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
Trigeminal pain includes such disorders as headache, migraine, trigeminal neuralgia, dental and temporomandibular joint pain. These disorders affect more than 10 % of the population and many of the afflicted get only partial relief from current treatments. Trigeminal pain is conveyed from the head to the brain via primary afferent nerves. Work in the current proposal focuses on transmission of information in the brainstem as well as in the primary afferent nerves. Previously our group has report ....Trigeminal pain includes such disorders as headache, migraine, trigeminal neuralgia, dental and temporomandibular joint pain. These disorders affect more than 10 % of the population and many of the afflicted get only partial relief from current treatments. Trigeminal pain is conveyed from the head to the brain via primary afferent nerves. Work in the current proposal focuses on transmission of information in the brainstem as well as in the primary afferent nerves. Previously our group has reported that adenosine- 5' triphosphate (ATP) causes an increase in excitatory neurotransmission from primary afferent nerves; such an increase has been reported to be painful in previous human and animal studies. Recently we have shown that the ATP induced increase in neurotransmission is dependant on activation of a specific excitatory receptor, the N-methyl D aspartate (NMDA) receptor, which has been widely implicated in other brain functions such as memory, and in disorders such as neuron death following stroke. The chief investigators involved in this application plan to study the role of the ATP receptor and the interaction with NMDA receptors in an inflammatory trigeminal pain model. Electrophysiological, pharmacological and immunohistochemical studies will be performed in order to address the aims of this proposal. A greater understanding of how these receptors modulate neurotransmission in pain pathways will lead to a greater understanding of trigeminal pain and the potential development of new therapeutics.Read moreRead less
The main purpose of this study is to understand how airborne fungi affect asthmatics who are allergic to them. Fungi or moulds release large numbers of spores into the air that are inhaled. In many cases fungal spores outnumber other particles that carry allergen, such as pollens or cat dander, by 100 to 1. This makes fungi the most common potential allergen in the environment. Fungi have been associated with respiratory diseases including fungal sinusitis, asthma, rhinitis, allergic alveolitis ....The main purpose of this study is to understand how airborne fungi affect asthmatics who are allergic to them. Fungi or moulds release large numbers of spores into the air that are inhaled. In many cases fungal spores outnumber other particles that carry allergen, such as pollens or cat dander, by 100 to 1. This makes fungi the most common potential allergen in the environment. Fungi have been associated with respiratory diseases including fungal sinusitis, asthma, rhinitis, allergic alveolitis and sick building syndrome. Largely due to their diversity and complexity, allergenic fungi have not been well studied and the ways in which individuals vary when inhaling spores is not known. Unlike other allergenic particles, it is unlikely that fungal spores release their allergen as soon as they are inhaled because we have shown in earlier in vitro studies that fungi continue to release allergen over time and this is likely to be the case when they are inhaled. Our laboratory has developed two new techniques that allow us to measure how many spores people inhale and whether they are allergic to them. This study will use these tools to detect and identify the important allergenic fungi involved in domestic and outdoor exposure of asthmatics, the degree of contribution to the total allergen load to which subjects are exposed and identify in what conditions fungi are the causal agents in location-specific symptoms. This study will also investigate allergen production of fungi in situ in the human nose, which will have application in allergic sinusitis and asthma amongst other respiratory diseases. We will investigate how readily allergenic spores germinate in the nose and under what conditions they release allergen.Read moreRead less
Bio-molecular Studies For Improved Diagnosis And Management Of Australian Children With Fish Allergy
Funder
National Health and Medical Research Council
Funding Amount
$496,602.00
Summary
Allergy to fish among children is often life-long and emerging as a significant healthcare issue worldwide, while management of fish allergy is challenging due to the lack of reliable diagnostic assays. This research grant will lead to the development of novel diagnostics for fish allergy in Australia, addressing aspects of the worldwide food allergy epidemic and forms the ideal platform for the study of fish specific allergens, generating novel knowledge for greatly improved patient management.