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[The development of immunity after vaccination of cattle against trichophytosis].

Trials were conducted with 262 one-month-old calves. Good immunity was found to have developed within the period of 21 to 28 days after the administration of the Czechoslovak live vaccine against bovine trichophytosis. After epicutaneous inoculation of a highly virulent culture of Trichophyton verrucosum, performed 28 and 35 days after re-vaccination, no clinical form of trichophytosis was observed to rise in the calves. The same doses of challenge inoculum induced profound trichophytic changes. In the groups of calves artificially infected on the day of re-vaccination and seven days after re-vaccination, the proportions of experimental animals that fell ill were 88.2% and 44.4%, respectively; in the majority of cases, the course of the disease was not so serious as in the controls. Calves challenged 11 to 21 days after the second administration of the vaccines were mostly resistant to experimental infection: slight changes occurred in 15.4 to 7.0% of the tested animals.

Animals↗

Drug-abbreviated infections of Trichostrongylus colubriformis and development of immunity in jirds (Meriones unguiculatus).

The objective of this study was to examine the development and the duration of immunity achieved with drug-abbreviated infections of Trichostrongylus colubriformis in jirds (Meriones unguiculatus). Jirds were primarily infected either by trickle infection with 6 x 100 infective larvae (L3) of T. colubriformis at 3-day intervals or by a single infection with 600 L3. On day 35 post-infection, one batch of jirds from each group was autopsied; the others were treated with oxfendazole at a dose of 5 mg/kg and were challenged with 1,000 L3 on either day 7 or day 42 post-treatment. All jirds were autopsied at 17 days post-challenge. Trickle infection resulted in lower levels of egg production during the primary infection period. The systemic IgM and IgG antibody response was significantly stronger in trickle- and single-infected groups as compared with the negative control group (P < 0.01-P < 0.05). Significantly higher levels of intestinal IgA were demonstrated in trickle- and single-infected groups than in the negative control group (P < 0.01). Numbers of mucosal mast cells increased following infection, but this was not dependent on the type of immunisation. After challenge the extent of worm reduction was greater in trickle-infected than in single-infected subgroups. The IgM and IgG response was significantly stronger in challenged subgroups as compared with negative control subgroups (P < 0.01). However, the IgG response was weaker in control challenged subgroups than in challenged subgroups (P < 0.01). There was a negative correlation between the IgG response and the worm burden after the second challenge (r = -0.73). The acquired immunity to T. colubriformis infection in jirds developed within 5 weeks of primary infection. The level of immunity was higher after trickle infection than after single infection. Furthermore, the immunity persisted for at least 6 weeks after oxfendazole treatment in the absence of a worm burden and larval intake, which is very similar to the situation in domestic ruminant hosts.

Animals↗

Development of immune functions related to allergic mechanisms in young children.

The newborn immune system differs quantitatively and functionally from that of adults. Development of the immune system has important implications for childhood diseases. The immaturity of the immune system in the first years of life may contribute to failure of tolerance induction and in the development of allergic disease. T cell function is diminished, especially the capacity to produce cytokines; production of interferon (IFN)-gamma, and IL-4 is strongly reduced. IFN-gamma has been found to be even lower in cord blood of newborns with a family history of atopy. Differences in other cell types (natural killer cells, antigen-presenting cells, and B cells) could also play a role in the development of allergic disease. Current data suggest that irregularities in IgE synthesis, helper T cell subsets (Th1, Th2, CD45RA, and CD45RO), cytokines (IL-4, IFN-gamma), and possibly other cell types may play a role in the development of allergy in childhood. Moreover, the role of cell surface molecules, like co-stimulatory molecules (CD28, CD40L), activation markers (CD25), and adhesion molecules (LFA-1/ICAM-1, VLA-4/ VCAM-1) is also discussed. These variables are modulated by genetic (relevant loci are identified on chromosome 5q, 11q, and 14) and environmental forces (allergen exposure, viral infections, and smoke). The low sensitivity of current predictive factors for the development of allergic diseases, such as cord blood IgE levels, improves in combination with family history and by measurement of in vitro responses of lymphocytes and skin reactivity to allergens. New therapeutic approaches are being considered on the basis of our current understanding of the immunopathology of allergic disease, for instance cytokine therapy and vaccination with tolerizing doses of allergen or peptides.

Child↗

Role of sympathetic nerves on early embryonic development and immune modulation of uterus in pregnant mice.

To determine the role of sympathetic nerves in the early embryonic development and the immune modulation of maternal uterus during pregnancy, a model of chemical sympathectomy in mice was established by intraperitoneal injection of 6-hydroxydopamine (6-OHDA). The embryonic development and the distribution of maternal uterine immunocytes were investigated during early pregnancy (E1-E9) with methods of histology, immunohistochemistry and ELISA. Our data showed that in the 6-OHDA-treated group, the number of implanted embryos was only 64.4% of that in the control group at E7, and the development of uterine glands and vessels was poor in pregnant mice. In addition, in uterine tissues of 6-OHDA-treated mice, the number of CD8+ T cells increased ten-fold and the concentration of IL-2 increased 3.6-fold at E5. However, no obvious changes to the number of CD4+ T cells and IL-4 were observed. Thus, the CD4+/CD8+ T cells ratio significantly decreased, while the IL-2/IL-4 ratio significantly increased. These findings indicated that the activation of sympathetic nerves might be favorable to fetal survival and development during early pregnancy through influencing on immune function and decidua formation of uterus.

Age Factors↗

Development of immune hyperinnervation in NGF-transgenic mice.

Sympathetic innervation of lymphoid tissues is localized to specific tissue compartments, but little is known of the "factors" that are important in establishing this pattern during development. Numerous studies have shown interactions of nerve growth factor (NGF) with the immune system, which may include modulation of immune innervation. We previously have shown that NGF transgenic mice, which overexpress NGF in skin and not immune tissues, have a dramatic hyperinnervation of splenic marginal zone and peripheral lymph node medulla and capsule. The purpose of the current studies was to determine if the presence of elevated NGF would alter immune system development and the process of sympathetic ingrowth. The results show that the splenic innervation in NGF transgenics gradually diverged from controls during the first two postnatal weeks, with the greatest change occurring between postnatal days 13 and 16 when the splenic organization was reaching the adult pattern. In contrast, the peripheral lymph nodes were hyperinnervated at an earlier age. mesenteric lymph nodes never diverged from the normal pattern. NGF levels in transgenic spleen were much higher than controls at postnatal days 1 and 2, when little innervation was present, and declined as the tissue matured, possibly because of NGF uptake by the ingrowing sympathetic fibers. This suggests that immune tissues are capable of concentrating NGF, which in turn may modulate the level of innervation by the sympathetic nervous system.

Animals↗

Effect of Mycobacterium phlei on the development of immunity to Babesia bigemina.

The immunomodulatory role of Mycobacterium phlei against intracellular blood protozoan Babesia bigemina was demonstrated following experimental immunisation and challenge in bovine calves. A lysate of erythrocytes infected (6 x 10(9)) with B. bigemina was used as a source of dead antigen either with Freund's complete adjuvant (FCA) or with a trypsinised culture of M. phlei as a non-specific immunomodulation (NSI) agent with appropriate controls. Following virulent challenge with B. bigemina infected erythrocytes (1 x 10(7)), the NSI printed calves showed 100% protection, while the dead antigen alone with FCA afforded 75% protection. The protective status of the immunising regimes was studied by clinicopathological parameters and assessment of humoral and cell-mediated immune responses. The role of babesial dead antigen and the effects of M. phlei on the development of immunity to B. bigemina is discussed.

Animals↗

Effects of dietary fat and protein on DMH-induced tumor development and immune responses.

Although in three different mouse tumor systems with corn oil as dietary fat we previously found that milk protein decreased tumor development compared with beef, the results were reversed in 1,2-dimethylhydrazine (DMH)-injected mice. The purpose of this study was to determine if the latter result was due to the protein source. BALB/c mice (n = 280) were divided into five diet groups and injected 10 times at weekly intervals with DMH (20 mg/kg wt) or saline. Four diets contained 11% protein (casein, milk, or beef) and 5% fat (corn oil or beef tallow), and the AIN-76A diet was used as a control diet. The source of fat was a significant modulator of tumor development. Corn oil markedly increased total tumor volume and the number of tumors per mouse compared with beef tallow. Its tumor-enhancing effects were evident when it was combined with milk but not with casein. In addition, significantly lower lymphoproliferation and T-cell cytotoxicity against colon tumor cell targets was associated with corn oil consumption, whereas nonfat milk as the protein source was related to normal oxidative burst capacity of phagocytes. These results demonstrate that the source of dietary fat, in addition to the protein source, has a profound effect on both tumor development and immune responsiveness in this animal tumor system.

1,2-Dimethylhydrazine↗

Immunity to airborne challenge with Venezuelan equine encephalitis virus develops rapidly after immunization with the attenuated vaccine strain TC-83.

Mice vaccinated subcutaneously with the attenuated vaccine strain of Venezuelan equine encephalitis virus (VEEV) rapidly develop immunity to subcutaneous or airborne challenge with virulent VEEV. The specificity of this immune response was demonstrated by challenge with a heterologous virus (St. Louis encephalitis virus). Examination of the levels of VEEV-specific antibody classes in serum and respiratory secretions suggested that the rapid development of immunity was coincident with the appearance of specific IgM and IgG (but not IgA) in the respiratory tract. In order to confirm the role of respiratory tract antibody, mice were passively immunised either intraperitoneally or intranasally with polyclonal VEEV-specific IgG. Intranasal administration of specific IgG significantly enhanced protection against airborne challenge. These results confirm the need to emphasise local antibody production in the development of improved VEEV vaccines.

Administration, Intranasal↗

Mutants of pertussis toxin suitable for vaccine development.

Immunization with chemically detoxified pertussis toxin can prevent severe whooping cough with an efficacy similar to that of the cellular pertussis vaccine, which normally gives unwanted side effects. To avoid the reversion to toxicity and the loss of immunogenicity that may follow chemical treatment of pertussis toxin, inactive toxins were constructed by genetic manipulation. A number of genetically engineered alleles of the pertussis toxin genes, constructed by replacing either one or two key amino acids within the enzymatically active S1 subunit, were introduced into the chromosome of strains of Bordetella pertussis, B. parapertussis, and B. bronchiseptica. These strains produce mutant pertussis toxin molecules that are nontoxic and immunogenic and that protect mice from the intracerebral challenge with virulent Bordetella pertussis. Such molecules are ideal for the development of new and safer vaccines against whooping cough.

Animals↗

Effects of pulsed magnetic stimulation on tumor development and immune functions in mice.

We investigated the effects of pulsed magnetic stimulation on tumor development processes and immune functions in mice. A circular coil (inner diameter = 15 mm, outer diameter = 75 mm) was used in the experiments. Stimulus conditions were pulse width = 238 micros, peak magnetic field = 0.25 T (at the center of the coil), frequency = 25 pulses/s, 1,000 pulses/sample/day and magnetically induced eddy currents in mice = 0.79-1.54 A/m(2). In an animal study, B16-BL6 melanoma model mice were exposed to the pulsed magnetic stimulation for 16 days from the day of injection of cancer cells. A tumor growth study revealed a significant tumor weight decrease in the stimulated group (54% of the sham group). In a cellular study, B16-BL6 cells were also exposed to the magnetic field (1,000 pulses/sample, and eddy currents at the bottom of the dish = 2.36-2.90 A/m(2)); however, the magnetically induced eddy currents had no effect on cell viabilities. Cytokine production in mouse spleens was measured to analyze the immunomodulatory effect after the pulsed magnetic stimulation. tumor necrosis factor (TNF-alpha) production in mouse spleens was significantly activated after the exposure of the stimulus condition described above. These results showed the first evidence of the anti-tumor effect and immunomodulatory effects brought about by the application of repetitive magnetic stimulation and also suggested the possible relationship between anti-tumor effects and the increase of TNF-alpha levels caused by pulsed magnetic stimulation.

Animals↗

Differential modulation of lymphocyte proliferative responses and lymphokine secretion in mice during development of immunity to Chlamydia psittaci.

A murine model was utilized to study immune responses occurring during the period of acquisition of immunity to chlamydial infection. C3H (H-2k) mice were immunized by intramuscular injection of 5 x 10(3) viable Chlamydia psittaci elementary bodies (EBs) by a protocol which permits animals to survive an otherwise lethal intraperitoneal challenge 10 days later with the homologous chlamydial strain. Spleen cells assayed during the 10-day period of development to immunity showed depressed proliferative responses in vitro to the T-cell mitogen, concanavalin A, and also exhibited suppressor cell activity. Spleen cell mitogen responses returned to normal levels by 30 days postimmunization, concomitant with the detectable development in vitro of responses to chlamydia-specific antigen. In marked contrast to the reduced proliferative responses, mitogen-stimulated production of the T-cell-derived lymphokines interleukin-2 and gamma interferon by spleen cells from immunized animals was within the normal range at 10 days postimmunization, and supernatant fluids containing these products had both microbicidal and microbistatic effects on chlamydial organisms in vitro. These results demonstrate that independent regulation of T-cell proliferation and lymphokine production occurs in vivo as part of the development of an antigen-specific protective immune response. These results also suggest that such differential modulation of T-cell responses may contribute to the development of protective immunity to chlamydiae in mice, perhaps through limited T-cell clonal expansion coupled with early or preferential maturation of cytokine-secreting helper T cells.

Animals↗

B-cell-deficient mice develop complete immune protection against genital tract infection with Chlamydia trachomatis.

We evaluated the ability of mice made genetically deficient for B cells to resolve a primary infection and to develop protective immunity against vaginal challenge with a human isolate of Chlamydia trachomatis bacteria. The B-cell-deficient microMT mice cleared a primary ascending infection with similar or faster kinetics compared with wild-type mice. The presence of chlamydial inclusion bodies and the degree of inflammation in the upper genital tract was comparable and showed similar kinetics in microMT as in wild-type mice. Following resolution of the primary infection the mice were challenged by 100 ID50 of live bacteria and the level of protection and the extent of local inflammation was assessed. Strikingly, all microMT mice, as well as most of the wild-type mice, demonstrated complete immune protection with no bacterial shedding. While high titres of chlamydia-specific antibodies were stimulated locally and systemically in wild-type mice, no antibodies were detected in microMT mice. However, in both strains, immunohistochemical analysis of the upper genital tract demonstrated the presence of large numbers of CD4+ T cells and increased levels of interferon-gamma (IFN-gamma)-producing cells. The results unequivocally demonstrate that antibodies are not required for full protection to develop against ascending infection with a high dose of C. trachomatis in the female genital tract. Our study confirms the notion that cell-mediated immunity, in particular that owing to CD4+ T helper I (Th1)-type cells, is critical for host resistance against C. trachomatis in mice.

Animals↗

Pneumococcal immunization: policy development and implementation from the ACIP perspective.

The Advisory Committee on Immunization Practices (ACIP) of the U.S. Public Health Service is responsible for making recommendations on the use of new vaccines and periodically revising those for established vaccines. Recommendations for pneumococcal vaccine were first issued in 1978 and revised in 1981. The changes which appear in the revision reflect the continuing maturation of the Committee's judgment on the vaccine and are a good example of the process by which the ACIP develops its recommendations on national immunization practices.

Bacterial Vaccines↗

Neuronal repellent Slit2 inhibits dendritic cell migration and the development of immune responses.

One of the essential functions of dendritic cells is to take up Ags in peripheral tissues and migrate into secondary lymphoid organs to present Ags to lymphocytes for the induction of immune responses. Although many studies have demonstrated that the migration of dendritic cells is closely associated with the development of immune responses, little is known about factors that inhibit dendritic cell migration and control the extent of immune responses to Ag stimulation. We show that Slit2, a neuronal repellent factor, is up-regulated in the skin by allergen sensitization and down-regulates the migration of Langerhans cells. The effect is mediated by direct interaction of Slit2 with cells that express a Slit-specific receptor, Robo1. Slit2-mediated inhibition of Langerhans cell migration results in suppression of contact hypersensitivity responses. These findings provide insights into a novel mechanism by which Slit2 functions as an anti-inflammatory factor for the initiation of immune responses.

Animals↗

Influence of helminth parasite exposure and strategic application of anthelmintics on the development of immunity and growth of swine.

Infection of pigs with the intestinal roundworm parasite Ascaris suum and strategic application of anthelmintic drugs during the growing phase of development were observed for specific effects on 1) development of immunity in feeder pigs and 2) growth rate during the finishing phase. Management treatments included maintenance in a parasite-free concrete environment, maintenance in a concrete environment and inoculation with 1,000 infective A. suum eggs every other day over a 52-d period, and maintenance on a dirtlot contaminated with A. suum and Trichuris suis eggs. Within each management environment, pigs were either untreated, treated with ivermectin or treated with fenbenzadole at strategic times during parasite exposure. Protective immunity, assessed by a challenge inoculation with A. suum eggs following management treatments, was not affected by ivermectin or fenbenzadole treatment during exposure, but adult worm burdens were reduced and the pattern of A. suum larval antigen serum antibody responses were different from those in control pigs not treated with drugs. Exposure to A. suum and treatment with anthelmintics during the growing phase reduced adult worm burdens following the finishing phase of growth. Rate, but not efficiency, of gain was significantly improved by anthelmintic treatment following natural exposure to parasites. Strategic treatment of pigs with anthelmintics following inoculation with A. suum eggs in a concrete management environment had no effect on rate of gain. Results suggest that natural exposure to parasites during the growing phase without therapeutic treatment causes permanent damage to growth potential.

Animals↗

Secretory immunoglobulin A: from mucosal protection to vaccine development.

Immune responses taking place in mucosal tissues are typified by secretory immunoglobulin A (S-IgA) molecules, which are assembled from proteins expressed in two cell lineages. The heavy and light chains as well as the J chain are produced in plasma cells, whereas the secretory component (SC) is associated to the immunoglobulin complex during transcytosis across the epithelial layer. S-IgA antibodies represent the predominant immunoglobulin class in external secretions, and the best defined entity providing specific immune protection for mucosal surfaces by blocking attachment of bacteria and viruses. S-IgA constitutes greater than 80% of all antibodies produced in mucosa-associated lymphoid tissues in humans. The existence of a common mucosal immune system permits immunization on one mucosal surface to induce secretion of antigen-specific S-IgA at distant sites. In addition, S-IgA antibodies not only function in external secretions, but also exert their antimicrobial properties within the epithelial cell during transport across the epithelium. Passive mucosal delivery of monoclonal IgA molecules neutralizes pathogens responsible for gastrointestinal and respiratory infections. Mucosal and systemic immunity can be achieved by orally administered recombinant S-IgA molecules carrying a protective bacterial epitope within the SC polypeptide primary sequence.

Animals↗

Development of immune response to cow's milk proteins in infants receiving cow's milk or hydrolyzed formula.

BACKGROUND: Development of humoral and cellular immune responses to orally administered antigens in human beings is poorly understood, although antigen administration has been suggested as a treatment for hypersensitivity disorders and autoimmune diseases. OBJECTIVE: The purpose of the study was to investigate the development of systemic immune response in infants fed with formula containing whole cow's milk proteins or hydrolyzed formula containing casein peptides. METHODS: In a double-blind trial, 10 infants received cow's milk-based formula, and 10 infants received a casein hydrolysate formula until the age of 9 months. Blood samples were taken at the ages of 6, 9, and 12 months. Cellular responses were assessed by proliferation assay of peripheral blood mononuclear cells to cow's milk proteins (beta-lactoglobulin, bovine serum albumin, and alpha-casein). Humoral responses to the same proteins were measured by ELISA for IgG antibodies. RESULTS: Feeding infants with cow's milk-based formula induced systemic humoral and cellular responses to cow's milk proteins. T-cell response later declined, supporting the concept of oral tolerization. Exposure to cow's milk proteins after the age of 9 months resulted in depressed cellular and humoral responsiveness to these proteins. CONCLUSION: Our results support the view that induction of oral tolerance in human beings is an age-dependent phenomenon.

Animals↗