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Immune regulation in the gut

26 April 2013

SCOPE 50

Our gut is our most important immunological organ.

The gut mucosa contains more immune cells than all other organs of the immune system combined. It is capable of driving powerful immune responses against invading viruses and bacteria, while protecting the harmless gut microbiota that we need for good digestion.

When the gut barrier becomes permeable, by way of lifestyle or for genetic reasons, the internal contents of the gut can start to leak into the bloodstream. Since these components do not belong outside of the gut, the immune system views them as a threat and attacks them. It is these misdirected immune responses against gut bacteria and food proteins that are thought to contribute to the development of several inflammatory diseases including inflammatory bowel disease and food allergy.

Malaghan Institute gastrointestinal allergy and inflammation specialist Dr Elizabeth Forbes-Blom believes that management of the gut immune response is key to a healthy gut. She is using experimental models of gut inflammation to address the emerging hypothesis that immune dysfunction in the gut leads to altered microbiota, inflammatory bowel disease, food allergy and metabolic syndrome.

Taken together these findings will provide therapeutic targets for the prevention and treatment of gut allergy and inflammation.

 

What is the link with jawed fish?

Scientists now believe the evolution of our highly specialised ‘adaptive’ arm of the immune system (this is the form of immunity that develops throughout life) is linked intrinsically with the gut.

Approximately 450 million years ago primitive jawed fish evolved by forming gill supports into the hinged jaw. This enabled the fish to capture and eat larger prey. The ‘jaw hypothesis’ suggests that the adaptive immune system evolved in the gut regions of these primitive fish to help fight infections resulting from injuries caused by their newfound ability to chew bones and scales.

Described as the biological equivalent of the ’Big Bang’, the evolution of adaptive immunity appears to have been made possible by the invasion of a putative immunoglobulin-like gene in the fish, by a gene from bacteria. This conferred on the ancestral gene the ability to rearrange itself and generate different immunoglobulin-like molecules – thus increasing the ‘weaponry’ available to the fish to fight infection.

 

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