Restorative effect of short term administration of thymulin on thymus-dependent antibody production in restraint-stressed mice

Thymulin is a well defined nonapeptide produced by thymic epithelial cells, and plays an important role in thymocyte differentiation. We investigated the restorative effect of thymulin on the stress-induced reduction in the production of antibodies against SRBC in mice. Antibody production in stressed mice was reduced to about 50% of that in normal mice. A 3-day period of administration of thymulin (1 ng/kg) restored antibody production to close to the normal level, whereas thymulin (1 ng−1 μg/kg) did not affect antibody production in normal mice. These results indicated that thymulin normalizes the altered thymus-dependent immune responses.     

The role of macrophages in the adjuvant effect on antibody production of Corynebacterium parvum.

Spleen cells from mice pre-treated with C. parvum gave an enhanced in vitro antibody response to SRBC, but not to DNP-POL. This enhancing activity was associated with the adherent, but not the non-adherent spleen cell population and was found to be radioresistant. It is concluded that macrophages are directly involved in the adjuvant effect of C. parvum and the possible mechanisms of action are discussed.     

The effect of antigen deprivation on thymus-dependent and thymus-independent lymphocytes in the small intestine of the mouse

Isografts of foetal small intestine, implanted under the kidney capsules of adult mice grow normally and, despite the lack of intraluminal antigenic stimulation, are populated by thymus-dependent and thymus-independent lymphocytes. The Peyer's patches in these grafts are very small, lack germinal centres and can be shown to have small thymus-dependent areas.

Quantitative intraepithelial lymphocyte counts were carried out in normally sited small intestine of immunologically intact and thymus-deprived mice, and in grafts implanted in intact and thymus-deprived mice. Counts were also performed in a group of neonatally thymectomized and control mice. The results show a significant depletion of intraepithelial lymphocytes in neonatally thymectomized mice, and a profound reduction in numbers of intraepithelial lymphocytes in grafts, deprived of antigen, when compared with normally sited intestine of the same age.

     

Further studies on the adjuvant effect of silica on IgE antibody production in mice.

The effects of amorphous silica (Aerosil) and of aluminium hydroxide on anti-DNP IgE antibody production were studied in Swiss mice preimmunized with Ascaris protein and then challenged 7 days later with DNP-ASC. Aerosil exerted an adjuvant effect especially when it was injected together with the DNP-ASC conjugate. Al(OH)3 had a weaker adjuvant effect than that produced by Aerosil and then only when it was injected with the DNP-ASC conjugate. Al(OH)3 given with Ascaris extract 7 days before complete antigen had an inhibitory effect on the anti-DNP IgE antibody production.     

Monoclonal antibody against pertussis toxin: effect on toxin activity and pertussis infections.

Antibody-producing hybridomas of myeloma SP2/O and spleen cells of BALB/c mouse immunized with pertussis toxoid and pertussis toxin were selected by the binding ability of the monoclonal antibody to the subunit protein of the toxin. Two monoclonal antibodies, 1B7 and 3F10, specific for a subunit which has no binding activity to haptoglobin and sheep erythrocytes, named S1, and one antibody, 1H2, for a subunit related to the binding activity of the pertussis toxin molecule to haptoglobin or sheep erythrocytes, named S4, were examined for mouse protective activity against pertussis infection. Antibody 1B7 not only neutralized leukocytosis-promoting and islet-activating activities of the toxin but also protected mice against intracerebral and aerosol challenge with Bordetella pertussis. The antibody, furthermore, showed therapeutic effects on mice showing severe clinical signs with pertussis infection. The other two antibodies, 3F10 and 1H2, showed neither neutralizing nor protecting activity, nor significant synergistic effects on antibody 1B7.     

On the mechanism of the adjuvant effect of Bordetella pertussis vaccine

Pertussis vaccine accelerates rather than retards, of antigen from the circulation and enhances the secondary as well as the primary response. Pertussis vaccine alone has an anamnestic effect and is capable of causing the appearance of homocytotropic antibody which reacts with antigens to which the animal has previously made a primary response. The effects of pertussis and Freund's adjuvant are additive. Increased insulin levels are not necessary for the adjuvant effect as alloxan diabetic animals are quite capable of enhanced antibody response after pertussis vaccine. Beta adrenergic blocking drugs increase and adrenergic agonists reduce antibody response slightly. It is concluded that pertussis exerts its effect directly on the precursor of the antibody-forming cells by increasing their rate of cell division Impairment of beta adrenergic receptors may be the mechanism of the effect.     

单磷酸脂质A佐剂对无细胞百日咳疫苗的免疫保护效果研究

目的 探讨单磷酸脂质A(MPLA)佐剂对无细胞百日咳疫苗(aP)的免疫保护效果影响.方法 aP中添加MPLA佐剂,在Balb/c小鼠上进行免疫以及感染保护实验.通过检测小鼠百日咳特异性IgG抗体及其分型抗体IgG1和IgG2a水平、感染后白细胞变化以及气管和肺组织细菌定植来进行免疫效果的评估.结果 aP+MPLA免疫的...     

A cell surface marker of thymus-dependent lymphocytes in Xenopus laevis is identifiable by mouse monoclonal antibody

A mouse monoclonal antibody (mAb), named XT-1 (IgG2b,lambda), was prepared against J strain Xenopus laevis thymocytes. The determinant recognized by this mAb (XT-1 determinant) was expressed by 92-98% thymocytes and 22-37% splenic lymphocytes from intact J strain frogs and larvae, as analyzed by flow cytofluorometry. The XT-1 determinant was also expressed by 20-30% peripheral blood lymphocytes and 5-11% bone marrow lymphocytes from adult, and 11-17% liver lymphocytes from larval J strain Xenopus. Early larval thymectomy depleted XT-1-positive cells in the spleen to less than 2% of the total lymphocyte population. Double immunofluorescence experiments revealed that XT-1+ lymphocytes in the spleen are surface IgM-. The strain distribution study on the expression of XT-1 determinant suggests the allelic polymorphism of the XT-1 determinant. The surface antigen identified by the present XT-1 mAb may provide an important marker for lymphocytes in thymus-dependent lineage in Xenopus.     

The effect of localized injection of adjuvant material on the draining lymph node: II. Circulating lymphocytes

The stimulation of a draining lymph node by the injection of a substance possessing adjuvanticity leads to a marked increase in the influx of lymphocytes into the node. The influx of cells has been followed in experimental mice injected intravenously with ⁵¹Cr-labelled normal mesenteric lymph node cells. The increase in size of the draining node is not due to an increased blood volume.     

Adjuvant effect of Bordetella pertussis vaccine to sheep erythrocytes: enhancement of antibody formation by using subcutaneous administration of adjuvant and antigen.

The subcutaneous route (s.c.) was used to study the adjuvant effect of Bordetella pertussis vaccine (pv) on the primary antibody response to sheep erythrocytes. The reasons for using the s.c. route are discussed. PV, besides enhancing the hemagglutinin response, also markedly increased the number of plaque-forming cells in the draining lymph nodes. A heated preparation of PV was tested and found to possess significant adjuvant activity. Interestingly, the enhancement occurred in the absence of marked enlargement of the lymph nodes, which was characteristic of the unheated preparation. In addition, a crude solubilized cell-free preparation of PV was tested and also found to possess significant adjuvant activity. The activity was only partially abolished by heat. Hence, it was concluded that both heat-labile as well as heat-stable factors contributed to the adjuvanticity of PV. The studies also support the view that the draining lymph nodes represent a principal locus of action of PV and that the s.c. route of administration of adjuvant and antigen provides a suitable model for studying and assaying the adjuvanticity of PV.     

The effect of adrenalectomy on the production of homocytotropic antibody in rats

Homocytotropic antibody against egg albumin was produced in female Wistar rats using pertussis vaccine as an adjuvant. Yields of antibody were greater and more reproducible when adrenalectomized rather than intact rats were used. The time course of antibody production in adrenalectomized animals was followed by passive cutaneous anaphylaxis in rats and by the BDB-haemagglutination technique. Maximal homocytotropic antibody production occurred acutely 12 days after sensitization, whereas haemagglutinating antibody levels were optimal on day 14.

The effect of dosing adrenalectomized rats with deoxycorticosterone acetate, or prednisolone or prednisone at low doses reduced the level of homocytotropic antibody at 12 days without appearing to change the level of haemagglutinating antibody. Homocytotropic antibody production was significantly lower in adrenalenucleated rats than in completely adrenalectomized rats. Adrenalectomy without adjuvant treatment was not a sufficient stimulus to cause an increase in homocytotropic antibody formation. Only one homocytotropic antibody could be detected in all of these experiments. It was shown to be of the reaginic type as described by Mota (1964a).