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Immunodeficiency (IDS) are the states which are characterized by decrease of the activity or inability of an organism to effective implementation of reactions of a cellular and/or humoral link of immunity.

Органы иммунной системы человека

Bodies of immune system of the person

Reasons of immunodeficiency:

By origin all IDS are subdivided on:

- physiological;

- primary (hereditary, inborn). They are result of the genetic defect causing disturbances of processes of proliferation, a differentiation and functioning of cells of immunocompetent system;

- secondary (acquired in the post-natal period). Develop under the influence of various factors of physical or biological character.

On preferential damage of cells of immunocompetent system distinguish 4 IDS groups:

- with preferential damage of cellular immunity (T-dependent, cellular);

- with preferential damage of humoral immunity (V-dependent, humoral);

- with defeat of system of phagocytosis (A-dependent);

- combined, with defeat of cellular and humoral links of immunity

Symptoms of immunodeficiency:

Physiological IDS.

Physiological IDS include immunodeficiencies (IDES) of newborns, pregnant women and persons of senile age.

1. Immunodeficiency of newborns. By the time of the birth at healthy children blood contains parent IgG and a small amount of own IgG, IgM, IgA. The immunoglobulins received from mother contain antibodies against all species of microbes to which mother contacted thanks to what the child is protected from them for the first months of life. Level of maternal immunoglobulins gradually decreases, and their maximum deficit is observed in 2-3 months after the birth. Then the level of own immunoglobulins of the child in blood begins to increase gradually, and the number of IgM reaches the normal level of the adult at the end of the 1st year of life at boys and the 2nd – at girls; IgG1 and IgG4 at the age of 6-8 years; IgG3 – in 10, and IgG2 - in 12 years. Concentration of IgE reaches the normal level of the adult only 10-15 years later after the birth. Secretory IgA are absent at newborns and appear in 3 months after the birth. Optimum concentration of secretory IgA is established at the age of 2-4 years. The plasma IgA level reaches that indicator at adults in 10-12 years. IDES of newborns it is caused by the fact that the high content of lymphocytes in peripheral blood at newborns is combined with their low activity. At newborn children also low phagocytal activity and the opsonizing ability of blood are noted. Complement level at newborns is reduced and reaches the adult's level by 3-6th month of life.

2. Immunodeficiency of pregnant women. The immune status of pregnant women differs in decrease in number T - and V-lymphocytes. Increase in activity S3komplementa is at the same time noted that explain with influence of placental steroids on its synthesis in a liver.

3. Immunodeficiency of persons of senile age. Insufficiency of immunity when aging is shown in decrease of the activity of its humoral and cellular links. When aging total number of peripheral blood lymphocytes decreases. Functional activity of T - and V-lymphocytes when aging falls, intensity of antibody formation in response to an antigen challenge decreases. At senile age class IgM antibodies are generally produced, products of IgA, IgG are sharply lowered, IgE synthesis in this connection the course of atopic allergic reactions weakens is suppressed. In process of aging phagocytal activity of macrophages, neutrophils decreases, activity of a complement, lysozyme and bactericidal activity of blood serum decrease.

Primary IDS.

Primary IDS are the genetically caused inability of an organism to realize this or that link of an immune response. Genetically caused defects of one of components of immune system endogenous, as a rule, lead to disturbance of system of protection of an organism and clinically come to light as one of forms of primary IDS. As many types of cells and hundreds of molecules participate in normal functioning of immune system and an immune response, numerous options of defects are the cornerstone of primary immunodeficience. The scientific group of WHO in 1997 marked out more than 70 identified genetic defects at various levels of transformation of stem cells of T - and V-lymphocytes or the subsequent stages of their differentiation which are the cornerstone of primary IDS.

Recently in connection with detection of the molecular defects making a basis of many immunodeficiencies and essential variability of a clinical picture and weight of their current, a possibility of their late manifestation, including at adults, it becomes clear that primary IDS are not so rare state as it was considered still. Frequency of a considerable part of primary IDS makes 1/25000 - 1/50000 though such options of inborn immune defects as the selection deficit of IgA, meets frequency of 1/500 - 1/700 people. According to a number of authors, insufficiency of V-system of lymphocytes and a humoral link of immunity is noted at 50-75% from total number of sick IDS; in 20% of cases the combined insufficiency of cellular and humoral immunity is noted; in 10% - the isolated insufficiency of cellular immunity, in 18% - insufficiency of phagocytosis and in 2% - insufficiency of system of a complement.

IDS with preferential disturbance of a cellular link of immunity.

Pathology of a cellular link of immunity is shown at various stages of maturing of T lymphocytes - from a stem cell before development of their specialized subpopulations.

At defects of preferential cellular link of immunity frequent infections of respiratory and urinary tract, persistent digestive disturbances, chronic generalized candidiasis of skin and mucous membranes of an oral cavity, digestive tract are characteristic. Candidosis defeat can come to light in the first months of life in the form of stomatitis, dermatitis, a reactive hyperplasia of adenoid fabric of almonds, lymph nodes, high intensity of caries is noted, bronchopulmonary pathology, a furunculosis develop, in saliva the maintenance of secretory IgA is increased. It should be noted that CD8 T lymphocytes exercise immunological surveillance behind internal environment, providing, in particular, elimination of the cells which underwent oncogenous transformation. In case of insufficiency of T-system of lymphocytes there is an onkogennoopasny situation.

1. Di Georgie's syndrome arises at hypo - and an aplasia of a thymus and epithelial bodies. The disease is caused by disturbance of an embryonal differentiation of an epithelium in the field of the 3rd and 4th pharyngeal pockets. The number of lymphocytes in peripheral blood is considerably reduced. Synthesis of humoral antibodys is not broken, but defect in a differentiation of stem cells in T lymphocytes is noted. At children with Di Georgie's syndrome skin transplants are not torn away, there are no reactions of GZT. The disease is shown in the neonatality period (a hypocalcemia, spasms, signs of a candidiasis, an infection of respiratory and urinary tract, persistent digestive disturbances).

2. A lymphocytic dysgenesis (Nezelof's syndrome) – quantitative and qualitative insufficiency of T-system as a result of an atrophy of a thymus gland and lymph nodes. It is characterized by lack of cellular reactions of immunological protection at the normal content of immunoglobulins in a blood plasma. It is shown in the first weeks and months of life. The arrest of development of the child, long septic process with the pyoinflammatory centers in internals and skin are noted. In peripheral blood extremely low maintenance of lymphocytes is noted; the blastogenic response of lymphocytes is sharply oppressed; reaction of GZT is poorly expressed. Content of immunoglobulins of all classes in peripheral blood – within norm. Children perish in the first months of life from sepsis more often.

IDS with preferential damage of V-system

Humoral immunodeficiencies carry to the most common forms of primary IDS.

1. Primary agammaglobulinemia - Bruton's disease. Arises at defect of maturing of predecessors of V-cells in V-lymphocytes. Only boys are ill. At an agammaglobulinemia the general maintenance of  globulin in blood of the child makes less than 2 g/l. A mode of inheritance of "a classical form" - recessive, linked to X-chromosome. Children with an inborn hypogammaglobulinemia can normally develop to 2-3 years though to their thicket early displays of a disease in the first months or on the first year of life are observed. Resistance to opportunistic pathogenic bacteriums, mushrooms is sharply reduced. Often there are pyoinflammatory diseases of mucous membranes, integuments and parenchymatous bodies. Low resilience to bacterial infections is not combined with decrease in resistance to viruses. Some viral infections (a rubella, measles, a viral hepatitis) at them proceed even easier, than at children with the kept immunological resistance. However high sensitivity of patients to a poliomyelitis virus is noted. The antigen challenge does not lead to strengthening of synthesis of antibodies. The indicators characterizing cellular immunity do not differ from those normal. Reduction or lack of lymphocytes and plasmocytes in marrow is noted, the last do not contain also in lymph nodes, a spleen.

2. General Variable Hypogammaglobulinemia (GVH). It is the IDS heterogeneous group which development is connected with disturbance of ability of V-lymphocytes to be transformed to plasmocytes against the background of an antigen challenge. The quantity of the V-lymphocytes circulating in blood does not differ from norm, however disturbance of their differentiation takes place. The hyperplasia of lymph nodes, a lymphoid pharyngeal ring, sometimes – increase in the sizes of a spleen are characteristic of patients. At children with OVG specific immunity after vaccination does not form; tendency to development of recurrent inflammatory processes of the infectious nature is found in them (sinusitis, otitises, chronic pneumonia, pharyngitises, tonsillitis, etc.). At adult sick OVG the ascending cholangitis and cholelithiasis, sometimes arthritises, atrophic gastritis often develop. Total quantity of immunoglobulins, especially IgG, is reduced.

Insufficiency of local immunity at sick OVG does not correlate with concentration of the plasmatic IgA level and is probably connected with disturbances of synthesis of secretory immunoglobulins. At many patients tendency to autoimmune processes is noted. It is established that at sick OVG natural cells killers are sharply activated, and their activity by 5 times exceeds normal values.

3. The selection deficit of immunoglobulins. Development of IDS with the selection disturbance of synthesis of IgG, IgA is possible. Their formations can be the cornerstone as blockade of development of separate subpopulations of V-lymphocytes, and, what is more often, increase in activity of CD8 of population of lymphocytes.

Deficit of the subclasses IgG. IDS develops at deficit of each of subclasses, but at a research of the general maintenance of IgG in blood deviations from normal values seldom are found, it is more often normal or it is raised. As maturing of clones of the V-lymphocytes cosecreting IgG2 and IgG4 happens not earlier than the 2nd year of life, children of early age have a physiological deficit of these subclasses. Deficit of IgG2 is found in 50% of patients with primary IDS, is very frequent at the general variable gipoglobulinemiya and, as a rule, at children of advanced age is shown by chronic pneumonia and a sprue. The selection deficit of IgG1 can be compensated for the account of antibody formation, belonging to other subclasses.

The isolated deficit of IgA - one of the most frequent anomalies of immune system. Lack of deficit of other classes of immunoglobulins, normal ability of an organism to products of antibodies, a little changed indicators of cellular immunity are characteristic of it the low maintenance of IgA in blood serum (less than 50 mg/l). As IgA - the main immunoglobulin of system of local immunity (secretory IgA), pay attention to communication of its deficit with recurrent and chronic respiratory diseases and ENT organs. At absence or the low maintenance of IgA in secrets conditions for development of allergic and autoimmune diseases, premises for development of dysbacteriosis and inflammatory diseases of digestive tract are created. Developing of recurrent herpetic stomatitis, ulcer colitis, regional enteritis, etc. can be connected with the selection deficit of IgA.

IDS with defeat of system of phagocytosis

On the development mechanism phagocytal insufficiency is divided into three main forms:

Leykopenicheskaya - develops owing to suppression of processes of proliferation and maturing of monocytes (ionizing radiation, a number of toxins, cytostatics, etc.) or as a result of hereditary blockade of division and a differentiation, for example a myeloid stem cell.

Dysfunctional - is characterized by frustration of various stages of processes of phagocytosis and the presentation of antigen (mobility of phagocytes, their adhesive properties, absorption of an object of phagocytosis, its processing and representation of antigen to lymphocytes).

Disregulyatorny - develops owing to disturbance of regulation of various stages of phagocytal reaction by biologically active agents (neurotransmitters, hormones, prostaglandins, biogenic amines, peptides, etc.).

The combined IDS.

Are characterized by disturbance of a differentiation of stem cells, T maturation block - and V-lymphocytes and their deficit. The combined forms of an immunodeficiency meet more often than the selection. As a rule, they are connected with disturbance of the central bodies of immune system. At the combined IDS the leading role belongs to defect of T-cells.

1. The syndrome of a reticular dysgenesis - is characterized by reduction in marrow of quantity of stem cells. Pre-natal death of a fruit is characteristic, or children perish soon after the birth.

2. The "Swiss" type of an immunodeficiency - is characterized by defeat of T - and V-systems and, therefore, disturbance of cellular and humoral reactions of immunological protection. At autosomal and recessive forms at least insufficiency of an adenosinedeaminase is found in 40% of patients that leads to disturbance of metabolism of adenosine, blockade of synthesis of hypoxanthine and blockade as a result of this maturing of T-cells. A part of children on membranes of T lymphocytes has no antigens of the Ministry of Taxes and Tax Collection of the 1st or 2nd class. The maintenance of V-cells can meet standard or exceed it, but these cells are not capable to cosecrete immunoglobulins in enough.

The disease is shown in the first months of life and often characterized by a malignant current. The body weight increase delay is observed, in the first days of life some children have korepodobny enanthesis that can be connected with reactions of incompatibility in relation to the maternal lymphocytes coming through a placenta to the child's blood stream. Symptoms of skin candidiasis, diarrhea, the acute intersticial pneumonia gaining long and recurrent character develop. Children are very susceptible to viral infections. In blood the considerable lymphopenia comes to light, the maintenance of T lymphocytes is especially low. Content of immunoglobulins of all classes is considerably reduced. The exception is made by babies with IgG received from mother. Patognomonichna of change of a thymus, hypoplasia of almonds and lymph nodes. There is an inability to show reactions of hypersensitivity of the slowed-down type. Children seldom live up to 2-year age.

3. The ataxy teleangiectasia syndrome (Louis Bar syndrome) is caused by defect of maturing, depression of function of T lymphocytes, reduction of their number in blood (especially T-helperov), deficit of immunoglobulins (especially IgA, IgE, is more rare than IgG). The syndrome is characterized by a combination of an ataxy and other neurologic deviations to telangiectatic changes of vessels of scleras, persons. Defeat of a nervous system is shown by symptoms of loss of functions of a cerebellum, subcrustal ганглиев, diencephalic area, pyramidal system. Their defeats are resulted by gait disturbance, slowness of autokinesias, hyperkinesias, vegeto-vascular dystonia. At many slow pneumonia is noted, atelectases, a pneumosclerosis and bronchiectasias develop. At a research of lymphatic system the hypoplasia of a thymus, lymph nodes, spleens is established. At many children reduction of content in blood of lymphocytes is noted, the blastogenic response of lymphocytes is lowered, IgA is not defined.

The disease is characterized by an autosomnoretsessivny mode of inheritance. The forecast of a syndrome is adverse. About 50% of lethal outcomes are caused by chronic defeat of bronchopulmonary system, about 20% - development of malignant processes which connect with loss of functional activity of timuszavisimy lymphocytes, and in the general plan – with lack of tsenzorny function of a thymus – functions of immunological surveillance. Some patients live up to 40-50 years.

4. Viskotta-Aldrich's syndrome is characterized by deficit of peripheral T lymphocytes, disturbance of their structure and physical and chemical properties of membranes, reduction of cellular immunity. Defect is probably connected with absence on a cellular membrane of lymphocytes and thrombocytes of a glycoprotein with a relative molecular weight of 110 kD. At this disease decrease in density of microvillis on lymphocytes, disturbance of activation of T lymphocytes and the instability of an expression of sialoglikoprotein which is not explained still come to light. Immunological insufficiency is caused by a hypothymism. Often are found deficit of IgM at the normal maintenance of IgG and increase in the level IgA, IgE in blood. Reduction of products of antibodies to antigens-polysaccharides is characteristic, but these patients normally react to proteinaceous antigens. Besides, inborn defects of thrombocytes (disturbance of adhesion, aggregation), thrombocytopenia take place. Only boys are ill. The disease is shown at early age, sometimes in the neonatality period. Children have frequent viral and bacterial infections. Recurrent purulent otitis, eczema, pyodermas, pneumonia, colitis are characteristic. The hemorrhagic syndrome can be the leader.

The forecast of severe forms is adverse, children perish aged up to 10 years. Lead to a lethal outcome infections, hemorrhages or malignant new growths of limforetikulyarny system.

Insufficiency of system of a complement.

The system of a complement is presented by proteolytic enzymes and regulatory proteins. In blood there are 20 complementary factors which activation can be carried out in the classical or alternative way. Complement activation provides protection of an organism against any alien agents; the damaging effects at development of allergic and autoimmune reactions also are connected with complement activation. At the inborn and acquired frustration of complementary factors processes of phagocytosis are broken and there is a release of biologically active agents.

At inborn deficit of C1 activation of system of a complement on a classical way therefore, owing to disturbance of phagocytosis and a lysis of microbes, repeated heavy purulent processes are observed is impossible. At inborn deficit of S3b inhibitor C3 complement therefore contents it in blood decreases is constantly activated. Though the quantity of the previous complementary factors (C1, C2, C4) does not change, however because of deficit of C3 processes of phagocytosis and a lysis of bacteria are broken that is shown by repeated purulent infections.

At inborn deficit of C5 tendency to an infection is also connected with disturbance of phagocytosis and a lysis because of impossibility of formation of the corresponding components of a complement.

The maintenance of a complement at children is 30% lower, than at adults that does clear their tendency to an infection and sepsis. Frustration of system of a complement of the acquired character are shown in change of quantity of complementary factors. At damages of a liver (cirrhosis, hepatitis, chronic cholecystitis) synthesis of C1, C3, C6, C9 is broken. On the other hand, at allergic, autoimmune diseases complementary factors decrease in blood because of binding by their cell-bound immune complexes.

Treatment of immunodeficiency:

Treatment depends on type of primary immunological insufficiency. 3 main directions of immunocorrection are allocated.

Immune engineering (organ and tissue transplantation of immune system: embryonal liver, thymus gland, complex thymus gland breast, marrow, cells of immune system; administration of globulins, immunoglobulins of separate classes; sorption methods: hemosorption, affine sorption, immunosorption).

Correction by hormones and mediators of immune system (timichesky hormonal factors, miyelopeptida, cytokines like interferon, interleykina).

Pharmacological correction - levamisole, Diuciphonum, polyanions, etc.

Also active immunization against frequent infections by means of inactivated vaccines is applied, antibiotics, streptocides, antifungal drugs are entered.

Drugs, drugs, tablets for treatment of Immunodeficiency:

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