Sanne Hoeks

General Introduction 9 1 GENERAL INTRODUCTION The prenatal and early postnatal immune system is highly dynamic and fundamentally different from the adult immune system. 1 The perinatal immune cells seem remarkably adapted to the different demands of their environment, the maternal-fetal interface and early postnatal life. Upon birth a neonate is suddenly exposed to thousands of new, mainly harmless, antigens present in food and in the microbiome colonizing the mucosae and skin. This new environment requests the active induction of immune tolerance on the one hand and the suppression of pro-inflammatory responses towards these harmless antigens on the other hand. This indicates that the initial dogmatic view of the neonatal immune system as immature and therefore deficient compared to that of an adult seems inadequate. The vulnerability of neonates to infections might simply be the price that needs to be paid by this highly advanced immune system that has priority in the effective induction of immune tolerance. Although challenging throughout the entire lifespan, especially newborns are highly pressured by the balance of immune tolerance and inflammation. Once tolerizing memory to most harmless environmental antigens is established, demands on the infant’s immune system shifts from a preferred tolerant state towards an immune system with priority in fighting harmful pathogens. This immune development from birth, throughout infancy, into adulthood is considered to be programmed but highly influenced by genes, environment and the interaction between them, so called epigenetics. Especially in the first weeks/months after birth this development is reflected in major shifts in immune cells. 2, 3 Of importance, evidence is also mounting that immune system programming that starts in early life influences the risk of developing conditions such as allergic, autoimmune, reproductive, and neuropsychiatric disorders in later life. In addition, immune regulation early in life might serve as a model to identify new therapeutic strategies to restore immune tolerance upon immune dysregulation in clinical conditions like autoinflammation, autoimmunity and allergy.