Factors contributing to development of tolerance

Genetic background

There are a number of factors which influence development of tolerance. Genetic background is an important factor. Atopy, defined as the genetic tendency to respond with IgE to exogenous proteins, is strongly associated with allergic symptoms. The risk of developing allergic disorders increases in children born to families with atopy. It is, however, unclear whether genetic differences in antigen clearance are associated with the capacity to induce oral tolerance.

Dose of antigen

Most of our knowledge in this area has originated from animal studies. Dose-response studies with rodent models have shown that the low-IgE responder phenotype develop specific tolerance in response to inhalation of nanograms of antigen, whereas high-IgE responders require much higher doses for tolerance.25 Ultimately, it may be that a person's sensitivity ot tolerance is governed by their genetic background.

Time of exposure

What happens when we encounter an antigen for the very first time has an important impact on what the outcome may be, i.e. whether we are sensitised or tolerised. We encounter most antigens early in life, during infancy, and as it happens this is the period when tolerance development is impaired. In fact, this delayed post-natal maturation of tolerance has been suggested as the reason for the increased frequency of allergic symptoms in infancy.26 So it appears that there is an immunological vulnerable period, perhaps due to the inability of the immature immune system to induce tolerance. Clearly, this is an exciting area and only further research will elucidate the current ambiguity.

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