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At least 991 records · Page 55Linked to original sources
PubMed1997

In vitro production of antigen-specific T cells from unprimed mice: role of dexamethasone and anti-IL-10 antibodies.

We describe here a culture system for studying the development, in vitro, of antigen-specific CD4 T cells from unprimed mice. T cells from young mice are initially exposed to antigen, such as pigeon cytochrome C or keyhole limpet hemocyanin, in the presence of adherent accessory cells and then allowed to proliferate in the absence of antigen but in the presence of IL-2, 10(-8) M dexamethasone, and antibodies to IL-10. Proliferation and IL-2 production by T cells harvested from such expansion cultures are antigen-dependent but not antigen-specific and at different doses can be either stimulated or inhibited both by the priming antigen and by irrelevant proteins. Antigen-specific T cell reactions can be elicited by any of three modifications of the culture protocol: (a) absorption of nonspecific cells on accessory cell monolayers bearing irrelevant proteins; (b) increased doses of dexamethasone during the expansion phase; or (c) a second cycle of antigen activation and antigen-free expansion. These observations provide a foundation for further analysis of in vitro maturation of primary immune responses and suggest an important role for IL-10 and glucocorticoids in regulating the early stages of activation and proliferation by naive T cells.

Animals↗
PubMed1999

Antibodies against Trypanosoma cruzi alkaline antigens are elicited in sera from acute but not chronic human chagasic patients.

The aim of this work was to study the antibody response of acute and chronic chagasic patients against a Trypanosoma cruzi alkaline fraction (FI) in comparison with the reactivity against a T. cruzi acidic antigen, the main cystein proteinase of the parasite named cruzipain, and "natural" antigens. FI-specific antibodies were detected only during the acute phase of the infection and IgM was the main isotype produced, whereas cruzipain-specific antibodies were detected during all phases of the infection. By means of immunoblot and sequencing analysis we identified a 47-kDa FI proteic band recognized by IgM from acute chagasic patients as the T. cruzi glutamate dehydrogenase (GluDH). Furthermore, the antibody response against isolated GluDH showed similar characteristics as the one against FI. We also observed a strict association between the reactivity of IgM against FI and GluDH and IgM natural antibodies. However, reactivity against these alkaline antigens was not modified after absorption of natural antibodies in sera from acute chagasic patients, indicating that these parasite antigens are not recognized by the polyspecific natural antibodies. The most important goal of this report is that for the first time the T. cruzi antigen isoelectric point has been associated with its ability to trigger immunological memory, raising a novel antigen property that should be considered in the selection of antigens used in Chagas' disease diagnostic test and in the design of a vaccine against T. cruzi infection.

Acute Disease↗
PubMed1999

Enhancement of the contact hypersensitivity reaction by acute morphine administration at the elicitation phase.

The present study investigated the effects of morphine on the irritant contact sensitivity (ICS) and contact hypersensitivity (CHS) reaction. ICS was induced by croton oil application on the pinnae of naïve rats. Morphine injected prior to croton oil application did not affect the ICS response when assessed by measurements of pinnae thickness. CHS was induced by applying the antigen 2,4-dinitro-1-fluorobenzene (DNFB) to the pinnae of rats sensitized to DNFB. Rats received an injection of morphine prior to either initial antigen exposure (sensitization) or antigen reexposure (challenge). Morphine prior to challenge, but not sensitization, resulted in a pronounced enhancement of the CHS response as measured by pinna thickness. Quantitative PCR also showed increased IFN-gamma mRNA levels in the inflamed tissue of morphine-treated rats. Naltrexone blocked the morphine-induced enhancement of the CHS response. The differential effects of morphine suggest that opioids have a more pronounced effect on in vivo immune responses that involve immunological memory.

Animals↗
PubMed1993

Plasmodium falciparum: the immune response in rabbits to the clustered asparagine-rich protein (CARP) after immunization in Freund's adjuvant or immunostimulating complexes (ISCOMs).

The Plasmodium falciparum clustered asparagine-rich protein (CARP) is a merozoite-associated antigen which contains approximately 30% asparagine. Analysis of the DNA sequences located 5' of the cloned 1.4-kb CARP gene in the P. falciparum genome suggests that this gene fragment may encode the complete CARP and that the gene product is a protein of M(r) 50,000. To analyze the immunogenicity of CARP, the gene was expressed as a fusion protein with staphylococcal protein A (SpA-CARP). Immunization of rabbits with SpA-CARP in Freund's complete adjuvant (FCA) resulted in a strong antibody response against CARP as measured in ELISA. This response was efficiently boosted and sustained over a long time while that induced by two immunizations with SpA-CARP in ISCOMs was weak and of shorter duration. In both instances, the antibody levels against CARP were further increased by a second booster injection consisting of either SpA-CARP or CARP fused to the serum albumin-binding region (BB) of streptococcal protein G (BB-CARP) in PBS, indicating that immunizations with SpA-CARP in FCA or ISCOMs had induced a CARP-specific immunological memory. Boosting with BB-CARP in PBS was more efficient than boosting with SpA-CARP in PBS. In all rabbits, the antibodies obtained after the booster with CARP in PBS were the most efficient inhibitors of merozoite invasion in vitro. The antisera reacted with the intracellular parasite in immunofluorescence and with a band of M(r) 50,000 in immunoblotting while several high-molecular-weight components as well as the one of M(r) 50,000 were immunoprecipitated. The specificity of the antibody responses varied between the different rabbits as indicated in ELISA, with short synthetic peptides representing different CARP sequences. Taken together, the results suggest that a previously cloned genomic DNA fragment may encode the complete P. falciparum blood-stage antigen CARP and that CARP is immunogenic in rabbits both when administered in FCA or ISCOMs.

Amino Acid Sequence↗
PubMed1996

Do human cancers express shared protective antigens? or the necessity of remembrance of things past.

A majority of CTL-recognized antigens of human melanomas have turned out to be unmutated differentiation antigens expressed on melanomas and melanocytes alike. Additional, relatively cancer-specific antigens which are expressed on a significant proportion of melanomas, but not on most normal tissues, have also been shown to be recognized by CTLs. Finally, CTLs have been shown to detect mutated oncoproteins which are expressed in a wide spectrum of cancers but not in normal tissues. These observations have given rise to a view that human cancers share a number of antigens, which can form the basis for their immunotherapy. In contrast, cancer antigens of mice and rats (which are detected by tumor rejection assays in vivo, rather than CTLs generated in vitro) have been observed, generally, to be individually distinct, i.e. unique for each individual cancer. No convincing examples of shared cancer antigens exist in animal models of cancer. This dichotomy between the nature of cancer antigens of humans ('shared'), and of rodents ('unique') is addressed, and hopefully, resolved in this article.

Animals↗
PubMed1997

Experimental measles. II. Infection and immunity in the rhesus macaque.

Measles infection and the host immune response to measles virus was compared using naive and immunized rhesus monkeys. The monkeys were experimentally challenged with a wild-type strain of measles virus inoculated intranasally. After pathogenic virus challenge, measles virus was detected in mononuclear cells of peripheral blood, lymph node, and spleen in naive monkeys and viremia peaked on Day 7. However, only one of five vaccinated monkeys had a lower virus titer in peripheral blood mononuclear cells at one time point after challenge. No virus was detected in the lymphoid tissues from an immunized monkeys that was euthanized on Day 7 of infection. Measles-specific IgM, IgG, neutralizing antibody, and cytotoxic T lymphocytes were detected in vaccinated monkeys before challenge, but antibody titers were significantly lower in immunized monkeys than in naive monkey after challenge. Measles-specific IgG antibody and cytotoxic T cell responses were still detected more than 1 year after vaccination or infection. This animal model is useful for the further study of measles pathogenesis, immunosuppression, and immunologic memories.

Animals↗
PubMed2004

Human milk protective mechanisms.

The survival of a nonimmune infant faced with a new pathogen depends in part on an array of specific and nonspecific human milk factors. Human milk protects via multiple redundant strategies. It targets shared virulence mechanisms to provide cross protection. By interfering with fundamental processes such as attachment to glycoconjugates, human milk anticipates new mutations and new pathogens that utilize carbohydrates as receptors. Furthermore, human milk IgA present appears to reflect long-term maternal immunologic memory. These overlapping protective strategies endow human milk with the unique ability to protect infants from organisms that mutate rapidly and are present in vast numbers.

Female↗
PubMed1987

Development of the immune system in human fetal liver.

Fetal liver is a major site of development of the human immune system. Pre-B and B-lymphocytes are present in the human fetal liver at 12 weeks in a random distribution and increase with gestation. Most fetal liver cells are pre-B but mature B-cells are also present. Functional assays and transplantation experiments indicate that these B-cells are functional and can transfer immunologic memory, albeit imperfectly, in fetal liver reconstituted recipients. T-cell development, in contrast, occurs predominantly in the thymus. Progenitors of T-cells are present in fetal liver and can restore T-cell immunity in irradiated recipients. Human fetal liver contains 1-2% mature T-cells; functional assays are likewise negative. NK cells have been detected in human fetal liver at low frequency. Fetal liver also contains non-T, non-B cells capable of suppressing the development of alloantigen reactive T-cells; these have been termed veto cells. In summary, human fetal liver contains progenitors of several types of lymphoid cells and is an important site of immune development. It also may play a role in the induction of self tolerance during maturation of the immune system. These features of fetal liver may have important implications for the success of fetal liver transplantation in man.

B-Lymphocytes↗
PubMed1998

[Vaccination against hepatitis B].

Three comparable vaccines against hepatitis B, consisting of recombinant HBsAg, are registered in Switzerland. After intramuscular administration (deltoid, thigh), they induce seroconversion in 95% of subjects following a 0, 1, 6 or 0, 1, 2 and 12 months schedule. The determination of antibody titers is thus not required in healthy subjects in absence of an increased risk of exposure (healthcare workers). Vaccine induced protection is extended beyond the disappearance of specific antibodies, through the persistence of immunological memory, which reactivates immune defense mechanisms upon viral exposure. A booster immunization is thus not necessary after a full immunization course, even if given in the first year of life or in newborns of HBsAg positive mothers. The excellent safety profile of these vaccines (local pain 3-29%, fever 1-6%) allows their universal administration. Two combined vaccines are already available, and new vaccines may yet facilitate prevention of hepatitis B in the future by allowing a reduction in the number of doses required for protection.

Adult↗
PubMed1985

The involvement of dendritic cells in the handling of the immune stimulant C. parvum. A morphological investigation using immunoperoxidase techniques.

In earlier experiments we showed that locally administered Corynebacterium parvum (C. parvum) stimulated the T-cell system and had a beneficial effect on the recurrence rate of surgically resected cancers of the uterine cervix. In this paper we report the use of an immunoperoxidase technique to trace C. parvum antigen in the draining lymph nodes. In a guinea pig model the popliteal lymph node was studied after the injection of 70 micrograms of C. parvum in the hind footpad. At 6 h, intact bacteria were detected in sinus histiocytes. A transient granuloma formation was apparent between days 2 and 6, originating in the subcapsular and interfollicular areas. Three antigen-positive cell types were observed in these granulomas: a) cytophagocytic macrophages which were weakly positive, the antigen being distributed in clumps; b) dendritic cells with a strong, fine-granular positivity and c) some epithelioid cells with a small positive cytoplasmic rim. The majority of epithelioid cells was negative. Antigen-positive dendritic cells were also observed just beyond the granulomas in the T-dependent paracortical area. These cells are known as interdigitating cells (IDC) and present antigen to T-cells. Ten days following C. parvum injection the lymph node follicles became positive and the antigen could be detected in the long cellular protrusions of the dendritic reticulum cells (DRC). DRC probably play a part in immunological memory by trapping antigen in the form of immune complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Vaccination with an adenoviral vector expressing calreticulin-human papillomavirus 16 E7 fusion protein eradicates E7 expressing established tumors in mice.

BACKGROUND: Cervical cancer remains a leading cause of cancer-related mortality in women, particularly in developing countries. The causal association between genital human papilloma virus (HPV) infection and cervical cancer has been firmly established, and the oncogenic potential of certain HPV types has been clearly demonstrated. Vaccines targeting the oncogenic proteins, E6 and E7 of HPV-16 and -18 are the focus of current vaccine development. Previous studies have shown that calreticulin (CRT) enhances the MHC class I presentation of linked peptide/protein and may serve as an effective vaccination strategy for antigen-specific cancer treatment. METHODS: Two replication-deficient adenoviruses, one expressing HPV-16 E7 (Ad-E7) and the other expressing CRT linked to E7 (Ad-CRT/E7), were assessed for their ability to induce cellular immune response and tested for prophylactic and therapeutic effects in an E7-expressing mouse tumor model. RESULTS: Vaccination with Ad-CRT/E7 led to a dramatic increase in E7-specific T cell proliferation, interferon (IFN)-gamma-secretion, and cytotoxic activity. Immunization of mice with Ad-CRT/E7 was effective in preventing E7-expressing tumor growth, as well as eradicating established tumors with long-term immunological memory. CONCLUSION: Vaccination with an adenoviral vector expressing CRT-E7 fusion protein represents an effective strategy for immunotherapy of cervical cancer in rodents, with possible therapeutic potential in clinical settings.

Adenoviridae↗
PubMed1997

In vivo antitumor effects of murine interferon-gamma-inducing factor/interleukin-18 in mice bearing syngeneic Meth A sarcoma malignant ascites.

Interferon-gamma-inducing factor/interleukin-18 is a novel cytokine that reportedly augments natural killer (NK) activity in human and mouse peripheral blood mononuclear cell cultures in vitro and has recently been designated IL-18. In this study, IL-18 exhibited significant antitumor effects in BALB/c mice challenged intraperitoneally (i.p.) with syngeneic Meth A sarcoma when administered i.p. on days 1, 2 and 3 after challenge. Intravenous (i.v.) administration also induced antitumor effects in the tumor-bearing mice; however, subcutaneous (s.c.) administration did not. When mice were twice pretreated with 1 microg IL-18 3 days and 6 h before tumor challenge, all mice survived whereas control mice died within 3 weeks of challenge. Inhibitory effects on Meth A cell growth in vitro were not observed with either IL-18 or interferon gamma. The effects of IL-18 pretreatment were abrogated by abolition of NK activity after mice had been injected with anti-asialo GM1 antibody 48 h before and, 24 h and 72 h after tumor challenge. Mice pretreated with IL-18 and surviving tumor challenge resisted rechallenge with Meth A cells but could not reject Ehrlich ascites carcinoma, and spleen cells from the resistant mice, but not control mice, exhibited cytotoxic activity against Meth A cells in vitro after restimulation with mitomycin C-treated Meth A cells for 5 days. The effector cells in the spleen cell preparations from resistant mice appear to be CD4+ cells because cytolytic activity was significantly inhibited after depletion of this subset by monoclonal antibodies and complement. In conclusion, IL-18 exhibits in vivo immunologically (primarily NK) mediated antitumor effects in mice challenged with syngeneic Meth A sarcoma and induces immunological memory and the generation of cytotoxic CD4+ cells.

Animals↗
PubMed2006

Immunoglobulins--basic considerations.

Immunoglobulins (Igs) or antibodies (Abs) are the principal operators of the adaptive humoral immune response. For optimum functional activity they acquire an optimized structure for antigen (Ag) recognition, precipitation, agglutination, phagocytosis (IgG1/3 and IgA), cytotoxicity (IgG1/3), transport through mucosa (IgA and IgM) and placenta (IgG1/3), complement activation (IgG1/3 and IgM) and release of inflammatory mediators (IgE). A diversity with potentially up to 10(15) different Ab specificities is generated during Ag-independent B cell development in the bone marrow by combinatorial V-D-J joining, creation of junctional diversity, and combinatorial association of L and H chains. Furthermore,Ab variety is created during Ag-dependent B cell maturation in peripheral lymphatic tissues by isotype class switching and somatic hypermutation. Two types of enzymes play a key role in Ab diverseness, i. e., the products of recombination-activating genes RAG1 and RAG2 and the affinity induced deaminase (AID). The prevailing adult-type B2 cells provide the basis for the acquired humoral immune response characterized by Ab production,Ag processing and presentation, immunological memory and tolerance along with the generation of the anti-idiotype network,whereas the fetal-type B1 cells may play a role in innate immunity and autoimmunity. Impairment of B cell immunity includes immunodeficiency (agammaglobulinemia), malignant transformation (leukemia, lymphoma, plasmocytoma) and immune dysregulation (allergy, autoimmunity). The diagnostic relevance of Abs comprises classical serology (immunoprecipitation, agglutination, complement binding, RIA, ELISA), immunocytochemistry and immunohistochemistry, immunofluorescence (microscopic and flow cytometric), cytotoxicity tests, immunoblots, immunospot assays and immunoabsorption (affinity chromatography). Therapeutic application of Abs (passive immunization) is directed against infections, intoxications, solid tumors, leukemias and lymphomas, graft rejection and graft-versus-host reaction, hemolytic anemia, and autoimmune diseases. The generation of genetically engineered monoclonal Abs (mAbs) has revolutionized the diagnostic and therapeutic potential of Abs in almost all disciplines of modern medicine.

Antibodies, Monoclonal↗
PubMed2005

Diphtheria, tetanus and pertussis antibodies in 10-year-old children before and after a booster dose of three toxoids: implications for the timing of a booster dose.

UNLABELLED: In an open study, 502 10-year-old children, who had received primary vaccination against diphtheria and tetanus in infancy and had varying histories of pertussis disease and vaccination, were vaccinated with diphtheria-tetanus vaccine (DT) alone or with the addition of 20 microg or 40 microg of pertussis toxoid. Diphtheria toxin neutralising antibodies, pertussis toxin IgG and tetanus toxoid IgG antibodies were measured before and 1 month after the booster. All toxoids were highly immunogenic. In pertussis toxoid recipients, median levels of pertussis toxin IgG increased to 16.5 U/ml (DTaP20) and to 36 U/ml (DTaP40) in children with non-detectable (<1 U/ml) antibodies before vaccination and to >400 U/ml in children (both DTaP20 and DTaP40) with detectable antibodies before vaccination. A total of 60 children (12%) with non-detectable (<0.01 IU/ml) diphtheria antibodies and 36 children (7%) with non-detectable (<0.01 IU/ml) tetanus antibodies before the booster had lower median antibody concentrations post-vaccination than children with detectable antibodies before the booster (diphtheria: 5.12 vs. 20.48 IU/ml; tetanus: 4.0 vs. 10.0 IU/ml). There were no differences in diphtheria and tetanus antibodies after vaccination between children who did and did not receive pertussis toxoid. CONCLUSION: 10-year-old children with non-detectable diphtheria and tetanus antibodies before the booster had lower post-vaccination antibodies than those with detectable antibodies before the booster indicating a poor immunological memory. Addition of pertussis toxoid to diphtheria-tetanus vaccine did not affect the antibody responses to diphtheria and tetanus toxoids when the three toxoids were combined as a booster. Even though immunity to diphtheria and tetanus was only estimated by surrogate markers (serum antitoxin antibodies) the results indicate that a lower age for the booster dose of diphtheria-tetanus vaccine or diphtheria-tetanus acellular pertussis vaccine should be considered.

Antibodies, Bacterial↗
PubMed2026

Single-cell multi-omics dissects transcript isoform and immune repertoire dynamics in human immunosenescence.

Immunosenescence, a major hallmark of systemic aging, refers to the progressive functional decline of the immune system. This decline not only compromises host defense and immunological memory but also fuels chronic inflammation and tissue degeneration (collectively known as inflammaging). While single-cell RNA sequencing (scRNA-seq) has revealed transcriptomic alterations associated with immune aging, analyses restricted to transcript abundance fail to capture deeper regulatory layers, such as transcript isoform diversity and the remodeling of immune receptor repertoires. To address this limitation, we present a human peripheral immune single-cell multi-omics atlas that integrates gene expression, transcript isoform diversity, and immune receptor repertoires. By combining single-cell full-length transcriptome sequencing (scCycloneSEQ), short-read scRNA-seq, and single-cell immune receptor sequencing (scTCR/BCR-seq), we systematically profiled peripheral blood mononuclear cells (PBMCs) from healthy donors aged 30-40 and 60-70 years. Our analyses uncovered extensive age-related remodeling of immune cell composition, functional states, and TCR/BCR diversity. Notably, we found that CD4+ effector memory T cells exhibited widespread differential isoform usage (DIU), 3'UTR length variation, and a marked reshaping of cytotoxic T lymphocyte (CTL) clonotypes-all of which were closely associated with aging-related inflammation and cellular senescence. This multi-omics atlas delineates key molecular features of immunosenescence and provides a high-resolution resource for deciphering the regulatory architecture underlying immune aging.

TCR/BCR↗
PubMed2006

Maternal allergen exposure as a risk factor for childhood asthma.

The role of early allergen exposure has been a central focus in the effort to curtail the rising rates of allergic disease. Exposures in pregnancy have been of interest because the first signs of disease are often seen in early infancy. However, so far, strategies to avoid or reduce allergen exposure in pregnancy have had disappointing results in reducing disease. Although there is growing evidence that the fetus is exposed to allergens, this appears to be physiologic and not a risk factor for allergic disease. It is still not clear if this exposure has some role in the context of normal tolerance. Although infants who later develop allergic disease show some differences in neonatal allergen-specific responses, these are not consistent. Furthermore, the magnitude and frequency of responses do not correlate well with maternal allergen exposure, and it now seems likely that these responses do not reflect true immunologic "memory." Despite this, there is accumulating evidence that a number of other exposures in pregnancy have the capacity to significantly influence immune development and alter the risk for allergic responses to allergens. This underscores the importance of further defining the events in this early period, to determine causal pathways and better strategies for prevention.

Allergens↗