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At least 631 records · Page 35Linked to original sources
PubMed1985

Mechanism of follicular trapping: double immunocytochemical evidence for a contribution of locally produced antibodies in follicular trapping of immune complexes.

Using two different antigen-enzyme conjugates and a double immunocytochemical staining technique, we demonstrate the localization patterns of two different specific antibodies in the same spleen section. During the early immune responses against simultaneously injected human gamma globulin (HGG), and bovine gamma globulin (BGG) in rabbits, the localization patterns of extracellular anti-HGG antibodies and extracellular anti-BGG antibodies in the follicles overlap only partly. It was shown in earlier studies that extracellular antibodies trapped in the follicles represent antigen-antibody complexes having free binding sites for the antigen. The fact that localization patterns do not overlap extensively, whereas it has been shown in earlier studies that follicular dendritic cells (FDCs) show no specificity with respect to the immune complexes to be captured, leads to the following conclusion. After formation of immune complexes from antibody molecules released by specific antibody-forming cells in the follicles and antigen present in excess between the cells, part of these complexes are trapped by adjacent FDCs. Results are discussed with respect to the possible role of follicular immune complexes in the generation of immunological memory.

Animals↗
PubMed1980

[Comparison of carminomycin and rubomycin action on the dynamics of the immune response to the T-independent Vi-antigen of S. typhi].

The effect of carminomycin and rubomycin on the dynamics of the primary immune response to T-independent Vi-antigen of S. typhi was studied. Differences in the character of the antibiotic effect indicative of the high selective effect of carminomycin on the multiplying cells or precursors of the antibody forming plasmocytes were noted. It was found that the carminomycin inhibitory effect on synthesis of hemagglutinins to Vi-antigen was higher than that to sheep red blood cells. Carminomycin was shown to impair the formation of the immunological memory, while rubomycin did not suppress the development of the "memory cell" clone to T-independent antigen.

Animals↗
PubMed1978

Genetic control of immunologic unresponsiveness to adjuvant-free solutions of beta-D-galactosidase. I. Inheritance of the Ir-Z1 and ir-Z2 loci in mice.

Two genetic loci, Ir-Z1 and ir-Z2, controlling the immune response to adjuvant-free bacterial beta-D-galactosidase (Z) are present in inbred mouse strains SJL/J and CE/J, respectively. Each locus segregates as a single, autosomal gene: Ir-Z1 as dominant and ir-Z2 as recessive. The response is characterized by production of activating and precipitating IgG. Maximal levels of circulating IgG occur between 16 and 20 days after immunization with a single, 50-microgram dose of enzyme. Failure of proteins other than Z to elicit an immune response indicates that the Ir-Z control is specific for determinant(s) of this enzyme. The immunogenicity of beta-D-galactosidase preparations cannot be attributed to either the catalytic activity of the enzyme or adjuvant contamination. Non-responder mice acquire immunologic memory without detectable increase in circulating specific IgG under the same conditions that elicit antibody production in responder strains.

Adjuvants, Immunologic↗
PubMed1976

Comparative studies on the actions of antigen and polyclonal B-cell activator in differentiation and proliferation of B-cells and B memory cells.

Using the capsular polysaccharide of Klebsiella pneumoniae (CPS-K) as a polyclonal B-cell activator (PBA) and sheep red blood cells (SRBC) as a T cell-dependent antigen, we compared the ability of PBA and antigen to differentiate (generate antibody-forming cells, AFC) and proliferate (generate immunological memory) virgin B cells and B memory cells. In vitro CPS-K induced the differentiation of IgM virgin B cells, IgM B memory cells and IgG B memory cells to AFC, as well as or better than SRBC. The differentiation of B memory cells to AFC by CPS-K did not require the participation of macrophages or T cells, whereas the action of SRBC depended strictly upon the helper actions of these cells. The responsiveness to CPS-K and SRBC of normal and antigen-primed spleen cells as judged by anti-SRBC PFC responses in vitro was markedly decreased after stimulation of virgin B cells and B memory cells in vivo by CPS-K injection into normal or primed mice but greatly increased after the injection of SRBC. The decrease in the responsiveness to CPS-K of spleen cells from mice treated with CPS-K appeared principally due to exhaustion of the functions of B cells and B memory cells. From the present data it has been concluded that the signals required for the differentiation and proliferation of B cells of B memory cells are different from each other, the signal for differentiation being provided by either antigen (SRBC) or PBA (CPS-K), while the signal for proliferation only by antigen.

Animals↗
PubMedDate not supplied

Oral administration of TNP-Lactobacillus conjugates in mice: a model for evaluation of mucosal and systemic immune responses and memory formation elicited by transformed lactobacilli.

Safe live vector systems are being developed for oral delivery of antigens. A transformation system for indigenous Lactobacillus species of the gastrointestinal tract is described. Model systems were set up to evaluate immune responses. Orally administered trinitrophenylized (TNP) Lactobacillus were examined for their ability to induce immunological memory formation via determination of specific antibody titres in serum. We demonstrate a direct correlation between the level of systemic memory formation, as revealed by specific anti-TNP IgG serum antibodies, and the TNP substitution ratio of the Lactobacillus suspension used for oral priming. The specific IgG anti-TNP serum titres were comparable to or even higher than the titres of parental intraperitoneally primed animals. These results demonstrate the feasibility of using orally administered antigen-Lactobacillus as a future approach to vaccination.

Administration, Oral↗
PubMed2000

Cytokines and T cells in host defense.

Soluble and cell-bound ligands profoundly influence the differentiative fate of lymphocytes during an immune response. Recent advances have been made in understanding the role of cytokine signals and costimulatory signals in the regulation of T cell responses associated with resistance or susceptibility to infection. There has also been recent progress in defining the requirements for the generation and maintenance of immunologic memory, a critical component of adaptive immunity.

Animals↗
PubMed2002

GATA-3 transcriptional imprinting in Th2 lymphocytes: a mathematical model.

Immunological memory involves the fast recall of cytokine expression by T helper (Th) lymphocytes. Two distinct profiles of cytokine expression, Th1 and Th2, can be induced by antigen and polarizing signals during activation of naive Th cells and can subsequently be reexpressed on stimulation by antigen alone. The transcription factor GATA-3 induces Th2 development. GATA-3 is activated by the Th2-polarizing stimulus, IL-4, and has recently been observed to autoactivate its transcription. Based on these experimental data, we developed a mathematical model of GATA-3 expression that assumes independent activation of GATA-3 transcription by IL-4 and by GATA-3. Cooperativity of GATA-3 transcriptional activation is shown to create a threshold for autoactivation, resulting in the coexistence of two distinct GATA-3 expression states: a state of basal expression and a state of high expression sustained by autoactivation. Suprathreshold IL-4 signals induce a transition from basal to high GATA-3 expression. Thus, GATA-3 autoactivation creates a bistable system that can memorize a transient inductive signal. The model further predicts conditions under which the state of high GATA-3 expression can be abolished, which may extinguish the Th2 cytokine memory.

Animals↗
PubMed1998

Contribution of cells at the site of DNA vaccination to the generation of antigen-specific immunity and memory.

Gene gun-mediated DNA vaccination stimulates an immune response characterized by the activation of IgG-secreting B cells and IFN-gamma-secreting T cells. To monitor the contribution of cells at the site of vaccination to this process, transfected skin was periodically removed and grafted onto naive recipients. Immediate removal of vaccinated skin abrogated the development of an immune response. Low-level IgG production was stimulated when the vaccination site was left in place for > or = 5 h, with the strength of this response increasing the longer the site remained intact (for up to 2 wk). Measurable primary T cell responses were observed in animals whose vaccination site remained in place for > or = 1 day. Skin grafts transferred 0 to 24 h postvaccination stimulated a primary immune response in naive recipients. Memory B and T cells were generated in animals whose site of vaccination remained intact for 5 to 12 h. Skin transferred within 12 h of vaccination triggered memory B and T cell development in graft recipients, while the removal of skin >12 h postvaccination did not reduce memory in vaccinated mice. These findings suggest that 1) primary immunity is induced by cells that migrate rapidly from the site of immunization, 2) nonmigratory cells influence the magnitude of this primary response, and 3) migratory cells alone are responsible for the induction of immunologic memory.

Animals↗
PubMed2006

Anti-idiotype antibody induced cellular immunity in mice transgenic for human carcinoembryonic antigen.

In the present study, we have analysed the detailed cellular immune mechanisms involved in tumour rejection in carcinoembryonic antigen (CEA) transgenic mice after immunization with dendritic cells (DC) pulsed with an anti-idiotype (Id) antibody, 3H1, which mimics CEA. 3H1-pulsed DC vaccinations resulted in induction of CEA specific cytotoxic T lymphocyte (CTL) responses in vitro and the rejection of CEA-transfected MC-38 murine colon carcinoma cells, C15, in vivo (Saha et al.,Cancer Res 2004; 64: 4995-5003). These CTL mediated major histocompatibility complex (MHC) class I-restricted tumour cell lysis, production of interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha), and expression of Fas ligand (FasL) and TNF-related apoptosis-inducing ligand (TRAIL) in response to C15 cells. CTL used perforin-, FasL-, and TRAIL-mediated death pathways to lyse C15 cells, although perforin-mediated killing was the predominant lytic mechanism in vitro. The cytokines IFN-gamma and TNF-alpha synergistically enhanced surface expression of Fas, TRAIL receptor, MHC class I and class II on C15 cells that increased the sensitivity of tumour cells to CTL lysis. CTL activity generated in 3H1-pulsed DC immunized mice was directed against an epitope defined by the idio-peptide LCD-2, derived from 3H1. In vivo lymphocyte depletion experiments demonstrated that induction of CTL response and antitumour immunity was dependent on both CD4+ and CD8+ T cells. The analysis of splenocytes of immunized mice that had rejected C15 tumour growth revealed up-regulated surface expression of memory phenotype Ly-6C and CD44 on both CD4+ and CD8+ T cells. The adoptive transfer experiments also suggested the role of both CD4+ and CD8+ T cells in this model system. Furthermore, mice that had rejected C15 tumour growth, developed tumour-specific immunological memory.

Animals↗
PubMed2003

Therapeutic limitations in tumor-specific CD8+ memory T cell engraftment.

BACKGROUND: Adoptive immunotherapy with cytotoxic T lymphocytes (CTL) represents an alternative approach to treating solid tumors. Ideally, this would confer long-term protection against tumor. We previously demonstrated that in vitro-generated tumor-specific CTL from the ovalbumin (OVA)-specific OT-I T cell receptor transgenic mouse persisted long after adoptive transfer as memory T cells. When recipient mice were challenged with the OVA-expressing E.G7 thymoma, tumor growth was delayed and sometimes prevented. The reasons for therapeutic failures were not clear. METHODS: OT-I CTL were adoptively transferred to C57BL/6 mice 21-28 days prior to tumor challenge. At this time, the donor cells had the phenotypical and functional characteristics of memory CD8+ T cells. Recipients which developed tumor despite adoptive immunotherapy were analyzed to evaluate the reason(s) for therapeutic failure. RESULTS: Dose-response studies demonstrated that the degree of tumor protection was directly proportional to the number of OT-I CTL adoptively transferred. At a low dose of OT-I CTL, therapeutic failure was attributed to insufficient numbers of OT-I T cells that persisted in vivo, rather than mechanisms that actively suppressed or anergized the OT-I T cells. In recipients of high numbers of OT-I CTL, the E.G7 tumor that developed was shown to be resistant to fresh OT-I CTL when examined ex vivo. Furthermore, these same tumor cells no longer secreted a detectable level of OVA. In this case, resistance to immunotherapy was secondary to selection of clones of E.G7 that expressed a lower level of tumor antigen. CONCLUSIONS: Memory engraftment with tumor-specific CTL provides long-term protection against tumor. However, there are several limitations to this immunotherapeutic strategy, especially when targeting a single antigen. This study illustrates the importance of administering large numbers of effectors to engraft sufficiently efficacious immunologic memory. It also demonstrates the importance of targeting several antigens when developing vaccine strategies for cancer.

Animals↗
PubMed2000

Dynamics of T lymphocyte responses: intermediates, effectors, and memory cells.

The immune response is initiated in organized lymphoid tissues where antigen-loaded dendritic cells (DCs) encounter antigen-specific T cells. DCs function as packets of information that must be decoded by the T cell before an appropriate immune response can be mounted. We discuss how the dynamics of DC-T cell encounter and the mechanism of T cell differentiation make the decoding of this information stochastic rather than determinate. This results in the generation of both terminally differentiated effector cells and intermediates that play distinctive roles in protection, immunoregulation, and immunological memory.

Animals↗
PubMed1978

Sensitivity to glucocorticoids of lymph node cells stimulated in vivo by oxazolone.

Sensitization of B10.A mice with oxazolone results in delayed-type hypersensitivity (DTH) and a two to three-fold increase in the weight of regional lymph nodes by the third day. Hydrocortisone treatment of the animals 3 days after sensitization suppresses the manifestation of DTH on the tenth day but not on the seventieth day and significantly decreases the weight of lymph nodes both in control and oxazolone-sensitized mice. The regional lymph node cells of oxazolone-stimulated mice were, like the controls, sensitive to dexamethasone in vitro, as judged by viability and thymidine incorporation. Dexamethasone binding capacity of the regional lymph node cells 72 h after oxazolone sensitization increased. However, the dissociation constant for dexamethasone, the binding specificity, and the nuclear transfer of the hormone were not altered. Since high doses of hydrocortisone given 3 days after sensitization were unable to erase permanently the DTH to oxazolone, it seems very likely that cells responsible for the immunological memory survive the high dose of hydrocortisone.

Animals↗
PubMed1986

[Mechanism of formation of antibody production stimulating ability of bone marrow cells of mice immunized with staphylococci].

The mechanism of the increase in immune response to particular staphylococcal antigen was studied in CBA and BALB/c mice injected by primed bone marrow cells (BMC). It was found that immunostimulatory effect of immune BMC is not mediated by macrophages or T cells, but is associated with staphylococcus-specific B memory cells present in the pool of primed BMC. Splenectomy performed in donor animals prior to immunization did not abolish the induction of stimulating BMC activity. It was concluded that primed B lymphocyte migration from spleen into bone marrow is not obligatory for the induction of staphylococcus-specific immunological memory in the bone marrow.

Animals↗
PubMed1985

[Immunoglobulin D--new insights into its structure and function].

The IgD is unique with regard to its structure, differences between species, genetic organization and behaviour in the immune response. With the successful analysis of the structure a new picture of the function has been emerged. The function of the membrane-bound IgD as a trigger receptor of B cells is qualitatively different from the mIgM. The secreted form could act as an intercellular messenger in the network regulation of the immune response. The mechanisms of the induction and maintenance of the immunological memory and tolerance remain unclear.

B-Lymphocytes↗
PubMed2002

In vitro induction of memory-driven responses against Neisseria meningitidis by priming with Neisseria lactamica.

Natural immunity against Neisseria meningitidis is acquired during childhood and youth through successive colonizations by commensal Neisseria, carrier N. meningitidis, and other bacterial genera sharing cross-reactive antigens with the meningococci. We have analyzed in mice the ability of Neisseria lactamica strains to induce immunological memory so that, upon a later contact with N. meningitidis, quickly raise protective responses against antigens that show cross-reactivity with meningococcal surface proteins. Sera obtained from mice immunized with N. lactamica and boosted with N. meningitidis were able to kill meningococci, with bactericidal activities variable depending on the immunizing strains used in the assays. Different mixtures of those sera resulted in higher killing activities, which agrees with the idea that successive colonizations by N. lactamica enhance the anti-meningococcal response. The existence of such outer membrane cross-reactive antigens has to be kept in mind when using outer membrane vesicle (OMV)-based anti-meningococcal vaccines because their use can affect colonization by N. lactamica and other species, hampering the natural mechanisms of acquisition of immunity to the meningococci, and leaving its ecological niche free for colonization by undesirable microorganisms.

Animals↗
PubMed1983

The effect of a single dose of cyclophosphamide on the kinetics of antibody production in the guinea pig.

Cyclophosphamide (CY) 250 mg/kg was given before, at the same time or after immunization with dinitrophenylated bovine gammaglobulin (DNP47-BGG) in Freund's incomplete adjuvant (FIA). CY, given on day +3 or +7 strongly suppressed both IgG subclasses. CY, on the day of immunization, reduced the IgG2 but not IgG1 anti-DNP antibody synthesis. Carrier BGG, injected 42 days after initial immunization, caused a secondary anti-hapten IgG1 response. This was not altered by CY treatment. The secondary anti-BGG response in animals pretreated with CY was also not affected. However, IgG1 anti-BGG in the other groups given CY on day 0, +3 or +7 was delayed and reduced. IgG2 anti-BGG was suppressed in guinea-pigs treated with CY, 3 or 7 days after primary immunization. DNP-BGG-specific IgE serum antibodies, not detectable in CY untreated animals, were found in guinea pigs given CY on days 0, +3 or +7. It is suggested that the kinetics of the IgG1 and IgG2 primary immune response differ, as does the development of IgG1 and IgG2 specific immunological memory.

Animals↗
PubMed2006

Generation and maintenance of mucosal memory B cell responses?

The mucosal immune system comprises B cells that can mount potent antibody responses against a variety of mucosal pathogens. Mucosal B cell responses can play a decisive role in protection against mucosal pathogens. Induction of mucosal B cell responses can be achieved through mucosal vaccination. However, mucosal administration of antigens without the use of adjuvants or delivery systems can lead to tolerance rather than immunity, and thus considerable efforts have been focused on development of effective immunopotentiating adjuvants and delivery systems. However, because the ultimate goal of vaccination is the induction and maintenance of immunological memory, the underlying mechanisms for induction of long-term mucosal B cell memory need to be analyzed for the selection of appropriate adjuvants. Moreover, as the antigen unspecific innate immune system invoked by adjuvants contributes significantly to the development of antigen-specific B cell responses, and presumably B cell memory, optimal interaction of B cells with cellular components of the innate immune system is required. To better understand the mechanisms that lead to the induction of mucosal antibody responses, antibodies against single epitopes from specific B cell clones as opposed to antibodies against large poly proteins from multiple B cell clones can be studied. This review deals with the concept of mucosal B cell memory with special emphasis on efforts to devise effective prophylactic or therapeutic vaccines.

Adjuvants, Immunologic↗
PubMed1983

Effects of gamma-irradiation on the rejection of transplanted scale melanophores in the teleost, Oryzias latipes.

The effects of gamma-irradiation on allograft rejection in the teleost, Oryzias latipes, were examined at 25 degrees C. The survival of melanophores in the transplanted scale was observed as an index of rejection. Allografts were rejected in non-irradiated fish within 7 days. In the gamma-irradiated recipients (2kR), the grafts were rejected more slowly, but still within 20 days. The gamma-ray effects, however, disappeared almost completely within 25 days after the irradiation. If the same recipient again received transplants, the secondary response occurred clearly and the melanophores were rejected very rapidly. The secondary response was suppressed by gamma-rays if the fish was irradiated just before the second transplantation. Immunologic memory against the first transplants disappeared within 30 days, a period shorter than that of mammals.

Animals↗