The key cells and molecules involved in the allergic immune response. The numbers indicate steps within the allergic pathway that our scientists are currently investigating. Image courtesy of Dr Lisa Connor and Dr Elizabeth Forbes-Blom.

Scope 49 - Halting the ‘allergic march’

02 November 2012, Asthma

The key cells and molecules involved in the allergic immune response. The numbers indicate steps within the allergic pathway that our scientists are currently investigating. Image courtesy of Dr Lisa Connor and Dr Elizabeth Forbes-Blom.

Numerous studies have shown that childhood allergic diseases can progress from one form to another throughout a child’s life – a phenomenon termed the ‘allergic march’.

Eczema is usually the first sign of allergic disease in young infants and is often associated with an underlying food allergy. As children outgrow their food allergies they are likely to go on to develop asthma. Then as their asthma improves, they can be affected by hay fever in their teenage years.

Scientists now believe that prevention of allergic disease early in life is critical, to halt progression along the allergic march. Since allergic disease is immune-mediated, the most obvious target for new therapies is the earliest stages of the allergic Th2 immune response.

The Th2 immune response normally functions to protect us from parasitic worm infections. Why it reacts to house dust mites or food proteins (referred to as allergens) in some children is unclear. What we do know however, is that a child doesn’t just suddenly become allergic – their immune system has to have seen the allergens beforehand and become sensitised to them.

Specialised immune cells called dendritic cells (DC) play a central role in this early sensitisation process (see diagram). They are present in tissues such as the skin, nose, lungs and gut, so are one of the first cell types to encounter potential allergens. The dendritic cells respond to the allergens by activating naïve T cells to Th2 cells, though surprisingly little is known about the mechanisms involved. This triggers a cascade of events - including IgE antibody production and release of histamine from mast cells – that cause the itching, swelling and wheezing we associate with allergy.

By unlocking the secrets of the allergic switch that signals the early development of allergy, our scientists are revealling key targets for therapies aimed at halting its progression.

 

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