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Immune responses

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Abstract

The indigenous bacterial microflora colonize the gut at birth and remain there throughout life. Approximately 1014 bacteria are present in the ileum and colon and they are clearly immunogenic. The evidence is strong that the vast majority of IgA plasma cells in normal human gut are responding to the antigens of the flora, and although the flora is also responsible for producing the large numbers of T cells which are present in the gut of healthy individuals, the types of T cell response which the flora elicits are less well understood. A major challenge for the immune system is to distinguish between the antigens of the flora and the antigens of pathogens. There is also a growing realization that the normal flora can also influence gene expression in antigen-presenting cells in the gut and so set the context in which T cells respond to food antigen and vaccines.

Section snippets

The evidence is strong in rodents that the normal bacterial flora elicits the development of the mucosal immune system

It is often stated that the gut immune system in healthy individuals is highly activated in response to food antigens, pathogens, and the normal flora, so-called physiological inflammation. This results in highly activated Peyer's patch lymphocytes, an abundance of CD8+ T cells in the epithelium, and CD4+T cells and IgA plasma cells in the lamina propria. However, the animal data are very clear that this response is elicited by the normal flora and not by pathogens or food antigens.

Mice that

Evidence for the role of the normal flora in the development of the human mucosal immune system

It is obviously not possible to render patients germ-free to study the effects of the gut flora on mucosal immunity, but important clues can be derived from studies on the mucosal immune system of new born babies because we are all born germ-free. During parturition, direct contact with the birth canal provides exposure to non-pathogenic commensal bacteria. After birth, the gut epithelium is exposed to novel antigens through a variety of sources. These antigens enter the gut directly from the

Functional interactions of the normal flora with the mucosal immune system

So far in this chapter we have concentrated on the normal commensal flora of the gut in terms of its antigenicity, that is, its ability to activate T and B cells and to elicit the large numbers of T and B cells in the gut. However, there is a less obvious but probably more important role for the flora, namely, as an immunomodulator. Bacteria contain large numbers of molecules with immunomodulatory activity. Eukaryotes have developed membrane receptors to allow them to recognize

Summary

We have emphasized the inherent immunogenicity of the normal bacterial flora which exists in the gut of mice and men. We show that the normal bacterial flora drives the large populations of T cells and B cells present in normal gut. As far as we know, IgA against normal flora plays no role, and it may be the price we pay for the ability to respond with a protective IgA response to a gut pathogen. For T cells, the situation is much less clear. While the flora drives the appearance of mucosal T

Acknowledgements

Karen Pickard is supported by the BBSRC, Ron Bremner by CICRA and John Gordon by an NHS R & D Training fellowship. The authors are grateful to Kirsteen Coombes for assistance in the preparation of the manuscript.

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