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PubMed2005

Cardiac arrest/cardiopulmonary resuscitation augments cell-mediated immune function and transiently suppresses humoral immune function.

Immune system activation has implications for cerebrovascular health, but little is known about the function of the immune system after a major cerebrovascular event, such as cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Cardiac arrest and cardiopulmonary resuscitation damages the hippocampus, an important component of the hypothalamic-pituitary-adrenal (HPA) axis, and alterations in HPA axis activity can affect immune function. We tested the hypothesis that CA/CPR (approximately 8 mins) would cause HPA axis dysregulation and alter the delayed type hypersensitivity (DTH) response to antigenic challenge. We also assessed the primary and secondary antibody response of mice exposed to CA/CPR. Of the mice exposed to CA/CPR, half had brains protected by hypothermia to isolate the effects of the CA/CPR procedure from the effects of CA/CPR-induced neuronal damage. Cardiac arrest and cardiopulmonary resuscitation-induced neuronal damage resulted in a persistent elevation of blood corticosterone concentration and a concomitant augmentation of the DTH response to antigenic challenge. Furthermore, immune activation before CA/CPR decreased survival after global ischemia. These data highlight the potential impact of neuronal damage on cell-mediated immune function and the role of humoral immune activation in outcome after global ischemia.

Animals↗
PubMed1991

Immune response gene regulation of the humoral immune response to Porphyromonas gingivalis fimbriae in mice.

Among various strains of mice immunized orally with Porphyromonas gingivalis fimbriae and adjuvant GM-53 in liposomes, BALB/c and DBA/2 mice (H-2d) were found to be high responders to the fimbriae, CBA/J and C3H mice (H-2k) were intermediate, while C57BL/6 mice were low responders in terms of serum IgG and salivary IgA responses. Furthermore, humoral immune responses were examined using congeneic mice of B10 background showing different H-2 haplotypes, and it was revealed that B10.D2 mice (H-2d), followed by B10.BR (H-2k), responded well to antigenic stimulation of the fimbriae, while C57BL/10 mice (B10, H-2b) were low responders to the fimbriae. Hybrids between BALB/c and C57BL/6 mice were found to reflect a phenotype of low responders. Thus, the humoral immune responses to P. gingivalis in mice are restricted by H-2 haplotype.

Animals↗
PubMed1998

Cytokine and hepatitis B virus DNA co-immunizations enhance cellular and humoral immune responses to the middle but not to the large hepatitis B virus surface antigen in mice.

Genetic immunization is a potentially useful strategy to prevent or treat hepatitis B virus (HBV) infection. We have previously shown that HBV envelope proteins are highly immunogenic using this technique. The large envelope protein (LHBs), however, induced significantly weaker humoral and cellular immune responses when compared with the middle envelope protein (MHBs). We studied the effect of co-immunizations with cytokine DNA expression constructs encoding for interleukin (IL)-2 and (GM-CSF) on the immunogenicity of LHBs at the B-and T-cell level. Co-immunizations of mice with plasmids encoding for MHBs and IL-2 or GM-CSF increased anti-HBs responses, helper T-cell proliferative activity, and cytotoxic T lymphocyte (CTL) killing. In contrast, co-immunizations of plasmids encoding for LHBs and IL-2 or GM-CSF had no effect on humoral and cellular immune responses. LHBs did not inhibit the production or secretion of IL-2 and GM-CSF. In addition, IL-2, tumor necrosis factor alfa (TNF-alpha), and interferon gamma (IFN-gamma) had no suppressive effect on HBV envelope protein expression in vitro. Based on these data, MHBs, but not LHBs, genetic immunization can be augmented by IL-2 or GM-CSF cytokines.

Animals↗
PubMed1999

Expression of interleukin-2 receptor alpha and CD45RO antigen on T lymphocytes cultured with rubella virus antigen, compared with humoral immunity in rubella vaccinees.

We studied the expression of interleukin-2 receptor alpha (CD25)+ CD45RO+ CD4+ T lymphocytes (T-cell activation) in response to the rubella virus (RV) antigen (Matsuura strain, Biken, Osaka, Japan) using three-color-staining flow cytometry. The subjects were 48 healthy children (3-14 years old, 31 boys and 17 girls), who had received either monovalent vaccine (n = 5; mean age, 13.2 years) or measles-mumps-rubella (MMR) vaccine (n = 21; mean age, 10.5 years), had been naturally infected (n = 5; mean age, 11.4 years), or had been neither vaccinated nor naturally infected (n = 17; mean age, 10.0 years) and 62 healthy adolescents and adults (15-37 years old; 19 males and 43 females), who had received monovalent vaccine (n = 26, mean age, 27.4 years), had been naturally infected (n = 8; mean age, 24.0 years), or had been neither vaccinated nor naturally infected (n = 8; mean age, 16.5 years). Ninety-four of 110 subjects had HI titers > or = 1:16. T-cell activation in these subjects was significantly higher than that in 6 seronegative (HI titers < 1:8) subjects (p < 0.05). T-cell activation did not differ significantly with the history of exposure to RV. HI antibody titers > or = 1:16 and T-cell activation persisted in vaccinated subjects for > or = 20 years and was similar to those in naturally infected subjects. Our results suggest that cell-mediated immunity and humoral immunity persist for at least 20 years after vaccination.

Adolescent↗
PubMed2000

Studies of the humoral immune response.

The humoral immune response arises from a complex choreography of cells and molecules that interact to produce lasting and effective defenses against pathogens. For more than fifteen years, our laboratory has studied how humoral responses are initiated, how they mature, and how they are remembered. This work has come from many hands and in this brief synopsis, I cannot provide the full recognition that my students, postdoctoral fellows, and collaborators merit. I hope that my colleagues can accept this translucence and know that their efforts are recognized and deeply appreciated, nonetheless.

Animals↗
PubMed1991

[Experimental study of schistosome immune RNA on transfer of cellular and humoral immunity to normal mice].

The present paper reported the extraction of immune RNA (iRNA) from spleen cells of Schistosoma japonicum infected rabbits and the activity of this schistosome iRNA (SiRNA) on transfer of cellular immunity and humoral immunity using macrophage migratory inhibition test (MMIT) and Dot-ELISA. The results indicated that specific cellular immunity could be transferred to normal mice by SiRNA either via in vivo or in vitro sensitization. Intraperitoneal inoculation of SiRNA to normal mice may result in production of specific antibodies.

Animals↗
PubMed2004

Pertussis-specific cell-mediated and humoral immunity in adolescents 3 years after booster immunization with acellular pertussis vaccine.

We evaluated pertussis-specific cell-mediated immunity (CMI) and humoral immunity in adolescents 3 years after they received an acellular pertussis booster immunization. Two hundred sixty-four adolescents were examined for immunoglobulin G antibodies, and 49 were examined for CMI against Bordetella pertussis antigens 40 months after receiving the booster. A control group of similarly aged adolescents who had received diphtheria and tetanus vaccination 3 years earlier was included for comparison. Pertussis-specific CMI persisted at greater than prebooster immunization levels. Although they had decreased by the 3-year follow-up, antibody levels remained significantly higher than prebooster immunization levels. Antibodies against pertussis antigens and CMI against filamentous hemagglutinin and pertactin were significantly higher in vaccinated adolescents than in control subjects. The acellular pertussis booster immunization provides long-term CMI and humoral immunity lasting for >or=3 years. The significantly higher immunity observed in the diphtheria, tetanus, and acellular pertussis vaccine recipients, compared with that in control subjects, indicates that these responses are more likely to have resulted from the booster immunization than from the boosting effects of natural B. pertussis infection.

Adolescent↗
PubMed1999

Humoral immune responses in periodontal disease may have mucosal and systemic immune features.

The humoral immune response, especially IgG and IgA, is considered to be protective in the pathogenesis of periodontal disease, but the precise mechanisms are still unknown. Immunoglobulins arriving at the periodontal lesion are from both systemic and local tissue sources. In order to understand better the local immunoglobulin production, we examined biopsy tissue from periodontitis lesions for the expression of IgM, IgG, IgA, IgE and in addition the IgG and IgA subclasses and J-chain by in situ hybridization. Tissues examined were superficial inflamed gingiva and the deeper granulation tissue from periodontal sites. These data confirm that IgM, and IgG and IgA subclass proteins and J-chain can be locally produced in the periodontitis tissues. IgG1 mRNA-expressing cells were predominant in the granulation tissues and in the gingiva, constituting approx. 65% of the total IgG-expressing plasma cells. There was a significantly increased proportion of IgA-expressing plasma cells in the gingiva compared with the granulation tissue (P < 0.01). Most of the IgA-expressing plasma cells were IgA1, but a greater proportion expressed IgA2 mRNA and J-chain mRNA in the gingival tissues (30.5% and 7.5%, respectively) than in the periodontal granulation tissues (19% and 0-4%, respectively). The J-chain or dimeric IgA2-expressing plasma cells were located adjacent to the epithelial cells, suggesting that this tissue demonstrates features consistent with a mucosal immune response. Furthermore, we were able to detect the secretory component in gingival and junctional epithelial cells, demonstrating that the periodontal epithelium shares features with mucosal epithelium. In contrast, deeper tissues had more plasma cells that expressed IgM, and less expressing IgA, a response which appears more akin to the systemic immune response. In conclusion, this study suggests that immune mechanisms involved in the pathogenesis of periodontitis may involve features of both the mucosal and systemic immune systems, dependent on tissue location.

Adult↗
PubMed1999

Constitutive expression of human cytomegalovirus (HCMV) glycoprotein gpUL75 (gH) in astrocytoma cells: a study of the specific humoral immune response.

The humoral immune response to gpUL75 (gH) was determined in different groups of human cytomegalovirus (HCMV) infected subjects using a full-length glycoprotein constitutively expressed in an astrocytoma cell line. The recombinant molecule consisted of two distinct isoforms resembling the authentic protein of infected cells. Separated from the interactions of other viral gene products gH failed to form an oligomeric complex, thus exhibiting exclusively epitopes present on the monomer. Ninety five percent of serum samples from latently-infected healthy adults revealed the presence of gH-specific IgG. Moreover, examination of sequential sera from immunocompromised and immunocompetent individuals undergoing active HCMV infection demonstrated that antibodies to gH occurred in most cases simultaneously with those to the abundant surface antigen gpUL55 (gB) and at similar titres. Appearance of this response was correlated with a considerable increase of the virus-neutralizing activity and most likely associated with restriction of viral dissemination during subsequent viremic episodes. Together, these results suggest that glycoprotein H of HCMV is like gB, a highly immunogenic component of the infectious particle.

Adult↗
PubMed1997

Systemic bias of cytokine production toward cell-mediated immune regulation in IDDM and toward humoral immunity in Graves' disease.

Disturbed immune regulation has been postulated to be crucial in the pathogenesis of IDDM and other autoimmune or allergic diseases. We therefore tested the hypothesis of a general bias in the peripheral immune system in patients with recent-onset IDDM or Graves' disease in comparison to healthy control subjects by studying whole blood cultures stimulated with phytohemagglutinin. Cells from IDDM patients (n = 53) produced significantly higher amounts of Th1 cytokines gamma-interferon (IFN-gamma) (P = 0.028) and tumor necrosis factor alpha (TNF-alpha) (P = 0.007) than normal control subjects (n = 56), while Th2 cytokine levels (interleukin [IL]-4, IL-10) were similar. Low levels of islet cell antibodies (ICAs) in IDDM patients were associated with high levels of Th1 and Th2 cytokines. Antibodies to GAD, ICA512, or insulin did not correlate with individual cytokine profiles. Also, HLA-DQ types did not significantly correlate with either Th1 or Th2 cytokine production. Conversely, whole blood cultures from patients with Graves' disease (n = 18) produced significantly less TNF-alpha and IL-4 than normal subjects (P = 0.001-0.006). However, when the balance between Th1 and Th2 cytokine production was analyzed in individuals, the ratio between IFN-gamma or TNF-alpha and IL-4 or IL-10 was clearly biased toward Th1 reactivity in patients with IDDM (P = 0.0001), while a dominance of Th2 cytokine production was seen in Graves' disease (P = 0.0001). The ratio of counterregulatory cytokines appeared to be the most reliable marker of the individual disease process. This study provides first evidence of a systemic bias in the immune regulation of humans, which might be either toward cell-mediated immunity (Th1) in IDDM or humoral immunity (Th2) in Graves' disease.

Adolescent↗
PubMed2005

Prenatal androgen exposure modulates cellular and humoral immune function of black-headed gull chicks.

Avian eggs contain considerable amounts of maternal yolk androgens, which have been shown to beneficially influence the physiology and behaviour of the chick. As androgens may suppress immune functions, they may also entail costs for the chick. This is particularly relevant for colonial species, such as the black-headed gull (Larus ridibundus), in which the aggregation of large numbers of birds during the breeding season enhances the risk of infectious diseases for the hatching chick. To test the effect of maternal yolk androgens on the chick's immune function, we experimentally manipulated, in a field study, yolk androgen levels within the physiological range by in ovo injection of either androgens (testosterone and androstenedione) or sesame oil (control) into freshly laid eggs. We determined cell-mediated immunity (CMI) and humoral immunity of the chicks at the beginning of the nestling period to evaluate early modulatory effects of yolk androgens on immune function. Embryonic exposure to elevated levels of androgens negatively affected both CMI and humoral immunity in nestling gull chicks. Consequently, maternal yolk androgens not only entail benefits of enhanced competitiveness and growth as previously shown, but also costs in terms of immunosuppression. The outcome of embryonic yolk androgen exposure thus likely depends on the post-hatching circumstances for the developing offspring such as parasite exposure and degree of sibling competition.

Androgens↗
PubMed2005

Adenoviral expression of a truncated S1 subunit of SARS-CoV spike protein results in specific humoral immune responses against SARS-CoV in rats.

The causative agent of severe acute respiratory syndrome (SARS) has been identified as SARS-associated coronavirus (SARS-CoV), but the prophylactic treatment of SARS-CoV is still under investigation. We constructed a recombinant adenovirus containing a truncated N-terminal fragment of the SARS-CoV Spike (S) gene (from--45 to 1469, designated Ad-S(N)), which encoded a truncated S protein (490 amino-acid residues, a part of 672 amino-acid S1 subunit), and investigated whether this construct could induce effective immunity against SARS-CoV in Wistar rats. Rats were immunized either subcutaneously or intranasally with Ad-S(N) once a week for three consecutive weeks. Our results showed that all of the immunized animals generated humoral immunity against the SARS-CoV spike protein, and the sera of immunized rats showed strong capable of protecting from SARS-CoV infection in vitro. Histopathological examination did not find evident side effects in the immunized animals. These results indicate that an adenoviral-based vaccine carrying an N-terminal fragment of the Spike gene is able to elicit strong SARS-CoV-specific humoral immune responses in rats, and may be useful for the development of a protective vaccine against SARS-CoV infection.

Adenoviridae↗
PubMed1994

Persistence of cell-mediated immunity and decline of humoral immunity to the intracellular bacterium Francisella tularensis 25 years after natural infection.

The humoral and cell-mediated immune responses to the facultative intracellular pathogen Francisella tularensis were studied in subjects who had tularemia 25 years earlier. Serum agglutinin titers were low. Of 53 subjects, only 2 had a titer > 40. The F. tularensis-induced T cell response, on the other hand, was vigorous and in fact similar in magnitude to the response to purified protein derivative (PPD) of Mycobacterium tuberculosis. T cells from 44 of 52 subjects showed a significant (P < .05) proliferative response in vitro to each of four membrane proteins of F. tularensis. Only 2 subjects did not respond to any of the proteins. In most cultures from 18 subjects tested, interferon-gamma was produced in response to the proteins. During the last 25 years, tularemia has been reported only rarely in the region where the subjects lived, suggesting that an antigen-specific T cell response may persist after tularemia independently of reexposure to F. tularensis.

Adult↗
PubMedDate not supplied

[Effect of extremely high frequency electromagnetic radiation of low intensity on parameters of humoral immunity in healthy mice].

The modification of indices of the humoral immune response to thymus-dependent antigen (sheep erythrocytes) after a whole-body exposure of healthy mice to low-intensity extremely-high-frequency electromagnetic radiation was studied. Male NMRI mice were exposed in the far-field zone of horn antenna at a frequency of 42.0 GHz and energy flux density of 0.15 mW/cm2 under different regimes: once for 20 min, for 20 min daily during 5 and 20 successive days before immunization, and for 20 min daily during 5 successive days after immunization throughout the development of the humoral immune response. The intensity of the humoral immune response was estimated on day 5 after immunization by the number of antibody-forming cells of the spleen and antibody titers. Changes in cellularity of the spleen, thymus and red bone marrow were also assessed. The indices of humoral immunity and cellularity of lymphoid organs changed insignificantly after acute exposure and series of 5 exposures before and after immunization of the animals. However, after repeated exposures for 20 days before immunization, a statistically significant reduction of thymic cellularity by 17.5% (p < 0.05) and a decrease in cellularity of the spleen by 14.5% (p < 0.05) were revealed. The results show that low-intensity extremely-high-frequency electromagnetic radiation with the frequency and energy flux density used does not influence the humoral immune response intensity in healthy mice but influences immunogenesis under multiple repeated exposures.

Animals↗
PubMed1999

Limited humoral immunity in hepatitis C virus infection.

BACKGROUND & AIMS: The extremely high rate of chronicity to hepatitis C virus (HVC) infection suggests an inefficient immune response. The humoral immune response to HCV was evaluated in 60 patients with chronic HCV infection and in 12 patients acutely infected with HCV. METHODS: A number of recombinant HCV antigens including the core, envelope 2 (E2), nonstructural (NS) 3, NS4, and NS5 proteins, and NS4a and E2-HVR-1 peptides were used in enzyme-linked immunoassays. RESULTS: Immunoglobulin (Ig) G antibody responses to these viral antigens, except for the HCV core, were highly restricted to the IgG1 isotype. The prevalence of antibodies of the IgG1 isotype specific for the HCV core, E2, E2-HVR1, NS3 (helicase domain), NS4, and NS5 antigens was 97%, 98%, 28%, 88%, 33%, and 68%, respectively. Antibodies of the IgG3 isotype specific for E2, E2-HVR-1, NS3, NS4, and NS5 were detected in a minority of serum samples. The IgG2 and IgG4 isotypes were rarely if ever detected. Furthermore, antibody responses to HCV viral antigens were of relatively low titer and, with the exception of anti-HCV core, were delayed in appearance until the chronic phase of infection. CONCLUSIONS: The IgG1 restriction, low titer, and delayed appearance of antibody responses elicited during HCV infection suggest that the immunogenicity of HCV proteins is limited in the context of natural infection. Inasmuch as recombinant HCV viral antigens perform as relatively normal immunogens in small animals, we suggest that the defective humoral immune responses during HCV infection may be attributable to an "immune avoidance" strategy.

Acute Disease↗
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↗