猪瘟基因疫苗免疫小鼠体液及细胞免疫动态变化研究

目的：探讨猪瘟基因疫苗免疫小鼠后机体产生体液和细胞免疫发生规律，为猪瘟基因疫苗推广应用提供科学依据。方法：应用FACS、MTT法及间接ELISA试验对猪瘟基因疫苗免疫小鼠脾脏及外周血中CD4^ 和CD8^ 淋巴细胞数、淋巴细胞的转化功能及特异的抗猪瘟病毒血清IgG抗体水平等动态变化进行了观察。结果：猪瘟基因疫苗免疫小鼠后脾细胞及外周血淋巴细胞对ConA和LPS均有明显的反应性。CD4^ 和CD8^ 细胞数量在免疫后20天开始反应，32天达到高峰后开始下降。鼠血清特异性猪瘟病毒血清抗体IgG随免疫时间延长而增加。结论：猪瘟基因疫苗免疫动物可诱导机体体液及细胞免疫。     

HIV-specific humoral and cellular immunity in rabbits vaccinated with recombinant human immunodeficiency virus-like gag-env particles

Recombinant human immunodeficiency virus type-1 (HIV-1)-like gag-env particles produced in mammalian cells were inoculated into two New Zealand white rabbits. In parallel, two control rabbits were inoculated with the homologous HIV-1 virions inactivated by ultra violet light (uv) and psoralen treatments. The humoral and cellular immune responses to HIV-1 were evaluated for both groups of animals. Recombinant particles elicited humoral immunity that was specific for all the viral structural proteins. The antibodies recognized both denatured and nondenatured proteins. Moreover, the sera neutralized the in vitro infectivity of the homologous virus in CEM cells. Importantly, the recombinant particles also generated a T helper response by priming with the HIV proteins. Similar results were observed with inactivated virus immunization. Therefore, our results suggest that the recombinant HIV-like particles elicit functional humoral immunity as well as cellular immunity and represent a novel vaccine candidate for AIDS.     

Cellular immunity in patients with meningococcal disease and in vaccinated subjects.

Cell-mediated immunity was studied in patients with group A meningococcal meningitis and in normal subjects given group A meningococcal vaccine. Lymphocytes responsiveness to phytohaemagglutinin and to meningococcal antigens was markedly depressed in patients with acute meningococcal infection. This defect was present when lymphocytes were cultured in autologous or foetal calf serum. Patients also showed a transient increase in the degree of inhibition produced by whole group A meningococci in leucocyte migration assays. Meningococci of other groups produced a similar degree of inhibition. Vaccination with group A meningococcal polysaccharide vaccine had no effect on lymphocytes responsiveness to meningococcal antigens or on the inhibitory effect of group A meningococci on leucocyte migration.     

State of humoral and cellular immunity in experimental amyloidosis]

On a model of caseine amyloidosis in 52 rabbits it was shown that in the preamyloid phase the humoral immunity was stimulated, but as soon as the first deposits of amyloid appeared, it was inhibited. The cellular immunity was inhibited starting from the 20th day of the experiment. On the 40th day of the experiment the cellular immunity was found to be less inhibited in the animals with initial deposits of amyloid as compared with the animals with no amyloidosis; on the 60--80th day in progressing of amyloidosis differences in the degree of inhibition of the cellular immunity were obliterated. The degree of fixation of IgG in amyloid was directly dependent on its content in the blood serum and on the "age" of amyloid.     

Antibody responses in acute and chronic Q fever and in subjects vaccinated against Q fever

An analysis is made of the antibody response to Coxiella burnettii Phase-1 and Phase-2 antigens, as measured by immunofluorescence in the IgM, IgG or IgA immunoglobulin classes, or by complement-fixation, in patients with acute and chronic Q fever and in vaccinated or skin-tested subjects. In acute (primary) Q fever, IgM specific antibodies to Phase-1 antigen are present in early convalescence together with IgM, IgG, IgA and CF antibodies to Phase-2 antigen. IgM specific antibody may persist for at least 678 days after onset of the acute illness. Patients with chronic Q fever have no IgM specific antibody to Phase-1 or -2 antigens, or only at very low levels; high levels of specific antibody in the IgG and IgA classes, together with CF antibody to both antigenic phases, appear to be characteristic. The serological response in initially seronegative, vaccinated subjects is mainly to Phase-1 antigen in the IgM fraction, and to a lesser degree to Phase-2 antigen by CF and in IgM and IgG classes. Subjects who were equivocally seropositive before vaccination showed IgA and IgG specific antibody responses to Phase-1 antigen and CF and IgG class responses to Phase-2 antigen. Similar antibody profiles were observed in patients who seroconverted after a positive skin-test. Data are also presented on the suitability of C. burnettii antigens for use in immunofluorescence and on the binding of IgM specific antibody by Phase-1 antigen but its failure to fix complement.     

Experimental humoral and cellular immunity to hog intrinsic factor

Humoral and cellular immunity to hog intrinsic factor (HIF) was studied in rabbits immunized with varying doses of HIF or HIF complexed to vitamin B₁₂. Animals immunized with large doses of HIF (1 mg) consistently produced high titres of blocking and binding antibodies to IF. At low dose immunization (10 μg), the humoral response was obviously blunted, with animals forming significantly reduced titres of antibodies to IF; several rabbits in this group made only binding antibodies and one rabbit produced neither blocking nor binding antibodies. No difference in humoral responsiveness was noted between those animals who received HIF or an equivalent amount of HIF complexed to vitamin B₁₂. By contrast, cellular immunity as measured by inhibition of leucocyte migration was readily induced to a similar degree in both high and low dose animals, including the rabbit which had no detectable antibodies to IF. When an intermediate dose of HIF (50 μg) was used as the immunogen, four rabbits gave positive leucocyte migration tests only with HIF—vitamin B₁₂ complex, suggesting that the interaction of HIF with vitamin B₁₂ may enhance its antigenicity in vitro. These data demonstrate that cellular and humoral immunity to HIF can be induced and partially dissociated from each other by varying the dose of immunogen. Although the mechanism responsible for this dissociation is not clear, one explanation would be differing sensitivities of lymphocyte-populations to different doses of antigen.     

In vivo effect of levamisole on cellular and humoral immunity in normal chickens.

The effect of levamisole in vivo was studied on the PHA and Con A responses of chicken peripheral blood lymphocytes and on the in vivo antibody response to a thymus dependent antigen (BSA) and to a thymus independent antigen (Brucella abortus). Levamisole (0.25 mg/kg) increased significantly both the PHA and Con A responses of chicken blood lymphocytes. The antigens were given at the time of enhanced mitogenic responses and a significant increase was observed in both IgM and IgG antibodies to BSA. In contrast, no effect was obtained on antibody responses to Brucella abortus organisms. The results show that levamisole is able to enhance both humoral and cellular immune responses in normal chickens. The effect is probably mediated by the activation of the T cell function and effects only antibody responses to thymus dependent antigen. These findings confirm and extend the observations regarding the ability of levamisole to modulate immune responses.     

Suppression of humoral and cellular immunity in normal mice by diazepam

Diazepam, a benzodiazepine derivative useful in the treatment of anxiety disorders, was found to depress both primary antibody to sheep red blood cells and delayed-type hypersensitivity responses in normal mice. This immunodepressant activity warrants further investigation owing to its potential consequences on human health and the putative involvement of specific receptors on immunocompetent cells.     

Contributions of humoral and cellular immunity to vaccine-induced protection in humans

Vaccines play a vital role in protecting the host against infectious disease. The most effective licensed vaccines elicit long-term antigen-specific antibody responses by plasma cells in addition to the development of persisting T cell and B cell memory. The relative contributions of these different immune cell subsets are context-dependent and vary depending on the attributes of the vaccine (i.e., live/attenuated, inactivated, and subunit) as well as the biology of the pathogen in question. For relatively simple vaccines against bacterial antigens (e.g., tetanus toxin) or invariant viruses, the immunological correlates of protection are well-characterized. For more complex vaccines against viruses, especially those that mutate or cause latent infections, it is more difficult to define the specific correlates of immunity. This often requires observational/natural history studies, clinical trials, or experimental evaluation in relevant animal models in order for immunological correlates to be determined or extrapolated. In this review, we will discuss the relative contributions of virus-specific T cell and B cell responses to vaccine-mediated protection against disease.     

Specific cellular and humoral immunity in children with grass pollen asthma

Lymphocyte stimulation, as determined by incorporation of thymidine, to rye grass extract in twenty-three children with bronchial reactivity to rye grass and to house dust mite, did not differ significantly from four children with reactivity to house dust mite alone, or from nine children with asthma but without a bronchial response to these allergens. Sixteen children underwent hyposensitization with rye grass extract or treatment with placebo. There was no consistent effect of hyposensitization on the lymphocyte stimulation indices to rye grass. A decrease in lymphocyte responsiveness occurred to rye grass and to house dust mite after the grass pollen season but was not statistically significant. Analysis of changes in lymphocyte responsiveness to both house dust mite and rye grass of the children most highly sensitized to rye allergen, showed that the lymphocyte responsiveness to rye grass fell during the pollen season (P<0.05) but this effect was not seen with house dust mite. The study suggests that a decrease in lymphocyte responsiveness to rye grass allergen in children with large amounts of anti-rye IgE antibodies is antigen specific and may be seen following seasonal exposure.     

Naturally occurring cellular and humoral immunity to teichoic acid in rats

Naturally occurring cellular and humoral immunity to a purified polyglycerophosphate (teichoic acid) have been observed in normal albino rats. Skin tests as well as in vitro correlates of delayed hypersensitivity yielded positive results in more than 50 per cent of rats between the ages of 24 and 40 weeks while rats 6–20 weeks old exhibited no cellular responses. Passive haemagglutination assays for natural antibodies to glycerol—teichoic acid revealed their occurrence in all rats between the ages of 6–20 weeks as well as in most of the older rats examined. These antibodies were usually found in the IgM fraction, but some animals possessed them in the IgG-containing fraction.

The regular appearance of antibodies before the appearance of cellular response, if confirmed, may imply that B-cell responses precede T-cell responses in certain circumstances.

     

Effect of indomethacin in vivo on humoral and cellular immunity in humans

We studied the effect of indomethacin on intradermal skin testing and antibody responses in humans. Since we and others have shown that prostaglandins are suppressor cell mediators, it was probable that in vivo inhibition of prostaglandin synthesis might enhance the humoral and/or cellular immune response. Administration of indomethacin (Indocin) in a dosage of 100 mg/day to 15 normal men and women resulted in a significantly increased antibody titer to A-Victoria (P less than 0.025) as compared with age- and sex-matched controls. There was no difference in titer to A-New Jersey. Since 90% of the subjects had antibody titers to A-Victoria before inoculation, whereas none had detectable titers to A-New Jersey, we interpret this data as suggesting that indomethacin enhances the secondary but not the primary humoral immune response. Indomethacin administration did not alter the intradermal skin test responses.     

Prolonged administration of antithymocyte serum in mice. I. Observations on cellular and humoral immunity

A colony of 400 CBA/He mice was divided into three groups: (a) mice injected continually throughout life with rabbit antimouse thymocyte serum (ATS), (b) mice treated in the same manner with normal rabbit serum (NRS), and (c) mice left untreated.

The cellular immune competence of all groups was tested by the transplantation of allografts or rat xenografts, by testing the ability of their lymphoid cells to mount a graft-versus-host reaction, by measuring the in vivo response of their lymphocytes to oxazolone skin-painting and the in vitro response to phytohaemagglutinin, and finally by measuring the organ distribution of the θ-positive, thymus-dependent lymphocyte population. Determinations were made of the antibody responses to sheep erythrocytes, allografts and rat xenografts, bovine serum albumin, keyhole limpet haemocyanin, and polyoma virus.

The ATS-treated mice grew and reproduced normally and did not succumb to bacterial infections. Polyoma virus, probably introduced in the rabbit serum, induced tumours in only some of the ATS-treated mice. Only two lymphomas (0·8%) occurred in this same group; tumours were not seen in the other groups.

These results do not support any hypothesis which attributes to lymphocytes a non-immunological function, nor do they support a simple form of the immunological surveillance theory in relation to cancer. Several possible explanations for the increased incidence of tumours in transplant patients are proposed, which take into account the difficulty experienced in this study in abrogating a `cellular immune response' with antilymphocytic serum alone.

     

Psychological stress may induce increased humoral and decreased cellular immunity

Stress alters immune function and affects different immune cell populations in different ways. The authors examined whether psychological stress has different effects on the production of macrophage, T-helper 1(Th1) cell, and T-helper 2(Th2) cell-derived cytokines. Forty-two college students were recruited and their blood was sampled on the day they were to take a stressful academic examination and again 4 weeks after the examination. The stress from the academic examination significantly increased IL-1 beta, IL-6, and IL-10 and decreased IFN-gamma production. These findings suggest that examination stress may increase Th2 cell-mediated humoral immunity and macrophage activities and may decrease Th1 cell-mediated cellular immunity.