Fetomaternal Immunological Interactions In The Aetiology Of Allergic Disease.
Funder
National Health and Medical Research Council
Funding Amount
$195,990.00
Summary
There is accumulating evidence that immune abnormalities that lead to allergy are present at birth, and may be linked with maternal factors in pregnancy. This study examines how immune interactions between the fetus and the mother during pregnancy predispose to allergic immune responses in the infant. Allergic diseases result from inappropriate Type 2 responses to the environment whereas Type 1 response dominate immune responses of nonallergic people. Type 2 immune responses are first initiated ....There is accumulating evidence that immune abnormalities that lead to allergy are present at birth, and may be linked with maternal factors in pregnancy. This study examines how immune interactions between the fetus and the mother during pregnancy predispose to allergic immune responses in the infant. Allergic diseases result from inappropriate Type 2 responses to the environment whereas Type 1 response dominate immune responses of nonallergic people. Type 2 immune responses are first initiated before birth when they are actually normal for fetal survival. In normal infants maturation of Type 1 immune responses plays a central role in switching off the Type 2 responses of fetal life. Allergic disease appears to be due to abnormal persistence of this Type 2 response pattern beyond the newborn period. One of the most striking abnormalities in allergic individuals is immature Type 1 function at birth. With rising rates of allergy, there is an urgent need to identify how the balance of Type 1 and Type 2 responses is regulated during this early period. Maternal factors appear to play a critical role. There is already evidence that Type 1 responses are lower in babies of allergic mothers compared to babies of allergic fathers, suggesting direct effects of the mother in pregnancy. Although pregnancy normally favours Type 2 immunity, there appears to be normal variation in the balance of Type 1 and Type 2 responses in pregnancy. We plan to determine if variations in this balance affect the fetal capacity for Type 1 responses. We propose that minor degrees of tissue mismatch (present in all pregnancies) will activate low grade Type 1 responses and enhance maturation of fetal Type 1 responses. We will determine if allergic mothers (prone to stronger Type 2 responses) have less developed Type 1 responses in pregnancy and if this plays a direct role in abnormal Type 1 responses observed in their babies.Read moreRead less
Effects Of Enteric Microflora On Mucosal And Systemic Immune Development In Infants At Risk Of Allergic Disease
Funder
National Health and Medical Research Council
Funding Amount
$219,750.00
Summary
The increase in allergic diseases over the last 20-30 years has been attributed to an increased immunological propensity to Type-2 allergic immune responses in the postnatal period. It has been proposed that this may be due to a relative deficiency of counter-regulatory Type 1 immune responses in early life. Thus, there is growing interest in factors that might affect Type 1 maturation in this early period. It has been proposed that progressively cleaner societies may have more allergies because ....The increase in allergic diseases over the last 20-30 years has been attributed to an increased immunological propensity to Type-2 allergic immune responses in the postnatal period. It has been proposed that this may be due to a relative deficiency of counter-regulatory Type 1 immune responses in early life. Thus, there is growing interest in factors that might affect Type 1 maturation in this early period. It has been proposed that progressively cleaner societies may have more allergies because there is less stimulation of the Type 1 responses during immune development. Bacterial products provide important maturation signals to the developing immune system, and may favour Type 1 responses. The largest early exposure to bacteria in occurs in the human gut, which is colonised with bacteria soon after birth. These bacteria play an important role in maintaining health, both in the protection from harmful bacteria, and in the development of food tolerance. There is evidence that infants in cleaner sociaeties may have alterations in bowel flora. For many years probiotic formulations (containing strains of these healthy bacteria) have been used safely to treat children with gastroenteritis to reduce the duration of diarrhoea. More recently it has been suggested that these formulations have a role in treating and even preventing allergic disease. Further research is needed to confirm this, and to define the underlying immunological processes. This randomised double blind control study will determine if supplementation with probiotic flora (in late pregnancy and in early infancy) can favourably influence gut colonisation, alter subsequent immune development, and help prevent allergic disease in infants at high risk (from allergic families).Read moreRead less
Role Of Maternal Dietary Omega3 Fatty Acids In Modulation Of Allergen-specific T Cell Responses In The Offspring
Funder
National Health and Medical Research Council
Funding Amount
$287,036.00
Summary
Environmental lifestyle changes are implicated in the concerning increase in allergic diseases such as asthma and allergic diseases over the 25 years. Despite the enormous personal, social and economic cost, the exact causes are not clear. Diet is one of the most important yet unstudied environmental exposures linked to the recent increase in both asthma and allergic disease. Authorities in this area have recommended diet as research priority in the search for allergy prevention strategies. Alle ....Environmental lifestyle changes are implicated in the concerning increase in allergic diseases such as asthma and allergic diseases over the 25 years. Despite the enormous personal, social and economic cost, the exact causes are not clear. Diet is one of the most important yet unstudied environmental exposures linked to the recent increase in both asthma and allergic disease. Authorities in this area have recommended diet as research priority in the search for allergy prevention strategies. Allergic diseases result from inappropriate inflammatory immune responses to protein substances such as dust mite (allergens), and it now evident that these patterns of immune responses are commonly initiated before birth. This study will address the influence of maternal diet in pregnancy on the developing human immune system, and how it contributes to the development of allergic immune responses in offspring. One of the most significant dietary changes associated with increasing urbanisation is the increasing intake of pro-inflammatory omega-6 fatty acids (which may promote allergic immune responses) and declining dietary levels of omega-3 fatty acids (which inhibit inflammatory immune responses). Omega-3 fatty acids have beneficial effects in many inflammatory diseases, and are important for healthy pregnancy. It is possible that maternal diets which are becoming increasingly deficient in omega-3 fatty acids may prime the fetus to respond more readily to allergens, and increase the risk of later allergic responses. This study will determine whether increasing dietary omega-3 fatty acids during pregnancy using fish oil supplements, can alter immune responses to house dust mite and other allergens at birth and later infancy. The findings will contribute to our understanding of the relationship between antenatal nutrition and immune development and may lead to dietary recommendations as a cost effective, non invasive strategy to help prevent allergic disease.Read moreRead less