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M-Cells

M cells (or microfold cells) are cells found in the follicle-associated epithelium of the Peyer's patch. They transport organisms and particles from the gut lumen to immune cells across the epithelial barrier, and thus are important in stimulating mucosal immunity. Unlike their neighbouring cells, they have the unique ability to take up antigen from the lumen of the small intestine via endocytosis or phagocytosis, and then deliver it via transcytosis to dendritic cells (an antigen presenting cell) and lymphocytes (namely T cells) located in a unique pocket-like structure on their basolateral side. STRUCTURE OF M-CELLS AND THEIR FUNCTION M cells differ from normal enterocytes in that they lack microvilli on their apical surface, but instead possess broader microfolds that give the cell its name. These cells are also far less abundant than enterocytes. M cells are readily accessible for antigens in the gut lumen to travel through to the Peyer's patch because they do not secrete mucus or digestive enzymes and the filamentous brush border glycocalyx (an extracellular polysaccharide layer found throughout the intestine attached to enterocytes) is much thinner or absent on M cells

PATHOLOGY M cells are exploited by several pathogens, including Shigella flexneri, Salmonella typhimurium, and Yersinia pseudotuberculosis, as well as infectious prions in Bovine spongiform encephalitis (Mad-cow disease), as a way to penetrate the intestinal epithelium. EPEC containing plasmids with genes for EAF(E coli Adherence Factor)will adhere to M cells. They are also exploited by viruses such as Polio and Reovirus for dissemination. CXCR4 tropic but not CCR5 tropic HIV has been noted to be able to bind to M cells and get transported across the epithelium by them. A significant quantity of lymphoid tissue is associated with human mucosa.

Mucosa-associated lymphoid tissue (MALT) is scattered along mucosal linings, measuring roughly 400 m2 It is the most extensive component of human lymphoid tissue. These surfaces protect the body from an enormous quantity and variety of antigens. The tonsils, Peyer patches within the small intestine, and the vermiform appendix are examples of mucosa-associated lymphoid tissue (MALT). The nomenclature incorporates location; therefore, mucosa-associated lymphoid tissue (MALT) includes gut-associated lymphoid tissue (GALT), bronchial/tracheal-associated lymphoid tissue (BALT), nose-associated lymphoid tissue (NALT), and vulvovaginal-associated lymphoid tissue (VALT). Additional mucosa-associated lymphoid tissue (MALT) exists within the accessory organs of the digestive tract, predominantly the parotid gland. Mucosa-associated lymphoid tissue (MALT) may consist of a collection of lymphoid cells, or it may include small solitary lymph nodes.

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The role of the M cells


is absorption, transport, processing, and presentation of antigens to subepithelial lymphoid cells. These subepithelial cells include CD4+ type 1 T-helper cells (THCs) and IgD/IgM+ B lymphocytes, the latter of which are antigen-presenting cells (APCs) and function as memory cells interacting with type 1 THCs. Under these M cells and in close proximity, B lymphocytes, CD4+ T lymphocytes, and APCs are found, of which dendritic follicular cells (DFCs) are one type. Together, this group of cells constitutes a "pocket" of M cells. Within this pocket, an area of follicles associated with the epithelium (follicle-associated epithelium) is observed. These follicles, having true germinal centers, are similar to the follicles of the spleen and lymph nodes. The direct secretion of secretory IgA onto mucosal epithelia represents the major effector mechanism of mucosa-associated lymphoid tissue (MALT). Major accumulations of lymphoid tissue are found in the lamina propria of the intestine. M cells in the intestinal epithelium overlying Peyer patches allow transport of antigens to the lymphoid tissue beneath.

The complex interplay among antigens, cells, and cytokines results in a very efficient immune response. The efficiency of mucosa-associated lymphoid tissue (MALT) also depends on the adequate function of IgA. Individuals with selective IgA deficiency are prone to infections along mucosal surfaces in the respiratory, gastrointestinal, and genitourinary tracts. Adequate function of IgA depends on the production and acquisition of a joining (J) chain. This glycoprotein is produced by plasma cells and is important in the formation of IgA dimers and IgM pentamers. It has been shown that in children who have recurrent tonsillitis, B lymphocytes in tonsillar crypts do not produce the J chain. The J chain is key in permitting secretory IgA and IgM to function as the first line of defense in mucosal epithelium

Peyer's Patch
The gastrointestinal tract is a lymphoid organ. The number of lymphocytes in the GALT is roughly equivalent to those in the spleen, and, based on location, these cells are distributed in Peyer's patches

Peyer's patches: Location and appearance:


Peyer's patches are observable as elongated thickenings of the intestinal epithelium measuring a few centimeters in length. Microscopically, Peyers patches appear as oval or round lymphoid follicles (similar to lymph nodes). In adults, B lymphocytes are seen to predominate in the follicles' germinal centers. T lymphocytes are found in the zones between follicles.

In the image of above, three lymphoid follicles of a Peyer's patch can be seen. The muscularis is at the top left, and mucosal epithelium in the bottom right.

Function:
Peyer's patches establish their importance in the immune surveillance of the intestinal lumen and in facilitating the generation of the immune response within the mucosa. Pathogenic microorganisms and other antigens entering the intestinal tract encounter macrophages, dendritic cells, B-lymphocytes, and T-lymphocytes found in Peyer's patches and other Mucosa Associated Lymphatic Tissue (MALT). Peyer's patches are covered by a special epithelium that contains specialized cells called microfold cells (M cells) which sample antigen directly from the lumen and deliver it to antigen-presenting cells (located in a unique pocket-like structure on their basolateral side). B-cells and memory cells are stimulated upon encountering antigen in Peyer's patches. These cells then pass to the mesenteric lymph nodes where the immune response is amplified. Activated lymphocytes pass into the blood stream via the thoracic duct and travel to the gut where they carry out their final effector functions.