Effect of hydrazide cysteine on the humoral immune response of mice to sheep erythrocytes

Hydrazide of cysteine, introduced intraperitoneally or per os in three doses for three consecutive days after immunization of mice with SRBC, caused a stimulation or an inhibition of the humoral immune response, determined on day 4 as a number of cells in the spleen producing antibodies of 19S and 7S class. The stimulation of the humoral immune response was induced by the dose of 100 micrograms per mouse and was more significant in the case of the 7S response. High doses of HD, on the other hand (1 mg per mouse i.p. and 1-5 mg per mouse per os) caused an inhibition of the humoral immune response which was more pronounced in the case of the secondary immune response. The mechanism of action of HD in the course of the immune response and its possible application in therapy is discussed.     

Immune response toSalmonella typhi Vi-antigen and tolerance to it in T cell deprived mice

The role of T suppressors in the regulation of the immune response toSalmonella typhi Vi-antigen was studied by comparing the immune response to this antigen in T cell deprived mice (B mice) with the immune response in intact animals. Deprivation of T cells was produced by thymectomy or by lethal irradiation and subsequent injection of embryonic liver cells into the mice. The level of the immune response to Vi-antigen was almost identical in the B mice and control animals. The absence of enhancement of the immune response in the B mice shows that not only induction but also regulation of the immune response to the optimal dose of Vi-antigen is thymus-independent in character. Tolerance to Vi-antigen could be induced in B mice by means of cyclophosphamide; the degree of specific inhibition of the immune response, moreover, was the same as in animals possessing T cells. This suggests that the cause of drug-induced tolerance to this antigen is not activation of T suppressors, but rather a true deficiency of immunocompetent clones of B cells.Laboratory of Immunologic Tolerance, N. F. Gamaleya Institute of Epidemiology and Microbiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR P. A. Vershilova.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 87, No. 1, pp. 33–36, January, 1979.     

Immune response in vaccinia virus infected mice treated with N,N'-bis/methylisatin-beta-thiosemicarbazone/-2-methylpiperazine

The effect of the compound N,N'-bis/methylisatin-beta-thiosemicarbazone/-2-methylpiperazine (bis-MIBTP) on immune response in BALB/c and Swiss mice have been studied in the course of vaccinia virus infection. Humoral response tested by neutralization and hemagglutination inhibiting antibodies was similar in compound-treated mice to this of untreated mice. Cell-mediated immune response, examined by spleen lymphocytes migration inhibition test, has been delayed or temporally depressed in bis-MIBTP treated mice as compared with the control group. High protective activity of the compound in vaccinia infected mice in spite of impairment of cellular immunity may indicate that antibodies have played an important role in recovery process from vaccinia infection.     

Effects of zoosocial conflict on immunological reactivity of C57Bl/6 mice

In aggressive C57Bl/6 mice, the immune response is shown to be enhanced after 20 confrontations with submissive mice. In submissive mice, the response is inhibited after 10–20 confrontations with aggressive partners. It is concluded that stimulation and inhibition of the immune response are associated with the formation of a neurochemical set which is dopaminergic in aggressive mice and serotoninergic in submissive ones. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, No. 11, pp. 541–543, November, 1996     

Relationships among differentiated T-cell subpopulations. IV. Preferential induction of delayed footpad reaction to xenografts and its radioresistant nature.

Immune response in mice to xenogeneic cells was characterized by positive delayed footpad reaction and negative macrophage migration inhibition. Mice immunized with allogeneic cells exhibited negative delayed footpad reaction and positive macrophage migration inhibition. Cytotoxic T lymphocytes were detected only in mice immunized with allogeneic tumour cells. Delayed footpad reaction against xenogeneic cells was radioresistant and the immune lymphocytes responsible for such a reaction were presumed to have some relation to xenograft rejection.     

The effect of delayed administration of folinic acid on immunological inhibition by methotrexate

Administration of folinic acid to mice 8 hours after various doses of methotrexate gave considerable protection against mortality and weight-loss. The immune response to T.A.B. vaccine, however, which was inhibited by methotrexate, was negligibly affected in these circumstances, there being little difference between the degrees of inhibition found in protected and unprotected mice. The action of methotrexate on the immune apparatus required for completion some 6–8 hours after its administration, and administration of folinic acid at earlier times resulted in partial or complete reversal of inhibition. It is suggested that, during the early stages of the immune response, antigenically stimulated cells may be irreparably damaged by only a few hours exposure to folic acid antagonists.     

Effect of doxycycline on immune response in mice.

The effect of doxycycline on immune response has been studied in mice, cell-mediated immunity being evaluated with the split heart allograft technique. Survival duration of heart transplants in animals treated with 2.5 mg of doxycycline per kg per day from the day of transplantation until rejection was slightly but significantly longer than in untreated animals, 18.8 days (P less than 0.05) as compared with 14.5 days. In doxycycline-treated animals, both agglutinating and hemolytic antibody response to sheep erythrocytes was slightly but significantly decreased, though there was no inhibition of splenic production of antibodies to sheep erythrocytes (as measured by the number of plaques of hemolysis detected). The results show the immune response in mice to be only moderately inhibited by doxycycline. The relevance of experiments in mice is also discussed.     

A simple method of blood exchange in mice and its application to immunology

A new method for blood exchange (up to 97 per cent) in mice was developed and used to carry out three immunological assays. We showed that it was not possible to influence the immune response appreciably by blood exchange immediately after antigen application. The observation that specific 7S antibodies inhibit immune response, even if these 7S antibodies were removed almost completely by blood exchange, and the comparison with other experimental data, gives rise to the belief that this inhibition might be based on the formation of anti-antibodies.

In another assay we tested the importance of `natural' antibodies for the immune response. Using mice we could not confirm the results of Murray (1968) that the removal of `natural' antibodies in the blood of rats by adsorption to sheep red cells causes an immune response. The act of adsorption adds antigen to the blood and this antigen is the reason for the immune response.

     

Immune response during activation of pre- and postsynaptic serotonin 5-HT(1A) receptors in C57Bl/6J mice at various stages of a depression-like state

The development of a depression-like state in C57Bl/6J mice with repeated defeat experience (10 and 20 days) was accompanied by inhibition of the immune response (evaluated from the number of IgM antibody-producing cells). Activation of postsynaptic 5-HT(1A) receptors with a selective agonist 8-OH-DPAT (1.0 mg/kg) in these animals had no effect on the immune reaction. In mice without the experience of confrontations, stimulation of postsynaptic receptors caused a decrease in the number of IgM antibody-producing cells at the peak of the immune response induced by sheep erythrocytes (5×10(8) cells). However, the count of these cells remained unchanged in mice with a depression-like state (irrespective of the stage of disorder). Activation of presynaptic 5-HT(1A) receptors with 8-OH-DPAT (0.1 mg/kg) in control animals and mice with 10-day defeat experience was followed by immune stimulation. These changes were not observed in mice with a depression-like state caused by 20-day social stress.     

Inhibition of Tumor Growth and Metastases in Mice Bearing a Malignant Fibrosarcoma by T Cell-Mediated Immune Response to Oncofetal Antigens

ABSTRACT: The presence of fetal antigens on a wide variety of tumors has been well-documented it has been attributed, for the most part, to de-repression of genes normally operative in the early stages of embryonic development. Controversy still exists, however, about the role of fetal antigens in antitumor immunity. It is not clear whether the tumor inhibition shown in some systems is due to an immune response. In the present study, conducted in a weakly immunogenic Lewis T241 fibrosarcoma, syngeneic for C57B1/ 6J mice, immunization of normal mice with syneneic fetal cells resulted in striking inhibition of growth and metastases of tumors. On the other hand, immunization with syngeneic normal, adult spleen cells or with allogeneic A/J fetal cells did not inhibit tumor growth or metastases. Mice that had gone through single pregnancy also showed inhibition in tumor growth and metastases. Immunization of female mice with syngeneic tumor cells or fetal cells, prior to pregnancy, resulted in a high incidence of fetal death in these mice. Further studies showed that tumor inhibitory response evoked by fetal cell immunization was due to fetal antigens the male-specific HY antigen was not responsible for antitumor response. When tumor cells were mixed with spleen cells from fetal antigen-immunized mice and then injected into normal mice (Winn neutralization assay), significant inhibition of tumor growth and metastases was observed. In this assay, mixing tumor cells with syngeneic fetal cells, normal adult spleen cells, or spleen cells from C57 mice immunized with allogeneic fetal cells did not inhibit the tumor growth or metastases. These results show that inhibition in tumor growth and metastases, following fetal cell immunization, was due to a specific immune response to the oncofetal antigens involved. Analysis of effector cells showed them to be T cells of Lyt-1⁺ and Lyt-2^? phenotype.     

Protective effectiveness of the blood sera and immune system cells from mice immunized with live or inactivated influenza virus

The results of the study of comparative protective role of humoral and cell-mediated immunity factors obtained from inbred donor mice immunized with live or inactivated influenza virus are presented. The superiority of the live virus over the inactivated preparation as the inducer of not only humoral but especially cell-mediated immune response was demonstrated by the effectiveness of passive intranasal protection of the infected mice, by the degree of inhibition of virus reproduction in the lungs of the protected mice, and by the capacity for interferon production by the cells of the immune system of donor mice.     

Induction of secondary immune response by reactivated Japanese encephalitis virus in latently infected mice.

Development of secondary immune response has been studied following reactivation of latent Japanese encephalitis virus (JEV) infection in mice. The virus could be reactivated in 43% of the latently infected mice at 27 weeks p.i. by treatment with cyclophosphamide. The reactivated virus induced delayed-type hypersensitivity (DTH) and leucocyte migration inhibition (LMI) responses in mice, with peak activity on Day 5 post-reactivation (p.r.). The DTH persisted at low levels for long periods. Humoral immunity measured by haemagglutination-inhibiting antibody showed a four-fold rise in antibody titres. DTH was transferable by immune spleen cells for 5 days p.r. only. It is, therefore, concluded that JEV reactivation generates a quick and short-lived secondary immune response.     

The regulation of the immune response of mice to Haemophilus influenzae type b capsular polysaccharide.

The regulation of age-related antibody response to Haemophilus influenzae type b polysaccharide (HITB-PS) was studied by measuring the splenic plaque forming cells (PFC) following immunization with this capsular polysaccharide. The magnitude of PFC response to HITB-PS was found to be dose-related, enhanced by Freund's complete adjuvant and influenced by the genetic strain of mice. Priming with a low dose of HITB-PS did not induce a state of immunological unresponsiveness. Treatment with antilymphocyte serum significantly increased the PFC response to HITB-PS. Athymic nude mice showed an enhanced ability to induce both IgG and IgA-PFC responses as well as a significant increase in the biosynthesis of protein and mitogenicity in spleen cells. These findings suggest that the immune response to HITB-PS is regulated by the suppressor T cell. The magnitude of the IgM-PFC response induced by HITB-PS in mice increased gradually from two weeks of age and reached a plateau at 8 weeks. Treatment with fetuin resulted in the inhibition of direct IgM and IgG-PFC responses to HITB-PS; the suppressive effect on the immune response was more profound and lasting in young than in adult mice.     

Genetically controlled immune responses of inbred mouse strains to conjugates of the ordered peptides (Tyr-Tyr-Glu-Glu) and (Tyr-Glu-Tyr-Glu) with multichain poly-DL-alanine as compared with the response to the random (T,G)-A--L

In previous studies we have shown that the immune response of different inbred mouse strains to the ordered synthetic antigen (Tyr-Tyr-Glu-Glu)-A--L is similar to that observed with the random polypetide (T, G)-A--L in the pattern of response and in the cross-reactivity of specific antibodies with it. By inhibition studies of the hemolytic plaque-forming cell (PFC) assay we have now further confirmed that T-T-G-G is the major determinant in the random (T, G)-A--L. C3H/HeJ mice were found to be nonresponders to (T-T-G-G)-A--L, whereas using the same techniques these mice produced low titers of antibodies to the random (T, G)-A--L. Using the hemolytic PFC technique low numbers of antibody-producing cells were detected in spleens of C3H/HeJ mice. However, the avidity of these antibodies as measured by inhibition of PFC was low as compared with that observed for antibody produced in C3H.SW mice in response to the ordered (Tyr-Tyr-Glu-Glu)-A--L. Genetic analysis experiments demonstrated a close linkage between the ability to respond to (Tyr-Tyr-Glu-Glu)-A--L and the major histocompatibility locus (H-2) of the mouse as was previously shown for (T, G)-A--L. In contrast, no linkage was observed between the immune response potential to (Tyr-Glu-Tyr-Glu)-A--L and the H-2 as indicated by the pattern of response of different inbred and congenic mouse strains and by genetic analysis. Thus, the change in the order of two amino acid residues within the sequence of the tetrapeptide caused an enormous change in the biological specificity of the antibodies produced and in the genetic control of the immune response.     

Relationships among differentiated T-cell subpopulations: II. Cytotoxicity and other functions of T cells specific for nucleated chicken erythrocytes

Relationships among T-cell mediated cytotoxicity, tuberculin type hypersensitivity, Jones-Mote type hypersensitivity and activation of helper T cells were studied in AKR mice by means of target cell destruction (⁵¹Cr-release), footpad reaction, migration inhibition test and antibody production against the trinitrophenyl group. (1) Immunization with chicken red blood cells (CRBC) in saline, Freund's incomplete (FIA) or complete adjuvant (FCA) and fixed-CRBC (FRBC) in FIA or FCA induced delayed hypersensitivity as demonstrated by footpad swelling. (2) Migration inhibition was positive in the group immunized with CRBC in saline or FCA, or FRBC in FCA, but negative in those immunized with CRBC or FRBC in FIA. This may suggest that the former has to be assigned to tuberculin type and the latter to Jones-Mote type. (3) T-cell mediated cytotoxicity by immune spleen cells was detected only in mice immunized with CRBC in saline. (4) Pre-treatment with cyclophosphamide augmented delayed footpad reaction in mice immunized with CRBC in saline, but suppressed cytotoxic activity. (5) FRBC in saline scarcely induced delayed footpad reaction and cytotoxic activity, whereas they activated helper function efficiently. Thus, four types of immunological phenomena, attributable to the functions of T cells, may depend upon distinct subpopulations of differentiated T cells which are raised by different methods of immunization.     

免疫反应对糖皮质激素受体的影响和意义

本文采用绵羊红细胞腹腔注入C_(57)BL小鼠产生抗绵羊红细胞的免疫反应。观察小鼠在免疫反应过程中,其脾脏淋巴细胞糖皮质激素受体(GCR)数的变化。发现在绵羊红细胞致敏后第五天小鼠脾淋巴细胞GCR数明显高于对照组(P<0.005),第七天达高峰,第十一天恢复至正常。用Dex抑制由植物血凝素(PHA)诱导的小鼠脾脏淋巴细胞的转化探讨致敏鼠脾淋巴细胞GCR变化的意义。结果提示Dex对淋转抑制程度可能与淋巴细胞GCR数有关。本文还用上述方法研究了妊娠小鼠,发现妊娠母体内脾淋巴细胞GCR数明显高于未孕小鼠(P<0.005),这在调节母胎免疫反应中有一定意义。     

The in vivo effects of concanavalin A on the cellular immune response in BALB-c mice. Inhibition of the delayed hypersensitivity reaction to tuberculin

The suppressive effect of concanavalin A (Con A) on the cell-mediated immune response was demonstrated in BALB/c mice made immune to challenge with tuberculin. 400 μg of Con A administered intraperitoneally simultaneously with injection of antigen into the footpad of primed animals resulted in suppression of the delayed hypersensitivity reaction as detected by a sensitive radioisotopic footpad assay. If Con A was given in a dose of 100 μg three times weekly to normal mice being sensitized to tuberculoprotein, the maximum immune response following complete immunization was significantly suppressed but not abolished. The suppressive effect of Con A appeared to be due to its binding to cell membranes, since splenic lymphocytes obtained from Con A-treated immune mice failed to respond in the local adoptive transfer reaction to tuberculin. The lymphocytes regained their immune reactivity to tuberculin if they were first incubated in α-methyl-D -mannoside. These findings represent the first demonstration of in vivo immunosuppression by Con A of the tuberculin immune response in the mouse. Both the inductive and established responses of the delayed hypersensitivity reaction appear to be affected. The reversible inhibition of the local adoptive transfer of tuberculin immunity suggests the depression of the response is due to binding to or alteration of antigen receptor sites by Con A.     

Immune recognition of porin and lipopolysaccharide epitopes of Salmonella typhimurium in mice

We investigated the antigenic specificity of the humoral immune response to infection by Salmonella typhimurium, by competitive inhibition enzyme-linked immunosorbent assay and Western immunoblots. A panel of eight murine monoclonal antibodies, raised to OmpC and OmpD porins and lipopolysaccharide (LPS)-O antigens, was used to define the specificity of the polyclonal immune response in mice. The monoclonal antibody panel recognized five distinct epitopes; these were localized to surface-exposed loops of OmpC and OmpD porin, to the "eye-let" forming loop L3 of OmpC/OmpD, and to LPS-O4 and O5 factors. The immune mouse serum raised to infections with S. typhimurium LT-2 strain WB600 (wild-type) competitively inhibited the binding of biotin-labelled monoclonal antibodies to the epitopes that they recognize, indicating that all five epitopes were targets of the host immune response to natural infection. However, only two epitopes, one within a surface-exposed loop of OmpC porin, and the other in the LPS-O4 factor, were immunodominant. Furthermore, the bacterial LPS core and O-antigen structure influenced the immune response to the porins. Surface epitopes of porins were dominant in the rough strain SH5014 (rfa), whereas the immune recognition of LPS epitopes was predominant in mice infected with the smooth, wild-type strain (WB600). Finally, the immune response to LPS epitopes O4 and O5 was more pronounced in mice immunized with heat-killed cells than those infected with live S. typhimurium.     

Macrophage Migration Inhibition Studies with Cells from Mice Vaccinated with Cell Walls of Mycobacterium bovis BCG: Characterization of the Experimental System

The macrophage migration inhibition test was applied to the study of delayed hypersensitivity in mice vaccinated intravenously with oil-treated cell walls of Mycobacterium bovis BCG. Migration inhibition of peritoneal exudate cells from sensitized mice was demonstrated directly upon incubation of the cells with purified protein derivative, but indicator cells such as normal peritoneal cells had to be included to demonstrate migration and migration inhibition with sensitized lung cells. Inhibition of migration induced by mouse cells was greatest 3 to 4 weeks after sensitization but was still considerable after 11 weeks. The migration inhibitory factor (MIF) was not detected in cells freshly isolated from sensitized mice but was released into the supernatant fluid when cells were incubated with purified protein derivative for 24 hr at 37 C in a tissue culture system. Production of MIF was inhibited by actinomycin D and puromycin. MIF was nondialyzable, resistant to heating at 56 C for 1 hr, and of a lower molecular weight than mouse gamma globulin. All data indicated that migration inhibition induced by cells from cell wall-vaccinated mice was very similar to that caused by guinea pig lymphocytes.