lecture 17- Allergy & Infections

lecture 17- Allergy & Infections - Asthma Asthma is...

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Asthma Asthma is a chronic disease of the lower respiratory tract, mainly affecting the lungs. It is due to an aberrant and uncontrolled immune response to inhaled allergens Asthma is usually diagnosed by the age of 5 Symptoms include shortness of breath, wheezing, coughing and reduced physical exertion. Involves an acute phase, known as an asthma attack However, the disease is chronic and progressive due to continual tissue damage and airway remodeling Besides removal of the antigen (when possible), there is no cure. Treatments include symptomatic controls, such as bronchodilators, steroids and epinephrine
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Induction of T-helper 1-like regulatory cells that express Foxp3 and protect against airway hyper-reactivity Stock et al, 2004, Nature Immunology What the authors knew when they began this study: Naturally occurring regulatory T cells (CD4+CD25+) can inhibit immune responses and pathology during experimental asthma Several distinct populations of regulatory T cells exist, and some of them are inducible from naïve T cells, called adaptive Tregs Heat-killed Listeria monocytogenes acts as an adjuvant to induce Th1 responses and also is able to prevent and reverse experimental asthma. However, the absence of inflammation suggests that these cells have anti-inflammatory properties Treatment of animals with a neutralizing anti-CD8 a antibody abolishes the protective effects of HKL Question: does HKL induce an adaptive Treg population by acting on regulatory CD8+ DCs?
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Figure 1 A. CD8 a DCs treated with OVA and HKL can transfer protective activity to naïve animals induced to develop airway hyper-reactivity (as shown by a reduction in lung constriction- peak enhanced pause) CD8 ab + T cells do not have the same protective activity when transferred to a recipient animal
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Figure 1 B. CD8 a DCs from IL-10-/- animals treated with OVA and HKL do not transfer protective activity to naïve animals induced to develop AHR C. CD8 a DCs from IL-12-/- animals treated with OVA and HKL do not transfer protective activity to naïve animals induced to develop AHR Both IL-10 and IL-12 produced by DCs are required for protection from experimental asthma
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Figure 2 A. OVA-specific T cells from animals that received CD8 a + DCs produce IL-10 when the donor animals were treated with OVA + HKL, but not OVA alone. These cells did not produce the Th2 cytokine IL-4, but did express the Th1 cytokine IFN g
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B. OVA-specific T cells from animals that received CD8 a + DCs produce IL-10 and IFN g when the donor animals were treated with OVA + HKL. The treatment did not induce the enhancement of IL-10+/IL-4+ T cells. The production of IL-10 and IFN
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This note was uploaded on 01/03/2012 for the course BI 144 taught by Professor List during the Fall '10 term at Caltech.