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Role of dendritic cells in integrating immune responses to luminal antigens
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Brian L. Kelsall, Maria Rescigno
Luminal antigens, including macromolecules, bacteria, and viruses, gain access to PPs and ILFs through specialized epithelial cells called M (microfold) cells in the follicle-associated epithelium (FAE) (see Chapter 15). cDC2 cells are present in the subepithelial dome (SED), the region just below the FAE, together with two populations that do not express F4/80 or CD64, normally present on mouse macrophages. One population expresses high levels of CD11b and MHC II, has a rapid turnover, is located just beneath the FAE, and can extend dendrites into the intestinal lumen through M cell–specific transcellular pores. Called “LysoDCs” because of their ability to present antigens to naïve T cells, these cells present antigen at much lower efficiency than cDCs. Another population of macrophages expresses low levels of CD11b and MHC II and does not present antigens to naïve T cells, similar to other macrophage populations. The expression of high levels of lysozyme by both LysoDCs and T-cell immunoglobulin mucin receptor 4 (Tim-4)− macrophages suggests that these cells have a role in innate defense against incoming microbes.
Cells and Organs of the Immune System
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
In addition to epithelium, lymphocytes, reticular cells, and macrophages, MALT contains specialized cells called microfold cells (M cells). These cells take up antigen at their luminal (apical) surfaces via endocytosis and pinocytosis. The vesicles are then transported through the cytoplasm to the basal surface where they are released. Thus, macromolecules are transported directly from the gut lumen to underlying lymphoid tissue. This process may be important both in initiating immune responses, and infection (some pathogens may exploit the system to traverse the epithelial barrier).
Peyer’s Patch Epithelium
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
Gary R. Burleson, Florence G. Burleson
Specialized epithelial cells designated membranous or microfold cells (M cells) provide access to Peyer’s patches (Figure 9.4). Antigen attaches and enters M cells that contain a specialized epithelium and are located above the lymphoid follicles. M cells continuously transport intestinal bacteria and antigens from the lumen into lymphoid tissues (Kanoi, 1991). These specialized M cells in the follicle-associated epithelium (FAE) sample foreign material and deliver it to the organized mucosal lymphoid tissue. The purpose is to initiate the specific immune response. While induction of the immune response occurs in M cells of the Peyer’s patches, the effector region is the lamina propria.
Recent strategies driving oral biologic administration
Published in Expert Review of Vaccines, 2021
Badriyah Shadid Alotaibi, Manal Buabeid, Nihal Abdalla Ibrahim, Zelal Jaber Kharaba, Munazza Ijaz, Ghulam Murtaza
All approved and most of the investigational oral vaccines target the small intestine [3,4]. Several studies have described the characterization of the colonic mucosal immune system [43]. Colon is traditionally believed an ideal target site for the delivery of oral vaccines. Colonic mucosa is different from the oral and stomach lining because it can identify foreign antigens and present them to the immune system [43]. Intestinal mucosa contains several inductor sites, collectively known as gut-associated lymphoid tissues (GALT). One leading example of GALT is the Peyer’s patch, which comprises the properly arranged and characteristic immune cells under the follicle-associated epithelium. Microfold cells (M cells) of this epithelium identify and assist the migration of antigens and pathogens into the Peyer patch. These M cells exhibit diverse receptors of the incoming antigens, such as pattern recognition receptors (PRRs) [44]. These PRRs are present on the apical side of M cells [43].
Gut microbiota: what is its place in pharmacology?
Published in Expert Review of Clinical Pharmacology, 2019
Aleksandra Tarasiuk, Jakub Fichna
In the stomach, which is lined with a single layer of squamous epithelium, its cells are responsible for the secretion of hydrochloric acid, digestive enzymes, and mucus. In the small intestine, a thick type of epithelium is present – single-layer cubic or columnar, constituting a natural protective barrier. It performs both secretory and transport functions, related to the absorption of many substances. The epithelial surface in the small intestine is characterized by the presence of numerous cavities and folds, formed by glands, crypts, and villi, which is an expression of the adaptation of this part of the GI tract to the function performed. The epithelium of the intestinal villi consists of capillary epithelial cells. It is formed by single tentacles, so-called microvilli that also increase its surface. Under the epithelium of the villi, in the middle of the lamina propria, a network of lymph vessels is located. Enterocytes are alternated with intestinal goblet cells secreting mucus. The core of the intestinal villi consists of cylindrical, straight cavities that extend to the muscular layer but are not penetrating. At the bottom of the crypts there are stem cells, and above them, Paneth cells, secreting antibacterial lysozyme. The epithelium located above the lymphoid cells of the intestine, in which Peyer’s patches are present, is a characteristic area of the intestine due to the microcavities and microfold cells located there. The main role of these cells is both the recovery of shortened or irregular villi or pits, as well as the transport of microorganisms from the intestinal lumen to deeper epithelial layers.
Subunit-based mucosal vaccine delivery systems for pulmonary delivery - Are they feasible?
Published in Drug Development and Industrial Pharmacy, 2019
Nirmal Marasini, Lisa M. Kaminskas
Particle surface charge is an important aspect of antigen presentation as it determines the degree of association the particles have with anionic cell membranes. Highly cationic particles may not be ideal for parenteral vaccination due to the high likelihood of cellular toxicity. However, owing to the presence of mucus in the respiratory compartment, cationic particles are considered safer when immunization is given via the pulmonary epithelium. Cationic particles interact with the anionic epithelium or mucus in the respiratory tract, rendering them mucoadhesive properties. This then prolongs antigen uptake by microfold cells (M-cells) or APCs. Cationic liposomes are usually preferred over anionic and neutral liposomes, as they produce higher levels of antigen-specific humoral immune responses [72]. For instance, immune responses from cationic lipids were shown to correlate with lipid chemical structure [73]. Regardless of the differences in the particle size of cationic liposomes (50, 100 and 1000 nm), even a simple physical mixture of cationic liposomes with protein antigens showed an adjuvant effect [72, 74]. Therefore, as long as particles are cationic, size may not be the determining factor influencing the immune response. Mechanisms by which cationic liposomes show enhanced immunity though, are largely unknown. However, several reasons have been suggested for their adjuvant effect, including long-term retention of antigens at administration sites, prolonged availability of antigens to APCs (depot effect) and enhanced uptake by APCs.