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| Project
4: Role of Chitin and Aspergillus fumigatus in chronic airway disease In the last 25 years, asthma and autoimmune diseases have increased in the industrialized world. The “hygiene hypothesis” relates this increase to a failure of proper microbial stimulation of the immune system due to increased sanitary conditions early in life. Scarlet Fever, caused by the Streptococcus pyogenes bacterium, is inversely correlated with asthma. S. pyogenes induces large amounts of antibody to cell wall-associated N-acetyl glucosamine (GlcNAc), which is also the major component of chitin, a component of many allergen-bearing organisms. We will study the link between innate and adaptive immunity and asthma induced by environmental allergens containing GlcNAc and other conserved carbohydrates. We will quantitate the specificity, clonality, airway association and longevity of the antibody response to S. pyogenes, chitin and Aspergillus fumigatus. We will determine the role of B cells and antibody in modifying innate cell functions and activation of CD4 T cells involved in the chronic inflammatory process and airway obstruction of asthma. Apart from the established paradigm involving the shift in TH1/Th2 functionality and the important but not definitive role of IgE in asthma, B cell and antibody functions in the disease have not been extensively studied. By focusing on the role of B cells and antibodies, we may shed light on the mechanisms involved in the developmental induction of allergic asthma and treatment of established disease. |
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| Fig 1. Reactivity
of monoclonal antibodies (Mabs) with A.f. The photomicrographs show
that Mabs raised against bacterial antigens also bind to conidia and
hyphae of A.f. Methods: A.f. conidia on poly-L-lysine coated slides
were incubated for 9 hrs in 10% fetal calf serum and RPMI 1640 medium
at 37C. After fixing in 95% ethanol for 30 min they were stained with
Mabs to alpha-1-3 glucan (green), sialyllacto-N-tetraose (red), GlcNAc
(blue) (left). Phase contrast of the same field with arrows showing the
swollen conidia with growing hyphae (right). |