RESUMO
Oral tolerance is defined as a state of systemic hyporesponsiveness to an antigen that has been previously administered by the oral route. Many factors affect oral tolerance induction; some of them related to antigen, and some related to the animal. The age of the animal is one of the most important factors that affect oral tolerance as ageing brings many alterations in immune responses. Herein, we demonstrated that both the oral tolerance and pattern of immune reactivity triggered in early life were kept up to 15 months regarding the magnitude of antibody production, cell proliferation and cytokine profile when compared to immune responses induced in old mice. Therefore, our results corroborate with a promising proposal for prevaccination during childhood and young age, and a booster in older age, to make sure that the primary immunization in early life is not lost in aged individuals.
Assuntos
Antígenos/imunologia , Hipersensibilidade Tardia/imunologia , Tolerância Imunológica , Administração Oral , Animais , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Exposição Ambiental , Feminino , Humanos , Imunidade Humoral , Imunização , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , VacinasRESUMO
BACKGROUND: Egg allergy is a leading cause of food allergy in young infants; however, little is known about early allergen-specific T-cell responses which predate the presentation of egg allergy, and if these are altered by early egg exposure. OBJECTIVE: To investigate the early T-cell responses to multiple egg proteins in relation to patterns of egg exposure and subsequent IgE-mediated egg allergy. METHODS: Egg-specific T-cell cytokine responses (IL-5, IL-13, IL-10, IFNγ and TNFα) to ovomucoid (OM), ovalbumin (OVA), conalbumin (CON) and lysozyme (LYS) were measured in infants with eczema at 4 months of age (n = 40), before randomization to receive 'early egg' or a placebo as part of a randomized controlled trial (Australian New Zealand Clinical Trials Registry number 12609000415202) and at 12 months of age (n = 58), when IgE-mediated egg allergy was assessed by skin prick test and food challenge. RESULTS: In 4-month-old infants, who had not directly ingested egg, those who subsequently developed egg allergy already had significantly higher Th2 cytokine responses to multiple egg allergens, particularly elevated IL-13 responses to OVA (P = 0.004), OM (P = 0.012) and LYS (P = 0.003) and elevated IL-5 to the same antigens (P = 0.031, 0.04 and 0.003, respectively). IL-13 responses (to OVA and LYS) and IL-5 responses (to LYS) at 4 months significantly predicted egg allergy at 12 months. All responses significantly declined with age in the egg-allergic infants, and this did not appear to be modified by 'early' introduction of egg. CONCLUSIONS & CLINICAL RELEVANCE: Elevated egg-specific Th2 cytokine responses were established prior to egg ingestion at 4 months and were not significantly altered by introduction of egg. Th2 responses at 4 months of age predicted egg allergy at 12 months, suggesting that this could be used as a biomarker to select infants for early prevention and management strategies.
Assuntos
Dermatite Atópica/imunologia , Hipersensibilidade a Ovo/imunologia , Proteínas do Ovo/imunologia , Interleucina-13/imunologia , Interleucina-5/imunologia , Dessensibilização Imunológica , Feminino , Humanos , Lactente , Masculino , Células Th2/imunologiaRESUMO
BACKGROUND: There is limited understanding of how maternal diet affects breastmilk food allergen concentrations, and whether exposure to allergens through this route influences the development of infant oral tolerance or sensitization. OBJECTIVE: To investigate how maternal dietary egg ingestion during early lactation influences egg protein (ovalbumin) levels detected in human breastmilk. METHODS: In a randomized controlled trial, women were allocated to a dietary group for the first six weeks of lactation: high-egg diet (> 4 eggs per week), low-egg diet (one-three eggs per week) or an egg-free diet. Breastmilk samples were collected at 2, 4 and 6 weeks of lactation for the measurement of ovalbumin. The permeability of the mammary epithelium was assessed by measuring the breastmilk sodium : potassium ratio. Egg-specific IgE and IgG4 were measured in infant plasma at 6 weeks, and prior to the introduction of egg in solids at 16 weeks. RESULTS: Average maternal egg ingestion was associated with breastmilk ovalbumin concentration. Specifically, for each additional egg ingested per week, there was an average 25% increase in ovalbumin concentration (95% CI: 5-48%, P = 0.01). Breastmilk ovalbumin concentrations were significantly higher in the 'high-egg' group (> 4 eggs per week) compared with the 'egg-free' group (P = 0.04). However, one-third of women had no breastmilk ovalbumin detected. No detectable associations were found between mammary epithelium permeability and breastmilk ovalbumin concentrations. Infant plasma egg-specific IgG4 levels were also positively associated with maternal egg ingestion, with an average 22% (95% CI: 3-45%) increase in infant egg-specific IgG4 levels per additional egg consumed per week (P = 0.02). CONCLUSIONS AND CLINICAL RELEVANCE: Increased maternal egg ingestion is associated with increased breastmilk ovalbumin, and markers of immune tolerance in infants. These results highlight the potential for maternal diet to benefit infant oral tolerance development during lactation.
Assuntos
Alérgenos/imunologia , Dieta , Ovos , Hipersensibilidade Alimentar/epidemiologia , Lactação , Leite Humano/imunologia , Ovalbumina/imunologia , Adulto , Animais , Especificidade de Anticorpos , Aleitamento Materno/efeitos adversos , Dieta/efeitos adversos , Ovos/efeitos adversos , Feminino , Hipersensibilidade Alimentar/etiologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Lactente , Recém-Nascido , Masculino , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: Vitamin D (25[OH]D3) status in early life has been linked to the risk of allergic disease in multiple observational studies. While immunomodulating properties are well recognized, there are few longitudinal studies of 25(OH)D3 status, immune function and allergic disease in infants. OBJECTIVE: To investigate 25(OH)D3 levels at birth [cord blood (CB)] and at 6 months of age in relation to immune function at 6 months of age, and clinical outcomes up to 30 months of age in infants with a maternal history of atopy. METHODS: In a subset of infants (n = 225) enrolled in a RCT (ACTRN12606000281594), 25(OH)D3 levels were assessed in relation to peripheral blood mononuclear cell cytokine responses to house dust mite (HDM), ovalbumin (OVA) and ß-lactoglobulin allergens, or Toll-like receptor (TLR) ligands (lipopolysaccharide, lipoteichoic acid, polyinosinic : polycytidylic acid and CpG oligonucleotide) at 6 months of age, in addition to clinical outcomes (eczema, wheeze and allergen sensitisation) up to 30 months of age. RESULTS: Infants with higher 25(OH)D3 at birth (≥ 75 nmol/L, compared with < 50 nmol/L) had lower IL-5 and IL-13 responses to HDM by 6 months (P < 0.001 and P = 0.003, respectively). This was also reflected in strong inverse correlations between CB 25(OH)D3 levels and HDM IL-13 (ρ = -0.57; P = 0.0002) and IL-5 (ρ = -0.59, P = 0.0001) responses, with a similar trend for IL-5 (ρ = -0.29; P = 0.009) responses to OVA. For innate stimulations, higher 25(OH)D3 levels at 6 months were associated with greater responses to TLR ligands. Additionally, higher CB 25(OH)D3 was associated with reduced risk eczema at 6 months (P = 0.011) and 12 months (P = 0.034). CONCLUSION: This suggests that improving 25(OH)D3 status in pregnancy or early infancy may reduce the development of allergic disease in high-risk infants by inhibiting cytokine profiles associated with allergy. Results of clinical trials are awaited to determine the efficacy of vitamin D supplementation in allergy prevention.
Assuntos
Imunidade Adaptativa/fisiologia , Calcifediol/sangue , Imunidade Inata/fisiologia , Gravidez/sangue , Adulto , Alérgenos/imunologia , Alérgenos/farmacologia , Calcifediol/imunologia , Pré-Escolar , Citocinas/sangue , Citocinas/imunologia , Feminino , Humanos , Hipersensibilidade/sangue , Hipersensibilidade/imunologia , Lactente , Masculino , Gravidez/imunologia , Fatores de RiscoAssuntos
Fístula Artério-Arterial/diagnóstico por imagem , Artéria Basilar/anormalidades , Artéria Carótida Externa/anormalidades , Osso Occipital/irrigação sanguínea , Artéria Vertebral/anormalidades , Adulto , Fístula Artério-Arterial/etiologia , Artéria Basilar/diagnóstico por imagem , Artéria Carótida Externa/diagnóstico por imagem , Feminino , Humanos , Angiografia por Ressonância Magnética , Osso Occipital/diagnóstico por imagem , Artéria Vertebral/diagnóstico por imagemRESUMO
The spatiotemporal evolution of both U and Th isotopes in a mine effluent highly polluted by acid mine drainage (AMD) was evaluated. The acidic tributary, which born from the outflows of an abandoned sulfide mine, flows into the Odiel River. AMD comprises an important source of natural radionuclides, presenting concentrations of 238U and 232Th, two and four orders of magnitude higher, respectively, than the background values of surface continental waters. These natural radionuclides behave conservatively along the mine effluent (pH < 2.5) throughout the hydrological year. Under AMD conditions uranium is in the hexavalent state U(VI) and the main dissolved species are uranyl sulfate complexes. The polluted tributary has a significant impact on the Odiel River acidifying its waters during the low flow season and increasing up to one order of magnitude the activity concentrations of U and Th isotopes. U presented a conservative behavior in the Odiel River during the low flow season (pH ≈ 3), however it is removed from the liquid phase in the wet season (pH ≈ 6), probably due its coprecipitation/adsorption onto Al-phases. Th shows a high sensitivity to small increases of pH, and it is strongly coprecipitated/adsorbed with or onto Fe-oxyhydroxydizes in the river.
RESUMO
BACKGROUND: Maternal fish oil supplementation during pregnancy has been associated with altered infant immune responses and a reduced risk of infant sensitization and eczema. OBJECTIVE: To examine the effect of early postnatal fish oil supplementation on infant cellular immune function at 6 months of age in the context of allergic disease. METHODS: In a double-blind randomized controlled trial (ACTRN12606000281594), 420 infants of high atopic risk received fish oil [containing 280 mg docosahexaenoic acid (DHA) and 110 mg eicosapentanoic acid (EPA)] or control oil daily from birth to 6 months. One hundred and twenty infants had blood collected at 6 months of age. Fatty acid levels, induced cytokine responses, T cell subsets and monocyte HLA-DR expression were assessed at 6 months of age. Infant allergies were assessed at 6 and 12 months of age. RESULTS: DHA and EPA levels were significantly higher in the fish oil group and erythrocyte arachidonic acid (AA) levels were lower (all P < 0.05). Infants in the fish oil group had significantly lower IL-13 responses (P = 0.036) to house dust mite (HDM) and higher IFNγ (P = 0.035) and TNF (P = 0.017) responses to phytohaemaglutinin (PHA). Infants with relatively high DHA levels had lower Th2 responses to allergens including lower IL-13 to ß-lactoglobulin (BLG) (P = 0.020), and lower IL-5 to BLG (P = 0.045). CONCLUSIONS AND CLINICAL RELEVANCE: Postnatal fish oil supplementation increased infant n-3 polyunsaturated fatty acid (PUFA) levels and associated with lowered allergen-specific Th2 responses and elevated polyclonal Th1 responses. Our results add to existing evidence of n-3 PUFA having immunomodulatory properties that are potentially allergy-protective.
Assuntos
Suplementos Nutricionais , Óleos de Peixe/farmacologia , Imunidade/efeitos dos fármacos , Fatores Imunológicos/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Fatores Etários , Citocinas/biossíntese , Citocinas/imunologia , Ácidos Graxos Insaturados/sangue , Feminino , Óleos de Peixe/administração & dosagem , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Imunidade Inata/efeitos dos fármacos , Fatores Imunológicos/administração & dosagem , Lactente , MasculinoRESUMO
BACKGROUND: Dietary changes may epigenetically modify fetal gene expression during critical periods of development to potentially influence disease susceptibility. This study examined whether maternal and/or fetal folate status in pregnancy is associated with infant allergic outcomes. METHODS: Pregnant women (n=628) were recruited in the last trimester of pregnancy. Folate status determined by both food frequency questionnaires and folate levels in maternal and cord blood serum was examined in relation to infant allergic outcomes at 1 year of age (n=484). RESULTS: Infants who developed allergic disease (namely eczema) did not show any differences in cord blood or maternal folate levels compared with children without disease. Although maternal folate intake from foods was also not different, folate derived from supplements was higher (P=0.017) in children with subsequent eczema. Furthermore, infants exposed to >500 µg folic acid/day as a supplement in utero were more likely to develop eczema than those taking <200 µg/day (OR [odds ratio] =1.85; 95% CI 1.14-3.02; P=0.013), remaining significant after adjustment for maternal allergy and other confounders. There was a nonlinear relationship between cord blood folate and sensitization, with folate levels <50 nmol/l (OR=3.02; 95% CI 1.16-7.87; P=0.024) and >75 nmol/l (OR=3.59; 95% CI 1.40-9.20; P=0.008) associated with greater sensitization risk than levels between 50 and 75 nmol/l. CONCLUSION: Fetal levels between 50 and 75 nmol/l appeared optimal for minimizing sensitization. While folate taken as a supplement in higher doses during the third trimester was associated with eczema, there was no effect on other allergic outcomes including sensitization. Further studies are needed to determine the significance of this.
Assuntos
Sangue Fetal/química , Ácido Fólico/sangue , Hipersensibilidade/etiologia , Gravidez/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Adulto , Dieta , Suplementos Nutricionais/efeitos adversos , Feminino , Humanos , Lactente , Recém-NascidoRESUMO
BACKGROUND: Previous studies have demonstrated that reduced T-cell protein kinase C zeta (PKCζ) expression is associated with allergy development in infants born to atopic mothers. This study examined whether this relationship extends to a general population and addressed the basis for the association. METHODS: A flow cytometry assay was developed for the measurement of T-cell PKCζ levels in PBMC, cord blood mononuclear cell and whole blood. Cord blood T-cell PKCζ levels were measured in 135 neonates, and allergic disease was evaluated by skin prick test and clinical examination at 12 months of age. RESULTS: Allergic children (particularly those with eczema) had significantly lower neonatal T-cell PKCζ expression than nonallergic children (P < 0.001). PKCζ levels predicted allergic disease with optimal specificity of 86% and sensitivity of 54%. The sensitivity was increased in the children of allergic mothers, who had significantly lower PKC levels than the children of nonallergic mothers. Cord blood PKCζ levels did not affect T-cell maturation in culture as assessed by CD45RA/RO expression, but low PKCζ expression was associated with reduced capacity for IFNγ production by matured T cells. Low cord blood PKC expression was further associated with increased IL-13 responses at 6 months. CONCLUSIONS: The findings suggest a potential role for the use of PKCζ levels in cord blood T cells as a presymptomatic test to predict allergy risk in children, particularly offspring of allergic mothers, and that the basis of this relationship is related to cytokine patterns in mature T cells.
Assuntos
Citocinas/metabolismo , Hipersensibilidade/enzimologia , Hipersensibilidade/imunologia , Fenótipo , Proteína Quinase C/metabolismo , Linfócitos T/enzimologia , Linfócitos T/imunologia , Citocinas/imunologia , Feminino , Citometria de Fluxo , Humanos , Hipersensibilidade/diagnóstico , Imunofenotipagem , Lactente , Recém-Nascido , Masculino , Prognóstico , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e EspecificidadeRESUMO
Maternal diet during pregnancy has long been recognised as an important determinant of neonatal outcomes and child development. Infant body composition is a potentially modifiable risk factor for predicting future health and metabolic disease. Utilising the Mediterranean Diet Score, this study focused on how different levels of Mediterranean Diet adherence (MDA) in pregnancy influence body fat percentage of the infant. Information on 458 pregnant women in their third trimester of pregnancy and their infants was obtained from The ORIGINS Project. The data included MDA score, body composition measurements using infant air displacement plethysmography (PEA POD), pregnancy, and birth information. Infants born to mothers with high MDA had a body fat percentage of 11.3%, whereas infants born to mothers with low MDA had a higher body fat percentage of 13.3% (p = 0.010). When adjusted for pre-pregnancy body mass index and infant sex, a significant result remained between high vs. low MDA and infant fat mass (FM) (2.5% less FM p = 0.016). This study suggests that high MDA in pregnancy was associated with a reduced body fat percentage in the newborn. Future studies are needed to understand whether small but significant changes in FM persist throughout childhood.
Assuntos
Dieta Mediterrânea , Tecido Adiposo , Composição Corporal , Índice de Massa Corporal , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Terceiro Trimestre da GravidezRESUMO
BACKGROUND: We aimed to estimate the prevalence of diabetes mellitus and study the associated factors in a rural population in Goa, India. METHODS: A cross-sectional study was done in the rural area of Mandur, Goa. Participants>20 years of age were selected by systematic random sampling. They were interviewed with the help of a structured, pretested questionnaire. This was followed by clinical examination, anthropometry and relevant laboratory investigations. Diabetes mellitus was defined as per the American Diabetes Association (ADA) criteria. Statistical analysis was done using the SPSS software package (version 14.0). RESULTS: The prevalence of diabetes mellitus in the study population was 10.3% (130/1266) with a prevalence of 8.4% among men and 12% among women. On bivariate analysis, the prevalence of diabetes mellitus was found to be significantly associated with age, occupation, family income, family history of diabetes, smoking, obesity, hypertension, and high serum cholesterol and triglycerides levels. Multiple logistic regression analysis identified age, family history, hypertension, smoking, total cholesterol and triglyceride as the Independently associated variables for diabetes mellitus. CONCLUSION: Innovative community outreach programmes are required to create awareness, and for screening and treatment of diabetes mellitus to curb the growing epidemic of diabetes in the population.
Assuntos
Diabetes Mellitus/epidemiologia , População Rural/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
Immune responsiveness of inbred mice to low doses of ovalbumin or ovomucoid is under control of single dominant genes closely linked to alleles of the H-2 locus. High responsiveness to ovomucoid is linked with the H-2(a) and H-2(k) alleles, and to ovalbumin with the H-2(b), H-2(d), and H-2(q) alleles.
Assuntos
Formação de Anticorpos , Genes Dominantes , Histocompatibilidade , Imunogenética , Isoantígenos , Mucoproteínas/farmacologia , Ovalbumina/farmacologia , Alelos , Animais , Feminino , Endogamia , Camundongos , Mucoproteínas/administração & dosagem , Ovalbumina/administração & dosagem , Anafilaxia Cutânea PassivaRESUMO
Senescence is characterized by several alterations in the immune system. Such modifications can be found in lymphoid organs as well as in the cellular components of the immune system. Several reports have suggested that immune dysfunction can affect both T and B cells, but T cells have been shown to be more susceptible to the effects of aging. B cell function may also be altered with reduction in germinal center formation, antibody response, and affinity maturation of antibodies. Herein we showed that although antigen-specific antibody response to a soluble antigen declines in 18-month old mice, total levels of serum antibodies as well as frequencies of spleen and bone marrow antibody-producing cells are increased in aged mice. In addition, proliferative response of non-stimulated spleen T cells from aged mice were augmented and insensitive to increasing doses of concanavalin A stimulation as compared to young mice that showed a typical dose-dependent response to mitogen stimulation in vitro. These data suggest that the higher activation mode of B and T cells in senescent mice is a result of an increased frequency of cells committed to previous antigenic experiences and with poor ability to respond to novel antigenic challenges.
Assuntos
Envelhecimento/imunologia , Linfócitos B/imunologia , Linfócitos T/imunologia , Animais , Afinidade de Anticorpos , Especificidade de Anticorpos , Antígenos/administração & dosagem , Células da Medula Óssea/imunologia , Feminino , Tolerância Imunológica , Imunoglobulinas/sangue , Técnicas In Vitro , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/administração & dosagem , Ovalbumina/imunologia , Baço/citologia , Baço/imunologiaRESUMO
Immunization of inbred strains of mice with repeated minute doses (0.1 to 1.0 microgram) of hapten-protein conjugates demonstrated wide differences in the magnitude of their antibody responses, which were related to the histocompatibility (H-2) type of the strains. Immunization with a single high dose (100 micrograms) of antigen failed to demonstrate these differences.
Assuntos
Formação de Anticorpos , Antígenos/administração & dosagem , Haptenos/farmacologia , Histocompatibilidade , Animais , Dinitrofenóis , Haptenos/administração & dosagem , Imunização , Imunoglobulina E , Endogamia , Camundongos , Mucoproteínas , Penicilina G , Ribonucleases , gama-GlobulinasRESUMO
For more than 2,000 years, it was thought that malignant spirits caused diseases. By the end of nineteenth century, these beliefs were displaced by more modern concepts of disease, namely, the formulation of the "germ theory," which asserted that bacteria or other microorganisms caused disease. With the emergence of chronic degenerative and of autoimmune diseases in the last century, the causative role of microorganisms has been intensely debated; however, no clear explanatory models have been achieved. In this review, we examine the current available literature regarding the relationships between infections and 16 autoimmune diseases. We critically analyzed clinical, serological, and molecular associations, and reviewed experimental models of induction of and, alternatively, protection from autoimmune diseases by infection. After reviewing several studies and reports, a clinical and experimental pattern emerges: Chronic and multiple infections with viruses, such as Epstein-Barr virus and cytomegalovirus, and bacteria, such as H. pylori, may, in susceptible individuals, play a role in the evolvement of autoimmune diseases. As the vast majority of infections pertain to our resident microbiota and endogenous retroviruses and healthy carriage of infections is the rule, we propose to focus on understanding the mechanisms of this healthy carrier state and what changes its configurations to infectious syndromes, to the restoration of health, or to the sustaining of illness into a chronic state and/or autoimmune disease. It seems that in the development of this healthy carriage state, the infection or colonization in early stages of ontogenesis with key microorganisms, also called 'old friends' (lactobacilli, bifidobacteria among others), are important for the healthy living and for the protection from infectious and autoimmune syndromes.
Assuntos
Doenças Autoimunes/imunologia , Autoimunidade , Infecções/imunologia , Inflamação/imunologia , Animais , Autoanticorpos/imunologia , Autoantígenos/imunologia , Doenças Autoimunes/etiologia , Modelos Animais de Doenças , Humanos , VacinaçãoRESUMO
The role of river discharge, wind and tide on the extension and variability of the Tagus River plume was analyzed from 2003 to 2015. This study was performed combining daily images obtained from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor located onboard the Aqua and Terra satellites. Composites were generated by averaging pixels with the same forcing conditions. River discharge shows a strong relation with the extension of the Tagus plume. The plume grows with the increasing river discharge and express a two day lag caused by the long residence time of water within the estuary. The Tagus turbid plume was found to be smaller under northerly and easterly winds, than under southerly and westerly winds. It is suggested that upwelling favoring winds provoke the offshore movement of the plume material with a rapidly decrease in turbidity values whereas downwelling favoring winds retain plume material in the north coast close to the Tagus mouth. Eastern cross-shore (oceanward) winds spread the plume seaward and to the north following the coast geometry, whereas western cross-shore (landward) winds keep the plume material in both alongshore directions occupying a large part of the area enclosed by the bay. Low tides produce larger and more turbid plumes than high tides. In terms of fortnightly periodicity, the maximum plume extension corresponding to the highest turbidity is observed during and after spring tides. Minimum plume extension associated with the lowest turbidity occurs during and after neap tides.
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Monitoramento Ambiental , Rios , Imagens de Satélites , Secas , Inundações , Espanha , VentoRESUMO
Paraphrasing what Gregory Bateson says on evolution, we might say that: "Immunology has long been badly taught. In particular, students--and even professional immunologists--acquire theories of immunological activity without any deep understanding of what problems these theories attempt to solve."
Assuntos
Evolução Biológica , Sistema Imunitário/fisiologia , Animais , Humanos , Sistema Imunitário/imunologia , Modelos Imunológicos , Linfócitos T/imunologia , Linfócitos T/fisiologiaRESUMO
Most contacts with food protein and microbiota antigens occur at the level of the gut mucosa. In animal models where this natural stimulation is absent, such as germ-free and antigen-free mice, the gut-associated lymphoid tissue (GALT) and systemic immunological activities are underdeveloped. We have shown that food proteins play a critical role in the full development of the immune system. C57BL/6 mice weaned to a diet in which intact proteins are replaced by equivalent amounts of amino acids (Aa diet) have a poorly developed GALT as well as low levels of serum immunoglobulins (total Ig, IgG, and IgA, but not IgM). In the present study, we evaluated whether the introduction of a protein-containing diet in 10 adult Aa-fed C57BL/6 mice could restore their immunoglobulin levels and whether this recovery was dependent on the amount of dietary protein. After the introduction of a casein-containing diet, Aa-fed mice presented a fast recovery (after 7 days) of secretory IgA (from 0.33 to 0.75 mg/mL, while in casein-fed mice this value was 0.81 mg/mL) and serum immunoglobulin levels (from 5.39 to 10.25 mg/mL of total Ig). Five percent dietary casein was enough to promote the restoration of secretory IgA and serum immunoglobulin levels to a normal range after 30 days feeding casein diet (as in casein-fed mice--15% by weight of diet). These data suggest that the defect detected in the immunoglobulin levels was a reversible result of the absence of food proteins as an antigenic stimulus. They also indicate that the deleterious consequences of malnutrition at an early age for some immune functions may be restored by therapeutic intervention later in life.
Assuntos
Proteínas Alimentares/imunologia , Suplementos Nutricionais , Isotipos de Imunoglobulinas/biossíntese , Animais , Caseínas/administração & dosagem , Dieta com Restrição de Proteínas , Proteínas Alimentares/administração & dosagem , Ensaio de Imunoadsorção Enzimática , Feminino , Isotipos de Imunoglobulinas/sangue , Camundongos , Camundongos Endogâmicos C57BL , Fatores de TempoRESUMO
B6D2F1 mice, which are very susceptible to tolerance induction by a single gavage with 20 mg of ovalbumin (Ova) at age 8 weeks, become less susceptible at age 25 weeks and totally refractory at age 70 weeks. However, 70-week-old mice may be rendered tolerant by repeated ingestion of Ova. Mice orally exposed to Ova at age 8 weeks remain tolerant at age 70 weeks. The isotypic pattern of anti-Ova antibodies formed by orally-tolerant and normal mice after immunization is similar and all isotypes are equally suppressed by oral tolerance. In old mice, oral exposures to Ova alone triggered an early transient antibody response; some of these responding animals were, nevertheless, tolerant to subsequent parenteral injection of Ova in adjuvant.
Assuntos
Envelhecimento/imunologia , Formação de Anticorpos/fisiologia , Tolerância Imunológica/fisiologia , Ovalbumina/imunologia , Inibidores de Serina Proteinase/imunologia , Administração Oral , Envelhecimento/fisiologia , Hidróxido de Alumínio/administração & dosagem , Hidróxido de Alumínio/imunologia , Animais , Anticorpos Anti-Idiotípicos/sangue , Anticorpos Anti-Idiotípicos/efeitos dos fármacos , Formação de Anticorpos/efeitos dos fármacos , Antígenos/administração & dosagem , Feminino , Tolerância Imunológica/efeitos dos fármacos , Imunização/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Ovalbumina/administração & dosagem , Inibidores de Serina Proteinase/administração & dosagemRESUMO
The oral administration of antigens is one of the means of inducing tolerance in adult mammals. In this report, the role of gamma delta T cells in the induction and maintenance of orally-induced tolerance to ovalbumin was investigated. The injection of a monoclonal anti-gamma delta T cell monoclonal antibody blocked the induction of oral tolerance, because the secondary immune responses to ovalbumin in these animals were comparable to the corresponding responses in ovalbumin-immunized control mice. Furthermore, depletion of gamma delta T cells either in vivo or in vitro abolished already established oral-tolerance. The fact that the state of tolerance could be adoptively transferred to naive recipients by CD3+ alpha beta- gamma delta + spleen cells from tolerant mice. These results suggest that systemic oral tolerance is induced and actively maintained by mechanisms involving gamma delta T cells.