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This special issue, BImmunocompetence of the Newborn^, is focused on the induction and regulation of immune responses in early life, because recent studies of early life immune ontogeny call into question the prevailing view of an immature newborn immune system. Infectious disease cause nearly one third of all neonatal deaths; in addition, a large proportion of stillbirths are presumed to be related to an infectious insult of the maternalfetal dyad [1]. This harsh clinical reality of an increased risk to suffer from infection in early life has historically been explained as the consequence of an Bimmaturity^ of the fetal or neonatal immune system [2]. Over the years, this Bimmaturity^ has most often been interpreted to imply that the immune system in fetal or neonatal stages of development was less able to develop effector responses than in the adult and much of the experimental data published over the last five decades appeared to support this notion [3]. However, reports of increased immune responses in the newborn also appeared over the years, challenging the prevailing view of generally lower immune responsiveness in early life [4]. Reconciliation of these apparently contradicting findings has more recently been achieved through the recognition that the fetal and newborn immune system is not simply less responsive, but functionally different from that of an adult, and that these differences reflect age-dependent differences in the demands [5, 6]. However, this new insight now begs to answer the question: If the fetus or newborn is capable of adult-like immune responses, why do they clinically suffer more readily from infectious insults? This special edition explores one possible answer: The fetus and newborn may suffer more readily from infection because their immune system responds not less but more than that of an adult, and in that stronger response appears more prone to do so in a host-damaging way (immunemediated pathology). In this special edition of Seminars in Immunopathology, Raz Somech’s group reviews the evidence that T as well as B cell repertoires begin to diversify in fetal life already [7]. The concept of functional fetal adaptive immune responses is further explored by the group around Richard Lo-Man, presenting evidence of in utero development of memory T cells [8], while Donna Farber and colleagues place this early life T cell development into the context of tissue compartmentalization [9]. These pre-natal immune events clearly do not happen in isolation, but are modulated by the maternal immune system, as reviewed byArnaudMarchant’s group [10]. The impact of such preand perinatal events on neonatal infection then is examined by Tobias Kollmann’s team [11], while Beate Kampmann and colleagues focus on this impact in regard to neonatal vaccination [12]. A particularly useful example for an evolutionary selection of age-dependent, advantageous response patterns is presented by Antonio Bertoletti and colleague in the case of hepatitis B infection around birth [13]. Furthermore, the events occurring before or during birth profoundly impact not only the acute response to infection or vaccination but also the immune ontogeny with clinical ramifications for years to come; specifically, with respect to the onset of type 1 diabetes, as reviewed This article is a contribution to the special issue on Immunocompetence of the Newborn Guest Editors: Arnaud Marchant and Tobias Kollmann