lecture 18 - the hygiene hypothesis and parasitic worms Flashcards
what do parasitic worms secrete?
Parasitic worms secrete bioactive molecules, which regulate or dampen down the immune system to ensure their survival for many years and also to reduce inflammatory responses, which can damage the host.
what happens in In chronic O. volvulus infection
atrophy of the skin may occur resulting in a “tissue paper” appearance.
what is the main cause of pathology in O. volvulus infection?
The main cause of pathology in O. volvulus infection, is the larval microfilaria stage, released by the adult female worm. These live in the skin or migrate into the eye, where they cause lesions such as sclerosing keratitis and ultimately blindness. Onchocerciasis is often called “River Blindness” because the larvae of the vector blackflies live in fast-flowing rivers.
what is the immune response during helminth or parasitic infection?
Classically helminths induce a Th2 response
Cytokines: IL-4, IL-5, IL-13 (decreased IFN-g) -
mainly derived from T cells (role for ILC2s)
- antibodies: IgE
Effector cells: mast cells, eosinophils
Helminths also induce an anti-inflammatory
response
Cytokines: IL-10, TGF-b; antibodies: IgG4
Effector cells: alternatively activated
macrophages; regulatory T cells (Tregs) and B
cells (Bregs)
Antigen-specific and non-specific lymphocyte
responses may be inhibited
what is cystatin and what is the effect associated and dependant on?
Cystatin is another helminth product, which can block Th2-dependent allergic lung disease in mice. Ovalbumin (OVA) is often used as a model allergen in mouse models of allergic lung disease.
Effect is associated with inhibition of eosinophil
recruitment, reduced specific and total IgE and down-
regulated IL-4
Effect dependent on macrophages and IL-10 induction
what’s the main method of action of es-62?
it blocks the th2 dependant lung disease
However, the main mechanism that ES-62 uses involves inducing a Th1 response (IFN-gamma is a Th1 cytokine), which directly antagonizes the Th2 response (Th1 and Th2 responses counter-regulate each other). ES-62 can also directly block mast cell activation in response to allergen cross-linking.ar
at does es-62 inhibit?
ES-62 inhibits allergic airway hyper-responsiveness
what are Secreted products of Heligmosomoides polygyrus and what do they target?
HpARI and HpBARI that target the IL-33 signalling pathway
what does HpARI do?
HpARI (alarmin release inhibitor): binds to IL-33 within necrotic cells preventing its release and thus blocking type 2 responses e.g. ILC2 and eosinophil responses to Alternaria antigen-induced asthma
what does HpBari do?
- HpBARI (binds alarmin receptor and inhibits): binds ST2 blocking interaction with IL-33, thus preventing IL-33-dependent responses relating to Alternaria-induced asthma
what are helminth therapies used with no therapeutic effect n allergic patients?
Trichuris suis (pig parasite) and Necator americanus (hookworm)
what are the helminth therapy reasons for failure?
Small studies, in some cases low patient number and low worm number (hookworm trials)
Timing of treatment versus onset of seasonal allergy
Mouse models generally try to prevent allergy developing rather than treating already established allergic disease
Location of parasite may not induce systemic response
