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Biomedical subjects

J Faro

Publications and source records attributed to J Faro.

At least 19 recordsLinked to original sources
PubMed2001

Defense factors of vaginal lactobacilli.

OBJECTIVE: To determine the antagonistic relationship between vaginal lactobacilli and endogenous vaginal microflora. STUDY DESIGN: Twenty-two Lactobacillus strains were studied for the production of lactic acid, hydrogen peroxide, and bacteriocin. RESULTS: Under standardized growth conditions, most strains increased their biomass by more than 4 times. Lactobacillus species grew best at a pH > or = 4.5, and growth was retarded at a pH < 4.5. Lactic acid levels were 0.68 to 2.518 mg/mL and were not related to the number of cells or the pH of media. The pH of the media was caused by the secretion of lactic and other organic acids. Approximately 80% of the strains produced H(2)O(2) and were graded as 2+ in one third of the strains and 1+ in others. No statistical correlation was found between H(2)O(2) lactic acid and bacteriocin production. Bacteriocin activity was tested on 4 strains of Gardnerella vaginalis. Approximately 80% of the lactobacilli tested produced bacteriocin that inhibited growth of G vaginalis. Six of the strains did not produce bacteriocin. Thirteen strains produced all 3 defense factors, whereas the others lacked 1 or 2 properties. CONCLUSIONS: Lactobacillus species grow best at a pH > 4.5. The pH of the media is dependent on the cell mass and on all organic acids produced by Lactobacillus species. Although all species produce organic acids, not all produce H(2)O(2) and bacteriocin. Not all strains of G vaginalis can be inhibited by lactobacilli-producing bacteriocin.

Adult↗
PubMed1997

Further studies on the problem of immune network modelling.

In a previous work we have analysed a family of antibody and B-cell network models (basic AB models) of the immune system. This analysis focused principally on the physiological interpretation of their parameters. Our approach consisted in building a detailed and general mathematical model (referred to as the GIB model) and then simplifying it formally to a version (named the RIB model) that belongs to the family of AB models, but which is more general than the basic AB models. From that study it was clear that some of the assumptions necessary to simplify the GIB model into the RIB one, as well as to recover the basic AB models from the RIB one, are quite unrealistic from a physiological point of view. All this raised the issue of the reliability, or even the heuristic value, of theoretical studies based on current network models for experimental immunologists. One approach to clarify this issue is to ask whether the unrealism of the assumptions implicit in the RIB and AB models entails qualitatively different behaviours between them compared to the GIB one. We initiate here such a work by performing a comparative study of a two-clone system of the AB and RIB models, and a variant of the GIB model in which the different molecular compartments were merged into a single one (labelled IGB model). Because all those models rely critically on certain B-cell activation functions, which constitute the core of an implicit model of individual B-cell reactivity or "local rules", we focused the present numerical study, to a great extent, on two parameters determining those activation functions (Hill coefficient and thresholds). Our results indicate that: (1) the RIB and IGB models display in general a much larger diversity of steady states than the AB models; (2) only under a very restricted parameter regime did all studied models behave similarly; (3) the parameter regime under which the AB and IGB models, but not the RIB one, behave similarly is still rather restricted through not as much as in (2); and (4) even relatively small quantitative changes (within reasonable values) in the postulated "local rules" can induce very large quantitative changes in the behaviour of the AB and RIB models but not the IGB model. In the light of the present results, we discuss the need of postulating a set of "local rules" solidly based on experimental evidence as a necessary condition for the reliability of current network models.

Animals↗
PubMed1996

A model of the immune network with B-T cell co-operation. I--Prototypical structures and dynamics.

Hitherto, "second generation" network models of the immune system have all been restricted to B-lymphocytes and the Ig molecules they produce. These models have not so far been able to provide a convincing mechanism for the distinction between a "Central Immune System" (CIS) composed of a connected network of lymphocyte clones which couple with "self" antigens in a tolerant mode, and a "Peripheral Immune System" (PIS) composed of clones with little or no supra-clonal organization and which produce classical immune responses when interacting with "non-self" antigens. Here, we present a new network model which explicitly incorporates B-T cell co-operation. In this model, B-cell activation is dependent on T-cell help, and activated T-cells are down-regulated by engagement of their TCRs by soluble Ig. We discuss the underlying biology on which we base the system of ordinary differential equations which defines the present network model. We then illustrate some basic features of the model by examining several prototypical situations with a small number of clones. Depending on the idiotypic connectivity structure, the model exhibits two distinct modes of coupling with antigens: an "immune response" mode in which T- and B-cell clones grow exponentially; and a "tolerant" mode in which T-cell clones are controlled by inclusion of all TCRs in the repertoire of an idiotypic B-cell network. Finally, we discuss the simplifying assumptions of the present model and argue that its range of validity is indeed the region of the state-space of the system where the discrimination between the CIS and the PIS take place.

B-Lymphocytes↗
PubMed1994

Numerical analysis of a model of ligand-induced B-cell antigen-receptor clustering. Implications for simple models of B-cell activation in an immune network.

B-cell activation driven by ligand-induced crosslinking of membrane immunoglobulin (mIg) is one of the most important processes in experimental and theoretical immunology. Although the activation of B cells through mIgs involves a complex series of intracellular processes, in immune network models it is usually assumed that there is a correlation between the degree of mIg crosslinking and the probability of B-cell activation. We explore the implications of this hypothesis by studying a model of ligand-induced B-cell receptor clustering proposed by Bell and further elaborated by Delisi and Perelson (BDP model). In this model, a critical time (tc) is defined at which the probability of infinite size complex formation (i.e., percolation) becomes non-zero. We use this variable, tc, as a means to characterize the degree of mIg crosslinking. To study the dependence of tc with respect to ligand valence, kinetic constants and ligand-receptor affinity x ligand concentration (K x C), we perform a systematic numerical study of the BDP model for parameter ranges including current empirical estimates for the kinetic constants. Concerning tc, we find that, for ranges of immunological interest (namely, those including current estimates of dissociation and receptor crosslinking rate constants), the curves obtained by plotting 1/tc vs. log(K x C) shift sensibly towards higher values of log(K x C), broadening and increasing its maximum amplitude, as the dissociation rate constant increases. As this finding suggests important consequences for immune network models, we further study the BDP model in an extended version for the case of two different ligands interacting simultaneously with a given B cell.3+

Animals↗
PubMed1993

Crosslinking of membrane immunoglobulins and B-cell activation: a simple model based on percolation theory.

In immune network models it is assumed that membrane immunoglobulin (mIg) crosslinking leads to B-cell activation. To analyse further the implications of this idea, a model of B-cell activation by ligand-induced mIg crosslinking in the absence of cell-to-cell interactions is proposed. The present model, based on a simple crosslinking mechanism previously proposed by other authors, assumes that activation of B-cells is possible once crosslinks of mIgs percolate and that percolation of crosslinks can only happen within a relatively short time tau. Given a lattice (regular or not), a molecular cluster is said to percolate or to become a percolating cluster if it spans the whole lattice (this is the case, for instance, of a polymer in a gel phase). From this model of B-cell activation we define the activation function fa (LK) as the fraction of B-cells activated after tau minutes of interaction with a ligand at concentration L and with affinity K. Numerical calculations show that, for current estimates of kinetic constants involved in the interaction of a given ligand with a B-cell clone, the activation function fa shifts when k-, the dissociation rate constant, is varied below 10(-3) s-1, this shift being linearly proportional to the variation of k-. This result contradicts and, therefore, challenges the assumption in immune network models that the activation function is identical for all ligands. This is important because the behaviour of at least some of those immune network models is quite sensitive to the relative values of the activation function thresholds.

Animals↗
PubMed1993

Studies on a recent class of network models of the immune system.

It is argued that the realism of computer simulations of network models of the immune system depends basically on the coherence of these models with the essentials of the known physiology of the cells and molecules selected to be modelled and on the incorporation in them of the different compartments of activated B cells. Focusing on these two aspects, here we analyse the simplifications and assumptions that go implicit in the formulation of a recently developed new class of network models that distinguish between immunoglobulins and B cells. This is approached by first building a general model which incorporates explicitly the kinetics of different B-cell compartments as well as a splenic compartment and a peripheric one for immunoglobulins, and then formally studying the simplifications on this model that are necessary to recover the initial simpler models. Following this procedure, it is shown that the effective coefficients of the different rate terms in the simpler models are particular combinations of the elementary rates obtained empirically. These relations reflect the particular assumptions associated with each simplification step. Also, it is shown that the usual biological interpretation of some of the coefficients in the ordinary differential equations of the simpler models is inconsistent with the more exact general model, unless one makes certain unreasonable assumptions about B-cell physiology. The relevance of this approach in providing variables with a biologically identifiable reality and for realistic, testable, computer simulations is discussed.

B-Lymphocytes↗
PubMed1990

Ontogenic characterization of thymic B lymphocytes. Analysis in different mouse strains.

We have characterized a population of murine B lymphocytes present in the thymus (TBL). They are a minor subset (0.2%-1% of total thymocytes), present from perinatal periods onwards and constituted by activated cells with a high proportion of Ig-secreting cells. They represent the first B lymphocytes detected that secrete IgG after birth. Functional analysis reveals that the frequency of lipopolysaccharide-responding cells in TBL is 5- to 10-fold lower than in the spleen. TBL from adult mice did not show any significant difference in their VH repertoire expression when compared to peripheral B lymphocytes. Furthermore, we have been able to isolate a subpopulation of B220+IgM-CD3- thymocytes whose putative B cell precursor potential needs to be directly analyzed. These and other findings support the intrathymic resident characteristics of TBL and suggest new ways of elucidating its physiological role in the complex selective processes occurring inside the thymus.

Aging↗
PubMed1990

Inside the thymus, Mls antigen is exclusively presented by B lymphocytes.

The ability to stimulate an Mls-1 mixed lymphocyte reaction (MLR) is predominantly expressed by low density B lymphocytes in the spleen and peritoneal cavity of normal adult mice, and is absent in splenic B cells 1 month after lethal irradiation and reconstitution from autologous bone marrow. Coreconstitution of these mice with normal syngeneic peritoneal cells restores the stimulatory potential of splenic B cells, but sorted CD5+ or CD5- IgM+ lymphocytes from peritoneum are equally good stimulators, suggesting that functional Mls-1 expression may require long life spans and selection. Bone-marrow-reconstituted DBA/2 mice that fail to express Mls-1 antigens in the periphery nevertheless maintain T-cell receptor V beta 6 and 8.1 deletions among the newly formed T cells. These findings led us to directly investigate the Mls stimulatory ability of purified antigen-presenting cell populations inside the thymus. We report here that thymic B lymphocytes seem to represent the only intrathymic cell population able to stimulate Mls-1 MLR.

Animals↗
PubMed1987

Immunoresponses to Neisseria meningitidis epitopes: immunomodulation by meningococcus B acts on more than one meningococcal surface epitope.

Neisseria meningitidis group B strain M986 (serotypes 2a, 7) (NMB) elicits a specific primary antiphosphorylcholine immune response in mice but not a secondary response. The ability of other serotype and serogroup meningococci to induce similar primary responses in mice was studied, as was the immunogenicity of trinitrophenyl coupled NMB (TNP-NMB) in primary and secondary antitrinitrophenyl responses. Except for NMB, all other strains tested (three serogroup B and one serogroup A meningococcal strains) were found to be very poor phosphorylcholine immunogens. TNP-NMB, however, though proving to be a very good TNP antigen, was only a weak phosphorylcholine antigen. Priming NBF1 female mice with TNP-NMB one month or more before challenging them with the same antigen induced a strong depression of anti-TNP response in the subsequent challenge. However, this effect was not observed with Xid NBF1 male mice. Furthermore, priming mice with NMB weakly affected the anti-TNP response, but greatly depressed the antiphosphorylcholine response, after TNP-NMB challenge. In addition, whereas apparently only one TNP-specific B cell subpopulation was responding in unprimed mice challenged simultaneously with TNP-NMB and TNP-Ficoll (non-additive response), priming mice with NMB appeared to facilitate the independent activation of two different TNP-specific B cell subpopulations (additive response).

Animals↗
PubMed1987

Immunoresponses to Neisseria meningitidis epitopes: in vivo analysis of immunocompetent cells involved in suppression of secondary response to phosphorylcholine.

The immune response to phosphorylcholine (PC) antigens has been extensively studied in recent years. Neisseria meningitidis serogroup B M986 (NMB) was recently reported to induce a PC-specific plaque-forming cell (PFC) immuno-response in mice, a characteristic useful for the study of immunomodulating properties of N. meningitidis. With this technique, priming mice with low doses of NMB has been shown greatly to impair their ability, one month after priming, to mount an anti-PC response induced by NMB; this suppression is permanent, does not involve switching from IgM to another immunoglobulin class, transiently affects the T15 idiotype expression and is carrier specific. We report, based on an analysis of spleen cells from NMB-primed mice in an adoptive transfer model, that this suppression does not appear to be mediated by B lymphocytes nor does it seem to be under the direct control of T lymphocytes; rather, it involves radio-resistant cells. Additionally, our results show that NMB modulates the idiotype composition of the anti-phosphorylcholine response, probably by enhancing the expression of so called hapten-augmentable PFC. These results demonstrate that NMB can interfere effectively with the immune response in a variety of ways.

Animals↗
PubMed1987

[Anti-phosphorylcholine response of autoimmune NZB/W mice: variations with age of serum titers and homogeneity].

Antibody titers and avidity of sera of autoimmune NZB/W mice in responses induced by different antigens were determined. Results show an age-dependent decrease of the antibody titer in sera from female mice immunized with phosphorylcholine coupled to keyhole limpet haemocyanin. This decrease was not detected when using as immunogen an antigenic preparation of Neisseria meningitidis that naturally induces anti-phosphorylcholine antibodies, but was detected with a modification of this antigen (heat inactivation and further coupling with the hapten). Determinations of inhibition profiles of antisera suggest that this loss of immune competence is paralleled by a decrease in avidity and homogeneity of antisera. This finding may be related to the loss of idiotypic clonal dominance recently reported to occur in these mice.

Aging↗
PubMed1986

Immunoresponses to Neisseria meningitidis epitopes: suppression of secondary response to phosphorylcholine is carrier specific.

Results of our previous work have shown that Neisseria meningitidis serogroup B M986 can induce a phosphorylcholine (PC)-specific plaque-forming cell immunoresponse in mice. Also, a single injection of a relatively low dose of meningococci in NBF1 female mice induced a priming time-dependent suppression on subsequent meningococcus challenge. This suppression was not due to switching to another class of immunoglobulin nor to the presence of a capsule on N. meningitidis. In this study we show that suppression induced by meningococcus is carrier specific. Furthermore, we offer evidence suggesting that the structure(s) on meningococcus that trigger this suppression is heat labile and different from the antigenic structure(s) recognized by the suppressed B cells. In addition, we found that there is a gradual increase in antibody secretion rates of N. meningitidis-induced anti-PC plaque-forming cells that correlates with N. meningitidis priming time. Rather unexpected was the fact that pretreatment of mice with PC-keyhole limpet hemocyanin (thymus-dependent antigen) had a great influence on the subsequent PC-specific immunoresponses induced by N. meningitidis and PC-coupled heat-inactivated meningococcus [PC-(NMB)HI], as shown by (i) a striking decrease in T15 idiotype expression, (ii) concomitant direct anti-PC plaque-forming cells reduction, (iii) switching to immunoglobulin G (N. meningitidis-induced immunoresponse) or immunoglobulin G plus immunoglobulin A [PC-(NMB)HI-induced immunoresponse], and (iv) a significant increase in heterogeneity of plaque-forming cell secretion rates. The possibility that N. meningitidis, PC-(NMB)HI, and PC-KLH stimulate B lymphocytes pertaining to three different subpopulations embedded in distinct regulatory circuits is discussed, with emphasis on the interrelationships between T-dependent and T-independent lymphocyte compartments. We focus on the possibility of the existence of high-level regulatory circuits in which lymphocyte subpopulations or sets of lymphocyte subpopulations with different requirements of activation are connected.

Animals↗
PubMed1986

Effects of antigen and internal environment on anti-phosphorylcholine immune responses of autoimmune aged NZB/W F1 mice.

The idiotypic profile of anti-phosphorylcholine plaque-forming cell responses and their evolution with ageing were studied in (NZB X NZW) F1 mice. Our results showed that the anti-phosphorylcholine plaque-forming cell response induced by phosphorylcholine coupled to keyhole limpet haemocyanin and, paralleling, the T15 idiotype clonal dominance declined with ageing. This loss of immune competence was also observed with another thymus-dependent (phosphorylcholine coupled to egg globulin) as well as thymus-independent (capsular polysaccharide of Streptococcus pneumoniae strain R36a) antigens. In contrast, old mice challenged with an antigenic preparation of Neisseria meningitidis showed an immune response not significantly different from that elicited by the same antigen in young mice. The hapten-augmentable plaque-forming cells were assayed to determine whether a putative auto-antiidiotypic regulation underlies this loss of immune competence. Only minimal numbers and non-significant differences between young and old mice immunized with any antigen could be detected. Further studies using an adoptive transfer system demonstrated that cells from aged mice were able to support a normal anti-phosphorylcholine response when transferred into lethally irradiated young recipients. Our results suggest that no permanent cellular defects, but rather internal environment or/and radioresistant suppressor cells, are involved in this loss of immune competence. The role played by these factors and their effect on distinct subpopulations of B cells are discussed.

Aging↗
PubMed1985

Immunoresponses to Neisseria meningitidis epitopes: primary versus secondary antiphosphorylcholine responses.

Specific antiphosphorylcholine immune responses were found to be elicited by different Neisseria meningitidis group B M986 preparations. Our results suggest the functional presence of phosphorylcholine in the bacteria. The immune responses, mostly immunoglobulin M, were measured with a plaque-forming cell assay. The secondary phosphorylcholine-specific immune response induced by intact meningococci was significantly lower than the primary phosphorylcholine-specific immune response induced by the same antigens. This suppression is priming time dependent and does not represent an early switching to the expression of other classes of immunoglobulins.

Animals↗
PubMed1983

Effect of clofibrate on the growth-kinetics of the murine P 1798(sc) lymphoma.

Clofibrate (CPIB) is a drug applied as an antilipidaemic agent in mammals. In this work we have tested its efficacy in vivo on the growth kinetics of P 1798(sc) lymphoma transplanted to recipient (BALB/c x AKR)F1 mice. Our results show a facilitation of the tumour growth rate in treated recipients. This fact may be related to an effect of the agent on the recipient which produces a decrease in the immune response as was confirmed on testing CPIB on thymus-dependent antigens in haemolytic plaque assays.

Animals↗
PubMed1982

[Analysis of the escape of tumor P1798(SC) from immunologic control in hybrid mice (Balb/c X AKR)F1 (BAF1)].

Expression of tumoral antigens and their masking by sialic acids were studied. Tumour with greater content in sialic acid [P1798(sc)] can surpass the histocompatibility barrier. Furthermore, removal of sialic acid residues from membrane by neuramidase treatment results in a retarded or inhibited tumoral growth. These results suggest an antigenic masking by sialic acids. On the other hand, in the anti-P1798(sc) humoral response are involved two antigens, at least, also expressed by syngeneic hepatocytes and thymocytes, as demonstrated by cytotoxicity assays.

Animals↗