Lecture 18: The hygiene hypothesis: parasitic worms and protection against asthma?

Question 1

What do parasitic worms (helminths) cause?

Answer 1

• Intestinal manifestasions
• General weakness
• Impaired cognitive and physical development
• Uncontrolled inflammation leading to elaphantiasis

Question 2

What are the symptoms of parasitic worm infections?

Answer 2

None or mild symptoms

Question 3

How do parasitic worms affect the immune system?

Answer 3

Parasitic worms secrete bioactive molecules, which regulate or dampen down the immune system to ensure their survival for many years and also to reduce inflmmatory responses, which can damage the host

Question 4

Describe adult hookworms

Answer 4

The worms are about 1cm in length and are attached to the villi of the small intestine

Question 5

What is the main cause of O. volvulus infection?

Answer 5

The larval microfilaria stage released by the adult female worm.

Question 6

Where do the adult female worm live?

Answer 6

These live in the skin or migrate into the eye

Question 7

What do adult female worms cause in the eye?

Answer 7

• Lesions such as sclerosing keratitis
• Blindness

Question 8

What is onchocerciasis often called?

Answer 8

River blindness because the larvae of the vector blackflies live in fast flowing rivers

Question 9

What do Schistosoma mansoni cause?

Answer 9

Schistosomiasis

Question 10

What is schistosomiasis?

Answer 10

• One of the most dangerous paristic worm infections
• The combination of enlarged, irregularly fibrosed liver and greatly enlarged spleen is commonly called “Egyptian hepatosplenomegaly”.

Question 11

What is a major cause of pathology in schistosomiasis?

Answer 11

Eggs released by adult female worms that may lodge ectopically in any tissues, where they cause characteristic granulomas.

Question 12

What is adult taenia saginata?

Answer 12

Beef tapeworm - can reach 10m in length

Question 13

What is adult taenia saginata?

Answer 13

Beef tapeworm - can reach 10m in length

Question 14

What response do helminths induce?

Answer 14

• Th2 response
• Anti inflmmatory response

Question 15

What is the Th2 response induced by helminths characterized by?

Answer 15

-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

Question 16

What is the anti-inflammatory response induced by helminths characterized by?

Answer 16

• 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

Question 17

What does filarial nematode cystatin do?

Answer 17

Suppresses Th2-related inflammation and associated asthma in OVA-induced allergic airway responsiveness model. Effect is associated with inhibition of eosinophil recruitment, reduced specific and total IgE and down regulated IL-4. The effect is dependent on macrophages and IL 10 induction

Question 18

What is cystatin?

Answer 18

Helminth product, which can block Th2-dependent allergic lung disease in mice

Question 19

What is OVA?

Answer 19

Ovalbumin (OVA) is often used as a model allergen in mouse models of allergic lung disease.

Question 20

What does ES62 do?

Answer 20

inhibits allergic airway hyper-responsiveness

Question 21

What is the effect of subcutaneous ES62

Answer 21

Sensitisation and challenge with OVA induces lung pathology in mice but this is greatly reduced

Question 22

What is the main mechanism involved in ES62?

Answer 22

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.

Question 23

What are HpARI and HpBARI?

Answer 23

Secreted products of Heligmosomoides polygyrus that target the IL-33 signalling pathway

Question 24

How does HpARI work?

Answer 24

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

Question 25

How does HpBARI work?

Answer 25

(binds alarmin receptor and inhibits): binds ST2 blocking interaction with IL-33, thus preventing IL-33-dependent responses relating to Alternaria-induced asthma.

Question 26

What are the reasons for helminth therapy failure?

Answer 26

• 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