Armando Hasandungan Biology and Medicine Videos, please make sure to subscribe, join the forum and group for the latest videos please visit Facebook ArmandoHasudungan please like, and here you can also ask questions, answer questions and post some interesting things including your artworks you can also change the quality settings to the highest one for better graphics in this video we'll look at the mucosal immune system of the gut (so the intestinal tract) before continuing on, if you haven't watched [uh] the overview of the mucosal immune system, I suggest you watch that first before watching this. So we begin by learning about the mucosal immune system of the gut by firstly learning about the mesenteric lymph nodes. Mesenteric lymph nodes are like any other lymph nodes in that they contain arteries and veins coming out of them and they also have lymph vessels coming in and out of them which connects to the surrounding intestinal tissues (the submucosas) Mesenteric lymph nodes are important to initiate an immune response. particularly an adaptive immune response Mesenteric lymph nodes, like the normal lymph nodes, contain lymphocytes naïve lymphocytes or inactivated lymphocytes they contain naïve CD8 and CD4 T cells there are areas in the lymph node known as follicles where naïve B cells reside these naïve B cells typically express IgM and sometimes IgD antibodies the mesenteric lymph nodes connect with areas around the gastrointestinal tract here we have the lymph vessel connecting to the regions around the body especially to regions below the mucosal surface of the gut because we are talking about the gut mucosal immune system these are the mucosal surface cells, the epithelial cells, and they form crypts, and they also contain villi which are important for food absorption. therefore, this area up here is known as the intestinal lumen because the lumen is where the food passes through, as well as where the bacteria is present. Now, there are regions all across, all around the gut tract, especially in the small intestines known as the Peyer's patches. Peyer's patches are lymphoid tissues and therefore they contain immune cells Peyer's patches are important in protecting the body from invasion and initiating an immune response. another important area is known as a lamina propria, which is also below the mucosal surface Lamina Propria are - is basically connective tissue which has many types of immune cells particularly the activated immune cells such as the CD8 and CD4 T cells now let's talk about Peyer's patches in a bit more detail. Peyer's patches contain special cells (epithelial cells) on the mucosal surface known as follicle-associated epithelial cells within this area we also have other special cells known as microfold cells or M cells M cells are important in antigen sampling, in taking in antigens to initiate an immune response Peyer's patches also contain follicles where B cells predominantly reside in as well as T cells in the surrounding area dendritic cells are also found here because dendritic cells are important in initiating, or activating, the adaptive immune response. we'll learn about the Peyer's patches more later on. now let's talk about the lamina propria. lamina propria, as I mentioned, is our connective tissue and they contain a vast array of actually activated immune cells the lymph vessels also connect to the lamina propria, where the immune cells can go in and out. the lamina propria contains macrophages, phagocytes, and also activated CD8 and CD4 T cells or T-Killer or T-Helper cells. they also contain plasma cells which are the activated B cells. and therefore the lamina propria is very important in essentially preventing infection beforehand Now the question is, where do these immune cells come from? particularly these naïve immune cells such as the naïve lymphocytes Well they come from the high endothelial venules, from the bloodstream. from the thymus and the bone marrow, the naïve lymphocytes actually circulate around the body and they're not predetermined to go to the gut they can go anywhere depending on where the signal takes them for example all lymphoid tissues secrete chemokines which attract the lymphocytes now, the receptors CCR7 and L-Selectin of the lymphocytes are attracted to chemokines CCL21 and CCL19,
which are secreted by lymphoid tissues including the Peyer's patches but also the chemokines can be secreted by other lymphoid tissues such as the spleen and the lymph nodes so these lymphocytes can literally go anywhere where these chemokines are being secreted from So here we have a lymphocyte in the high endothelial venules with L-selectin and the CCR7 receptor, which has attracted the CCL21 and CCL19 chemokines coming from the Peyer's patches the lymphocytes will enter the Peyer's patches if it's a naïve T cell it will stay within the outside of the follicle and if it was a naïve B cell it would be within the follicle now if no antigen is present within the Peyer's patches, or there's no antigen presented to the lymphocyte for the dendritic cells the lymphocytes will re-circulate through the bloodstream. because they still have these CCR7 and L-selectin receptors so they will re-circulate to other lymphoid tissues such as the lymph nodes or the spleen So what happens if an antigen is present, what happens to these lymphocytes? and how does an antigen get presented to these lymphocytes? well the M cells play a critical role here the M cells take up the antigen - a process known as "antigen sampling" and they transport it across to dendritic cells where the dendritic cells can then present it to the lymphocytes. So how does this process occur - how does the M-cell take up the antigen and essentially tell the dendritic cell that there is an antigen and where is the communication between the M cell and the dendritic cell Well, if here we have the associated follicle epithelial cells and here have the M cell here the intestinal lumen where the food passes through and where the pathogens are, and the antigens of the pathogens and here are the Peyer's patches where all the immune cells are residing - or some of them so the antigen and pathogen - if the antigen and pathogen is present, the cells particularly the follicle-associated epithelial cells, will begin secreting chemokines CCL20 and CCL19 and remember, these are the chemokines that attract the lymphocytes but they also attract dendritic cells they attract the dendritic cells with the receptors CCR6 and CCR1. so now the dendritic cells knows that an antigen is present and that the M cell is about to take it up the M cell takes it up through phagocytosis (also known as endocytosis) and the process where it is transported from the lumen to the Peyer's patches is known as transcytosis "trans" as in "across" so it transports this molecule, the antigen, from the lumen to the Peyer's patches where they will just excrete it out and now the dendritic cells, which are there, can engulf it and present it on the Major Histocompatibility Complex and present it to the adaptive immune cells Now let's look at the bigger picture. Because the antigen is present now, because the M cell has already taken it up and brought it into the Peyer's patch, the lymphocytes will lose the receptors L-selectin and the CCR7 and now, and therefore it cannot leave the Peyer's patches per se. so this dendritic cell with the antigen will now activate this naïve T cell and it can be a naïve CD8 or naïve CD4 T cell the dendritic cells also uses retinol and converts it to retinoic acid in the process to activate the T cells. Why does it do this? it does this in order for the T cells to begin expressing new receptors these new receptors are known as "homing receptors" which will tell where the lymphocytes have to go next now if this activated T cell were a CD4 cell, it would become an activated T helper cell. which can then activate naïve B cells within the follicles. the naïve B cells, as I mentioned earlier, only express typically IgM antibodies and sometimes IgD antibodies. but once activated, particularly in the mucosal immune system, they begin expressing IgA antibodies IgA antibodies are important for the mucosal immune system because IgA antibodies are the antibodies which prevent infection. The activated CD8, the activated CD4, and the activated B cell will then leave the Peyer's patches and travel through the body via the lymph vessel they will travel around the body and typically end up in the lamina propria, if you remember, the other area beneath the mucosal surface. so after the antigen-presenting cells interact with the lymphocytes the lymphocytes begin expressing the homing receptors which will direct them to the lamina propria homing receptors are induced by the retinoic acid and by dendritic cells so remember the lymphocytes lost their initial receptors CCR7 and L-selectin which brought them to lymphoid tissues and once these lymphocytes are activated they begin expressing homing receptors here - these homing receptors which will allow them to leave the Peyer's patches through the lymphatic vessel. and head to the mesenteric lymph nodes, and following that to the lamina propria or other areas around the body so here are the activated CD8 and the activated CD4 cells in the mesenteric lymph nodes now, travelling from the Peyer's patches as well as the activated B cell
