Intricate immune interactions maintain health
7 March 2008
The immune system’s ability to recognise the difference between a harmless fragment of the body’s own tissue and piece of a threatening virus or bacterium is the key to healthy immune reactions. Fail to identify a threat and infection can rage unchecked. Label a piece of self-tissue as dangerous and the body begins to attack itself.
Now, research led by Dr Alexander Betz at the MRC Laboratory of Molecular Biology has discovered a mechanism by which immune system cells achieve a healthy balance when there are no danger signals present. It’s all down to interactions between immune system cells called T cells and those presenting potential fragments of danger.
The results could help to explain why the immune system can launch an attack on part of the body’s own tissue (autoimmune disease) if an adjuvant, something else that kick starts the immune system, is present. It might also explain why infections increase the risk of miscarriage if a woman is pregnant; the presence of bacteria or a virus could act as an adjuvant and prompt the immune system to attack the foetus it previously ignored.
Three types of T cells are involved in ongoing monitoring of the internal body environment. Regulatory T cells keep the immune system in check to prevent it overreacting when no danger is present. Helper T cells prompt activity of the immune cells that produce antibodies and those that destroy infected cells labelled as dangerous.
Patrolling immune system cells called dendritic cells constantly pick up bits of other cells they have found in body tissues, these fragments are called antigens. The dendritic cells carry antigen to the lymph nodes and spleen where the helper and regulatory T cells sift through them. T cells carry receptors that recognize antigens presented by these dendritic cells. Until a T cell has met its antigen match it is described as ‘naïve’. Once it encounters the matching antigen it becomes activated. Both helper T cells and regulatory T cells require such activation in order to perform their specialized functions.
Dr Betz’s team has found that when there are no signals for inflammation or other alerts to the immune system present, regulatory T cells and naïve helper T cells interact with dendritic cells differently. Regulatory T cells appear to have an advantage as they can spend longer checking the antigen that is presented by the dendritic cell than helper T cells.
Further investigation revealed that these longer interactions are due to the presence of a protein on the regulatory T cells that the helper T cells lack, called neuropilin-1.
The presence of the neuropilin-1 protein on the surface of a regulatory T cell appears to give it an advantage over helper T cells that match to the same antigen.
This leads to a default suppression of immune responses in the absence of ‘danger signals’ and so may prevent the body from attacking itself or in the case of pregnancy, the foetus.
Dr Betz explains:
“It appears that in the absence of ‘danger signals’ regulatory T cells have the upper hand over helper T cells. By expressing neuropilin-1 they can scan dendritic cells for a little longer, which in turn makes them more sensitive to the antigens presented to them. In a scenario in which both helper T cells and regulatory T cells recognise the same antigen, the regulatory T cells win. In the presence of ‘danger signals’ however this advantage is lost.”
Future research will investigate how neuropilin-1 prolongs the interactions between regulatory T cells and dendritic cells and what other molecules it needs to cooperate with to achieve the longer interaction.
‘‘It would be interesting to investigate other scenarios of cell-cell interactions in the immune system and how they may regulate the initiation or progression of immune responses.’’ Dr Betz concludes.
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