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* * * * Dá carinho Protege Cuida Alimenta Orienta * * As mesmas necessidades para o ser humano ..... Alimentação, proteção, cuidado, orientação, carinho ..... Não só no início - em toda a vida- mas particularmente nos extremos da vida * * Variações fisiológicas da resposta imunitária Maria Imaculada Muniz-Junqueira Imunologia Médica * * Idoso Lactante Gestante Criança * * Desenvolvimento do sistema imunitário na infância * * * * Mussi-Pinhata MM , Rego MAC Immunological peculiarities of extremely preterm infants: a challenge for the prevention of nosocomial sepsis. Jornal de Pediatria, 81 (Suppl I): S59-S68; 2005. * * * * Mecanismos de defesa inespecíficos * * Imunidade Inata Sistema de Fagócitos Neutrófilos Monócitos Sistema do Complemento * * NEUTRÓFILOS Número Reserva na medula óssea Fagocitose Quimiotaxia Mecanismos microbicidas * * Número de Neutrófilos * * NEUTRÓFILOS Número aumentado Reserva na medula óssea diminuída Fagocitose Quimiotaxia Mecanismos microbicidas * * NEUTRÓFILOS Número aumentado Reserva na medula óssea diminuída Fagocitose Quimiotaxia Mecanismos microbicidas * * Muniz-Junqueira MI , Figueira-Peçanha LM, Silva-Filho VL, Cardoso MCA, Tosta CE. Novel Microtechnique for Assessment of Postnatal Maturation of the Phagocytic Function of Neutrophils and Monocytes. Clinical and Diagnostic Laboratory Immunology, 10: 1096–1102 ; 2003. * * NEUTRÓFILOS Número aumentado Reserva na medula óssea diminuída Fagocitose deprimida/exacerbada Quimiotaxia diminuída Mecanismos microbicidas reduzidos * * Monócitos/macrófagos Fagocitose Quimiotaxia Mecanismos Função apresentadora de antígeno * * Muniz-Junqueira MI , Figueira-Peçanha LM, Silva-Filho VL, Cardoso MCA, Tosta CE. Novel Microtechnique for Assessment of Postnatal Maturation of the Phagocytic Function of Neutrophils and Monocytes. Clinical and Diagnostic Laboratory Immunology, 10: 1096–1102 ; 2003. * * Monócitos/macrófagos Fagocitose normal/exacerbada Quimiotaxia reduzida Mecanismos microbicidas reduzidos Função apresentadora de antígeno deficiente * * RESPOSTA INFLAMATÓRIA Retardo para migrar para foco inflamatório Retardo no desvio de neutrófilos para monócitos no foco inflamatório CONSEQUÊNCIAS Dificuldade para localização Dispersão aumentada de microorganismos Mecanismos de defesa inadequados * * Sistema do complemento VIA CLÁSSICA C1q (75%) C2 (50%) C4 (55%) VIA ALTERNATIVA Properdina (80%) Fator B (70%) C5 (60%) C6 (50%) C7 (70%) C8 (50%) C9 (10-25%) CH50 (50%) * * IMUNIDADE ADQUIRIDA Linfócitos T Linfócitos B * * Tamanho do Timo * * Garly ML. Thymus Size at 6 Months of Age and Subsequent Child Mortality J Pediatr 2008 153:683-8 Timo menor = fator de risco para mortalidade * * Número de Linfócitos no sangue * * Linfócitos T - funções Função auxiliar do LT CD4+ deprimida IL2, IL4, Interferon-, GM-CSF produção diminuída LT requer maior quantidade de sinais co-estimulatórios tem menor densidade de receptores do linfócito T tem menor expressão de moléculas de adesão (LFA-1, CD2) consequência: resposta imune deficiente Desvio LTa2 imaturidade de células acessórias (macrófago, célula dendrítica, linfócito B) Resposta ao BCG * * Linfócito T CD8+ Função supressora aumentada Função citotóxica deprimida Célula NK Atividade citotóxica diminuída Conseqüência Aumento da gravidade das infecções virais * * Yerkovich ST, Wikstro ME, Suriyaarachchi D, SUSAN L. Prescott SL, Upham JW, Holt PG. Postnatal Development of Monocyte Cytokine Responses to Bacterial Lipopolysaccharide. Pediatric Research, 62: 547-552; 2007. TNF- IL-6 IL-10 * * Figure 1. Age-related changes in cytokine mRNA expression and protein production following LPS stimulation. Mononuclear cells were stimulated with LPS/IFN, and (A) maximal mRNA expression was measured 6 h post-LPS stimulation (CB, n 10; 1 y olds, n 7; 4 y olds, n 10; 13 y olds, n 10; and adults, n 8), except for IL-18, which is expressed constitutively (open bars) and has maximal mRNA expression (black bars) at 2 h post-LPS stimulation (CB, n 10; 1 y olds, n 9; 4 y olds, n 7; 13 y olds, n 9; and adults, n 10). (B) Protein levels were determined 24 h post- LPS stimulation (n 10 per age group) and presented as mean SE. *p 0.050 vs unstimulated (control) cultures; †p 0.01 vs 1 y olds; §p 0.050 vs 4 y olds; ‡p 0.040 vs 13 y olds; ¶p 0.040 vs adult. CB= cord blood Yerkovich ST, Wikstro ME, Suriyaarachchi D, SUSAN L. Prescott SL, Upham JW, Holt PG. Postnatal Development of Monocyte Cytokine Responses to Bacterial Lipopolysaccharide. Pediatric Research, 62: 547-552; 2007. Produção de citocinas * * Upham JW, Lee PT, Holt BJ,Heaton T, Prescott SL, Sharp MJ, Sly PD, Holt PG. Development of Interleukin-12-Producing Capacity throughout Childhood. Infection and Immunity, 70: 6583–6588; 2002. Estimulada com IFN- - LPS Estimulada com S. aureus * * Upham JW, Lee PT, Holt BJ,Heaton T, Prescott SL, Sharp MJ, Sly PD, Holt PG. Development of Interleukin-12-Producing Capacity throughout Childhood. Infection and Immunity, 70: 6583–6588; 2002. DESVIO TA2 IL10>IL12 Ta2 * * Anticorpos * * * * Journal of Infection (2015), in press * * Journal of Infection (2015), in press DESVIO Ta2 * * Susceptibilidade às doenças Recém-nascido Imaturidade imunológica: resposta inflamatória aguda, deficiência do sistema do complemento, deficiência de IgM, função auxiliar, memória. Agentes: enterobactérias, Staphylococcos, Streptococcos, vírus * * Susceptibilidade às doenças Lactente Imaturidade imunológica: resposta inflamatória aguda, deficiência de IgG e IgA, função auxiliar, memória Agentes: bactérias encapsuladas, vírus * * Susceptibilidade às doenças Pré-escolar Imaturidade imunológica: memória imunológica a antígenos polissacarídeos Agentes: vírus, Streptococcos pneumoniae * * * * * * * * * * DESVIO Ta2 WCC - contagem de células brancas * * Sacks G, Sargent I, Redman C. An innate view of human pregnancy. Immunology Today 114: 20; 1999 IMUNIDADE INATA * * Luppi P. How immune mechanisms are affected by pregnancy. Vaccine, 21: 3352–3357; 2003. * * * * Lesourd B, Lynda Mazari L. Nutrition and immunity in the elderly. Proceedings of the Nutrition Society, 58, 685–695; 1999 CD2 = molécula de adesão- LFA2 diminui CD57 – NK aumenta CD45RA- Linfócito T de memória diminui CD45RO - Linfócito T virgem aumenta NÚMERO * * Lesourd B, Lynda Mazari L. Nutrition and immunity in the elderly. Proceedings of the Nutrition Society, 58, 685–695; 1999 FUNÇÃO proliferação diminui CD25 = rIL2 (LT e LB ativados) diminui produção de citocinas diminui * * Olga DelaRosa , Graham Pawelec, Esther Peralbo, Anders Wikby, Erminia Mariani, Eugenio Mocchegiani, Raquel Tarazona, Rafael Solana Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology (2006) 7:471–481 Fenótipo de Risco Imune * * Infecção Disfunção do Sistema imunitário Imaturidade Senescência Gestante MORTE * * * * * * * * Moléculas de defesa inespecífica Antimicrobianos * * Moléculas anti-inflamatórias * * Journal of Infection (2015), in press* * * * * * * * * * * * * * * * PrabhuDas et al. Nature Immunology 12: 189-195, 2011 * * CD57 - NK * * * * * * Marchant A, Goldman M. Clinical and Experimental Immunology 141: 10–18, 2005. * * * * Monócitos/macrófagos Fagocitose normal/exacerbada Quimiotaxia reduzida Mecanismos microbicidas reduzidos Função apresentadora de antígeno deficiente * * NEUTRÓFILOS Número aumentado Reserva na medula óssea diminuída Fagocitose deprimida/exacerbada Quimiotaxia diminuída Mecanismos microbicidas reduzidos * * * * Aagaard-Tillery KM, Silver R, Dalton J. Immunology of normal pregnancy. Seminars in Fetal and Neonatal Medicine. 11, 279-295; 2006. * * Danielle AW, Silva AB, Palmer DB. Immunosenescence: emerging challenges for an ageing population. Immunology. 120: 435–446; 2007. * * * * Lesourd B, Lynda Mazari L. Nutrition and immunity in the elderly. Proceedings of the Nutrition Society, 58, 685–695; 1999 * * Lesourd B, Lynda Mazari L. Nutrition and immunity in the elderly. Proceedings of the Nutrition Society, 58, 685–695; 1999 * * Cuida Orienta Protege Alimenta Dá carinho * As mesmas necessidades para o ser humano ..... * Gestante Criança Lactante Idoso * Desenvolvimento do sistema imunitário na infância * neutrófilos * Mecanismos de defesa inespecíficos * Número de Neutrófilos * FIG. 3. Influence of age on phagocytosis of sensitized S. cerevisiae yeasts by neutrophils from peripheral blood. Cs newborn, 31 healthy newborn children delivered by caesarean section (group a); Vd newborn, 29 healthy newborn children delivered vaginally (group b); Inf, 30 healthy infants ages 1 to 11 months (group c); PSch, 29 healthy preschool children ages 1 to 5 years (group d); Sch, 30 healthy schoolchildren ages 5 to 12 years (group e); Ad, 30 healthy adult individuals (group f). Neutrophils were incubated with 2.5 105 S. cerevisiae yeasts sensitized for 30 min at 37°C with 10% fresh serum from the individual donor in Hanks-Tris solution. The data are expressed as medians (solid line in each box), quartiles (the tops and bottoms of each box), and minimum and maximum values (bars). The dotted lines indicate the medians for the adult population. (A) Average number of S. cerevisiae yeasts ingested by phagocytosing neutrophils; (B) proportion of neutrophils engaged in phagocytosis; (C) phagocytic index. In panel A, the values for group a were statistically significantly higher than those for groups b, c, and e; and the values for group d were statistically significantly higher than those for groups b and e (P 0.001 by the Kruskal-Wallis test, followed by the Dunn’s method for multiple comparisons). In panel B, the values for group b were statistically significantly lower than those for groups a, c, d, e, and f (P 0.001 by ANOVA, followed by the Student-Newman-Keuls method for multiple comparisons). In panel C, the values for group a were statistically significantly higher than those for groups b, c, d, e, and f; and the values for group b were statistically significantly lower than those for groups a, c, d, e, and f (P 0.001 by ANOVA, followed by the Student-Newman-Keuls method for multiple comparisons). * FIG. 4. Influence of age on phagocytosis of sensitized S. cerevisiae yeasts by monocytes from peripheral blood. Cs newborn, 29 healthy newborn children delivered by cesarean section (group a); Vd newborn, 30 healthy newborn children delivered vaginally (group b); Inf, 30 healthy infants ages 1 to 11 months (group c); PSch, 30 healthy preschool children ages 1 to 5 years (group d); Sch, 29 healthy schoolchildren ages 5 to 12 years (group e); Ad, 31 healthy adult individuals (group f). Monocytes were incubated with 2.5 105 S. cerevisiae yeasts sensitized for 30 min at 37°C with 10% fresh serum from the individual donor in Hanks-Tris solution. The data are expressed as medians (solid line in each box), quartiles (the tops and bottoms of each box), and minimum and maximum values (bars). The dotted lines indicate the medians for the adult population. (A) Average number of S. cerevisiae yeasts ingested by phagocytosing neutrophils; (B) proportion of neutrophils engaged in phagocytosis; (C) phagocytic index. In panel A, the values for group a were statistically significantly higher than those for groups b, c, d, e, and f; the values for group f were statistically significantly higher than those for groups c and d; and the values for group c were statistically significantly lower than those for groups a, b, e, and f (P 0.001 by the Kruskal-Wallis test, followed by Dunn’s method for multiple comparisons). In panel B, the values for group b were statistically significantly lower than those for group e (P 0.032 by ANOVA, followed by the Student-Newman-Keuls method for multiple comparisons). In panel C, the values for group a were statistically significantly higher than those for groups c and d (P 0.002 by the Kruskal-Wallis test, followed by Dunn’s method for multiple comparisons * Tamanho do Timo * Timo menor- fator de risco para mortalidade * Número de Linfócitos * IL-10 * Produção de citocinas * Estimulada com S. aureus * Ta1 * Anticorpos * DESVIO Ta2 * WCC contagem de células brancas * IMUNIDADE INATA * NÚMERO CD2 molécula de adesão- LFA2 CD57 NK CD45RA Linfócito T de memória * CD25 r IL2 (LT e LB ativados) * Fenótipo de Risco Imune * Moléculas de defesa inespecífica * Moléculas anti-inflamatórias * PrabhuDas et al. Nature Immunology 12: 189-195, 2011 * * Marchant A, Goldman M. Clinical and Experimental Immunology 141: 10–18, 2005. * *
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