Carrier-specific unresponsiveness in reaginic antibody formation. I. Induction of helper cell tolerance in rats.

Rats pretreated with 10 mg soluble sheep gamma globulin (soluble SGG or SGGSo) showed a marked reduction in IgE anti-TNP antibody upon challenge with TNP-SGG in alum. This effect was found to be carrier-specific since SGGSo tolerant rats gave normal IgE anti-TNP responses when challenged with TNP-KLH. Carrier tolerance persisted when a secondary challenge with TNP-SGG was given. The degree of tolerance induction was shown to be tolerogen dose-dependent. As expected, IgE anti-SGG responses were also reduced in this system by pretreatment with SGGSo. These results indicate that carrier-specific helper cells for IgE antibody responses can be rendered functionally unresponsive. However, in contrast to the long duration of carrier-specific tolerance for IgM and IgG responses, IgE tolerance in this system appeared to be only short-lived. This difference suggests that IgE helper and/or suppressor T cells may represent a separate subclass from those involved in IgM and IgG responses.     

Induction of IgE-secreting cells and IgE isotype-specific suppressor T cells in the respiratory lymph nodes of rats in response to antigen inhalation

Repeated exposure of high-IgE-responder Brown Norway (BN) rats to an aerosol of ovalbumin (OVA) once weekly triggered progressively increasing levels of OVA-specific IgG in serum. In contrast, responses in the IgE class were transient, declining from peak titers during the third week to background levels by Week 5, despite continuing aerosol exposure. Subsequent parenteral challenge of these animals revealed a state of antigen- and IgE isotype-specific tolerance. Adoptive transfer of splenocytes or pooled respiratory tract lymph node (RTLN) cells from aerosol-exposed animals to naive rats abrogated subsequent OVA-specific primary IgE responses in the recipients, but did not affect specific IgG responses, and kinetic studies indicated that these suppressor cells arose first in the RTLN. Transfer studies employing individual lymph node groups which constituted the RTLN pool pinpointed the superficial cervical nodes, which drain the uppermost portion of the respiratory tract, as the major source of suppressor cells. Fractionation of cell populations before adoptive transfer employing monoclonal antibodies directed against T-cell markers, defined a population of suppressor cells generated by aerosol exposure which expressed both the W3/13 (pan T-cell) and OX8 (cytotoxic/suppressor T-cell) antigens, but which was negative for the W3/25 (helper T-cell) marker. Analysis of the IgE and IgG responses induced by OVA inhalation was performed employing the ELISA plaque technique, recently developed in this laboratory. These studies revealed the parathymic and posterior mediastinal nodes draining the lower lung, as the major sites of specific IgE and IgG production; smaller numbers of OVA-specific IgG-secreting cells (but none secreting specific IgE) were detected in the nodes draining the upper respiratory tract, while antibody secretion outside the respiratory tract was restricted to comparatively few cells in the spleen. The ELISA plaque assay was also employed to enumerate total numbers of cells secreting the IgE isotype in aerosol-exposed and control rats, employing samples from 10 different lymphoid organs. Approximately 50% of the IgE-secreting cells in these animals were localized in RTLN, as opposed to 25% in gut-associated lymphoid tissues. These data are discussed in relation to the pivotal role of respiratory-tract associated lymphoid tissues in regulation of IgE responses to aeroallergens.     

Thymic control of secretory antibody responses in the rat.

The effect of neonatal thymectomy on salivary and serum antibody responses was studied in rats. Local immunization of thymectomized rats with a T-dependent antigen (DNPBGG) elicited negligible amounts of IgA anti-DNP antibody in saliva. In contrast, both normal and sham-thymectomized animals demonstrated substantial levels of salivary IgA antibody. All thymectomized rats locally injected with a T-independent antigen (DNP-Lys-Ficoll) exhibited salivary IgA antibody production. Salivary IgG antibodies were somewhat decreased in thymectomized rats injected with either antigen; however, the final effect of T cell deprivation on IgG synthesis was not as pronounced as on IgA synthesis. Serum IgA antibody was induced in control rats injected with DNPBGG, whereas this Ig class of antibody was absent in thymectomized rats. The results suggest that thymus-derived cells exert a regulatory influence on both serum and secretory IgA responses to antigens.     

Effect of antigen load on development of milk antibodies in infants allergic to milk.

The phenomenon that large amounts of antigen, such as are absorbed during the neonatal period, suppress the IgE response while low-dose exposure enhances it was investigated by analysing the antibody responses of infants allergic to milk according to their degree of exposure to cows''-milk protein. IgG, IgA, and IgM milk-specific antibodies in these infants and in age-matched controls were measured by enzyme-linked immunosorbent assay. Milk-specific IgE and total IgE were also measured. Children allergic to milk who were breast fed and had had minimal exposure to cows'' milk had decreased titres of IgG, IgA, and IgM milk antibodies compared with infants allergic to milk who, before diagnosis, had been fed substantial volumes of cows'' milk. Conversely, the infants with minimal exposure to cows'' milk showed vastly increased total and milk-specific IgE antibodies compared with the milk-fed infants. These results support recent experimental evidence that appreciable amounts of allergen suppress rather than stimulate IgE production. These data may have important implications for dietary regimens in at-risk infants. The results also lend support for the role of IgE in immediate-type allergic reactions and suggest that various non-IgE immune mechanisms play a part in the aetiology of intolerance to cows''-milk protein in some children.     

Carrier-specific unresponsiveness in reaginic antibody formation. II. Suppression of hapten and carrier responsiveness in presensitized rats.

By inducing carrier-specific tolerance to sheep γ-globulin (SGG) in rats challenged with TNP-SGG in alum, it has been possible to study the effect of helper T-cell Unresponsiveness on IgE anti-TNP antibody formation. Rats primed to either the carrier (SGG) or the hapten (TNP as TNP-KLH) were treated with a single high dose (10 mg) of soluble SGG resulting in a suppression of both IgE anti-TNP and anti-SGG antibody which was maintained following a normally immunogenic secondary challenge with TNP-SGG in alum. This suppression was relatively long lasting, with no detectable IgE responsiveness to hapten or carrier observed for up to 8 weeks after tolerance induction. Suppressed animals were able to respond to the hapten when challenged with TNP-KLH, indicating that the induced effect did not directly involve the IgE antibody producing cells, but rather the carrier-specific helper cells. These results parallel our previous findings for IgM and IgG responses in a similar system. Such relatively long lasting and easily induced suppression in IgE antibody formation to specific protein antigens in primed animals may eventually provide a clinically useful means of allergic desensitization to large protein allergens.     

Oral tolerance revisited: prior oral tolerization abrogates cholera toxin-induced mucosal IgA responses

Oral delivery of a large dose or prolonged feeding of protein Ags induce systemic unresponsiveness most often characterized as reduced IgG and IgE Ab- and Ag-specific CD4(+) T cell responses. It remains controversial whether oral tolerance extends to diminished mucosal IgA responses in the gastrointestinal tract. To address this issue, mice were given a high oral dose of OVA or PBS and then orally immunized with OVA and cholera toxin as mucosal adjuvant, and both systemic and mucosal immune responses were assessed. OVA-specific serum IgG and IgA and mucosal IgA Ab levels were markedly reduced in mice given OVA orally compared with mice fed PBS. Furthermore, when OVA-specific Ab-forming cells (AFCs) in both systemic and mucosa-associated tissues were examined, IgG AFCs in the spleen and IgA AFCs in the gastrointestinal tract lamina propria of mice given OVA orally were dramatically decreased. Furthermore, marked reductions in OVA-specific CD4(+) T cell proliferative and cytokine responses in spleen and Peyer's patches were seen in mice given oral OVA but were unaffected in PBS-fed mice. We conclude that high oral doses of protein induce both mucosal and systemic unresponsiveness and that use of mucosal adjuvants that induce both parenteral and mucosal immunity may be a better way to assess oral tolerance.     

Glucocorticoid regulation of the humoral immune system. I. In vivo effects of dexamethasone on IgA and IgG in serum and at mucosal surfaces

The present studies were undertaken to determine whether glucocorticoids influence the levels of Ig in serum, saliva, and vaginal secretions. When measured by RIA, IgA levels in serum were elevated when increasing doses of dexamethasone, a potent synthetic glucocorticoid, were administered to intact- and adrenalectomized-ovariectomized rats. In contrast, IgA levels decreased in saliva and vaginal secretions over the same dose range. Time course studies indicated that the decline in salivary IgA, observed at 24 h after a single injection of dexamethasone, preceded a rise in serum IgA detected at 24 h after the second hormone treatment. Both responses were maximal at day 2 and did not change with further hormone exposure. After immunization and boosting with SRBC at two mucosal sites (intestinal Peyer's patch and uterine lumen), dexamethasone increased anti-SRBC IgA antibody levels in serum and reduced their presence in vaginal secretions. In contrast, anti-SRBC IgG-antibody levels in serum and vaginal secretions were reduced with hormone treatment. In the absence of hormone treatment, pooled sera from nonimmunized animals, when analyzed by HPLC, contained polymeric and dimeric IgA that was present in roughly equal proportion. In response to dexamethasone, polymeric IgA increased to a greater extent than did monomeric IgA. In summary, these studies demonstrate that dexamethasone alters the levels of IgA as well as specifically directed IgA and IgG antibodies in secretions and serum. Further, it suggests that glucocorticoid controlled IgA increases in serum and decreases in vaginal and salivary secretions may be due, in part, to a redistribution of polymeric IgA from mucosal surfaces to serum.     

Rotavirus vaccine administered parenterally induces protective immunity.

We performed experiments to determine whether parenteral immunization with SA11 rotavirus can induce active protective immunity in a rabbit model of rotavirus infection. After one or two intramuscular injections of 1 ml of live or formalin-inactivated SA11 virus, we evaluated the mucosal and serologic immune response and protection from challenge with a high dose of live, virulent rabbit (Ala) rotavirus. Inactivated SA11 virus preparations, evaluated by enzyme-linked immunosorbent assay (ELISA) with a panel of VP4- and VP7-specific neutralizing and nonneutralizing monoclonal antibodies, did not show a loss of epitopes from the inactivation procedure compared with live virus. Administration of two doses of vaccine, one at zero days postvaccination (DPV) and a booster shot at 49 DPV, followed by challenge at 71 DPV with 3.5 x 10(5) PFU of Ala virus resulted in protection from challenge. None of the two-dose virus-vaccinated rabbits shed virus after challenge, while virus shedding was detected in all control rabbits (P = 0.001, Fisher's exact two-tailed test). Differences in total serum immunoglobulin (Ig) antirotavirus ELISA titers (P < 0.05, Wilcoxon's rank sum test) were observed between groups vaccinated with virus in aluminum phosphate or Freund's adjuvant but not between groups vaccinated with live or inactivated virus in either adjuvant. All rabbits given two doses of vaccine had detectable antirotavirus intestinal antibody of the IgG, but not IgA, isotype. After challenge, fourfold or greater increases in intestinal IgG antibody responses were observed in three rabbits, whereas all controls and all but one virus-vaccinated rabbit had an intestinal IgA antibody response. In contrast, vaccination of rabbits with one dose of SA11 followed by challenge at 21 DPV did not protect from challenge; no difference in the mean number of days of virus shedding between any of the vaccinated groups and controls was observed. A serologic, but not a mucosal, antibody response was observed after the one-dose vaccination regimen. Differences in serologic antibody titers were not observed between any of the one-dose virus-vaccinated groups. These data indicate that parenteral vaccination with two, but not one, doses of rotavirus in either Freund's adjuvant or aluminum phosphate can induce active protection from challenge.(ABSTRACT TRUNCATED AT 400 WORDS)     

Assessment of the diagnostic value of specific anti-<Emphasis Type="Italic">Toxocara</Emphasis> IgA in Slovakian patients suspected to have toxocarosis

Human toxocarosis is one of the most widespread and prevalent helminthic zoonosis in many countries, including Slovakia. The aim was to evaluate the usefulness of IgA anti-Toxocara antibody detection in the serodiagnosis of toxocarosis. The levels of specific IgA antibodies were determined by excretory-secretory (ES)-enzyme-linked immunosorbent assay (ELISA). The IgA seropositivity in IgG anti-Toxocara seropositive patients (n?=?52) was 32.7% and found to be highest in the oldest age groups (P?=?0.026). The presence of IgA in suspected patients for toxocarosis were evaluated in respect to some characteristics of examined persons. Substantially higher IgA seropositivity was detected in patients with increased total IgE (44.8%) than in subjects with a normal level of IgE (17.4%; P?=?0.036). No associations (P?>?0.05) were found between IgA seropositivity and sex, level of specific IgG antibodies, avidity of IgG, eosinophilia, domicile, geophagia, traveling abroad, dog/cat ownership, or clinical symptoms. The IgA-ELISA showed sensitivity of 57.1% and specificity of 100%. Mild correlations (r?=?0.302, r?=?0.305, r?=???0.409) were observed between the levels of anti-Toxocara IgA antibodies and age, the amounts of eosinophils and IgA antibody levels, the amounts of eosinophils, and the values of IgG avidity, respectively. The presence of anti-Toxocara IgA may facilitate the diagnosis of toxocarosis and may well be useful for the determination of acute Toxocara infection. Moreover, this test should be accompanied by other immunological markers of examined patients (e.g., increased total IgE, eosinophilia, and low-avidity IgG antibodies).     

Differential recognition of oral indigenous bacteria by salivary immunoglobulins A and G

Assuming that salivary immunity to indigenous microorganisms could develop, we assessed antibacterial reactivities of natural salivary antibodies in specific pathogen-free inbred mice. An ELISA was set up, using whole bacterial cells, to map reactivities of salivary IgA and IgG which accounted respectively for 91% and 8.7% of salivary Ig's in the BALB/c mouse. Representative strains of seven species from three genera (Lactobacilli, Staphylococci, and Streptococci), including major and minor components of the murine oral flora (38, 43, and 8%, respectively), were used to determine the presence and level of specific antibodies in individual saliva. It was verified that naturally occurring IgA antibodies can display diverse antibacterial reactivities. A characteristic profile emerged for salivary IgA where antibodies to Streptococcus faecalis predominate. Natural salivary IgG antibodies did not show the same reactivity pattern as IgA, anti-Lactobacilli and anti-Staphylococci reactivities being much less frequent in the salivary IgG repertoire. However, antibodies to S. faecalis occurred at the same high frequency for both isotypes (62-70% of the samples). Besides being species-specific, antibacterial reactivities were also found to be strain-specific. Broad variations in antibacterial titers were detected among individual mice under standardized experimental conditions. Present data thus suggest that the dynamics of salivary antibody production in the mouse reflect a differential natural sensitization of the secretory (IgA) versus the systemic (IgG) immune systems by distinct populations of indigenous bacteria.     

Anti-Rhinosporidial Antibody Levels in Patients with Rhinosporidiosis and in Asymptomatic Persons,in Sri Lanka

The only report hitherto, from India in 1982, on anti-rhinosporidial antibody levels in patients with rhinosporidiosis recorded that antibody was not detected in Indian patients. The present report describes the use of the dot-ELISA assay of serum anti-rhinosporidial IgG, IgM and IgA and salivary sIgA in patients with diverse clinical presentations, in rural asymptomatic persons who had bathed in ground waters that probably harboured the causative pathogen, Rhinosporidium seeberi, and in laboratory persons who were exposed to R. seeberi. Ultrasonic extracts of purified endospores and sporangia of R. seeberi were used as antigen. The geometric mean (reciprocal) titres of serum antibody detected in patients were IgM 142.1, IgG 178.5, IgA 84.6, with ranges of 0-640, 30-960 and 0-160 respectively, salivary sIgA titres ranged from 0 to 18 with a mean of 4.6. The levels of antibody had no correlation with the site, the number of sporangia, duration and recurrence of the disease. Asymptomatic persons from the same endemic area as patients showed mean titres of IgM 89.6, IgG 69.1, IgA 95.5, with salivary sIgA titres of 3.1. Asymptomatic personnel who had been working in a laboratory where rhiniosporidial work was being done, showed mean titres of 169.6 IgM, 62.8 IgG, and 6.5 salivary sIgA. These results indicate that an anti-rhinosporidial antibody response occurs in rhinosporidial patients, as well as in asymptomatic persons who were exposed to R. seeberi in the environment. Anti-R. seeberi antibody does not appear to be protective in rhinosporidiosis since appreciable titres were present in patients with recurrent, single, multiple or disseminated lesions of long duration.     

Immunologic tolerance to allergenic protein determinants: properties of tolerance induced in mice treated with conjugates of protein and a synthetic copolymer of D-glutamic acid and D-lysine (D-GL).

Conjugates of proteins and the synthetic copolymer of D-glutamic acid and D-lysine (protein-D-GL) reproducibly induce significant unresponsiveness to the protein antigens in experimental mice. Proteins studied include ovalbumin and antigen E of ragweed extract, the major allergen of ragweed pollen. The unresponsive state 1) can be induced in both unsensitized and previously sensitized experimental animals, 2) is selectively confined to responses of the IgE antibody class, 3) is long lasting, and 4) is highly antigen specific. IgE antibody responses can also be suppressed by administering comparable doses of unconjugated protein alone; however, the unresponsive state induced in this manner is only transient and rebound production of IgE antibody is often observed. Results from the studies of the cellular basis of the protein-D-GL induced unresponsiveness demonstrate that 1) protein-D-GL conjugates do not induce unresponsiveness at the level of protein-specific B cells, 2) tolerance is not induced by virtue of a detectable antigen-specific suppressor T cell mechanism, 3) tolerance is most probably induced in the antigen-specific helper T cell populations. The significant IgE-selective and antigen-specific tolerogenic activity of protein-D-GL conjugates make these compounds potential candidates for use as therapeutic agents in the treatment of IgE-mediated human allergic disorders induced by protein allergens.     

IL-4-dependent IgE switch in membrane IgA-positive human B cells

IgE responses by human B cells, separated according to membrane Ig classes, were analyzed in a clonal assay using EL-4 thymoma cells as helper cells, T cell supernatant, and rIL-4. In cultures seeded by means of the autoclone apparatus of the FACS, IgE responses were generated frequently by either IgM (mu+/gamma-alpha-) or IgA (alpha +/mu-)-positive B cells (16 and 14% of the Ig producing wells, respectively), but rarely by IgG (gamma +/mu-)-positive B cells (1.3% of Ig producing wells). The total amounts of Ig secreted by IgM-, IgG-, or IgA-positive cells and the total proportions of responding autoclone wells (23-27%) were comparable. All IgE secretion was IL-4 dependent. When the Ig secretion patterns from alpha +/mu- vs alpha +/mu-epsilon- B cells were compared, most autoclone wells from both types of cells produced IgA only, and similar proportions of IgA producing wells (6.2 and 6.0%) also secreted IgE. In addition, IgE restricted responses occurred 6 times more frequently with alpha +/mu- than with alpha +/mu-epsilon- cells, which suggests that membrane IgA+E double-positive, IgE committed B cells occur in vivo. The isotype pattern generated by alpha +/mu-epsilon- B cells cannot be explained by a chance assortment of separate IgA and IgE precursors or by cytophilic antibody. Thus, IL-4 dependent switch to IgE occurred frequently in IgM- or IgA-positive, but rarely among total IgG-positive, B cells. This could be relevant to IgE production in mucosal tissues rich in IgA expressing B cells.     

Effects of early antigen exposure through lactation on later specific antibody responses in mice

This study characterized totally the effects of early Ag exposure by the suckling route on later specific antibody responses. When mother mice of BALB/c or C57BL/6 strains were injected with deaggregated human gamma-globulin (HGG) immediately after delivery, total amounts of HGG in sera of offspring increased until 2 wk of age. The catabolism of transferred HGG was extremely slow and the half-life was about 3 wk in both strains. Hence, small amounts of Ag in mothers, 0.5 micrograms in C57BL/6 and 50 micrograms in BALB/c, could tolerize their offspring effectively. As these were minimum tolerogenic doses, the strain difference in ease of tolerance induction is apparent already during suckling. The study on timing dependent effects of HGG-specific antiserum on tolerance induction by mothers given 50 micrograms HGG demonstrated that the tolerance is achieved within the 1st wk of lactation in C57BL/6 offspring, but not in BALB/c offspring, and the restoration from the tolerance needs more than 6 wk under circumstances, supposedly, without free Ag. Whereas the tolerance was induced in a dose-dependent manner in each class of antibody, the dissociation of tolerant states between IgM, IgG, and IgE antibody classes was found in C57BL/6 offspring. It is interesting that C57BL/6 offspring were sensitized weakly, but significantly, by mothers given subtolerogenic doses. However, this was not apparent in BALB/c. Thus, the Ag dose and the animal strain are related closely to the consequences of this Ag exposure. The aging of suckling mice within the first 2 wk of life or immunomodulators administered early in life did not seriously affect the consequences. Studies on a cellular basis showed that the tolerance is caused by the selective defect in helper T cell function and the suppressor cell activity is not associated with the mechanisms. This contrasts with other models of oral tolerance.     

Contact hypersensitivity reactions to dinitrofluorobenzene mediated by monoclonal IgE anti-DNP antibodies

Several studies have suggested a possible role for IgE antibodies in the pathogenesis of cutaneous hypersensitivity reactions that reach maximum intensity 24 to 48 hr after antigen challenge. The recent availability of murine monoclonal IgE anti-hapten antibodies has made possible the direct examination of the range of cutaneous inflammatory reactions that can be mediated by such antibodies. We have examined the effects of passively sensitizing BALB/c mice with monoclonal IgE anti-dinitrophenyl (DNP) antibody 48 hr before antigen challenge. Inflammatory responses were assessed by measuring ear swelling in mice challenged on the ears with the reactive hapten 2,4-dinitrofluorobenzene (DNFB). Compared with unsensitized controls, the ears of mice passively sensitized with IgE anti-DNP displayed a biphasic pattern of ear swelling after DNFB challenge. An early, transient response (present within 15 to 30 min of challenge and returning to control levels within 4 to 9 hr) was followed by a second, more persistent increase in ear swelling that peaked 24 to 48 hr after challenge. This biphasic pattern of ear swelling seen in IgE-sensitized mice was temporally indistinguishable from that observed in mice conventionally sensitized for allergic contact dermatitis reactions by epicutaneous application of DNFB 5 days before DNFB ear challenge. Antigen specificity of the IgE-mediated contact hypersensitivity reactions was demonstrated by the failure of mice passively sensitized with IgE anti-DNP to display early or delayed ear swelling greater than unsensitized controls when challenged with either of two noncross-reacting haptens, fluorescein isothiocyanate or oxazolone. Mice passively sensitized with a monoclonal IgA anti-DNP antibody (MOPC 315) 48 hr before DNFB challenge failed to display early or delayed ear swelling greater than unsensitized controls. Heat inactivation of the IgE anti-DNP ascitic fluid at 56 degrees C for 30 min completely abolished its capacity to passively sensitize mice for contact hypersensitivity reactions after DNFB challenge. These results document the existence of an antigen-specific, IgE-mediated, delayed-in-time cutaneous hypersensitivity response that can be elicited by epicutaneous challenge (contract) with a reactive hapten.     

Salivary immunoglobulin classes in Nigerian smokers with periodontitis

AIM:To determine the levels of salivary immunoglobulin classes in Nigerian smokers and non-smokers with periodontitis.METHODS:Sixty-nine individuals were recruited into this study after obtaining informed consent.They were subdivided into three groups that consisted of 20(aged 46 ± 11 years) cigarette smokers with periodontitis(S+P);24(40 ± 12 years) smokers without periodontitis(S-P);and 25(53 ± 11 years) non-smokers with periodontitis(NS+P).An oral and maxillofacial surgeon used radiographs for periodontal probing for the diagnosis of periodontitis.The smokers included subjects who smoked at least six cigarettes per day and all the periodontitis patients were newly diagnosed.About 5 mL of unstimulated saliva was expectorated by each subject into plain sample bottles.Salivary immunoglobulin levels were estimated using enzyme linked immunosorbent assay.Student's t test was used to deter-mine significant differences between the means.Values of P 0.05 were regarded as significant.RESULTS:No significant differences were observed in the mean salivary levels of the immunoglobulin classes(IgG,IgA,IgM and IgE) when S+P was compared with S-P.Mean salivary levels of IgA(520.0 ± 155.1 ng/mL vs 670.0 ± 110 ng/mL,P = 0.000) and IgM(644.5 ± 160.0 ng/mL vs 791.4 ± 43.7 ng/mL,P = 0.000) were significantly lower in the S+P compared with NS+P group.Salivary IgA(570.4 ± 145.6 ng/mL vs 670.0 ± 110 ng/mL,P = 0.008) and IgM(703.1 ± 169.3 ng/mL vs 791.4 ± 43.7 ng/mL,P = 0.012) levels were significantly lower in the S-P compared with NS+P group.Only one(5%) periodontal patient had detectable levels of salivary IgE(0.20 IU/mL).Similarly,only one smoker(4.17%) had detectable levels of salivary IgE(0.04 IU/mL) and two non-smokers(9.52%) had detectable levels of IgE(0.24 IU/mL).CONCLUSION:Our study suggests that reduced salivary IgA and IgM levels in smokers with periodontitis could enhance increased susceptibility to periodontitis.     

Nonspecific enhancement of mouse antihapten IgE antibody response: Involvement of a T-cell subpopulation and its product for the potentiation

A concomitant administration of Nippostrongylus brasiliensis saline extract (Nb) with dinitrophenylated ovalbumin (DNP-Ov) significantly enhanced the anti-DNP IgE antibody response in mice which had been irradiated and given a combination of spleen and mesenteric lymph node cells from syngeneic, infected donors and cells from DNP-keyhole limpet hemocyanin (DNP-KLH)-primed donors. The treatment of lymphocytes from infected mice with anti-mouse brain-associated θ serum and C abrogated the enhancing activity. The potentiation occurred in mice receiving nylon wool-nonadherent cells but not in mice receiving adherent cells. Challenge with Nb plus DNP-Ov failed to induce potentiation in C3H mice which are known as nonresponders to low doses of Ov, whereas challenge with Nb plus DNP-bovine gamma globulin (BGG) potentiated the response. However, further increase of the enhanced response was not obtained by adding carrier (BGG or Ov)-primed cells to the transferred lymphocyte populations. When a T-independent antigen, DNP-Ficoll, was used for challenge concomitantly with antigen Nb, no potentiation occurred, even though DNP-Ficoll did not give any tolerogenic or suppressive effect on the IgE antibody response to DNP-Nb. An enhancing activity on the IgE class of antibody response but not on the IgG class was observed in supernatants of in vitro culture of lymphocytes from infected mice upon stimulation of the cells with 10 to 50 μg Nb. These results indicate that the potentiation is mediated by Nb specific T cells via a soluble factor(s) that enhances specifically the IgE class of antibody responses but nonspecifically in terms of antigens used for immunization. The results also suggest that the potentiating factor displays its activity in the presence of other T cells reactive to carrier determinants of the challenging antigen but not of cells which already have committed themselves to the carrier and differentiated as helper cells.     

The absence of VPAC2 leads to aberrant antibody production in Aspergillus fumigatus sensitized and challenged mice

Vasoactive intestinal peptide (VIP) facilitates a “pro-allergy” phenotype when signaling through its G protein-coupled receptor, VPAC₂. We have shown that VPAC₂ knock-out (KO) mice developed an allergic phenotype marked by eosinophilia and elevated serum IgE. Therefore, we hypothesized that the humoral response to allergen challenge in these mice was T_H2 dominant similar to wild-type (WT) C57BL/6 mice. Antibody responses in WT and KO mice were measured after Aspergillus fumigatus conidia inhalation. In contrast to previous reports, basal levels of serum IgG_2a and IgA were significantly higher in naïve VPAC₂ KO animals. Antibody availability in the serum as well as the bronchoalveolar lavage fluid after fungal challenge was dominated by the pro-inflammatory isotype IgG_2a and the mucosal isotype, IgA. IgA localizing cells dominated in the peribronchovascular areas of allergic KO mice while IgE immune complexes were found in WT allergic lungs. This research shows for the first time that VPAC₂ has a significant effect on antibody regulation, in the context of allergy.     

Humoral immune response to filarial antigens in chyluria

Humoral immune parameters like total immunoglobulins and specific antibody levels in serum were studied in filarial chyluria patients. Mean serum IgG was significantly reduced in this group compared to normal controls, while IgA and IgM levels remained comparable to controls. Anti-filarial antibody titre as measured by enzyme-linked immunosorbent assay also was significantly reduced. However, the total and specific IgE antibody titre was similar to that of controls. Specific IgE contents of the patients’ sera could be related to their microfilaraemic status.     

Tolerance induced by chronic inhaled antigen in a murine asthma model is not mediated by endotoxin

Ovalbumin (OVA)-sensitized wildtype (WT) and endotoxin-resistant (ER) mice developed similar degrees of airways eosinophilia and serum OVA-specific IgE levels after acute aerosolized OVA challenge. WT mice demonstrated methacholine hyperreactivity, whereas ER mice showed no change in responsiveness. With chronic aerosolized OVA challenge, both WT and ER mice developed local tolerance, with resolution of airway eosinophilia but persistence of anti-OVA IgE in serum. Thus, the development of local tolerance with chronic aerosol exposure to OVA is independent of any potential effects of endotoxin in the OVA aerosol solution.