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

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.

Polymeric Nanoparticle Receptors as Synthetic Antibodies for Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

The wide usage and subsequent leakage of nonsteroidal anti-inflammatory drugs (NSAIDs) into the environment present an urgent need to create materials for selective binding of NSAID drugs, which are highly similar to one another in structure and functionality. Surface–core double-cross-linking of cationic micelles containing Naproxen or Indomethacin as the template yielded molecularly imprinted nanoparticles (MINPs) for these drugs. The nanoparticle receptors resembled water-soluble proteins in their hydrophilic exterior and hydrophobic core with guest-tailored binding pockets. Their binding selectivity for their templates over other NSAID analogues rivaled that of antibodies prepared through much lengthier procedures

Contrasting patterns of selection between MHC I and II across populations of Humboldt and Magellanic penguins

The evolutionary and adaptive potential of populations or species facing an emerginginfectious disease depends on their genetic diversity in genes, such as the major histocompatibilitycomplex (MHC). In birds, MHC class I deals predominantly with intracellularinfections (e.g., viruses) and MHC class II with extracellular infections (e.g.,bacteria). Therefore, patterns of MHC I and II diversity may differ between species andacross populations of species depending on the relative effect of local and global environmentalselective pressures, genetic drift, and gene flow. We hypothesize thathigh gene flow among populations of Humboldt and Magellanic penguins limits localadaptation in MHC I and MHC II, and signatures of selection differ between markers,locations, and species. We evaluated the MHC I and II diversity using 454 next-generationsequencing of 100 Humboldt and 75 Magellanic penguins from seven differentbreeding colonies. Higher genetic diversity was observed in MHC I than MHCII for both species, explained by more than one MHC I loci identified. Large populationsizes, high gene flow, and/or similar selection pressures maintain diversity but limitlocal adaptation in MHC I. A pattern of isolation by distance was observed for MHC IIfor Humboldt penguin suggesting local adaptation, mainly on the northernmost studiedlocality. Furthermore, trans-speciesalleles were found due to a recent speciationfor the genus or convergent evolution. High MHC I and MHC II gene diversity describedis extremely advantageous for the long-termsurvival of the species.Fil: Sallaberry Pincheira, Nicole. Pontificia Universidad Católica de Chile; Chile. Universidad Andrés Bello; ChileFil: González Acuña, Daniel. Universidad de Concepción; ChileFil: Padilla, Pamela Solange. Pontificia Universidad Católica de Chile; ChileFil: Dantas, Gisele P. M.. Pontificia Universidade Catolica de Minas Gerais.; BrasilFil: Luna Jorquera, Guillermo. Universidad Católica del Norte; ChileFil: Frere, Esteban. Universidad Nacional de la Patagonia Austral. Unidad Académica Caleta Olivia. Centro de Investigaciones Puerto Deseado; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Valdés Velásquez, Armando. Universidad Peruana Cayetano Heredia; PerúFil: Vianna, Juliana A.. Pontificia Universidad Católica de Chile; Chil

Immunological changes in nestlings growing under predation risk

Predation is one of the most relevant selective forces in nature. However, the physiological mechanisms behind anti-predator strategies have been overlooked, despite their importance to understand predator-prey interactions. In this context, the immune system could be especially revealing due to its relationship with other critical functions and its ability to enhance prey's probabilities of survival to a predator's attack. Developing organisms (e.g. nestlings) are excellent models to study this topic because they suffer a high predation pressure while undergoing the majority of their development, which maximizes potential trade-offs between immunity and other biological functions. Using common blackbirds Turdus merula as model species, we experimentally investigated whether an elevated nest predation risk during the nestling period affects nestlings' immunity and its possible interactions with developmental conditions (i.e. body condition and growth). Experimental nestlings modified some components of their immunity, but only when considering body condition and growth rate, indicating a multifaceted immunological response to predation risk and an important mediator role of nestlings' developmental conditions. Predation risk induced a suppression of IgY but an increase in lymphocytes in nestlings with poor body condition. In addition, experimental but not control nestlings showed a negative correlation between growth and heterophils, demonstrating that nest predation risk can affect the interaction between growth and immunity. This study highlights the importance of immunity in anti-predator response in nestlings and shows the relevance of including physiological components to the study of predation risk.</p