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PubMed1990

Effects of varying the injection routes of PSK or OK-432 on development of immune responses against a superimposed antigen.

The present study examined functional and morphological modifications of development of immune responses to an unrelated antigenic stimulus by an ongoing response to a biological response modifier such as PSK or OK-432. Development of the immune responses was found to be strictly dependent upon the site where the ongoing response was occurring. In some cases, injection into the intraperitoneal site slightly augmented the development of a humoral immune response against a superimposed antigen, sheep erythrocytes, when the antigen had been injected into the site within 3 h after an injection of PSK. Thereafter, however, inhibition of the response was observed. Subcutaneous injection into the foot pad, but not into the upper chest, augmented the response. This augmentation occurred only when a superimposed antigen was injected into the site "prepared" with a previous injection of PSK, and showed a bell-shaped dependence on the dose of PSK. The foot pad site was also associated with an augmented development of a delayed type hypersensitivity against sheep erythrocytes when the antigen was injected into the "prepared" site. Morphological examination shows accumulation of inflammatory cells at the sites 2 to 7 days after an injection of PSK. The macrophages in the foot pad retained their "activated" state for at least 7 days after the injection whereas those in the peritoneal cavity were not sufficiently "activated" even after 2 days.

Animals↗

PubMed1992

Physiological mechanisms mediating enhanced force generation during development and immune sensitization.

We examined the development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by acetylcholine (ACh) in a swine model of maturation and a dog model of allergic bronchospasm. Strips of TSM were tethered isometrically at optimal length and responses were expressed as a percentage of the maximum to KCl-substituted perfusate (% KCl). Maximal contraction (ATmax) to ACh in 2-week-old swine (168 +/- 8% KCl) was greater than in 10-week-old swine (142 +/- 2% KCl; p less than 0.02). The AChase inhibitor, physostigmine, augmented ACh-elicited ATmax in 10-week-old (27% increase; p less than 0.01) but not in 2-week-old swine (2% increase; p is NS) and caused a greater increase in sensitivity to muscarinic activation in 2 versus 10 week-old swine (p less than 0.02), thus demonstrating increased contraction of TSM in 2 versus 10-week-old swine, which results at least in part from reduced AChase activity in immature animals. In another study, TSM from ragweed-sensitized dogs demonstrated augmented efficacy to ACh-elicited contraction (180 +/- 6% KCl) compared with TSM from sham-sensitized, littermate controls (163 +/- 4% KCl; p less than 0.05). In the presence of physostigmine, ATmax was not different between ragweed-sensitized and control TSM.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed2002

The development of immunity in a social insect: evidence for the group facilitation of disease resistance.

The extraordinary diversity and ecological success of the social insects has been attributed to their ability to cope with the rich and often infectious microbial community inhabiting their nests and feeding sites. Mechanisms of disease control used by eusocial species include antibiotic glandular secretions, mutual grooming, removal of diseased individuals from the nest, and the innate and adaptive immune responses of colony members. Here we demonstrate that after a challenge exposure to the entomopathogenic fungus Metarhizium anisopliae, dampwood termites Zootermopsis angusticollis have higher survivorship when individuals develop immunity as group members. Furthermore, termites significantly improve their ability to resist infection when they are placed in contact with previously immunized nestmates. This "social transfer" of infection resistance, a previously unrecognized mechanism of disease control in the social insects, could explain how group living may improve the survivorship of colony members despite the increased risks of pathogen transmission that can accompany sociality.

Animals↗

PubMed1980

Oral immunization with Streptococcus mutants in rhesus monkeys and the development of immune response and dental caries.

The oral route of immunization with Streptococcus mutants was compared with the subcutaneous route in rhesus monkeys. Significant levels of serum IgG, IgM and IgA antibodies in Strep. mutans were elicited only in monkeys immunized subcutaneously. Similarly, the skin delayed hypersensitivity reaction to Strep. mutans was elicited only in the subcutaneously immunized monkeys. Oral immunization induced a modest increase in salivary IgA antibodies to Strep. mutans, though a slight increase in IgA antibodies was also found in the saliva of all other groups of immunized and control monkeys. A small though not significant reduction in dental caries was found in the monkeys immunized orally, whereas subcutaneous immunization with Strep. mutans consistently elicited a significant reduction in caries. Oral feeding of Strep. mutans failed to induce tolerance to a subsequent subcutaneous challenge by the same organism. Furthermore, sequential subcutaneous followed by oral immunization had little effect on the titre of salivary or serum antibodies.

Administration, Oral↗

PubMedDate not supplied

Overview of immune system development in the dog: comparison with humans.

Dogs play an important role in toxicology because of their importance as a large animal, pre-clinical model for evaluating potential toxicity in human drug development including the effects of investigational drugs on the immune system. The purpose of this paper is to review the development of the canine immune system during the fetal, neonatal and postnatal periods and to compare it with that of the human immune system. Unlike rodents, the development of the canine immune system shares many similarities to that of the human. In both dogs and humans, the immune system, including the mucosal immune system, is fully developed before birth although the maturity of the immune response may continue into the postnatal period.

Age Factors↗

PubMed1994

Rapid establishment of a stable IL-4/IFN-gamma production profile in the antigen-specific CD4+ T cell response to protein immunization.

Development of the antigen-specific murine T cell response to immunization with keyhole limpet hemocyanin (KLH) in adjuvant has been monitored with direct limiting dilution analysis of CD4+ cells in draining lymph nodes (LN) and measurement of the cytokines produced by their clonal progeny. In vivo, the response to immunization suggested a major role for IL-4 and a minor role for IFN-gamma since IL-4 mRNA levels increased and IFN-gamma mRNA levels declined in LN over the first 3 days, and KLH-specific serum antibodies were mainly of IgG1 class with lower levels of IgE and IgG2a. Antigen-specific clonogenic cells were first detected in LN at day 4, at which time they comprised approximately 8% of the total CD4+ LN cell pool, declining to 1-2% from day 7 until at least 6 weeks after immunization. These clonogenic cells expressed high levels of surface CD44 (Pgp-1) both early and late in the in vivo response. Over the whole of the time span from day 4 to 6 weeks after immunization, most antigen-specific cells gave rise to clones that secreted IL-4 and a smaller proportion gave rise to IFN-gamma-secreting clones. By contrast, polyclonally activated CD4+ cells from untreated mice preferentially gave rise to clones with the converse cytokine profile. We conclude that a stable ratio of antigen-specific CD4+ cells committed to IL-4 or IFN-gamma synthesis is established within the first 4 days after KLH immunization and, contrary to prediction, does not evolve towards a more restricted cytokine profile during the primary response.

Animals↗

PubMed2007

Oral vaccination with modified vaccinia virus Ankara attached covalently to TMPEG-modified cationic liposomes overcomes pre-existing poxvirus immunity from recombinant vaccinia immunization.

Development of a safe and effective vaccine for induction of mucosal immunity to the human immunodeficiency virus (HIV) envelope glycoprotein (Env, gp160) represents the best hope for containing the spread of an HIV epidemic worldwide. The highly attenuated modified vaccinia virus Ankara (MVA) is a laboratory virus well suited as a safe vaccine vector. However, the presence of pre-existing immunity to Vaccinia virus in the adult population represents a hindrance that limits the application of the MVA vector for inducing immunity to HIV antigens. Here, cationic liposomes were covalently attached to the surface of recombinant MVA expressing the HIV-1 strain IIIB Env glycoprotein and beta-galactosidase (MVA(IIIB/beta-gal)) using tresylmonomethoxypolyethylene glycol (TMPEG) grafted into a lipid membrane without compromising viral infectivity in vitro and in vivo. The orally administered MVA(IIIB/beta-gal)-TMPEG/liposome complexes were capable of delivering the transgenes to mucosal tissues in mice with pre-existing poxvirus immunity based on beta-galactosidase gene expression in intestinal tissues measured 18 h after infection. Importantly, the MVA(IIIB/beta-gal)-TMPEG/liposome complexes enhanced Env-specific cellular and humoral immune responses in the mucosal and systemic tissues after repeated oral immunization of BALB/c mice. This approach may prove useful for induction of protective immunity against infectious diseases and cancer in populations with pre-existing immunity to vaccinia from smallpox vaccination.

Adjuvants, Immunologic↗

PubMed2004

Development of immunity to serogroup B meningococci during carriage of Neisseria meningitidis in a cohort of university students.

Understanding the basis of protective immunity is a key requirement for the development of an effective vaccine against infection with Neisseria meningitidis of serogroup B. We have conducted a longitudinal study into the dynamics of meningococcal acquisition and carriage in first-year university students. The detection of carriage of serogroup B meningococci correlated with an increase in detection of serum bactericidal activity (SBA) against both colonizing and heterologous serogroup B strains. Once induced, SBA remained high throughout the study. Although students showed increases in antibodies reactive with capsular polysaccharide and lipopolysaccharide (LPS), these antibody responses were transitory, and their decline was not accompanied by a corresponding decline in SBA. In contrast, there was a significant correlation between the presence of antibodies to the PorA outer membrane protein and SBA against both homologous and heterologous strains. SBA induced by a PorA-negative mutant confirmed the contribution of PorA to heterologous activity. Increases in SBA against a range of serogroup B strains were also observed in students in whom no meningococcal carriage was detected. This heterologous protection could not be associated with the presence of antibodies reacting with capsule, LPS, PorA, PorB, Rmp, Opa, Opc, or pilin, demonstrating that other, as yet unidentified, antigens contribute to the development of immunity to serogroup B meningococci. Identification of such antigens with the ability to induce an effective cross-reactive bactericidal response to a range of strains would be a major step in the production of a universally effective vaccine against infections caused by serogroup B meningococci.

Adolescent↗

PubMedDate not supplied

Therapeutic activity of sulphadimethoxine and bifuran against E. tenella and effect of medication on the development of immunity.

Therapeutic activity of sulphadimethoxine and Bifuran in drinking water against different levels of infection (5,000 10,000, 25,000 and 50,000 oocysts per chick) with Eimeria tenella and effect of medication on development of immunity was assessed. Medication was started after 96 hours of the infection. Sulphadimethoxine gave better control (performance indices: 234, 193, 155 and 112, respectively) than Bifuran (performance indices: 194, 129, 74 and 40, respectively) against all levels of the infection tested. Effectiveness of both the drugs decreased with increasing levels of the infection. Both the drugs interfered in the development of immunity which was inversely proportionate to the level of infection. Interference in development of immunity was more with sulphadimethoxine but these chicks were still solidly immune to the challenge infection.

Animals↗

PubMed1999

Development of immune complex trapping: experimental study of lymphoid follicles and germinal centers newly induced by exogenous stimulants in mouse popliteal lymph nodes.

The development of immune complex trapping in newly-induced lymphoid follicles of draining popliteal lymph nodes was investigated in young adult mice, which had been given bilateral injection of hemocyanin (KLH) or phytohemagglutinin (PHA), each absorbed onto alumina. HRP-anti-HRP immune complex was injected into the footpad 1 day before sacrifice. Using three series of semi-serial cryostat sections prepared from each popliteal node, the number of lymphoid follicles in each node was counted, and follicular localization of the in vivo injected and in vitro applied immune complexes in each follicle was determined. By day 5, a large germinal center had developed within each preexisting follicle. A large number of 'new' secondary follicles, each containing a small PNA-positive germinal center, appeared outside pre-existing follicles, from day 5 through day 11 in KLH-treated nodes, and from day 7 through day 14 in PHA-treated nodes. Shortly after their appearance, new secondary follicles showed no in vitro or in vivo trapping, but subsequently, many of the new follicles began to display in vitro trapping, at first weakly but later intensely. Occurrence of in vivo trapping in new follicles took some time and was first recognized when new follicles showed intense in vitro trapping. At day 21 or 25, many of the new follicles showed both in vitro and in vivo trapping. It was concluded that in lymph nodes treated with a stimulant, secondary follicles containing germinal centers can be formed de novo in the extrafollicular zone where the follicular trapping microenvironment is absent, but subsequently the microenvironment capable of trapping immune complexes develops at the site of formation of new follicles.

Alum Compounds↗

PubMed2002

Maternal selenium nutrition and neonatal immune system development.

We evaluated the impact of dietary selenium intake on neonatal immune cell differentiation and function. A low selenium intake during pregnancy and lactation produced reductions in maternal plasma selenium (33%, p = 0.0001), milk selenium (36%, p = 0.001), and corresponding neonatal plasma selenium (47%, p = 0.008). Thymocytes from neonates receiving low-selenium milk showed an impaired activation in vitro (p = 0.001). The percentages of CD8 cytotoxic T cells (p = 0.03), CD2 T cells (p = 0.09), panB cells ( = 0.02), and natural killer cells (p = 0.07) were all decreased in neonates nursed by mothers fed a low-selenium diet. The results indicate that maternal selenium intake impacts neonatal selenium status which in turn influences the neonatal immune system development.

Animals↗

PubMed1985

Morphological observations during developing concomitant immunity against a C3H/He mammary tumor.

During the developing phase of concomitant immunity against primary s.c. implants of the mammary carcinoma MC2, responder cells identified as Lyt 1 and Lyt 2 T-cell subsets and B-cells showed little tendency to infiltrate among the cells of the implants and did not appear to have any direct cytotoxic effect. Macrophages were also not cytotoxic at this time, but they were closely associated with the formation of a fibrous cellular capsule, always found around tumors in arrested growth or in regression. After a period of growth, about 20% of the MC2 implants regressed spontaneously. Surgical disruption of the capsules formed around 5-week-old primary tumor implants did lead to more frequent regressions, showing that a capsule that could destroy a tumor slowly also shielded the tumor against highly activated and effective systemic rejection mechanisms. In mice less than fully immunized with 3-week-old primary implants, the accumulation of responder cells at a second implant was rapid, and the development of a capsule was accelerated. Only the macrophages had developed a tendency to infiltrate among the tumor cells. Implants in partially immune mice had a lower mitotic index than did implants in normal mice. Of the second implants, 30% did not reach palpable size, and 42% regressed after a period of growth. Only after at least 5 weeks of immunization did a rapid destruction of second implants become evident. The tumor-destructive process was associated with infiltration by activated macrophages and was completed in 3 to 6 days.

Animals↗

PubMed1970

Relationship between staphylococcal antiserum titer and zone development on immune serum plates.

A workable relationship was established between the standard serum titers of staphylococcal immune antisera and the development of precipitin zones on serum agar around colonies of staphylococcal strains producing homologous antigens (enterotoxins). The standard titer of a serum is defined as the reciprocal of that serum dilution which, with 10 mug of pure enterotoxin per ml, will give a precipitin zone 10 mm in length in single gel-diffusion tubes after 7 days of incubation at 25 C. A numerical scale was set up for determining the intensity of precipitin zones on serum agar. A reading of 3 was considered optimum. This correlated well with a standard serum titer of 25, when 1 ml of such a serum was used per 20 ml of medium per serum plate. From this relationship, the minimum volume of serum required to give optimum precipitin zone development can be calculated.

Agar↗

PubMed1986

A model for the selective loss of major histocompatibility complex self-restricted T cell immune responses during the development of acquired immune deficiency syndrome (AIDS).

Functional analyses of peripheral blood leukocytes (PBL) from high risk HTLV-III antibody-negative and antibody-positive donors, as well as from patients with acquired immune deficiency syndrome (AIDS), lymphadenopathy syndrome (LAS), and AIDS-related complex (ARC) were performed by the in vitro generation of cytotoxic T lymphocyte (CTL) and proliferative responses to the HLA self-restricted antigens of influenza virus (S + X) and to nonself restricted HLA alloantigens (ALLO). All 40 antibody-negative donors tested responded to both S + X and ALLO in the CTL response, whereas six of 14 antibody-positive, two of three LAS, four of five ARC, and seven of 17 AIDS patients exhibited a selective absence of CTL to S + X, but generated normal or elevated CTL responses to ALLO. Of the remaining 10 AIDS patients, nine did not respond to either S + X or ALLO, and one responded to both S + X and ALLO. A similar selective loss of the proliferative response to S + X was found. We also observed antibody-positive donors who initially generated CTL responses to S + X and ALLO, but lost the S + X response as a function of time. We were able to restore the selective loss of S + X CTL activity in vitro by the addition of IL 2 and, to some extent, by co-stimulation with S + X plus ALLO. Depletion of CD4+ T helper cells and removal of autologous antigen-presenting cells from the PBL of healthy antibody-negative donors indicated that distinct T helper cell subsets exist in human PBL, and that S + X responses must use a CD4+ T helper population, whereas ALLO responses can utilize an alternate CD4- T helper pathway. A model is presented indicating the selective depletion of CD4+ T helper function in the developmental stages of AIDS. The functional test for T helper activity to self restricted antigens may be the earliest indicator of immune functional loss in the development of AIDS, and may precede a reduction in the absolute number of CD4+ cells.

AIDS-Related Complex↗

PubMed2002

Immune responses of sheep to quadrivalent double emulsion foot-and-mouth disease vaccines: rate of development of immunity and variations among other ruminants.

Despite representing the majority of the world's foot-and-mouth disease (FMD)-susceptible livestock, sheep and goats have generally been neglected with regard to their epidemiological role in the spread of FMD. In the present investigations, FMD virus quadrivalent double emulsion (Montanide ISA 206) vaccines were tested in sheep. The oil adjuvant elicited a better immune response at any time than did aluminum hydroxide gel vaccine, and the response developed quicker. The animals maintained their neutralizing antibody titers at >3 log(10) for the duration of the trial (90 days). Sheep were found to be late responders to serotypes A, C, and Asia-1; a clear upward shift in titer was observed at 60 days postvaccination. However, development of the immune response to serotype O in sheep was superior to that in cattle and goats.

Adjuvants, Immunologic↗

PubMed1993

Infection build-up and development of immunity in calves following primary Dictyocaulus viviparus infections of different levels at the beginning or in the middle of the grazing season.

An experiment was carried out to study the build-up of infection and development of immunity against Dictyocaulus viviparus infections in calves. Six groups of four calves were used. Groups 1-5 grazed on separate pastures and Group 6 served as a permanently housed control group. To simulate 'low' and 'very low' overwintered pasture infectivity, Groups 1 and 2 were infected experimentally six times with ten and two larvae, respectively, during the first 3 weeks on pasture in May. From the middle of July, Groups 2-4 were experimentally infected six times in 3 weeks with 10, 10 and 100 larvae, respectively, to simulate 'low' and 'moderate' pasture contamination by carriers. Group 5 served as a non-infected pasture control group. After housing of Groups 1-5 in October, all calves were treated with oxfendazole and challenged with 5000 larvae of D. viviparus to evaluate the development of immunity. The results showed a similar population build-up of lungworm infections in Groups 1-4. After the beginning of patency, 24-35 days after primary infection, an increase in faecal larval counts occurred 31-35 days later as a result of re-infection. For Group 2, this was only true when the infections with a total of 12 larvae in May were ignored, as these did not result in patent infections. Faecal larval counts were highest in Group 4, which was the only group with mild signs of lungworm disease occurring in the re-infection period. The worm counts at necropsy showed the development of immunity in Groups 1-4 but not in Group 5. This is consistent with the fact that Group 5 did not develop patent lungworm infections throughout the grazing season.

Animals↗

PubMed2000

The effect of oxfendazole terminated infections with Haemonchus contortus on the development of immunity in sheep.

The relative contribution of third (L3), fourth (L4) or adult stages of Haemonchus contortus to the development of immunity was evaluated in three groups of sheep subjected to infections terminated by oxfendazole treatments at the L3, L4 or adult stage. A control group did not receive immunising infections. All the groups were challenged with 5000 L3, to evaluate the protection provided by the different protocols. All sheep were necropsied at the end of the experiment to count the abomasal worm burdens. A marked reduction in egg counts after challenge infection was only observed in sheep in which the infection was terminated in the adult stage (Group 4). A significant reduction in worm burden was also observed in Group 4. The immunising infections and/or the challenge infection resulted in moderately elevated IgG antibody levels against L3, L4 and adult somatic antigens in all the groups. In contrast, a strong IgG response against H. contortus excretory/secretory (ES) antigens was observed in the groups in which the immunising infection was terminated in the L4 and the adult stage. An elevated lymphocyte proliferation response against Haemonchus ES antigens was found only in the group that had their immunising infection terminated at the adult stage. The combined data suggest that exposure to and elicited immunological responses to ES antigens are important for the development of immunity against H. contortus.

Abomasum↗

PubMed1977

Toxoplasmosis in nude mice.

Immunity to the intracellular protozoan, Toxoplasma gondii, in mice is of the premunition type. Chemoprophylaxis with sulfadiazine normally permits mice to develop immunity to virulent organisms. However, nude (nu/nu) mice, which lack the thymus, failed to develop immunity to toxoplasma during 3 weeks of drug therapy while their hirsute littermates developed immunity during this period. When nude mice were injected intraperitoneally with thymus cells from hirsute littermates, they became able to develop immunity to toxoplasma during drug prophylaxis. The injection of bone marrow cells or high-titered specific antibody did not prolong survival after sulfadiazine was discontinued. Therefore, it appears that immunity to toxoplasma in mice is dependent upon active cellular immunity while the role of antibody is uncertain.

Animals↗