Sanne Hoeks

General Introduction 17 1 The immune system undergoes major alterations after birth: it matures and gradually a better functional protection from invasive pathogens is established. The total DC number shows an inverse correlation with age across the lifespan, and so do the absolute numbers of circulating myeloid DCs (mDCs) and plasmatocytoid DCs (pDCs). 31 It has been observed that at birth pDCs outnumber mDCs, so that the pDC-to-mDC ratio is inversed in comparison to adults. 32, 33 Major functional maturation of circulating monocytes and DCs occurs during the first years of life, reflected by changes in the responsiveness to TLR stimulation, although the pattern of TLR expression by APCs has been reported to be similar between neonates and adults and among children of different ages. 34-37 The highest counts of NK cells are found in cord blood but they decline significantly (by 2–3 times) during the first postnatal days. Their levels further decrease progressively throughout infancy and early childhood, to reach adult levels around the fifth year of age. 38 There are no significant changes of the NK cell circulating subsets, CD56 bright, and CD56dim, until adulthood, apart from a slightly higher proportion of CD56bright NK cell numbers in neonates. It was shown that the responses of NK cells are determined by the balance between activating and inhibitory signals from relative cell surface receptors. Several phenotypic changes on NK cells regarding the expression of these receptors have been reported during the first years of life. 39 C8 and especially C9 are the most markedly reduced at birth. 30 No data on functional maturation of basophils and eosinophils exist.