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F Celada

Publications and source records attributed to F Celada.

At least 19 recordsLinked to original sources
PubMed1992

A model for simulating cognate recognition and response in the immune system.

We have constructed a model of the immune system that focuses on the clonotypic cell types and their interactions with other cells, and with antigens and antibodies. We carry out simulations of the humoral immune system based on a generalized cellular automaton implementation of the model. We propose using computer simulation as a tool for doing experiments in machine, in the computer, as an adjunct to the usual in vivo and in vitro techniques. These experiments would not be intended to replace the usual biological experiments since, in the foreseeable future, a complete enough computer model capable of reliably simulating the whole immune would not be possible. However a model simulating areas of interest could be used for extensively testing ideas to help in the design of the critical biological experiments. Our present model concentrates on the cellular interactions and is quite adept at testing the importance and effects of cellular interactions with other cells, antigens and antibodies. The implementation is quite general and unrestricted allowing most other immune system components to be added with relative ease when desired.

Antibodies↗
PubMed1992

A computer model of cellular interactions in the immune system.

The power of modern computers allows the modeling and simulation of complex biological systems. The last decade has seen the emergence of a growing number of simulations of the immune system. In this article, Franco Celada and Philip Seiden present a model that, they suggest, is rich enough to allow computer experiments to be used as practical adjuncts to the usual biological experiments, at a saving of cost and time.

Animals↗
PubMed1992

Guidelines for the PhD degree in immunology. International Union of Immunological Societies Education Committee.

The International Union of Immunological Societies, recognizing the need for internationally acceptable standards for the PhD degree in immunology, commissioned the IUIS Education Committee to prepare recommendations on the subject. This document, the result of a two-year study of PhD programs in many countries, presents these recommendations.

Academic Dissertations as Topic↗
PubMed1992

Kinetic immunodominance: functionally competing antibodies against exposed and cryptic epitopes of Escherichia coli beta-galactosidase are produced in time sequence.

The murine antibody response to Escherichia coli beta-galactosidase (GZ) was analyzed in vivo and in vitro by focusing on two families of antibodies that exert distinct conformational/functional activity on the antigen. Activating antibodies--defined by their capacity to increase the enzymatic activity of defective GZ produced by mutant strains of E. coli--are detected early after secondary challenge. Inhibiting antibodies, which interfere with antibody-mediated enzyme activation, appear later and cause the abrupt fall of activating titer, a scenario suggesting either idiotype/anti-idiotype interaction or opposite pulsions exerted on the antigen molecule. Supporting the latter mechanism, the confrontation of mAbs of the two families produced classical competitive inhibition curves when the readout was enzyme activation, although they recognize two different epitopes of the same molecule: the activating mAb a quaternary conformation-dependent site of wild-type GZ, the inhibiting mAb a sequential determinant exposed only in denatured or in defective enzyme. The different timing of generation of these antibodies during the response may depend on a processing step necessary for unfolding of native antigen and consequent display of certain cryptic epitopes before they can trigger specific B cells. A picture emerges where the response to the various epitopes of a complex antigen is sequentially connected and where the uptake by antigen-presenting cells of antigen complexed with antibodies specific for the exposed epitopes may favor revelation of the cryptic ones.

Animals↗
PubMed1992

Inhibitory activity of HIV envelope gp120 dominates over its antigenicity for human T cells.

HIV-1 envelope glycoprotein (gp120), as a CD4-binding reactant, has been shown to inhibit in its native form human T cell responses to several antigens. Here we show that gp120 in soluble form also inhibits activation of a specific human T cell line that responds to gp120-pulsed autologous antigen-presenting cells. In addition the inhibitory property of gp120 for antigen-driven T cell proliferation depends upon its ability to bind CD4 and is lost when CD4-binding capacity is abolished by denaturation, or blocked by complexing with soluble CD4 or with polyclonal antibodies. In contrast, antigenicity of denatured or complexed gp120 for specific human T cells is preserved. Similar effects are also observed with another CD4-binding reactant (i.e. anti-Leu 3a MoAb), which stimulates and/or inhibits human T cells specific for mouse immunoglobulins depending on native or denatured conformation.

Antibodies, Monoclonal↗
PubMed1991

Effect of antigen/antibody ratio on macrophage uptake, processing, and presentation to T cells of antigen complexed with polyclonal antibodies.

Activation of a galactosidase-specific murine T hybridoma clone and of a human tetanus toxoid-specific T clone by antigen-presenting cells (APC) was used to evaluate the regulatory function of antibodies complexed with the relevant antigen. Complexed antigen, in fact, is taken up with high efficiency thanks to Fc receptors borne by APC. Antibody/antigen ratio in the complexes proved to be a critical parameter in enhancing antigen presentation. Complexes in moderate antibody excess provided optimal T cell activation independently of the physical state of the complexes (precipitated by a second antibody or solubilized by complement). Complexes in extreme antibody excess, on the contrary, did not yield T cell activation although taken up by APC efficiently. The effect of antibodies at extreme excess was observed with substimulatory dose of antigen (loss of potentiation) and with optimal dose of antigen (loss of stimulation). An excess of specific polyclonal antibodies hampers proteolytic degradation of antigen in vitro, supporting the view that a similar mechanism may operate within the APC that have internalized immune complexes in extreme antibody excess. The possibility that immune complex forming in extreme antibody excess may turn off the T cell response is proposed as a regulatory mechanism.

Animals↗
PubMed1990

Antibody raised against soluble CD4-rgp120 complex recognizes the CD4 moiety and blocks membrane fusion without inhibiting CD4-gp120 binding.

We studied the humoral response of mice immunized with soluble CD4-rgp120 complex, testing polyclonal and monoclonal antibodies (mAbs) with the aim of identifying molecular changes that take place after the first interaction between human immunodeficiency virus and the cell surface. The antisera had a paradoxically high syncytia-blocking titer associated with anti-CD4 specificity, while their capacity to inhibit CD4-gp120 binding was relatively modest. One of the mAbs produced from these responders blocks syncytia formation but does not inhibit CD4 interaction with gp120. Apparently, this mAb interacts with the CD4 moiety of CD4-gp120 complex and prevents a post-binding event necessary for membrane fusion and viral infection.

Animals↗
PubMed1990

Monoreactive and polyreactive rheumatoid factors produced by in vitro Epstein-Barr virus-transformed peripheral blood and synovial B lymphocytes from rheumatoid arthritis patients.

The CD5 membrane molecule, initially identified as an exclusive T-cell marker, also defines a phenotypically and functionally distinct B-lymphocyte population. In normal individuals, CD5+ B cells are committed to secrete 'natural' polyreactive (auto)antibodies, that is antibodies, mainly IgM, endowed with multiple antigen-binding capabilities, including rheumatoid factor (RF) activity. At variance with this, in rheumatoid arthritis (RA) as well as in other autoimmune conditions, monoreactive autoantibodies binding with high affinity and specificity to a given self antigen have been isolated and the cells from which they originate differently related to the CD5+ B-lymphocyte subset. Here, we studied the proportions of CD5+ B cells and the characteristics, in terms of polyreactivity and monoreactivity, of RF produced by B lymphocytes in RA patients with classified disease activity. Our results suggest that patients with a more severe disease activity have higher proportions of CD5+ B cells and higher frequencies of B lymphocytes committed to secrete RF, with the characteristics of polyreactive antibodies. On the other hand, we did not find a significant difference between the proportions of peripheral B cells producing monoreactive RF in patients with high- versus patients with low-activity RA. However, in two highly active RA patients, we found that synovial fluid, compared with peripheral blood, was significantly enriched for (IgG and IgA) monoreactive RF-producing B cells.

Adult↗
PubMed1989

Use of bispecific hybrid antibodies for the development of a homogeneous enzyme immunoassay.

Hybrid bispecific monoclonal antibodies reacting with carcinoembryonal antigen (CEA) and with the E. coli enzyme beta-galactosidase (GZ) were produced by fusion of hybridomas or chemical linkage of half-antibodies. Since the original anti-GZ antibody used in these experiments was capable of protecting GZ from thermal denaturation, it was possible, by hybridizing it with two different non-competitive anti-CEA antibodies, to design a homogeneous enzyme immunoassay for quantitation of CEA. In fact, a mathematical analysis of the reaction indicates that, under appropriate concentrations of the reactants, circular complexes can be formed which contain the two hybrid antibodies, the GZ enzyme and the CEA antigen. The stability of these complexes can be expected to be substantially greater than that of the more labile CEA-free GZ-antibody complexes, prompting a significant increase in the amount of enzyme molecules which are bound to antibody and are consequently protected from thermal denaturation. These expectations were supported by experimental results: under appropriate conditions, heat-resistant enzyme activity was indeed proportional to concentration of CEA in the range up to 75 ng/ml. As predicted by theory, however, in the presence of excess CEA - in fact at CEA concentrations which are higher than those of possible clinical relevance - circular complexes tended to open up, leading to a marked prozone effect.

Antibodies, Monoclonal↗
PubMed1989

Sideways killing: the cytolysis of Fc receptor-bearing cells through bridging to cytolytic T lymphocytes by antibodies specific for the T-cell receptor-T3 complex.

Cytolytic T lymphocytes (CTL) cause cytolysis of foreign or virus-infected syngeneic cells when recognition of the target plus major histocompatibility complex (MHC) occurs via the T-cell receptor (TCR). The recognition event leads to intimate contact between the two cells and activation of the cytolytic effector. Activation and target cell lysis can also occur in the presence of antibodies to the TCR. This is accomplished by bridging the effector cell TCR to the target cell FcR by an anti-TCR monoclonal antibody (MoAb). Recent findings have placed the role of the FcR in this event in a questionable light. We confirm the importance of Fc gamma R by demonstrating that: (a) melanoma cells are killed by CTL clones in the presence of anti-TCR-CD3 antibodies only when the melanoma cells express the Fc gamma R on their surface; (b) native Ig, heat-aggregated Ig, or an Fc fragment from an antibody expressing the same isotype as the anti-TCR antibody can block the killing of high avidity Fc gamma RI-bearing cells mediated by anti-TCR antibody (F23.1); and (c) anti-Fc gamma R MoAb (2.4G2) and a truncated soluble Fc gamma RII molecule inhibit the killing of low-avidity Fc gamma RII-bearing cells mediated by anti-CD3 MoAb (145-2C11). Thus, we show that both high-avidity Fc gamma RI and low-avidity Fc gamma RII can mediate sideways killing depending upon the isotype of the anti-TCR antibody and the type of FcR present on the target cell surface.

Animals↗
PubMed1988

Differential activation of T cell clones stimulated by macrophages exposed to antigen complexed with monoclonal antibodies. A possible influence of paratope specificity on the mode of antigen processing.

We have used the enhanced uptake by FcR-bearing cells observed when Ag is administered as an immune complex to investigate the possible impact of specific antibodies on processing and presentation of antigen by accessory cells. The Ag Escherichia coli beta-galactosidase alone or bound to different mAb was incubated with peritoneal macrophages. These were subsequently exposed to a battery of Ag-specific T hybridoma clones. The resulting production of IL-2 was taken as a measure of effective presentation. The results of 43 mAb-T clone combinations showed a potentiation of presentation of Ag at substimulatory concentration in the majority of the cases, indicating that each mAb is conducive to FcR-mediated uptake by macrophages, and that each T clone can be stimulated by properly presented Ag. In contrast, nine combinations yielded a lower response, two of them falling to baseline values. We attribute these results, which corroborate our previous evidence of directional help in the beta-galactosidase system, to a modulation in enzymatic processing of Ag and its subsequent presentation imposed by the paratope of the mAb binding to the relevant epitope.

Antibodies, Monoclonal↗
PubMed1988

Detection of parasite related antigens associated with conglutinin binding immune complexes in patients with Schistosoma haematobium.

An ELISA assay was designed to detect the presence of parasite related antigens associated with circulating immune complexes in patients affected by urinary schistosomiasis. The assay makes use of bovine conglutinin as the immune complex recognition unit and of human anti-Schistosoma antibody as the antigen recognition unit. Using this method we showed that 10 of 15 (67%) patients with a positive polyethylene glycol assay had circulating immune complexes in which parasite antigens could be detected.

Antigen-Antibody Complex↗
PubMed1988

Preferential pairing of T-B specificities in the same antigen: the concept of directional help.

It is important for an effective planning of the new generation of vaccines to consider that the eventual response is regulated by the interplay of stimulating and suppressing epitopes, resulting in dominance of certain sites over others, and that in order for a molecule to be crossimmunogenic with the outside invader both B and T epitopes must be present. However, T-B cooperation is not random but is guided by preferential pairing of sites within a single macromolecule; this situation can be explained by antigen processing by B cells and paratope mediated interference with endosomial degradation.

Antibodies↗
PubMed1988

Effect of cyclosporine on the antigen-presenting function of human and murine accessory cells.

Recent reports have challenged the belief that accessory cells are resistant to cyclosporine. Such a tenet was based on the observation that several functions of accessory cells, such as IL-1 production and phagocytosis, are resistant to the drug. On the other hand, when a less primitive, more refined function of accessory cells was examined--i.e., the capacity to take up, process, and present antigen in an MHC-restricted fashion to antigen-specific T lymphocytes, CsA proved to be an effective inhibitor. In contrast to this finding, when antigen was provided in the form of an immune complex prepared with a monoclonal antibody, uptake of antigen--likely mediated by the Fc receptors--and subsequent processing and presentation were not affected by CsA. These results suggest that, depending on whether the antigen is taken up by constitutive or by receptor-mediated endocytosis, accessory cells can be functionally defined as resistant or sensitive to CsA.

Animals↗