Characteristic of humoral response of elderly to inactivated influenza vaccine

Eighty persons immunized with inactivated influenza vaccine in 1990-1991 epidemic season were examined. Serological tests: hemagglutination inhibition (HI), lectin neuraminidase (LN) and Western blot were performed with serum specimens taken before and 3-4 weeks after vaccination. Distribution of anti-influenza antibodies in the subclass was also examined. The results revealed humoral response to vaccine strains of influenza virus and also to strains caused infections in the past.     

Aqueous-based microencapsulation enhances virus-specific humoral immune responses in mice after parenteral inoculation

Vaccines are commonly administered by the parenteral route. Therefore, adjuvant strategies which include parenteral immunization may improve the efficacy of a number of current vaccines. The capacity of aqueous-based microencapsulation to enhance virus-specific IgG responses in mice inoculated intramuscularly with small quantities of antigen was evaluated. Mice were inoculated with either 10(4), 10(3), or 10(2) p.f.u. of microencapsulated rotavirus (bovine strain WC3), placebo microcapsules plus free virus, or virus alone. Mice were subsequently bled 1, 2, 4, 6, and 9 months after inoculation. Microencapsulation of rotavirus enhanced virus-specific humoral immune responses. In addition, virus-containing microcapsules composed of spermine-chondroitin sulfate induced levels of virus-specific antibodies greater than those found after inoculation with virus-containing microcapsules composed of spermine-alginate. Mechanisms by which microencapsulation may enhance virus-specific humoral immunity are discussed.     

IgD-receptor up-regulation on human peripheral blood T cells in response to IgD in vitro or antigen in vivo correlates with the antibody response to influenza vaccination

Aged individuals (more than 65 years) were classified as antibody (Ab) responders on the basis that they showed increases to more than or = 1:40 in serum Ab titers to all influenza virus strains present in the trivalent influenza vaccine within 4 weeks after immunization. The peripheral blood mononuclear cells (PBMC) from pre-immunization samples of blood taken from seven Ab-responders and seven Ab-nonresponders were examined for their ability to exhibit up-regulation of IgD-receptor (IgD-R) after exposure for 2 h to immobilized cross-linked IgD, as shown by rosetting with IgD-coated ox erythrocytes. The responsiveness to IgD was found to be predictive of the ability to produce Ab responses to viral protein Ag: the IgD-R up-regulation was greater than 5% in all Ab-responders and less than 4% in all the Ab-nonresponders. In addition, there was an excellent correlation between mean Ab titers (to the three viruses in sera collected 4 weeks after immunization) and the percentage of IgD-R+ cells obtained in response to IgD in PBMC from the same individual prior to immunization: p = 0.894. Injection of influenza vaccine itself also induced IgD-R on PBMC in vivo. The percentage of IgD-R+ cells peaked after 24 h, was still detectable above background by day 7 or 14, and returned to pre-injection levels by day 28 in young subjects and aged Ab-responders, but not in Ab-nonresponders. Similarly, purified peripheral blood T cells obtained from aged Ab-responders exhibited IgD-R upon immunization in vivo. These findings suggest that Ag injection causes rapid up-regulation of IgD-R by cross-linking IgD in humans as well as in mice as shown previously. In analogy with results in mice, the present data are consistent with a role for IgD-R+ T cells in the humoral response in man. Proliferative responses to influenza proteins in peripheral blood T cells from vaccinated individuals were found to peak on day 7 and were higher in Ab-responders than in Ab-nonresponders.     

Human humoral immune response to Dirofilaria species

BACKGROUND: Keloids are relatively common sequelae of trauma to the skin of the head and neck. A wide variety of treatment approaches developed over the years document the difficulty in eradicating these lesions. OBJECTIVE: To review the senior author's (W.H.L) 15-year experience in treating keloids both medically and surgically. DESIGN: A retrospective analysis of 202 patients with histologically documented keloids of the head and neck with at least a 2-year follow-up. RESULTS: A combination of precise surgical excision, postoperative steroid infiltration, silicone sheeting, and conservative auricular radiotherapy has resulted in an acceptable 15% recurrence rate overall. CONCLUSIONS: The treatment of facial keloids remains a challenge for the facial plastic and reconstructive surgeon. Precise surgical techniques with adjuvant therapies have resulted in a relatively low recurrence rate.     

Protective immune response of chickens against Newcastle disease, induced by the intranasal vaccination with inactivated virus

Intranasal vaccination of chickens with inactivated Newcastle disease virus (NDV) induced both local and systemic antibody responses, resulting in protection against intranasal challenge with a lethal dose of a virulent NDV strain. The immune response was enhanced by the use of cholera toxin B subunit (CTB) as an adjuvant and only small amounts of the challenge virus were recovered from the birds vaccinated together with CTB. On the other hand, subcutaneous vaccination with the same antigen induced only a serum antibody response in chickens, allowing the challenge virus to replicate in the sinus. The present results indicate that secretory antibodies induced on the respiratory mucosal surface by intranasal vaccination with inactivated NDV protected chickens from lethal infection by inhibiting virus replication at the portal of entry for the virus.     

Dysregulation of the humoral immune response in old mice

The increase in autoantibodies with age of both experimental animals and humans has been thought to reflect a shift in the antibody repertoire from foreign to self antigens. In mice, before immunization, the age-associated increase in antibodies reactive with a prototypic autoantigen, bromelain-treated autologous erythrocytes (BrMRBC), reflected a 3-fold increase in serum IgM and the number of IgM-secreting spleen cells in old compared with young mice. However, the percentage of the IgM-secreting spleen cell repertoire reactive with BrMRBC in old mice was actually approximately 50% that in young mice. In contrast, after immunization with sheep erythrocytes (SRBC), old mice showed a 5-fold increase in the percentage of IgM-secreting cells reactive with BrMRBC while young mice showed no significant increase. The converse is true for the percentage of IgM-secreting spleen cells in old mice specific for SBRC, which is 10% the number generated by young mice. The increased autoantibody response of old mice is not, however, linked to their poor response to the nominal antigen. Thus, immunization with phosphorylcholine (PC) conjugated keyhole limpet hemocyanin, an antigen that induces a comparable anti-PC response in old and young mice, also induced more autoantibody forming cells in old than young mice. The increased autoantibody response of old mice after immunization can be accounted for by both an increased number of Ig-secreting spleen cells as well as an increased percentage of the expressed repertoire of IgM-secreting spleen cells that react with autoantigens.(ABSTRACT TRUNCATED AT 250 WORDS)     

Systemic and local immune responses after parenteral influenza vaccination in juvenile diabetic patients and healthy controls: results from a pilot study

Diabetes patients suffer frequent complications and some excess mortality after influenza virus infection. Despite widespread agreement that diabetic patients should be routinely vaccinated against influenza, some reports claim that diabetics have a poor immune response to influenza vaccine. We have performed a pilot study to examine the humoral immune response of juvenile diabetics and matched healthy controls vaccinated with inactivated trivalent influenza vaccine. By enzyme-linked immunospot assay we found that both groups had comparable magnitude and kinetics of influenza-specific antibody secreting cell response. The influenza-specific antibody response in both serum and oral fluid were similar for both groups, and also showing a kinetic profile in accordance with our earlier data for healthy adults. Our study did not detect a difference in the humoral immune response between juvenile diabetics and healthy controls.     

An antigen valence theory to explain the evolution and organization of the humoral immune response

The three modes of antibody production, natural, T independent (TI) and T dependent (TD) are conserved among vertebrate species suggesting an important role for each in protection against pathogens. Here, I use an artificial 'universe' to argue that the three modes of antibody production represent layers that evolved to deal optimally with antigens of different valence. Thus, the apparently more sophisticated TD response has not superseded the natural and TI components of the humoral immune response. Furthermore, the characteristic differences in isotype, somatic mutation and memory displayed by each antibody layer are appropriate for their targeted range of surface structures. It is also suggested that the TD and TI activation arms are at the extremes of a continuum, with signal integration of antigen and T cell-derived signals contributing to B cell decisions about isotype selection, proliferation and secretion that minimize the time to protection.     

Effect of diarrhea on the humoral response to oral polio vaccination

OBJECTIVE: The purpose of this study was to measure the effect of concurrent diarrheal illness on seroconversion to trivalent oral polio vaccine (OPV). METHODS: Six- to 16-week-old infants with acute diarrhea and age-matched controls received single doses of OPV at enrollment, 4 weeks after enrollment and 8 weeks after enrollment. Serum specimens were obtained at enrollment, before the second OPV dose and 4 weeks after the third OPV dose for measurement of antibody titers to polio virus by the microneutralization assay. RESULTS: Four weeks after the first OPV dose, the serologic responses to poliovirus types 2 and 3 in the case cohort were lower by 26 and 34%, respectively, than in the control cohort (P < 0.002 for both comparisons). Poliovirus type 2 and 3 geometric mean antibody titers in the diarrhea cohort were approximately 50% of the geometric mean antibody titers in the control cohort (235 (95% confidence interval (CI) 154 to 359) vs. 446 (95% CI 350 to 569) and 64 (95% CI 45 to 90) vs. 112 (95% CI 88 to 143), respectively, P < 0.01 for both comparisons). After the third OPV dose the seroconvertion rates to poliovirus types 2 and 3 each remained about 10% lower in the case cohort than in the control cohort, but the differences were not statistically significant. CONCLUSION: Concurrent acute diarrhea adversely affects seroconvertion rates of type 2 and 3 polioviruses among infants in Bangladesh receiving the first dose of trivalent OPV.     

Cross-talk between gammadelta T lymphocytes and immune cells in humoral response

The role of gamma delta T cells in immunoregulation is largely unknown. In the current study we noted that gamma delta T cells play a positive role in the humoral response. These positively acting gamma delta T cells are required for the successful adoptive cell transfer of the humoral response, as well as for in vitro generation of plaque-forming cells (PFC). The presented results show that gammadelta T cells cause an increase in interleukin-10 (IL-10) production, which partly elucidates the mechanism of action of these cells. However, experiments with cell culture inserts strongly suggest that direct cell-cell contact between immune and gamma delta H-2-compatible regulatory T cells is critical to the exertion of the positive immunoregulatory function of gamma delta cells. The mechanism of cross-talk between these two cell populations is still not clear but we regard as most likely that the positively acting gamma delta T cells may interact with a complex of heat-shock protein-non-polymorphic MHC (IB) on the surface of T helper type 2 and/or B cells. This could provide, by direct cell-cell contact, the cognate recognition between gamma delta T-cell receptors and heat-shock protein-MHC that leads to positive internal signalling in the immune cells.     

Preliminary studies on humoral immune response of sheep to wohlfahrtiosis

The humoral immune response of sheep to wohlfahrtiosis was studied. An enzyme-linked immunosorbent assay was developed to compare four different types of antigens obtained from the third-stage larvae of Wohlfahrtia magnifica. The antigen prepared from salivary glands detected a humoral response in all 35 infested sheep and was more specific in the ELISA than cuticular, intestinal or whole larval antigens. The level of the humoral response in sheep to wohlfahrtiosis differed according to the location of the wounds.     

Randomized comparison of early and late vaccination with inactivated poliovirus vaccine after allogeneic BMT

Forty-five adult HLA-matched sibling BMT recipients were randomized to receive inactivated poliovirus vaccine (IPV) at 6, 8 and 14 months (early group, n = 23) or at 18, 20 and 26 months after BMT (late group, n = 22). Ninety-five percent of the early group patients had protective antibody titres of > or = 4 to poliovirus type 1 (PV1), poliovirus type 2 (PV2) and poliovirus type 3 (PV3) by a microneutralization assay prior to the first vaccination, at 6 months after BMT. The corresponding proportion for the late group patients was only 67% at 18 months. The antibody responses 1 month after each of the three IPV doses were similar in the two vaccination groups, except that four-fold responses occurred more frequently after the first dose to PV2 and PV3 in the late group. All patients had a protective antibody titre to all poliovirus serotypes 1 and 22 months after the third vaccine dose, except one patient in the early group who lacked antibodies to PV3 at 22 months. Acute GVHD accelerated the decrease of poliovirus antibody titres prior to vaccination but had no influence on vaccination response. Chronic GVHD neither influenced the patient's ability to retain poliovirus antibodies prior to vaccination nor impaired responses to vaccinations. A vaccination schedule consisting of three IPV doses was equally immunogenic when started at 6 or 18 months after allogeneic BMT.     

Genetic analysis of the humoral immune response of White Leghorn chicks

Total agglutinin antibody titers, 2-mercapto ethanol (2-ME) sensitive and 2-ME resistant antibody titers were determined in 598 White Leghorn chicks after intramuscular injection with sheep red blood cells. Antibody titers were determined on day 0 and on days 3, 7, 10, 13 postinjection. Mean total tier (5.2, log2 value) was highest on day 7. Females showed a significantly higher response to injection with sheep red blood cells than males. Also, significant hatch effects were noted. Heritability estimates generally varied from 0 to .5 for all parameters. In the earlier stages of the immune response the sire estimate of heritability for total and 2-ME sensitive antibody titer was higher than the dam estimate. Additive genetic correlations between 2-ME sensitive (days 3 to 13) and resistant (days 7 to 13) antibody titers were negative, varying from -.30 to -.93. The response to selection for total antibody titer is, therefore, not easily predicted.     

Group selection for adaptation to multiple-hen cages: humoral immune response

A selected line of White Leghorns, which has shown improved survivability and reduced feather loss in large multiple-hen cages, was evaluated for humoral immune response to SRBC under both stressed and unstressed conditions. Three lines of chickens (selected, control, and commercial) were housed in either single- (1 hen) or multiple-hen cages (12 hens, social competition) and subjected to a cold ambient temperature (0 C) at 33 wk of age and to two heating episodes (38 C) at 44 wk of age. Each hen was challenged intravenously with 1 mL of a 7% saline suspension of SRBC at the time that cold exposure was initiated. Hens subjected to high ambient temperatures had been exposed previously to a cold temperature, but were not challenged with SRBC until 16 to 18 h following the end of the second heating episode. Exposure to cold caused immunosuppression in single-caged hens, but not in hens in colony cages. Single- vs colony-caged hens of the control environment challenged with SRBC at 33 wk of age had similar primary hemagglutinin responses to SRBC. Hens subjected to heat experienced immunosuppression at 9 and 12 d following challenge to SRBC when compared to the controls. Hens of multiple-bird cages challenged with antigen at 44 wk of age had a significantly lower hemagglutinin response to SRBC than those reared in single-bird cages. The three lines of genetic stock had similar primary hemagglutinin responses to SRBC; the interactions of genetic stock with cage size or environmental temperature were not significant. It was concluded that genetically selecting hens for survival in multiple-hen cages did not affect their humoral immune response to SRBC.     

Fetal immune response following prematurely ruptured membranes

Concentrations of immunoglobulins (Ig)A1, and IgA2, IgD, IgE, IgG, and IgM have been determined in cord blood, amniotic fluid, and maternal serum in a group of patients with a history of prematurely ruptured membranes (PRM) prior to the onset of labor and in a control group of patients undergoing normal delivery and without a history of infection during pregnancy. IgA and IgD were determined by sensitive hemagglutination-inhibition tests; IgG and IgM, by radial immunodiffusion; IgE, by a radioimmunoassay. There was evidence for an immune response in 10 of 16 cases of PRM: five of 16 had increased IgA but normal IgM; three of 16 had increased IgA and IgM; two of 16 had high IgM and normal IgA in cord blood. In patients with significantly increased levels of either IgA or IgM or both, there was a decreased level of IgD. These changes are most likely the result of the immune response to ascending infection from the maternal genitals. The sensitive testing method employed could demonstrate the presence of IgD in 53 per cent of normal cord blood samples and 72 per cent of amniotic fluid samples obtained at term. IgE was found in all normal cord blood and amniotic fluid samples tested. By concentrating the amniotic fluid up to 180-fold, IgM was demonstrated in all normal samples tested. The potential importance of IgA determinations in cord blood in addition to IgM determination for detection of intrauterine infections is stressed.     

Pneumococcal vaccination in HIV-1-infected adults in Uganda: humoral response and two vaccine failures

OBJECTIVES: To assess the feasibility of establishing a pneumococcal vaccine trial among HIV-1-infected adults in Uganda and to characterize their responses to 23-valent pneumococcal polysaccharide vaccine. DESIGN: An open-label pilot trial to assess recruitment and compliance of HIV-1-infected adults in Uganda to vaccination and to determine the immunogenicity of the vaccine. SETTING: A community clinic for HIV-1-infected adults in Entebbe, Uganda. METHODS: Levels of capsule-specific IgG to four common vaccine capsular serotypes were measured before vaccination and 1 month after vaccination. Subsequent rates of disease episodes and deaths, and immunologic responses in two vaccine failures, were followed. RESULTS: One month after-vaccination, both HIV-1-infected (n = 77) and seronegative control subjects (n = 10) demonstrated a significant rise in capsule-specific immunoglobulin G (IgG) for three of four serotypes tested, but levels were significantly lower among HIV-1-infected patients. In 149 patient-years of follow-up, two (2.6%) developed pneumococcal pneumonia, one bacteremic with serotype 1 and one non-bacteremic with serotype 13, a non-vaccine serotype; both patients showed inadequate killing of the organism in vitro. In this same follow-up period, 29 (38%) patients died. CONCLUSION: HIV-1-infected adults in Uganda are at high risk of pneumococcal disease and show a significant but suboptimal response to pneumococcal vaccine. Although reliable recruitment and follow-up of vaccinees is feasible, evaluation of vaccine efficacy may be compromised by limited responses to common vaccine serotypes, an unknown incidence of disease with non-vaccine serotypes, and a high rate of mortality unrelated to Streptococcus pneumoniae infection.     

Mechanisms of chorionic gonadotropin action on splenocytes, suppressed in their humoral immune response

Chorionic gonadotropin (CG) used at 10 and 50 IU/ml concentrations was introduced into a short-term macroculture of splenocytes of CBA mice suppressors fractionated on a nylon wool column. Regulatory effects of CG were evaluated in a syngeneic transfer system by the degree of inhibition of a humoral immune response in recipients. It was found that CG (50 IU/ml) inhibits the functional activity of splenocyte suppressors. The observed effect of the hormone was blocked by introduction into the incubation medium of the inhibitor, inositol-1-monophosphatase (lithium), and did not depend on cyclooxygenase (voltaren) or potential-independent Ca(2+)-channel (verapamil) inhibitors. Determination of the intracellular cAMP level by radioimmunoassay revealed a reliable increase of this secondary messenger in splenocyte suppressors during their incubation with CG. The ability of CG (50 IU/ml) to inhibit the functional activity of intact T-lymphocytes (but not B-cells) was established. The suppressive hormone activity was also followed by cAMP level increase in target cells. These findings suggest that the mechanism of a transmembrane transfer of the CG signal in splenocyte suppressors is related to the adenylate cyclase system and, probably, to phosphoinositide metabolism products.     

The influence of sequential annual vaccination and of DHEA administration on the efficacy of the immune response to influenza vaccine in the elderly

The present study examined the effect of repeated vaccination and of dehydroepiandrosterone (DHEA) treatment on the immune response to influenza vaccine in elderly subjects. Seventy-one elderly volunteers, aged 61-89 years, enrolled in a prospective randomized, double-blind study to receive either DHEA (50 mg qd p.o. for 4 consecutive days starting 2 days before immunization) or placebo. Antibody response against the three strains of vaccine was measured before and 28 days after vaccination, and compared between previously vaccinated and non-vaccinated subjects. DHEA treatment did not enhance established immunity. A significant decrease in attainment of protective antibody titer (titer of 1:40 or greater) against A/Texas in subjects with non-protective baseline antibody titer was recorded following DHEA treatment compared to placebo (52 vs. 84%, P < 0.05). Post-immunization titers against influenza A strains were significantly higher in those subjects who were never immunized before. Additionally, post-vaccination protective titers against the A/Johannesburg strain were more prevalent in those subjects who were never vaccinated before. The results were not the same for anti-B/Harbin antibodies-repeated vaccination caused a non-significant increase in HI titer in previously vaccinated subjects.     

Autoimmune thrombocytopenia following peripheral blood stem cell autografting

A 22-year-old woman diagnosed as AML (M3) received myeloablative chemotherapy followed by autologous peripheral stem cell transplantation (PBSCT). Rapid hematopoietic reconstitution occurred. By day 10, the neutrophil count was > 0.5 x 10(9)/l and the platelet count > 50 x 10(9)/l. The platelet count was 145 x 10(9)/l on day 20. Purpura developed on the anterior chest and legs on day 50, at which time the platelet count fell to 17 x 10(9)/l. The BM was hypocellular with an increase in megakaryocytes. Platelet-associated IgG (PAIgG) was 88.1 ng/10(7) platelets (normal range 9-25 ng/10(7)); a diagnosis of idiopathic thrombocytopenic purpura (ITP) was made. Prednisolone administration led to an increase in the platelet count and a decrease in PAIgG. Analysis of lymphocyte subsets revealed an increased number of CD3+ gamma/delta T cells. It is postulated that the thrombocytopenia in this case was due to an autoimmune mechanism such as ITP.