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Immune response induced in mice oral immunization with cowpea severe mosaic virus.

There is increasing interest in the immune response induced by plant viruses since these could be used as antigen-expressing systems in vaccination procedures. Cowpea severe mosaic virus (CPSMV), as a purified preparation (300 g of leaves, 2 weeks post-inoculation), or crude extract from cowpea (Vigna unguiculata) leaves infected with CPSMV both administered by gavage to Swiss mice induced a humoral immune response. Groups of 10 Swiss mice (2-month-old females) were immunized orally with 10 daily doses of either 50 microg viral capsid protein (boosters of 50 microg at days 21 and 35 after immunization) or 0.6 mg protein of the crude extract (boosters of 0.6 mg at days 21 and 35 after immunization). Anti-CPSMV antibodies were quantified by ELISA in pooled sera diluted at least 1:400 at days 7, 14, 21, 28, 35 and 42 after the 10th dose. IgG and IgA against CPSMV were produced systemically, but IgE was not detected. No synthesis of specific antibodies against the proteins of leaf extracts from V. unguiculata, infected or not with CPSMV, was detected. The use of CPSMV, a plant-infecting virus that apparently does not induce a pathogenic response in animals, induced a humoral and persistent (at least 6 months) immune response through the administration of low antigen doses by gavage. These results raise the possibility of using CPSMV either as a vector for the production of vaccines against animal pathogens or in quick and easy methods to produce specific antisera for viral diagnosis.

Administration, Oral↗

Cross-immunity among allogeneic tumors in rats immunized with gamma-irradiated ascites tumors.

Non-inbred rats of the Gifu strain were intraperitoneally challenged with Hirosaki sarcoma (tetraploid type, 10(5) cells) after repeated immunization with gamma-irradiated (13,000 rads 60Co) allogeneic non-viral tumors of ascites type (tetraploid or diploid type of Hirosaki sarcoma, Usubuchi sarcoma or AH130). In rats immunized not only with the same tumor as the immunizing tumor but also with a different tumor, the growth of the challenge tumor was markedly inhibited as compared with the control in non-immunized rats. It is considered that these tumors retained common antigen(s) by the resistance to irradiation because of their form of ascites tumor. The marked cross-immunity in rats immunized with AH130 may be explained by the fact that gamma-irradiated AH130 cells were alive longer in the peritoneal cavity than other tumors on account of its high resistance to irradiation.

Animals↗

Taenia crassiceps cysticercosis: protective effect and immune response elicited by DNA immunization.

The nucleotide sequence of a protective recombinant antigen of Taenia crassiceps cysticerci present in all stages of Taenia solium (KETc7), cloned into pcDNA3 plasmid with the signal peptide sequence of the beta-glycan receptor (pTc-sp7), has been shown to be effective in protecting mice against experimental infection of T. crassiceps. To explore further the possibilities of this form of immunization and the immune response induced, mice were injected intramuscularly (i.m.) or intradermally (i.d.) with 3 doses of pTc-sp7. Similar levels of resistance were found using either i.m. or i.d. immunization. Spleen cells from i.d. and i.m. DNA immunized mice induced a specific T-cell response to T. crassiceps antigens and to a synthetic peptide from the immunogen itself (GK-1). Proliferated cells were especially enriched in CD8+ CD4- T-lymphocytes. A clear increase in the percentage of CD3+ cells that produce gamma-interferon and interleukin-2 was detected when measuring the intracellular cytokine production, an indication of the pTc-sp7 capacity to induce an effective cellular response. These results provide encouraging information on the use of KETc7 in the prevention of cysticercosis as well as a first insight into the characterization of the immune response induced by pTc-sp7 that hints to the relevance of cellular immunity in protection.

Animals↗

Magnetic fields, brain and immunity: effect on humoral and cell-mediated immune responses.

Magnetic fields (MF) can influence biological systems in a wide range of animal species and humans. We report here on the influence of static MF, locally applied to the brain area, on immune system performances in the rat. In the first series of experiments two AKMA micromagnets (M) with the influx density of 600 Gauss were bilaterally implanted (with "N" polarity facing the cranial bones) and fixed to the skull posterior to the fronto-parietal suture (parietal brain exposure). Rats implanted with iron beads (I) and sham-operated (SO) rats served as controls. Animals were exposed to MF or I during different periods of time before and after immunization with several soluble or cellular antigens. We report here on the in vivo immunoregulating effects of centrally applied MF on plaque-forming cell (PFC) response, local hypersensitivity skin reactions and experimental allergic encephalomyelitis. The selective influence of MF applied to different brain regions on PFC response was evaluated, as well. For this purpose, two M were bilaterally implanted in the area of (a) frontal, (b) parietal and (c) occipital brain regions. Rats were under the influence of MF for 20 days before and 4 days after immunization with sheep red blood cells. Groups of nonimmunized rats were exposed for 14, 24 and 34 days to parietally implanted M or I, and the number of peripheral blood CD4+ and CD8+ cells determined by mouse anti-rat W3/25 and MRC OX 8 monoclonal antibodies. The results show an overall in vivo immunopotentiation of humoral and cell-mediated immune responses in rats exposed to MF. Furthermore, these immunomodulating effects of centrally applied MF depend on at least two basic parameters, time of exposure and brain region exposed. The highest immune performance was obtained after exposure of the occipital brain region for a total period of 24 days. The results provide further evidence of the complex interrelationship between the environment, the central nervous system and the immune system.

Animals↗

Immunity and immune privilege elicited by autoantigens expressed on syngeneic neonatal neural retina grafts.

Achieving the long-term goal of successful engraftment of retinal tissues into eyes blinded by endogenous retinal failure will depend, at least in part, on controlling the immune response to antigens expressed on retinal grafts. Since histoincompatible tissues will have to be used for such transplants, methods to control immune rejection directed at transplantation alloantigens must be devised. In addition, it has recently been observed in mice that developing neural retinal tissues express retina-specific antigens that have the potential to contribute to graft failure. To examine the potential risk of this contribution, syngeneic neonatal neural retinas were implanted into the anterior chamber, vitreous cavity, and subconjunctival space of adult BALB/c mice. During two weeks post-implantation, the fate of these grafts was observed clinically and histologically, and the retina-specific immune responses of the recipients were evaluated. Whereas grafts placed intraocularly thrived, carried out their inherent developmental potential, and were healthy and intact at the end of the observation interval. Grafts placed extraocularly expressed their differentiation program poorly. These grafts underwent rapid decline and attrition, although the process was not accompanied by significant inflammation. Recipients of subconjunctival, but not AC or VC, implants developed retina-specific delayed hypersensitivity. Alternatively, mice bearing AC and VC implants of neonatal neural retina developed retina-specific anterior chamber associated immune deviation. It is concluded that retinal autoantigens are expressed on developing neural retinal tissues and these antigens are highly immunogenic when retinal grafts are placed at conventional body sites. When similar grafts are placed in immune privileged compartments of the normal eye, they enjoy significant survival. Circumstantial evidence indicates that intraocular retinal grafts are protected and maintained in part by the emergence of systemic retinal auto-antigen-specific immune suppression.

Animals↗

Immunization of the gastrointestinal tract with bacterial and viral antigens: implications in mucosal immunity.

The effects of oral immunization with Pseudomonas aeruginosa (PAOI), Chlamydia trachomatis or respiratory syncytial virus (RSV) on the development of specific antibody responses in the intestine, respiratory tract and genital secretions was studied in several animal models. Oral immunization resulted in the development of specific immunity in distant mucosal sites. However, its role in influencing the outcome of reinfection challenge at the distant site varied with the antigen. Little or no protection was observed against infection with Pseudomonas aeruginosa in the respiratory tract. Limited protection was observed against respiratory tract infection with RSV. On the other hand oral immunization appeared to be quite effective in preventing respiratory or genital infection with Chlamydia trachomatis. Finally, preliminary studies have suggested that intestinal immunization via the process of breast feeding can also be employed as an effective means to induce anti-idiotypic immunity against RSV in the breast feeding neonates.

Animals↗

Membrane Fas ligand activates innate immunity and terminates ocular immune privilege.

It has been proposed that the constitutive expression of Fas ligand (FasL) in the eye maintains immune privilege, in part through inducing apoptosis of infiltrating Fas(+) T cells. However, the role of FasL in immune privilege remains controversial due to studies that indicate FasL is both pro- and anti-inflammatory. To elucidate the mechanism(s) by which FasL regulates immune privilege, we used an ocular tumor model and examined the individual roles of the membrane-bound and soluble form of FasL in regulating ocular inflammation. Following injection into the privileged eye, tumors expressing only soluble FasL failed to trigger inflammation and grew progressively. By contrast, tumors expressing only membrane FasL 1) initiated vigorous neutrophil-mediated inflammation, 2) terminated immune privilege, and 3) were completely rejected. Moreover, the rejection coincided with activation of both innate and adaptive immunity. Interestingly, a higher threshold level of membrane FasL on tumors is required to initiate inflammation within the immune privileged eye, as compared with nonprivileged sites. The higher threshold is due to the suppressive microenvironment found within aqueous humor that blocks membrane FasL activation of neutrophils. However, aqueous humor is unable to completely block the proinflammatory effects of tumor cells that express high levels of membrane FasL. In conclusion, our data indicate that the function of FasL on intraocular tumors is determined by the microenvironment in conjunction with the form and level of FasL expressed.

Animals↗

IL-23 induces stronger sustained CTL and Th1 immune responses than IL-12 in hepatitis C virus envelope protein 2 DNA immunization.

IL-23 is a heterodimeric cytokine consisting of p19 and the p40 subunit of IL-12. IL-23 has been shown to possess IL-12-like biological activities, but is different in its capacity to stimulate memory T cells in vitro. In this study, we investigated whether IL-23 could influence envelope protein 2 (E2)-specific cell-mediated immunity induced by immunization of hepatitis C virus E2 DNA. We found that IL-23 induced long-lasting Th1 and CTL immune responses to E2, which are much stronger than IL-12-mediated immune responses. Interestingly, IL-23N220L, an N-glycosylation mutant showing reduced expression of excess p40 without changing the level of IL-23, exhibited a higher ratio of IFN-gamma- to IL-4-producing CD4(+) T cell frequency than did wild-type IL-23, suggesting a negative regulatory effect of p40 on Th1-prone immune response induced by IL-23. These data suggest that IL-23, particularly IL-23N220L, would be an effective adjuvant of DNA vaccine for the induction of durable Ag-specific T cell immunity.

Adjuvants, Immunologic↗

Delayed immune reactions in mice immunized with malarial antigen.

Mice were immunized subcutaneously, intravenously or in a footpad with antigens prepared from a lethal strain of Plasmodium berghei yoelii. A delayed footpad swelling (DFS) reaction was observed 4 days after immunization, and was detectable at least 42 days after immunization. However, IV immunization was the least efficacious is producing hypersensitivity. Regardless of the type of antigen used for immunization, mice responded similarly when live parasites were used to elicit DFS. This study revealed that hypersensitivity depended on route of immunization and type of antigen.

Animals↗

Immunity to larval Brugia malayi in BALB/c mice: protective immunity and inhibition of larval development.

The objective of this study was to analyze the immune response of mice to the larval stages of Brugia malayi. Male BALB/c mice were inoculated with 3 doses of irradiated third-stage larvae (L-3) of B. malayi and were subsequently challenged with L-3 implanted ip within diffusion chambers. After 3 weeks, larvae were recovered to determine their viability, length, and stage of development. A significant reduction in parasite survival was observed in immunized mice. Furthermore, larvae recovered from immunized mice were significantly shorter than larvae recovered from control mice. All larvae recovered from immunized mice were L-3, whereas 96% of larvae recovered from controls were fourth-stage larvae (L-4). Sera collected from control and immunized mice were tested for the presence of antibodies reactive with L-3 and L-4 antigens using an indirect fluorescent antibody assay employing frozen larval cross-sections as antigen. Sera recovered after challenge of control mice reacted with internal, but not surface, antigens of L-3 and L-4. Alternatively, sera from immunized mice reacted with both internal and external antigens of both L-3 and L-4.

Animals↗

The effect of ubiquinone-7 and its metabolites on the immune response. III. The effect on the immune response to sheep erythrocytes and DNP-Lys-Ficoll in mice.

The effects of Q acid-11, Q-7 and vitamin A palmitate on humoral immune response to two different types of antigens were examined. Particulate T-dependent antigen (SRBC) and T-independent antigen (DNP-Lys-Ficoll) were used to study the mode of action on immune system. Sodium-salt of Q acid-II (Q acid-11 Na) in the form of saline solution or water-in-oil emulsion showed suppressive effect on the direct and indirect PFC responses when administered simultaneously with SRBC. The suppressive effect of Q acid-II Na, however, was not observed when Q acid-II Na was administered two days before immunization. When Q acid-II Na was administered one day after immunization, the suppressive effect of Q acid-II Na was diminished and the level of PFC response was nearly equal to that of the control group. On the other hand, Q acid-II Na, Q-7 and vitamin A palmitate markedly enhanced the immune response to DNP-Lys-Ficoll (T-independent antigen). From the comparison of these humoral immune response, their modes of action are discussed.

Animals↗

[Comparison of specific immune responses to duck hepatitis B virus in infected, immune, and uninfected ducks].

OBJECTIVE: To explore the factor in determining whether hepadnavirus infection is cleared or becomes chronic. METHODS: Experimental groups were established by inoculation with duck hepatitis B virus (DHBV) at different age and schedule. The kinetics of virus replication and the humoral and cell mediated immune response (CMI) by ducks acutely and chronically infected with, or immune to DHBV infection was measured. RESULTS: Infection of the adolescent animals with DHBV led to a transient viremia. The levels of anti-DHBs and anti-DHBc were higher in acutely infected group than in chronically infected group (P<0.05), but lower than in immune group (P<0.01). CMI analysis showed the response to DHBsAg and DHBcAg by peripheral blood mononuclear cells from acutely infected ducks (10 day pi) was stronger than that from chronically infected ones (P<0.05); however, the level of the response reduced over a period of 5 weeks. There were no differences regarding CMI response in acutely infected or immune ducks. CONCLUSIONS: The immune response especially antigen -specific immune response is the key factor in determining the outcome of the infection.

Animals↗

Anti-fecundity immunity in mice immunized with anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum.

OBJECTIVE: To observe the effects of anti-fecundity and anti-embryonation immunity of anti-idiotypic monoclonal antibody NP30 of Schistosoma japonicum on female adult worm. METHODS: The active immunization of C57BL/6 mice was conducted by means of three intraperitoneal injections of NP30. The control group was injected with SP2/0 ascites intraperitoneally. RESULTS: On the twenty-seventh day after challenge infection, the number of eggs in the liver tissue and in uterus of the group immunized with NP30 decreased by 30.91% and by 38.55%, respectively. On the thirty-ninth day after the challenge infection, the number of mature eggs in the liver tissue of the group immunized with NP30 decreased by 66.63% and the number of dead eggs increased by 60.66%. CONCLUSIONS: NP30, with which mice were actively immunized, possesses double effects of anti-fecundity and anti-embryonation immunity on female adult worm of Schistosoma japonicum, therefore it can be used as a promising candidate of anti-pathologic vaccine molecule against Schistosomiasis japonica.

Animals↗

[Influence of multiplicity of immunizations of children with inactivated influenza vaccine on immune response and the effectiveness of protection].

The formation of immunity and epidemiological effectiveness of inactivated influenza vaccines in children, regularly immunized against influenza for three years, were evaluated. The study revealed that a year after each immunization the number of children having antibodies in liters regarded as protective decreased 2-2.5 times. At the periods of epidemics morbidity rate among the vaccines dynamically decreased in these years 1.3, 2.0 and 2.8 times. Considering that a year after the second immunization a high immune stratum (60-78%) was retained in the group under study, we propose that annual immunization of the same children be limited by a period of three years, followed by an interval of one year.

Adolescent↗

Individual differentiation of innate antiviral immunity in humans; the role of endogenous interferons and tumor necrosis factor in the immunity of leukocytes.

The natural antiviral immunity of human lymphocytes, leukocytes from peripheral blood and whole-blood cultures was studied using the method of infection with two viruses belonging to different taxonomic groups, vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV). The kinetics of virus replication in the kinds of cultures and the dependence of culture infection on pre-infection incubation time were studied. When the cultures were infected immediately after preparation, most of them were found to be resistant to the viruses. However, when they were infected after several (1-5) days of incubation, VSV and EMCV multiplied in the cultures to high titers. The time of losing resistance was individually differentiated. The results indicate the presence of a non-specific antiviral immunity characteristic for individuals. The antiviral immunity of healthy donors was compared with that of people suffering from recurrent infections of the upper respiratory tract. This latter group expressed statistically significant lower innate immunity than healthy donors. However, there were no differences in interferon (IFN) and tumor necrosis factor (TNF) production between these groups. In order to examine the contribution of the endogenous IFNs and TNF-alpha in maintaining innate immunity, specific antibodies against IFN-alpha, IFN-beta, IFN-gamma and TNF-alpha were added to VSV-infected leukocytes resistant to infection. The antibodies reduced the antiviral resistance in 9 of 16 experiments. The results suggest that both endogenous interferons and TNF-alpha may participate in the constitution of innate immunity, though they are not the only mediators of it.

Animals↗

Origin and fate of IgE-bearing lymphocytes. II. Gut-associated lymphoid tissue as sites of first appearance of IgE-bearing B lymphocytes and hapten-specific IgE antibody-forming cells in mice immunized with benzylpenicilloyl-keyhole limpet hemocyanin by various routes: relation to asialo GM1 ganglioside+ cells and IgE/CD23 immune complexes.

The organs in which B cells bearing membrane-bound IgE (sIgE+) and benzylpenicilloyl (BPO)-specific IgE antibody-forming cells (AFC) first appeared were determined in BALB/c mice given BPO-keyhole limpet hemocyanin (10 micrograms) in aluminum hydroxide by various routes (i.p, gavage, s.c., i.v., or i.m.). In mice immunized by the i.p. route, the numbers and location of sIgE+ B cells and asialo GM1 ganglioside (AsGm1+) cells, the location of IgE/CD23 immune complexes, and the numbers of BPO-specific IgE AFC in lymphoid organs were determined. With all routes of immunization, no sIgE+ B cells or BPO-specific IgE AFC were ever detected in any organ before day 8. On day 8, with the s.c., i.v., or i.m. routes, sIgE+ B cells and IgE AFC appeared exclusively in Peyer's patches (PP); with the i.p. or gavage routes, sIgE+ B cells simultaneously appeared in both PP and mesenteric lymph nodes, whereas IgE AFC appeared only in PP. In mice immunized by the i.p. route, IgE/CD23 immune complexes and strikingly increased numbers of AsGm1+ cells transiently appeared only in PP after the appearance and preceding the "disappearance" of the sIgE+ B cells and IgE AFC. The data suggest that specific IgE responses originate in gut-associated lymphoid tissue and appear later in spleen. The data also associate the appearance of IgE/CD23 immune complexes and AsGm1+ cells with the "disappearance" of sIgE+ B cells and IgE AFC from PP.

Animals↗

Modulation of the avian immune system: suppression versus induction of immunity.

Knowledge of the potential, but also of the vulnerability of the avian immune system is not only of academic interest. The intact immune system, beginning in the embryo, is of central significance to safeguarding health and productivity in poultry flocks. Interactions between cellular and soluble constituents of the avian immune system on one hand, and the nature of immunosuppressants on the other, determine whether the avian immune system is able to cope with microbial and non-microbial challenges. Modulation of the immune response can be achieved in the classical way by specific vaccinations or possibly in the future by DNA vaccination. Cytokine inducing compounds may provide additional tools to enhance immune reactivity. The future will tell whether these approaches will be applicable in disease preventation or treatment in poultry medicine. In concert with these tools, however, strict hygiene measures from incubation until production, slaughter and processing are equally of vital significance as part of disease prevention strategies, ultimately leading to high quality food products originating from animal production.

Animals↗

[Immune response in experimental animals immunized with Burkholderia pseudomallei surface antigens].

The influence of the chromatographic fractions of B. pseudomallei surface antigenic complex (C, C1, D, H) on immune response in white rats and white mice was under study. These antigenic complexes were noted to produce perceptible stimulating effect on the immune system of white rats, in contrast to that of white mice. The immunization of the mice the above-mentioned fractions suppressed the phagocytic activity of peritoneal macrophages (PM) and slightly enhanced cell-mediated immunity. In experiments on white rats, fraction C induced the growth of specific antibody titers and stimulated the phagocytic activity of PM, as well as the indices of delayed hypersensitivity (DH). Fraction D showed a lower level of the induction of the phagocytic activity of PM and was inactive in the manifestation of cell-mediated immunity, but induced a high level of humoral immunity. Antigenic complexes C1 and H increased the phagocytic activity of PM and DH characteristics with a low level of antibody production. The studied fractions of the causative agent of melioidosis decreased the content of bactericidal cationic proteins (BCP) in rat blood neutrophils, and in mice a decreased content of BCP in phagocytes was registered. The fractions increased the activity of myeloperoxidase in blood neutrophils in mice and rats. As revealed with the use of immunoelectrophoresis, SDS PAAG electrophoresis and immunoblotting, the surface antigenic complex contained proteins of 18, 22, 39 kD and glycoproteins 42, 55, 90 kD. The latter glycoprotein was found in all the fractions under study, having protective properties.

Animals↗