Immunoglobulin A

From the following article:

Do symbiotic bacteria subvert host immunity?

Lora V. Hooper

Nature Reviews Microbiology 7, 367-374 (May 2009)

doi:10.1038/nrmicro2114

Immunoglobulin A (IgA) makes up 75% of the total immunoglobulin produced in the body, and most IgA is secreted across intestinal epithelia71. Humans produce a tremendous amount of intestinal IgA, secreting approximately 3 grams per day39. IgA is therefore a key element of the mucosal adaptive immune system, and is a central mechanism by which intestinal bacteria are compartmentalized on the luminal side of the epithelial barrier.

IgA specific for intestinal bacteria is produced with the help of dendritic cells. Dendritic cells located beneath the epithelial dome of specialized intestinal lymphoid structures, called Peyer's patches, sample the small numbers of bacteria that penetrate the overlying epithelium. These bacteria-laden dendritic cells interact with B and T cells in the Peyer's patches to induce B cells to produce IgA that is specific for intestinal bacteria38. IgA+ B cells home to the intestinal lamina propria and secrete IgA that is taken up by intestinal epithelial cells and transcytosed to the apical surface. The transcytosed IgA binds to luminal bacteria and prevents their translocation across the epithelial barrier. There is also evidence that IgA is important for reducing the densities of surface-associated bacterial populations72. Thus, production of specific IgA against surface-associated bacteria functions as a negative feedback mechanism that maintains compartmentalization of the microbiota by limiting bacterial access to and penetration of the epithelial surface. The mechanisms by which IgA confines bacteria to the lumen probably include trapping of bacteria in the mucus layer39, recruitment of complement with subsequent bacterial killing40, and promotion of phagocytosis of bacteria that breach the epithelial barrier41.

Dendritic cells that reside in the intestinal lamina propria may also participate in this negative feedback loop. Lamina propria dendritic cells express tight junction proteins, allowing them to extend their dendrites between epithelial cells to sample live bacteria on the apical surface42. These cells then carry their live bacterial cargo to mesenteric lymph nodes (specialized lymphoid structures that are attached to the intestinal wall), where they induce B cells to produce bacteria-specific IgA38. Lamina propria dendritic cells may therefore function specifically to sample bacteria that penetrate the mucus layer and enter the protected zone at the apical epithelial surface, inducing protective IgA responses that limit these mucosa-associated populations.