Macrophage biology and pathobiology in the evolution of immune responses: a functional analysis

A number of general principles of macrophage biology and pathobiology are formulated to define the contribution of macrophages to the kinetics and sequencing of innate and adaptive immune responses more precisely. The application of these principles to modelling immune responses and to macrophage-based treatments of immune disorders is discussed. The concept of innate peripheral tolerance is developed. It is suggested that macrophage activation could be a primary determinant of nearly every aspect of immune responsiveness, both normal and abnormal, as might be predicted from the innate immune response to 'danger' being evolutionarily more primitive than the adaptive.