Development of Immune Functions Related to Allergic Mechanisms in Young Children

Abstract

The newborn immune system differs quantitatively and functionally from that of adults. Development of the immune system has important implications for childhood diseases. The immaturity of the immune system in the first years of life may contribute to failure of tolerance induction and in the development of allergic disease. T cell function is diminished, especially the capacity to produce cytokines; production of interferon (IFN)-gamma, and IL-4 is strongly reduced. IFN-gamma has been found to be even lower in cord blood of newborns with a family history of atopy. Differences in other cell types (natural killer cells, antigen-presenting cells, and B cells) could also play a role in the development of allergic disease. Current data suggest that irregularities in IgE synthesis, helper T cell subsets (Th1, Th2, CD45RA, and CD45RO), cytokines (IL-4, IFN-gamma), and possibly other cell types may play a role in the development of allergy in childhood. Moreover, the role of cell surface molecules, like co-stimulatory molecules (CD28, CD40L), activation markers (CD25), and adhesion molecules (LFA-1/ICAM-1, VLA-4/ VCAM-1) is also discussed. These variables are modulated by genetic (relevant loci are identified on chromosome 5q, 11q, and 14) and environmental forces (allergen exposure, viral infections, and smoke). The low sensitivity of current predictive factors for the development of allergic diseases, such as cord blood IgE levels, improves in combination with family history and by measurement of in vitro responses of lymphocytes and skin reactivity to allergens. New therapeutic approaches are being considered on the basis of our current understanding of the immunopathology of allergic disease, for instance cytokine therapy and vaccination with tolerizing doses of allergen or peptides.

Imunidade relacionada à resposta alérgica no início da vida

“…Frente ao estímulo antigênico, o sistema imune (inespecífico e específico) do recém-nascido e de crianças mais jovens mostra diferenças quantitativas e funcionais em relação ao adulto, podendo influenciar significativamente o desenvolvimento de atopia, segundo suas características genéticas, perfil de citocinas, células apresentadoras de antígenos, tipos de alérgenos e via de acesso destes ao sistema imune 8,10,[11][12][13] .…”

“…A menor produção desta citocina, no entanto, é um dos fatores que propiciam o desenvolvimento de atopia, uma vez que o INF-g atua na inibição da síntese de IgE 11,21 .…”

“…Elevam-se quantitativamente no fígado e baço após a décima quarta semana, migrando para a circulação sangüínea a partir da décima quarta semana 5,8,9,22 , quando então podem ser ativados frente à exposição antigênica 5,6,11,23 .…”

“…Por isso, os níveis de fragmentos solúveis destes receptores (sCD23) são mais elevados ao nascimento e declinam com a progressão da idade, ao contrário da IgE, possivelmente por mecanismos de feedback negativo do sistema imune 11,44 . As doenças alérgicas estão relacionadas ao aumento da expressão de CD23 nas células ativadas que os possuem (células B e T, macrófagos, eosinófilos e plaquetas), refletindo de certo modo o aumento na síntese de IL-4 nessas doenças, bem como a capacidade desta citocina hiperativar a expressão de tais receptores 45 .…”

Lipopolysaccharide-Induced Immunostimulation Produces A Dose- and Time-Dependent Decrease in General Activity and Weight Gain in Preweanling Rats

“…Because behavior change induced by immunostimulants depends upon the status of the immune system, the central nervous system, and the endocrine system, the developmental changes that occur in each of these systems during and beyond the preweaning period in rodents (and the comparable periods in humans) (Adkins, Ghanei, & Hamilton, 1993;Ba & Seri, 1995;Koning, Baert, Oranje, Savelkoul, & Neijens, 1996;Tice, Hashemi, Taylor, & McQuade, 1996;Witek-Janusek, 1988) could affect the appearance of sickness behavior. Any residual manifestation of a stress-hyporesponsive period (Guillet, Saffran, & Michaelson, 1980;Witek-Janusek, 1988) could, for instance, intensify sickness behavior caused by a reduction in the glucocorticoid negative feedback effect on cytokine production (Chrousos, 1995).…”