Idiotypic Networks and Other Preconceived Ideas

Jerne, Niels K.; Cocteau, Jean

doi:10.1111/j.1600-065x.1984.tb00484.x

Cited by 507 publications

(219 citation statements)

References 71 publications

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“…Via idiotypic interactions clones should thus be able to interact in a stimulatory and/or inhibitory manner. The collection of idiotypic interactions defines a profound idiotypic network of a complexity comparable to that of the neural network (Jerne, 1974;Hoffmann, 1986).…”

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confidence: 99%

Unreasonable implications of reasonable idiotypic network assumptions

Boer

Hogeweg

1989

Bltn Mathcal Biology

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We first analyse a simple symmetric model of the idiotypic network. In the model idiotypic interactions regulate B cell proliferation. Three non-idiotypic processes are incorporated: (1) influx of newborn cells; (2) turnover of cells; (3) antigen. Antigen also regulates proliferation.A model of 2 B cell populations has 3 stable equilibria: one virgin, two immune. The twodimensional system thus remembers antigens, i.e. accounts for immunity. By contrast, if an idiotypic clone proliferates (in response to antigen), its anti-idiotypic partner is unable to control this. Symmetric idiotypic networks thus fail to account for proliferation regulation.In high-D networks we run into two problems. Firstly, if the network accounts for memory, idiotypic activation always propagates very deeply into the network. This is very unrealistic, but is an implication of the"realistic" assumption that it should be easier to activate all cells of a small virgin clone than to maintain the activation of all cells of a large (immune) clone. Secondly, graph theory teaches us that if the (random) network connectance exceeds a threshold level of one interaction per clone, most clones are interconnected. We show that this theory is also applicable to immune networks based on complementary matching idiotypes. The combination of the first "percolation" result with the "interconnectance" result means that the first stimulation of the network with antigen should eventually affect most of the clones. We think this is unreasonable.Another threshold property of the network connectivity is the existence of a virgin state. A gradual increase in network connectance eliminates the virgin state and thus causes an abrupt change in network behaviour. In contrast to weakly connected systems, highly connected networks display autonomous activity and are unresponsive to external antigens. Similar differences between neonatal and adult networks have been described by experimentalists.The robustness of these results is tested with a network in which idiotypic inactivation of a clone occurs more generally than activation. Such "long-range inhibition" is known to promote pattern formation. However, in our model it fails to reduce the percolation, and additionally, generates semi-chaotic behaviour. In our network, the inhibition of a clone that is inhibiting can alter this clone into a clone that is activating. Hence "long-range inhibition" implies "long-range activation", and idiotypic activation fails to remain localized.We next complicate this model by incorporating antibody production. Although this "antibody" model statically accounts for the same set of equilibrium points, it dynamically fails to account for state switching (i.e. memory). The switching behaviour is disturbed by the autonomous slow decay of the (long-lived) antibodies. After antigenic triggering the system now performs complex cyclic behaviour. Finally, it is suggested that (idiotypic) formation of antibody complexes can play only a secondary role in the network.In conclusion, our results ca...

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confidence: 99%

Unreasonable implications of reasonable idiotypic network assumptions

Boer

Hogeweg

1989

Bltn Mathcal Biology

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“…This suggests that primarily the synthesis of K -b earing immunoglobulins is affected in juvenile onset MCTD, This may reflect a disturbed immune response or an antibody reaction, primarily provoked against a still unknown antigen. This light chain restricted antibody re action may be associated with T-cell imbalance as found in MCTD (28). Consequently, cross reaction of the pro duced antibodies would cause reaction against RNP in prone individuals.…”

Section: Discussionmentioning

confidence: 96%

Altered immunoglobulin concentrations and light chain ratios in juvenile onset mixed connective tissue disease

et al. 1995

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Immunological disturbances may result in altered immunoglobulin concentrations and kappa/lainbda light chain (k/X) ratios. We measured the k/X ratios of total serum immunoglobulins and of polyclonal IgG, A, and M separately as well as concentrations of these immunoglobulins in fourteen patients with juve nile onset mixed connective tissue disease. When comparing the patient group with a reference group the mean serum IgG and IgA concentrations were respectively 2.98 G/L (p=0.0012) and 0.79 G/L (p=0.0114) higher in the group of patients with juvenile onset mixed connective tissue disease. The mean IgM concentration was 0,39 G/L (p = 0.0002) lower. The mean k/X ratios of total serum immunoglobulins, serum IgG, and serum IgA were respectively 0.20 (p=0.0226), 0.28 (p~0.0016) and 0.10 (p=0.0732), higher in the group of patients with mixed connective tissue disease as compared with the reference group. Mean serum IgM k/X ratio, however, was 0.21 (p = 0.0046) lower. The alterations of the serum immunoglobulin concentrations and of the k/X ratios reflect immunological disturbances in patients with juvenile onset mixed connec tive tissue disease. The increased concentration of serum IgG and raised IgG k/X ratio and decreased concentration of serum IgM with decreased IgM K/X ratio in dicate that the synthesis of K-bearing immunoglobulins mainly is affected.

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“…In 1974 Jerne [13] hypothesized the concept of idiotypic network dysregulation. Animal and human data supporting the idiotypic network hypothesis is increasing.…”

Section: Discussionmentioning

confidence: 99%

Two patients with heparin‐induced thrombocytopenia followed by idiopathic (immune) thrombocytopenic purpura: Case Report

et al. 2003

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Heparin-induced thrombocytopenia (HIT) and idiopathic thrombocytopenic purpura (ITP) are separate and well-recognized clinical syndromes, both having potential for disastrous outcomes. Sequential occurrence of these two diseases has not been reported in the literature. We report herein two patients who were initially diagnosed as having HIT but whose later clinical course was similar to ITP. Although dysfunction of immune system seems to play a role, the precise mechanisms for the development of these diseases are unclear. As both conditions have different natural histories and require different treatment modalities, it is important to recognize that these two diseases may be seen sequentially. Am. J. Hematol. 73:290-293, 2003.

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Idiotypic Networks and Other Preconceived Ideas

Cited by 507 publications

References 71 publications

Unreasonable implications of reasonable idiotypic network assumptions

Unreasonable implications of reasonable idiotypic network assumptions

Altered immunoglobulin concentrations and light chain ratios in juvenile onset mixed connective tissue disease

Two patients with heparin‐induced thrombocytopenia followed by idiopathic (immune) thrombocytopenic purpura: Case Report

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