IMMUNOGLOBULINS

From Big Medical Encyclopedia

IMMUNOGLOBULINS (Latin immunis the free, saved from something + by globulus ball) — the proteins of the person or animals which are carriers of activity of antibodies. K I. carry also proteins with similar chemical structure — so-called myelome globulins at which, however activity of antibodies, and also subunit of molecules I, as a rule, is not found. and Bens-Jones's proteins. On electrophoretic mobility And. treat generally gamma-globulins and beta2-globulins, i.e. the fractions moving at an electrophoresis to the anode with the smallest speed in comparison with other fractions of serum proteins. And. are present both at blood, and at other liquids and body tissues — at cerebrospinal liquid, limf, nodes, a spleen, saliva, etc.

According to the classification accepted in 1964. Committee of WHO experts, And. are subdivided into three main classes designated as IgG, IgA and IgM. Is later at the person existence of two more classes — IgD and IgE was established. And. all classes are constructed of molecules of heavy and light polypeptide chains. Light chains about a pier. it is powerful apprx. 20 000 are identical to all And. also can belong to two types — κ (kappa) and λ (lambda). In each molecule I. light chains always belong to any one type. Heavy chains And. different classes have a pier. weight 50 000 — 70 000 also differ on primary structure and antigenic specificity. Division And. on classes it is carried out on the basis of distinctions of their heavy chains designated respectively by letters γ, α, μ, δ and ε. According to designations of chains molecular formulas can be given. And., in which the class of chains and their quantity in a molecule is specified. E.g., molecular formulas for two IgG types will be γ2κ2 and γ2λ2, for IgM — (μ2κ2) 5 and (μ2λ2) 5, for IgA — α2κ2 and α2λ2, for the polymeric IgA forms — (α2κ2) n and (α2λ2) n where n = 2 and above. And. all classes support carbohydrate groups and therefore can be considered as glycoproteins.

Immunoglobulin G (IgG) in the weight relation makes the main part (70 — 80%) of all And. (concentration in serum of the person apprx. 1,2%). Methods of allocation of IgG are developed rather well. One of the most widespread ways is fractionation of serum proteins by means of ethanol at temperatures below 0 according to Kohn. The high cleaning drugs IgG can be received by means of a column chromatography with ion exchangers — DEAE-cellulose or DEAE-sephadex. In different degree the purified drugs IgG allocate also by fractionation with ether, a rivanolovy method, by means of electrophoretic convection, etc.

Fig. 1. The scheme of an immunoelektroforegramma of proteins of a blood plasma of the person (the arch of precipitation corresponding to IgG — 7, extends to a zone of alpha globulins — it is specified by an arrow that testifies to the big range of electrophoretic mobility): 1 — prealbumins; 2 — albumine; 3 — an alfa1-glycoprotein; 4 — ceruloplasmin; 5 — gaptoglobin; 6 — transferrin; 8 — IgA; 9 — IgM; 10 — fibrinogen; 11 — alfa2-macroglobulin; 12 — an alfa2-lipoprotein.

IgG has a pier. weight apprx. 150 000 and a sedimentation constant 6,7S. The average electrophoretic mobility corresponding to top of peak of IgG at a free electrophoresis is equal to 1,1*10 - 5 cm 2 / volt-sec. in the veronalovy buffer with pH 8,6 and ionic strength 0,1. However the molecules IgG differ in considerable heterogeneity concerning electrophoretic mobility. At an immunoelectrophoretic research it is established that the arch of precipitation corresponding to IgG extends to a zone of alpha globulins (fig. 1). By means of a method of isoelectric focusing the drugs IgG can be divided into a large number of fractions according to distinctions of isoelectric points of molecules of it And. in the range of pH of 5,5 — 8,0.

Fig. 2. Scheme of a structure of the molecule IgG: the molecule is constructed of two light and two heavy polypeptide chains connected by three mezhtsepyevy S — S-bridges. The dotted line designated variable parts of chains in which active centers of antibodies are localized. The wavy line — the «hinged area» sensitive to proteolysis as a result of which the molecule IgG breaks up to fragments. At the proteolysis caused by enzyme papain (the scene of action is designated by an arrow), the molecule is split on Fc and two Fab-fragments; The N-trailer site of a polypeptide chain from free NH 2 - group; The S-trailer site of a polypeptide chain with COOH group.

The molecule IgG has the extended form and was considered as the «flattened» cylinder with a length of 24 nanometers and cross sectional dimensions of 1,9 and 5,7 nanometers earlier. Later data, confirmable elektronnomikroskopichesk, indicate that the molecules IgG consist of three compact subunits located in the form of a letter Y. These data meet modern expectations of a structure of the molecule IgG — from two light and two heavy polypeptide chains connected by disulfide bridges as it was for the first time established by R. Porter's works. The arrangement of these chains is illustrated by the scheme (fig. 2). At impact of enzyme of papain on the molecule IgG it breaks up to three fragments. Two of them have an identical structure, and everyone consists of the light chain connected to that site of a heavy chain which corresponds to the N-tail. These so-called Fab-fragments, being allocated from antibodies (see), keep ability to connect specifically antigens (see). The name Fc is appropriated to the third fragment consisting of G-trailer sites of heavy chains. Three subunits making the native molecule IgG are similar to the described papainovy fragments and are connected with each other by flexible pieces of heavy chains. This site of a molecule called by hinged area is exposed to splitting at influence of papain and other proteases. Owing to features of a structure of hinged area the corner between Fab-fragments can change that is, apparently, of great importance for reaction of the active centers located on the ends of Fab-fragments with determinants of molecules of antigens which can have various configuration (see. Antigen — an antibody reaction ).

Within each of Fab-fragments there is only one active center reacting with determinants of antigen. Therefore these monovalent fragments though contact antigen, but are not capable to cause formation of large units antigen — an antibody, revealed in precipitation tests or flocculation. At impact of pepsin on IgG at pH apprx. 4 there is eliminating of a large bivalent fragment of F (ab1) 2 to a sedimentation constant 5 S, consisting of two Fab-fragments connected by a disulfide bridge, and the site of a molecule corresponding to the Fc-frag-cop breaks up to low-molecular splinters. Fragments of F (ab1) 2 keep ability to give seen serol, reactions with multivalent antigenic molecules. Processing by pepsin is applied in the field of applied immunology to receiving the purified antitoxins. F (ab1) 2 fragments of anti-toxic immunoglobulins of a horse have a little less expressed sensibilizing properties, than native I.

Ustanovleno that heavy gamma chains have some distinctions in a chemical structure and antigenic specificity that gave the grounds to subdivide the class IgG into 4 subclasses designated as IgG1, IgG2, IgG3 and IgG4. In blood of the person these subclasses contain respectively in the following quantities: 70 — 77%, 11-18%, 8 — 9% and 3%. Also distinctions and in biol, properties of separate subclasses are found: IgG2, unlike other subclasses, do not sensibilize skin in reactions of a passive skin anaphylaxis, IgG4 — are not capable to fix a complement.

For studying of primary structure light and heavy chains of IgG were received in the isolated state. Dissociation of the molecule IgG on the chains making it is reached as a result of splitting of the disulfide bridges and noncovalent bonds connecting these chains. For this purpose use, as a rule, 2 mercaptoethanol in combination with konts. solutions of amides (urea, muriatic guanidine) or organic to - t (acetic, propionic). In view of various molecular weight of light and heavy chains after their dissociation they can be received in the isolated state with the help gel filtering on sefadeksa (see. Gel filtering ).

Big difficulty during the studying of chemical, in particular amino-acid, structure normal And. show I considerable degree of their heterogeneity. As it is stated above, IgG from serum of one person differ as the light chains which are contained in them and are subdivided also into subclasses depending on a structure of heavy chains. Besides, And. have the subtle differences determined by a structure of those sites of polypeptide chains which cause, obviously, specific activity (variable sites). Unlike normal, myelome And. are characterized by high homogeneity. In view of the fact that these homogeneous And. normal molecules P. are constructed according to the same block diagram, as, they were used for a research of primary structure. Bens-Jones's proteins secreted with urine at some myelomatoses (see. Bens-Jones of squirrels ), turned out consisting of lungs a kappa - or a lambda chains that considerably facilitated a problem of allocation and a research of these components I.

As a part of light and heavy chains And. the person availability of 19 amino acids is established and some distinctions in their quantitative ratios are found. During the studying of the sequence of the amino-acid remains essential features are established. So, at a research of lungs of a cap chains from Bens-Jones's proteins it was revealed that they contain 213 — 221 amino-acid rest, and in them it is possible to distinguish two sites, approximately equal on length — constant (C) and variable (V). The S-site includes 107 amino-acid remains which are identical for a kappa chains in all investigated myelome by I. Isklyucheniye makes only valine in situation 191, instead of to-rogo there can be a leucine depending on the characteristic of an allotype of Inv. The V-site occupying a N-trailer half of the H-chain contains from 107 to 113 amino-acid remains; at the same time more than 70 remains can vary in this site in myelome And. from various people. Similar pattern takes place and for a lambda chains which are also divided into the S-site and the V-site in which one amino acids can be replaced with others approximately in 50 provisions in And. from different individuals. V-and S-sites are found also during the studying of the heavy gamma chains containing apprx. 450 amino-acid remains. V-sites in these chains are located also since the N-end and consist approximately of the same quantity of the amino-acid remains, as well as in light chains. With - uchas-current of a chain is constructed of three pieces with nek-ry gomologiya in the amino-acid sequence. It is very probable that V-sites of light and heavy chains create area of an active center in molecular composition And.

It is similar to others And., IgG contains the carbohydrate components making on weight apprx. 2,5 — 3%. The galactose and mannose (1,2%), a fukoza (0,3%), geksozamin (1,4%) and sialine to - that are among carbohydrates (0,2%). Carbohydrate components in the form of oligosaccharides are connected to the S-site of a gamma chain by means of a N-glycosidic linkage from the rest asparaginic to - you. The main oligosaccharide containing everything listed sugar, is fixed in that part of a gamma chain, edges corresponds to hinged area of the molecule IgG. Biol, value of a carbohydrate component I. it is not found out.

Immunoglobulin A (IgA) makes on weight apprx. 15% of all And. Its content in normal blood serum of the person equally on average apprx. 200 mg of %. Presence of IgA at various secretory liquids — in women's colostrum (151 mg of %), saliva (28 mg of %), tears (7 mg of %), and also in nasal and bronchial secrets and in a mucous membrane of intestines is characteristic.

Allocation of IgA from serums of patients with an IgA-myeloma is considerably facilitated in view of high content in them it And. As a starting material for receiving IgA of the person use also women's colostrum and saliva.

Pier. the weight of IgA apprx. 170 000. However partially IgA in serum is in a type of polymers. A sedimentation constant of the monomeric IgA form — 7 S, for polymeric forms 9 — 13 S. The electrophoretic mobility corresponding to top of peak at a free electrophoresis is equal to 2,2*10 - 5 cm 2 / volt-sec. At an immunoelectrophoresis of IgA gives an asymmetric arch in a zone beta1 and beta2. The molecule IgA is constructed according to the same plan, as IgG: from two heavy alpha chains and two lungs a kappa - or a lambda chains. 2 subclasses of IgA on the basis of various antigenic specificity of α-chains are established. In secrets of IgA is present at a type of polymers as a part of which the additional base unit called by a secretory (S) component is found. On the molecular weight of S - the lump - ionent is similar to light chains, but antigenically differs from them. Assume that secretory IgA are formed locally in the lymphoid cells located directly in the field of this or that gland, and the S-component is synthesized in fabric of the gland allocating a secret. Contains in IgA apprx. 10% of the carbohydrates attached in the form of oligosaccharides to constant sites of α-chains. The same are a part of the carbohydrate IgA component of sugar, as IgG.

Immunoglobulin M (IgM) (γ-macroglobulin, 19 S γ-globulin)))))))))) from 3 to 10% of total quantity make And. Content in serums of adult healthy people averages it apprx. 100 — 120 mg of %.

At Valdenstrem's macroglobulinemia concentration of IgM increases in serum and can reach 40% of all proteins of serum and more. The cleared IgM is isolated from the deposit of euglobulin allocated at dialysis of normal or myelome serum against solution with low ionic strength. At gel filtering of euglobulin on columns with sephadex G — 200 IgM is eluated in the first fraction. Further defecation of other globulinovy components can be reached by a chromatography on DEAE-cellulose and a preparative electrophoresis.

Fig. 3. Scheme of a structure of the molecule IgM: the molecule consists of 5 subunits connected in the field of a Fc-fragment by disulfide bridges.

IgM has a pier. weight 900 000 and sedimentation constant 19S. In this regard it is provided in some schemes of allocation of IgM ultracentrifuging (see), allowing to separate this high-molecular globulin from other components smaller a pier. weight. Electrophoretic mobility of IgM corresponds to a zone β2-глобулинов and a little less mobility of IgA. On immunoelektroforegramma of IgM gives slightly curved line, the most remote from a trench with an antiserum. The maintenance of the carbohydrate IgM component fixed on μ-chains makes 9,8%. On a nek-eye to data, as a part of IgM-fraction it is possible to distinguish two groups of the molecules unequal on the content of carbohydrates (on average 10,69% and 7,71%). The molecules IgM consist of five subunits constructed on the general for all And. to the plan from two heavy μ-chains and two lungs κ-or λ-chains. These subunits are connected in the field of Fc-fragments by disulfide bridges, forming structure of a star-shaped form (see the scheme on Dorringlon a. Mihaesco, fig. 3). Such star-shaped, or arachnoid, figures are found at electronic microscopic examination of drugs of the allocated IgM. Because each of five subunits which are a part of the molecule IgM possesses two active centers, the maximum number of the valencies revealed at reactions with antigen is equal to 10. At impact on IgM of the reducing agents (2 mercaptoethanol, cysteine) there is a disintegration of molecules on 78 subunits owing to splitting of disulfide bridges. At the same time the molecules IgM lose activity of antibodies, obviously, in connection with disturbances of a configuration of active centers. This phenomenon is used for differentiation 19S-also by 78 antibodies in serums of the person and animals. Division of IgM into two subclasses differing on antigenic specificity of a mu chains is established. Recently existence in IgM (and in IgA polymers) was shown to an additional polypeptide J-chain.

Immunoglobulin D (IgD) it was for the first time allocated from D-myelome serums of the person, and then it is found in normal serums in low concentrations (3 — 40 mg of %). Pier. the weight of IgD apprx. 180 000, a sedimentation constant 6,6S; but to electrophoretic mobility of IgD it is close to IgA and IgM. The gradient chromatography on DEAE-cellulose with the subsequent gel filtering of the fractions enriched with it is applied to isolation of IgD from myelome serums And., on G-200 sephadex.

Immunoglobulin E (IgE) contains in normal serums of the person in trace quantities (0,01 — 0,2 mg of %). Physical. - chemical

IgE properties are studied generally on the drugs emitted from seldom meeting IgE of myelome serums. Pier. the weight of IgE apprx. 190 000, a sedimentation constant of 7,7 — 8,0 S. Interest in IgE is connected with the fact that the reagins participating in allergic reactions are a part of this fraction.

Immunoglobulins of animals. IgG, IgA and IgM are available for rabbits, mice, Guinea pigs, horses and other mammals. At some animals additional classes I are established, besides. So, in serum of horses in a zone of beta2-globulins also IgT and IgB and globulinovy fraction with a sedimentation constant 10S are found [Odiber and Sandor (F. Audibert, G. Sandor), 1972].

Antigenic properties of immunoglobulins are defined by various antigenic determinants located generally in a proteinaceous part of a molecule. Existence in molecular composition of all And. light chains κ-or BB\-type causes the known degree of antigenic similarity And. different classes according to type of the light chains which are their part. Differentiation And. on classes and subclasses depends on distinction of determinant groups in constant sites of heavy chains («isotypical determinants»). There are also antigenic distinctions connected with features of structure of variable sites of light and heavy chains («idiopathic determinants»). These distinctions can cause individual antigenic specificity of various antibodies or myelome globulins.

The phenomenon of an allotypy consisting in that is important as. at different individuals can differ on antigenic specificity due to some genetically determined features of primary structure of polypeptide chains of molecules I. These antigenic options (allotypes) And. are inherited according to G. Mendel's laws irrespective of a floor and a blood group. For the first time the phenomenon of an allotypy was revealed Uden (J. Oudin, 1956) at a research of serum proteins of rabbits. For And. the person existence of two groups of allotypes — Gm and Inv — with numerous options is established (24 Gm options and 4 — Inv). The determinants defining specificity of Gm-allotypes And., are localized in heavy γ-chains of the class IgG, and Inv-determinants are connected with easy κ-chains and are found in And. all classes. Like blood groups of the AB0 system, definition of an allotype And. matters at hemotransfusion, in court. to medicine at the solution of questions of a doubtful paternity or motherhood (see. Blood groups ).

Quantitative definition of immunoglobulins is carried out most often by method of radial immunodiffusion. The studied serums or solutions I. bring in the holes made in a plate of the agar mixed with monospecific antiserum against this or that And., and through a nek-swarm time measure diameter of a zone of the specific precipitation arising around a hole. Diameter of a zone of precipitation is proportional to concentration of the corresponding P1., to-ruyu it is possible to calculate easily, using the standard curve constructed on the basis of data of the reaction put in the same conditions with standard serum. Monospecific serums are produced by immunization of animals by vysokoochshtsenny drugs I. Such anti-immunoglobin serums or plates of an agar, ready for use, with antiserums are produced as ready drugs. For obtaining comparable data at quantitative definition And. in different laboratories the international standard of WHO representing drug of the lyophilized human serum in each ampoule to-rogo the maintenance of IgG is used, IgA and IgM is accepted equal 100 ME.

Metabolism of immunoglobulins

And. are synthesized in lymphoid cells according to the general patterns of synthesis of proteic matters and come both to a blood channel, and to extravasated space. IgG and IgA in the weight relation are distributed approximately equally in a blood plasma and in extravascular cavities (a lymph, intercellular liquids of fabrics, etc.). IgM and IgD contain preferential (70 — 80%) in plasma.

Contents And. in an organism is defined by a ratio of their synthesis and a catabolism. In the conditions of normal exchange the speed of synthesis per 1 kg of body weight a day makes 20 — 40 mg for IgG, 3 — 50 mg for IgA, 3 — 17 mg for IgM and 0,03 — 1,4 mg for IgD. Catabolism various And. it is carried out with unequal intensity. In normal conditions the smallest speed of exchange is noted for IgG: in day catabolizes apprx. 3% of the general content of this protein in an organism, and half-life makes 23 days. For IgA and IgM the speed of a catabolism makes respectively 12 and 14% a day, and half-life — 6 and 5 days. The largest speed of exchange is inherent to IgD for which half-life is equal 2,8 days.

Contents And. in serum of the person changes depending on age. During pre-natal development synthesis own And. it is insignificant. From And. mothers only IgG comes to a circulatory bed of a fruit. IgM and IgA almost completely are late a placental barrier. Ability of IgG to pass through a placenta is caused by features of a structure of its Fc-fragment. IgG of mother is found in a fruit already on the 11th week of pregnancy. Its concentration gradually increases and by the time of childbirth is equal to concentration of IgG at mother. Within the first months of life parent IgG catabolizes, and own IgG of the child begins to be synthesized only on 4 — 8th week of life. In this regard the general concentration of IgG in serum of the child is minimum in 3 — 4-month age; during this period the child least rezistenten to various infections. Slow increase of IgA begins on 3 — 4 weeks of life. The maintenance of IgM in serum increases soon after the delivery, reaches considerable level by 9 months, but in 2 — 3 falls, and then again begins to increase slowly. Maximum level concentration of all And. reaches by 20 — 30 years. By 60 years reduction of maintenance of IgG and IgM is noted a nek-swarm [Buckley and Dorsey (S. of Buckley, F. Dorsey), 1970].

Role And. in an organism consists in their participation in processes of immunity. Protective function I. it is caused by the various antibodies capable which are contained in this fraction specifically to connect alien antigens. Numerous observations demonstrate that the isolated antibodies on chemical structure and the general structure are identical with nonspecific to I. Ochevidno, the assumption is close to the truth that all molecules I. are antibodies, but it is not always possible to establish in relation to what antigens their specific action is directed. Specific reaction antigen — an antibody (see. Antigen — an antibody reaction ) it is caused by existence in molecules I. the active centers located in Fab-fragments and constructed with participation of a number of the amino-acid remains both in heavy and in light chains. Apparently, these remains are located in variable sites of both types of chains. Ability to complement deflection and to participation in reaction of a passive skin anaphylaxis is connected with a Fc-fragment of immunoglobulins.

The IgG fraction of serum of the person contains antibodies against many viruses and bacteria, and also antitoxins. Antibodies of this class are most active in precipitation tests and fixations of the complement, but concede on activity to IgM-antibodies in agglutination tests and a lysis. The IgM fraction contains the main part of antibodies against lipopolisakharidny O-antigens (endotoxins) of gram-negative bacteria, normal isohemagglutinins, heterophyllous antibodies. In IgA fraction antibodies against some bacteria, viruses and toxins are also found. Assume that antibodies of IgA take part in development of local immunity of some fabrics.

Pathology of synthesis of immunoglobulins

Patol, quantitative and functional changes of PI. can be caused by disturbance of their synthesis or increase in speed of a catabolism. And gammaglobulinemiya (see) it is expressed in almost total absence And. in an organism that is connected at this disease with sharp reduction of quantity of lymphoid cells or with their inability to synthesize molecules I. Absence of fraction I. in serum easily is established by means of the electrophoretic analysis. There are different types of the inborn and acquired agammaglobulinemia. In some cases only partial disturbance of synthesis takes place And., the reduced content in serum causing them (hypogammaglobulinemia). Diseases at which there is no synthesis are described And. not everything, and any one or two classes (dysgammaglobulinemia). E.g., at the hereditary disease which is characterized by a so-called syndrome of Viskott — Aldrich (see. Viskotta-Aldrich syndrome ), in serum there is almost no IgM, and the maintenance of IgG and IgA can even be increased. Types of dysgammaglobulinemias at which there is the selection defect of synthesis or IgA, or IgA + IgM, or IgG + IgA are observed. Nature of such selective disturbances of fractional composition And. define by an immunoelectrophoresis of serums of patients and quantitative definition And. different classes.

Peculiar patol, change of synthesis And. education myelome or patol is. I. Eti of P1, at different patients can belong to various classes and reach in serum of the concentration considerably exceeding normal. At Valdenstrem's macroglobulinemia (see. Valdenstrema disease ) accumulation of IgM takes place. There are IgG-and IgA-myelomas, meet the myelomas which are followed by accumulation of IgD and IgE less often. For myelome And. high homogeneity of primary structure of polypeptide chains is characteristic that is explained by their origin from one clone of lymphoid antiteloobrazuyushchy cells. While at normal synthesis in structure of various molecules I. light chains either a kappa - or a lambda types, all myelome enter And. at one patient contain light chains only of any one type. At multiple myeloma (see) with urine Bens-Jones's proteins about a pier can be secreted. it is powerful apprx. 40 000 which represent dimeasures it is excessive the formed light chains of one of types. At some patol, disturbances of synthesis And. with urine the proteins representing Fc-fragments of IgG with small pieces of N-trailer area of gamma chains («a disease of heavy chains») are secreted.

Decrease in maintenance of IgG at the expense of the increased rate of decay is noted at a hereditary disease — a dystrophic myatonia. In the observed cases half-life of IgG made 11,4 days instead of 23. Considerable decrease in maintenance of IgG and IgA was observed also at patients with nephrotic syndrome (see) due to the strengthened disintegration and release of these immunoglobulins.

Increase in contents And. in serum (hypergammaglobulinemia) it is noted often at acute and hron, bacterial and viral infections, and also at diseases of a liver. Cases of the selection hypergammaglobulinemia, i.e. selective increase in contents are described And. only one or two classes, e.g. IgM at trypanosomic diseases (see. Trypanosomiasis ).

Drugs of immunoglobulin (gamma-globulin) and their use

Drugs represent the solutions of the fraction of serum proteins of the person cleared gamma globulinovoy containing in konts. a type of an antibody against a virus of measles and other activators, present at blood of healthy people.

Drugs of gamma-globulin are included in GFH (article 304) under the name «Gamma-globulin for Prevention of Measles» («Gamma-globulinum ad prophylaxim morbillorum»). The committee of WHO experts recommended as the international name «Normal Immunoglobulin of the Person» («Immunoglobulinum humanum normale»).

For receiving gamma-globulin use plasma or serum of donor blood, serum of intraplatsentarny and retroplatsentariy blood, extracts of the placenta, and also blood serum allocated at operations of artificial abortion. Each series of gamma-globulin is prepared from mix of serums, plasma or placentae not less than from 1000 people that causes leveling immunol. properties also provides commonality of drug. Gamma globulinovoy fractions in the USSR and abroad apply generally various schemes of fractionation of serum proteins to allocation by ethanol at temperatures below 0 ° according to Kohn, use fractionation by ammonium sulfate less often. These methods allow to receive drugs of gamma-globulin, safe concerning transfer of a virus of hepatitis even if single ikterogenny serums get to original serumal stocks.

During the receiving gamma-globulin in large scales use the modern technical equipment with use of methods of mechanization and automation. Fractionation by ethanol is made in the big cooled reactors on 500 — 1000 l with automatically adjustable temperature. Department of proteinaceous rainfall is carried out on highly productive flowing supercentrifuges in refrigerators. For removal of residual ethanol and receiving gamma-globulin in a dry form the crude rainfall of this protein received as a result of fractionation subjects lyophilizing.

The purified gamma-globulin is dissolved in 0,9% NaCl solution at pH 7 — 7,5. Glycine (0,3 M), and as preservative — mertiolat can be applied to stabilization (0,01%). In the USSR in drugs of gamma-globulin establish 10% concentration of protein.

Solutions of gamma-globulin will sterilize by filtering through bacterial, filters (asbestobumazhny plates, milliporovy filters, porous ceramic candles) and control on sterility, harmlessness (on mice and Guinea pigs) and lack of the pyrogenic properties (on rabbits).

According to GFH, gamma globulinovaya the fraction shall make not less than 97% of crude protein in drugs. In drugs of IgG gamma-globulin is the main component; IgA, IgM and IgD are included into drug only in very small amounts. Works on receiving and a research of the drugs of gamma-globulin enriched with IgM and IgA are carried out.

In gamma-globulin antibodies against viruses of measles, flu, poliomyelitis, a variolovaccine, pertussoid agglutinins, staphylococcal anti-alpha toxin, anti-Au streptolysin, diphtheritic and tetanic antitoxins, etc. are found.

During the accepted three-year shelf-life immunol, properties of drugs considerably do not change. However in some series of gamma-globulin, especially from placental and abortion blood, under the influence of impurity of proteases there is a fragmentation of a part of the molecules IgG that can reduce efficiency of drugs.

Gamma-globulin is homologous and almost areaktogenny drug. However it contains mix of the molecules IgG belonging to various allovariants and therefore as a result of administration of drug the phenomena of isoimmunization and antibody formation — anti-gamma globulins are possible. In this regard vaccinated can have very rare reactions of anaphylactic type, especially at repeated administrations of gamma-globulin. Also impurity of fabric, in particular placental, antigens can cause a sensitization.

Drugs of gamma-globulin enter usually intramusculary. Apply doses of 1,5 — 3,0 ml to prevention of measles. For prevention of infectious hepatitis enter 1,0 ml to children from 6 months to 10 years and — to children 10 years and the adult are more senior than 1,5 ml.

At intravenous administration of gamma-globulin there can be strong reactions which are followed by lowering of blood pressure and the shock phenomena. These reactions are caused by the units of the molecules IgG which are present at drugs finding anticomplementary activity. The drugs of gamma-globulin which underwent special processing for destruction or removal of units are deprived of anticomplementary properties, but keep activity of antibodies and can intravenously be entered (e.g., gamma venin and intraglobin, released in Germany, venoglobulin — in France). Intravenous use of gamma-globulin allows to administer large volumes of the drug (25 — 50 ml of 5% of solution above) and quickly occurring effect at some bacterial infections provides (sepses) and an agammaglobulinemia

Drugs of specific gamma-globulins, or gamma-globulins of the directed action, have the increased concentration of antibodies against certain causative agents of infections or the toxins emitted by them.

For the purpose of receiving specific And. use plasma or blood serum of specially immunizirovanny donors. Antitetanic gamma-globulin is received from plasma of donors, immunizirovanny tetanic anatoxin. This homologous drug has advantages in comparison with heterological antitoxins from horse serums: does not cause reactions in the persons sensitive to horse protein, and it is much more slowly brought out of an organism after an injection. The antirabic gamma-globulin of the person produced from plasma or serum of the faces imparted by a vaccine against rage has similar advantage. Antistaphylococcal gamma-globulin is received in the USSR both from plasma of immunizirovanny donors, and from serums of placental blood of women, immunizirovanny during pregnancy by staphylococcal anatoxin. Gamma-globulin against a virus of a tick-borne encephalitis can be made of blood sera of donors, immunizirovanny by an entsefalitny vaccine, or of serums of the placental blood with the raised credits of antiencephalitic antibodies collected in the local centers of encephalitis. Apply also anti-influenza, antismallpox, antipertussoid gamma-globulins.

Drugs antirezusny And. the person, intended for prevention of a hemolitic disease of newborns, receive from serums with the high content of incomplete anti-Rh0 (D) - antibodies. This drug is administered to the primapara rezusotritsatelny women who gave birth to the rezuspolozhitelny child during the first 48 — 72, hour after the delivery. Antirezusny I. connects D - the antigen of a fruit getting into blood of mother and prevents her isoimmunization, eliminating a possibility of a hemolitic disease of newborns at new pregnancy (see. Hemolitic disease of newborns , Rhesus factor ).

Use of drugs of immunoglobulin (gamma-globulin) for children. And. enter to children with various purpose: a) for prevention of some viral and bacterial infections (infectious hepatitis, measles, heavy postvaccinal reactions after smallpox vaccination, is more rare — whooping cough, flu, chicken pox, scarlet fever); b) for treatment of a staphylococcal infection, flu, whooping cough, postvaccinal complications and for the purpose of stimulation in the period of reconvalescence after many infectious diseases; c) for treatment of an antibody deficiency syndrome.

Gamma-globulin gained universal and deserved recognition as valuable prophylactic of measles. It is appointed to the children who were in contact with the patient with measles, aged from 3 months up to 3 years and to the weakened children after 3 years who earlier did not have measles and not vaccinated against it. The drug is administered in a dose of 1,5 ml for mitigation a wedge, currents and 3 ml for the prevention of measles pe is later than the 6th day from the beginning of contact.

As a result of timely administration of drug the children who were in contact with the patient with measles or do not get sick at all or the disease at them passes benign. Administration of gamma-globulin for the purpose of prevention of infectious hepatitis is made at the beginning of seasonal rise in incidence in preschool child care facilities and to pupils of 1 — 4 classes intramusculary in a dose of 1 ml. Preventive action also the smaller dose of gamma-globulin — 0,1ml possesses. The entered gamma-globulin provides passive active immunity lasting up to 6 months. On epid, to indications gamma-globulin is appointed also in a dose of 1 ml to children in the centers of infectious hepatitis (in a family or in child care facility). At full isolation of groups in kindergartens and a day nursery drug is used only in that group where there was a case of infectious hepatitis, and in the absence of isolation — to children of all establishment.

Anti-staphylococcal gamma-globulin is applied to treatment of a staphylococcal infection. Indications for its introduction are all forms of a staphylococcal infection at children of early age. The drug should be administered in the first days of a disease intramusculary on 3 — 5 ml (100 ME) in 1 — 2 day, all on a course of treatment of 3 — 5 injections. In the absence of effect in especially hard cases (at the abscessing pneumonia) it is possible to carry out a repeated course of treatment. Under the influence of therapy by gamma-globulin and antibiotics toxicosis decreases, the septic centers disappear, temperature and blood are normalized.

Antismallpox donor gamma-globulin is used for prevention and mitigation of postvaccinal complications at children with relative contraindications for inoculations. The instruction of M3 of the USSR (1975) children 3 years are more senior introduction of 3 ml of specific drug from placental blood and 1,5 ml of drug from donor blood is recommended. With the therapeutic purpose for treatment of heavy postvaccinal complications (encephalitis, vaccinal eczema, a generalized vaccine) antismallpox gamma-globulin appoint from the first days of a disease in a dose 0,5 — 1 ml to 1 kg of body weight intramusculary; the drug is administered repeatedly before receiving resistant a wedge, effect.

Anti-influenza gamma-globulin is widely applied to treatment less often for prevention of flu. Lech. effect of drug is shown in reduction of duration of the feverish period, intoxication, in decrease in number and weight of various virus superinfections. As indications for administration of anti-influenza gamma-globulin serve the expressed phenomena of intoxication, and also early damage of lungs. Gamma-globulin it is necessary to enter intramusculary one-silt and twice in the following doses: to children aged till 1 year on 1,5 ml, from 1 to 2 years on 2 ml, from 2 to 7 years on 3 ml and children 7 years on 4 — 4,5 ml are more senior. It is reasonable to carry out a repeated injection in 6 — 8 hours after the first or next day. In hard cases it is desirable to raise a dose of the entered gamma-globulin by 1,5 — 2 times.

As means of the nonspecific stimulating immunotherapy gamma-globulin is recommended to apply in a dose 0,2 ml on 1 kg of three times bucketed body weight between injections in 2 days.

According to the recommendation of Committee of WHO experts (1968) gamma-globulin is applied to treatment of an antibody deficiency syndrome on 1,2 — 1,8 .ml by a pas of 1 kg of body weight intramusculary once a month. During acute infections the same doses of gamma-globulin shall be combined with simultaneous introduction of antibiotics. The drugs of gamma-globulin made of placental blood along with undoubted positive effect can have the sensibilizing effect (formation of anti-gamma globulins), and with the changed reactivity to cause development of allergic reactions in some children. Drugs of gamma-globulin shall be appointed only according to reasonable indications. It is necessary to show care at use of gamma-globulin from preventive and to lay down. the purpose to children with the changed reactivity and infectious and allergic diseases in an active form. If nevertheless introduction is necessary on weighty a wedge. - epid, to indications, it is reasonable to replace placental and abortion gamma-globulins with gamma-globulin from donor blood. During the use of placental gamma-globulin it is necessary to consider contraindications for administration of this drug; e.g., it is contraindicated to children in whose anamnesis there are instructions on the expressed reaction (a Quincke's edema, allergic rashes, an acute anaphylaxis) after administration of drug.


Bibliography: Gamma-globulin and other blood preparations, under the editorship of G. Ya. Gorodiyes-kaya, century 1 — 2, Gorky, 1968 — 1972; Immunoglobulins and other blood preparations, under the editorship of I. N. Blochina, L., 1976; Use of immunoglobulin of the person, sulfurs. tekhn. dokl. No. 327, WHO, M., 1968; To at-d and sh about in N. I. Use 7 globulins for treatment of flu at children, Pediatrics, No. 1, page 83, 1973, bibliogr.; Sack-@ of e r A. Ya. Immunoglobulins as biological regulators, M., 1975, bibliogr.; Molecules and cells, the lane with English, under the editorship of G. M. Frank, century 4, page 41, M., 1969; H e z l and R. S. Stroyeniye's N and biosynthesis of antibodies, M., 1972; Prokopenko L. G. and Ravich-Shcherbo M. I. Exchange of immunoglobulins, M., 1974, bibliogr.; Requirements to immune globulin of the person, it is gray. tekhn. dokl. No. 361, page 48, Geneva, WHO, 1968; X about l of the p e in N. B. Modern drugs of immunoglobulins for a medical use, in book: Drugs normal and spetsifich. immunoglobulins of the person, under the editorship of I. I. Shatrov, page 5, M., 1976, bibliogr.; The development of plasma derivatives for clinical use, ed. by G. A. Jamieson, Basel a. o., 1972; Gamma globulins, ed. by F. FranSk a. D. Shugar, L. — N. Y., 1969: Gamma globulins, Proc. 3D Nobel Symp., ed. by J. Killander, Stockholm, 1967; Immunoglobulins, ed. by S. Kochwa a. H. G. Kunkel, N. Y., 1971; International symposium on purity of human plasma proteins, Budapest, 1973, Proceedings, Basel, 1974; Methods in immunology and immunochemistry, ed. by C. A. Williams a. M. W. Chase, v. 1 — 3, N. Y. — L., 1967 — 1971; Sgouris J. T. a. Mat z M. J. Observations on the fragmentation of venous and placental immune serum globulins, Vox Sang. (Basel), v. 13, p. 59, 1967.

H. V. Holchev; H. I. Kudashov (ped.).

Яндекс.Метрика