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Hypersensitivity, immunity and Haemonchus contortus in sheep
thesisposted on 2017-03-02, 23:04 authored by Azam, MD Shakif-Ul
GIN parasite infections are a major disease problem in small ruminants. Haemonchus contortus is one of the most economically important GIN parasites causing global production losses. Anthelmintic drugs are the commonly used control method for most parasitic infections. However, development of widespread resistance to most current anthelmintics suggests alternative controls are needed. Such strategies may include breeding parasite-resistant sheep and the development of effective vaccines. Currently these approaches are limited due to deficits in our understanding of host-parasite relationships. In this thesis research is described which examined the potential role of cutaneous hypersensitivity reactions to measure and better understand the complexity of the sheep immune response to H. contortus. The first question focused on whether cutaneous hypersensitivity reactions to intradermal injections using distinct antigens (allergens and bacterial antigens) could predict worm resistance or susceptibility in sheep with known genetic worm resistance status. Hypersensitivity reactions were observed to various antigens but their use as a predictive tool for natural resistance in this cohort of sheep appeared limited as there was no correlation with parasitological values. The second aim was to quantify immunological responsiveness to different adjuvants and identify the T1 and T2 pathways contributing to their suitability for use with parasite vaccines. This study found that the putative T2 adjuvant DEAE showed persistence and significant correlations with faecal egg counts (FEC) and various immune parameters. The third aim was to determine whether an efficacious adult sheep vaccine could induce protection in young sheep and determine the immune correlates of the lamb response. This study showed that young vaccinated sheep had significant type 2 parasite specific post-vaccination and post-infection hypersensitivity reactions. A lack of a key immune cell in parasite resistance development, the eosinophil response, was inadequate in comparison to adult vaccine experiments suggesting an inability of young sheep to recruit eosinophils, which may play a role in loss of protective efficacy. In conclusion, these studies have demonstrated that cutaneous hypersensitivity responses with relevant antigens are an effective method of studying the inflammatory response against worm infection. They also allowed analysis of the inflammatory effects of adjuvants but were of limited value as a predictive tool for genetic resistance. Thus, it is suggested that further studies relating dermal hypersensitivity reactions to host-parasite responses may lead to a better understanding of host-parasite interactions and provide useful and easily measured markers to identify specific immune reactions in vaccinated and infected animals.