19 Variações fisiológicas da RI

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Variações fisiológicas 
da resposta imunitária
Maria Imaculada Muniz-Junqueira
Imunologia Médica
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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.
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Mecanismos de defesa inespecíficos
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Imunidade Inata
Sistema de Fagócitos
 Neutrófilos
 Monócitos
Sistema do Complemento
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NEUTRÓFILOS
Número
Reserva na medula óssea
Fagocitose
Quimiotaxia
Mecanismos microbicidas
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Número de Neutrófilos
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NEUTRÓFILOS
Número aumentado
Reserva na medula óssea diminuída
Fagocitose
Quimiotaxia
Mecanismos microbicidas
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NEUTRÓFILOS
Número aumentado
Reserva na medula óssea diminuída
Fagocitose
Quimiotaxia
Mecanismos microbicidas
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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. 
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NEUTRÓFILOS
Número aumentado
Reserva na medula óssea diminuída
Fagocitose deprimida/exacerbada
Quimiotaxia diminuída
Mecanismos microbicidas reduzidos
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Monócitos/macrófagos
Fagocitose
Quimiotaxia
Mecanismos
Função apresentadora de antígeno
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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. 
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Monócitos/macrófagos
Fagocitose normal/exacerbada
Quimiotaxia reduzida
Mecanismos microbicidas reduzidos
Função apresentadora de antígeno deficiente 
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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
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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%)
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IMUNIDADE ADQUIRIDA
Linfócitos T
Linfócitos B
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Tamanho do Timo
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Garly ML. Thymus Size at 6 Months of Age and Subsequent Child Mortality J Pediatr 2008153:683-8
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Número de Linfócitos
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Linfócitos T
Função auxiliar do LT CD4+ deprimida
IL2, IL4, Interferon-, GM-CSF produção diminuída
LT requer maior quantidade de sinais co-estimulatórios 
 menor densidade de receptor do linfócito T
 menor expressão de moléculas de adesão 
 (LFA-1, CD2)
 resposta imune deficiente
Desvio LTa2 
 imaturidade de células acessórias
 (macrófago, célula dendrítica, linfócito B)
Resposta ao BCG
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Linfócito T CD8+
Função supressora aumentada
Função citotóxica deprimida
Célula NK
 Atividade citotóxica diminuída
Conseqüência
Aumento gravidade das infecções virais
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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.
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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
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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.
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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
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Anticorpos
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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
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Susceptibilidade às doenças
Lactente
Imaturidade imunológica: 
resposta inflamatória aguda,
deficiência de IgG e IgA, 
função auxiliar, 
memória 
Agentes: 
bactérias encapsuladas, vírus
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Susceptibilidade às doenças
Pré-escolar
Imaturidade imunológica: 
memória imunológica a antígenos 
 polissacarídeos
Agentes: 
vírus, Streptococcos pneumoniae
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Moléculas de defesa inespecífica
Antimicrobianos
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Moléculas anti-inflamatórias
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Sacks G, Sargent I, Redman C. 
An innate view of human pregnancy. 
Immunology Today 114: 20; 1999
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Luppi P. How immune mechanisms are affected by pregnancy. Vaccine, 21: 3352–3357; 2003. 
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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 
CD57 – NK
CD45RA- Linfócito T de memória
CD45RO - Linfócito T virgem
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Lesourd B, Lynda Mazari L. Nutrition and immunity in the elderly. Proceedings of the Nutrition Society, 58, 685–695; 1999
CD25 = rIL2 (LT e LB ativados)
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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
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Infecção
Disfunção do
Sistema imunitário
Imaturidade
Senescência
Gestante
MORTE
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PrabhuDas et al. Nature Immunology 12: 189-195, 2011
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CD57 - NK
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Marchant A, Goldman M. Clinical and Experimental Immunology 141: 10–18, 2005.
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Monócitos/macrófagos
Fagocitose normal/exacerbada
Quimiotaxia reduzida
Mecanismos microbicidas reduzidos
Função apresentadora de antígeno deficiente 
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NEUTRÓFILOS
Número aumentado
Reserva na medula óssea diminuída
Fagocitose deprimida/exacerbada
Quimiotaxia diminuída
Mecanismos microbicidas reduzidos
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Aagaard-Tillery KM, Silver R, Dalton J. Immunology of normal pregnancy. Seminars in Fetal and Neonatal Medicine.
11, 279-295; 2006.
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Danielle AW, Silva AB, Palmer DB. Immunosenescence: emerging challenges for an ageing population.
Immunology. 120: 435–446; 2007.
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Lesourd B, Lynda Mazari L. Nutrition and immunity in the elderly.Proceedings of the Nutrition Society, 58, 685–695; 1999
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Lesourd B, Lynda Mazari L. Nutrition and immunity in the elderly. Proceedings of the Nutrition Society, 58, 685–695; 1999
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Mecanismos de defesa inespecíficos
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Número de Neutrófilos
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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).
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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
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Tamanho do Timo
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Número de Linfócitos
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IL-10
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Ta1
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Anticorpos
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Moléculas de defesa inespecífica
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Moléculas anti-inflamatórias
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CD2 molécula de adesão- LFA2 
CD57 NK
CD45RA Linfócito T de memória
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CD25 r IL2 (LT e LB ativados)
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PrabhuDas et al. Nature Immunology 12: 189-195, 2011
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Marchant A, Goldman M. Clinical and Experimental Immunology 141: 10–18, 2005.
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