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PubMed2026

Characterization of the Immune Response after Oral Cholera Vaccination (OCV) and Effects of Mycophenolate Mofetil on Priming of this Immune Response-A Randomized, Placebo-Controlled Trial.

Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used by solid organ transplant recipients. Although it is known that MMF suppresses immune responses, its exact effects on specific vaccinations have not been investigated yet. Mucosal vaccinations are increasingly used, such as a cholera vaccination consisting of two oral immunizations (oral cholera vaccination; OCV). This study aimed to investigate the specific immunosuppressive effects of MMF use during the first dose of OCV in a randomized, placebo-controlled trial in healthy volunteers. Moreover, the study aimed to characterize the immune response provoked by OCV in detail. This randomized, placebo-controlled, single-blind trial included 16 healthy volunteers, each receiving two doses of Dukoral® and an intranasal rechallenge. Outcome measures were serum antibody responses (IgA and IgG) and IgA levels in saliva. Additionally, peripheral blood mononuclear cells (PBMCs) of participants were investigated for ex vivo cytokine production and expression of tissue-specific homing markers after OCV. There were considerable serum IgA and IgG responses after vaccination. MMF-treated volunteers still showed a significant cholera antibody response, though data suggest a potential suppression by MMF without reaching statistical significance. There was no substantial IgA response in saliva. Investigation of PBMCs from OCV-treated participants showed a Th2 skewing with increased ex vivo production of TNF, IL-2, IL-5, IL-13, and IL-22 compared to the placebo group. Taken together, this study provides a framework for future clinical pharmacology studies building on OCV as a challenge model and for further investigation of specific effects of MMF on mucosal vaccination responses.

Humans↗
PubMed1979

Genetic control of the immune response to collagen. II. Antibody responses produced in fetal liver restored radiation chimeras and thymus reconstituted F1 hybrid nude mice.

The level of antibody produced in response to calf skin collagen in mice is influenced by genes which are closely linked to the I region of the H-2 major histocompatibility complex. This influence is shown to be expressed during lymphoid maturation by testing the antibody responsiveness to collagen in two types of chimeric mice. First, high responder and low responder parental strain mice were lethally irradiated and restored with fetal liver cells from (high X low responder) F1 mice. These F1 leads to parent chimeras exhibited an immune response phenotype characteristic of the irradiated parental strain animals, establishing that H-2 determinants of the host affect antigen responsiveness. Second, (high X low responder) F1 congenitally athymic (nude) mice were restored with fetal thymus transplants from either high or low responder parental strain mice. After a period of maturation these mice were shown to be competent for a T-dependent IgG response to SRBC. The responsiveness to collagen in these mice was characteristic of the parental strain thymus donors, indicating that the expression of H-2 determinants in thymic tissue during lymphoid maturation influences the antibody response phenotype expressed by mice.

Animals↗
PubMed1976

In vivo and in vitro cell-mediated responses in coccidioidomycosis. I. Immumologic responses of persons with primary, asymptomatic infections.

Chest roentgenograms of 58 children who were skin test positive to coccidioidin and resided in an area endemic for coccidioidomycosis revealed that 34 per cent had roentgenographic evidence of an inflammatory process, 14 per cent showed calcific densities, and 52 per cent showed no evidence of infection. The in vitro lymphocyte responses of children who had evidence of an inflammatory process (Group I) were compared with those of children who had calcific densities (Group II); those of children who were coccidioidin skin test negative and had normal chest roentgenograms (Group III); and those of patients who had active coccidioidomycosis (Group IV). The mean lymphocyte transformation responses (expressed as cpm times 10-(4)) of Groups I, II, III, and IV to a coccidioides antigen were 16.8, 19.5, 4.2, and 7.0, respectively. The mean migration inhibitory factor responses of these groups were 22.4, 20.0, 1.2, and 4.0 per cent, respectively. Thus, the over-all responses of children in Groups I and II were comparable to each other, whereas the responses of patients in Group IV were depressed to the extent that they were indistinguishable from those of coccidioidin skin test-negative donors in Group III. Follow-up chest roentgenograms taken 3 months after the immunologic assays were performed revealed that the one subject in Group I who had been nonresponsive in the lymphocyte assays had now stabilized his infection, as evidenced by calcifications. In contrast, the 2 subjects in Group I who had yet to stabilize their infection had exhibited strong in vitro lymphocyte responses. These findings suggest that primary, asymptomatic coccidioidomycosis is not associated with an immunologically nonresponsive state. However, patients with active, progressive coccidioidomycosis do have a depressed immunologic response to coccidioides antigens.

Adolescent↗
PubMedDate not supplied

Brain stem and other responses in electric response audiometry.

For electric response audiometry of young children who require sedation, an indicator is desired that is more reliable than the slow vertex potential. There are four leading candidates: 1) The electrocochleogram (ECochG) is very reliable with a transtympanic electrode on the promontory, but this is a surgical procedure and requires a general anesthetic. 2) The early midbrain responses give similar information with external electrodes, but they are complex and low in voltage. 3) The muscle reflexes (sonomotor responses) are a crude indicator with high and variable thresholds and are not suited to precise audiometry. 4) The "middle" responses, perhaps cortical in origin, are good candidates, but they have not yet been adequately validated in the clinic. For the midbrain responses and particularly for the ECochG, close synchronization of nerve impulses is essential. This requires a compromise with selectivity of frequency. High-tone audiometry by electrocochleography and midbrain responses is satisfactory, but limitations are increasingly severe below 2 kHz, where each sound wave is a separate acoustic stimulus. Low-frequency tones stimulate the basal turn of the cochlea at relatively low sensation levels. This makes assessment of the apical portion of the cochlea very difficult, even with the midbrain "frequency-following response" (FFR).

Acoustic Stimulation↗
PubMedDate not supplied

Comparison of hearing threshold determined by auditory pathway electric responses and by behavioural responses.

In order to evaluate their reliability for determing the hearing threshold, the cochlear microphonic potentials, the auditory nerve and brain stem neural evoked responses as well as the cortical evoked responses were compared with the behavioural hearing thresholds of the same subjects in the same session. The threshold for recording the cochlear microphonic potnetial was found to be appreciably higher than the behavioral threshold. The threshold for recording the auditory nerve and brain stem responses was within a few decibels of the behavioural threshold. The thresold of the cortical evoked response was several decibels higher. It is concluded that (1) the auditory nerve and brain stem neural evoked responses are the best indicators of hearing threshold; (2) the cortical evoked responses are usually comparable, and (3) all types of evoked responses are indispensable aids in the evaluation of hearing and the determination of site of lesion in the auditory system.

Audiometry↗
PubMed1979

Trials with the auditory response cradle. 1--Neonatal responses to auditory stimuli.

The Auditory Response Cradle enables physiological response measures to be recorded from the neonate. Auditory responses are detected in the form of head rotation, startle, body activity and respiration changes. This paper reports the results of trials with 203 neonates using 250 and 1000 Hz pure tone and broad band noise stimuli. Response criteria are determined and spontaneous control 'responses' compared with those resulting from stimulus presentation. The response rate is correlated with the measured intra-meatal sound pressure level. Clear response thresholds are determined for all three stimuli. The sharpness of these motor thresholds is discussed and found to have significant implications for cost-effective neonatal auditory screening.

Head↗
PubMed1976

Immune response in asymptomatic paraproteinemia. I. Primary and secondary antibody response to Helix pomatia hemocyanin.

In a group of 20 patients with asymptomatic paraproteinemia, as judged after at least 3 years of follow-up, the primary and secondary antibody response to Helix pomatia hemocyanin (HPH) was defective as compared with the response in controls. The class of antibody was assessed by mercaptoethanol (ME) treatment of serum. A lowered response was found not only in the total but also in the ME-resistant (mainly 7S, IgG) antibody titer. Low anti-HPH antibody titers were preferentially found in the patients with high serum paraprotein levels, whereas in half of the patients with low serum paraprotein levels a completely normal antibody response was found. No differences in the total or 7S anti-HPH antibody response were found between patients with IgG, IgM, or IgA paraproteinemia. The polyclonal serum Ig levels were not predictive for the measured anti-HPH response. The anamnestic diphtheria and tetanus antibody response was not different from that of controls.

Adult↗
PubMed1975

Sera and the in vitro induction of immune responses. II. Inhibitory effects of newborn calf sera on primary humoral responses.

The effect of newborn calf (NBC) sera on the in vitro generation of immune responses were studied. NBC sera inhibited the generation of primary humoral responses to SRBC. The inhibitory activity was dose-dependent and diluted out rapidly. Adding inhibitory doses of NBC serum to test cultures at zero or 24 hr resulted in approximately the same amount of inhibition. Pulsing experiments showed that the test cultures were most sensitive to the inhibitory effects of NBC serum during the 24- to 48-hr period. In contrast to its inhibitory effects on primary humoral responses, NBC sera supported the in vitro generation of secondary humoral responses and significantly increased the responses of some of these over control levels. We found that sera obtained from newborn calves before nursing were not inhibitory for primary responses but sera obtained from the same calves 7 days later did inhibit these responses. We postulate that the inhibitory effects of NBC sera may represent a physiologic control mechanism which becomes active when immunologic maturity develops and that it possibly involves the inactivation of cell mediators.

Animals↗
PubMed1979

Human immune responses to hapten-conjugated cells. II. The roles of autologous and allogeneic histocompatibility determinants in proliferative responses in vitro.

Proliferative responses of human lymphocytes primed in vitro to autologous TNP-cells were found to be associated with autologous D-region determinants irrespective of HLA-B locus antigens. Family studies of secondary TNP-conjugate proliferative responses demonstrated a gene dosage effect in this phenomenon. Moreover, co-culture with allogeneic cells did not affect the net TNP-conjugate proliferative responses of primed responder cells, suggesting that HLA-D region preference was due to a requirement for representation of TNP-molecules in association or combination with autologous MHC structures. Alloantigens were found to influence the sensitization of lymphocytes to autologous hapten-conjugated cells. Co-culture of allogeneic and TNP-modified autologous stimulator cells in primary cultures enhanced the secondary TNP proliferative response. Sensitization of human lymphocytes to allogeneic cells alone did not prime responses to autologous modified cells. However, priming lymphocytes to modified autologous cells potentiated responses to allogeneic cells. The data suggest a complex relationship between responses to alloantigens and modified autologous cells.

Antibody Formation↗
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↗
PubMed1977

Effect of concanavalin A on lymphocyte interactions involved in the antibody response to type III pneumococcal polysaccharide. II. Ability of suppressor T cells to act on both B cells and amplified T cells to limit the magnitude of the antibody response.

When administered 2 days after immunization with 0.5 microgram Type III pneumococcal polysaccharide (SSS-III), the T lymphocyte mitogen concanavalin A (Con A) stimulates a 2.6-to 7-fold enhancement of the plaque-forming cells (PFC) response to SSS-III in vivo. This enhancement requires the presence of amplified T cells, which act by driving PFC or their precursors to extra rounds of proliferation. The extra proliferation that can be stimulated by Con A is not seen in the normal primary response to SSS-III; but treatment with anti-lymphocyte serum (ALS) to remove suppressor T cells will permit the additional proliferation to occur. This indicates that in the primary response to SSS-III, suppressor T cells act on amplifier T cells to limit the magnitude of the antibody response. Only suppression of B cells can account for the further suppression induced by Con A given at the time of immunization or by low-dose paralysis of the SSS-III response. The relatively late development of amplified activity compared to suppressor activity appears to account for the absence of amplifier activity after primary immunization with SSS-III. It is apparent that one can explain the regulatory effects observed during the development of an immune response to SSS-III only by considering both T cell- B cell and T cell- T cell interactions, together with the temporal relationships involved in those interactions.

Animals↗
PubMed1978

Studies on the immune response to fixed antigens. III. Induction of helper function for antibody-dependent cellular cytotoxicity responses.

Heavy trinitrophenylated sheep red cells (TNP128SRC) and glutaraldehyde-treated SRC (G-SRC) could not induce cellular cytotoxicity against 51Cr-SRC. In contrast, the native antigen SRC could stimulate a cytolytic response against the radiolabeled homologous target cell. However, fixed SRC could stimulate a priming function that accelerated and augmented the secondary cytotoxic response to SRC. Such fixed antigens could stimulate a delayed-type hypersensitivity (DTHS) response also. Thus, the immunologic memory to the chemically modified antigen, as well as the DTHS response, are completely dissociated from the primary cytotoxic responses. The primary and the secondary cytotoxic responses that were developed in the spleens of the injected mice were mediated by antibody-dependent cellular cytotoxicity (ADCC), since the active supernatant that was released from the spleen cells could lyse the target cells in the presence of normal splenocytes. The active supernatant was identified as antibody. We suggest that B effector cells cytolyzed the antibody-coated target cells. Normal cells from nude mice could mediate the cytolytic process as efficiently as spleen cells from other strains of mouse. The results are discussed in terms of selective stimulation of T cell subpopulations.

Absorption↗
PubMed1975

Genetic control of immune responses to parasites: selection for responsiveness and non-responsiveness to Trichuris muris in random-bred mice.

Populations of Schofield strain, random-bred mice were shown to have a bimodal variation in ability to bring about immune expulsion of the nematode Trichuris muris. This variation was genetically determined and independent of the size of infection experienced. The proportion of mice unable to achieve worm expulsion (non-responders) was relatively constant in various populations of the strain but was increased by selective breeding from mice of known status. Crosses made between non-responder and responder mice produced progeny that were almost all (92%) of responder phenotype, showing that the ability to achieve worm expulsion was inherited as a dominant characteristic. It is suggested that the genetic control involves a small number of genes; the possible immunological mechanisms by which control is mediated are briefly discussed.

Animals↗
PubMed1975

Regulation of the immune response by subclasses of T lymphocytes. II. The effect of adult thymectomy upon humoral and cellular responses in mice.

The immunologic consequences resulting from thymectomy in adult life were investigated. Primary humoral responses were not diminished shortly after adult thymectomy, as judged by responses of intact thymectomized mice as well as by the ability of spleen cells from such mice to transfer primary responses. However, secondary humoral responses were substantially reduced in irradiated recipients of spleen cells from primed adult-thymectomized mice, suggesting that the thymus is required in adult life to maintain a population of cells important in the generation of immunologic helper memory. By contrast, small doses of anti-thymocyte serum, which primarily affect recirulating T cells, abrogated the primary humoral response, but allowed the subsequent development of immune memory. Using a technique permitting in vitro sensitization of purified T cells to alloantigens, it was shown that adult thymectomy increases the ability of T cells to generate primary cytotoxic responses, but had little effect upon the development of cytotoxic T memory activity. These experiments suggest that in adult life the thymus maintains a regulatory population of T cells in peripheral tissues which suppress early T cell differentiation to cytotoxic effector cells and potentiates the development of immune memory.

Age Factors↗
PubMed1975

The genetic control of T cell-mediated immunity against the DBA/2 mastocytoma P-815. II. Low responsiveness in T cell-mediated cytotoxicity accompanied by the inability to produce antibodies in a secondary response.

Low responsiveness of DBA/1 mice in T cell-mediated cytotoxicity against the DBA/2 mastocytoma P-815 (H-2d) is genetically controlled and inherited as a recessive trait. For an analysis of the humoral anti-H-2d response of DBA/1 mice after immunization with P-815 mastocytoma cells both complement-dependent lysis (CDL) and the cytotoxicity inhibition assay (CIA) were used to demonstrate antibodies. Both assays show that DBA/1 mice are unable to produce anti-H-2d antibodies in a secondary response. Even high doses of immunizing cells give only a weak response. The response is fully recovered upon allogeneic interaction. A transient primary anti-H-2d activity can be found in the CIA but not by CDL. The data show that the genetically controlled determinant-specific defect in T cell-mediated cytotoxicity among DBA/1 mice has its correlate in a blockade of memory formation or expression in the humoral anti-H-2d response.

Animals↗
PubMed1977

Immune response genes in chickens: the multifarious responsiveness to (T,G)-A--L.

Immune response in chickens to the multichain copolymer (T,G)-A--L 2030 is analysed. Previous work has shown that responsiveness is not linked to the B-complex. Three different antibody specificities could be distinguished. From the data it is proposed that the response to the backbone of (T,G)-A--L (poly-DL-alanine) influences the responses to the side chain determinants (primarily the (T,G)-determinant). Thus the anti-(T,G) response in chickens is determined by at least two different loci, the B-complex, and another, as yet unidentified locus which determines the response to the poly-DL-alanine determinant. A third antibody specificity is directed against G-A--L and is only detectable in chickens which are high responders to poly-DL-alanine.

Alanine↗
PubMed1978

Response characteristics of semicircular canal and otolith systems in cat. II. Responses of trochlear motoneurons.

1. The electrical activity of single trochlear motoneurons (TMns) and axons of second order vestibular neurons presumably terminating on these motoneurons were studied during natural stimulation of semicircular canals and otolith organs in cats anesthetized with Ketamine. 2. Null point analysis showed that TMns received an excitatory canal input from the contralateral posterior canal, and labyrinthine lesion experiments suggested that the functionally synergistic, ipsilateral anterior canal provides an inhibitory input. A small number of motoneurons showed orthogonal canal convergence. 3. In addition to the canal projections most TMns received an otolithic input. Firing rate was proportional to lateral head tilt and was of the beta type. Most units also responded to pitch with an increase and decrease in firing rate on nose-up and nose-down positioning, respectively. Lesion experiments indicated that the otolith responses are the results of reciprocal innervation of TMns by contralateral (excitatory) and ipsilateral (inhibitory) otolith projections. 4. During sinusoidal rotation in yaw (canal only stimulation) the mean phase lag re acceleration of the response of TMns increased from 60 degrees at 0.025 Hz to 126 degrees at 1.0 Hz. In roll (canal plus otolith stimulation) the phase lag of TMn responses measured 180 degrees and 130 degrees at 0.025 and 1.0 Hz, respectively. Phase-lags measured in Vi and Vc axons were less by ca. 15 degrees. 5. The otolith contribution to TMn responses in roll was calculated by vectorial subtraction of the yaw from the roll responses: A phase lag of 10 (0.025 Hz) to 90 degrees (0.5 Hz) re. displacement was noted and gain was constant over the same range. Similar lag dynamics were revealed in TMns when studied during ramp displacement of the head. 6. The possible functional role of central canal-otolith convergence and the differences between the response of primary vestibular afferents and secondary vestibular neurons and TMns will be discussed.

Animals↗