Human immune responses to influenza virus vaccines administered by systemic or mucosal routes

Healthy adult volunteers were immunized by parenteral or oral routes with trivalent inactivated influenza vaccine (A/Chile/1/83 (H1N1), A/Mississippi/1/85 (H3N2), and B/Ann Arbor/1/86), or intranasally with live attenuated, cold-adapted influenza type A/Texas/1/85 (H1N1) reassortant virus. In all volunteers, cells spontaneously secreting IgA, IgG or IgM antibodies specific to influenza virus were detected in peripheral blood on days 6-13 after immunization, and specific IgA, IgG and IgM antibodies to influenza vaccine were measured in sera and external secretions (saliva and nasal lavage). Following systemic immunization, a raise in specific antibodies of all isotypes was observed in sera beginning on day 13. Although small variations in IgA and IgM antibodies in saliva and nasal lavages were detected, antigen-specific IgG significantly increased between days 13 and 27. Intranasal administration of attenuated virus induced IgA and IgG antibodies in serum as well as in secretions. Serum antibodies were not substantially influenced by oral immunization, only a small increase in all isotypes was observed in volunteers' sera 21 days after ingestion of vaccine. However, in secretions, antigen-specific IgA and IgG responses were detected one week after immunization and reached a peak response on day 20. These studies show that different routes of immunization can be effective for the induction of specific antibodies, and support the concept of the common mucosal immune system in humans by demonstrating that the oral or intranasal administration of antigen-induced specific antibodies of IgA isotype in external secretions, preceded by the transient appearance in peripheral blood of specific antibody-producing cells.     

Control of immune responses by gene immunization

AIMS OF THE STUDY: To determine the risk factors for local and distant failure in node-negative breast cancer treated with breast-conservative surgery and radiotherapy and to determine the relationship between these two events. MATERIAL AND METHODS: We retrospectively selected 908 patients who received conservative surgery and radiotherapy but no chemotherapy between 1980 and 1995, for a node-negative breast cancer. Patients were divided in two groups according to the status of the margins of resection. All pathology specimens were reviewed. RESULTS: In case of negative margins, the risk factors for local recurrences picked up by the Cox model were histologic multifocality (P = 0.0076), peritumoral vessel invasion (P = 0.021) and age < or = 40 years (P = 0.024), and in case of involved margins, negative oestrogen receptors (P = 0.0012), histologic multifocality (P = 0.0028), and absence of hormonal therapy (P = 0.017). The 10-year local recurrence rate was 18% in case of negative margins and 29% in case of involved margins, although in the latter case patients received high-dose adjuvant radiotherapy. Accordingly, the 10-year distant failure rates were 16% and 27%, respectively. Many arguments suggest that local and distant failures are closely related. CONCLUSION: Patients with histologic multifocality or positive margins are at high risk of local failure and then of distant failure, and require a more aggressive initial treatment.     

Cognitive styles and responses to the threat of frustration.

Compared 60 6-, 8-, and 10-yr-old boys on measures of the cognitive styles reflection-impulsivity (Matching Familiar Figures Test) and field dependence-independence (Children's Embedded Figures Test). A story completion test eliciting responses to the threat of frustration was also administered. All measures showed developmental changes. Older Ss were more reflective, field independent, and optimistic about the outcome of potentially frustrating events. Ss scoring high on measures of impulsivity were also more field dependent and pessimistic in the face of threatened frustration. Implications for personality theory and education are discussed. (French summary) (29 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differential modulation by extracellular ATP of carotid chemosensory responses

The possibility that the carotid body has ATP surface receptors that mediate O2 chemoreception was tested. To distinguish between the event(s) initiating chemoreception and those at the neurotransmitter level, we also tested the chemosensory response to nicotine before and after ATP administration. Carotid bodies from cats anesthetized with pentobarbital sodium were perfused and superfused in vitro with modified Tyrode solution (PCO2 < 1 Torr, pH 7.4, 36 degrees C) equilibrated at PO2 > 400 or approximately 150 Torr while chemosensory discharge was recorded extracellularly. ATP and adenosine 5'-[gamma-thio]triphosphate stimulated discharge with similar dose dependence, whereas adenosine had little effect. ATP infusion for > or = 2 min evoked an initial stimulation of discharge followed by a decline to baseline (desensitization). Desensitization did not affect the response to hypoxia (perfusate flow interruption) but inhibited the response to nicotine (4-nmol pulse). Therefore, 1) the carotid body has surface ATP receptors that may mediate the chemosensory response to nicotine but not to hypoxia and 2) nicotinic receptors are not required for carotid body O2 chemoreception.     

Evaluation of humoral immune responses in cattle grazing endophyte-infected or endophyte-free fescue

Anecdotal reports suggest cattle with fescue toxicosis may not respond to vaccination and thus, experience increased incidence of Bovine Respiratory Disease Complex (BRDC) when shipped to feedlots. Fescue toxicosis causes hypoprolactemia in cattle. Hypoprolactemia decreases humoral immune responses in mice. Therefore, a study was conducted to compare the magnitude of primary and secondary humoral immune responses against specific antigens in cattle grazing endophyte-infected or endophyte-free fescue. Angus steers were blocked by weight and allocated into four groups. Two groups grazed endophyte-infected (EI) fescue and the other two groups grazed endophyte-free (EF) fescue. All steers were injected IM on d 0 and 21 with lysozyme without adjuvant and concanavalin. A (Con A) with sheep red blood cells (SRBC) in incomplete adjuvant of Freund. Steers were bled on days 0, 21 and 35 post-vaccination. Average daily gains (ADG), alkaline phosphatase (ALP) activity, cholesterol concentrations, rectal temperatures, and serum prolactin concentrations were measured to confirm fescue toxicosis in steers grazing EI fescue. Antibodies to Con A and SRBC were determined by ELISA and hemagglutination assay, respectively. The ADG were decreased for the EI group during the first month. Rectal temperature were elevated and serum prolactin concentrations were decreased in the EI group. Cholesterol and ALP concentrations also were decreased in the EI group. Primary and secondary immune responses against Con A tended to be increased and were increased against SRBC in the EI group. Antibodies against lysozyme were not induced in either group. In conclusion, cattle grazing EI fescue mounted similar humoral immune responses to vaccination, despite hypoprolactemia, as cattle grazing EF fescue. Increases in bovine respiratory disease in cattle maintained on EI fescue probably is not associated with lack of humoral immune response to vaccination protocols as a result of fescue toxicosis.     

VIP modulation of immune cell functions

Neuropeptides have recently been shown to modulate the immune response. Vasoactive intestinal peptide (VIP) released from nerve endings and from immune cells modulates the mobility and adherence of lymphocytes and macrophages, phagocytic cell functions (phagocytosis and free radical production), the lymphocyte proliferative response, lymphokine and immunoglobulin production and the natural killer cell activity, with opposite effects in vitro on these immune cell functions. The VIP receptor heterogeneity and the different action mechanisms of VIP-mediated immunoregulation could explain, at least in part, the different VIP effects observed on lymphoid and phagocytic cells. The evidence supports the theory that VIP acts not as an inhibitor, but as a modulator of immune functions, as previously thought, and that this neuropeptide may play a relevant role in vivo.     

In vitro immune modulation by antibodies coupled to tumour cells

Modification of autologous tumour cells to express the immune costimulator B7.1 is a potential strategy for immunotherapy of cancer. Previously, this has involved introduction of genetic material into cells, in vitro culture, and confirmation of the protein product on the cell surface. This is possible only if sufficient tumour is obtainable and efficiently modified in a short time. Whilst progress has been made on ex vivo tumour cell culture and transfection/infection procedures there are still tumour types for which the present means of gene transfer are not efficient enough. We describe a highly efficient in vitro procedure for the modification of over 99% of the cells in a population, allowing the expression of cell surface proteins with potential immune modulatory activities. This procedure, which can be completed in as little as 24 h with no upper limit on cell number, utilizes succinimide esters to label cell surface proteins with biotin covalently. Biotinylated cell membrane proteins then anchor an avidin bridge for immobilizing protein G'-biotin. This can serve to bind immunoglobulin (Ig) molecules via their Fc region such that the variable region of the antibody is freely and functionally available. In the present study the binding of a stimulatory mouse anti-human CD28 monoclonal antibody to the surface of tumour cells is used to show that the modified cells are capable of co-stimulating T cells in vitro. The simplicity of the method, and the use of common reagents, represents a further step towards a realistic, truly 'off-the-shelf', nongene immunotherapy protocol.     

Aggression and blood pressure responses of high- and low-guilt subjects following frustration.

After completion of the Forced-Choice Guilt Inventory, a total of 64 females were randomly assigned to frustration or neutral conditions. Frustrated Ss were told by E that their performance on a counting task was unsatisfactory and were not given an expected reward. Frustrated Ss showed (a) a significant increase in diastolic blood pressure during the task; (b) more aggression toward E on a postexperimental Research Evaluation Questionnaire (REQ); and (c) a significant decrease in diastolic pressure after the REQ, especially in low-guilt Ss. No differences were found between groups in systolic pressure, and not all high-guilt Ss inhibited their aggression. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

MHC regulation of immune responses

The major histocompatibility complex is a group of complex genes situated on the short arm of chromosome 6 in humans. They play an important role in the regulation of the immune response. Autoimmune blistering disease provides an ideal model for studying the role of MHC in autoimmunity. The diseases are organ specific, and in some of them the relevant antigen has been cloned and sequenced. Such information on the antigen will help further define the interactions of the Ag, MHC, and TCR. Use of family studies hopefully will define and localize susceptibility alleles, so that any genetic susceptibility can be identified at the molecular level. It is from these molecular perspectives that molecular therapies could be assigned to restore the immune system.     

Fast modulation of glutamate and GABA receptor--mediate electrophysiological responses by glucocorticoid]

Endothelin (ET) is a powerful vasoconstrictor and bronchoconstrictor peptide that may be involved in the pathogenesis of bronchial asthma. We have investigated the effect of ET on the secretion of IL-6, IL-8, GM-CSF and G-CSF in a bronchial epithelial cell line (BEAS-2B). Incubation of BEAS-2B cells with ET-1 (10(-13) to 10(-7) M) for 4 h caused dose-related increases in the release of IL-8 (68% increase above control, P < 0.001) and IL-6 (43% increase above control, P < 0.001), compared to untreated control cells. After 48 h incubation, ET-1 also increased the release of IL-8 by 35% (P < 0.001) and GM-CSF by 38% (P < 0.01). ET-1 had no significant effect on G-CSF release. ET-1 did not induce cell proliferation at 24 or 48 h. Since ET-immunoreactive materials are expressed in epithelial cells in asthma, it is possible that ET-1 of epithelial origin may act in a paracrine or autocrine fashion on airway epithelial ET receptors to stimulate IL-8, IL-N6 and GM-CSF release. Thus, ET-1 may play a role in the regulation of the cytokine responses involved in inflammation of the airway mucosa.     

Lithium ion modulation of the neuronal responses evoked by monoaminergic receptor agonists

The authors studied the action of lithium ions on the responses of rat dorsal root ganglion neurons and frog spinal motoneurons evoked by monoamine agonists using the microelectrode technique. Lithium ions reversibly inhibit the depolarizing responses of spinal sensory neurons and motoneurons evoked by activation of muscarinic choline-, alpha 1-adreno-, and 5-hydroxytryptamine2 receptors, but enhance the hyperpolarizing neuronal responses evoked by activation of 5-hidroxytryptamine1A receptors.     

Prejunctional modulation by nociceptin of nerve-mediated inotropic responses in guinea-pig left atrium

Pediatric migraine differs from adult migraine in its epidemiology and symptom profile. Recent studies demonstrate the need to revise diagnostic criteria for pediatric migraine, demonstrate its epidemiology and suggest that its prevalence is increasing. These studies support the need for clinical trials to assess the utility of emerging therapies for pediatric migraine.     

Selective inhibition of T-cell-dependent immune responses by bisbenzylisoquinoline alkaloids in vivo

The bisbenzylisoquinoline (BBI) alkaloids, chondocurine, tetrandrine, isotetrandrine and cepharanthine, were tested for immunosuppressive activity in mice. A plaque-forming cell (PFC) response to a T-cell-dependent antigen, sheep red blood cell, was significantly suppressed by a 7 day treatment of chondocurine or tetrandrine at 1 mg/kg/day and of isotetrandrine at 50 mg/kg/day, but not suppressed by cepharanthine treatment. The suppressive effect of chondocurine was greater when it was given after immunization rather than before or concurrently. However, it did not affect the PFC response to a T-cell-independent antigen, lipopolysaccharide. A delayed-type hypersensitivity was also suppressed by chondocurine treatment. There was no significant change in lymphocyte number and proportion of T-cell subsets in the BBI alkaloid-treated mice. These data suggest that there is selective inhibition by chondocurine and tetrandrine of the T-cell-dependent immune reactions.     

Spaceflight and development of immune responses

The NIH.R1 Space Shuttle experiment was designed to study the effects of spaceflight on rodent development. Pregnant rats were flown on the Space Shuttle for 11 days, and pregnant control rats were maintained in animal enclosure modules in a ground-based chamber under conditions approximating those in flight. Additional controls were in standard housing. The effects of the flight on immunological parameters of dams, fetuses, and pups were determined. Blastogenesis of spleen cells in response to mitogen was inhibited in flown dams but was not inhibited in cells from their pups. Interferon-gamma production by spleen cells showed a trend toward inhibition in flown dams but not in their pups. The response of bone marrow cells to colony-stimulating factor showed a trend toward inhibition after spaceflight in dams, but the response of fetus and pup liver cells was not inhibited. Total serum IgG was not affected by spaceflight. None of the examined immune parameters that were altered in rat dams after spaceflight was found to be altered in their offspring.     

Effect of nitric oxide donors on neutrophil responses induced by immune complexes

The present study characterizes the effect of two nitric oxide (NO) donors, S-nitrosoglutathione (GSNO) and sodium nitroprusside (SNP), on the ability of neutrophils to perform different responses triggered by immune complexes (IC). Pretreatment of neutrophils with either GSNO or SNP exerted a biphasic action on antibody-dependent cellular cytotoxicity (ADCC) performed against erythrocytes (E) coated with IgG antibodies (IgG-E), depending on the amount of IgG employed. While with high amounts of antibodies ADCC was markedly inhibited, at low amounts of antibodies it was significantly increased. Both effects were prevented by haemoglobin, a NO scavenger. Moreover, these effects were reproduced by the cell-permeable analogue of cGMP, dibutyryl cGMP (Bt2cGMP). Other neutrophil functions triggered by IgG-E were also examined. It was found that NO donors did not affect either the phagocytosis of IgG-E or the emission of chemiluminescence (CL). Finally, neutrophil functions triggered by soluble IC (sIC) and precipitating IC (pIC) were analysed. It was observed that NO donors did not modify either cytotoxicity performed towards non-sensitized target cells or CL emission. The significance of these results is discussed.