IMMUNE DEVELOPMENT IN CHILDREN: INNATE AND ADAPTIVE IMMUNITY

A. Durandy

INSERM U 429, Paris, France

The various defense mechanisms of innate and adaptive immunity develop gradually in-utero but are not completely efficient at birth, leading to the particular susceptibility to infections observed in neonates, and especially premature infants.

Innate immunity. The polymorphonuclear cell count is normal at birth and cells exhibit normal oxidative metabolism, but have defective chemotaxis, which impairs migration to sites of infection. This is especially true in neonates, and particularly premature or stressed infants. A similar chemotactic defect has been described in neonatal monocytes.

Natural killer (NK) cell numbers and cytotoxic function are depressed at birth compared with adult values and progressively rise during the first months of life.

However, most of the abnormalities observed in phagocytic and NK cells are not due to an intrinsic defect but are secondary to impaired cytokine production by T cells.

The complement system is also not mature at birth since serum levels of most of the components are about 50% of adult levels and rise to normal values during the first year of life. This defect is responsible for impaired opsonization of newborn sera and also plays a role in the impaired chemotaxis of neonatal polymorphonuclear cells.

Adaptive immunity. T (CD3+) lymphocyte numbers are increased during the first year of life, although the proportion of CD4+ (helper) and CD8+ (cytotoxic) T cells is normal. The main characteristic is the fact that they are "naive" T cells (CD45RA+) encountering antigens for the first time. This leads to a primary, delayed T cell response and cytokine production. This defect disappears progressively following antigenic stimulation. Other T cell dysfunction has been described in newborns, including week ability to express the CD40-ligand, a molecule required for full T/B cell interaction, and poor cytotoxic function against viral infections.

The number of B cells is slightly increased in newborns as compared with adult values.

Neonate B cells are also "naive" cells, characterized by their phenotype (±, ±, CD27-). Their response to antigenic stimulation is primary, leading essentially to the production of low affinity IgM. The defect in immunoglobulin switching observed in neonates can be related to an intrinsic abnormality of B cells, but primarily, to defective T cell help (defect of CD40 ligand expression, and poor cytokine production by T cells). The ability to produce high affinity IgG and IgA appears progressively after birth and the serum levels of the different isotypes slowly increase to reach adult values during the 2nd decade of life. Another important characteristic of infant B cells is their poor ability to produce antibodies to polysaccharide antigens (IgM and IgG2 isotypes) during the first two years of life.

In conclusion, the impaired innate immune response is mainly responsible for the particular susceptibility to infections observed in neonates. Adaptive immunity, which is not fully mature at birth, progressively achieves complete maturation following antigenic stimulation.