The Immune System Out of Shape?

During pregnancy, a fetus is protected from a large part of the pathogens of the environment. As a result, a newborn’s immune system is immature and unexperienced, and mainly composed of innate leukocytes and naive lymphocytes. Immunological memory, and concomitant functional immunity, needs to be formed in response to various pathogen encounters. Most of the immune maturation occurs during the first few years of childhood, during which the child comes into contact with a large variety of pathogens. Though most of the pathogens are cleared, after which life-long immunity is generated, some viruses evade virus clearance and induce a state of latency and viral persistence. Due to their continuous presence and pressure on the immune system, persistent viral infections are known to have a strong impact on the immune system of especially elderly.

The research described in this thesis was set out to characterize immune maturation during early childhood, in response to various environmental determinants with a specific focus on persistent viral infections. Combined, these studies underline the complexity of the childhood immune dynamics, and stress the plasticity of the childhood immune system upon viral infection with herpesviruses and the HIV virus. Children seem to control persistent herpesvirus infections without the negative effects that have been observed in elderly. This information will be important, not only for our basic understanding of healthy immune maturation, but might also contribute to our understanding of immune dysfunction during chronic immune stimulation and provide more understanding of the processes that underlie the formation of long-lasting immunity.