Autoreactivity, dynamic tuning and selectivity - Opinion

The immune system adjusts its response to the context in which antigens, in cluding self-antigens, are recognized. Recent observations support a concep tual framework for understanding how this may be achieved at the cellular a nd cell-population levels. At both levels, 'perturbations' elicit competiti on between excitation and de-excitation, resulting either in adaptation or in various responses. The responsiveness of individual cells is dynamically tuned, reflecting their recent experience. The tuning of T-cell activation thresholds by self-ligands facilitates positive selection and continuously regulates the level of autoreactivity in the periphery. Autoreactivity app ears to be involved in regulation of the immune response, homeostasis, main taining of the functional integrity of naive and memory cells, and in other physiological functions.