[Role of secretory immunoglobins in the pathogenesis of chronic inflammatory diseases of the biliary tracts in children].
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Biomedical subjects
Publications and source records attributed to D V Stefani.
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The work presents the data on the dynamics of accululation of the main classes of immunoglobulins (A, G and M) in coprofiltrates obtained from patients with alimentary toxicoinfections (bacteriologically confirmed salmonellosis and diseases of unknown etiology). The levels of immunoglobulins of all classes (mainly IgA and IgG) were shown to be elevated in the process of the disease. The dynamics of the increase in the level of IgA (both general and secretory) was supposed to indicate the formation of local immunity in the intestinal wall. The presence of serum IgA and the characteristic IgG dynamics seemed to be indicative of destructive processes occurring in the intestinal wall. Thus, the dynamics of accumulation of immunoglobulins in coprofiltrates obtained from patients with alimentary toxicoinfections reflects the main local pathological and immunological processes.
The levels of the first 3 subclasses of IgG, as determined by the radial immunodiffusion test, proved to be similar in the blood sera obtained from mothers and newborns in Moscow. The concentration of IgG4 was 0.64 +/- 0.02 g/l iently indicative of a limited passage of IgG4 molecules through the placenta. The inhabitants of an isolated northern village were found to have the inheritable combined deficit of IfG2 and IgG3 synthesis in their blood sera, which was probably due to the prolonged processes of inbreeding and the progenitor effect.
Rabbit antilymphocyte serum (ALS) and complement were used in doses killing 50% of lymphocytes (staining with a 1% solution of trypan blue). In rosette-forming and blast-cell transformation reactions the counts of rosette forming and transformed cells were 60 and 24% respectively, as compared to those in controls. After adding 0.1 ml of 10 mM solution of potassium hydroxyethylene-diphosphonate belonging to a group of synthetic diphosphonates, the protective effect was observed shown by that the counts of rosette-forming and transformed lymphocytes did not differ from the control ones, wherein the reactions were produced with intact cells.
Aerosol and intranasal methods of influenza vaccination were studied on volunteers. Aerosol vaccination induced intensive S-IgA-producing reaction and increase of the specific antibody titres in the saliva and nasal secretions. Intranasal vaccination led to increase of influenza antibodies in the washings from the nasopharynx. The presence of a wide spectrum of antiviral and antibacterial normal secretory antibodies was revealed in the fluids under study. Along with stimulation of specific secretory antibodies, the methods of influenza vaccination under study led to increase of the titre of antibodies nonspecific of the vaccine used.
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Guinea pigs were used for preparing antisera to human IgG subclasses for anti-IgG1, and rabbits--for anti-IgG2, anti-IgG3, and anti-IgG4. Schemes of laboratory animals immunization with myeloma paraproteins of four IgG subclasses were determined. Methods of antisera absorption for bringing them up to strict monospecificity were worked out. Antisera specificity were determined by the precipitation test after Ouchterlony with standard myeloma proteins in the concentration of 1 mg/ml, and in the passive hemagglutination test with erythrocytic antigenic diagnostic agents. Precipitating antisera to four human IgG subclasses were obtained.
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Rabbit antilymphocytic serum and complement were taken in quantities provoking the death of 50 per cent of human lymphocytes secreted in the phycol-verographin density gradient. Compounds (dinatrium salt of oxyethylendiphosphonate acid, alkylated oxyethylendiphosphonate acid, aminoethyloxyethylendiphosphonate acid, aminobenzyldiphosphonate, and aminoisopropyldiphosphonate acids) of 10 mM diphosphonic composition solutions in quantities of from 0.001 ml to 0.2 ml were added to experimental samples of 0.2 ml lymphocytes suspension containing 2.4 X 10(4)--6.0 X 10(4) cells. A decrease in the dead cell count in staining with a 0.1 per cent trypan blue solution was observed. Dinatrium salt of oxyethylendiphosphonate acid and alkylated oxyethylendiphosphonate acid proved to be most effective: it showed protective properties already in a dose of 0.01 ml. All the tested components had a pronounced protective action in a dose of 0.1 ml.
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A combination of the methods of preparative electrophoresis in agar gel and of the ion-exchange chromatography on DE-32 cellulose permitted to obtain 32 immunochemically pure human myelomic IgG. The proteins of the first three subclasses were obtained by elution in the 0.01 phosphate buffer at pH 7.6. IgG4 was eluted with the increase of the gradient to 1 M NaCl in the phosphate buffer. Of the 32 human myelomic IgG 26 represented IgG1,4--IgG2, 1--IgG3, and 1--IgG4. Among the 26 IgG1 11 were of the Gm(a) allotype, and 15 proteins had the Gm(f) determinant; one IgG2 protein was Gm(n+) and 3--Gm(n-). One IgG3 protein was referred to the Gm(b) variant. The majority of the IgG proteins of the subclass I had chi-type of the L-chains, and the chi: lambda ratio constituted 2.71.
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Immunoglobulin composition was studied in the amniotic fluid (AF) and in the urine of newborn babies. IgA was revealed with the aid of anti-secretory component of the serum in 50 of 57 AF samples; in the urine of babies in the course of the first 24 hours after birth it was revealed in 2 of the 21 cases only. This fact and also the detection of the secretory IgA in the AF at the early periods of pregnancy permit to suppose the synthesis of IgA or of its C-fragment in the amniotic membranes.
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Volunteers were vaccinated subcutaneously and orally against typhoid fever; a determination was made of immunological reactions in the digestive tract secretions. Oral vaccination caused a much greater production of the secretory IgA than the subcutaneous one. Immunoglobulins of classes G and M were revealed in the intestinal contents only in a few volunteers. In studying the coprofiltrates obtained before the vaccination there was shown for the first time the presence of normal coproantibodies to typhoid fever, dysentery, tetanus, diphteria, botulism and gas gangrene; in the majority of the cases there was found a correlation between the presence of normal serum and secretory antibodies. Subcutaneous and oral vaccination caused an increase of coproantibodies specific for the vaccines used. Besides, the same vaccines stimulated the nonspecific response expressed in a rise of the level of other species of antibodies. Specificity of coproantibodies in the inhibitary passive hemagglutination reaction was demonstrated in the majority of the coprofiltrates examined.