Immune reactions to Nippostrongylus brasiliensis in the rat. II. Primary and secondary immune response: in vitro characterization.
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The in vitro secondary stimulation of the production of anti-hapten antibody has been analyzed with a view to elucidating the role of the carrier molecule and cell-to-cell interactions in this response. Stimulation was carried out on fragment cultures of the spleens of irradiated BALB/c mice which had been reconstituted with 3-4 x 10(7) spleen cells from isologous mice previously immunized with DNP-Hy. The results indicated that the response was maximized by stimulation with DNP-Hy, the homologous complex, however anti-DNP antibody production could be obtained by stimulation with DNP on several nonhomologous carriers including poly-D-lysine, a poor immunogen. The results also indicated that while DNP-Hy and DNP-nonhomologous-carrier complexes were stimulatory at equally low DNP concentrations, at DNP concentrations over 10(-6)M DNP-Hy was stimulatory, while DNP on nonhomologous carriers was inhibitory. The results are interpreted as indicating that: (a) the affinity of the antigen-cell interaction is more likely determined by multivalent binding than by carrier recognition, (b) that a stimulatory interaction of a polyvalent antigen with a B-lymphocyte cannot be excluded, (c) that if cell-to-cell interaction is necessary for stimulation, then both cells may recognize the same determinant, and (d) that the marked enhancement of antigenic stimulation attributable to carrier recognition may result from stimulatory interactions of cells recognizing different antigenic determinants. A mechanism is postulated whereby stimulation is dependent on the formation of stable complexes resulting from two cells sharing in the binding of numerous antigen molecules. Cells recognizing carrier determinants would increase the probability of such interactions particularly at high antigen concentrations.
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The characteristics of the primary response, as well as those of the secondary response, to different doses of Salmonella typhosa when elicited at two different time intervals were analysed. The antibody response demonstrates that the size of the primary dose, and the size of the secondary dose, have significant effect on the subsequent synthesis of the secondary IgM and IgG antibody response to both 'H' and 'O' antigens. The time elapsed between the primary and secondary response tends to decrease the IgG response. Due to the high immunogenicity of the 'H' antigen the maximum IgG levels were reached within the range of doses used. These high levels of antibody inhibited the secondary IgM response by a feedback mechanism. Enhanced or equivalent response of predominant anti 'O' IgM system was recorded.
Trypanosoma congolense and T vivax infections in cattle were shown to have a suppressive effect on the secondary humoral immune response to M mycoides. The trypanosome infections caused an involution of the thymus. The secondary response was biphasic in nature and was unrelated to infection with trypanosomes.
It was demonstrated by autoradiography using 125I-labeled antigens that in the secondary response to bovine serum albumin (BSA), a considerable amount of antigen is localizing in the germinal centers (GC) of chicken spleen prior to the onset of antibody production. A similar early antigen capture, although of a lesser degree, was also noted when birds originally immunized with BSA were injected with human serum albumin (HSA) on a second occasion. Early antigen localization in GCs was scarcely demonstrable in the primary response. Since antigen capture requires specific antibodies, it was concluded that the antigen binding cells correspond with B lymphocytes of GCs formed during the primary immune response or with their descendants. On antigenic stimulus, these cells transform to antibody producing cells after one or more mitoses. GCs can therefore be regarded as memory units composed of cells committed to one and the same antigen. Cells of the thymus-system probably play a cooperative role in the antigen-induced formation of GCs.
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BACKGROUND AND PURPOSE: Moderate exercise conducted over a 4- to 8-week period enhances secondary antibody response and is mediated, in part, by endogenous opioids. Because changes in circulating levels of endogenous opioids occur after each exercise session, the researchers in this study tested the hypothesis that a shorter exercise program of 2 weeks may be sufficient to enhance secondary antibody response. Another purpose of this study was to examine the effects of a moderate exercise program completed prior to the primary immunization on the secondary antibody response in mice. SUBJECTS AND METHODS: Young (8- to 10-week-old), syngeneic, female C57BL/6 mice were randomly assigned to exercise (2 or 8 weeks) and sedentary intervention protocols. Mice were immunized against human serum albumin (HSA), and serum anti-HSA antibody levels were measured (in micrograms per milliliter) using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The secondary antibody response was comparable in mice exercising for 2 or 8 weeks and was enhanced over sedentary controls. DISCUSSION AND CONCLUSION: A moderate exercise program of 2 weeks may be sufficient to improve secondary antibody production and may be a useful strategy to enhance antibody response to vaccinations in humans. Furthermore, an exercise program that includes exercise prior to the primary immunization in addition to exercise following primary immunization may not provide additional enhancement of secondary antibody response.
The present study was conducted to determine if a selenium deficiency affects the primary and secondary humoral immune response of calves challenged with infectious bovine rhinotracheitis virus (IBRV) and to evaluate changes in glutathione peroxidase (GSH-Px) and creatine phosphokinase activities associated with selenium deficiency and viral stress. Treatments included 1) +Se (0.2 mg/kg diet) and 2) -Se (0.03 mg/kg diet). Calves were adapted to their assigned diets during an 84-d depletion period. By d 42 of the depletion period, whole-blood GSH-Px was lower for -Se calves than for +Se calves. Differences between treatments in plasma GSH-Px were observed by d 14. On d 84, Se-dependent GSH-Px activity in liver was higher in +Se calves. After depletion of -Se calves, animals in both treatments were intranasally inoculated with IBRV on d 0 and 35 of the 70-d challenge phase. Whole-blood and plasma GSH-Px increased after IBRV inoculation in +Se calves but not in Se-deficient calves. Serum IgM was higher for +Se calves throughout the challenge phase. Serum IgM increased in both treatments after primary IBRV inoculation but was unaffected by secondary challenge. Serum IgG was not affected by selenium status but increased in both treatments after secondary IBRV challenge. Serum IBRV antibody titers increased after inoculation on d 0 and 35. By d 49, IBRV antibody titers were higher for +Se calves than in Se-deficient calves. These results indicate that selenium deficiency may depress the immune response of calves challenged with a foreign pathogen.
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We have investigated the effects of interferon-gamma (IFN-gamma) administered with "G" glycoprotein of vesicular stomatitis virus (VSV), on the neutralizing antibody response. Treatment of mice or cattle with recombinant DNA-derived IFN-gamma at the time of primary immunization with "G" glycoprotein enhanced the secondary virus-neutralizing antibody response that followed a booster administration of the same antigen without IFN-gamma treatment. Enhancement was statistically significant, and occurred at relatively low doses of IFN-gamma in the absence of any additional adjuvants. Cattle treated with IFN-gamma at the time of primary immunization were also more resistant to VSV challenge than those immunized without IFN-gamma treatment. Such treatment in conjunction with primary immunization may therefore provide a practical means of enhancing protection from viral challenge without inflammatory adjuvants or boosters.
This study was conducted to determine the effect of dietary selenium (Se) and vitamin E (Vit E) on various blood characteristics and the primary and secondary humoral immune response of lambs challenged with parainfluenza3 virus (PI3 V). Treatments included: 1) +Se/+Vit E, 2) -Se/+Vit E, 3) +Se/-Vit E and 4) -Se/-Vit E. The basal diet (-Se/-Vit E) was deficient in Se and Vit E. Sodium selenite (.2 mg Se/kg diet) and alpha-tocopherol acetate (20 mg Vit E/kg diet) were added to +Se and +Vit E diets, respectively, to provide adequate levels of each according to NRC recommendations. Following a 10-wk dietary adaptation and depletion period, lambs in all treatment groups were intratracheally inoculated with PI3 V on d 0 and 35 of the 70-d study. Prior to inoculation, whole blood and plasma glutathione peroxidase (GSH-Px) activities were higher (P less than .01) for +Se lambs. Whole blood and plasma GSH-Px increased (P less than .01) after primary viral inoculation in +Se lambs but not in -Se lambs. Serum immunoglobulin M (IgM) concentrations were enhanced (P less than .05) by Se supplementation on d 14, 35 and 49 of the study. Selenium and (or) Vit E did not affect serum immunoglobulin G (IgG) levels. Serum PI3 V antibody titers increased after inoculation on d 0 and 35 in all treatment groups. Titer levels appeared to increase more substantially for +Se lambs after primary inoculation, but increases were greater (P less than .01) for +Vit E lambs after secondary challenge.(ABSTRACT TRUNCATED AT 250 WORDS)
OBJECTIVES: As interleukin (IL)-2 therapy increases CD4 cell counts in HIV infected subjects, it emerged as a candidate for the partial restoration of immune competence in this disease. METHODS: We studied the frequencies of antigen-specific T cells using single cell resolution cytokine ELISPOT assays and titers of specific antibodies before and after immunization of HIV infected subjects who were treated with HAART or HAART plus IL-2. RESULTS: Subjects seronegative to hepatitis A were vaccinated with hepatitis A antigen. In the non-IL-2 treated group, hepatitis A-specific T cells producing IL-2 and IL-4 along with specific antibodies were induced, showing that these subjects are immune competent and capable of mounting a primary immune response. Additional IL-2 treatment had no significant effect on this primary T cell response; however, booster immunizations with tetanus toxoid or the gp120 depleted HIV vaccine Remune induced higher frequencies of specific interferon (IFN)-gamma producing T cells in IL-2 treated subjects. No impact of IL-2 treatment on these secondary B cell responses was seen. CONCLUSION: Overall, our study showed that IL-2 therapy had no immune enhancing effect on the induction of a primary response, but increased the frequency of IFN-gamma producing memory cells after booster immunization.
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Adult mice react with an increased production of PFC (plaque-forming cells) against sheep erythrocytes (SE). in the primary immune response after application of BCG. Animals receiving 0,5 mg of BCG 10 days before SE show an increase in direct PFC of more than 50%. No effect was observed after injecting BCG 14 or 5 days before SE or using a dose of 0,1 mg of BCG. The results indicate that the effect of BCG on the humoral immune response is influenced by the interval between application of BCG and the SE as well as the BCG-dose. By contrast, BCG had no significant influence on the secondary humoral immune response. In a few cases the immune response seemed to be suppressed.
We have analyzed the hierarchy of epitope-specific T cell populations during a primary and a secondary CD8 T cell response. MHC-peptide tetramers were used to track the in vivo kinetics of expansion of T cell populations specific for two Kd-restricted epitopes simultaneously presented by a murine tumor cell following primary or recall immunizations. Individual syngeneic mice generated remarkably different primary CTL responses, as reflected by up to 60-fold differences in the relative contribution of each peptide-specific T cell population to the overall response. In these primary immunizations, the CTL dominance was not dictated by the respective abundance of the presented epitopes. In sharp contrast, the secondary response was systematically associated with a selective expansion of the same epitope-specific population both in vitro and in vivo. In vitro experiments indicated that the extent of expansion of each epitope-specific memory population is modulated by the epitope density. We conclude that, at least for this set of epitopes, the CTL hierarchy is not controlled by the same parameters in a primary vs a secondary response.
The variations in anti-Salmonella typhimurium antibody levels was measured in BALB/c mice which had been orally and nasally vaccinated with S. typhimurium live mutants of different lipopolysaccharide lengths. Together with the demonstration of immunological memory, the intensity of the secondary response was correlated with the length of the polysaccharide chain at intestinal and serum levels. Nasally administered antigen seemed to be at least as immunogenic as when orally administered.