Inhibition of specific immune responses by feeding protein antigens. III. Evidence against maintenance of tolerance to ovalbumin by orally induced antibodies.
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Biomedical subjects
Publications and source records attributed to D G Hanson.
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We studied the effect of a single intragastric administration of ovalbumin (OVA) on the subsequent development of OVA-specific cell-mediated immune (CMI) responses in BDF1 mice. In animals fed OVA 7 days before subcutaneous sensitization with OVA-CFA, we observed a concomitant dose-dependent decrease in both the humoral and CMI responses specific for OVA. The CMI tolerance was found to be antigen-specific when assayed in vivo by ear swelling or in vitro by an antigen-induced T cell proliferation assay because OVA-fed mice responded normally to sensitization with horse gamma-globulin. It was also shown that either spleen or lymph node cells, but not serum, from OVA-fed donors transferred suppression to normal recipients. The transfer was mediated by antigen-specific suppressor T cells (Ts) that appeared to inhibit the induction phase (afferent limb) of the CMI response, since the Ts were only effective when transferred before or shortly after the onset of sensitization.
A reliable animal model for acute otitis media due to Streptococcus pneumoniae was used to study the accumulation of lactate dehydrogenase (LDH) in middle ear effusion during acute pneumococcal otitis media and after penicillin treatment. The findings indicate that LDH levels rise in the middle ear effusion during the early phase of acute infection and decrease as the infection resolves over time. Penicillin treatment affects the natural course of infection by resolving most visible signs of inflammation and by sterilizing the middle ear. However, once middle ear infection was established, penicillin treatment did not reduce the elevated levels of effusion LDH, suggesting that inflammation persists after sterilization of infected middle ears.
Specific immune unresponsiveness was induced in inbred mice (BDF1) by the administration of soluble ovalbumin (OVA) by gastric intubation. Anti-hapten (DNP) responses likewise were specifically diminished when animals were fed autologous carrier (OVA or keyhole limpet hemocyanin). Adoptive transfer of spleen cells demonstrated that the tolerant state could be maintained in irradiated recipient mice, and specific anergy could be transferred to normal recipient animals. Adoptive suppression was mediated by T lymphocytes, as demonstrated by nylon wool fractionation and susceptibility of the cells to anti-Thy 1.2 and complement. Transferred B cells had neither suppressive nor augmentative effects. Enteric administration of OVA also specifically diminished antigen-induced DNA synthesis of primed lymph node T cells, although suppressor cells were not identified in the lymph nodes per se.
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Profound and prolonged states of specific immunologic tolerance were induced in adult mice of high-responder genetic background by a single exposure to moderate doses of the specific antigen by digestive route.
A large panel of inbred strains of mice and some of their Fl hybrids were tested on their sensitivity to the hemoconcentrating effects of intravenous injections of histamine alone, serotonin alone, or histamine-serotonin mixtures. Major differences in susceptibility were observed. Crosses and backcrosses were made between susceptible (SJL/J) and less susceptible (RF/J, C57BL/6J) strains; it was found that the sensitivity to vasoactive amines is, at least partially, inheritable.
Pretreatment with Bordetella pertussis was determined to increase significantly the hypovolemia induced by intravenous injections of histamine either alone or in mixture with serotonin in a total of 26 different strains of mice. Two factors affecting the mortality rates observed by challenge after B. pertussis treatment were: the sensitivity of the strains to vasoactive amines before B. pertussis treatment, and their resistance to acute hypovolemic shock. Appropriate crosses and backcrosses between resistant and susceptible strains failed to demonstrate a clear pattern of inheritance of the susceptibility to B. pertussis effects.
A profound and long-lasting state of specific immune unresponsiveness may be induced in adult inbred mice given a single dose of protein immunogens--such as ovalbumin or hemocyanin--by the digestive route. The degree of unresponsiveness induced by intragastric exposure to ovalbumin could not be achieved by intravenous injection of deaggregated ovalbumin solutions across a wide range of doses. Unresponsiveness induced by intragastric exposure to hapten-protein conjugates is specific to the carrier protein.
This paper describes a method of endolymphatic sac decompression and drainage. The method emphasizes widely exposing dura, avoiding skeletonization of the posterior semicircular canal and draining the sac via a T tube. The results of this procedure in 75 patients, including statistics in 46 ears are discussed. In patients with unilateral disease good results were obtained in control of vertigo in 94 percent of patients and significant improvement in cochlear function in over 30 percent.
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BACKGROUND: The purpose of this study was to determine the temporal characteristics and patterns of glottic closure during normal swallow using concurrent videofluoroscopy and videoendoscopy. METHODS: Three swallows each of four bolus types were examined in eight healthy volunteers with the endoscope in two positions: at the level of the uvula and at the laryngeal vestibule. Data analysis compared: (1) temporal relationships between laryngeal behaviors and oropharyngeal swallow events and (2) airway conditions at the time of key oropharyngeal events. RESULTS: Although arytenoid adduction and subsequent arytenoid contact occurred as one of the initial events during swallow, the timing of these events was highly variable. On the other hand, true vocal cord (TVC) closure occurred mainly after the onset of laryngeal elevation, and it was affected by bolus volume. CONCLUSIONS: In normal swallow, arytenoid closure did not always mean complete TVC closure, and complete TVC closure might be accomplished during the process of laryngeal elevation and arytenoid tilting.
In order to evaluate tolerance, toxicity, and in vivo antigenicity, 29 HIV-1-infected patients (eight with ARC and 21 with AIDS) were vaccinated with a synthetic peptide derived from the gp41 transmembrane protein of the HIV-1. This peptide had been coupled with 2.4 dinitrophenyl-Ficoll (F46), a T-cell independent adjuvant. The patients received a single intradeltoid injection of either 0.1 or 0.3 mg of F46. Five of the individuals with AIDS were boostered, four of them twice. Anti-F46 antibody titers were measured before vaccination, and on days 7, 14, 21, 28, 90, 180 and 270 after vaccination. Anti-F46 titers rose at least twofold over prestudy values in 10/21 individuals with AIDS and in 1/8 individuals with ARC at least once during the observation period. The overall response, however, consisted of only weak antibody production that was independent of the dose or patient characteristics. No signs of toxicity or of clinical progression related to the vaccination were observed in this phase I/II trial of a T-cell independent therapeutic vaccine.
We investigated the effect of variation in superior laryngeal nerve stimulation (SLNS) on vocal fold vibration. Photoglottography (PGG), electroglottography (EGG), and subglottic pressure (Psub) were measured in seven mongrel dogs using an in vivo canine model of phonation. The PGG, EGG, and Psub signals were examined at three SLNS frequencies (100 Hz, 130 Hz, and 160 Hz) using a constant rate of air flow. Increasing SLNS, which causes a contraction of the cricothyroid muscle, produced a marked increase in Fo, little change in Psub, an increase in the open quotient, and a decrease in the closed quotient of the glottal cycle.
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