IMMUNOLOGICAL INSUFFICIENCY

From Big Medical Encyclopedia

IMMUNOLOGICAL INSUFFICIENCY (synonym immunodeficiency) — the inborn or acquired defect of immune system which is expressed inability of an organism to carry out reactions of cellular and (or) humoral immunity.

Purposeful diagnosis, studying and treatment of the diseases of the person caused And. N, began to develop after publication in 1952 by the English researcher Bruton (O. S. of Bruton) case histories of the young man with an agammaglobulinemia and recurrent bacterial infections. Positive to lay down. the effect of regular introduction of immunoglobin fraction of blood serum formed the basis for establishment of interrelation between disturbance of antibodyformation and development hron, bacterial infections at the person.

In 50 — the 60th many diseases at which these or those forms I are found were described. N, napr, a number of diseases with an aplasia or a hypoplasia thymus (see): Di George's syndrome, Nezelof's syndrome, the Swiss type heavy combined And. N (TKIN), etc.

Significant progress in studying of a pathogeny And. the N was outlined in the late sixties when two effector mechanisms of an immune response were installed (cellular — connected with activity of T lymphocytes, humoral — with activity of V-lymphocytes) and essentially new methods of assessment immunol are developed. reactivity of the person. A big contribution to studying of diseases with And. the N was brought by group of researchers led by an amer. pediatrician-immunologist R. A. Good. In 1971 the group of experts of WHO published classification of inborn diseases with And. N.

The diseases caused by primary, or inborn, immunological insufficiency. Under primary And. the N can understand genetically caused defect of development of this or that link of immune system. The genetic researches conducted in families of patients with And. N, convincingly testify to the hereditary nature of most of them. A number of diseases is linked to a floor; e.g., at Bruton's agammaglobulinemia (see. Agammaglobulinemia ), at Viskott's syndrome — Aldrich (see Viskotta-Aldrich a syndrome) only boys are ill. Other diseases are inherited on autosomal recessively type, napr, Nezelof's syndrome, an autosomal and recessive form heavy combined And. N (see. Alymphocytosis ), etc. Some diseases develop sporadic without accurate hereditary communication.

the Scheme of the block of genesis of T - and V-immune system.

In pathogenetic classification And. the N (Yu. M. Lopukhin and R. V. Petrov) are entered levels of possible genetic defects of immune system taking into account the last ideas of genesis of T - and V-systems of immunity. Genesis of T - and B-lymphocytes and possible levels of the block of this process are presented on the scheme. Places of 6 possible genetic blocks which are switching off this or that part of system immunol, reactions are allocated. Existence of defect at the level of a stem hemopoietic cell leads to a full aplasia a shelter - and a lymphopoiesis and or is limited to inability of a stem hemopoietic cell to turning into of T - and V-lymphocytes. Existence of single genetic blocks leads to full or partial switching off of T - or B-systems of immunity. Combinations of genetic blocks give various combinations And. N. Total number of optional versions according to the offered scheme is equal to 12. The optional versions of defects of immune system and disease caused And. N, are presented to table. It is necessary to notice that in process of development and improvement of methods of assessment of T - and B-systems of immunity new forms inborn will be revealed And. N and, perhaps, are brought in this basic table.

Clinical manifestations

Despite variety of immunodeficiency, are rather fully studied only some diseases with inborn And. N, it is described their wedge, a picture, methods of treatment are proved. The most difficult disease is heavy combined And. N.

Several forms heavy combined are known And. N: autosomal and recessive; linked to a floor; sporadic, etc. Quite often heavy combined And. the N is combined with deficit of enzyme of an adenosinedeaminase. In immunol, the plan heavy combined And. the N is characterized by almost full switching off of T - and V-systems of immunity in connection with disturbance of a differentiation of a stem hemopoietic cell in T - and B-lymphocytes. A thymus gland at patients heavy combined And. the N is at an early stage of embryonic development, in a spleen and in limf, nodes deficit of lymphocytes and the germinal centers, in peripheral blood a lymphopenia is noted. Reactions of cellular and humoral immunity are sharply oppressed.

Clinical manifestations of deficit of T - and B-systems of immunity are heavy recurrent inflammatory processes (infections of a respiratory and digestive tract, the milkwoman), and also lag in weight, etc. Without treatment children with heavy combined And. N usually perish in the first 6 — 12 months of life.

Two forms I are rather fully described. the N developing against the background of an aplasia or a hypoplasia of the central body of immune system — a thymus: Di George's syndrome and Nezelof's syndrome.

At Di George's syndrome the aplasia of a thymus is combined with an aplasia of epithelial bodies and characterized by deficit of T-system of immunity. Development of a number of the bodies which are put in 3 — the 4th branchiate arches is broken: epithelial component of a thymus, epithelial bodies, part of an aortic arch, handle of a breast, lobe of an ear, etc. Heart disease is found in a part of children. In peripheral bodies of immune system deficit of lymphocytes in timuszavisimy zones. Reactions of cellular immunity at preservation of humoral immunity are oppressed. The tetany which is giving in to treatment by hormone of epithelial body, but not calcium is characteristic. Children with Di George's syndrome are highly sensitive to skin infections, infections of a respiratory and digestive tract.

Other option of selective deficit T-system is Nezelof's syndrome. Patients with an autosomal and recessive form have aplasia of the thymus proceeding without aplasia of epithelial bodies, the underdevelopment timuszavisimy a component of peripheral bodies of immune system with deep deficit of reactions of cellular immunity is observed; reactions of humoral immunity can be kept. Since the neonatal period children suffer from recurrent infectious processes, hl. obr. virus and fungal etiology.

The selection deficit of V-system of immunity at preservation of reactions of cellular immunity develops at children with the agammaglobulinemia like Bruton linked to a floor. Clinically the disease is characterized by recurrent hl. obr. piogenic infections which develop from the middle of the first year of life when the immunoglobulins received from mother cease to have protective action. Conjunctivitis, otitises, pneumonia and abscesses are most characteristic of sick children, at the same time resistance to a nek-eye to gram-negative microorganisms, viruses, fungi remains. Patients with Bruton's agammaglobulinemia practically have no plasmocytes and reactions of humoral immunity whereas reactions of cellular immunity can be kept are sharply oppressed. The thymus gland is usually kept, deficit of humoral immunity is connected with disturbance of development of the central body of immunity — an analog of a bag of Fabrition of birds.

The selection deficit of IgA is especially distinguished (see. Immunoglobulins ). The disease can proceed asymptomatically; in most cases at patients note infections of a respiratory and digestive tract, quite often at them develop auto-immunnye processes.

Considerable group of inborn diseases with And. N make the combined defects of immune system. Holds a specific place autosomal and recessive And. N with an ataxy teleangiectasia — Louis Bar syndrome (see. Ataxy ). The disease is characterized by multisystem frustration: neurologic (an ataxy, a lack of coordination), vascular (teleangiectasias of skin and a conjunctiva), mental (mental retardation), endocrine (dysfunction of adrenal glands, gonads and so forth), the sinusopulmonalny infections recuring since the early childhood. Function of T lymphocytes is oppressed in various degree, at a number of patients reveal a hypoplasia less often an aplasia of a thymus. Defeat of B-system of immunity is shown in deficit or in total absence of IgA (at a number of patients products of IgA can be kept) and is frequent in deficit of IgE. In blood serum of most of patients determine embryonal proteins of type alpha and beta fetoproteins, by IgMs — IgM monomer. Frequency of tumors at such patients increases up to 10%. More often tumors are localized in lymphoid system: lymphosarcoma, lymphoreticulosarcoma, etc.

And. the N, linked to a floor (boys are ill), is characterized by eczema and thrombocytopenia (Viskott's syndrome — Aldrich). At the this form combined And. in N, despite normal number of B-lymphocytes, products of natural antibodies and development of antibodies in response to immunization are sharply oppressed by polisakharidny antigens. In blood serum of patients concentration of IgM is reduced and the IgA level is quite often increased. At first after the birth the T-system is not struck, but the number of lymphocytes in timuszavisimy zones of peripheral bodies of immune system decreases over time and reactions of cellular immunity are oppressed. At the same time along with the normal answer of lymphocytes of in vitro to nonspecific mitogens (e.g., on phytohemagglutinin) at patients the answer of lymphocytes to antigens and to allogenic cells can be violated. Apparently, defect develops at the level of an initial stage of an immune response. In addition to skin defeats, recurrent inflammatory processes, approximately malignant new growths develop in 10% of cases.

Less often such immunodeficiency as I.n meet. with a thymoma (Goode's syndrome), And. N at dwarfism with the shortened extremities, a hypoplasia of a thymus gland with the reduced level of immunoglobulins (Gitlin's syndrome), etc. The most various combinations of defects of T - and B-lymphocytes which are difficult for carrying to this or that famous group of diseases with I.n., allocate as variable immunodeficient diseases with not classified forms. Conducting a wedge, signs at patients with such diseases are recurrent inflammatory processes. This pathology is characterized by switching off or decrease in products of immunoglobulins of one or several classes (disimmunoglobulinemiya) with oppression or without oppression of functional properties of various populations of T lymphocytes (see. Immunocompetent cells ). For patients with inborn And. N the variety patol, the changes connected with defeat of other systems is characteristic. As a rule, against the background of And. N develop the recurrent inflammatory processes leading to destructive processes in various bodies. Apprx. 90% of patients with And. N suffer from sinusopulmonalny inflammations separately or in combination with a septicaemia. intestinal defeats, etc. Frequent causative agents of pneumonia at patients with I.n. Pneumocystis carinii and Mycoplasma pneumoniae are.

Often the alimentary system is surprised. So, at heavy combined And. and. quite often diarrhea with the subsequent exhaustion develops hron. Disturbance of food, the exhausting ponosa develop at children with insufficiency of timuszavisimy system more often and patients with the selection deficit have IgA. The disease of intestines can be followed by deficit of disaccharides. Skin defeats which quite often can be one of the first signs I.n are eurysynusic. The most frequent recurrent skin disease is the pyoderma caused by staphylococcus or a streptococcus. Eczematic dermatitis develops at patients with an aimmunoglobulinemiya and at Viskott's syndrome — Aldrich. At deficit of cellular immunity heavy recurrent herpes infections, and also fungal infections of skin and mucous membranes quite often develop (milkwoman). In certain cases the skin defeats similar to damage of skin at autoimmune diseases can be found in patients with an aimmunoglobulinemiya: a dermatomyositis, a sclerodermitis and so-called Teleangiektaza on skin and conjunctivas are characteristic at Louis Bar syndrome. In a special form of skin diseases allocate hron, skin and mucous Candidiasis. Apparently, at this disease the special immunodeficiency which is followed by defeat of cellular immunity with hypersensitivity to fungi of the sort Candida takes place.

At inborn I.n. also various internals are surprised: liver, pancreas, closed glands and others, hl. obr. against the background of recurrent infections.

The interrelation between insufficiency of immune system and emergence of malignant new growths at patients with I.n is established. As a result of the analysis of the big statistical material which is carried out by R. Gatti and Goode it is shown that the frequency of malignant new growths among patients with inborn And. and. increases approximately in 10 thousand times in comparison with the general population of people of the same age. More often tumors develop at the patients suffering I.n. with an ataxy teleangiectasia, with eczema and thrombocytopenia (apprx. 10% of cases). Tumors are localized by hl. obr. in lymphoid system: lymphoma, lymphoreticulosarcomas, lymphoid leukoses, etc.

Diagnosis

For inborn I.n's diagnosis. careful collecting the anamnesis is of great importance. In the anamnesis of patients with I.n. most often the heavy recurrent mixed inflammatory processes, the localized hl come to light. obr. in bodies of respiratory system, in went. - kish. a path, on skin and mucous covers (otitis, bronchial pneumonia, enteritis, a pyoderma, the milkwoman, etc.). And the bacterial infections caused by pneumococci, streptococci, meningokokka whereas at patients with deficit of T-system the infections caused by viruses, fungi, mycobacteria, brucellas, etc. develop more often are more characteristic of a disease with deficit of B-system. Children with deficit of T-system hard have viral infections. Cases of a lethal outcome after vaccination of the children suffering I.n are described., nek-ry antiviral and antibacterial vaccines (antismallpox, antipoliomyelitic vaccines, BTsZh). At the combined forms I. the N degree of manifestation of infectious defeats depends on the level of the genetic block of development of T - and V-lymphocytes. For different forms I.n. various terms of emergence of inflammatory processes are characteristic. At deficit of humoral immunity bacterial infections arise more often after the first half of the year of life whereas at deficit of cellular immunity fungal, viral infections develop soon after the birth.

At a number of diseases syndrome And. the N is combined with other characteristic syndromes; e.g., at Di George's syndrome signs of deficit of epithelial bodies — spasms since the neonatal period come to light, And. the N with an ataxy teleangiectasia is combined with conjunctival and skin teleangiektaza and a cerebellar ataxy, Viskott's syndrome — Aldrich — with skin eczema with hemorrhages, etc. Importance for diagnosis I.n. has identification of cases of an immunodeficiency in a family which are quite often diagnosed as autoimmune diseases, collagenoses, limforetikulyarny tumors, etc. It is not excluded that one of causes of death at early age of children with symptoms of heavy pneumonia or enteritis is not recognizable inborn I.n.

Immunological researches

the Level of the genetic block of this or that link of an immunogenesis can be established only with the help immunol, tests. In a wedge, practice tests are developed for the selection quantitative and quality standard of T - and V-lymphocytes.

For assessment of cellular immunity of patients from inborn I.n. the next researches are recommended: 1) in vivo — a research of a thymus gland rentgenol, methods; a biopsy limf, nodes for judgment of a condition of timuszavisimy zones; statement of skin tests with the drugs inducing development of reactions of hypersensitivity of the slowed-down type (tuberculine, kandidin, hapten-2,4-dinitrobenzene chloride, etc.); determination of terms of rejection of an allogenic skin rag; 2) in vitro — definition of absolute number of T lymphocytes in the test of spontaneous rosetting with erythrocytes of a ram (see. Immunocompetent cells ); ability of T lymphocytes to a blastotransformation (see. Blastotransformation of lymphocytes ) under the influence of such mitogens as phytohemagglutinin, concanavalin A in the mixed culture of lymphocytes; allocation by sensibilized lymphocytes of mediators of cellular immunity (lymphokines); cytopathic action of lymphocytes against target cells and other tests.

For assessment of humoral immunity at patients with And. N are recommended tests: 1) in vivo — a biopsy limf, nodes for definition of timusnezavisimy zones, plasmocytes; biopsy of marrow; immunization by inactivated vaccines (AKDS, Vi-antigen, lipopolisakharidny antigen, etc.) and definition of credits of specific antibodies; 2) in vitro — qualitative and quantitative test of serumal and secretory immunoglobulins; definition of credits of isohemagglutinins and heterophyllous antibodies to eurysynusic antigens (to erythrocytes of animal different types, to staphylococcus, colibacillus, etc.); definition of absolute number of V-lymphocytes in the test of an immunofluorescence with identification of immunoglobin receptors, and also in tests of rosetting with identification of receptors for a Fc-fragment of IgG, for C3 component of a complement; ability of lymphocytes to a blastotransformation under the influence of timusnezavisimy antigens (e.g., lipopolisakharid from colibacillus, etc.); the lymphocytotoxicity of lymphocytes mediated by antibodies and other tests.

Extent of defeat of immune system of the person can be revealed only at complex use of tests for assessment of T - and V-lymphocytes. Separate tests in this sense of a maloinformativna. As assessment of the immune status represents long multi-stage process, development of the optimum scheme of inspection of the patient with suspicion of a disease with I.n is of great importance. Can be one of the recommended schemes following: the first day — capture of blood for definition of total number of leukocytes and lymphocytes, the quantitative and qualitative characteristic of T - and V-lymphocytes in tests of rosetting and a blastotransformation, concentration of immunoglobulins, credits of isohemagglutinins and heterophyllous antibodies, and also statement of skin tests of the slowed-down hypersensitivity with intradermal administration of tuberculine, a kandidin, etc.; the third day — assessment of skin tests, active immunization by AKDS or other vaccines, cutaneous application of solution of dinitrobenzene chloride (at negative tests of hypersensitivity of time lag action); in two weeks — capture of blood for determination of level of antibodies in response to active immunization, cutaneous application of solution dinitrochlorine-benzene in the allowing dose and in a day assessment of skin reaction.

For early diagnosis of inborn I.n. the following tests can be used: definition of absolute number of lymphocytes in peripheral blood (a lymphopenia — one of precursory symptoms of defeat of timuszavisimy system as apprx. 70% of lymphocytes of blood are presented by T lymphocytes), the analysis of serumal immunoglobulins (the low indicator of IgM after the Second and the next weeks of life can be an important sign of deficit of B-system), definition of credits of isohemagglutinins (at deficit of B-sistemy'uroven of such antibodies it is reduced or they are absent). Methods of cultivation of lymphocytes of newborn in vitro and definition of their ability to produce immunoglobulins are developed.

Treatment

Establishment of levels of defeat of various stages of an immunogenesis at a number of immunodeficient diseases of the person opened ways for purposeful use of various methods of an immunotherapy. Are most widespread recovery (transplantation of hemopoietic and immunocompetent fabrics) and replaceable (administration of immunoglobulins, a transfer factor, etc.) methods of an immunotherapy; the stimulating methods (e.g., use of BTsZh or other vaccines) were inefficient at inborn immunodeficient diseases.

Transplantation of marrow — the only effective way of treatment of one of the most difficult defects of immune system — heavy combined I.n. Thanks to bone marrow transplantation the children perishing in the first half a year of life remain live. However bone marrow transplantation requires the most careful selection of the donor for all known systems of histocompatability: antigens of the AB0 systems, a Rhesus factor, HLA (see. Immunity transplant ). Donors are selected among sibling (children of one family) or among unrelated persons; in the latter case it is difficult to pick up the identical donor for antigens of system of histocompatability (usually 1 among 2 thousand inspected persons). Careful selection of couple the donor — the recipient is necessary in connection with danger of development of reaction «a transplant against the owner» since immunological competent fabric is transplanted in immunological 6ez a protective organism (see. Incompatibility immunological ). Quite often reaction leads «a transplant against the owner» to a lethal outcome, however in cases of overcoming takes it place expressed to lay down. effect. Similar reaction can develop at children with heavy combined I.n. after repeated transfusions of fresh blood, in a cut there are lymphocytes capable to carry out reaction «a transplant against the owner». For prevention of this reaction use the blood which is previously irradiated with in vitro for injection. For the purpose of reduction of a share of immunocompetent cells in suspension of marrow works on allocation of pure fraction of stem hemopoietic cells are conducted, in particular using a method of fractionation of cells in a gradient of density of a bull seralbumin. For recovery of immune system at patients with heavy combined I.n. apply also transplantation of cells of the embryonal liver of the person containing trunk elements.

By other method of a recovery immunotherapy at inborn And. the N serves transplantation of a thymus. As the indication for transplantation of a thymus serve diseases with an aplasia or its hypoplasia. Transplantation of a thymus is made in the form of suspension of cells (a method ineffective), in the form of fragments by the size apprx. 1 mm which transplant to the area of a direct muscle of a stomach or intraperitoneally, in the form of the whole body in a complex with a breast (see. Thymus, operations ). As well as in cases of bone marrow transplantation, selection of couple the donor — the recipient on system of histocompatability since cases of development in recipients of reaction «a transplant against the owner» are described is necessary. Positive to lay down. the effect of change of a thymus is gained at patients with Di George's syndrome, Nezelofa, at I.n. with an ataxy teleangiectasia, etc.

Among replaceable methods of an immunotherapy gained distribution of an injection of fractions of immunoglobulins of a blood plasma of healthy people or people, immunizirovanny against any antigen (anti-staphylococcal serum, etc.), and also a fresh blood plasma. The indication for an immunoglobulinoterapiya are syndromes with and - hypo - or a disimmunoglobulinemiya.

For treatment of a disease with deficit of cellular immunity the drug which received the name «transfer factor» gains distribution. It is dialyzed extract of leukocytes of people, sensibilized against any antigen (e.g., tuberculine, a kandidin, etc.) which is capable to transfer to not immune recipient a specific immune response as hypersensitivity of the slowed-down type, and force of an immune response of the recipient on this antigen can be comparable with a force of the answer of the donor. Use of a transfer factor appeared the most successful at a number of syndromes with deficit of T-system of immunity.

New approach to treatment And. the N is use of humoral factors of a thymus (Timosinum) for induction of a differentiation of stem cells in T-cells: after an incubation of in vitro of cells of marrow healthy or sick with I.n. it was succeeded to receive cells with characteristics of T lymphocytes.

It is necessary to notice that much widely used in to lay down. to practice drugs (e.g., corticosteroids, number of antibiotics, etc.) have the expressed immunodepressive properties and their use can aggravate in a bigger degree deficit of immune system of patients with I.n. In this regard symptomatic therapy shall be applied with care.

For protection against infectious diseases of the children who were born with I.n., place in specialized chambers with gnotobiotichesky conditions (sterile air, sterile food, etc.). There are messages on carrying out childbirth by means of Cesarean section at suspicion on I.n. at a fruit and the room of the child in sterile conditions with long contents in such boxes.

The secondary, or acquired, immunological insufficiency

Unlike primary, secondary And. by N it is not connected directly with the genetic block of any stage of an immunogenesis, and develops under the influence of the numerous striking factors operating on originally not changed immune system. The acquired immunodeficient diseases are extremely various, are followed by defeat both T - and B-systems of immunity, and is frequent also both systems (see. Immunodepressive states ).

I.n. it can be found in the patients suffering from heavy inflammatory processes (e.g., heavy inflammatory processes of abdominal organs). Some causative agents of infectious diseases (measles, rubella, leprosy, etc.) have immunodepressive properties. A specific place is held by the acquired I.n. in group onkol, patients. Insufficiency of immune mechanisms can be result of the heavy toxic processes developing at such patients or effects of cytostatic drugs which are used at treatment of tumoral diseases. On the other hand, I.n. arises because cells of immune system are involved in tumoral process (e.g., leukoses of T - and B-cells) and do not perform the direct functions. The expressed deficit of T-system of immunity is characteristic of patients with a lymphogranulomatosis.

The reason acquired I.n. there can be a loss of serum proteins, and including immunoglobulins, as a result of plentiful and long bleedings, loss of proteins through intestines (e.g., at lymphangiomas) or through kidneys.

A peculiar immunodeficiency takes place at children at first after the birth when there is a formation of immune system (tranzitorny I.n.), and at persons of senile age against the background of withering of immune system.

Diagnosis acquired And. the N is carried out by the same criteria, as inborn I.n's diagnosis. The principles of treatment of diseases with I.n. — purposeful recovery of the struck stages of an immunogenesis.

Value of immunological insufficiency in the theory and practice of medicine

Studying of patients with And. led N to essentially new approach to mechanisms of formation and functioning of immune system of the person. Detection wedge, forms I. N with the isolated defeat of cellular or humoral immunity was practical confirmation of theoretical data on existence of T - and B-systems of immunity. The isolated forms I. N give the chance to study functional and structural features of «pure» populations of T - and B-lymphocytes. So, on the example of diseases with And. to N it is established that the T-system of immunity has the leading value for protection of an organism against viruses, fungi, plays an important role in atrepsy, in rejection of alien fabrics, in control of autoimmune processes. Pathogenetic approach to treatment of various diseases of immune system became possible only after assessment of action of various methods of an immunotherapy at patients with And. N.

More and more diseases of the person in which pathogeny the important role is played by insufficiency of immune mechanisms come to light. The new concept postulating increase in frequency of malignant new growths at patients with nek-ry forms inborn is widely adopted And. N against the background of defeat of functions immunol, supervision that testifies to an important role of immune system in atrepsy (see. atrepsy ). More often tumors are registered at patients with inborn deficit of the timuszavisimy system of immunity, and also in cases acquired And. N at long immunodepressive therapy.

Insufficiency of immune mechanisms is found quite often at a number of the diseases proceeding allegedly with a hyperimmune component (autoimmune diseases, allergic processes). In this regard assume that in some cases the raised products of autoantibodies against the most various antigens of an organism (e.g., against erythrocytes, nucleinic to - t and so forth) it can be connected with deficit of T-limfotsitov-supressorov with overwhelming function in relation to antibody producers.

In some cases at patients with I.n. (e.g., at And. N with an ataxy teleangiectasia) in blood serum can be found embryonal proteins of type alpha and beta fetoproteins, IgMs — IgM monomer; in this regard assume that twisted-point gland can play a role in regulation of fetalis systems.

Similarity of many changes at patients with And. N and occurring in the course of aging of an organism and similarity of defeats of immune system at patients with And. N and during the aging (e.g., oppression of immune system, hl. obr. functional activity of T-system, increase in frequency of new growths and autoimmune processes) theories of aging served as justification immunol.

Table. CLASSIFICATION of OPTIONS of DEFEAT of CELLULAR AND HUMORAL IMMUNITY with GENETIC DEFECTS of DEVELOPMENT of T - And V-SISTEM of IMMUNITY (Lopukhin Yu. M, Petrov R. V., 1974)

Bibliography: Alexander Dzh. At. and Goode of R. A. Immunologiya for surgeons, the lane with English, M., 1974; Inborn immunodeficiency at children, under the editorship of Yu. M. Lopukhin and R. V. Petrov, M., 1975, bibliogr.; Lopukhin Yu. M. and Petrov R. V. New classification of primary immunological insufficiency, Vestn. USSR Academy of Medical Sciences, No. 3, page 35, 1974; Primary immunological insufficiency, Bulletin WHO, t. 45, No. 1, page 123, 1972, bibliogr.; Clinical aspects of immunology, ed. by P. G. H. Gell a. o., p. 649, Oxford a. o., 1975, bibliogr.; Good R. Immunodeficiency in developmental perspective, Harvey Lect., ser. 67, p. 1, 1973.

Yu. M. Lopukhin, L. V. Kovalchuk.

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