Flashcards in 13. Mucosal Immune System Deck (71)
the mucosal immune system is divided into two distinct sites, inductive sites and effector sites - explain?
1. inductive sites for mucosal immunity (ie where immune response are induced) = organized mucosa-associated lymphoid Tissue (MALT)
2. effector sites (ie whre the immune system acts against a pathogen) are the mucosal epithelia and underlying lamina propria
what are the 2 genera (overarching)l functions of the mucosal immune system? (hint: think about the bacteria/pathogens in the gut)
1. first line of defense against microbial pathogens (induction, amplification of local immune responses; preserve intestingal barrier, prevent organisms from entering into circulation)
2. tolerance: prevent undesired host reaction vs food and commensals (IMMUNE REGULATION)
the mucosal immune system containst ___-% of all lymphocytes?
70% and produces the largest amount of immunoglobulins
what are 4 distinct features of the mucosal immune system compared to the systemic immune system?
1. intimate association with epithelial cells
2. defined (ILF and PP = isolated lymphoid follicles and peyer's patches) and diffuse lymphoid structures
3. secretory antibodies
4. unique regulatory mechanisms
what are the mucosal secondary lymphoid tissues?
peyer's patches (GALT), appendix, tonsils and adenoids (NALT) and mesenteric lymph nodes
the GI tract's first line of protection is what?
mucus that covers the epithelial cells
what is the major immune compartment?
the mucosal compartment (60-70% of total lymphocytes in the body)
what are the 2 major effector cells of the mucosal immmune system?
plasma cells and CD4 Th2 cells
(M = microfold or membranous) - specialized epithelial cells lacking microvilli They are located selectively over lymphoid tissue and have a major role in transport of substances between the mucosal lumen and underlying lymphoid tissue. They are responsible for ~90% of uptake of larger, antigenic substances (both soluble and particulate) from lumen, the remainder is done by absorptive epithelia
located near the base of the crypts adjacent to or surrounding the multipotent stem cells. They represent a relatively stable cell population in the intestine and exhibit a secretory phenotype, releasing anti-microbial peptides such as defensins.
secrete mucins and epithelial cell-protective peptides and are scattered among absorptive epithelial cells of the villus associated epithelium
connective tissue region that underlies the epithelium. The lamina propria includes abundant numbers of lymphoid and myeloid cells and is considered an immune effector site.
lymphoid tissue embedded in the lamina propria is in which region?
follicle associated epithelium
develops only over lymphoid tissue, such as a Peyer’s patch. The FAE does not contain mucus-secreting goblet cells, but it does contain M cells. The M cell microfolds are readily observed microscopically due to the relatively sparse distribution of mucus over the apical surface of these cells.
the overlaying mucous layer of the GI tract has a viscous, gel-like consistency, due to the presence of what?
mucins - long, fibrous peptides decorated with oligosaccharides. The precise biochemical composition of mucus is specific to each site, due to variations in the locally synthesized peptides and oligosaccharides
A ______ region lies under the mucous layer of the GI tract, but over the microvilli of epithelial cells.
glycocalyx region - a dense layer of glycoproteins, comprised in part of mucins that remain anchored in epithelial cell membranes (the epithelial cell microvilli extend into an aqueous region below the glycocalyx)
how does Shigella work?
taken up by M cells and infects underlying macrophages causing apoptosis. Bacteria released from apoptotic macrophages can infect epithelial cells from the basolateral side and spread through the epithelial cell barrier.
isolated lymphoid follicles (ILF) are present throughout the intestine. What do they contain? When are they induced?
They contain germinal centers but few T cells and no distinct T cell-zones. They are induced after birth by the colonizing microflora –which is then controlled by the IEL (intraepithelial lymphocytes).
peyer's patches - where are they present (ie which part of GI tract), what do they consist of?
present in the small intestine. They consist of B follicles with germinal centers.
how are PP and ILF connected to the lymphatics?
draining mesenteric lymph nodes
development of PP depend on the presence of what?
the presence of lymphoid tissue inducer cells which produce Lta and Ltb and stromal cells, which secrete IL-7
outer vs inner mucus layer?
outer: non sterile, microbes
inner: relatively sterile, rich in antimicrobials, antibodies
what are the epithelial cell-derived antimicrobial proteins of the mucosal immune system? (think innate function of mucosal immune system)
defensins, cathelicidins, C-type lectins
intestinal epithelial stem cell
crypt intestinal epithelial stem cell niche contains epithelial, stromal and haematopoietic cells, controls continuous renewal of epithelial cells. Differentiated IEC (except paneth cells) migrate up the crypt-villus axis
Action of M cells?
are actively pinocytotic, and much of what they take up is transported to the underlying lymphoid area. Once transported through the M cell, these substances become directly available to existing dendritic cells and macrophages, some of which are present just below the surface of the invaginated, basal-lateral pocket of the M cell
DC action re: gut epithelia (physical action of DCs as it corresponds to gut epithelium)
a specialized subset of dendritic cells (DCs) that can extend their dendrites through the epithelial cell tight junctions into the lumen of the corresponding tract. The antigen-laden dendrites of the DCs cells can then return their load directly into the lymphoid area, where the constitutive proteins and peptides can be presented to lymphocytes.
peyer's patches compared to lymph nodes and the spleen
in contrast to peripheral lymph nodes, B cells predominate in Peyer’s patches as in the spleen. However, unlike the spleen where B cells are rich source of IgG, the Peyer’s patches represent a major source of B cells programmed to secrete IgA in the intestine.
Also, in contrast to peripheral lymph nodes, Peyer’s patches and other mucosal lymphoid tissues have no afferent lymphatic and no outer capsule. Instead, such sites represent aggregates of lymphocytes, dendritic cells and macrophages that are organized into follicular and interfollicular regions--essentially B cell and T cell zones, respectively--and embedded in the lamina propria.
what is the major lymphocyte population in the lamina propria?
B cells, most secrete IgA
what are three functions of the epithelial cells of the gut (and mucosal immunity) besides the barrier function?
1. production of cytokines/chemokines (anti and pro-inflammatory/to attract lymphocytes and DC) to provide signals to the underlying mucosal cells
2. express MHC I and II and can present Ags to CD4 T cells
3. transport of polymeric IgA