Author
Jacques Rene Hiernaux
Bio: Jacques Rene Hiernaux is an academic researcher from Université libre de Bruxelles. The author has contributed to research in topics: Antigen & Antibody. The author has an hindex of 12, co-authored 26 publications receiving 497 citations.
Topics: Antigen, Antibody, Idiotype, Monoclonal antibody, Cytotoxic T cell
Papers
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TL;DR: The activation of A48 Id+ anti-BL clones anti-A48 Id antibody is specific because the pretreatment of newborn mice with anti-MOPC 384 Id antibody, followed by immunization with BL, does not lead to its activation.
Abstract: BALB/c mice immunized with bacterial levan (BL) produce an immune response that fails to generate antibody expressing the idiotype (Id) of the beta (2 leads to 6) fructosan-binding myeloma protein ABPC 48 (A48). Pretreatment of newborn BALB/c mice (at 1 d of age) with 0.01-10 microgram of affinity purified BALB/c anti-A48 Id antibody followed by immunization with BL 1-2 mo later produces an anti-BL response that expresses the A48 Id. This shows that A48 Id+ anti-BL clones belong to a normally silent fraction of the anti-BL repertoire. The activation of A48 Id+ anti-BL clones anti-A48 Id antibody is specific because the pretreatment of newborn mice with anti-MOPC 384 Id antibody, followed by immunization with BL, does not lead to its activation. Moreover, pretreatment of mice with anti-A48 Id antibody does not alter the MOPC 460 Id+ component of the anti-TNP response. It is also important to note that the activation of the A48 Id+ clone in pretreated mice requires subsequent immunization with BL.
100 citations
TL;DR: The onset of a morphogenetic gradient and pattern formation are combined in a single coherent model and size invariance and its biological implications are discussed.
Abstract: Models based on molecular mechanisms are presented for pattern formation in developing organisms. It is assumed that there exists a diffusion governed gradient in the morphogenetic field. It is shown that cellular differentiation and the subsequent pattern formation result from the interaction of the diffusing morphogen with the genetic regulatory mechanism of cells. In a second stage it is shown that starting from a homogeneous distribution of morphogen, polarity can be generated spontaneously in the morphogenetic field giving rise to the establishment of a gradient. The stability of these gradients is demonstrated. The onset of a morphogenetic gradient and pattern formation are combined in a single coherent model. Size invariance and its biological implications are discussed.
67 citations
TL;DR: In this paper, Isoelectric focusing (IEF) data showed that in 1-mo old mice an UPC10-like spectrotype was observed, whereas in 3-mo-old mice, a new spectro type binding bacterial levan (BL) rather than inulin (In) was identified.
Abstract: The anti-beta 2 leads to 6 fructosan antibodies sharing the idiotypes (Id) of ABPC48 (A48) monoclonal protein represent a silent fraction of the anti-beta 2 leads to 6 fructosan repertoire, since these antibodies cannot be detected during a conventional immune response elicited by bacterial levan (BL). However, the administration at birth of minute amounts of anti-A48 Id antibodies causes a long-lasting activation of A48 Id+-bearing clones. This activation is related to direct interaction of anti-A48 Id antibodies with precursors bearing the A48 Id+ immunoglobulin receptor, since an A48 Id+ response can be transferred with highly purified B cells in lethally irradiated mice. The maturation of these precursors into A48 Id+ anti-beta 2 leads to 6 fructosan antibody-secreting cells requires challenge by the antigen. Isoelectric focusing (IEF) data showed that in 1-mo-old mice an UPC10 (U10)-like spectrotype was observed, whereas in 3-mo-old mice, a new spectrotype binding BL rather than inulin (In) was identified. This spectrotype was observed only in CXBJ mice, the single strain in which an A48 Id+ response was observed. The antigenic challenge can be replaced by a monoclonal anti-A48 Id antibody (i.e., 17-38). Interestingly, in 1-mo-old BALB/c mice treated with anti-A48 Id antibodies, the challenge with 17-38 monoclonal antibody led to the activation of A48 Id- anti-beta 2 leads to 6 fructosan-reactive clones with BALB/c type IEF spectrotypes, whereas in 3-mo-old BALB/c mice treated with anti-A48 Id antibodies, the challenge with 17-38 monoclonal antibody led to the activation of W3082 IdX+ anti-beta 2 leads to 6 and beta 2 leads to 1 fructosan-reactive clones. In these animals, inhibition of A48 Id+ anti-beta 2 leads to 6 fructosan clones was observed. This antibody probably represents a homobody carrying the internal image of the antigen, which through its paratope suppresses the A48 Id+ response and through its Id activates an A48 Id- anti-beta 2 leads to 6 fructosan response in 1-mo-old mice and in 3-mo-old mice leads to an anti-beta 2 leads to 6 and beta 2 leads to 1 fructosan response dominated by the W3082 IdX.(ABSTRACT TRUNCATED AT 400 WORDS)
62 citations
TL;DR: The data suggest that shared idiotopes are common for antibodies for an antigenic family in Gram-negative bacteria.
Abstract: Shared idiotypes (Ids) were identified on monoclonal antibodies specific for different immunodominant sugars in the lipopolysaccharide (LPS) of Gram-negative bacteria. The first group of monoclonal antibodies is specific for Escherichia coli 0113 LPS, whereas the second group is specific for Salmonella tranaroa LPS. The shared idiotopes borne by these two groups of monoclonal antibodies were identified with monoclonal anti-Id antibodies specific for E. coli LPS-binding monoclonal antibodies and with syngeneic anti-384Id antibodies specific for MOPC 384 and MOPC 870 myeloma proteins. Our data suggest that shared idiotopes are common for antibodies for an antigenic family.
44 citations
TL;DR: It is shown how each mode of the immune response may be interpreted as a transition from one steady state to another one, following antigenic or any other stimulation.
Abstract: The regulation of the immune response is a complex phenomenon whose details are not yet well known. Recently, Jerne has described the immune system as a complex idiotypic network. He has proposed that the interactions between elements involved in the latter are responsible for the main regulatory patterns of the immune system. Some experimental results are in favour of this hypothesis. A few theoretical models have been developed to described more precisely the nature of the interactions between the lymphocytes and the antibodies inside the network as well as their implications. In such a model, the time evolution of the concentration of those elements is described by kinetic equations whose integration over time can reproduce roughly the dynamic behaviour of the immune system. Those theoretical models should at least account for phenomena such as a memory or tolerance, which implies the maintenance of a stationary state. This latter statement can be directly related to the mathematical concept of stability. We illustrate this point on various models. More precisely, we show how each mode of the immune response may be interpreted as a transition from one steady state to another one, following antigenic or any other stimulation.
40 citations
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TL;DR: A dynamical model for the immune system is described that is based on the network hypothesis of Jerne, and is simple enough to simulate on a computer, and has a strong similarity to an approach to learning and artificial intelligence introduced by Holland, called the classifier system.
Abstract: The immune system is capable of learning, memory, and pattern recognition. By employing genetic operators on a time scale fast enough to observe experimentally, the immune system is able to recognize novel shapes without preprogramming. Here we describe a dynamical model for the immune system that is based on the network hypothesis of Jerne, and is simple enough to simulate on a computer. This model has a strong similarity to an approach to learning and artificial intelligence introduced by Holland, called the classifier system. We demonstrate that simple versions of the classifier system can be cast as a nonlinear dynamical system, and explore the analogy between the immune and classifier systems in detail. Through this comparison we hope to gain insight into the way they perform specific tasks, and to suggest new approaches that might be of value in learning systems.
1,326 citations
TL;DR: The model exhibits a number of phenomena that are seen in vivo, including immunostimulation of tumor growth, "sneaking through" of the tumor, and formation of a tumor "dormant state".
Abstract: We present a mathematical model of the cytotoxic T lymphocyte response to the growth of an immunogenic tumor. The model exhibits a number of phenomena that are seen in vivo, including immunostimulation of tumor growth, "sneaking through" of the tumor, and formation of a tumor "dormant state". The model is used to describe the kinetics of growth and regression of the B-lymphoma BCL1 in the spleen of mice. By comparing the model with experimental data, numerical estimates of parameters describing processes that cannot be measured in vivo are derived. Local and global bifurcations are calculated for realistic values of the parameters. For a large set of parameters we predict that the course of tumor growth and its clinical manifestation have a recurrent profile with a 3- to 4-month cycle, similar to patterns seen in certain leukemias.
789 citations
TL;DR: By computer simulations, the theory accounts for much of the regulatory phenomena observed, including signalling to regenerate removed parts, and the resulting pattern is, to a large extent, independent of the details provided by initial conditions and inducing signals.
Abstract: Summary In 1972, we proposed a theory of biological pattern formation in which concentration maxima of pattern forming substances are generated through local selfenhancement in conjunction with long range inhibition. Since then, much evidence in various developmental systems has confirmed the importance of autocatalytic feedback loops combined with inhibitory interaction. Examples are found in the formation of embryonal organizing regions, in segmentation, in the polarization of individual cells, and in gene activation. By computer simulations, we have shown that the theory accounts for much of the regulatory phenomena observed, including signalling to regenerate removed parts. These selfregulatory features contribute to making development robust and error-tolerant. Furthermore, the resulting pattern is, to a large extent, independent of the details provided by initial conditions and inducing signals. BioEssays 22:753‐760, 2000. fl 2000 John Wiley & Sons, Inc.
651 citations
TL;DR: Many years of immunochemical research were required before a concentrated, biologically active, and safe preparation of immune globulin suitable for intravenous use became available.
Abstract: ALMOST as soon as a therapeutically useful concentrated immune globulin product became available for intramuscular use, it was obvious that a preparation that could be administered intravenously would be advantageous.1 , 2 However, many years of immunochemical research were required before a concentrated, biologically active, and safe preparation of immune globulin suitable for intravenous use became available. In the past decade, chemists have learned how to prevent protein aggregation while concentrating immune globulin. Purification can be achieved by chromatography, and stabilization of the intact immune globulin is then promoted by acidification with pepsin or the addition of sugars, amino acids, or both. . . .
650 citations
TL;DR: A brief introduction to the biology of the immune system is provided and a number of immunological problems in which the use of physical concepts and mathematical methods has increased the authors' understanding are discussed.
Abstract: The immune system is a complex system of cells and molecules that can provide us with a basic defense against pathogenic organisms. Like the nervous system, the immune system performs pattern recognition tasks, learns, and retains a memory of the antigens that it has fought. The immune system contains more than 10{sup 7} different clones of cells that communicate via cell-cell contact and the secretion of molecules. Performing complex tasks such as learning and memory involves cooperation among large numbers of components of the immune system and hence there is interest in using methods and concepts from statistical physics. Furthermore, the immune response develops in time and the description of its time evolution is an interesting problem in dynamical systems. In this paper, the authors provide a brief introduction to the biology of the immune system and discuss a number of immunological problems in which the use of physical concepts and mathematical methods has increased our understanding. {copyright} {ital 1997} {ital The American Physical Society}
591 citations