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Results for “Immunity, Humoral”

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PubMed1990

Humoral immune activity in CBA/Ca mice during late pregnancy and the post-partum period.

Syngeneically mated CBA/Ca mice were used to measure "spontaneous" immunoglobulin (Ig) secretion in the Peyer's patches (PP), spleen and the para-aortic lymph nodes (PALN), employing a protein A plaque assay, during the latter part of pregnancy and in the post-partum period. The lactating and non-lactating females were compared with respect to humoral immune activity (plaque-forming cells) and serum Ig levels (ELISA technique). The pregnancy-induced weight changes in some lymphoid organs and the elevation in the number of plaque-forming cells in spleen (IgG and IgM PFC), PALN (IgG and IgM PFC) and the PP (IgA PFC) lasted longer in the lactating than in the non-lactating mice (owing to hormonal differences). A very strong decrease in serum IgG was observed during pregnancy and after parturition IgG levels remained depressed longer in lactating than in non-lactating mice. Interest has been focused on IgA in the study and this has been discussed as well as the possible reasons for the increased turnover of maternal serum Ig (especially IgG).

Animals↗

PubMed2001

Evidence for an antigen-driven humoral immune response in medullary ductal breast cancer.

A minority of breast cancers is characterized by lymphoplasmacytic infiltrates that have been correlated with improved patient survivals. The association of improved prognosis with plasmacytic infiltrates has been classically linked with the rare medullary carcinoma subtype but is also evident in the smaller infiltrated fraction of the more abundant nonmedullary (not otherwise specified) tumors. It is our hypothesis that these plasma cell (PC) infiltrates represent a host humoral response driven by one or more tumor-derived neoantigens. As the index study group, two primary medullary carcinoma tumors were examined. Immunophenotyping confirmed a large number of IgG PCs in contradistinction to normal breast, which typically contains a lesser number of mainly IgA isotypes. IgG heavy and light chains were expressed as combinatorial phage Fab libraries. VH and VL sequences showed a preponderance of clonal groups in both patients, as identified by germ-line gene usage and junctional mutation patterns. Panning of phage Fab libraries against purified antigens excluded Her2/neu and p53 as the eliciting antigen, and failure of clonal enrichment by cell panning suggested that the neoantigen was not membrane expressed or was expressed at low levels. Cognate, original VH+VL pairs were obtained by single cell PCR of tumor PCs, which showed overlap with the pooled IgG libraries. Tumor-derived IgG V genes exhibited mutational patterns that were consistent with antigenic selection and affinity maturation. Where examined, IgG1 was the predominant isotype, consistent with a T-dependent (i.e., protein) antigen. From these data, we infer that the breast tumor PC infiltrates of the medullary carcinoma subtype are compatible with an autogenic tumor neoantigen-driven humoral immune response.

Antibodies, Neoplasm↗

PubMed2005

Multigene/multisubtype HIV-1 vaccine induces potent cellular and humoral immune responses by needle-free intradermal delivery.

Gene vaccination encounters problems different from those of gene therapy since both a short half-life of the gene and a strong immune response to the gene product are desirable. We have evaluated a DNA vaccine consisting of seven plasmids encoding nine HIV-1 proteins. Using a needle-free delivery device, the Biojector, together with recombinant mouse GM-CSF, this vaccine induced strong gp160 Env- and p24 Gag-specific cellular and humoral immune responses in mice. The rGM-CSF was crucial for inducing both antibodies and antigen-specific CD8(+) T cell responses against both gp160 and p24. A GMP-produced lot of this vaccine, intended for human use, was delivered intradermally or intramuscularly into BALB/c mice at a GLP-accredited animal facility. This vaccine induced strong cellular responses independent of the route of immunization; moreover, no signs of toxicity were detected after histopathological examination of various tissues. Overall, the results indicate that the intradermal delivery of multigene/multisubtype HIV DNA in combination with recombinant GM-CSF is a safe and efficacious strategy for inducing high levels of specific CD8(+) T cells and unusually high titers of antibodies. This vaccine has been approved by the Swedish Medicinal Products Agency and is currently in a Phase I clinical trial.

AIDS Vaccines↗

PubMed1979

Nutritional status and the nonspecific cellular and humoral immune response in esophageal carcinoma.

In carcinoma of the esophagus, two major factors are operative, both of which are capable of suppressing the immune response, namely starvation and the presence of a malignant tumor. Twenty patients who were treated by palliative intubation for unresectable carcinoma of the esophagus were investigated. All patients were suffering from protein-calorie malnutrition and were shown to be in negative nitrogen balance. Lymphocyte counts and the nonspecific cellular and humoral immune response were evaluated before and after correction of the nutritional deficit. No attempt was made to reduce tumor bulk. The cellular immune response was compromised in all patients. The DNCB skin test was negative, absolute lymphocyte counts and T-lymphocyte numbers were significantly depressed, and the mitogenic response to phytohaemagglutinin (PHA) stimulation also significantly depressed. Immunoglobulin A levels were significantly elevated but serum complement concentrations were normal. Reversal of the negative nitrogen balance resulted in a significant increase in absolute and T-lymphocyte numbers, and a significant increase in the mitogenic response to PHA. The DNCB skin test, however, remained nonreactive. Nutritional repletion also significantly increased serum C(3), C(4) and C(3)PA concentrations. Reversal of negative nitrogen balance may reverse in vitro evidence of immunoparesis and produce an increase in complement concentrations, without therapeutic reduction in the tumor load.

Body Weight↗

PubMed2000

Characterization of the humoral immune response and virus replication in cats experimentally infected with feline foamy virus.

Cats were experimentally infected with cell culture-adapted feline foamy virus (FFV, spumaretrovirinae) isolate FUV. FFV was consistently recovered from peripheral blood leukocytes and throat samples of FFV-infected cats starting 2 to 3 weeks postinfection (p. i.), indicative of the establishment of persistent FFV infections. Viral persistence was established, even despite neutralizing antibodies that appeared early after infection. The humoral immune response toward FFV was quantitatively and qualitatively analyzed over time. FFV Gag-specific antibodies were first detected 2 weeks p. i. and increased further; reactivities to the other structural and nonstructural FFV proteins appeared slightly delayed. Reactivities against FFV Pol and Gag proteins were detectable by immunoblotting and radioimmunoprecipitation, whereas the latter techniques had to be employed for the unambiguous detection of FFV Env-, Bet-, and Bel 1-specific antibodies.

Animals↗

PubMed1997

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.

Animals↗

PubMed2004

Regulation of dendritic cell trafficking by the ADP-ribosyl cyclase CD38: impact on the development of humoral immunity.

Mice lacking CD38, an ectoenzyme that generates the calcium-mobilizing metabolite cADPR, make reduced T cell-dependent antibody responses. Despite the predicted role for CD38 in B cell activation, we find that CD38 regulates the migration of dendritic cell (DC) precursors from the blood to peripheral sites and controls the migration of mature DCs from sites of inflammation to lymph nodes. Thus, T cells are inefficiently primed in Cd38(-/-) mice, leading to poor humoral immune responses. We also show that CD38 and cADPR modulate calcium mobilization in chemokine-stimulated DCs and are required for the chemotaxis of immature and mature DCs to CCL2, CCL19, CCL21, and CXCL12. Therefore, CD38 regulates adaptive immunity by controlling chemokine receptor signaling in DCs.

ADP-ribosyl Cyclase↗

PubMed1999

Humoral immune response to equine chorionic gonadotropin in ewes: association with major histocompatibility complex and interference with subsequent fertility.

In dairy ewes, the use of eCG as a convenient hormone for the induction of ovulation is necessary for out-of-season breeding and artificial insemination (AI). In this report we show the presence of anti-eCG antibodies in plasma of treated ewes. The major histocompatibility complex (MHC) was involved in the individual variability of the humoral immune responses to eCG. We found significant associations between the anti-eCG response phenotype and some MHC class II alleles. The low immune response phenotype was associated with one MHC class II allele only in Lacaune ewes, and the high immune response phenotype was associated with one MHC class II allele both in Manech and in Lacaune ewes. In herds, the impact of residual anti-eCG antibodies on subsequent fertility after AI seems minimal because of an indirect elimination of high-responder ewes from AI breeding. Therefore, the true magnitude of the association between residual anti-eCG antibody concentration and fertility has been underestimated. An additional experiment without any high-responder female elimination showed a significant correlation between high residual antibody concentrations and lower lambing rate after AI at a fixed time, possibly because of a delayed preovulatory LH surge. The results suggest that anti-eCG antibody concentration is one risk factor for infertility after AI.

Aging↗

PubMed2005

Induction of humoral immunity in response to immunization with recombinant Mycobacterium bovis BCG expressing the S1 subunit of Bordetella pertussis toxin.

Two recombinant Mycobacterium bovis BCG (rBCG) vaccine strains were developed for the expression of cytoplasmically located S1 subunit of pertussis toxin, with expression driven by the hsp60 promoter of M. bovis (rBCG/pPB10) or the pAN promoter of Mycobacterium paratuberculosis (rBCG/pPB12). Both strains showed stable expression of equivalent levels of recombinant S1 in vitro and induced long-term (up to 8 months) humoral immune responses in BALB/c mice, although these responses differed quantitatively and qualitatively. Specifically, rBCG/pPB12 induced markedly higher levels of IgG1 than did rBCG/pPB10, and mice immunized with the former strain developed specific long-term memory to S1, as indicated by the production of high levels of S1-specific IgG in response to a sublethal challenge with pertussis toxin 15 months after initial immunization. When considered in combination with previous studies, our data encourage further evaluation of rBCG as a potential means of developing a low-cost whooping cough vaccine based on defined antigens.

Animals↗

PubMedDate not supplied

[The humoral immunity system of mice with experimental slow influenzal infection].

The status of the interferon system and level of immunoglobulins were studied in C57BL6 mice with slow influenza infection. These mice showed signs of immunosuppression: low endogenous interferon production, synthesis of alpha- and gamma-interferon by splenocytes of these mice in vitro 4-8 times lower than by those of the controls, lower levels of IgG in the blood serum. These data indicate general suppression of humoral immunity.

Aging↗

PubMed1990

Humoral immune responses in seals infected by phocine distemper virus.

Recently the isolation and characterisation of a morbillivirus which caused high mortality in common seals (Phoca vitulina) in 1988 have been reported. Because of the clinical and pathological similarity of the disease in seals to that of distemper in dogs, the name phocine distemper virus (PDV) has been proposed. There are marked differences in the virus-induced proteins of PDV compared to other morbilliviruses and the humoral immune response of moribund and dead seals to PDV was restricted to some of the internal antigens of PDV, similar to the response described earlier for canine distemper virus infection in dogs.

Animals↗

PubMed1986

Humoral immune response in hereditary and overt diabetes mellitus.

The inbred diabetic mutant mouse, C57BL/KsJ db +/db + (db +/db +), spontaneously develops diabetes mellitus when allowed food ad libitum. However, restriction of food intake prevents the expression of this genetic predisposition for diabetes. This experimental design has been used previously to demonstrate a deficient neutralizing antibody response to coxsackievirus B4 (CB4) in mutants with the genetic predisposition only. These observations demonstrate that in the genetically predisposed diabetic mutant, deficient humoral immunity extends further to a general impairment in both total IgM and IgG production after CB4 infection. Furthermore, these mice are unable to produce a virus-specific IgG response but do show a high level of nonspecific antibody suggesting a polyclonal activation following CB4 challenge. In addition, we observed an increase in the number of spleen IgM antibody-forming cells to sheep erythrocytes (SRBC) in the overtly diabetic animal following CB4 infection with little change apparent in the genetically predisposed animal after infection. These results were identical to the changes seen in total spleen cell numbers. Our animal model provides an opportunity to distinguish between the genetic predisposition to diabetes and the overt disease and suggests that some of the immune impairment found prior to diabetes onset may be partially diminished afterwards.

Animals↗

PubMed1984

Postabortal pelvic infection associated with Chlamydia trachomatis and the influence of humoral immunity.

Among 1101 women undergoing legal abortion by vacuum aspiration within 14 weeks of gestation, 69 (6.3%) harboured Chlamydia trachomatis in the cervix and/or urethra. Of the chlamydia-positive women, 16 (23.2%) developed endometritis and 10 (14.5%) developed salpingitis during the first postoperative month. The corresponding figures among the chlamydia-negative women were 59 (5.7%) and 5 (0.6%). These differences are highly significant (p less than 0.001). To study the significance of systemic and local humoral immunity to C. trachomatis in these complications, chlamydial antibodies were determined in serum and cervical secretions. No difference in frequency of local IgA antibodies in chlamydia-positive women was observed between those with and those without complications. On the other hand, there was a strong indication that chlamydia-positive women who developed salpingitis had a lower mean titer (17) of serum IgG chlamydial antibodies than carriers without symptoms (82, p less than 0.02). The group of endometritis patients did not differ in this respect from chlamydia-positive women who were free of infectious complications. These results suggest that C. trachomatis may be an etiologic agent in postabortal salpingitis and probably also in endometritis. Serum antibodies seemed to offer some protection against salpingitis in chlamydia-positive cases, whereas local antibodies did not.

Abortion, Induced↗

PubMed1996

Humoral immune response to immunocomplexed HIV envelope glycoprotein 120.

To further our understanding of the nature of HIV-1 immunogenicity, we injected mice with the virus envelope protein gp120 in different configurations: free, complexed with its receptor CD4, and as an immunocomplex with a monoclonal antibody directed against the V3 loop of the protein. Analyses of the polyclonal sera, as well as of monoclonal antibodies produced in each case, allowed us to conclude that the quality of the humoral immune response depended on the complexation state of the antigen. For the free gp120 and gp120-CD4 complex the responses were directed mainly toward conformational epitopes. However, gp120 immunocomplexed with anti-V3 loop Mab produced, in addition, numerous MAbs directed toward linear epitopes. Epitopes were mapped using immunoblots of gp120 cleaved with S. aureus V8 protease and a combinatorial epitope phage-display library. It was found that some of the linear epitopes had been previously identified as T cell epitopes. These results suggest that the immunocomplexed gp120 may be particularly well taken up by antigen-presenting cells, leading to the processing of the gp120 and the efficient presentation of T cell epitopes. Thus immunocomplexation should afford a means for enhancing the immunogenicity of gp120 and improving its presentation.

Amino Acid Sequence↗

PubMed1989

[The secretory and systemic humoral immune response to polysaccharide A in patients with rheumatism].

The level of sIgA saliva antibodies and Ig(M + G + A) serum antibodies to group polysaccharide A of streptococcus was studied in healthy donors and patients with streptococcal angina and rheumatic fever. It was shown that an elevated level of secretory and serum antibodies to polysaccharide A was registered in patients with angina and rheumatic fever reliably more frequently than in healthy donors. Independence of local and systemic humoral immune response to polysaccharide A was established.

Humans↗

PubMed1978

Establishment of paired tumor cells and autologous virus-transformed cell lines to define humoral immune responses in melanoma and sarcoma patients.

Peripheral blood lymphocytes and skin fibroblasts from 12 cancer patients were infected with Epstein-Barr virus (EBV) or SV40 virus. The EBV-transformed lymphoblasts and SV40-transformed fibroblasts were grown as continuous cell lines and expressed the same histocompatibility antigens as tumor cell lines established from the same cancer patients. Sera from 350 melanoma and 195 sarcoma patients were tested for antibody reactive with membrane antigens on three of these tumor cell lines (two melanomas and one sarcoma) by immune adherence (IA) and indirect immunofluorescence (IMI) assays. Antibodies to HLA and other non-tumor-related antigens were completely removed from the most reactive sera by quantitative absorption with 4 x 10(7) lymphoblasts or 10(7) transformed fibroblasts autologous to the tumor target cells. These paired cell lines were used to monitor humoral immune responses in melanoma and sarcoma patients receiving allogeneic tumor cell vaccines.

Antibodies, Neoplasm↗

PubMed2000

Humoral immune response during coronary artery bypass grafting: A comparison of limited approach, "off-pump" technique, and conventional cardiopulmonary bypass.

BACKGROUND: The introduction of limited approaches to the heart and the avoidance of cardiopulmonary bypass (CPB) aim to reduce the invasiveness of CABG by decreasing the systemic release of inflammatory cytokines, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8, as well as the anti-inflammatory agent IL-10. This study compares the humoral immune response in patients undergoing CABG with standard, minimally invasive, and "off-pump" techniques. METHODS AND RESULTS: Thirty patients were divided into 3 operative groups: full sternotomy approach plus CPB (group A); full sternotomy approach, off pump (group B); and limited left anterior thoracotomy, off pump (group C). Plasma levels of TNF-alpha receptors p55 and p75, IL 6, IL-8, and IL-10 were taken at baseline, during CPB, and at 4, 24, and 48 hours and 6 days after surgery. A significant increased release of activated complement factors C5a and C3d, IL-8, and IL-10 was observed in patients subjected to CPB (group A) during the initial period and for a short time after perfusion (P:<0.05). TNF-alpha receptors p55 and p75 showed a prolonged elevation (up to 48 hours) in the CPB group compared with the 2 off-pump groups. IL-6 showed no different release among the 3 surgical groups throughout the entire period. There was no significant difference in any parameter measured in relation to the type of operative approach. CONCLUSIONS: There is an inflammatory, as well as an anti-inflammatory, response during CABG that is related to the general surgical trauma. The release of immune mediators is enhanced by the use of CPB during various perioperative and postoperative phases. The type of operative approach did not influence this immune response.

Aged↗

PubMed2003

The ocular humoral immune response in health and disease.

This review focuses on several aspects of humoral immunologic defence of the ocular surface and intraocular compartment. Secretory IgA (sIgA) is a major component of lacrimal fluid and contributes to the first line of defence against infection of the ocular surface. Recent findings show that part of the lacrimal gland (LG) IgA repertoire consists of so-called natural IgA antibodies. How B cells responsible for these natural IgA antibodies are distributed to effector mucosal sites like the LG is not known. Extensive data are now available on the regionalization of mucosal IgA responses in murine gut, involving peritoneal B cells, the prototypic natural antibody producing cells. By comparing elaborate experiments done in mice with the much less extensive data on the LG, it becomes clear that this gland is a unique, but poorly investigated effector organ of the mucosal immune system. In addition to the humoral immune response at the surface of the eye, the production of antibodies within the ocular compartment also has several fascinating features. The detection of pathogen-specific antibodies in intraocular fluid (IOF) of uveitis patients is accepted as a diagnostic tool, but the specificity of these intraocular antibodies was not investigated in much detail. Recent data however, demonstrate that even antibodies recognizing the same antigen in both serum and IOF still differ in the epitopes they recognize. This reveals that the intraocular compartment largely determines its own antibody profile in the defence against intra-ocular pathogens. Several models as to how an exclusive intra-ocular B cell repertoire may be generated are presented.

Animals↗