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[Effect of guizhi decoction on CD4+, CD8+ T-lymphocytes and SIgA in mucosal immune system in intestine of mice with Bi syndrome (collagen induced immune arthritis)].

OBJECTIVE: To observe the effect of Guizhi Decoction (GZD) on immunological indexes in intestinal mucosal immune system of mice with Bi syndrome (collagen induced immune arthritis). METHODS: Eighty male DBA mice were randomly divided into 4 groups, the normal group, the model group and the high and low dosage GZD groups. Model of Bi syndrome was induced by collagen type II. CD4+, CD8+ T-lymphocytes and SIgA in mice' small intestine and PP node were labeled by immunohistochemical staining and their number was calculated using imaging analyzer. RESULTS: Compared with the normal group, in the model group, after immunization with collagen type II, numbers of CD4+ and CD8+ T-lymphocytes and SIgA in mice' intestinal mucosal immune system reduced significantly (P < 0.05 or P < 0.01). After treatment with GZD of both high and low dosage, CD4+ T-lymphocytes and SIgA increased significantly, but significant difference only showed in comparison between the high dosage GZD group and the model group (P < 0.05 or P < 0.01). CONCLUSION: GZD could enhance the immune function in intestinal mucosa in mice with Bi syndrome, thus it might induce immune tolerance and immune inhibition.

Adjuvants, Immunologic↗

Effects of postoperative immune-enhancing enteral nutrition on the immune system, inflammatory responses, and clinical outcome.

OBJECTIVE: This study was conducted to evaluate the effects of postoperative immune enhancing enteral nutrition on the immune system, inflammatory responses, and clinical outcome of patients undergoing major abdominal surgery. METHODS: This study was designed as a multicenter, prospective, randomized and controlled clinical trial. One hundred twenty-four patients undergoing major abdominal surgery were randomly assigned to receive either an immune enhancing enteral diet or an isocaloric and isonitrogenous control enteral diet for seven days. Enteral feeding was initiated 24 hours after surgery. Host immunity was evaluated by measuring levels of IgG, IgM, IgA, CD4, CD8, and CD4/CD8, and the inflammatory response was determined by assessing IL-1alpha, IL-2, IL-6, IL-10, and TNF-alpha levels. Infectious complications were also recorded. RESULTS: One hundred twenty patients completed the study and four patients were excluded. On postoperative day 9, among patients receiving an immune enhancing diet, IgG, IgA, CD4 and CD4/CD8 levels were significantly higher and TNF-alpha and IL-6 concentrations were significantly lower compared to the control group. Moreover, among patients receiving an immune enhancing diet, when comparing preoperation to day 9 postoperation levels, increases in IgA, CD4, and CD4/CD8 levels were significantly higher than in control patients and increases in TNF-alpha concentrations were significantly lower. No statistically significant differences were found between the two groups with regard to infectious complications. CONCLUSIONS: Postoperative administration of immune enhancing enteral nutrition in patients undergoing major abdominal surgery can positively modulate postoperative immunosuppressive and inflammatory responses.

Abdomen↗

[Immune proteasomes and immunity].

A lot of facts that require understanding have been accumulated since immune proteasomes were discovered and their relationship with the immune response was established. For example, why are immune proteasomes present in all studied mammalian organs and tissues, including nonlymphoid tissues? What is responsible for differences in the ratio of immune to constitutive proteasomes in different organs? Are the functions of immune proteasomes related to the T-cell immune response alone, as was shown initially, or not? Are immune proteasomes formed simultaneously in different organs during ontogenesis? An attempt is made in this review to answer these and other related questions.

Animals↗

Acute poliomyelitis in children: comparison of epidemiological and clinical features among immunized, partially immunized and unimmunized.

This study was conducted to compare the epidemiological and clinical features of acute poliomyelitis among immunized, partially immunized and unimmunized, as these have been postulated to be different amongst these subgroups. Of 614 children with acute poliomyelitis admitted at the Institute of Child Health, Madras, 162 (26.4%) were immunized, 183 (29.8%) were partially immunized and 269 (43.8%) were unimmunized. Poor environmental sanitation, unprotected water source and parental illiteracy were significantly more common among unimmunized group compared to the immunized group. It is concluded that there is no significant difference in symptoms, signs, clinical types, severity of paralysis and case fatality between the immunized, partially immunized and unimmunized.

Child, Preschool↗

Cellular and humoral immune responses to Plasmodium falciparum gametocyte antigens in malaria-immune individuals. Limited response to the 48/45-kilodalton surface antigen does not appear to be due to MHC restriction.

We have examined immune responses to a cultured Plasmodium falciparum gametocyte lysate and to an affinity-purified preparation of the 48/45-kDa gamete surface Ag in a group of 30 malaria immune individuals and in 24 Europeans with no previous exposure to malaria. Cellular responses were assessed in vitro by lymphoproliferation and production of IFN-gamma; antigamete antibodies were detected by immunofluorescence, Western blotting, and competitive ELISA. Cells from all the malaria immune donors responded to the gametocyte lysate in both assays while cells from nonimmune donors gave only weak proliferative responses. Antigamete antibodies were detected in the serum of all the immune donors but not in serum from nonimmunes. Nonimmune donors were completely unresponsive to the purified 48/45-kDa surface Ag while cells from 40% of immune donors responded by either proliferation or IFN-gamma production. Only 3 of 30 immune donors had detectable antibodies to the 48/45-kDa Ag. Class II HLA type was determined for 27 of the immune donors but no relationship between HLA-DR or -DQ and responsiveness to the 48/45-kDa Ag was discerned. The possible reasons for limited recognition of this gamete surface Ag are discussed.

Animals↗

[Immune response and reactions to simultaneous administration of hepatitis B vaccine with routine vaccine in children. II. Immune response and reactions to simultaneous administration of hepatitis B vaccine with Japanese B encephalitis vaccine and measles vaccine].

This paper reports the result of the immune response and reactions to simultaneous administration of Japanese B encephalitis vaccine, measles and hepatitis B vaccine. 215 children (0-9 months of age) were divided into three groups. Group one was vaccinated with hepatitis B vaccine alone, group two was vaccinated with Japanese B encephalitis vaccine, measles vaccine, and group three was Vaccinated with hepatitis B vaccine, Japanese B encephalitis vaccine and measles vaccine simultaneously. The result of the immune response to the combination of hepatitis B vaccine with Japanese B encephalitis vaccine were similar to that observed after immunization with each vaccine alone. But the result of the immune response to the combination of hepatitis B vaccine with measles vaccine were lower than to that observed after immunization with measles vaccine alone. The general reaction of all vaccine were mild, no significant difference between each group was noted. The study demonstrated that children can not be immunized with hepatitis B vaccine and measles vaccine simultaneously but can be immunized with hepatitis B Vaccine and Japanese B encephalitis vaccine.

Encephalitis Virus, Japanese↗

Removal of glomerular deposits induced by either preformed immune complexes or by a chronic immune complex model in NZB/W mice.

The solubilization and removal of defined glomerular immune complex deposits by excess antigen was examined in NZB/W female mice. Glomerular deposits were induced by administering preformed immune complexes to young (2 to 4 mo) mice before they naturally acquired deposits from endogenous disease and to old (7 mo) mice with deposits from naturally acquired disease. The administration of excess antigen specifically removed deposits of preformed immune complexes in both groups. This was associated with a reduction in circulating large latticed complexes containing more than two antigen and two antibody molecules (greater than Ag2Ab2). Established deposits in old mice therefore did not interfere with removal of newly induced deposits of preformed immune complexes. Glomerular deposits were also induced in young mice by a chronic human serum albumin (HSA) immune complex model. The antigen in immune deposits induced by 2 wk of chronic antigen administration was solubilized and was removed within 48 hr of administering excess antigen. Circulating antibodies to the antigen were also reduced by excess antigen. Glomerular deposits of mouse immunoglobulin and complement were not significantly reduced by excess antigen but remained more intense than in mice of comparable age given preformed complexes. Thus deposits of other antigen antibody systems and possibly endogenous disease were induced by the chronic HSA immune complex model in NZB/W mice. However, defined antigen deposits within deposits containing multiple antigen antibody systems can clearly be removed by administering excess antigen.

Age Factors↗

Immunity to Trichinella spiralis. II. Expression of immunity against adult worms.

Thoracic duct lymphocytes or purified T or B cells obtained from specifically immunized (Lewis x DA)F1 hybrid rats can protect normal recipients against an oral challenge infection with T. spiralis. The immune cells increase the rate of expulsion of adult worms from the small intestine. Immune TDL do not affect adult worm fecundity, as they do in other strains of rats, or the penetration and development of newborn larvae in muscle cells. Irradiated F1 rats reconstituted with either immune TDL or class-enriched populations of immune T or immune B cells also expel adult Trichinella more rapidly than do unprotected controls. However, unfractionated TDL and inocula enriched in B cells are more efficient than T cells in promoting worm expulsion. The above finding, taken in conjunction with the tissue disposition of labelled lymphocytes in the tissues of recipient rats, implies that immune T cells have a 'helper' function in promoting the formation of protective B cells.

Animals↗

Immunocytolocalization of two protection-inducing antigens of Trichinella spiralis during its enteral phase in immune and non-immune mice.

Monoclonal antibodies (mAb) recognizing epitopes on the 48K (beta stichocyte specific) and the 50/55K antigen (alpha stichocyte specific) were used as first ligands for immunocytolocalization on de-paraffinized sections of infected gut tissue of non-immune and immune CFW strain mice. The enteral phase was studied at 6, 14, 23, 30 hr and 7 days after initiation of infection via the oral route, times corresponding in worm development to the first (L1), second (L2), and third (L3) stage larva and adult. No change in the intensity of the immune reaction with either mAb was noted in parasites developing within immune or non-immune mice for any of the time-points studied. The 48K and the 50/55K antigens were present within the stichocytes at 6 hr. Enterocytes adjacent to some worms also stained positive for both epitopes at this time. Throughout worm development, the amount of each antigen within the worm diminished, until almost none was left at 30 hr. At day 7, the 48K antigen was present within a few stichocyte cells, the canalicular tree, and within the lumen of the midgut. The 50/55K antigen at this time point was localized within only a few stichocyte granules and on the lining of the worm's gut. Embryo stages did not possess either the 48K or 50/55K epitopes. A marked increase in cells bearing IgG in the lamina propria was noted in immune mice when compared with their non-immune counterparts.

Animals↗

Induction of protective immunity against Schistosoma mansoni by a non living vaccine. I. Partial characterization of antigens recognized by antibodies from mice immunized with soluble schistosome extracts.

A single intradermal injection of frozen and thawed schistosomula in conjunction with the bacterial adjuvant Mycobacterium bovis strain Bacille Calmette Guerin, Phipps substrain (BCG) induced significant levels of resistance to challenge Schistosoma mansoni infection in C57BL/6 mice. Immunization with the aqueous fraction remaining after 100,000 X G centrifugation of the larval lysate was also protective under these conditions, suggesting that some immunogenic determinants may not be membrane associated. Frozen-thawed cercariae and soluble components of adult worms also protected against challenge infection in these experiments. These observations indicate that soluble immunogens are present in both early and late developmental stages of the parasite, and therefore may be good candidate antigens for an immunochemically defined vaccine against schistosomiasis. Induction of humoral reactivity against soluble or membrane antigens was examined in mice protected against cercarial challenge by prior exposure to frozen-thawed larvae, soluble larval, or soluble adult antigens plus BCG. Animals that were immunized with frozen-thawed larvae produced low but significant levels of antibodies against larval surface antigens when examined by indirect immunofluorescence or by immunoprecipitation of surface-labeled schistosomula. Mice immunized with soluble antigens, however, showed negligible antibody reactivity against surface membrane antigens. Because mice immunized with soluble antigens were resistant to challenge infection, these results strongly suggest that anti-surface membrane reactivity is not required in the mechanism of protective immunity in this model. Sera from mice immunized with either total freeze-thaw larval lysate or soluble schistosome extracts all showed strong reactivity against soluble antigens, as detected by ELISA. Western blot analysis showed these antisera to react with a restricted number of high m.w. antigens that were present both in schistosomula and in adult worms. These antigens are therefore likely to play a major role in the development of resistance in this model as immunogens and/or as targets of protective immune response.

Adaptation, Physiological↗

Characterization of the cellular immune response following in vivo immunization with pneumococcal polysaccharides in man.

The in vivo and in vitro immune responses following in vivo immunization with pneumococcal polysaccharides (PPS) has been analyzed in man. Within 6 days following immunization, specific PPS antigen-binding cells (ABC), specific plaque-forming cells (PFC) and cells capable of spontaneously synthesizing in vitro substantial amounts of specific anti-PPS IgG and IgA and lesser amounts of specific IgM appeared in the peripheral blood. The ABC, PFC and total amounts of specific spontaneous antibody production in vitro followed nearly identical kinetics after immunization. The ABC were isolated and shown to be large B cells, predominantly surface IgG positive and surface IgD negative, and to express an activation antigen called 4F2. Low doses of in vitro irradiation markedly inhibited spontaneous anti-PPS antibody production by lymphocytes obtained 7 or 8 days after immunization, suggesting a requirement for in vitro proliferation for full expression in vitro of antibody secretion following in vivo activation. Spontaneous secretion by B lymphocytes in vitro was independent of T cells, unmodified by the addition of T cell factors, and readily suppressible by pokeweed mitogen (PWM). These findings strongly suggest that the in vivo immunization with PPS delivered to these spontaneously secreting PPS-specific B cells the signals for proliferation as well as differentiation, both of which were expressed in vitro. By 2 weeks after immunization, spontaneous anti-PPS antibody production in vitro was no longer detected. Subsequent stimulation of lymphocytes with a wide range of concentrations of specific antigen did not trigger either proliferation or specific antibody synthesis. Despite the unresponsiveness of these cells to antigenic stimulation, they were capable of specific anti-PPS antibody production following stimulation with PWM. This finding demonstrates that PPS-specific B cells are indeed present in the circulation at this time. The lack of ability of PPS antigen itself to trigger these B cells at this point in time strongly suggests that PPS-specific T cells are either not present or are untriggerable, and PWM can bypass the need for specific T cells by polyclonally stimulating the T cell pool. This system should prove useful in delineating certain aspects of B cell physiology not readily approachable with standard soluble protein antigens.

Adult↗

Direct in vitro evidence for different susceptibilities to 4-hydroperoxycyclophosphamide of antigen-primed T cells regulating humoral and cell-mediated immune responses to sheep erythrocytes: a possible explanation for the inverse action of cyclophosphamide on humoral and cell-mediated immune responses.

Suppressor T cells of humoral immune responses, effector T cells mediating DTH, suppressor T cells of DTH, and helper T cells of humoral immune responses, all with specificity to SRBC, were produced in mice. The biologic activity was tested in adoptive transfer experiments. In vitro treatment with different doses of 4-hydroperoxycyclophosphamide (4-HPCy) yielded the result that the various activities tested were not uniformly sensitive to the action of this drug: Suppressor T cells of humoral immune responses and effector T cells mediating DTH were resistant to doses of 4-HPCy that eliminated the activities of suppressor T cells of DTH and helper cells of the humoral immune response. These findings help to explain the various effects cyclophosphamide has on the in vivo immune response and may help to form a basis for the rational manipulation of the immune response by drugs that selectively affect different subgroups of immune cells.

Animals↗

Enhancement of systemic immune response by immunization into chronically inflamed lungs.

Intrapulmonary instillation of proteins into rabbit lungs with BCG-induced granulomatous inflammation results in greater transport of these molecules into the blood, and the primary route is probably the pulmonary lymphatics. In addition, rabbits with inflamed lungs develop a more potent systemic immune response when exposed to soluble antigens as an aerosol. The current study was done to further study the mechanisms of this phenomenon using the Jerne plaque technique. Intrapulmonary immunization with soluble antigens (solubilized SRBCs and HSA) resulted in a greater PFC response to both antigens when the lungs exhibited BCG-induced granulomatous inflammation. A previous study demonstrated that more antigen administered intratracheally was found in the HLNs when the lungs displayed granulomatous inflammation. However, in the present study, we did not observe an enhanced PFC response in HLN cells when antigens were introduced into inflamed lungs. When rabbits with BCG-inflamed lungs were immunized i.v., they did not develop an enhanced PFC response in the spleen. Immunization into the respiratory tract of normal rabbits with large doses (300 micrograms) of soluble antigens also resulted in a substantial PFC response in the spleen that was quantitatively greater than that induced by the same i.v. dose. These data indicate that (1) administration of antigens into inflamed lung results in an enhanced systemic immune response, (2) although larger quantities of soluble antigens administered by the pulmonary route accumulate in the HLN when lungs are inflamed, cells from this tissue do not exhibit an enhanced PFC response, and (3) large doses of soluble antigens instilled into normal lungs induce a greater systemic immune response that the same doses administered i.v. This study further demonstrates the importance of pulmonary inflammation and the immune response to inhaled antigens and provides insight as to how individuals with chronic inflammatory lung disease can react in an augmented fashion to environmental antigens.

Alveolitis, Extrinsic Allergic↗

Induction of mucosal and systemic immune responses by immunization with ovalbumin entrapped in poly(lactide-co-glycolide) microparticles.

We have examined the range of mucosal and systemic immune responses induced by oral or parenteral immunization with ovalbumin (OVA) entrapped in poly(D,L-lactide-co-glycolide) (PLG) microparticles. A single subcutaneous immunization with OVA-PLG primed significant OVA-specific IgG and delayed-type hypersensitivity (DTH) responses. The DTH responses were of similar magnitude to those obtained using immunostimulating complexes (ISCOMS) as a potent control adjuvant, although ISCOMS stimulated higher serum IgG responses. Both vectors also primed OVA-specific in vitro proliferative responses in draining lymph node cells following a single immunization and strong OVA-specific CTL responses were found after intraperitoneal (i.p.) immunization. ISCOMS were more efficient in inducing cytotoxic T lymphocytes (CTL), requiring much less antigen and only ISCOMS could stimulate primary OVA-specific CTL responses in the draining lymph nodes. Multiple oral immunizations with OVA in PLG microparticles or in ISCOMS resulted in OVA-specific CTL responses and again ISCOMS seemed more potent as fewer feeds were necessary. Lastly, multiple feeds of OVA in PLG microparticles generated significant OVA-specific intestinal IgA responses. This is the first demonstration that PLG microparticles can stimulate CTL responses in vivo and our results highlight their ability to prime a variety of systemic and mucosal immune responses which may be useful in future oral vaccine development.

Adjuvants, Immunologic↗

The immune response of the genital tract of the female rabbit following systemic and local immunization.

Female rabbits were immunized with a model antigen, horseradish peroxidase (HRP), either locally in the reproductive tract or systemically via the intramuscular route. A sensitive immunoassay was developed to detect antibodies to the HRP in both serum and reproductive tract flushings. Systemic immunization resulted in circulating and reproductive tract antibodies of the IgG class, but none of the IgA class. Local immunization produced IgA and IgG antibodies in the reproductive tract, and also IgG antibodies in serum. Cell-mediated immunity was examined by circulating lymphocyte transformation and skin sensitivity to HRP. Cell-mediated immune responses occurred after systemic immunization, but not after local immunization. The relevance of the results to immunological methods of fertility control is discussed.

Animals↗

Genetic immunization of seronegative one-day-old piglets against pseudorabies induces neutralizing antibodies but not protection and is ineffective in piglets from immune dams.

Immune response inhibition by maternal antibodies is a major impediment to the vaccination of the young born to immune dams. This study explored the efficiency of genetic immunization of the neonates at bypassing this inhibition, by testing the muscular inoculation of the gD glycoprotein gene of pseudorabies virus (PRV) in piglets. Plasmid DNA (400 micrograms) was inoculated in four groups of one-day-old piglets, from sows vaccinated or not against PRV. Half of the groups received a booster injection on day 42. All piglets were challenged on day 115. Only piglets from non-immune sows and which received a booster injection developed a medium level of neutralizing antibodies, but they were not significantly protected against the challenge. Piglets from immune sows neither developed an antibody response nor were primed against PRV, as demonstrated by the antibodies kinetics after challenge. It can therefore be concluded that genetic immunization was inefficient at efficiently preventing the immune response inhibition by colostral antibodies.

Animals↗

Immunization against epitopes in the human melanoma antigen gp100 following patient immunization with synthetic peptides.

gp1OO is a melanocytic lineage-specific antigen recognized by tumor-infiltrating lymphocytes, the adoptive transfer of which is associated with tumor regression in melanoma patients. In this study, peripheral blood mononuclear cells (PBMCs) were harvested from HLA-A2+ melanoma patients before and after immunization with G9-209 (ITDQVPFSY), G9-280 (YLEPGPVTA), or G9-154 (KTWGQYWQV) peptides in Incomplete Freund's Adjuvant and were tested for the ability to be sensitized in vitro using PBMCs pulsed with the native peptides. In addition, PBMCs from patients receiving the G9-209 or G9-280 peptide were stimulated in vitro with peptides modified at anchor residues to enhance binding to HLA-A2: G9-209/2M (IMDQVPFSY) or G9-280-9V (YLEPGPVTV). In patients immunized with G9-209, a single in vitro restimulation with G9-209/2M resulted in the generation of specific antipeptide lymphocytes from seven of seven postimmune PBMCs and only three of seven preimmune PBMCs. In patients immunized with G9-280, a single in vitro restimulation with G9-280/9V resulted in the generation of specific antipeptide lymphocytes from five of six postimmune PBMCs and four of six preimmune PBMCs. In almost all cases, CTLs raised against modified epitopes were capable of recognizing targets displaying the native nonamers. Several anti-G9-209 and anti-G9-209/2M CTLs also demonstrated specific lysis of, and specific IFN-gamma release in response to, gp1OO+-established cell lines. Thus, using peptides modified to enhance immunogenicity for in vitro stimulation improved the sensitivity of immune monitoring of patients immunized with synthetic peptides. These results demonstrate that immunization with a peptide derived from a tumor-associated protein such as gp100 can provoke a measurable antitumor immune response in cancer patients.

Adoptive Transfer↗

Some data concerning immune processes in concomitant tumor immunity experimental models. Comparative in vivo and in vitro investigations II. In vitro experiments.

The humoral and cellular immune status of C57BL/6 male mice and "R" male rats bearing MC-induced sarcomas were investigated in vitro, using 51Cr-releasing and mixed hemadsorption assays. Analysis was performed on mice subjected to concomitant tumor immunity (CTI) model experiments or bearing primary tumors of different sizes, that was done also in rats. Chromatographic fractions, assumed to contain tumor specific antigens, antibodies or antigen-antibody complexes were identified by their absorption capacity upon specially prepared syngeneic immune sera. Free antibody and antigen-antibody complexes, accompanied with a weak cell mediated immunity (CMI) were correlated with efficient CTI in 2--3% TW/TBW tumor bearers. Homoral immunity (HI) showed sometimes an important increase after challenge administration. High levels of free antigen and antigen-antibody complexes, lack of antibodies and CMI were correlated with CTI absence in huge tumor bearers, representing 30--37% of total body weight. Conditions determining variability of results reported by different authors and the possible mechanisms by which serum immune factor may impair the tumor bearer's immune status are discussed.

Animals↗