Essential Pentosuria in Two Brothers:

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A study of nitrogen metabolism in a case presenting short paroxysms of fever of unknown origin

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Immunological tolerance: Danger – pathogen on the premises!

AbstractRecent results show that immune responses can be induced in neonatal mice. Do they really refute the traditional view that the ability to discriminate between ‘self’ and ‘non-self’ is a fundamental property of the immune system

Inferring processes underlying B-cell repertoire diversity

We quantify the VDJ recombination and somatic hypermutation processes in human B-cells using probabilistic inference methods on high-throughput DNA sequence repertoires of human B-cell receptor heavy chains. Our analysis captures the statistical properties of the naive repertoire, first after its initial generation via VDJ recombination and then after selection for functionality. We also infer statistical properties of the somatic hypermutation machinery (exclusive of subsequent effects of selection). Our main results are the following: the B-cell repertoire is substantially more diverse than T-cell repertoires, due to longer junctional insertions; sequences that pass initial selection are distinguished by having a higher probability of being generated in a VDJ recombination event; somatic hypermutations have a non-uniform distribution along the V gene that is well explained by an independent site model for the sequence context around the hypermutation site.Comment: acknowledgement adde

Statistical mechanics of clonal expansion in lymphocyte networks modelled with slow and fast variables

We study the Langevin dynamics of the adaptive immune system, modelled by a lymphocyte network in which the B cells are interacting with the T cells and antigen. We assume that B clones and T clones are evolving in different thermal noise environments and on different timescales. We derive stationary distributions and use statistical mechanics to study clonal expansion of B clones in this model when the B and T clone sizes are assumed to be the slow and fast variables respectively and vice versa. We derive distributions of B clone sizes and use general properties of ferromagnetic systems to predict characteristics of these distributions, such as the average B cell concentration, in some regimes where T cells can be modelled as binary variables. This analysis is independent of network topologies and its results are qualitatively consistent with experimental observations. In order to obtain full distributions we assume that the network topologies are random and locally equivalent to trees. The latter allows us to employ the Bethe-Peierls approach and to develop a theoretical framework which can be used to predict the distributions of B clone sizes. As an example we use this theory to compute distributions for the models of immune system defined on random regular networks.Comment: A more recent version (accepted for publication in Journal of Physics A: Mathematical and Theoretical) with improved figures, references, et

A Multi-Scale Model for Correlation in B Cell VDJ Usage of Zebrafish

The zebrafish (\emph{Danio rerio}) is one of the model animals for study of immunology because the dynamics in the adaptive immune system of zebrafish are similar to that in higher animals. In this work, we built a multi-scale model to simulate the dynamics of B cells in the primary and secondary immune responses of zebrafish. We use this model to explain the reported correlation between VDJ usage of B cell repertoires in individual zebrafish. We use a delay ordinary differential equation (ODE) system to model the immune responses in the 6-month lifespan of a zebrafish. This mean field theory gives the number of high affinity B cells as a function of time during an infection. The sequences of those B cells are then taken from a distribution calculated by a "microscopic" random energy model. This generalized $NK$ model shows that mature B cells specific to one antigen largely possess a single VDJ recombination. The model allows first-principles calculation of the probability, $p$, that two zebrafish responding to the same antigen will select the same VDJ recombination. This probability $p$ increases with the B cell population size and the B cell selection intensity. The probability $p$ decreases with the B cell hypermutation rate. The multi-scale model predicts correlations in the immune system of the zebrafish that are highly similar to that from experiment.Comment: 29 pages, 10 figures, 1 tabl

Parallel processing in immune networks

In this work we adopt a statistical mechanics approach to investigate basic, systemic features exhibited by adaptive immune systems. The lymphocyte network made by B-cells and T-cells is modeled by a bipartite spin-glass, where, following biological prescriptions, links connecting B-cells and T-cells are sparse. Interestingly, the dilution performed on links is shown to make the system able to orchestrate parallel strategies to fight several pathogens at the same time; this multitasking capability constitutes a remarkable, key property of immune systems as multiple antigens are always present within the host. We also define the stochastic process ruling the temporal evolution of lymphocyte activity, and show its relaxation toward an equilibrium measure allowing statistical mechanics investigations. Analytical results are compared with Monte Carlo simulations and signal-to-noise outcomes showing overall excellent agreement. Finally, within our model, a rationale for the experimentally well-evidenced correlation between lymphocytosis and autoimmunity is achieved; this sheds further light on the systemic features exhibited by immune networks.Comment: 21 pages, 9 figures; to appear in Phys. Rev.