Idiotypic networks incorporating T-B cell co-operation. The conditions for percolation

Boer, Rob J. de; Hogeweg, Paulien

doi:10.1016/s0022-5193(89)80055-4

Cited by 13 publications

(6 citation statements)

References 43 publications

(51 reference statements)

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“…Thus, in T cell-dependent B cell responses, other cell surface receptors need to be engaged to generate a response, and the degree of their engagement may modulate the response to cross-linking (cf. De Boer and Hogeweg, 1989;Carter and Fearon, 1992; Neumann and Perelson, manuscript in preparation). This means that responses may differ in their requirement for cross-linking, a phenomenon seen in histamine release from human basophils (cf.…”

Section: Cellular Responsementioning

confidence: 99%

Cross-linking reconsidered: binding and cross-linking fields and the cellular response

Sulzer¹,

Boer²,

Perelson³

1996

Biophysical Journal

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We analyze a model for the reversible cross-linking of cell surface receptors by a collection of bivalent ligands with different affinities for the receptor as would be found in a polyclonal anti-receptor serum. We assume that the amount of cross-linking determines, via a monotonic function, the rate at which cells become activated and divide. In addition to the density of receptors on the cell surface, two quantities, the binding field and the cross-linking field, are needed to characterize the cross-linking curve, i.e., the equilibrium concentration of cross-linked receptors plotted as a function of the total ligand site concentration. The binding field is the sum of all ligand site concentrations weighted by their respective binding affinities, and the cross-linking field is the sum of all ligand site concentrations weighted by the product of their respective binding and cross-linking affinity and the total receptor density. Assuming that the cross-linking affinity decreases if the binding affinity decreases, we find that the height of the cross-linking curve decreases, its width narrows, and its center shifts to higher ligand site concentrations as the affinities decrease. Moreover, when we consider cross-linking-induced proliferation, we find that there is a minimum cross-linking affinity that must be surpassed before a clone can expand. We also show that under many circumstances a polyclonal antiserum would be more likely than a monoclonal antibody to lead to cross-linking-induced proliferation.

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Section: Cellular Responsementioning

confidence: 99%

Cross-linking reconsidered: binding and cross-linking fields and the cellular response

Sulzer¹,

Boer²,

Perelson³

1996

Biophysical Journal

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“…Other models that have considered the interaction between different antigen-specific cells for the most part have focused on idiotype-antiidiotype networks (30)(31)(32). In this paper, we develop models that combine the dynamics of antigen-specific stimulation and interaction between different lineages (see refs.…”

mentioning

confidence: 99%

Models of immune memory: On the role of cross-reactive stimulation, competition, and homeostasis in maintaining immune memory

Antia

Pilyugin

Ahmed

1998

Proc. Natl. Acad. Sci. U.S.A.

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There has been much debate on the contribution of processes such as the persistence of antigens, cross-reactive stimulation, homeostasis, competition between different lineages of lymphocytes, and the rate of cell turnover on the duration of immune memory and the maintenance of the immune repertoire. We use simple mathematical models to investigate the contributions of these various processes to the longevity of immune memory (defined as the rate of decline of the population of antigen-specific memory cells). The models we develop incorporate a large repertoire of immune cells, each lineage having distinct antigenic specificities, and describe the dynamics of the individual lineages and total population of cells. Our results suggest that, if homeostatic control regulates the total population of memory cells, then, for a wide range of parameters, immune memory will be long-lived in the absence of persistent antigen (T 1͞2 > 1 year). We also show that the longevity of memory in this situation will be insensitive to the relative rates of cross-reactive stimulation, the rate of turnover of immune cells, and the functional form of the term for the maintenance of homeostasis.Although the ability to maintain memory after an encounter with an antigen is one of the central features of the immune system, the mechanism(s) by which immune memory is maintained are not yet fully understood. The initial view (1) suggesting that ''memory'' lymphocytes might be very longlived cells could be rejected because lymphocytes have turnover rates much shorter than the lifespan of the host (2, 3). The relatively high rates observed for the turnover particularly of antigen-specific cells after stimulation led to the hypothesis that maintenance of an elevated population of antigen-specific immune cells might require restimulation, either by persistent antigen or by repeated exposure to antigen. Several observations were marshaled in support of this hypothesis. First, antigen-antibody complexes were found to remain on follicular dendritic cells long after initial exposure to the antigen (4). Second, the transfer of lymphocytes (either B cells or CD4ϩ T-helper or CD8ϩ cytotoxic T lymphocyte) from an antigen-stimulated to a naive host (in the absence of transferred antigen) was followed by a rapid decline in the population of these cells (5-7). Although persistent antigen or repeated stimulation is likely to result in long-lasting immune memory, the question of the duration of immune memory in the absence of such restimulation remained. Several lines of evidence in support of the hypothesis that immune memory may be long-lived in the absence of persisting antigen include the long-standing ''natural history'' studies, which showed long-lived immunity to viruses such as the measles virus and yellow fever virus persisted for decades after infection under conditions in which repeated exposure was highly unlikely (8-10), and recent experimental studies that have followed populations of antigen-specific immune cells in the absence of their ...

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“…DeBoer and Hogeweg concluded that idiotype-anti-idiotype network models based on proliferation of antibody production due to antigen stimulation were unable to explain basic immunological phenomena such as regulation, immunity (memory), and self-non-self discrimination making them poor candidates to explain autoimmunity [95]. Whether the inability to successfully model the immune system using idiotype-anti-idiotype network approaches is a mathematical problem or an intrinsic failure of Jerne’s network theory to describe immune system behavior remains to be determined.…”

Section: 4 Theoriesmentioning

confidence: 99%

“…Whether the inability to successfully model the immune system using idiotype-anti-idiotype network approaches is a mathematical problem or an intrinsic failure of Jerne’s network theory to describe immune system behavior remains to be determined. In contrast, Sulzer and Weisbuch [96] developed a differential equation-based model of an immune system regulated by idiotype-anti-idiotype interactions that resolves many of the intrinsic problems that DeBoer and Hogeweg [95] had attributed to network models. Sulzer and Weisbuch found that in the instance where one or both of the idiotype anti-idiotype clones are self-reactive, the system could take on any of three states [96].…”

Section: 4 Theoriesmentioning

confidence: 99%

“…But it is interesting to note that independent of the specific mathematics used in idiotype-anti-idiotype models of the immune system, when idiotype and anti-idiotype are symmetrically activated (that is to say, when both the idiotype and the anti-idiotype are stimulated simultaneously and equally), the system loses the ability to regulate itself [95, 96, 207]. Since these mathematical models have assumed that idiotype-anti-idiotype interactions in a naïve immune system would naturally start from a state of symmetrical activation, the failure of the models to produce self-regulated behavior has generally been characterized as a failure of the mathematical model [95, 207]. On the other hand, one of the unique predictions made by ACT that sets it apart from other theories of autoimmunity is precisely that pairs of complementary idiotypes (i.e., the equivalent of idiotype-anti-idiotype pairs) will be symmetrically activated, resulting in loss of immunological regulation.…”

Section: 4 Theoriesmentioning

confidence: 99%

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Unresolved issues in theories of autoimmune disease using myocarditis as a framework

Root‐Bernstein

Fairweather

2015

Journal of Theoretical Biology

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Many theories of autoimmune disease have been proposed since the discovery that the immune system can attack the body. These theories include the hidden or cryptic antigen theory, modified antigen theory, T cell bypass, T cell-B cell mismatch, epitope spread or drift, the bystander effect, molecular mimicry, anti-idiotype theory, antigenic complementarity, and dual-affinity T cell receptors. We critically review these theories and relevant mathematical models as they apply to autoimmune myocarditis. All theories share the common assumption that autoimmune diseases are triggered by environmental factors such as infections or chemical exposure. Most, but not all, theories and mathematical models are unifactorial assuming single-agent causation of disease. Experimental and clinical evidence and mathematical models exist to support some aspects of most theories, but evidence/models that support one theory almost invariably supports other theories as well. More importantly, every theory (and every model) lacks the ability to account for some key autoimmune disease phenomena such as the fundamental roles of innate immunity, sex differences in disease susceptibility, the necessity for adjuvants in experimental animal models, and the often paradoxical effect of exposure timing and dose on disease induction. We argue that a more comprehensive and integrated theory of autoimmunity associated with new mathematical models is needed and suggest specific experimental and clinical tests for each major theory that might help to clarify how they relate to clinical disease and reveal how theories are related.

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Idiotypic networks incorporating T-B cell co-operation. The conditions for percolation

Cited by 13 publications

References 43 publications

Cross-linking reconsidered: binding and cross-linking fields and the cellular response

Cross-linking reconsidered: binding and cross-linking fields and the cellular response

Models of immune memory: On the role of cross-reactive stimulation, competition, and homeostasis in maintaining immune memory

Unresolved issues in theories of autoimmune disease using myocarditis as a framework

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