The state of immunodeficiency. Immunodeficiencies. VI. Autoimmune diseases

Immunodeficiency is a condition that is characterized by a decrease in the function of the immune system and the body's resistance to various infections.

From the point of view of etiology (reasons for the development of the disease), we distinguish between primary and secondary immunodeficiencies.

Primary immunodeficiencies- This is a group of diseases that is characterized by a decrease in the function of the immune systemoccurring against the background of various genetic disorders. Primary immunodeficiencies are quite rare, about 1-2 cases per 500,000 people. In primary immunodeficiencies, individual components of immunity may be impaired: the cellular link, the humoral response, the phagocyte and compliment system. So, for example, immunodeficiencies with a violation of the cellular link of immunity include such diseases as agamaglobulinemia, DiGiorgio syndrome, Wiskott-Aldrich syndrome, Bruton's disease. Violation of the function of micro and macrophages are observed during chronic granulomatosis, Chediak-Higashi syndrome. Immunodeficiencies associated with a violation of the compliment system are based on a deficiency in the synthesis of one of the factors of this system. Primary immunodeficiencies are present throughout life. Patients with primary immunodeficiency, as a rule, die from various infectious complications.
Secondary immunodeficiencies are much more common than primary ones. Usually, secondary immunodeficiencies develop against the background of exposure to the body of adverse environmental factors or various infections. As in the case of primary immunodeficiencies, in secondary immunodeficiencies, either individual components of the immune system, or the entire system as a whole, can be disturbed. Most secondary immunodeficiencies (with the exception of immunodeficiency caused by infection with the HIV virus) are reversible and respond well to treatment. Below we consider in more detail the significance of various adverse factors in the development of secondary immunodeficiencies, as well as the principles of their diagnosis and treatment.

Reasons for the development of secondary immunodeficiency
Factors that can cause secondary immunodeficiency are very diverse. Secondary immunodeficiency can be caused by both environmental factors and internal factors of the body.

In general, all adverse environmental factors that can disrupt the body's metabolism can cause the development of secondary immunodeficiency. The most common environmental factors that cause immunodeficiency include environmental pollution, ionizing and microwave radiation, poisoning, long-term use of certain drugs, chronic stress and overwork. A common feature of the factors described above is a complex negative effect on all body systems, including the immune system. In addition, factors such as ionizing radiation have a selective inhibitory effect on immunity associated with inhibition of the hematopoietic system. People living or working in a polluted environment are more likely to suffer from various infectious diseases and more likely to suffer from cancer. It is obvious that such an increase in the incidence in this category of people is associated with a decrease in the activity of the immune system.

Internal factors that can provoke secondary immunodeficiency include:

Diagnosis of immunodeficiency
Primary immunodeficiency usually appears immediately after the birth of a child or some time after it. To accurately determine the type of pathology, a series of complex immunological and genetic analyzes are carried out - this helps to determine the place of impaired immune defense (cellular or humoral link), as well as determine the type of mutation that caused the disease.

Secondary immunodeficiencies can develop at any time in life. Immunodeficiency can be suspected in the case of frequently recurrent infections, the transition of an infectious disease to a chronic form, the ineffectiveness of conventional treatment, a small but prolonged increase in body temperature. Various tests and tests help to establish an accurate diagnosis of immunodeficiency: complete blood count, determination of blood protein fractions, specific immunological tests.

Treatment of immunodeficiency
Treatment of primary immunodeficiencies is a difficult task. To prescribe a complex treatment, it is imperative to establish an accurate diagnosis with the definition of a disturbed link in the immune defense. With a lack of immunoglobulins, lifelong replacement therapy is carried out with sera containing antibodies or ordinary donor plasma. Immunostimulating therapy with drugs such as Bronchomunal, Ribomunil, Taktivin is also used.

If infectious complications occur, treatment with antibiotics, antiviral or antifungal drugs is prescribed.

In secondary immunodeficiencies, disorders of the immune system are less pronounced than in primary ones. As a rule, secondary immunodeficiencies are temporary. In this regard, the treatment of secondary immunodeficiencies is much simpler and more effective than the treatment of primary disorders of the immune system.

Usually, treatment of secondary immunodeficiency begins with determining and eliminating the cause of its occurrence (see above). For example, the treatment of immunodeficiency against the background of chronic infections begins with the sanitation of foci of chronic inflammation.

Immunodeficiency against the background of vitamin and mineral deficiency is being treated with the help of complexes of vitamins and minerals and various food supplements (BAA) containing these elements. The regenerative capacity of the immune system is great, therefore, the elimination of the cause of immunodeficiency, as a rule, leads to the restoration of the immune system.

To speed up recovery and specific stimulation of immunity, a course of treatment with immunostimulating drugs is carried out. At the moment, a large number of different immunostimulating drugs are known, with different mechanisms of action. Preparations Ribomunil, Christine and Biostim contain antigens of various bacteria and, when introduced into the body, stimulate the production of antibodies and differentiation of active clones of lymphocytes. Timalin, Taktivin - contain biologically active substances extracted from the thymus of animals. Cordyceps - is the most effective immunomodulator that normalizes the immune system as a whole as a system. These drugs have a selective stimulatory effect on a subpopulation of T-lymphocytes. Sodium nucleinate stimulates the synthesis of nucleic acids (DNA and RNA), cell division and differentiation. Various types of interferons increase the overall resistance of the body and are successfully used in the treatment of various viral diseases.

Immunomodulatory substances of plant origin deserve special attention: Immunal, Echinacea rosea extract, and especially Cordyceps.

Bibliography:

Khaitov R.M., Secondary immunodeficiencies: clinic, diagnosis, treatment, 1999
Kirzon S.S. Clinical immunology and allergology, M. : Medicine, 1990
Modern problems of allergology, immunology and immunopharmacology, M., 2002

The site provides reference information for informational purposes only. Diagnosis and treatment of diseases should be carried out under the supervision of a specialist. All drugs have contraindications. Expert advice is required!

Immunodeficiency is a combination of various conditions of the body in which the functioning of the human immune system is disrupted. In this state, infectious diseases occur more often than usual, are very difficult and last a long time. By origin, immunodeficiency is hereditary (primary) and acquired (secondary). With different types of immunodeficiency, infections affect the upper and lower respiratory tract, skin and other organs. The severity, variety and nature of the course of the disease depends on the type of immunodeficiency. With immunodeficiency, a person can develop autoimmune pathologies and allergic reactions.

Primary immunodeficiency

Primary immunodeficiency is a disease of the immune system of a hereditary nature. This disease is transmitted from parents to children and persists throughout a person's life. There are many different forms of primary immunodeficiency. According to medical statistics, this condition occurs in one newborn in ten thousand. Some of the known forms of primary immunodeficiency appear immediately after the birth of a child, while other forms of the disease may not appear at all for many years. In about 85% of cases, the disease is diagnosed at a young age (up to twenty years). Primary immunodeficiency in 70% of cases is diagnosed in boys, since most of the disease syndromes are directly related to the X chromosome.

Genetic defects in primary immunodeficiency in humans are divided into several groups. With humoral immunodeficiency in the human body, the synthesis of immunoglobulins is disrupted, cellular immunodeficiency is characterized by an insufficient number of lymphocytes in the blood.

Defects in phagocytosis are manifested in the defective capture of bacteria by leukocytes. With a defect in the system, the proteins of the body are not able to destroy foreign cells.

Among primary immunodeficiencies, combined immunodeficiency is distinguished separately. Combined immunodeficiency is associated with genetic defects that lead to impaired function of B cells and T lymphocytes. With this disease, the production of antibodies is disrupted and the function of cellular immunity is reduced.

Secondary immunodeficiency

Secondary immunodeficiency is the presence in the human body of acquired diseases of the immune system. Due to weakened immunity, the human body is very often attacked by various infectious diseases. AIDS is the best-known example of secondary immunodeficiency. This disease can develop under the influence of radiation, drugs, various chronic diseases.

This condition can also develop with protein-calorie deficiency, as well as with a lack of vitamins and trace elements in the body. Deficiency of zinc, selenium and vitamin A has a particularly detrimental effect on the state of immunity. People with chronic metabolic disorders often suffer from secondary immunodeficiency. With this disease, it is very important to identify bacterial infections in time and begin the necessary treatment.

Signs of immunodeficiency

Various treatments for immunodeficiency are currently being practiced, but some of them are still under experimental development. Treatment of immunodeficiency is not complete without the general principles of care - vaccination, infection control, substitution therapy.

For immunodeficiency in humans, the manifestation of severe bacterial infections of a recurrent nature is characteristic. Bacterial infections lead to the development of bronchitis, sinusitis, otitis media. Patients with this disease often develop thrush, periodontitis, papillomas and warts form on the body, baldness and eczema occur. In this condition, various hematological disorders are often diagnosed. In some cases, disorders of the digestive system, vasculitis, convulsions, encephalitis, arthritis can be observed. According to some reports, immunodeficiency increases the risk of developing stomach cancer.

Treatment of immunodeficiency

Nowadays, immunocorrection is carried out in several ways - bone marrow transplantation, the use of immunoglobulins, immunomodulators. Usually, treatment for immunodeficiency is carried out using subcutaneous or intravenous administration of immunoglobulins.

With any type of immunodeficiency, it is very important to avoid infection and follow the principles of a healthy lifestyle. It is also very important for patients with this disease to detect bacterial and fungal infections in time and take measures to treat them. In some conditions of the body, it is necessary to carry out regular prophylactic antibiotic therapy. For chest infections, it is advisable to use physiotherapy methods, as well as regularly perform special physical exercises.

Video from YouTube on the topic of the article:

Secondary immunodeficiency- symptoms and treatment

What is secondary immunodeficiency? We will analyze the causes of occurrence, diagnosis and treatment methods in the article by Dr. E.Yu. Bychkova, an immunologist with 21 years of experience.

Publication date September 19, 2019Updated October 04, 2019

Definition of disease. Causes of the disease

Secondary immunodeficiency is a pathological condition of the body in which a defect in one or more mechanisms of the immune response leads to a violation of the immune system as a whole. It develops against the background of the underlying disease.

Secondary immunodeficiency is formed in people over 16 years of age with an initially normally functioning immune system. Usually its appearance is associated with environmental influences or some other factors, but in many of the patients it is possible to identify a genetic predisposition to the formation of immunity problems.

An immunologically healthy organism is able to control and prevent the development of infections, tumor processes, that is, to exercise immunological control of the internal environment. With the development of secondary immunodeficiency, the main "marker" of the problem is the development of infections caused by opportunistic agents (viruses, bacteria and fungi), and the activation of infections that usually do not occur in people with healthy immunity. Therefore, the main signs of secondary immunodeficiency are relapses and exacerbations of infections - acute, subacute and chronic.

Reasons for the development of secondary immunodeficiency states:

If you experience similar symptoms, consult your doctor. Do not self-medicate - it is dangerous for your health!

Symptoms of secondary immunodeficiency

Clinical manifestations of secondary immunodeficiency are varied. Very often, the symptoms of the underlying disease, which led to the formation of immunodeficiency, come to the fore. But the main manifestations of problems with immunity, which indicate the need for an immunological examination, are still present. These include:

frequent colds - more than six times a year in children and more than four times a year in adults;
the duration of each episode of the infectious-inflammatory process is more than two weeks;
recurrence of infections that usually do not occur in people with healthy immunity (herpes, infections caused by Candida fungi,);
recurrence of bacterial infections (furunculosis, hidradenitis, gynecological and ENT diseases);
a slight increase in temperature of an unclear nature, that is, such possible causes as tuberculosis and oncological diseases are excluded;
recurrence of lymphadenitis and lymphadenopathy (inflammation of the lymph nodes);
asthenic syndrome - weakness, fatigue, decreased performance, feeling of weakness after an 8-hour sleep;
chronic ulcers and non-healing wounds.

All chronic infections and inflammation occur against the background of a weakened immune defense. Therefore, any chronic infection will indicate the failure of the immune system, which cannot cope with the disease during an acute inflammatory process.

It should be remembered that the optimal variant of immune protection in acute infection should result in recovery on average within 2-4 weeks from the onset of the disease.

The pathogenesis of secondary immunodeficiency

During life, the body is exposed to various damaging factors that cause secondary immunodeficiency. They lead to inhibition of cellular immunity reactions, a decrease in leukocytes and interferons - proteins of the immune system that are produced by leukocytes and immune cells and block the spread of the virus. As a result, chronic infectious and inflammatory processes appear, often recurring.

Some trace elements are able to regulate the functioning of the immune system, such as zinc, iodine, lithium, copper, cobalt, chromium, molybdenum, selenium, manganese and iron. Their lack exacerbates immune dysfunction.

Lack of vitamins, an imbalance of macro- and microelements caused by an unbalanced diet lead to a violation of the cellular immune system: the response of lymphocytes to mitogens (substances that stimulate T-cells) decreases, atrophy of the lymphoid tissue is observed, and the function of neutrophils (blood cells that suppress harmful substances) is impaired. ) .

Most clearly, the mechanism of development of secondary immunodeficiency can be demonstrated using the example of viruses of the herpes family. Many viruses (herpes simplex viruses of the first and second types, cytomegalovirus, Epstein-Barr virus, rhinoviruses, enteroviruses) are constantly present in the cells of the body. Periodically activated under the influence of stress, unbalanced nutrition, concomitant pathology or immunosuppressive therapy, they contribute to the appearance of various clinical manifestations.

Tumors that arise in the body with a weakened immune defense deplete the immune system as they grow, and the ongoing treatment (surgery, radiation and chemotherapy) also aggravates the resulting immunodeficiency. In this case, the cellular link of immunity suffers:

All severe diseases also lead to the development of immune deficiency. For example, in diabetes mellitus, chemotaxis (the movement of microorganisms in response to a chemical) and phagocytic activity of neutrophils (the number of cells involved in the capture of viruses and bacteria) are inhibited, protection against bacterial infections is impaired, resulting in skin pyoderma (purulent diseases) and abscesses.

The body reacts to stress by releasing such active substances as catecholamines and glucocorticoids, which have an important modulating effect on the functioning of immune system cells. Under their influence, pro-inflammatory cytokines are released, processes are launched aimed at combating a possible infectious agent. In chronic stress, due to the prolonged effect of glucocorticoids on the cells of the immune system, the level of immunoglobulins and the activity of phagocytosis decrease. As a result, the process of apoptosis and cell damage is triggered during oxidation - programmed death in the cells of the immune system. If there was no excess load and the body had enough rest, then the work of the immune system returns to normal.

Classification and stages of development of secondary immunodeficiency

The form of secondary immunodeficiency can be:

According to the duration, two types of secondary immunodeficiency are distinguished:

Based on the study of the immune status, secondary immunodeficiency is distinguished by the localization of the main defect:

1. combined deficiency - changes affect several links of the immune defense;
2. T-cell deficiency;
3. predominantly B-cell deficiency;
4. defect of natural killers;
5. deficiency of macrophages and granulocytes;
6. deficiency of the complement system;
7. deficiency of the platelet system;
8. deficiency of the interferon system.

It is practically impossible to establish the localization of damage to the immune system, based only on symptoms, without a laboratory study of immune defense indicators, since a similar clinical picture can be observed with different types of secondary deficiency. For example, a person may be prone to viral infections in both T-cell deficiency and deficiency of the interferon system.

Separately, it should be said about physiological immunodeficiency in pregnant women. It is reversibly formed in a woman's body for the growth and development of the fetus and does not require immunocorrection.

Complications of secondary immunodeficiency

Secondary immunodeficiency, which develops against the background of an underlying infectious and/or inflammatory disease, causes severe life-threatening conditions. The lack of timely correction of this state of immunity closes the pathological circle and worsens the course of the underlying disease.

The most common complications of secondary immunodeficiency are severe infectious diseases: sepsis, abscess and phlegmon. Their main manifestations are high fever and signs of inflammation. With pneumonia, shortness of breath, cough, chest pain are observed. Sepsis develops when an infection enters the blood and is accompanied by a systemic inflammatory response, multiple organ failure, and is a life-threatening condition. With abscesses and phlegmon, there is a focus of purulent inflammation in the body with severe pain, swelling, hyperemia (redness).

Taking into account the great heterogeneity of these diseases, the prognosis and possible complications should be determined individually, based on the course and severity of the underlying disease, against which secondary immunodeficiency arose.

Diagnosis of secondary immunodeficiency

The diagnosis of "secondary immunodeficiency" is made on the basis of history, physical examination and examination of the function of the immune system.

To prescribe effective measures to correct immunity, it is very important to identify the factors that contributed to the development of immunodeficiency. Therefore, for a consultation with an immunologist, the patient should bring all the examinations he has, and the doctor will ask in great detail about the diseases he has undergone, the treatment performed, operations and the patient's lifestyle.

If secondary immunodeficiency is suspected, the doctor prescribes a blood test and an immunogram - immunological tests that evaluate the quantitative and qualitative characteristics of the components of the immune system.

The immunogram consists of several blocks:

Secondary immunodeficiency can be indicated by both low and high immunogram scores.

Since the immune system works according to a system of modules, in the early stages, a violation of immunity may be accompanied, for example, by an increase in T-link indicators or a deficiency in interferon status indicators. This pattern is observed at the beginning of the chronic course of herpetic infections. At later stages of secondary immunodeficiency, a decrease in indicators can already affect both links, which can often be seen in the immunograms of patients with common oncological diseases.

If you suspect an imbalance of key nutrients (vitamins, trace elements, etc.), an immunologist may prescribe studies:

In his conclusion, an immunologist can make a diagnosis of "secondary immunodeficiency" as a main diagnosis, as well as a concomitant one. It all depends on the clinical picture.

Treatment of secondary immunodeficiency

Treatment of a patient with secondary immunodeficiency is carried out in conjunction with a doctor who supervises the patient about the underlying disease. The task of an immunologist is to select immunocorrective therapy. "Correction of immunity" in this case means treatment aimed at restoring the body's weakened immune defenses, correcting the imbalance of its components and immune reactions, weakening pathological immune processes and suppressing autoimmune reactions.

Treatment of secondary immunodeficiency begins with determining and eliminating the cause of its occurrence. For example, in violation of immunity caused by an infectious-inflammatory process, sanitation (purification) of foci of chronic inflammation is required.

If secondary immunodeficiency arose as a result of vitamin and mineral deficiency, then complexes containing deficient components are prescribed. For example, with aging of the thymus gland and depletion of the lymph nodes, vitamins B6 are prescribed. With an exacerbation or the onset of autoimmune and lymphoproliferative diseases, vitamins E are indicated.

Important minerals for the immune system are zinc, iodine, lithium, copper, cobalt, chromium, molybdenum, selenium, manganese, iron. These trace elements are necessary for the activation of enzymes involved in immune responses. For example, zinc prevents the death of immune system cells.

Sometimes the immune system cannot cope with the pathological process due to a deficiency of any protective factors (cells and cytokines). In such cases, the immunologist prescribes immunostimulating drugs to speed up recovery and stimulate immunity.

Taking immunomodulators in acute infectious inflammation allows you to:

reduce the depth of damage in inflamed tissues;
reduce the time of rehabilitation and recovery;
reduce the risk of fatal complications in severe cases;
prevent chronic disease and the formation of resistant strains of infectious agents.

In chronic infectious inflammation, immunomodulators contribute to:

a significant reduction in the symptoms of the disease or complete recovery;
a significant increase in the period of remission between exacerbations of recurrent infection.

The degree of effectiveness of immunocorrection is affected by the frequency of its use and the stage of the disease. The duration of action of immunomodulators depends on the nature of the drug, indicators of the immune status and the type of disease that caused secondary immunodeficiency.

Elimination of the deficiency of one link of immunity can lead to compensation of another link, since the immune system works on the principle of interconnected modules.

It can be prescribed as one immunomodulator, or several, that is, a combination of them. Under combined immunocorrection understand the sequential or simultaneous use of several modulators with different mechanisms of action. Today, a large number of immunomodulatory drugs with different mechanisms of action are known.

Indications for combined immunotherapy are:

chronicity of the main pathological process (when the disease lasts more than three months);
frequent relapses of the underlying disease (more than four times a year);
the presence of complications of the underlying pathological process;
severe intoxication syndrome;
disturbed metabolism;
unsuccessful immunocorrection with one drug for a month;
damage to several links (phagocytosis, T- and B-links of immunity);
the need for a multidirectional effect on the links of immunity - stimulation of one link and restraint of another.

IMPORTANT: It is impossible to prescribe immunocorrectors on your own, since their uncontrolled use can only provoke the development of secondary immunodeficiency.

Forecast. Prevention

In secondary immunodeficiency, disorders of the immune system are less pronounced than in primary. In most cases, several factors that suppress the immune response are identified.

As a rule, the prognosis of the course of secondary immunodeficiency is determined by the severity of the disease that caused it. For example, an immunodeficiency caused by a lack of vitamins or a violation of the work and rest regimen is much easier to compensate than an immunodeficiency provoked by a tumor process, diabetes mellitus or HIV infection.

In a child's body, individual parts of the immune system are still immature. T-lymphocytes are just beginning to "get acquainted" with various infectious agents, so the child often suffers from various acute respiratory viral infections. Over time, there is an accumulation of "memory cells". As they grow older, a wide "repertoire" of T-lymphocytes is formed that can recognize and quickly launch an immune response, and therefore the incidence decreases.

As the body ages, so does the immune system. For example, due to age-related changes in the response to new antigens, fewer T-cells are involved, cooperation between cells of the immune system worsens, and the efficiency of phagocytosis (absorption of viruses and dead cells) decreases. Therefore, many infectious and inflammatory diseases proceed much more severely with age and more often give complications.

The primary prevention of secondary immunodeficiency is to maintain a healthy lifestyle, a balanced diet, and smoking cessation. All this helps to prevent the development of various diseases.

Secondary prevention can be carried out with the timely treatment of infectious and general somatic diseases.

People with secondary immunodeficiency need "special conditions" that will prevent aggravation of impaired immunity.

The human immune system is designed to respond in time to the invasion of foreign elements. Its correct functionality is the recognition of a threat and its destruction. Primary immunodeficiency means that the child did not develop a protective mechanism during fetal development, or he did not receive it due to a hereditary factor. As a result, harmful microorganisms entering his body will bring him maximum harm. The same can be said about atypical cells that have a negative impact on health and cause pathologies of varying severity.

A distinction should be made between primary and secondary immunodeficiencies. Primary is determined in the infant shortly after birth. His body is deprived of the ability to defend itself against antigens, it is susceptible to infectious invasion. This is expressed in the fact that the baby is often sick, he is overcome by repeated ailments, he can hardly endure them, and gets complications. Severe forms of primary immunodeficiency lead to death in infancy.

Rare cases are known when primary immune deficiency manifested itself in adults. This is possible, but for this a person must have a high compensation for a certain type of disease.

The clinic of the disease is a re-infection, the transition of diseases to a chronic form. What does primary immunodeficiency lead to?

The patient suffers from bronchopulmonary anomalies.
It affects the mucous membranes and skin.
There are problems with ENT organs.
PIDS, as a rule, leads to lymphadenitis, abscesses, osteomyelitis, meningitis, sepsis.
Certain forms of primary immunodeficiency provoke allergies, autoimmune diseases, and the growth of malignant neoplasms.

The study of violations of the functions of immune defense is carried out by immunology - the science of the development and formation of a protective mechanism that counteracts the penetration of antigens into the body and destroys cells damaged by harmful substances and microorganisms.

The earlier PIDS is diagnosed, the more likely the child is to survive and continue life in a satisfactory state of health. It is important to timely determine the gene mutation, which makes it possible to decide on family planning.

Immunodeficiency is considered a persistent anomaly of the protective mechanism, which causes a failure in the immune response to the influence of antigens. This failure can be of four types:

age, that is, arising in childhood or in old age;
acquired due to malnutrition, lifestyle, medication, AIDS virus, etc.;
developed as a result of various infections;
congenital or primary ID.

PIDS are classified according to the forms and severity of the disease. Primary immunodeficiencies include:

ID characterized by damage to several cell complexes;
Reticular dysgenesis, in which stem cells are absent, dooms the newborn to death.
Severe combined ID is a hereditary disease caused by dysfunction of B and T-lymphocytes.
Di George syndrome - or anomalies of the thymus, parathyroid glands - underdevelopment or absence of the thymus gland. As a result of the defect, T-lymphocytes are affected, congenital heart defects, deformations in the bone structure, the structure of the facial bones, kidney defects and dysfunction of the central nervous system occur.
Primary immunodeficiency due to damage to B-lymphocytes.
Disorders in myeloid cells that provoke chronic granulomatous disease (CGD) with an abnormality in oxygen metabolism. A defect in the production of active oxygen leads to chronic fungal and bacterial infections.
Defects in complex blood proteins that impair humoral protection. Several components may be missing from the complement system.

Need to know! Cellular immunodeficiency is characterized by a deficiency of immunocompetent cells, which include lymphocytes, plasma cells, macrophages. Humoral immunodeficiency means dysfunction in the production of antibodies.

Symptoms of primary immunodeficiencies

Primary immunodeficiencies are indicated by signs and symptoms. Studying the clinical picture of the course of the disease, the doctors of the clinic identify a type of immune deficiency. This is facilitated by examination, tests, history taking to determine the genetic pathology.

Primary deficiencies of cellular immunity give rise to viral and fungal infections. Characteristic signs are repeated colds, severe ARVI, chickenpox, mumps, frequent manifestations of herpes. The patient suffers from thrush, inflammation of the lungs, gastrointestinal tract, caused by fungi. Cellular immunodeficiency increases the risk of oncology, lymphoma.
Lack of humoral protection provoke bacterial infections. These are pneumonia, ulcers on the skin, erysipelas, staphylococcus aureus, streptococcus.
Insufficiency of the level of secretory immunoglobulin A causes damage to the mucous membranes in the mouth, nose, eyes, intestines, bronchi suffer.
Combined ID are characterized by complications of viral and bacterial infections. Manifestations of this form of primary immunodeficiency are non-specific - they are expressed in malformations, tumor processes, lymphoid tissues, thymus gland, megaloblastic anemia.
Congenital neutropenia and dysfunction of phagocytosis of granulocytes generates bacterial inflammatory processes with ulcers, abscesses. The result may be sepsis.
Complement-associated primary immunodeficiencies cause bacterial infections, autoimmune diseases, as well as recurrent edema on the body and limbs - hereditary angioedema (HAE).

Causes of Primary Immunodeficiencies

Dysfunctions of the immune system are formed in the embryo inside the womb. This process is influenced by various factors. Prenatal diagnosis shows a combination of congenital malformations of the fetus with immunodeficiency. The etiology of PIDS is based on three pathologies.

Genetic mutations, meaning that changes have occurred in the genes on which the performance of their functions by immunocompetent cells depends. That is, the process of development and differentiation of cells is disrupted. The inheritance of the anomaly is autosomal recessive when both parents are carriers of the mutagen. Only a small number of mutations develop spontaneously or germinally (in germ cells).
A teratogenic factor is the effect of dangerous toxins on the embryo, leading to congenital primary immunodeficiency. Provoke ID TORCH-infection - cytomegalovirus, herpes, rubella, toxoplasmosis in pregnant women.
Unclear etiology. Immune deficiency, the cause of which is not clear.

Such conditions include asymptomatic ID, which are manifested by infectious complications in provocative situations. If even one of the elements of the defense mechanism undergoes an anomaly, then the defenses weaken, the patient becomes an object for the invasion of various infections.

Diagnosis of primary immune deficiency

Immunodeficiency states are identified by type, since the primary ID is most often congenital, its variety is determined in the first months or weeks. A visit to the doctor is required for frequent illnesses of the baby, colds, the development of fungal, viral, bacterial infections. Anomalies in the development of the child may also depend on the primary immunodeficiency. To solve the problem requires urgent diagnosis and immediate treatment.

The disease identification method includes the following procedures:

general examination, during which attention is paid to damage to the skin, mucous membranes, pustular processes, subcutaneous edema of adipose tissue;
a study of the leukocyte formula according to a general blood test, ID is indicated by the presence of leukopenia, neutropenia, agranulocytosis, and other disorders;
blood biochemistry shows dysgammaglobulinemia, the presence of uncharacteristic metabolites, indicative of primary humoral ID;
a specific study on the response of the immune system. The indicators of the activity of immunocompetent cells are studied;
molecular genetic analysis - a method of gene sequencing for the type of mutation. This is a way to determine the syndromes of Bruton, DiGeorge, Duncan, Wiskott-Aldrich.

The doctor differentiates immunodeficiency states with acquired secondary ID, arising from the influence of radiation, toxic substances, autoimmune diseases, and oncology. In adults, the diagnosis is difficult to make, since the signs are smoothed out, the symptoms are implicit.

Prenatal diagnosis

Determination of primary ID by chorionic villus biopsy is called prenatal identification of the form of the disease. In addition, cell culture of fetal waters, fetal blood is being studied. These are complex tests that are indicated in cases where the mutagen is detected in the parents.

But for the detection of X-linked severe combined immunodeficiency, this method gives an accurate result, and also clarifies the diagnosis in primary ID syndromes, chronic granulomatosis, and other conditions of SCID.

Treatment of primary immunodeficiencies

Different etiology and pathogenesis of diseases do not allow to develop a common method for treating pathology. In severe forms, therapeutic treatment is not relevant, it brings only temporary relief, but death is inevitable from complications of immunodeficiencies. In these cases, only bone marrow transplantation or the embryonic substance of the thymus gland helps.

The deficiency of cellular immunity is compensated by the method of using specific colony-stimulating drugs. This is replacement immunotherapy with thymalin, taktivin, levamisole and other means, the choice of which is made by the immunologist. Fermentopathies are corrected by enzymes, metabolites. A common drug of this series is biotin.

Dysglobulinemia (lack of humoral protection) is treated with immunoglobulin replacement, depending on the missing substances of this kind. But the main obstacle to the progress of the disease is the prevention of infections. Moreover, vaccination of children with primary ID has no effect, it is dangerous.

Forecast 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 the timely access to a doctor and care for children. It is impossible to allow infection of the child with viral, bacterial, fungal pathogens.

If you are planning the birth of a child and you have problems with a gene mutation, then consultation with an immunologist is required. During pregnancy, you need to undergo prenatal diagnosis, beware of infections and follow all the doctor's recommendations.

For patients with ID, it is important to observe personal hygiene, take care of the oral cavity, nasal mucosa, and eyes carefully, without damaging their integrity. A balanced diet, exclusion of contact with patients during epidemics, drug prevention of infections are necessary.

Complications after immunodeficiency

Primary immunodeficiencies lead to formidable complications. The result of the consequences can be the death of a person. Such conditions are considered sepsis, abscesses, pneumonia, severe infections. Autoimmune diseases are possible when the failure of the immune system is that it destroys its own cells. The risk of oncological diseases and imbalance of the gastrointestinal tract and the cardiovascular system increases.

Conclusion

Primary immunodeficiency is not always a sentence. It is necessary to be observed by an immunologist constantly, this will help maintain a satisfactory quality of life and live long.

- a group of pathological conditions of a predominantly congenital nature, in which there is a violation of the work of certain parts of the immune system. Symptoms vary, depending on the type of disease, mainly there is an increased susceptibility to bacterial and viral agents. Diagnosis of pathology is carried out by means of laboratory research methods, molecular genetic analysis (for hereditary forms), and the study of the patient's history. Treatment includes replacement therapy, bone marrow transplantation, and infection control measures. Some forms of immunodeficiency are incurable.

General information

Primary immunodeficiencies have been actively studied since the 50s of the XX century - after the first condition of this type, which received his name, was described in 1952 by the American pediatrician Ogden Bruton. At the moment, more than 25 varieties of pathology are known, most of them are genetically determined diseases. The incidence of different types of immunodeficiency ranges from 1:1,000 to 1:5,000,000. The vast majority of patients are children under the age of 5 years, mild forms may first be detected in adults. In some cases, an immunodeficiency state is detected only according to the results of laboratory tests. Some types of the disease are combined with numerous malformations, have a high mortality rate.

Causes of Primary Immunodeficiencies

Immunodeficiency states of a primary nature begin to form at the stage of intrauterine development under the influence of various factors. Often they are combined with other defects (dystrophies, anomalies of tissues and organs, fermentopathy). According to the etiological basis, there are three main groups of congenital pathologies of the immune system:

due to genetic mutations. The vast majority of diseases arise due to defects in the genes responsible for the development and differentiation of immunocompetent cells. Autosomal recessive or sex-linked inheritance is usually noted. There is a small proportion of spontaneous and germline mutations.
As a result of teratogenic effects. Congenital problems with immunity can be caused by the influence of toxins of various nature on the fetus. Immunodeficiency often accompanies malformations caused by TORCH infections.
Unclear etiology. This group includes cases when it is not possible to identify the cause of the weakness of the immune system. These may be as yet unexplored genetic anomalies, weak or unidentified teratogenic effects.

The study of the causes, pathogenesis and search for methods of treatment of primary immunodeficiencies continues. There are already indications of a whole group of similar conditions that do not manifest themselves as pronounced symptoms, but under certain conditions can provoke infectious complications.

Pathogenesis

The mechanism of development of immunity deficiency depends on the etiological factor. In the most common genetic variant of the pathology, due to the mutation of some genes, the proteins encoded by them are either not synthesized or have a defect. Depending on the functions of the protein, the processes of formation of lymphocytes, their transformation (into T- or B-cells, plasma cells, natural killers) or the release of antibodies and cytokines are disrupted. Some forms of the disease are characterized by a decrease in the activity of macrophages or a complex insufficiency of many links of immunity. Varieties of immunodeficiency, caused by the influence of teratogenic factors, most often occur due to damage to the rudiments of immune organs - thymus, bone marrow, lymphoid tissue. The underdevelopment of individual elements of the immune system leads to its imbalance, which is manifested by a weakening of the body's defenses. Primary immunodeficiency of any origin causes the development of frequent fungal, bacterial or viral infections.

Classification

The number of types of primary immunodeficiencies is quite large. This is due to the complexity of the immune system and the close integration of its individual links, as a result of which the disruption or "turning off" of one part contributes to the weakening of the entire body's defenses as a whole. To date, a complex branched classification of such conditions has been developed. It consists of five main groups of immunodeficiencies, each of which includes several of the most common types of pathology. In a simplified version, this classification can be represented as follows:

Primary deficiencies of cellular immunity. The group combines conditions caused by insufficient activity or low levels of T-lymphocytes. The cause may be thymus deficiency, fermentopathy and other (mainly genetic) disorders. The most common forms of this type of immunodeficiency are DiGeorge and Duncan syndromes, orotaciduria, lymphocyte enzyme deficiency.
Primary deficiencies of humoral immunity. A group of conditions in which the function of predominantly B-lymphocytes is reduced, the synthesis of immunoglobulins is impaired. Most of the forms belong to the category of dysgammaglobulinemia. The best known syndromes are Bruton, West, IgM or transcobalamin II deficiencies.
Combined primary immunodeficiencies. An extensive group of diseases with reduced activity of both cellular and humoral immunity. According to some reports, this type includes more than half of all types of immune deficiency. Among them, severe (Glanzmann-Rinicker syndrome), moderate (Louis-Bar disease, autoimmune lymphoproliferative syndrome) and minor immunodeficiencies are distinguished.
Primary failure of phagocytes. Genetic pathologies that cause reduced activity of macro- and microphages - monocytes and granulocytes. All diseases of this type are divided into two large groups - neutropenia and defects in the activity and chemotaxis of leukocytes. Examples are Kostman's neutropenia, lazy leukocyte syndrome.
Complement protein deficiencies. A group of immunodeficiency states, the development of which is due to mutations in the genes encoding complement components. As a result, the formation of the membrane attack complex is disrupted, and other functions in which these proteins are involved suffer. This causes complement-dependent primary immunodeficiencies, autoimmune conditions or.

Symptoms of primary immunodeficiencies

The clinical picture of various forms of immunity deficiency is very diverse, it can include not only immunological disorders, but also malformations, tumor processes, and dermatological problems. This allows pediatricians or immunologists to differentiate different types of pathology even at the stage of physical examination and basic laboratory tests. However, there are certain general symptoms that are similar in diseases of each group. Their presence indicates which link or part of the immune system was affected to a greater extent.

In primary deficiencies of cellular immunity, viral and fungal diseases prevail. These are frequent colds, more severe than normal, the course of childhood viral infections (chickenpox, mumps), pronounced herpetic lesions. Often there is candidiasis of the oral cavity, genital organs, there is a high probability of fungal infections of the lungs, gastrointestinal tract. Individuals with deficiencies in the cellular link of the immune system have an increased risk of developing malignant neoplasms - lymphomas, cancer of various localization.

The weakening of the humoral defense of the body is usually manifested by increased sensitivity to bacterial agents. Patients develop pneumonia, pustular skin lesions (pyoderma), often taking on a severe character (staphylo- or streptoderma, erysipelas). With a decrease in the level of secretory IgA, the mucous membranes (the conjunctiva of the eyes, the surfaces of the oral and nasal cavities), as well as the bronchi and intestines, are mainly affected. Combined immunodeficiencies are accompanied by both viral and bacterial complications. Often, it is not manifestations of a lack of immunity that come to the fore, but other, more specific symptoms - megaloblastic anemia, malformations, tumors of the thymus and lymphoid tissue.

Congenital neutropenia and impaired granulocyte phagocytosis are also characterized by the frequent occurrence of bacterial infections. Pyoinflammatory processes with the formation of abscesses in various organs are not uncommon; in the absence of treatment, the formation of phlegmon, sepsis is possible. The clinical picture of complement-associated immunodeficiencies is presented either as a decrease in the body's resistance to bacteria, or in the form of autoimmune lesions. A separate variant of complement-dependent immunity disorders - hereditary ANO - is manifested by recurrent edema in various parts of the body.

Complications

All types of primary immunodeficiency are united by an increased risk of severe infectious complications. Due to the weakening of the body's defenses, pathogenic microbes cause severe damage to various organs. Most often, the lungs (pneumonia, bronchitis, bronchiectasis), mucous membranes, skin, and organs of the gastrointestinal tract are affected. In severe cases of the disease, it is the infection that causes death in infancy. Accompanying disorders can lead to aggravation of the pathology - megaloblastic anemia, anomalies in the development of the heart and blood vessels, damage to the spleen and liver. Some forms of immunodeficiency states in the long term can cause the formation of malignant tumors.

Diagnostics

In immunology, a huge number of techniques are used to determine the presence and identification of the type of primary immunodeficiency. More often, immunodeficiency states are congenital, so they can be detected already in the first weeks and months of a child's life. The reason for contacting a specialist is frequent bacterial or viral diseases, burdened hereditary history, the presence of other malformations. Varieties of mild immunodeficiencies can be determined later, often discovered by chance during laboratory tests. The main methods for diagnosing hereditary and congenital disorders of immunity are:

General inspection. It is possible to suspect the presence of severe immunodeficiency even when examining the skin. In sick children, severe dermatomycosis, pustular lesions, atrophy and erosion of the mucous membranes are often detected. Some forms are also manifested by swelling of the subcutaneous fatty tissue.
Lab tests. The leukocyte formula in the general blood test is disturbed - leukopenia, neutropenia, agranulocytosis and other anomalies are noted. With some varieties, an increase in the level of certain classes of leukocytes is possible. A biochemical blood test in primary immunodeficiency of the humoral type confirms dysgammaglobulinemia, the presence of unusual metabolites (with fermentopathy).
Specific immunological studies. To clarify the diagnosis, a number of methods are used to determine the activity of the immune system. These include an analysis for activated leukocytes, phagocytic activity of granulocytes, the level of immunoglobulins (in general and individual fractions - IgA, E, G, M). Also, a study is made of the level of complement fractions, interleukin and interferon statuses of the patient.
Molecular genetic analysis. Hereditary varieties of primary immunodeficiencies can be diagnosed by sequencing genes whose mutations lead to one form or another of the disease. This confirms the diagnosis in DiGeorge, Bruton, Duncan, Wiskott-Aldrich syndromes and a number of other immunodeficiency states.

Differential diagnosis is primarily made with acquired secondary immunodeficiencies, which can be caused by radioactive contamination, poisoning with cytotoxic substances, autoimmune and oncological pathologies. It is especially difficult to distinguish the cause of the deficiency in smoothed forms, which are determined mainly in adults.

Treatment of primary immunodeficiencies

There are no uniform treatment principles for all forms of pathology due to differences in etiology and pathogenesis. In the most severe cases (Glanzmann-Rinicker syndrome, Kostman's agranulocytosis), any therapeutic measures are temporary, patients die due to infectious complications. Some types of primary immunodeficiencies are treated with bone marrow or fetal thymus transplants. Insufficiency of cellular immunity can be alleviated by the use of special colony-stimulating factors. With fermentopathy, therapy is carried out using the missing enzymes or metabolites - for example, biotin preparations.

With dysglobulinemia (primary humoral immunodeficiency), replacement therapy is used - the introduction of immunoglobulins of the missing classes. In the treatment of any form, it is extremely important to pay attention to the elimination and prevention of infections. At the first signs of a bacterial, viral or fungal infection, patients are prescribed a course of appropriate drugs. Often, for the complete cure of infectious pathologies, increased dosages of drugs are required. In children, all vaccinations are canceled - in most cases they are ineffective, and some are even dangerous.

Forecast and prevention

The prognosis of primary immunodeficiency varies greatly in different types of pathology. Severe forms can be incurable, leading to death in the first months or years of a child's life. Other varieties can be successfully controlled through substitution therapy or other therapies, with little impact on the patient's quality of life. Mild forms do not require regular medical intervention, however, patients should avoid hypothermia and contact with sources of infection, and if there are signs of a viral or bacterial infection, contact a specialist. Prevention measures, given the hereditary and often congenital nature of primary immunodeficiencies, are limited. These include medical genetic counseling for parents before conceiving a child (with aggravated heredity) and prenatal genetic diagnosis. During pregnancy, women should avoid contact with toxic substances or sources of viral infections.