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At least 1,207 records · Page 67Linked to original sources
PubMed1997

Antibody persistence and Haemophilus influenzae type b carriage after infant immunisation with PRP-T.

OBJECTIVES: To assess the persistence of serum Haemophilus influenzae type b antibodies and the prevalence of H influenzae type b carriage in a group of preschool age children previously vaccinated in infancy. DESIGN: Names were randomly selected from immunisation records. Families were visited on five occasions over a period of 12 months and throat swabs were taken from all family members present, with blood obtained from children at the first and last visits. RESULTS: One hundred and fifty three children at a median age of 3.6 years had a geometric mean titre (GMT) of 1.06 micrograms/ml (95% CI 0.80 to 1.38). Eight per cent had an undetectable antibody concentration, received a booster dose of plain PRP vaccine, and responded with concentrations > 2 micrograms/ml. GMT at 4.5 years of age was 0.89 microgram/ml (0.69 to 1.16). Twelve children who had been exposed to H influenzae had a GMT of 4.7 v 0.8 micrograms/ml for those without exposure. CONCLUSIONS: Accelerated immunisation against H influenzae without a second year booster results in persistence of satisfactory serum concentrations of antibody to 4.5 years of age. In those with undetectable antibody, immunological memory may still be present.

Antibodies, Bacterial↗
PubMed2002

The UK Hib vaccine experience.

Haemophilus influenzae type b (Hib) is an important pathogen in children <5 years of age. The Hib conjugate vaccines were the first polysaccharide-protein conjugate vaccines to be used in routine childhood schedules. Their introduction in the UK in 1992 has resulted in the near elimination of Hib disease. The UK Hib vaccine programme has a number of unique features including an accelerated schedule, absence of a booster dose, and the inclusion of a catch up component at the beginning of the programme. Collaboration between UK paediatricians, microbiologists, and public health physicians has allowed active national surveillance of Haemophilus influenzae disease and enabled important conclusions to be drawn. These include high vaccine effectiveness, the presence of herd immunity, and the frequency of risk factors in cases of vaccine failure and in cases of invasive disease due to non-b H influenzae. Parallel studies have shown the immunogenicity, induction of immunological memory, and persistence of immunity following vaccination at the UK schedule, as well as measuring the impact of vaccination on pharyngeal Hib carriage. Cases continue to occur and complacency is ill advised, particularly as other vaccines and combinations are introduced. Surveillance of H influenzae disease in the UK remains important.

Carrier State↗
PubMed1995

Presence of secretory IgA antibodies to an enteric bacterial pathogen in human milk and saliva.

The concept of a common mucosal immune system in man was tested by examining the concurrent presence of specific-secretory IgA (SIgA) antibodies in human milk and saliva from three groups of subjects: 64 Sri Lankan women living in Sri Lanka; 20 immigrant Asian women living in Birmingham (median duration of residence in the United Kingdom five years); and 75 Caucasian women living in Birmingham (controls). Enzyme linked immunosorbent assays (ELISA) were developed to detect enterotoxigenic Escherichia coli (ETEC) colonisation factor/1 (CFA/1) specific SIgA antibodies in milk and saliva. ETEC CFA/1 specific SIgA antibody activity was detectable in milk (37.5% and 25%) and saliva (42.1% and 35%) of Sri Lankan and immigrant Asian women, respectively, but not in any of the Caucasian controls. Eighty five point two per cent of subjects who were positive had specific antibodies detectable in both milk and saliva; 5% of all Sri Lankan women and 10% of all immigrant Asian women had detectable antibody only in saliva. These observations lend further strong support to the idea that a common mucosal immune system exists in man. The continuing presence of specific SIgA antibodies in Asian immigrants to previously encountered antigens suggests that there may be an 'immunological memory' in the human secretory immune system.

Adolescent↗
PubMed1992

The T cell receptor as a multicomponent signalling machine: CD4/CD8 coreceptors and CD45 in T cell activation.

The T cell receptor is a multicomponent signalling machine. The three main components are the hypervariable alpha: beta heterodimer that confers specificity and its attendant invariant chains CD3 gamma, delta, and epsilon and the zeta:zeta or zeta:eta, the CD4 or CD8 coreceptor, and CD45. Each of these components is required for efficient signal transduction, and each has relevant enzymatic activity associated with it. The invariant part of the T cell receptor is associated with the tyrosine kinase p59fyn, the coreceptors are associated with the tyrosine kinase p56lck, and the cytoplasmic domain of CD45 has tyrosine-specific phosphatase activity. Moreover, there is strong evidence that these components interact in the plane of the membrane, and that these interactions are relevant for signal transduction. Finally, changes in the structure of CD45 that occur during differentiation of T cells alter the interactions of these three components of the signal transducing machinery, perhaps accounting for changes in signal transduction that accompany T-cell development in the thymus and the development of immunological memory cells.

Animals↗
PubMed2004

PT-100, a small molecule dipeptidyl peptidase inhibitor, has potent antitumor effects and augments antibody-mediated cytotoxicity via a novel immune mechanism.

The amino boronic dipeptide, PT-100 (Val-boro-Pro), a dipeptidyl peptidase (DPP) inhibitor, has been shown to up-regulate gene expression of certain cytokines in hematopoietic tissue via a high-affinity interaction, which appears to involve fibroblast activation protein. Because fibroblast activation protein is also expressed in stroma of lymphoid tissue and tumors, the effect of PT-100 on tumor growth was studied in mice in vivo. PT-100 has no direct cytotoxic effect on tumors in vitro. Oral administration of PT-100 to mice slowed growth of syngeneic tumors derived from fibrosarcoma, lymphoma, melanoma, and mastocytoma cell lines. In WEHI 164 fibrosarcoma and EL4 and A20/2J lymphoma models, PT-100 caused regression and rejection of tumors. The antitumor effect appeared to involve tumor-specific CTL and protective immunological memory. PT-100 treatment of WEHI 164-inoculated mice increased mRNA expression of cytokines and chemokines known to promote T-cell priming and chemoattraction of T cells and innate effector cells. The role of innate activity was further implicated by observation of significant, although reduced, inhibition of WEHI 164 and A20/2J tumors in immunodeficient mice. PT-100 also demonstrated ability to augment antitumor activity of rituximab and trastuzumab in xenograft models of human CD20(+) B-cell lymphoma and HER-2(+) colon carcinoma where antibody-dependent cytotoxicity can be mediated by innate effector cells responsive to the cytokines and chemokines up-regulated by PT-100. Although CD26/DPP-IV is a potential target for PT-100 in the immune system, it appeared not to be involved because antitumor activity and stimulation of cytokine and chemokine production was undiminished in CD26(-/-) mice.

Administration, Oral↗
PubMed2007

Delivery of CCL21 to metastatic disease improves the efficacy of adoptive T-cell therapy.

Adoptive T-cell transfer has achieved significant clinical success in advanced melanoma. However, therapeutic efficacy is limited by poor T-cell survival after adoptive transfer and by inefficient trafficking to tumor sites. Here, we report that intratumoral expression of the chemokine CCL21 enhances the efficacy of adoptive T-cell therapy in a mouse model of melanoma. Based on our novel observation that CCL21 is highly chemotactic for activated OT-1 T cells in vitro and down-regulates expression of CD62L, we hypothesized that tumor cell-mediated expression of this chemokine might recruit, and retain, adoptively transferred T cells to the sites of tumor growth. Mice bearing metastatic tumors stably transduced with CCL21 survived significantly longer following adoptive T-cell transfer than mice bearing non-CCL21-expressing tumors. However, although we could not detect increased trafficking of the adoptively transferred T cells to tumors, tumor-expressed CCL21 promoted the survival and cytotoxic activity of the adoptively transferred T cells and led to the priming of antitumor immunity following T-cell transfer. To translate these observations into a protocol of real clinical usefulness, we showed that adsorption of a retrovirus encoding CCL21 to OT-1 T cells before adoptive transfer increased the therapeutic efficacy of a subsequently administered dose of OT-1 T cells, resulting in cure of metastatic disease and the generation of immunologic memory in the majority of treated mice. These studies indicate a promising role for CCL21 in enhancing the therapeutic efficacy of adoptive T-cell therapy.

Animals↗
PubMed2005

Combination B7-Fc fusion protein treatment and Treg cell depletion therapy.

PURPOSE: A B7.1 fusion protein consisting of the extracellular domains of human B7.1 and the Fc portion of human IgG1, called B7.1-Fc, was generated and evaluated for its antitumor potential when used alone or in combination with regulatory T (Treg) cell depletion. METHODS: A human B7.1-Fc fusion protein was constructed, expressed, purified, and examined for its antitumor activity in experimental mouse tumor models. RESULTS: Soluble B7.1-Fc showed costimulatory activity of T-cell proliferation in vitro, and when given in vivo, it induced complete regression of Colon 26 tumors after a 5-day treatment regimen. Parallel studies with human B7.2-Fc gave very similar results in the Colon 26 tumor model. Even in mice with established RENCA and Madison 109 tumors, which are poorly immunogenic, B7.1-Fc treatment slowed tumor growth dramatically. In these models, more potent antitumor activity was achieved when B7.1-Fc was used in combination with Treg depletion by i.p. administration of antibody PC61. Rechallenge experiments done with mice that had sustained complete tumor regressions showed that these mice had immunologic memory by their ability to reject subsequent implants. Histologically, B7.1-Fc treatment induced multiple areas of necrosis and infiltration of CD4+ and CD8+ T cells in tumors along with a concomitant dramatic increase in T-cell proliferation in tumor-draining lymph nodes. CONCLUSIONS: The B7.1-Fc fusion protein seems to be an effective antitumor agent especially in combination with Treg depletion. Its potency in stimulating immune responses and its human origin suggest that clinical studies may be warranted in the future.

Animals↗
PubMedDate not supplied

The IgE antigen receptor: a key regulator for the production of IgE antibodies.

Immunoglobulins in general form a substantial component of serum proteins, and play a role in homeostatic mechanisms, a first line of defense against pathogenic organisms and in immunological memory. In the secreted form, immunoglobulins represent the effector arm of the humoral immune system. However, immunoglobulins are not only secreted, but can also be expressed on the surface of a B lymphocyte (membrane immunoglobulin), and, in this physical state, most likely convey signals to steer the B cell along its differentiation pathway. A step forward in the understanding of the role of membrane immunoglobulins other than membrane IgM or IgD was achieved with two mouse lines with mutations in the epsilon heavy chain gene. In IgE(DeltaM1M2) mice serum IgE is reduced to less than 10% of normal mice, while IgE(KVKDeltatail) mice show a reduction of 50%, reflecting a serious impairment of the IgE-mediated immune response. We think that the cytoplasmic tail of IgE is involved in a signal transduction which leads to the expression of high quantities and qualities of secreted IgE immunoglobulins.

Animals↗
PubMed2003

Construction of an sIgE:FLAG-mIgE:GFP reporter mouse strain.

Like all other immunoglobulins, IgE can be secreted into the blood or expressed as a membrane receptor on the surface of B lymphocytes. Secreted immunoglobulins trace the antigen and contribute to its destruction. Membrane immunoglobulins accompany the B cell along its differentiation pathway, regulating processes like the induction and maintenance of immunological memory and differentiation of plasma cells. The regulation of the expression of IgE is very complex. A lot of positive and negative regulators influence the synthesis of IgE. In previous publications, we were able to show that the membrane IgE (mIgE) antigen receptor itself controls the quantity and quality of serum IgE produced. However, the knowledge about the regulatory function of the antigen receptor on these processes is at best limited. In the present paper, we present the construction of a reporter mouse strain, which will help us to follow an mIgE-bearing B cell during the immune response more precisely.

Animals↗
PubMed1989

The effect of opiates on the intestinal immune response to cholera toxin in mice.

We studied the effect of opiates on the intestinal immunoglobulin A response in mice. C57BL mice were orally immunized by two doses of 10 micrograms of cholera toxin, 2 weeks apart. Experimental groups received subcutaneous injections of morphine, either 10 or 20 mg/kg/day, in two divided doses. Morphine was given for 4 days, starting 1 day prior to each cholera toxin dose. Intestinal secretions were collected by lavage 1 week after the last cholera toxin dose, and assayed for specific anticholera toxin antibody and total immunoglobulin A. Results were expressed as units of anticholera toxin per nanogram immunoglobulin A. It was found that morphine, 20 mg/kg/day, reduced the response from 30.9 +/- 3.11 to 9.78 +2- 1.42 units/ng (M +/- SEM; p less than 0.0001). 10 mg/kg/day of morphine slightly reduced the immune response to 21.38 +/- 3.51 units/ng (M +/- SEM), but failed to achieve statistical significance. Naloxone administration prior to morphine injections abolished the inhibitory effects of morphine. Morphine administration had no effect on the response to a booster dose of cholera toxin 3 months after the initial cholera toxin immunization and morphine administration. It is concluded that morphine has a significant inhibitory effect on the intestinal immune response, but does not effect long-term mucosal immunological memory. The effect is probably mediated by a specific opiate receptor, as it is blocked by naloxone. This effect may have clinical implications.

Animals↗
PubMed1990

IgA antigliadin antibodies and persistence of jejunal lesions in adult coeliac disease.

In 46 adult patients with coeliac disease, 41 (89%) of whom were positive for IgA and/or IgG antigliadin antibodies (AGA) when untreated, we investigated after a gluten-free diet the relationship between the persistence of AGA, the persistence of jejunal lesions, and the duration and compliance with the diet. IgG AGA were positive in 21 coeliac patients (46%) after variable periods of gluten-free diet and were associated with IgA positivity only in 4 cases (9%). Both IgA and IgG AGA positivity appeared to be more related to the lack of improvement of the jejunal lesions than to the strictness and duration of gluten withdrawal. Nine coeliacs showed no improvement of jejunal lesions after the gluten-free diet. Of these 9, 4 showed persistent IgA AGA, while the remaining 5 resulted IgAAGA-negative as before when untreated. Though intestinal biopsy remains the best means of determining the positive effect of gluten withdrawal, the persistence of IgA AGA in treated coeliacs is always predictive of the persistence of severe jejunal lesions. The persistence of IgG AGA, on the contrary, should be regarded as an immunological memory.

Adult↗
PubMed1989

Prolonged elevations of soluble interleukin-2 receptors in tuberculosis.

In order to determine whether tuberculosis is associated with elevated levels of soluble interleukin-2 receptors (SIL-2R), patients with both pulmonary (n = 12) and extrapulmonary (n = 8) disease were studied. SIL-2R were measured in sera using an enzyme-linked immunosorbent assay (ELISA). Prior to treatment, all 20 patients had levels of SIL-2R significantly greater than those of the 14 control subjects. Longitudinal study of patients with pulmonary disease revealed that levels of SIL-2R remained elevated in 11 of 12 patients after 2 months, and in four of six patients after 3 months of treatment. These findings suggest that tuberculosis is characterized by prolonged activation of the immune system despite optimal chemotherapy and that SIL-2R may distinguish active immunity from immunologic memory to this infection.

Adult↗
PubMed1994

Interleukin-10 inhibits apoptotic cell death in infectious mononucleosis T cells.

T lymphocytes from patients with acute EBV-induced infectious mononucleosis rapidly die by apoptosis in vitro. Because human and viral IL-10 are likely to be induced during acute EBV infection and display a variety of functions on human T cells, we examined IL-10 effects on infectious mononucleosis T cell death. After 12 h of incubation in medium alone, only 35.6 (+/- 8.2%) of the originally seeded infectious mononucleosis T cells were viable. Addition of human IL-10 (100 U/ml) to T cell cultures significantly improved recovery of viable cells (71.3 +/- 6.2%, P = 0.0156). Viral IL-10 had comparable effects to human IL-10 in this system. Protection from death by human and viral IL-10 (100 U/ml) was dose dependent and continued over a 6-d culture period. The human IL-10 effect was neutralized by the anti-human IL-10 mAb 19F1. Morphology and analysis of DNA after separation on agarose gels showed that IL-10 inhibits loss of cell volume, chromatin condensation, and DNA fragmentation, characteristics of death by apoptosis. As assessed by [3H]thymidine incorporation, the T cells were not induced to proliferate by IL-10 above the level exhibited when first removed from blood. T cells protected from death by IL-10 proliferated to IL-2 and spontaneously killed sensitive targets as effectively as medium-precultured T cells. Thus, IL-10 promotes the survival of infectious mononucleosis T cells otherwise destined to die by apoptosis and may be critical for the establishment of immunologic memory after resolution of the illness.

Adolescent↗
PubMedDate not supplied

Meningococcal conjugate vaccine in adolescents and children.

Disease caused by Neisseria meningitidis is associated with high mortality rates and significant sequelae. Quadrivalent (A, C, Y, W-135) polysaccharide meningococcal vaccine has been available for more than 20 years, and although used widely for adolescents entering college, it has a number of limitations, including short duration of immunity and lack of a herd effect. A quadrivalent meningococcal conjugate vaccine has recently been licensed and endorsed for use in adolescents 11 to 12 years of age, at age 15, or at college entry. Among the key features of the new meningococcal conjugate vaccine are stimulation of both B-cell-dependent and T-cell-dependent immune responses, induction of immunologic memory and booster effects, long-term protection, reduction of nasopharyngeal carriage of N. meningitidis, and herd immunity. Large randomized, double-blind studies in adolescents and 2- to 10-year olds have demonstrated the immunogenicity as well as the safety and tolerability of the new meningococcal conjugate vaccine formulation.

Adolescent↗
PubMed1991

Leukocyte adherence inhibition test: cell-mediated reactivity to tumor antigens in colorectal and lung tumor long survivors.

Cell-mediated immunity versus tumor antigens (cytosols) of the same histotype and site was evaluated by means of the leukocyte adherence inhibition (LAI) test in 44 colorectal adenocarcinoma and 17 lung squamous-cell carcinoma patients 3-10 years after surgical resection. LAI-positivity was observed in 17/44 (38.6%) and 13/17 (76.5%) patients, respectively, together with serum blocking factors in 7/17 (41.2%) compared to 0/13. These results indicate that a high percentage of long survivors retain an immunologic memory of the tumor antigen to which they have been exposed. The prognostic significance of serum blocking factors is less clear.

Adenocarcinoma↗
PubMed1997

Hepatitis B vaccine: current issues.

OBJECTIVE: To review two main issues concerning the hepatitis B vaccine: (1) the management of unresponsive subjects and (2) the need for routine booster doses. DATA SOURCES: Pertinent literature identified via MEDLINE (1980-1996) search as well as references cited in published articles. DATA SYNTHESIS: The optimal procedure for management of subjects unresponsive to hepatitis B vaccine has not been well established. Most unresponsive subjects are not absolute nonresponders, since most of them can develop protective concentrations of antibodies to hepatitis B surface antigen (anti-HBsAg) after hepatitis B revaccination, consisting of a fourth or a fifth dose or a new complete course of immunization. In subjects who do not respond to the hepatitis B vaccine after four or more injections, the benefits of the combination of cytokines (e.g., interferon-alfa, interleukin-2 [aldesleukin]) and vaccine have not been clearly shown. There are two main opinions regarding the need for routine booster doses. Experts from the US, claiming long-term protection from immunologic memory, suggest delaying booster doses for at least a decade after vaccination in subjects with normal immune status. Furthermore, postvaccination antibody testing should be restricted only to high-risk subjects. Once a vaccinated subject has responded satisfactorily, further antibody tests are unnecessary. Only hemodialysis patients should be tested annually for adequate antibody concentrations and the booster dose administered when concentrations decline to less than 10 IU/L. Experts from Europe suggest that vaccine-induced antibody responses should be assessed in all subjects and booster doses administered at intervals, with the theory being that protection correlates with the presence of antibody. However, indications about appropriate timing for booster doses and target titers of anti-HBsAg remain controversial. CONCLUSIONS: It is possible to obtain seroconversion in nonresponders by using variations in vaccination strategies (i.e., > 3 doses, double amounts of HBsAg). Adjuvants such as interferon-alfa or aldesleukin are of limited use. The opinions of American experts regarding routine booster doses, as expressed by the statement of the Immunization Practices Advisory Committee, seem to be well defined and helpful to clinicians trying to resolve controversies for individual patients. The opinions of the European experts are not unanimous and are sometimes impractical. A consensus conference is needed.

Antibodies, Viral↗
PubMed2004

PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12.

Epstein-Barr virus (EBV)-specific immunologic memory is not transferred from mother to child. In vitro infection of cord blood cells can therefore readily lead to the outgrowth of transformed B lymphocytes. We found that the immunomodulator polysaccharide K (PSK) or the mitogenic cytokine truncated thioredoxin (Trx80) inhibited the EBV-induced B-cell proliferation. Using signaling lymphocytic activation molecule (SLAM)-associated protein (SAP) induction as a sign for T- and natural killer (NK) cell activation, we could follow it without any need for cell separation because neither macrophages nor B lymphocytes express SAP. The results suggest the following scenario: EBV infected and activated B lymphocytes. Upon interacting with these cells, T cells became posed for responding to cytokines produced by monocytes. Both PSK and Trx80, which is a secreted C-terminally truncated thioredoxin, activated the monocytes, which then produced cytokines in the presence of the primed T cells. PSK induced interleukin-15 (IL-15), while Trx80 induced IL-12 production. Both cytokines activated the T cells for function. Phosphatidylinositol 3-(PI 3)-kinase and reactive oxygen species (ROSs) were involved in the PSK-induced activation of monocytes. Restimulation of the cultures with EBV-transformed B cells generated specific cytotoxic activity.

Antibodies, Blocking↗