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PubMed2006

Immune components (IgA, IgM, IgG, immune cells) of colostrum of Bangladeshi mothers.

BACKGROUND: Colostrum is the first defense for neonates. It is rich in immune components including immunoglobulins and viable immune cells. In the present study, human colostrum collected from 105 postpartum mothers was analyzed for its IgA, IgM, IgG levels, and peripheral immune cells. METHODS: Enzyme-linked immunosorbent assay was used to analyze the serum immunoglobulin concentrations. Immune cells were estimated by counting 200 cells. RESULTS: IgA was the dominant immunoglobulin and ranged from 2.84 to 8.69 g/L (mean 5.61 g/L). Mean IgM and IgG concentrations were 0.4 g/L (0.16-0.66 g/L) and 0.095 g/L (0.04-0.15 g/L), respectively. Neutrophil-macrophage (neu-mac) predominated in cell count (59%) followed by lymphocyte-plasma cells (lymph-plasma; 40%). The influence of maternal nutritional status, age, parity and income levels on the colostral immunological factors was studied. No significant association could be traced for immunoglobulin content, suggesting that maternal characteristics do not have any bearing on the immunoglobulin content of colostrum. Mean value of eosinophils was found to be higher among the underweight than the normal mothers (F= 3.143, r=-0.101). Maternal age was positively correlated with eosinophil (F= 3.296, r= 0.162). Concentration of neu-mac had a positive significant correlation with parity (t=-2.07, r= 0.205), while it was negatively significant for lymphocyte-plasma cells (t= 2.073, r=-0.101). However, the correlation coefficients of the immunologic parameters with other maternal characteristics were statistically insignificant. CONCLUSION: Colostrum has enough humoral and cellular elements to protect babies. Therefore, immune protection derived from breastfeeding depends on the immunoglobulin level of the colostrum as well as the amount of colostrum ingested.

Adolescent↗
PubMed1979

Genetic control of the immune response to mammalian chymotrypsins in mice. I. The immune response to high doses of bovine alpha-chymotrypsin.

The primary and secondary immune response to the antigen bovine pancreatic alpha-chymotrypsin was investigated in inbred mice. It was found that strain differences in the immune response only became apparent after secondary immunization. The genetic control of the immune response was investigated in twelve different strains of mice, F1, F2 and F1 backcross hybrids, following secondary immunization. A continuous distribution for the mean antibody responsiveness was obtained. High responsiveness was associated with both the H-2 haplotype and three non-H-2 loci. Furthermore the F1 hybrids produced a greater quantitative antibody response to chymotrypsin than either of the corresponding parental strains.

Animals↗
PubMed1987

Enkephalins and immunity. I: In vivo suppression and potentiation of humoral immune response.

BALB/c mice and Wistar rats immunized with sheep red blood cells and ovalbumin were treated intraperitoneally with different doses of methionine-enkephalin, leucine-enkephalin, and naloxone. Large doses of enkephalins (10-5 mg/kg b.w.) induced a significant decrease in hemolysin-forming cell response and production of hemagglutinating antibody. Immunosuppression induced by enkephalin was dose-dependent. In rats met-enkephalin was a more potent immunosuppressor than leu-enkephalin. Rats injected with 2.5 mg/kg b.w. of enkephalins into the lateral ventricle of the brain showed more pronounced immune suppression than did animals treated intraperitoneally with 5 mg/kg b.w. of enkephalins. These neuropeptides, and met-enkephalin in particular, exhibited a protective action against anaphylactic shock in rats sensitized to ovalbumin. In those animals, passive cutaneous anaphylaxis and elaboration of precipitating anti-ovalbumin antibody were considerably reduced. On the other hand, small doses of enkephalins stimulated humoral immune responses in the rat. Thus, it appears that enkephalins both suppress and potentiate immune responsiveness, depending on the dose used. As for naloxone, a large dose of this blocker of opioid receptors enhanced humoral immune reactions in the rat.

Adjuvants, Immunologic↗
PubMed1994

Immune response in the lungs following oral immunization with bacterial lysates of respiratory pathogens.

We have investigated the local immune response of the BALB/c mouse respiratory tract after oral immunization with a bacterial lysate of seven common respiratory pathogens. After two immunization on five consecutive days, we examined the immunoglobulin (immunoglobulin G [IgG], IgM, and IgA) secretion rates of cells isolated from the lungs and compared them with those of spleen cells of orally immunized and nonimmunized animals by using a new test system based on time-resolved fluorescence. The procedure followed the principle of the classical ELISPOT test with nitrocellulose-bottomed microtiter plates, but europium (Eu3+)-linked streptavidin rather than enzyme-conjugated streptavidin was used, with the advantage of quantifying secreted immunoglobulins instead of detecting single antibody-secreting cells. Lymphocytes isolated from the lungs of treated animals revealed significant increases in total and antigen-specific IgA synthesis compared with the rates of the controls, whereas IgG and IgM production rates showed no remarkable differences. In addition, the sera of treated mice revealed higher antigen-specific IgA titers but not increased IgM and IgG levels. We conclude that priming the gut-associated lymphoid tissue with bacterial antigens of pneumotropic microorganisms can elicit an enhanced IgA response in a distant mucosal effector site, such as the respiratory tract, according to the concept of a common mucosa-associated immune system.

Adjuvants, Immunologic↗
PubMed1982

Characterization of the immune response in subcutaneous chambers of guinea pigs immunized with a ribosomal preparation from Neisseria gonorrhoeae.

Immunization of guinea pigs with ribosomal preparations has been previously shown to be protective against chamber infection with Neisseria gonorrhoeae, and this protection could be correlated with the presence of serum bactericidal antibody. Analysis of the chamber fluids from ribosome-immunized and nonimmunized guinea pigs has demonstrated that the chamber fluid may accurately reflect serum antibody levels and proteins. At least one major population of antiribosomal antibodies is present in both immune serum and chamber fluid as revealed by lines of identity between these components. Antibody- and complement-mediated bactericidal assays revealed that matched chamber fluids and sera from immune animals had comparable bactericidal titers. These results suggest that the antibody-complement-mediated bactericidal activity plays a major role in the protection against N. gonorrhoeae infection. Protection could not be explained on the basis of the cellular components of the inflammatory response since both immune and nonimmune chambers had comparable increases in polymorphonuclear neutrophils, monocytes, and lymphocytes after challenge.

Animals↗
PubMed1986

Simultaneous administration of diphtheria-tetanus-pertussis-polio and hepatitis B vaccines in a simplified immunization program: immune response to diphtheria toxoid, tetanus toxoid, pertussis, and hepatitis B surface antigen.

We studied the interactions of hepatitis B vaccine with other vaccines used in the World Health Organization expanded programs of immunization. Three groups of Senegalese children were vaccinated with hepatitis B vaccine (HB) alone, diphtheria-tetanus-pertussis (DTP)-polio vaccine alone, or a combination of hepatitis B vaccine and DTP-polio vaccines simultaneously. The immune responses to HBsAg, tetanus toxoid, diphtheria toxoid, and pertussis were measured after one and two vaccinations at 6-month intervals. The immune responses to the combination of HB vaccine and DTP-polio vaccines were similar to the immune responses observed after administration of each vaccine alone. In addition, no adverse reactions were noted. These experimental trials also demonstrated that with a DTP-polio vaccine containing 30Lf of tetanus and diphtheria toxoids, two doses given at 6-month intervals are sufficient to provide a satisfactory immune response. In the case of pertussis and HB vaccines; however, a third dose is necessary.

Antibodies, Bacterial↗
PubMed1990

Kinetics of Cryptosporidium parvum sporozoite neutralization by monoclonal antibodies, immune bovine serum, and immune bovine colostrum.

Monoclonal antibodies, immune bovine serum, and immune bovine colostral whey neutralized infectivity of Cryptosporidium parvum sporozoites for mice in a time-dependent manner. Immune colostral whey neutralized sporozoites more rapidly and completely than immune serum, monoclonal antibody (MAb) 18.44, or a combination of MAb 18.44 and MAb 17.41. Mice were partially protected against oral challenge with C. parvum oocytes when treated with immune colostral whey, MAb 17.41, or a combination of MAb 17.41 and MAb 18.44.

Animals↗
PubMed1994

Pulmonary immunity to Pseudomonas aeruginosa in intestinally immunized rats roles of alveolar macrophages, tumor necrosis factor alpha, and interleukin-1 alpha.

The aims of this study were to assess the role played by alveolar macrophages, tumor necrosis factor alpha (TNF-alpha), and interleukin-1 alpha (IL-1 alpha) in pulmonary immunity against Pseudomonas aeruginosa in animals that have been immunized via the gut-associated lymphoid tissue. Following intra-Peyer's patch immunization and subsequent intratracheal challenge with live bacteria, significantly enhanced bacterial clearance from the lungs correlated with an increase in bronchoalveolar neutrophils, increased recruitment and phagocytic activity of alveolar macrophages, and accelerated production of TNF-alpha in the bronchoalveolar space, while levels of IL-1 alpha remained low. Administration of recombinant TNF-alpha in physiological concentrations did not affect the proliferation of P. aeruginosa in vitro, but when given intratracheally to rats at the time of infection, recombinant TNF-alpha significantly increased bacterial clearance from the lungs. In these animals, phagocytic activity of bronchoalveolar neutrophils was enhanced, while the recruitment of alveolar macrophages and neutrophils remained unchanged. In acutely infected nonimmune animals, bronchoalveolar concentrations of soluble IL-1 alpha and TNF-alpha increased until the time of death. Levels of prostaglandin E2 and thromboxane B2 were similar in each experimental group. These results indicate that infection in immune animals enhanced both recruitment and phagocytic activity of alveolar macrophages as well as induced an accelerated production of TNF-alpha. In immune challenged animals, this cytokine enhanced the phagocytic activity of neutrophils and improved bacterial clearance from the lung. Levels of soluble IL-1 alpha and TNF-alpha in nonimmune rats increased consistently following infection until the time of death, thus implicating these cytokines in the pathogenesis of acute P. aeruginosa pneumonia.

Animals↗
PubMed1999

A controlled clinical study of the effect of nasal immunization with a Streptococcus mutans antigen alone or incorporated into liposomes on induction of immune responses.

Recent attention to mucosal immunization strategies has been focused on the nasal route for vaccine delivery. This study was designed to determine the effectiveness of a liposome-protein vaccine compared to that of a protein-only vaccine in inducing immune responses in humans. Healthy subjects were randomly assigned to two groups and immunized intranasally with a crude antigen preparation rich in glucosyltransferase (C-GTF) from Streptococcus mutans, alone or in liposomes. Parotid saliva, nasal wash, and serum were collected prior to and at weekly intervals following immunization and were analyzed for anti-C-GTF activity by enzyme-linked immunosorbent assay. The levels of immunoglobulin A (IgA) anti-C-GTF activity in the nasal wash from both groups after immunization increased to a mean peak of fivefold over the baseline level on day 28. Salivary IgA anti-C-GTF responses were induced to a lesser extent. IgG and IgA anti-C-GTF responses in serum were detected on day 14. The IgA responses were predominantly of the IgA1 subclass. These results show that C-GTF vaccines were more effective in inducing a local secretory IgA antibody response than a salivary or serum response when they were given intranasally. The IgA1 anti-C-GTF response in nasal wash samples for liposomal antigen versus antigen only was the only response which was significantly different (P < 0.04). This suggests that the form of the antigen affects the magnitude of the local mucosal response but not that of a disseminated response. These results provide evidence for the effective use of a nasal protein vaccine in humans for the induction of mucosal and systemic responses.

Administration, Intranasal↗
PubMed2001

Intranasal immunization with recombinant Ascaris suum 14-kilodalton antigen coupled with cholera toxin B subunit induces protective immunity to A. suum infection in mice.

Animals can be rendered immune to Ascaris parasites by immunization with infectious-stage larvae. The specific parasite gene products that mediate protective responses in ascariasis are unknown. We have identified a cDNA encoding Ascaris suum 14-kDa antigen (As14) and evaluated the vaccinal effect of the Escherichia coli-expressed recombinant protein (rAs14). GenBank analysis showed that As14 has low similarity at the amino acid level to a Caenorhabditis elegans gene product and to antigens of the filarial nematodes but not to other known proteins. In addition, As14 homologues were found to be expressed in human and dog roundworms. In mice that received intranasal administration of rAs14 coupled with cholera toxin B subunit (rAs14-CTB), there was a 64% reduction of recovery of larvae compared with that in the nontreated group. The vaccinated mice showed a significant increase in the total serum immunoglobulin G (IgG) levels and the mucosal IgA responses. Elevation of the rAs14-specific IgE response was also seen. Measurement of the IgG subclasses showed a higher level of IgG1 and a lower level of IgG2a antibody response in the sera of the immunized mice, suggesting that protection was associated with a type II immune response. As14 is the first protective antigen against A. suum infection to be identified. Our immunization trial results in laboratory animals suggest the possibility of developing a mucosal vaccine for parasitic diseases caused by ascarid nematodes.

Administration, Intranasal↗
PubMed2002

Herpes simplex virus vectors elicit durable immune responses in the presence of preexisting host immunity.

Herpes simplex virus (HSV) recombinants are being developed as vaccine vectors for the expression of heterologous antigens. There is concern, however, that preexisting HSV immunity may decrease their effectiveness. We have addressed this issue in an animal model. Immunized mice were inoculated with a replication-defective HSV-1 vector that expressed the Escherichia coli beta-galactosidase protein as a model antigen. We assessed vector efficacy by analyzing the immunoglobulin G (IgG) antibody response and cellular proliferative response directed against beta-galactosidase. We report that the ability of the vector to induce antibody or proliferative responses was not diminished by preexisting immunity to HSV. Of further note, the anti-HSV and anti-beta-galactosidase IgG responses following vector administration were extremely durable in both immunized and naive mice. These results indicate that the ability of a replication-defective HSV-derived vaccine vector to elicit long-lived immune responses in mice is not impaired by prior HSV exposure.

Animals↗
PubMed2003

Induction of protective immune responses against R5 human immunodeficiency virus type 1 (HIV-1) infection in hu-PBL-SCID mice by intrasplenic immunization with HIV-1-pulsed dendritic cells: possible involvement of a novel factor of human CD4(+) T-cell origin.

The potential of a dendritic cell (DC)-based vaccine against human immunodeficiency virus type 1 (HIV-1) infection in humans was explored with SCID mice reconstituted with human peripheral blood mononuclear cells (PBMC). HIV-1-negative normal human PBMC were transplanted directly into the spleens of SCID mice (hu-PBL-SCID-spl mice) together with autologous mature DCs pulsed with either inactivated HIV-1 (strain R5 or X4) or ovalbumin (OVA), followed by a booster injection 5 days later with autologous DCs pulsed with the same respective antigens. Five days later, these mice were challenged intraperitoneally with R5 HIV-1(JR-CSF). Analysis of infection at 7 days postinfection showed that the DC-HIV-1-immunized hu-PBL-SCID-spl mice, irrespective of the HIV-1 isolate used for immunization, were protected against HIV-1 infection. In contrast, none of the DC-OVA-immunized mice were protected. Sera from the DC-HIV-1- but not the DC-OVA-immunized mice inhibited the in vitro infection of activated PBMC and macrophages with R5, but not X4, HIV-1. Upon restimulation with HIV-1 in vitro, the human CD4(+) T cells derived from the DC-HIV-1-immunized mice produced a similar R5 HIV-1 suppressor factor. Neutralizing antibodies against human RANTES, MIP-1alpha, MIP-1beta, alpha interferon (IFN-alpha), IFN-beta, IFN-gamma, interleukin-4 (IL-4), IL-10, IL-13, IL-16, MCP-1, MCP-3, tumor necrosis factor alpha (TNF-alpha), or TNF-beta failed to reverse the HIV-1-suppressive activity. These results show that inactivated HIV-1-pulsed autologous DCs can stimulate splenic resident human CD4(+) T cells in hu-PBL-SCID-spl mice to produce a yet-to-be-defined, novel soluble factor(s) with protective properties against R5 HIV-1 infection.

AIDS Vaccines↗
PubMed1976

DNA synthesis in vitro by cells from mice immunized with picryl chloride: effect of injection of immune cells.

Mice were immunized with picryl chloride and the regional nodes taken at various times afterwards. These cells spontanesouly synthesized DNA in vitro as measured by thymidine incorporation over an 18-hour period and the peak incorporation occurred when the cells were takin on day 3. When the mice were injected with cells taken 5 days after immunization with picryl chloride and then immunized, there was a depression of the spontaneous DNA synthesis in vitro. This was absent on day 2, most marked on day 3 and still present on day 4. Cells from donors immunized with 4-ethoxymethylene-2-phenyloxazolone had a smaller but definite effect. Attempts to reproduce the phenomenon by in vitro mixtures of cells taken at various times after immunization in vivo were unsuccessful.

Animals↗
PubMed1983

IgA isotype restriction in the mucosal but not in the extramucosal immune response after oral immunizations with cholera toxin or cholera B subunit.

Intestinal mucosal as well as extramucosal antibody responses were studied in mice after peroral immunizations with cholera toxin or cholera B subunit. The immunizations with cholera toxin gave rise to a marked response with antitoxin-secreting cells (PFC) in Peyer's patches (PP), mesenteric lymph nodes (MLN) and spleen showing isotype distribution of IgG greater than IgA greater than IgM and with PFC kinetics in MLN and spleen that suggested migration of cells from PP after peroral administration rather than cells stimulated in situ by adsorbed antigen. Highest numbers of PFC were obtained after 2 immunizations, and further administrations resulted in a decrease in the PFC response in MLN and spleen, while the PP responsiveness was relatively unchanged, and interestingly, protective immunity and IgA-dominated antitoxin titers in intestinal washings increased markedly by the additional boosters. Animals immunized with cholera B subunit, which lacks the adenylate cyclase-stimulating capacity of cholera toxin, showed similar PFC responses in extramucosal organs as those receiving cholera toxin but were poorly protected and had correspondingly lower IgA antitoxin titers in intestinal washings. These results suggest that the mucosal IgA antitoxin predominance is mainly due to regulatory mechanisms operating on the end-stage differentiation of the committed B cells in lamina propria and that this differentiation, as judged from the different results with cholera toxin and its B subunit, might be influenced by cyclic AMP.

Animals↗
PubMed1977

Clinical relevance of circulating immune complexes in human leukemia. Association in acute leukemia of the presence of immune complexes with unfavorable prognosis.

The occurrence of circulating immune complexes was investigated in 467 serum samples from 230 leukemia patients using the [(125)I]Clq-binding test. There was an increased serum [(125)I]Clq-binding activity in 40% of patients with acute myeloid leukemia, 23% with acute lymphatic leukemia, 46% in blastic crisis of chronic myeloid leukemia, 12% with chronic lymphatic leukemia, and 13% with chronic myeloid leukemia. In 48 patients, serum was also tested for soluble immune complexes by the Raji cell radioassay; the correlation between results of the two tests was significant. The Clq-binding material had properties identical with those of immune complexes. It sedimented as 14-28s material on sucrose density gradient. It contained IgG which could be dissociated at acid pH. Its Clq-binding properties could be removed after passage through anti-IgG immuno-absorbant or after a mild reduction-alkylation treatment, but were not sensitive to deoxyribonuclease treatment. Circulating immune complexes were found most commonly during the blastic stage of leukemia.Remission took place in 75.4% of patients with no detectable circulating immune complexes at the onset of acute leukemia, but in only 32.7% of those with detected complexes during this period. Median survival times of the former group of patients were more than 18 mo in acute myeloid leukemia and acute lymphatic leukemia and more than 8(1/2) mo in blastic crisis of chronic myeloid leukemia. The corresponding median survival times in the latter patient group were 64, 135, and 90 days. These findings were unrelated to prognostic features already known.

Adolescent↗
PubMed1995

Immune and non-immune actions of interferon-beta-Ib on primary human neural cells.

Systemic interferon-beta-Ib (IFN-beta-Ib) reduces the frequency of clinical exacerbations and the number of magnetic resonance imaging (MRI)-defined lesions in patients with relapsing-remitting MS. The basis for this clinical effect is not understood. While IFN-beta-Ib has been demonstrated to have antiproliferative and immunomodulatory effects on the systemic immune system, its actions on neural cells could also contribute to its therapeutic efficacy. In this study, we have examined possible immune and non-immune effects of IFN-beta-Ib on CNS-derived primary human cells. With respect to immune-related effects, application of IFN-beta-Ib did not decrease basal expression of HLA-DR on astrocytes or microglia, and it reduced the IFN-gamma-enhanced HLA-DR expression on adult human astrocytes only at high concentrations (1000 IU ml-1); IFN-beta-Ib at all concentrations tested did not reduce the IFN-gamma-enhanced HLA-DR expression by fetal astrocytes or adult microglial cells. In contrast, but in correspondence with the literature, the IFN-gamma-enhanced HLA-DR expression on a glioma cell line was attenuated by IFN-beta-Ib in a dose-dependent manner. With respect to non-immune effects, the number of adult human oligodendrocytes and their state of morphological differentiation were not affected by IFN-beta-Ib. Proliferation of the mitotically active fetal human astrocytes, however, was reduced by IFN-beta-Ib treatment. Lactate dehydrogenase assays revealed that IFN-beta-Ib was not toxic to neural cells, including adult oligodendrocytes and fetal human neurons. We conclude that IFN-beta-Ib lacks efficacy in down-regulating HLA-DR expression by primary human neural cells and that regulation of MHC class II antigens is unlikely to be a mechanism for its beneficial effect in MS. Finally, the lack of toxicity of IFN-beta-Ib on human neural cells is important for a drug that will probably be used widely.

Cell Differentiation↗
PubMedDate not supplied

Humoral immune response kinetics in Philander opossum and Didelphis marsupialis infected and immunized by Trypanosoma cruzi employing an immunofluorescence antibody test.

Philander opossum and Didelphis marsupialis considered the most ancient mammals and an evolutionary success, maintain parasitism by Trypanosoma cruzi without developing any apparent disease or important tissue lesion. In order to elucidate this well-balanced interaction, we decided to compare the humoral immune response kinetics of the two didelphids naturally and experimentally infected with T. cruzi and immunized by different schedules of parasite antigens, employing an indirect fluorescence antibody test (IFAT). Both didelphids responded with high serological titers to different immunization routes, while the earliest response occurred with the intradermic route. Serological titers of naturally infected P. opossum showed a significant individual variation, while those of D. marsupialis remained stable during the entire follow-up period. The serological titers of the experimentally infected animals varied according to the inoculated strain. Our data suggest that (1) IFAT was sensitive for follow-up of P. opossum in natural and experimental T. cruzi infections; (2) both P. opossum and D. marsupialis are able to mount an efficient humoral immune response as compared to placental mammals; (3) experimentally infected P. opossum and D. marsupialis present distinct patterns of infection, depending on the subpopulation of T. cruzi, (4) the differences observed in the humoral immune responses between P. opossum and D. marsupialis, probably, reflect distinct strategies selected by these animals during their coevolution with T. cruzi.

Animals↗
PubMed1999

Immune surveillance and antigen conformation determines humoral immune response to the prion protein immunogen.

Transmissible spongiform encephalopathies (TSE) are progressive degenerative disorders of the central nervous system. PrP(Sc) is a TSE-specific marker derived from the host-encoded glycoprotein, PrPc. The generation of antibodies to PrP plays an important role in the diagnosis of these diseases. In this study the role of the PrP immunogen and the species being immunized was examined in relation to specific epitopes. Various mammals (mice, hamsters, rabbits and PrP null mice) were immunized with formic acid-treated PrP(Sc) isolated from mice, hamsters and sheep. Both the species being immunized and the source of immunogen played an important role in the antibody response. Response to a limited number of linear epitopes was seen among the various immunized animals. One region in the C-terminal portion of PrP appeared highly immunogenic in all species. Comparison of immunoreactivity and the pepscan-defined linear epitope sites suggests both linear and conformational directed responses in many of the animals. Information on the forces directing immune responses to PrP will lead to a better understanding of host-PrP interactions. It will also assist in the development of new strategies for generating additional tools for immunodiagnosis.

Amino Acid Sequence↗