Modulation of the immune response by passive antibodies. IV. Effects of IgG1 and IgG2 anti-hapten antibodies.

The effects of IgG1 and IgG2 anti-hapten antibodies waere studied on celluar and humoral reactions induced by immunization with a hapten-carrier complex. IgG2 was shown to depress delayed hypersensitivity reactions to the carrier and to enhance anaphylactic reactions to both the hapten and the carrier whereas IgG1 appeared to have no activity except a little enhancing effect on antibody synthesis to the carrier. The regulatory role of IgG2 antibodies, which were cytophilic for macrophages, in the immune response to a hapten-carrier conjugate is discussed.

Enhancing effect of passive immunization with mycobacterial antibodies on humoral and cellular immunity in BCG-infected mice.

The present paper is an attempt to get insight about the mechanisms involved in the enhancing phenomenon that occurs in bacterial infections. Mice infected with small doses of the BCG strain of M. bovis and treated with a M. tuberculosis H37Rv antiserum investigated at various intervals for their capacity to synthesize haemagglutinating antimyco-bacterial antibodies and to develop delayed hypersensitivity to PPD. As controls, BCG-infected mice were treated with the antiserum freed from its mycobacterial antibodies. It was found that the passive immunization of BCG-infected mice promotes the growth of bacilli in their spleen and induces a late formation of antimycobacterial antibodies which do not seem to be related to the development of delayed hypersensitivity.

Biological properties of goat immunoglobulins G.

Ther serum concentration of normal adult goat total IgG was established to be 19.97 +/- 1.55 mg/ml, the IgG1 10.92 +/- 0.84 mg/ml and IgG2 9.07 +/- 0.78 mg/ml. No significant variations were found to be associated with the seasons of the year but changes in concentration, especially in serum IgG1 occur ante- and post-partum. In goat colostrum, the IgG concentration is about 2.4-2.8 times greater than in serum and the IgG1 subclass accounts for 95-98 per cent. During the immune response the IgG1 rises sharply whereas variations in IgG2 concentration are less evident. Both IgG subclasses are active in haemagglutination, although the IgG1 is 22-52 times more efficient. As in all ruminants, only IgG1 fixes complement in the classical test. Differences exist between IgG subclasses in their ability to induce PCA reactions. IgG2 subclass is active only in homologous species whereas the IgGl in heterologous species. Cytophilic activity is associated with IgG2 subclass.

An immunological enhancement phenomenon in experimental brucella infection of the chicks.

The passive transfer of chicken anti-brucella immune globulins promote the survival of Brucella abortus in the spleen of chickens infected with this bacteria. This enhancing effect was reduced significantly when the immune globulins were absorbed with heat-killed brucella cells to remove all the anti-brucella agglutinins and immune adherence antibodies. Therefore, it is most probable that the enhancing effect is related to the presence of brucella antibodies.

Preferential transport into colostrum of Fc fragment derived from serum IgG1 immunoglobulin in the goat.

The selective transport of blood IgG1 into colostrum in ruminant species is not well understood. Therefore, the transport of Fc fragments isolated from serum IgG1 (Fc gamma 1) and IgG2 (Fc gamma 2) in normal and pregnant goats was studied. The animals were injected intravenously with radio-labelled 125I-Fcgamma1 and 131I-Fcgamma2 fragments. The plasma disappearance rate of both fragments showed that at parturition the Fcgamma1 fragment had a higher disappearance rate than Fcgamma2. Over 70 per cent of the inoculated dose of 125I-Fcgamma1 and only 11-12 per cent of 131I-Fcgamma2 could be recovered in the 24 h colostrum. The results indicated that structural differences between the H chains of IgG1 and IgG2 were implicated in the selective transport of IgG1 into colostrum in ruminants.

Partial characterization of a factor extracted from sensitized lymphocytes that inhibits the growth of Mycobacterium tuberculosis within macrophages in vitro.

Spleen lymphocytes of BCG-immunized mice contain a soluble factor that inhibits in vitro the growth of the H37Rv strain of Mycobacterium tuberculosis within normal peritoneal macrophages. The water-soluble extracts of sensitized lymphocytes, disrupted by freezing and thawing, although less active than the corresponding viable cells retained a significant growth-inhibiting activity. Dialysis against distilled water, lyophilization, exposure to ribonuclease and deoxyribonuclease, and storage at -20 degrees C of the water-soluble extracts did not affect their antimycobacterial activity, whereas extracts heated at 100 degrees C were completely devoid of such an activity. All the inhibiting activity was recovered in the void volume of the column after chromatography on Sephadex G-200. Water-soluble constitutents of sensitized lymphocytes did not affect BCG grown in vitro, and on repeated treatments of tuberculous mice they led to a negligible protection against pulmonary tuberculosis. Preliminary observations seem to indicate that other soluble factors in lymphocytes of BCG-sensitized mice have the capacity to potentiate in vitro the phagocytic activity of normal macrophages.

The role of colorstrum on the occurrence of immunoglobulin G subclasses and antibody production in neonatal goats.

Quantitative determinations of IgG1 and IgG2, in one group of colostrum-fed and one group of colostrum-deprived neonatal goats revealed that the occurrence of the IgG1 subclass preceeded that of the IgG2 in both cases. In the colostrum-fed animals the IgG2 appeared, on an average, in the fourth week of life whereas in the colostrum-deprived animals the IgG2 was detected as early as three weeks after birth. At the age of twelve weeks the mean concentrations for IgG, and IgG2 were higher in the animals deprived of colostrum. The immune response to human gamma globulin was studied in colostrum-fed and colostrum-deprived neonatal goats which were immunized at birth and again after four and eight weeks. Following the first two antigen administrations a significantly higher response was obtained in the colostrum-fed neonates. However, the third injection determined a similar response in both groups. A marked suppressive effect on the immune response was observed in colostrum-fed neonatal goats when specific antibodies were present in the colostrum after preimmunization of the mothers with human gamma globulin.

Modulation of the immune response by passive antibodies. II. Effects of passive anti-hapten and anti-carrier antibodies on the immune response to a sustained antigenic stimulation.

The present work is an attempt at understanding the modulating effects of passive antibodies on the immune response to a sustained antigenic stimulation. Passive anti-carrier and anti-hapten antibodies were injected 24 h before immunization with the hapten carrier conjugate into guinea pigs subsequently injected intradermally with the carrier alone on days 11 and 23. The results showed that passive anti-carrier antibodies blocked the effects of intradermal injections of carrier, i.e., desensitization and increase of antibody synthesis to the carrier. Passive anti-hapten antibodies did not prevent desensitization and delayed antibody synthesis to the carrier. The mechanisms whereby passive antibodies modulate the response to a sustained antigenic stimulation are discussed.

Hapten and carrier specificities of cellular and humoral responses to highly substituted dinitrophenyl-human gamma-globulins in guinea-pigs.

Delayed hypersensitivity (DH) and antibody reactions to the carrier and to the hapten have been studied in guinea-pigs immunized with different doses of highly substituted dinitrophenyl-human gamma-globulins (DNP56-HGG) in Freund's complete adjuvant (FCA). The results confirm that DH reactions are specific for the carrier while antibody-mediated reactions are specific for the hapten in the early stages of the immune response. Later in the response, however, DH reactions to the hapten as well as a transient humoral reaction to the carrier could be observed. T cells specific for the hapten and B cells specific for the carrier are therefore triggered after a single infection of a highly substituted hapten-carrier conjugate in FCA. Their regulatory functions in the immune response to hapten-carrier conjugates are discussed.

Carrier and hapten functions in immune deviation. II. Role of hapten and carrier on the helper functions of the T cells.

The kinetics of haemagglutinating and haemolytic antibody synthesis to the hapten and to the carrier determinants were studied in guinea-pigs injected intravenously with large doses of the carrier, or of the hapten conjugated to an homogous or heterologous protein carrier and subsquently immunized with the hapten-carrier conjugate in Freund's complete adjuvant. The animals treated with the heterologous conjugates exhibited enhanced reactions to the hapten and supressed reactions to the carrier, whereas the animals injected with the homologous conjugate showed depressed reactions to the hapten but unaffected reactions to the carrier. Pretreatment with the carrier alone-seemed to have no effect. These experiments confirm that the hapten determinant must act at the T-cell level but do not exclude the possibility that it could also act at the B-cell level. On the other hand, they allow the dissociation of the different components of the immune response directed against the hapten and carrier determinants of the antigen molecule in immune deviation.

Carrier and hapten functions in immune deviation. I. Contrary effects of hapten and carrier on cellular and helper functions of T cells.

Carrier and hapten functions have been studied in the immune deviation phenomenon. Delayed hypersensitivity to the carrier and anaphylaxis and Arthus hypersensitivities to the hapten and to the carrier were studied in guinea-pigs injected intravenously with large doses of carrier, homologous and heterologous hapten-carrier conjugates and subsequently immunized with the hapten-carrier conjugate in Freund's complete adjuvant. Pretreatment with DNP-BSA or with HGG were found to modify, in opposite directions, the hypersensitivity reactions induced by DNP-HGG in adjuvant. It is suggested that the hapten and carrier moieties of the antigen molecule might have antagonistic effects on the T cells responsible for cellular immunity as well as on T cells involved in helper functions for B cells.

Modulation of the immune response by passive antibodies. I. Anti-hapten antibodies enhanced delayed hypersensitivity to the carrier and depressed antibody synthesis to the hapten.

The modulating effects of passive antibodies on both delayed hypersensitivity to the carrier and antibody synthesis to carrier and hapten determinants were studied in guinea pigs. Animals were injected with antibodies directed against either the carrier or the hapten prior to immunization with the hapten-carrier conjugate in Freund's complete adjuvant. Anti-hapten antibodies have been shown to have an enhancing effect on delayed hypersensitivity to the carrier and a suppressive effect on antibody synthesis to the hapten. In this experiment, anti-carrier anti-bodies seemed to have had no effect on delayed hypersensitivity to the carrier and on antibody synthesis to the hapten.

Enhancement activity of homologous anti-staphylococcal sera in experimental staphylococcal synovitis of chicks: a possible role of immune adherence antibodies.

Homologous anti-staphylococcal sera passively potentiated the development of experimental staphylococcal synovitis infection of chickens. These antisera obtained from chickens hyperimmunized with live Staphylococcus aureus were selected according to their immune adherence and agglutinating properties. While the agglutinins rose steadily for 11 weeks during the hyperimmunization schedule, the immune adherence antibody titers reached a peak at 8 weeks and dropped to almost zero 2 to 4 weeks later. The enhancement activity of these antisera was associated with a relatively high level of immune adherence antibodies and seemed not to be correlated with their agglutinin titers.