection with secondary diseases.
As the virus enters the subclinical stage, immunodeficiency gradually increases, a person’s lymph nodes enlarge, while at the same time the rate of HIV reproduction slows down. This stage is quite long: it sometimes lasts up to twenty years, although it average duration is about six years. Later the patient develops acquired immunodeficiency syndrome .
Acquired immunodeficiency syndrome
The world first learned about acquired immunodeficiency syndrome in the mid-80s of the twentieth century. At that time, doctors discovered an unknown disease, which was characterized by the manifestation of immunodeficiency in adults. It was found that their immune deficiency manifested itself in adulthood. Consequently, this disease was then called acquired immune deficiency syndrome, or AIDS for short. Today, AIDS has spread to epidemic levels.
When a patient develops acquired immunodeficiency syndrome, his body cannot resist attacks from even relatively harmless microorganisms.
Diagnosis of HIV infection is made using special laboratory methods research. However, there are currently no drugs that effectively act on the AIDS virus.
Treatment is mainly aimed at overcoming secondary infections that develop as a result of immunodeficiency.
Doctors
Treatment of immunodeficiencies
Most important point for people diagnosed with immunodeficiency of any type, it is the maximum adherence to the principles healthy image life and avoiding infections. It is equally important to have regular dental checkups.
It is important for patients with immunodeficiency to be diagnosed in a timely manner fungal And bacterial infections , and carry out their subsequent adequate therapy.
There are conditions in which constant preventive treatment . If a person has an infection chest, then in this case it is advisable to treat with physiotherapy, as well as regular implementation of special physical exercise. Sometimes as prophylactic agents It is necessary to take drugs with antiviral effects, for example , .
In most cases, therapy for immunodeficiency is carried out using intravenous or subcutaneous administration immunoglobulins . However, it should be noted that immunoglobulin treatment is contraindicated in patients with heart failure. Today, other types of treatment for immunodeficiency are also practiced, but some of them are still at the experimental development stage.
In the process of treating primary immunodeficiency, it is important to determine in each specific case how justified the use of liquid vaccines is. In all cases, it is important for patients who have been diagnosed with primary immunodeficiency not to drink alcohol or smoke.
Immunocorrection today is carried out using several methods. This is a transplant bone marrow, the use of immunomodulators, immunoglobulins.
In the treatment of secondary immunodeficiency, general principles of care are used. This includes vaccination, infection control, and replacement therapy.
Prevention of immunodeficiencies
To prevent the occurrence primary immunodeficiencies, it is necessary to identify probable carriers of defective genes in families that have a positive history. For certain pathologies, prenatal diagnosis is possible.
Due to the hereditary nature of primary immunodeficiencies, there are currently no preventive measures for this type of disease.
As a preventative measure to prevent secondary immunodeficiencies It is important to avoid contracting HIV infection. For this it is very important to never allow unprotected sexual contacts, make sure that the ones used medical instruments sterile, etc. The risk group for HIV infection also includes drug addicts who, even with a single injection of a drug, risk contracting the virus.
List of sources
- Freidlin I.S., Smirnov V.S. Immunodeficiency states. - St. Petersburg, 2000;
- Khaitov R.M., Ignatoeva G.A., Sidorovich I.G. Immunology.- M.: Medicine. - 2000;
- Yarilin A.A. Fundamentals of immunology // M. Medicine, 1999;
- Petryaeva M.V., Chernyakhovskaya M.Yu. Formalization of knowledge about HIV/AIDS infection. Part 1. Vladivostok: Far Eastern Branch of the Russian Academy of Sciences. 2007;
- Pokrovsky V.V., Ermak T.N., Belyaeva V.V. HIV infection. Clinic, diagnosis, treatment. M.: GEOTAR-Media, 2003.
When diagnosing immunodeficiencies, two main indicators are used: the clinical condition of the individual, assessed on the basis of the diagnosis clinical diagnosis, and her condition immune status, i.e. quantitative indicators and functional activity of the immune system.
The assessment of immune status is carried out in the following main cases:
in order to confirm the clinical diagnosis and to determine the impaired immunity in various disorders of the immune system;
to assess the effectiveness of rational immunotherapy and immunoprophylaxis;
if there is a suspicion of a disorder of the immune system in practically healthy individuals under the influence of unfavorable factors of a biological, chemical or physical nature (prenosological diagnosis);
to assess the degree of impact on the immune system of the environment (natural factors and products of anthropogenic activity) and emotional stress;
when monitoring the immune status of large contingents of individuals in order to identify immunodeficiencies and predict their possible formation (ecological immunology).
Based on WHO data and accumulated clinical experience diagnostics of immunodeficiency states, RB. Petrov, Yu.M. Lopukhin, A.N. Cheredeev et al. developed a methodology for two-level assessment of immune status.
Level 1 is aimed at identifying the link(s) of the immune system with insufficiency of its (their) quantitative and/or functional parameters.
Defined parameters include:
determination of the total number of lymphocytes in peripheral blood;
determination of the number of T- and B-lymphocytes in peripheral blood;
determination of the functional activity of T- and B-lymphocytes (response to T- and B-cell mitogens, respectively);
determination of the level of immunoglobulins of classes IgM, IgG, IgA in blood serum;
characteristics of the phagocytic activity of peripheral blood leukocytes.
Level 2 analytical tests are aimed at clarifying the localization of immunodeficiency in the identified link of the immune system with immunological deficiency.
If necessary, additional assessment of allergological, immunogenetic and hormonal status individuals.
In 1988, WHO experts analyzed the information content of the used methods for assessing immune status and characterized the “correct” and “incorrect” methods for determining it. The two-level system for assessing immune status is still effective today and can be used to assess the immune status of not only humans, but also domestic animals. However, in connection with the development of immunology, the development of new and improved methods for determining the quantitative and functional parameters of the immune system, and the accumulated experience in identifying immunological deficiency, it seems that additions and individual clarifications of the methodological basis of the proposed system are necessary. R.M. Khaitov and B.V. Pinegin proposed the following modification of level 1 tests:
determination of the absolute number of leukocytes, neutrophils, lymphocytes and platelets;
determination of the absorption and bactericidal activity of leukocytes and their ability to form reactive oxygen species;
determination of the level of serum immunoglobulins of classes IgG, IgA, TgM;
determination of hemolytic activity of the complement system;
determination of the surface structures of lymphocyte subpopulations - CD3, CD4, CD8, CD19/20.
This battery of tests allows the identification of congenital immunological deficiencies, including chronic granulomatous disease and HIV infection.
For secondary immunodeficiencies, depending on clinical signs diseases, especially if sexually mature individuals have symptoms of a chronic, sluggish, recurrent infectious-inflammatory process of different localization that is difficult to adequately treat etiotropically, the following tests can be effective.
1. Phagocytosis:
- phagocytic index of neutrophils and monocytes;
- opsonic index;
- bactericidal and fungicidal properties of leukocytes;
- formation of active forms of oxygen and nitrogen;
- chemotaxis;
- expression of adhesion molecules on leukocytes.
2. Humoral immunity:
- main classes and subclasses of immunoglobulins: IgG, IgA, IgM, IgE, IgD (in mucosal secretions), IgY (Δ Fe) (in birds), IgG1, IgG2, etc.;
- antibody titers to some opportunistic microbes;
- antibody affinity and level of glycosylation of immunoglobulins;
- circulating immune complexes.
3. Complement system:
- hemolytic activity of the complement system;
- components of the complement system: C3, C4, C5, C1-inhibitor, etc.
4. Immunophenotyping of lymphocytes: CD3+, CD3+CD4+, CD3+CD8+, CD3+HLA-DR+, CD3-HLA-DR+, CD3+CD16/56% CD25+, etc.
5. Functional activity of lymphocytes:
- cytotoxic activity of NK cells;
- proliferative response of lymphocytes to T- and B-cell mitogens;
- Th1 and Th2 cells;
- spontaneous and induced synthesis of cytokines by peripheral blood mononuclear cells;
- apoptosis of lymphocytes during specific and nonspecific activation and apoptosis of neutrophils during phagocytosis.
6. Interferon status.
- the level of interferon-α and interferon-γ in the blood serum and in the supernatant of activated leukocytes.
At the State Scientific Center “Institute of Immunology of the Federal Medical and Biological Agency of Russia” (Moscow), monoclonal antibodies are used to identify immunodeficiencies; most of the methods used are modified for quantitative assessment by flow laser cytometry.
The problem of diagnosis and treatment of immunodeficiency conditions is currently extremely relevant for clinical medicine.
This is due to the fact that in recent years A large amount of new information has accumulated about the structure and functioning of the human immune system.
Immunomodulatory therapy has begun to be actively introduced into the practice of not only immunologists, but also doctors of other specialties, many new immunomodulatory drugs have appeared, and the number of nosological forms in the treatment of which immunotropic drugs are used has increased.
All immunodeficiency states are usually divided into primary and secondary.
Primary immunodeficiencies (PIDs) are congenital diseases caused by defects in genes that control the immune response; in this case, the defect may affect one or more components of the immune system: cellular and humoral immunity, phagocytosis, and the complement system.
PID is characterized by persistent disturbances in immune parameters. Clinically, PID manifests itself as recurrent infectious diseases, a tendency to autoimmune pathology, tumor diseases. These immunodeficiencies usually debut in early childhood.
Secondary immunodeficiency states (SIDS) are characteristic changes in the functioning of the immune system that develop in the late postnatal period or in adults, not associated with genetic defects.
With secondary immunodeficiency, the immune system, which is completely normal at birth, for some reason begins to malfunction.
There are three forms of VIS: acquired, induced and spontaneous.
The most typical acquired form of secondary immunodeficiency is AIDS, which develops as a result of damage to human lymphoid tissue by a virus.
The reasons for the development of the induced form can be varied: often recurrent bacterial, fungal, viral infections various localizations; allergopathology ( atopic dermatitis, bronchial asthma, hay fever, eczema with infectious syndrome); autoimmune pathology; neoplasms of different localization; blood diseases; gastrointestinal pathology; pathology endocrine system; aging; surgical interventions; injuries; eating disorders; x-ray radiation; cytostatic therapy.
In spontaneous form of secondary immunodeficiency obvious reason disorders of immune reactivity cannot be identified (in some cases this is due to the insufficient diagnostic capabilities of modern clinical medicine). 
Clinical signs of secondary immunodeficiency states (SIS) are chronic, often recurrent, sluggish, difficult to treat traditional means infectious and inflammatory diseases of any localization caused by opportunistic or opportunistic microorganisms, as well as pathogenic flora with atypical biological properties and/or multiple antibiotic resistance.
The state of the immune system has great value for the formation of infectious resistance. The main task of the anti-infective defense system is to eliminate infectious agents, preserving the memory of them (memory lymphocytes) for a faster and more effective response in the event of re-infection.
The development of a chronic disease indicates that there are malfunctions in the body's complex defense system. When infected, natural resistance factors are activated instantly and in the early stages are practically the only defenders of the body. Only after 2-3 weeks do the elements of specific protection begin to function.
In the dynamics of the development of the disease, these two components of the body’s defense reaction (innate and acquired immunity) function in parallel, complementing and reinforcing each other.
The specific immune response includes the production of antibodies (classes IgG, IgA, IgM, IgE), the formation of a clone of antigen-specific T-lymphocytes (Th1, Th2, cytotoxic T-lymphocytes, T-effector cells in delayed-type hypersensitivity reactions) and memory cells .
Detected changes in immune status depend on the nature of the infectious agent, causing inflammation, on the severity of inflammation and its duration.
It should be emphasized that the immune response to the same infections may vary in different patients, and the functioning of the immune system is strictly individual.
The works of numerous researchers describe the most frequent changes in the immune status, characteristic of viral, bacterial infections, extra- and intracellular pathogens.
Processes caused by bacterial pathogens are characterized by changes in the phagocytic and humoral components of the immune system.
The adequate response of the immune system to acute bacterial inflammation consists of an increase in indicators characterizing the absorption and digestive ability of phagocytes, and an increase in the levels of immunoglobulins of classes A, M and G. On the contrary, with VIS in this case, a decrease in phagocytosis and hypogammaglobulinemia are noted in the immune status.
The quantitative ratios of immunocompetent cells are variable, clinical significance for the prescription of immunomodulators has only a pronounced decrease in the number of mature T cells. 
At chronic course In the infectious-inflammatory process, changes in the immune status may be absent or depletion of the functions of the macrophage-monocyte link and antibody formation is determined, which, as in acute bacterial inflammation, is accompanied by a decrease in phagocytosis rates and hypogammaglobulinemia.
Identification of the viral pathogen in chronic infectious and inflammatory processes is quite difficult. As a rule, we are talking about viral-bacterial associations. Therefore, the problem of the influence of viral pathogens on the state of immunity in chronic infectious and inflammatory processes is much less studied, the same applies to intracellular pathogens.
The atypical clinical course of the infectious-inflammatory process is typical for infectious agents, the recognition of which by immunocompetent cells is difficult. With viral and intracellular infections, patients with the highest frequency usually present signs of VIS.
Chronic viral infection, in contrast to acute, is often accompanied by lymphopenia and a decrease in the number of immunocompetent cells, depletion of the IFN system.
With an adequate response of the immune system to a viral pathogen, an increase in IgM level and other classes of immunoglobulins, the immunodeficiency state is characterized by hypogammaglobulinemia.
Changes in immunological parameters can be transient and develop in the later stages of IIS in the absence of adequate therapy for the underlying disease.
Cause-and-effect relationships between immune status and clinical picture diseases are very complex, and most often it is not possible to decide what is primary and what is secondary.
The most common clinical conditions associated with infection that require observation and examination by an immunologist:
- chronic bronchitis, often recurring, with a history of pneumonia, in combination with diseases of the ENT organs (purulent sinusitis, otitis, lymphadenitis);
- frequently recurring pneumonia, bronchopleuropneumonia;
- bronchiectasis;
- bacterial infections of the skin and subcutaneous tissue (pyoderma, furunculosis, abscesses, cellulitis, septic granulomas, recurrent paraproctitis in adults);
- aphthous stomatitis in combination with an increased incidence of acute respiratory viral infections;
- recurrent herpesvirus infection of various localizations;
- gastroenteropathy with chronic diarrhea unknown etiology, dysbacteriosis;
- lymphadenopathy, repeated lymphadenitis;
- prolonged low-grade fever, fever of unknown etiology;
- generalized infections (sepsis, purulent meningitis etc.).
The number of clinical situations in which the inclusion of immunomodulators in the complex therapy of patients is justified is quite large.
In clinical practice, before prescribing immunomodulatory therapy, patients are examined to clarify the nosological form of the disease associated with VIS syndrome.
Not all conditions that are often accompanied by the formation of VIS syndrome require the inclusion of immunomodulatory drugs in therapy. In many cases, correctly selected basic therapy for the underlying disease can eliminate signs of immune deficiency without the use of immunomodulators.
Thus, secondary immune deficiency syndrome is a disorder of the immune system that develops in the late postnatal period or in adults and is characterized by chronic infectious and inflammatory diseases that are responsive to traditional (standard) therapy.
For effective therapy the attending physician must determine the cause-and-effect relationships in the formation of immunodeficiency, adequately select basic therapy according to the underlying disease, assess immunological disorders, and choose the right immunotropic therapy.
is a condition in which the functioning of the immune system and the body’s resistance to various infections decrease.
Immunodeficiencies are divided into:
Primary immunodeficiencies
A group of diseases characterized by decreased functioning of the immune system resulting from genetic disorders. Primary immunodeficiencies are very rare (one to two cases per 500,000). With primary immunodeficiency, there is a violation of individual components of immunity: the complement system and phagocytes, the humoral response, the cellular link.
Immunodeficiency with a violation of the cellular component of the immune system includes agamaglobulinemia, Wiskott-Aldrich syndrome, DiGiorgio syndrome, Bruton's disease. Failure of the function of micro and macrophages occurs during the period of Chediak-Higashi syndrome and chronic granulomatosis.
Immunodeficiencies that are associated with a malfunction of the compliment system are based on a lack of synthesis of one of the factors of this system. Primary immunodeficiencies accompany a person throughout life. People suffering from primary immunodeficiency often die from infectious complications.
Secondary immunodeficiencies
These immunodeficiencies are more common than primary ones. As a rule, the development of secondary immunodeficiency occurs as a result of exposure to adverse environmental factors and various infectious diseases.
With secondary immunodeficiency, just as in the case of primary immunodeficiency, either individual components of the immune system or the entire system may be impaired. Many secondary immunodeficiencies are treatable. However, this does not apply to immunodeficiency caused by HIV infection.
Causes of secondary immunodeficiency.
Factors that can cause secondary immunodeficiency are quite diverse. This can be caused by environmental factors or internal factors of the body. Unfavorable environmental factors can disrupt the metabolism of the entire body, or cause secondary deficiency.
The most common causes of immunodeficiency are poisoning, long-term use of certain medications, microwave and ionizing radiation, overwork, chronic stress and environmental pollution.
Internal factors that can cause secondary immunodeficiency:
Malignant tumors(neoplasms) that disrupt all body systems. A more obvious decrease in immunity is manifested in the replacement of bone marrow by tumor metastases and when malignant diseases blood (leukemia). Against the background of leukemia, the number of immune cells in the blood increases many times. However, they cannot provide protective function, since they are non-functional.
Autoimmune diseases, which are formed as a result of a malfunction of the immune system. As a result of this type of disease, the immune system begins to work insufficiently, which leads to damage to its own tissues and a lack of ability to fight infection.
Malnutrition, exhaustion of the body, which lead to decreased immunity. As a result of exhaustion of the body, malfunction occurs internal organs. The immune system is especially sensitive to deficiencies of vitamins, nutrients and minerals. A decrease in immunity often occurs during periods of vitamin deficiency - in winter and spring.
Loss of immune defense factors, which is observed with burns, kidney disease and severe blood loss. A feature of these diseases is the loss of blood plasma or the dissolution of proteins in it, some of which are immunoglobulins or other components of the immune system ( C-reactive protein or compliment system proteins). During the period of bleeding, loss of plasma and blood cells occurs, which leads to a decrease in immunity, which is cellular-humoral in nature.
Endocrine diseases, which lead to a decrease in the function of the immune system as a result of metabolic failure. A more intense decrease occurs in hypothyroidism and diabetes mellitus, since in these diseases the production of tissue energy is significantly reduced, which entails a failure in cell differentiation and division processes. Diabetes mellitus increases the incidence of infectious diseases, which is associated with suppression of the immune system and high content glucose in the blood, which promotes the growth of bacteria.
Serious operations and injuries that occur with a decrease in the performance of the immune system. Any serious illness can lead to secondary immunodeficiency, which may be associated with intoxication of the body, metabolic disorders, or the release of large amounts of hormones by the adrenal glands after operations or injuries, which can lead to suppression of the immune system.
Taking drugs and medications that have an intense immunosuppressive effect. This is especially evident after taking antimetabolites, glucocorticoid hormones and cytostatics.
Decreased immunity in the elderly, children and pregnant women, which is associated with physiological or age characteristics body.
Diagnosis of immunodeficiency.
Primary immunodeficiency appears at birth or after some time. To identify pathology, a series of complex genetic and immunological tests are carried out, which can determine the area of the immune system disorder and determine the type of mutation that caused the disease.
Secondary immunodeficiency develops at any age. The presence of secondary immunodeficiency can be suspected if there are recurrent infectious diseases, which can go to chronic form, in the absence of treatment results and with prolonged slight increase body temperature.
To ensure accurate diagnosis, tests and analyzes are carried out: specific immunological tests, determination of blood protein fractions, general blood test.
Treatment of primary immunodeficiency.
Challenging task is the treatment of primary immunodeficiencies. To get started complex treatment it is necessary to determine the accuracy of the diagnosis of the disease with the identification of the damaged part of the immune system.
If the amount of immunoglobulin is insufficient, lifelong replacement therapy using serums that contain regular donor plasma or antibodies.
Immunostimulating therapy is used with drugs such as Taktivin, Ribomunil, Bronchomunal. If infectious complications develop, treatment with antifungal, antiviral drugs and antibiotics is prescribed.
Treatment of secondary immunodeficiency.
With secondary immunodeficiency, the failure of the immune system does not occur as intensely as with primary immunodeficiency. Secondary immunodeficiency has a transient nature, which contributes to greater effectiveness of treatment.
As a rule, treatment begins with eliminating the causes that contributed to the development of the disease. For example, treatment of immunodeficiency, which arises as a result of chronic infection, begins with the sanitation of foci of inflammation.
Immunodeficiency, which was caused by vitamin and mineral deficiency, is treated with nutritional supplements, minerals and vitamins. The restorative ability of the immune system is so high that eliminating the cause of immunodeficiency leads to the restoration of immunity.
In order to speed up recovery, you can undergo a course of treatment with drugs that promote immunostimulation.
Drugs such as Biostim, Christine and Ribomunil contain antigens of various bacteria and, when introduced into the body, stimulate the differentiation of leukocyte clones and the production of antibodies. Taktivin and Timalin contain biological active substances that are extracted from thymus gland animals. The most effective immunomodulator is Cordyceps, which helps normalize the immune system in general.
These drugs promote a selective stimulating effect on a subpopulation of T-lymphocytes. Varieties of interferons can increase the body's resistance and are used as an effective remedy for the treatment of viral diseases. Sodium Nucleinate is used to stimulate the synthesis of nucleic acids (RNA and DNA), differentiation and cell division.
Special attention You should pay attention to immunomodulatory substances of plant origin: rosea Echinacea extract, Immunal and especially Cordyceps.