Immunodeficiency states of genetic nature: a new look at the problem. Primary immunodeficiency signs of aplastic anemia

The human immune system is intended to respond in time to the invasion of alien elements. Its proper functionality is the recognition of the threat and its destruction. The primary immunodeficiency means that the child did not have a protective mechanism for intrauterine development, or he did not receive it for the hereditary factor. As a result, malicious microorganisms falling into his body will bring it maximum harm. The same can be said about atypical cells that have a negative impact on the state of health, cause pathology of various severity.

Primary and secondary immunodeficiency should be distinguished. Primary is determined by the baby shortly after birth. His body is devoid of opportunity to protect against antigens, is subject to infectious invasion. This is expressed in the fact that the baby often sick, he is overcome by repeated aahs, it hardly tolerates them, gets complications. Heavy forms of primary immunodeficiency lead to death in infancy.

The rarest cases are known when primary immune failure manifested itself in adults. This is possible, but for this, a person should have a high compensation for a certain variety of illness.

The disease clinic is re-infection, the transition of diseases in chronic form. What the primary immunodeficiency leads to:

1. The patient suffers from bronchopile anomalies.
2. He is amazed with mucous membranes and skin.
3. There are problems with ENT authorities.
4. PIDS, as a rule, leads to lymphadenitis, abscesses, osteomyelitis, meningitis, sepsis.
5. Certain forms of primary immunodeficiency provoke allergies, autoimmune diseases, the growth of malignant neoplasms.

Immunology is engaged in violations of immune defense functions - the science of the development and development of a protective mechanism opposing the penetration of antigens into the body and destroying the cellular cells damaged by malicious substances and microorganisms.

The sooner the PIDTS was diagnosed, the greater the chance of the child to survive and continue life with a satisfactory health condition. The timely determination of the gene mutation is important, which makes it possible to determine the family planning.

The immunodeficiency is considered a persistent anomaly of the protective mechanism, which generates a failure in an immune response to the effect of antigens. This failure can be four types:

• age, i.e. arising in childhood, or in old age;
• acquired due to improper nutrition, lifestyle, drug reception, AIDS virus, etc.;
• developed as a result of various infections;
• congenital or primary ID.

PIDTS are classified depending on the forms and severity of the disease. Primary immunodeficiency includes:

• ID characterized by the defeat of several cellular complexes;
• Dysgenesis is reticulous, in which stem cells are absent, it obes the newborn to death.
• A heavy combined ID is a hereditary disease due to dysfunction in both T-lymphocytes.
• Syndrome Di George - or the Anomalies of Timus, parachitoid glasses - underdevelopment, or the lack of a forkneck. As a result of the defect, T-lymphocytes are affected, congenital heart deformations arise, deformation in the bone structure, structure of facial bones, renal defects and CNS dysfunctions.
• Primary immunodeficiency due to lesion in lymphocytes.
• Disorders in myeloid cells provoking chronic granulomatous disease (CGB) with an anomaly in oxygen exchange. The defect of the production of active oxygen leads chronic fungal and bacterial infections.
• Defects of complex blood proteins that violate humoral protection. There may be several components in the complement system.

Need to know! The cell immunodeficiency is characterized by the insufficiency of immunocompetent cells, which include lymphocytes, plasmocites, macrophages. Humoral immunodeficiency means dysfunction in the development of antibodies.

Symptoms of primary immunodeficiency

The primary immunodeficitations indicate signs of manifestation and symptoms. Studying the clinical picture of the course of the disease, the doctors of the clinic reveal a variety of immune failure. This contributes to inspection, analyzes, collection of anamnesis to clarify genetic pathology.

1. Primary deficiencies of cellular immunity generate infections of viral and fungal nature. Characteristic signs are repeated colds, the heavy flow of ORVI, windmills, vapotitis, frequent manifestations of herpes. The patient suffers from the thrush, inflammation of the lungs, the gastrointestinal organs caused by fungi. Cellular immunodeficiency helps to increase the risk of oncology, lymphoma.
2. Insufficiency of humoral protection provoke bacterial contamination. These are pneumonia, fries on the skin, face, staphylococcus, streptococcus.
3. Inspection of the level of secretory immunoglobulin A causes the defeat of the mucous membranes in the mouth, the nose, eyes, the intestines, suffer from bronchi.
4. Combined IDs are characterized by complications of viral and bacterial infections. The manifestations of this form of primary immunodeficiency are nonspecific - they are expressed in the defects of development, tumor processes, lymphoid tissues, forks of the gland, megaloblastic anemia.
5. Congenital neutropenia and phagocytosis dysfunction of granulocytes generates bacterial inflammatory processes with glasses, abscesses. The result may be sepsis.
6. Complement-associated primary immunodeficiency infections include bacterial infections, autoimmune diseases, as well as recurrent edema on the body, limbs - hereditary angioedema edema (NAO).

Causes of primary immunodeficiency

The dysfunction of the immune system is formed at the embryo inside the womb. Different factors affect this process. Prenatal diagnostics shows a combination of congenital malformations of fetal development with immunodeficiency. Etiology PIDs is based on three pathologies.

1. Genetic mutations meaning that in genes on which the execution of immunocompetent cells depends on their functions, changes occurred. That is, the process for the development and differentiation of cells is disturbed. The inheritance of the anomaly goes on an autosomal-recessive type, when both parents are Mutagena carriers. Only a small amount of mutations develops spontaneously either germinative way (in sex cells).
2. The teratogenic factor is an influence on the embryo of dangerous toxins, leading to congenital primary immunodeficiency. Provocate Torch infection - cytomegalovirus, herpes, rubella, toxoplasmosis in pregnant women.
3. Unclear etiology. Immune failure, the cause of which is not clarified.

Such states include asymptomatic IDs, which are manifested by infectious complications in provocative situations. If even one of the elements of the protective mechanism is exposed to anomalies, the protective forces weaken, the patient becomes an object for the invasion of various infections.

Diagnostics of primary immune failure

Immunodeficiency states are identified by type, since the primary ID is most often congenital, then its variety is determined in the first months or a week. A visit to the doctor is obligatory with frequent diseases of the baby, colds, the development of fungal, viral, bacterial infections. Anomalies in the development of the child also may depend on the primary immunodeficiency. To solve the problem, urgent diagnostics and immediate start of treatment are needed.

The method of identifying the disease includes the following procedures:

• a general inspection at which they draw attention to the damage to the skin, mucous membranes, mercury processes, subcutaneous tanks of adipose tissue;
• the study of the leukocyte formula on the general analysis of blood, on the IDA indicates the presence of leukopenia, neutropenia, agranulocytosis, other violations;
• blood biochemistry shows disbammaglobulinemia, the presence of uncharacterted metabolites, indicating the primary humoral ID;
• specific study on the reaction of the immune system. The indicators of the activity of immunocompetent cells are being studied;
• molecular genetic analysis is a gene sequencing method on a type of mutation. This is a way to determine the syndromes of Bruton, Di Georgie, Duncan, Viscott-Aldrich.

The doctor differentiates immunodeficiency conditions with acquired secondary IDs arising from the influence of radiation, toxic substances, autoimmune diseases, oncology. In adults, the diagnosis is difficult to put, as signs are smoothed, the symptoms are implicit.

Prenatal diagnostics

The definition of the primary ID with the help of biopsy Village of chorion is called prenatal identification of the form of the disease. In addition, the culture of fruit water cells, fetal blood is studied. These are complex analyzes that are shown in cases where the parents have been identified by Mutagen.

But to identify the X-clutched heavy combined immunodeficiency, this method gives an accurate result, and also specifies the diagnosis of primary idios, chronic granulomatosis syndromes, other states of TKID.

Treatment of primary immunodeficiency

Different etiology and pathogenesis of diseases do not allow to develop a general methodology of pathology therapy. In severe forms, therapeutic treatment is not relevant, it brings only temporary relief, but the death is inevitable from the complications of immunodeficiency. In these cases, only bone marrow transplant or embryonic substance of the fork gland helps.

The deficiency of cellular immunity is compensated by the method of applying specific colonist drugs. These are replacement immunotherapy of tylimaline, stabbing, levamizol and other means, the choice of which makes an immunologist. Enzymes are corrected by enzymes, metabolites. A common preparation of this series is biotin.

DGlobulinemia (inadequate of humoral protection) is treated with immunoglobulin substitution, depending on the missing substances of this species. But the main obstacle to the progress of the disease is the prevention of infections. Moreover, the vaccination of patients with the primary ID of children does not give effect, it is dangerous.

Prediction and prevention

With severe primary ID, the child is doomed, he dies in the first year of life. Other pathologies of the immune system are cured as described above. The main task of parents is timely appeal to the doctor and child care. It is impossible to infection a child with viral, bacterial, fungal pathogens.

If you are planning the birth of a child and you have the problems of gene mutation, then consultation with the immunologist is obligatory. During pregnancy, you need to pass a prenatal diagnosis, take care of infections and comply with all the recommendations of the doctor.

For patients ID, it is important to comply with personal hygiene, the care of the oral cavity, the nasal mucosa, the eye is careful, without damaging their integrity. Balanced nutrition is needed, elimination of contacts with patients during epidemics, drug prevention of infections.

Complications after immunodeficiency

Primary immunodeficiency leads to formidable complications. The result of the consequences may be the death of a person. Such states are considered sepsis, abscesses, pneumonia, severe infections. Autoimmune diseases are possible when the immune system failed is that it destroys its own cells. The risk of cancer and imbalance of the tract, cardiovascular system increases.

Conclusion

Primary immunodeficiency is not always a sentence. It is necessary to observe the immunologist constantly, it will help preserve satisfactory quality of life and live long.

To help a practical doctor

UDC 612.216-112.

Received 31.04.08

LM Karzakova, OM Mochukova,
N.L. Ratary

Primary and secondary immunodeficiency

Republican clinical hospital

Children's City Hospital №3, Cheboksary

The principles of diagnosis and treatment of immunodeficiency states are considered. Much attention is paid to primary immunodeficient diseases. Posted by composed authors Register primary immunodeficiency Chuvashia.

Here Are The Principles of Diagnoctic and Treatment of Immuno-Deficient States. The Great Attention Is Attracted to Primary Immuno-Deficient Diseases. IT CONTAINS THE LIST OF THE PRIMARY IMMUNO-DISEAST DISEASES IN CHUVASHIA, MADE by The Author.

Immunodeficiency, impaired immune response, are divided into two large groups - primary (congenital) and secondary (acquired) caused by various endogenous (diseases) and exogenous effects (for example, negative environmental factors). Primary immunodeficiencies (PID) are usually due to genetic defects and only sometimes non-treats arising in the embryonic period. A typical manifestation of PID is a violation of anti-infectious resistance with the development of recurrent and / or chronic infections of various localization. The type of infectious pathogens to which the body exhibits increased sensitivity depends on the defect of one or another level of the immune response. Thus, the antibody defect (the insufficiency of the humoral immune response) leads to a decrease in resistance mainly against bacteria (staphylococcus, streptococcus, pneumococcus, intestinal wand, protea, klebseyella) and enteroviruses. In order to violate the cellular immune response, an increased predisposition to viral, protozoa infections, tuberculosis, cryptococcosis, leishmaniasis is characterized. With phagocytosis defects, the most often caused by the infectious syndrome is microorganisms producing catalase (staphylococci, E. coli, Serratia Marcescens, Nocardia, Aspergillus, etc.), most gram-negative bacteria and mushrooms (Candida Albicans, Aspergillus). The defect in the complement system is manifested by infections caused by Kokkkil Flora and Neisseria. With a combined impaired immune response (combined immunodeficiency), the infectious syndrome is caused both bacteria and viruses, mushrooms, simplest.

In some cases, infectious syndrome is combined with non-immunological manifestations - with clearly defined symptoms from other organs and systems. Thus, DJ syndrome is manifested not only in violation of the cellular immunity, but also aplasia or hypoplasia of the Timus Agenesia of parachitoid glands, vices of the heart and large vessels, stigs of disisembridgenesis (the splitting of the sky, the absence of uches, etc.). In the Louis-bar syndrome, the combined immune failure (a decrease in the number of T-lymphocytes, a decrease in IGA levels) is combined with cerebulic attacks and telegangectasia on the skin and eye gluits. The combined immune defect (decrease in the number of T-lymphocytes, the decrease in the level of IGM) in combination with eczema and thrombocytopenia occurs in the syndrome of Viscott-Oldrich.

Primary immunodeficiency

The first case of a congenital immunodeficiency state (Aghamaglobulinemia due to the genetically determined impairment of immunoglobulin products) was described by Bruton in 1952. Since then, more than 100 different primary defects of the immune system are recognized. Some PIDs are quite common. For example, the frequency of selective deficiency IGA reaches 1: 500. For most other PIDs, this figure is 1:50,000 - 1: 100,000. According to numerous publications, there is clear hypodiagnostics and lag in the diagnosis of PID in the world. At the initiative of Jeffrey Model Foundation (USA) and ESID (European Society for the Study of Immunodeficiency), criteria are developed to suspect PID in patients.

PID criteria:

1. Durable diseases otitis (6-8 times a year).

2. Durable sinusitis diseases (4-6 times a year).

3. More than two confirmed pneumonia.

4.Force deep abscesses of the skin and internal organs.

5. Credit in long-term therapy (more than 2 months) antibiotics to relieve infection.

6.The care in intravenous administration of antibiotics to relieve infection.

7. More than two severe infections (meningitis, osteomyelitis, sepsis).

8. Establishing a breast child in growth and weight.

9. The microbic skin lesion over the age of 1 year.

10. The presence of the relatives of the PID, early deaths from severe infections or one of the listed symptoms.

Discovery in a patient more than one of the listed symptoms should be alerted against PID and appear to be a signal for immunological research. The roles and facilities of the PID in the structure of morbidity and mortality in the world are of great importance, which caused the creation in Western Europe, America, Australia National PID registers. Analysis of the data included in the registers allows you to judge the frequency of the occurrence of the PID at various points of the globe, ethnic populations, to establish the prevailing form of pathology and thereby create prerequisites for improving the quality of diagnosis of rare forms of diseases by comparing new cases with analogues available in the register. In Russia since 1992, the PID register is also conducted on these analysis of cases of hospitalization and treatment of patients in the Department of the SSC RF "Institute of Immunology". However, many cases of PID diagnosed in the regions remain unaccountable. The formation of any register should be based on a single classification of diseases. In connection with the brevity of the history of the study of the PID, it is still not final. Scientific group of WHO every 2-3 years publishes reports and recommendations on the PID systematics, with the introduction of modern diagnostic methods the number of the described forms of the disease and the procedure for their classification change significantly . In accordance with the last classification of WHO (2004), PIDs are divided into the following groups:

1. PID with predominantly defects of antibodies (humoral immunodeficiency):

· Covered with X-chromosome Aghamaglobulinemia (Hwagg);

· Common variable immune failure (OVIN);

· Agamaglobulinemia with a normal or elevated IGM level;

· Selective deficiency of IGA;

· Transient hypogammaglobulinemia of infant age (late immunological start).

2.Pid with mainly T-cell defects:

• primary deficiency CD4 +-cells;
• iL-2 deficiency;
• multiple cytokine deficiency;
• defect of signal transduction + myopathy;
• calcium influenza defect with myopathy.

3. Combined immunodeficiency states:

• severe combined immunodeficiency (TKID);
• wiscott Syndrome - Oldrich;
• ataxia - Elaangiectasia (Louis-Bar syndrome).

4. Phagocytosis defects:

• chronic granular disease;
• chediaiac - Higashi syndrome.

5. Complete system defects.

6. Immunodeficiency associated with other main defects outside the immune system:

• hyper-IgE syndrome (Job syndrome);
• chronic skin-mucous candidiasis;
• intestinal lymphangectocation;
• enteropathic Akrodermatitis.

7. Immunodeficiency associated with lymphoproliferative processes.

The most common functions of the PID are most common.

X-clutched Agammaglobulinemia, or Bruton's disease (1:50 000), is observed in boys at the 5-9th month of life, when the transpostentarly obtained maternal immunoglobulins are depleted. The disease is manifested by recurrent pyrogen infections (pneumonia, sinusites, mesothympanites, meningitis). An important diagnostic symptom is lymph nodes, the spleen does not react to an increase in the inflammatory process. In an immunolaboratory study, it is detected: 1) a decrease or absence of γ-globulins in blood serum; 2) reducing whey level IgG (less than 2 g / l) in the absence or sharp decrease in IGM and IGA levels; 3) the absence or a sharp decrease in the number of B-lymphocytes (CD19 + or CD20 +) in circulation less than 2%; 4) absence or hypoplasia almonds; 5) Small dimensions of lymph nodes; 6) The preserved function of T-lymphocytes.

OVIN (1:10 000 - 1:50 000) is a heterogeneous group of diseases with a defect of antibody and a different type of inheritance. The term "variable" means the manifestation of the disease at different ages (children's, adolescent, adult) with individual variations of the type and degree of immunodeficiency severity. According to the clinical picture, the Ovin resembles Bruton's disease, the main difference on the cause of the disease manifestation: the average age of the clinical manifestation of Avin - 25, diagnosis - 28 years. The survival rate of patients depends on the degree of reduction in IgG levels and the insufficiency of the cellular immune response: the more they are expressed, the earlier patients are died. This PID shape is equally affecting both men and women. Like all the humoral immunodeficials of the Avin clinically manifested by recurrent and chronic pneumonia, sinusitis, otitis, bronchiectases are often formed, a gastrointestinal tract is affected with symptoms of malabsorption, a decrease in body weight, diarrhea, hypoalbumine, vitamins deficiency. Chronic inflammatory processes in the intestines (enterovirus infections) are characterized with the development of a nodular lymphoid hyperplasia. About one third of the patients have splenomegaly and / or diffuse lymphadenopathy. In 22% of cases, autoimmune manifestations are developing (pernicious or hemolytic anemia, thrombocytopenia, neutropenia, rheumatoid arthritis, violation of the function of the thyroid gland). In immunolaboratory study, it is detected: 1) a normal or somewhat reduced number of circulating B-lymphocytes; 2) reduction in serum levels of IgG and IgA, to a lesser extent - level IgM; Reducing the total concentration of IgG + IgA + Igm less than 3 g / l; 3) the total number of T cells is normal or somewhat reduced by reducing the number of T-helper subpopulation; 4) Reduced immunoregulatory index CD4 + / CD8 +.

The selective IGA deficiency (1: 700 in the Europeanoids; 1:18 500 in the Japanese) is characterized by a decrease in serum IGA level up to 0.05 g / l and below (quite often up to 0) in the normal content of other classes of immunoglobulins. If the IGA concentration is above 0.05 g / l, but below 0.2 g / l, then the diagnosis of "partial (partial) deficiency of IGA should be denied. In most cases, IGA deficiency proceeds asymptomatic ,.Ohodno, part of individuals is manifested by synopoulmonal infections in combination with allergic manifestations (atopic dermatitis, polynosis, bronchial asthma, swelling, etc.) and autoimmune (sclerodermia, rheumatoid arthritis, vitiligo, thyroiditis).

Transient hypogamaglobulinemia in children ("Slow immunological start") is characterized by low levels of immunoglobulins. The beginning of the disease from 5-6 months, when the child suddenly, without visible reasons begins to hurt with recurrent piogenic kidney infections, respiratory tract. This is due to the fact that the Maternal IGG, received by the child transplanetary, is catabolized to this age, and the products of their own IgG, usually starting from the 4th month, delays. With this form of immunodeficiency, the levels of IgG and Iga are more often reduced, while the IGM level is within normal limits or even increased. B-lymphocytes, lymph nodes and almonds are not changed. Such a transient immunodeficiency state occurs in 5-8% of infants (usually in premature children or children from immunodeficiency families) and usually passes without treatment by 1.5-4 years.

Hyper-IgE syndrome (Job syndrome). The diagnosis of "Job's syndrome" is based on the repeated (minimum two-time) increase in serum concentration of total IgE above 1000 me / ml in the presence of dermatitis and repeated deep purulent infections with a "cold" flow: skin abscesses, subcutaneous fiber, lymph nodes, otites. Special danger is the heavy episodes of sharp pneumonia, including destructive, with an outcome in pneumatic, liver abscesses. Characterized skeleton anomalies spontaneous fractures of tubular bones, coarse dysplastic features. The pathogenetic mechanism of the disease lies in the fact that TX1 is not able to produce interferon-γ. This leads to an increase in the activity of TX2, which manifests itself in increased IGE products. The latter causes the release of histamine, which blocks the development of the inflammatory response (the formation of cold abscesses is associated with this). In addition, histamine oppresses chemotaxis neutrophils.

Chronic skin-mucous candidiasis. It is characterized by candidal lesions of the skin, mucous membranes, nails, the scalp. The disease is based on a unique defect of T-lymphocytes, which consists in the fact that these cells are not able to develop a normal response, in particular, produce a factor inhibiting the migration of macrophages (myth) on the Candida Albicans antigen. The Skin Test of the PCTF on this antigen is also negative. At the same time, patients have a normal number of T-lymphocytes, and their response to other antigens is not disturbed. Not changed a humoral response to the Candida antigen. The syndrome is combined with autoimmune polyglandular endocrinopathy. Treatment use symptomatic antifungal therapy.

Chronic granulomatous disease (HGB). It is a congenital form of a phagocytosis defect. Neutrophils have normal chemotaxis, absorbing activity, but the formation of a "respiratory explosion" is broken. Catalazo-positive microorganisms (Staphylococcus aureus, E. coli, Klebsiella, Serratia Marcescens, Salmonella, Aspergillus mushrooms) form granulomas in lymph nodes, liver, lungs, gastroy. The development of recurrent lymphhadenitis, abscesses (hepatic, pulmonary, periphetal), osteomyelitis, ulcerative stomatitis, rhinitis, conjunctivitis are characteristic. Some patients with a child diagnosed in childhood live up to 30 years. The diagnosis is confirmed by the NST-test (the test of the nitrosine tetrazolium reduction) having zero values \u200b\u200bin the pathology under consideration. Treatment: Daily Preventive Taking Antistaphococcal Antibiotics, subcutaneously interferon-γ 3 times a week.

On the basis of observations, we have created a PID register of Chuvashia, which includes 19 patients with 7 forms of immune failure (Table 1).

Table 1

Register of primary immunodeficiencies Chuvashia

From more than 100 known verified PID forms, we have 7. In the national register of Russia, 19 forms of PID are described. Attention is drawn to the fact that 15 of the PID presented in the register is diagnosed only after the transition of patients in the adult network of medical service. The register does not include children with a transient hypogammaglobulinemia of young age. This is due to the lack of clear criteria for the diagnosis of this PID form and with difficulties in differentiation with secondary immunodeficient states of children under 3 years. In addition, there are no TKIN in the register, due to, as well as defects, both humoral and cellular immune response mechanisms, and leading children at their earlier age. They are usually diagnosed retrospectively on autopsy by clinical and pathoanatomic comparison. Unfortunately, in our republic, the pathoanatomy bureau does not register TKIN, writing off the deaths of cases of pronounced defects of the immune system to certain severe infections (sepsis, meningitis, etc.). The republican incidence rate selective IGA deficiency is also not true. According to many authors, the prevalence of this PID form is 1: 500. For example, in the PID register of the South Ural region, this disease is in the first place in the frequency of occurrence, and the prevailing majority with selective deficiency of IGA are children. Our republican register includes only adult patients with the PID under consideration. The low detectability of selective IGA deficiency is most likely associated with the variability of clinical manifestations of the immunological defect, often very poorly pronounced. A significant number of immunopathology patients have an increased frequency of respiratory viral infections. It is essential that the increased frequency of infections, often noted in early childhood, in subsequent years is significantly reduced. More than 20% of patients with selective IGA deficiency suffer from allergic and autoimmune diseases. In some patients, the immunological defect is not clinically manifested. Probably the low frequency of the representation of the selective IGA deficiency in the republican register is due to its insufficient detectability by experts. An example of a well-detected PID is served by Avive, located in the national register of the Russian Federation in the second place in the prevalence after the selective IGA deficiency. The reason for the effective detection of Avin is a good awareness of the adult network of the criteria for the diagnosis of this pathology due to a repeated demonstration of patients on clinical disclaimers and conferences of the Association of Chuvashi therapists.

Thus, in Chuvashia, the detectability of combined immunodeficiency, selective IGA deficiency, which seems to be due to the deficiency of the doctors of various specialties of basic knowledge of clinical immunology (including on issues relating to clinical manifestations, diagnosis of PID), as well as Insufficient use of physicians of immunological diagnostic methods.

Secondary immunodeficiency. Among the adult contingent, secondary immunodeficiency states are predominantly distributed. More often, the acquired defects of the cellular immune response are observed, less often - humoral. The reason for this apparently is that T cells are more sensitive to apoptogenic factors than Bcl-expressed antigen-expressed BCL antigen expressed on their membrane, and apoptosis, as is known, is the main mechanism of death of the immune system cells and development immune failure. Any factors that can induce the processes of apoptosis of T-cells (ionizing radiation, stress, increasing the content of glucocorticosteroids and ethanol, infection, etc.), can play a causal role in the occurrence of secondary T-cell immunodeficiency. The secondary insufficiency of a humoral immune response is usually developing against the background of already existing serious diseases. The main states that cause acquired insufficiency of the humoral mechanism of adaptive immunity are the following:

1) protein insufficiency associated with malabsorption syndrome, chronic pancreatitis, gluten enteropathy, burn disease (synthesis of immunoglobulin molecules is broken due to the lack of "building material" - amino acids);

2) conditions leading to the loss of immunoglobulins and immunocompetent cells - nephrotic syndrome (when glomerulonephritis, the glomerular filter is carried out not only for low molecular weight proteins, but also high molecular weight globulins, incl. And immunoglobulins), bleeding, lemforming, burns;

3) myelomal disease (myelomal clone of in lymphocytes, which has received the properties of rampant growth, producing immunoglobulins of one class, one specificity, the growing myeloma replaces normal clones in lymphocytes in the bone marrow, producing immunoglobulins of others, about 108, various specificities, during development IgA myeloma reduced IgG and IgM levels, IgG-myeloma is accompanied by a decrease in IGA and IGM, and with IGD myeloma and light chains disease, three main class of immunoglobulins are reduced);

4) Splenectomic syndrome (when the spleen is removed to a lesser extent, the cellular immune response suffers, however, a humoral link is significantly oppressed, since the spleen is predominantly anti-flavoring organ).

With these states, there may be a decrease in the content of antibodies to the level of hypocholas, Agamaglobulinemia. In contrast to congenital forms in the secondary defect of the humoral mechanism of the immune response, immunoglobulin levels vary depending on the flow and severity of the main process, their content may normalize (without replacement therapy with immunoglobulin drugs) during the remission of the underlying disease.

Guided by the WHO expert data, as the etiopathogenic factors of the secondary failure of the cellular immune response, be called:

1) Impact of physical and chemical factors:

• physical (ionizing radiation, microwave, high or low air temperature in arid climatic zones, etc.);
• chemical (immunosuppressors, chemotherapy, corticosteroids, drugs, herbicides, pesticides, technogenic pollution of environmental salts of heavy metals);

2) the modern lifestyle of a person (hypodynamia, an excess of information with the development of "information" disease);

3) dysfunction (deficiency of essential micronutrients in a daily water-food diet - zinc, copper, iron, vitamins - retinol, ascorbic acid, alpha tocopherol, folic acid; protein-energy failure, exhaustion, cachexia, metabolic disorder, obesity);

3) Viral infections:

• sharp - cort, rubella, epidemic parotitis, chickenpox, influenza, hepatitis, herpes, etc.;
• persistent - chronic hepatitis B, subacute sclerosing pankenefalitis, AIDS, etc.;
• congenital - cytomegaly, rubella (Torch complex);

4) protozoa invasion and helminthiasis (malaria, toxoplasmosis, leishmaniasis, trichinosis, ascaridosis, etc.);

5) bacterial infections (staphylococcus, pneumococcal, meningococcal, tuberculosis, etc.);

6) malignant education, especially lymphoproliferative;

7) autoimmune diseases;

1. conditions leading to the loss of immunocompetent cells (bleeding, limification);
2. exogenous and endogenous intoxication (poisoning, thyrotoxicosis, decompensated diabetes mellitus);
3. violation of neurogormonal regulation (stressful impact - severe injury, operations, physical, incl. sports, overload, mental injuries);
4. natural immunodeficiency - early children's age, gerontological age, pregnant women (first half of pregnancy).

Secondary immunodeficiency are sharp(due to acute infectious disease, injury, intoxication, stress, etc.) and chronic(developing against the background of chronic purulent-inflammatory diseases, tumors, chronic stresses, immunosuppressive therapy, while living in regions with unfavorable ecological and geochemical conditions, etc.). Acute immunodeficiency is diagnosed based on the detection of deviations in the immunogram indicators - decrease in the number of T-lymphocytes (CD3 +), T-helpers (CD4 +), reducing the immunoregulatory index (CD4 + / CD8 +). They, as a rule, transient and gradually stop under a favorable course and adequate etiopathogenetic treatment of the underlying disease with the connection of well-known, so-called clothing drugs and funds (vitamins, adaptagents, physiotherapy procedures, etc.), as well as energy-metal therapy (Vamzimis, Coenzyme Q10) . Chronic immunodeficiency requirements can flow in three versions: 1) with clinical and laboratory signs, 2) with clinical signs in the absence of laboratory deviations, 3) with a causal factor (for example, living in conditions of ecological disadvantage), the lack of clinical manifestations and the presence of immunological disorders . The first type is more common. With the second type, when the immunodeficiency is manifested only clinically, but do not change in a typical immunogram, the impaired of the functioning of the immune system on a thinner level is not detected during a routine study. Formally, the normal values \u200b\u200bof immune status indicators, which are reflected by the individual response of the immune system, can be "pathological" for this individual, which are not able to provide a sufficiently high level of body resistance. The third type that detects itself only by immunolaboratory signs of immunodeficiency, in essence, is presets, a factor in the risk of diseases conjugate with secondary immunodeficiency - infectious, autoimmune, oncological, etc. Often the third type of immunodeficiency is accompanied by signs of chronic fatigue syndrome.

Chronic fatigue and immune dysfunction syndrome (SHU). First described A.Llaud and co-authors in 1984 and characterized as chronic fatigue experienced by the patient, which does not disappear after rest and leads to a significant decrease in performance, both mental and physical. The detection of pronounced imbalance of the immune system in patients with CXU was the basis of the transformation of the name of the disease in chronic fatigue syndrome and immune dysfunction. SHU is registered mainly in environmentally unfavorable regions with a high level of environmental pollution with chemically harmful substances or with an increased level of radiation. These factors negatively affect the state of the immune system (first of all, the cellular mechanism of adaptive immunity), which apparently supports the persistence of latent viruses with the defeat of the central nervous system and the activation of latent viruses (herpes virus, Epstein-Barra virus). The beginning of the clinical manifestations of the CHU, as a rule, is associated with the transmitted cold, less often - emotional stress. The symptoms of the CHU consists of pronounced fatigue, muscle weakness, not passing after night sleep, the difficulty of falling asleep, superficial sleep with nightmarish dreams, periodically emerging states of depression. For patients with schu, especially young age, sensitivity to respiratory viral infections are typical. Patients complain of pain and throat (non-ascending pharyngitis). Part of the patients marked weight loss, a pale skin color lowered by the tour. According to a number of researchers, immunological disorders lie in the pathophysiological basis. Indeed, most patients find a decrease in the number of T cells, a decrease in their proliferative activity, a decrease in the function of NK cells, disimumunoglobulinemia. Complex treatment of patients with CHU includes the purpose of tricyclic antidepressants, non-steroidal anti-inflammatory drugs, immunograms and adaptogens under the control of the immunogram.

Principles of immunodeficiency state correction. The correction of humoral insufficiency includes the prescription of replacement immunotherapy and antibody stimulants. Replacement immunotherapy is shown in reducing the total concentration of immunoglobulins below 5 g / l. The drugs of immunoglobulins (sandoglobulin, octagam, intraproglobin or normal immunoglobulin of a person for in / in administration) are introduced in / 2 times a week in a dose of 0.1-0.2 g / kg in a monthly dose to 1.2 g / kg. Antibody stimulants are shown in Aghammaglobulinemia by type of Ovin: myelopid 3 mg (0.3% solution 1 ml) per / m through day 6-8 injections, sodium nucleicate - 0.2 g 3 times a day in 14 days or Derinate 1.5% solution of 5 ml with intervals of 2-3 days 8-10 intramuscular injections.

Under the defeat of the phagocytic element, the polyoxidonium 0.006-0.012 g adults in the day is the first 5 injections, then at intervals of 2-3 days, for course 7-10 intramuscular injections; Licopid 1 Tablet 1 time per day under the tongue for 10 days (Tablet for adults - 0.01 g); Derinat 0.25% solution - 2 drops in the nose 3-4 times a day for 10 days.

In defects of cellular adaptive immunity, use: 1) preparations of thymus origin (Timalin 0.010-0.020 g per night at night 7-10 injections; thymogen 0.01% -1 ml in / m daily - 3-10 injections; immunophan 0.005% - 1.0 ml of p / k or per / m 5-7 injections every other day or in 2-3 days, per course 8-10 injections); 2) Interferon preparations (Interferon human leukocytarial 1,000,000 meters 2 times a week to 6 months; Refaferon 3,000,000-5,000,000 meters 2 times a week from 4 weeks to 6 months); 3) recombinant analogue of IL-2 - Roncolekin 500 000-1 000 000 000 ° C / in drip or p / k with an interval of 48-72 hours 3-5-10 injections; 4) stimulants of endogenous interferonogenesis (amaxine 0.125 g - on the first day 2 tablets after meals, then a day 1 tablet; cycloferon - tablets 0.15 g and an injection solution 12.5% \u200b\u200b- 2 ml, prescribed by baseline on 1 , 2, 4, 6, 8, 11, 14, 17, 20, 23, 26, 29 days).

LIST OF REFERENCES

1. Kovalchuk L.V., Camelseev A.N. Apoptotic immunodeficiency // Modern problems of allergology, clinical immunology and immunopharmacology: Tez. Dokl. 2nd nat. Congress Rahaki. M., 1998. P. 615-619.
2. Reznik I.B. The current state of the question of primary immunodeficiency products // Pediatrics. 1996. №2. P. 4-14.
3. Yartsev M.N., Yakovlev K.P. Register of primary immunodeficiency states of the Institute of Immunology of the Ministry of Health of the Russian Federation // Immunology. 2005. №3. P. 23-27.
4. Bruton O.C. AgammagLobulinemia // Pediatrics. 1952. Vol. 9. P. 722-726.
5. Cunningham-Rundles C. CLINICAL AND IMMUNOLOGICAL ANALYSIS OF 103 PATIENTS WITH COMMON VARIABLE IMMUNODEFICIENCY // J. Clin. Immunol. 1989. Vol. 9. P. 22-33.
6. Lloyd A.r. et al. Immunological Abnormalities in the Chronic Fatigue Syndrome // Med. J. AUST. 1989. Vol. 151. P. 122-124.
7. Matamoros F.N. et al. PRIMARY IMMUNODEFICIENCY SYNDROME IN SPAIN: FIRST REPORT OF NATIONAL REGISTRY IN CHILDREN AND ADULTS // J. Clin. Immunol. 1997. Vol. 17. P. 333-339.

Each person has an immune system designed to recognize and protect the organism from alien substances. The ultimate goal of immunity lies in the destruction of microorganisms, atypical cells, causing a negative impact on human health. Depending on the origin, primary and secondary immunodeficiency are isolated. In case of immunodeficiency, all infections and diseases proceed more difficult, more often go into chronic shape and have complications.

What is primary immune failure?

Primary immunodeficiency is hereditary or acquired during the period of intrauterine development, the condition in which problems in the work of the immune system are observed. In other words, the child is born without ability to defend against any infections and viruses. Primary immunodeficiency in children is diagnosed at an early age. Patients with severe form, as a rule, die. In some forms of the disease, the first symptoms can be detected in adulthood. This occurs if the patient has a good compensation for a certain form of illness. The clinical picture is expressed by repeated and chronic infectious processes. Often amazes the bronchopulmonary system, ENT organs, leather and mucous membranes. Primary immunodeficiency can lead to the development of purulent lymphadenitis, abscess, osteomyelitis, meningitis and sepsis.

Some forms are manifested by allergies, autoimmune diseases, can provoke the development of malignant tumors. It will help to recognize the primary immunodeficiency immunology - science, engaged in the study of the mechanisms of self-defense of the body from any malicious substances.

Congenital immunodeficiency is diagnosed enough. Early diagnosis is extremely important for the following reasons:

• in time, the diagnosis and correct assigned therapy contribute to the preservation of high-quality life in patients over long years;
• the diagnosis of primary immune failure and recognition of defective genes makes it possible to clarify family members in an affordable form of physician-genetic conclusion and carry out intrauterine diagnostics.

Primary Immunodeficiencies: Classification

The immunodeficiency indicates a stable change in the immune system, the cause of which the defect becomes in one or several mechanisms of the immune response. Distinguish four of his kind:

1. Age-related, emerging in early childhood or in old age.
2. Purchased.
3. Infectious, provoked by the virus.
4. Congenital (primary immunodeficiency).

The classification of primary immune failure is as follows:

1. Immune deficiency associated with the defeat of several types of cells:

   ● Reticular disgenesis is characterized by a complete absence of stem cells. This form of the disease is incompatible with life.
   ● Heavy combined immunodeficiency caused by defects both in T-lymphocytes and in in lymphocytes.

2. Immune deficiency due to the defeat of predominantly T-cells: George's syndrome, for which the absence or underdevelopment of the thymus (forks of the gland) and parachitoid glands, congenital heart deformations, deformation in the structure of the face are characteristic. The disease can be accompanied by anomalies in the development of a skeleton, kidneys, nervous system.
3. Immune deficiency, with preferably defeat in cells.
4. The damage to myeloid cells provokes primary immunodeficiency. Chronic granulomatous disease has a pronounced defect in the development of active forms of oxygen. As a result, chronic infections arise, provoked by bacteria or fungi.
5. Immunodeficiency associated with defects in the complement system. These defects lead to a lack of or the complete absence of different component components.

Cellular, cell-humoral and primary humoral immunodeficiency differ also. The cellular form of immune failure include defects associated with deficiency of lymphocytes, macrophages, plasmocites. The humoral form is due to the deficit of antibodies.

What is secondary immunodeficiency?

This type of immunodeficiency is not a hereditary disease. It is purchased throughout life. Its development can be the impact of biological, chemical and environmental factors. Not protected from secondary immunodeficiency and people leading the wrong lifestyle, incorrectly feeding in constant condition of stress. Sick most often are adults.

Classification of secondary immunodeficiency

Among the secondary states of immune failure, we allocate three forms:

• acquired, the example of which is considered AIDS provoked by the damage to the immune system by the human immunodeficiency virus;
• induced arising from the impact of specific irritants in the form of X-ray radiation, the use of corticosteroids, injuries and surgical interventions;
• spontaneous, characterized by the absence of an explicit reason, led to the emergence of immune failure.

Secondary immunodeficiency are also divided into reversible and irreversible. An embodiment of reversible immune failure may be starvation and the associated shortage of vital components. HIV infection is an example of an irreversible form of immunodeficiency.

Signs of immunodeficiency

The main feature of the disease is the predisposition of a person to frequent diseases of an infectious nature. The primary immunodeficiency is distinguished by repeating respiratory infections. Here it is necessary to clearly distinguish between people with immunodeficiency and with weakened immunity.

A more characteristic symptom characteristic of this disease is the occurrence of bacterial infections, with frequent relapses. This is manifested in repetitive sore throat, itching in the nose, which leads to the development of chronic sinusitis, bronchitis and otites. The body in the process of treatment is not able to completely get rid of the causative agent of the disease, therefore relapses arise. Primary immunodeficiency in children can lead to autoimmune diseases, such as autoimmune endocrinopathy, hemolytic anemia, rheumatoid arthritis. Children in this state are susceptible to several causative agents of infections immediately. Also typical of this state is the disorder of the digestive system. Primary immunodeficiency in adults can manifest themselves the presence of a large amount of warts and a papillom on the body.

Diagnostics of primary immune failure

The diagnosis of the disease begins with the collection of anamnesis. The doctor must explore the family history, especially if a child with a primary form is diagnosed. An inspection of the patient should be made, the condition of the mucous and skin, the size of the liver and spleen is estimated. For such a diagnosis, manifestations in the form of eye inflammation, edema nostrils, chronic protracted cough are also characteristic.

To form an accurate diagnosis, a detailed blood test should be carried out, which will show the number of different cells in the body, the level of immunoglobulin. The analysis is obligatory, which will show the content of proteins in the blood, which indicates the ability of the body to resist various infections.

Prenatal diagnostics

It is established that the primary immunodeficiency is a hereditary disease and not so rare, as it was believed. To date, it became possible to identify the carriage of a mutated gene and consulting families who plan to give birth to a child with the risk of the disease. If the family already has a child with such a state, it analyzes the mutation analysis, after which a diagnostic study of the embryo is carried out. To do this, a molecular analysis of the oilopal water, which contains the cells of the fetus.

Complications after immunodeficiency

Primary and secondary immunodeficiency may lead to complications in the form of severe infectious diseases, such as sepsis, pneumonia and abscesses. In view of a rather wide variety of diseases caused by immunodeficiency, possible complications should be determined individually.

Treatment of immunodeficiency state

Primary immunodeficiency, the treatment of which is a process complex and long, requires knowledge of a healthy lifestyle and avoid any infections. Before appointment of comprehensive treatment, you should establish an accurate diagnosis, determining the disturbed link in the immune protection system. If the lack of immunoglobulin is revealed, replacement therapy is carried out by serums containing antibodies throughout life. The emerging complications in infectious diseases are treated with antibiotics, antiviral and antifungal drugs. In some cases, the primary immunodeficiency is treated with immunoglobulin, which is subcutaneously introduced or intravenously.

Immocorrection is also carried out by bone marrow transplantation and the use of immunomodulators.

Children with such a disease can not be vaccinated by alive vaccines. Adults living with the child are instilled only inactivated polyovaccinia.

Secondary immunodeficiency has not so pronounced violations in the work of the immune system.

This disease is provoked by violations in a hematopoietic system, which can be both congenital and acquired. The bone marrow simply ceases to produce blood cells. The disadvantage of red blood cells, platelets and leukocytes is detected.

The occurrence may be provoked by individual intolerance, in particular some drugs. The reason for this sensitivity is not always clear, but can be associated with the genetic defect of blood-forming cells.

Other reasons for occurrence may also be:

Signs of aplastic anemia

The symptoms of this state include:

• constant fatigue and weakness;
• irregular heart rhythm;
• pallitude of the skin;
• frequent bleeding from the nose;
• long bleeding after cuts;
• bleeding gums;
• frequent infectious diseases;
• dizziness and migraine.

Treatment of aplastic anemia

Easy cases of the disease require only constant patient observation. In more complex states, blood transfusion, bone marrow transplant, special preparations, stimulating blood formation cells are used. Often, immunosuppressants are used in the treatment, which help to weaken the immune response of the body, forcing the cells of the immune system without reacting to bone tissue. In recent years, the doctors have increasingly prone to the early bone marrow transplant, which avoids many complications.

Prevention of primary immune failure

Primary immunodeficiency syndrome is a hereditary disease, and, accordingly, there is no prevention measures for it. In order to avoid manifestations of the immunodeficiency state, it is necessary to determine the possible carrier of the defective gene in the family, where the history is positive. For such pathology, such as severe combined immunodeficiency, it is possible to conduct intrauterine diagnostics.

As the prevention of the emergence of secondary immunodeficiency, the correct lifestyle should be conducted, to have moderate physical exertion, avoid hich infection in the body. And for this it is necessary to avoid unprotected sexual relations and make sure to apply sterile medical instruments. Diseases provoked by immune failure are complex and covered in any manifestation. Careful attitude towards their health, an integrated approach and timely appeal to doctors will help save our future - our children.

Citation:Reznik I.B. Immunodeficiency states of genetic nature: a new look at the problem // RMG. 1998. №9. P. 3.

Currently it becomes clear that the primary immunodeficiency is not such a rare state, as was customary. However, despite the achievements in the field of diagnostic methods, more than 70% of patients, the immunodeficiency state is not diagnosed. The article presents clinical criteria and panel of primary laboratory methods for diagnosing primary immunodeficiency. NowAdays, IT Becomes Clear That Primary ImmunodeFiciency Is Not Such A Rare Condition As Considered Before. However, Despite Diagnostic Advances, ImmunodeFiciency Is Not Diagnosed In More Thank 70% of Patients. The Paper Gives Clinical Criteria and a Panel of Primary Laboratory Diagnostic Assays for Primary Immunodeficiencies. I.B. Reznik Head of the Clinical Immunology Department of Children's Hematology of the Ministry of Health of Russia, Doctor of Medical Sciences, Professor RGMU.

I.B.Reznik, MD, Head, Department of Clinical Immunology, Research Institute Of Pediatric Hematology, Ministry of Health of the Russian Federation; Professor, Russian State Medical University.

Introduction

With the normal course of pregnancy in the intrauterine period of development, the child is under sterile conditions. Immediately after birth, he begins colonized by microorganisms. Since the main microflora is not a pathogenic, this colonization does not cause illness. Subsequently, the exposition of pathogenic microorganisms with which the child did not meet, causes the development of an appropriate infectious disease. Each contact with the pathogen leads to an expansion of immunological memory and forms long-term immunity.
The four main components of the immune system are involved in the protection of the individual from the constant attacks of viruses, bacteria, mushrooms and the simplest, capable of causing infectious diseases. These components include antibodies mediated by antibodies, or in-cell, immunity, T cell immunity, phagocytosis and complement system. Each of these systems can act independently, but usually the interaction of the components of the immune system occurs during the immune response.
Endogenous, as a rule, genetically determined defects of one of the components of the immune system lead to a violation of the body protection system and are clinically detected as one of the forms of the primary immunodeficiency state (PID). Since many types of cell types and hundreds of molecules are involved in the normal functioning of the immune system and the immune response, the PID is based on numerous defects. WHO Scientific Group, publishing every 2 years reports on the Problem of PID, in the last report allocates more than 70 identified defects underlying the PID, while 2 years ago their number was 50, and 4 years ago - only 17. Examples of the PID are given in Table . one .
Recently, due to the detection of molecular defects underlying many immunodeficiency, and the essential variability of the clinical picture and the severity of the PID's current, the awareness of the possibility of their late manifestation, including adults, it becomes clear that the PID is not such a rare condition, As it was previously thought. For a significant part of the PID, the frequency is 1/25 000 - 1/100 000, although such options for congenital immune defects, as selective IGA deficiency, are found at the representatives of the White race with a frequency of 1/500 - 1/700 people. The total prevalence of PID is unknown, however, according to Immune Deficiency Foundation - IDF (USA), this figure is 4 times higher than the frequency of fibrosis.