We must first look at the immune system of an infant and the necessity of its proper development in the prevention of immune disorders. The infant’s immune system differs from that of an adult. During gestation, the immune system of the fetus is actively down-regulated to avoid immunological reactions that would end in termination of the pregnancy. This adaptation is demonstrated by high levels of Treg cells, by the down-regulation of antigen-specific T-cell proliferation, and by removal of activated T cells via FasL-induced apoptosis. The immune system remains in this state through birth and doesn’t fully develop until several years after birth.17,18 Th1 cytokines, such as interleukin-2 (IL-2), interferon-g (IFN-gamma) and Th2 cytokines, mainly interleukin-4 (IL-4), are seen at different levels in infants versus adults. Infants have more IL-2 and IL-4, with less IFN-gamma than seen in adults, giving them a predominately Th2-driven immune system.19 Infants have less Th1 memory effector function compared to adults.20 Even though infants produce ample amounts of IL-2, it does not induce the increase in IFN-gamma necessary to incite a Th1 response.21 When looking at the immunological cytokine response in infants, we see the production of Th1 cytokines tumor necrosis factoralpha (TNF-alpha), IFN-gamma, IL-12, and IL-1 are downregulated, whereas the cytokines IL-6, IL-8, IL-10, and IL-23 that are associated with inflammation and autoimmunity are up-regulated.
All of these contribute to a down-regulation of the Th1 immune response in infants. The immune response of tolerance, which modulates rampant Th1 or Th2 reactions, is vital to the immune development and health of the infant. A study that examined children with no clinical or pathological diagnosis, children with multiple food allergies, children with celiac disease, and children with inflammatory enteropathies showed that the deciding factor in the allergic group was the reduction of a Th3 response with a corresponding reduction in TGF-beta.23 The celiac and inflammatory enteropathies groups showed a dominance of the Th1 response, typical of inflammatory autoimmune diseases in which the control of the Th3 Treg cells is a necessity.
The production of IL-10, a cytokine released by Treg cells, was lower in infants of atopic mothers compared with non-atopic mothers. Oral TGF-beta has demonstrated a preventive role for allergic diseases in infants, again highlighting the importance of immune tolerance in the prevention of immune disorders. Research into the etiology of necrotizing enterocolitis (NEC) has found another difference in the immunological state of adults and infants. The immature enterocytes that line the infant’s intestine react with an excessive pro-inflammatory cytokine production after inflammatory stimulation. This reaction leaves infants vulnerable to the influence of excessive inflammation. Another difference in the infants’ mucosa is the variety of glycoproteins as compared to adults. Lining the gastrointestinal and respiratory tracts are glycoproteins, such as mucins, which cover the entire epithelial layer with protective mucus. These glycoproteins play an important role in inflammatory and antigen control in these mucosal tracts. The composition and glycosylation of the mucus layer differs significantly between infants and adults. An infant’s gastrointestinal tract not only has low levels of mucus, but it also has increased permeability and low levels of secretory immunoglobulin A.Although much is known, more studies are needed to complete our understanding of the immunological workings of infants. Research highlights the infant’s need for Th1 support to protect against infection and the damage that can ensue, a refined and effective Th3 response that can control rampant immune responses, and a healthy mucosal lining to ensure proper immune development and potentially prevent allergy, asthma, and autoimmune disorders.