T-Cell activation: a queuing theory analysis at low agonist density

We analyze a simple linear triggering model of the T-cell receptor (TCR) within the framework of queuing theory, in which TCRs enter the queue upon full activation and exit by downregulation. We fit our model to four experimentally characterized threshold activation criteria and analyze their specificity and sensitivity: the initial calcium spike, cytotoxicity, immunological synapse formation, and cytokine secretion. Specificity characteristics improve as the time window for detection increases, saturating for time periods on the timescale of downregulation; thus, the calcium spike (30 s) has low specificity but a sensitivity to single-peptide MHC ligands, while the cytokine threshold (1 h) can distinguish ligands with a 30% variation in the complex lifetime. However, a robustness analysis shows that these properties are degraded when the queue parameters are subject to variation—for example, under stochasticity in the ligand number in the cell-cell interface and population variation in the cellular threshold. A time integration of the queue over a period of hours is shown to be able to control parameter noise efficiently for realistic parameter values when integrated over sufficiently long time periods (hours), the discrimination characteristics being determined by the TCR signal cascade kinetics (a kinetic proofreading scheme). Therefore, through a combination of thresholds and signal integration, a T cell can be responsive to low ligand density and specific to agonist quality. We suggest that multiple threshold mechanisms are employed to establish the conditions for efficient signal integration, i.e., coordinate the formation of a stable contact interface

On the Stability of a Mathematical Model for Coral Growth in a Tank

A mathematical model for coral growth in a well stirred tank is proposed based on nutrient availability. The proposed model is a system of ODEs. Stability analysis of the solutions of the system of ODEs is done for various acceptable parameter regions. Growth forms of corals in different parameter regions are observed based on the solution of the model equations. Numerical calculations and qualitative analysis reveal some interesting global behaviors such as limit cycles, homoclinic connections and heterioclinic connections of the solution trajectories. Unstable growing limit cycles are observed for some parameter values where the corresponding largest limit cycle approaches a homoclinic connection. These behaviors of the solutions of the system closely have biological consequences on coral growth