GI Immunity Flashcards
What are the levels of defense in the GI immune system?
Enterocyte epithelia
Goblet Cells
Mucin
Paneth Cells
Microfold M cells
How do the epitheial enterocytes contribute to the GI immunity?
Single layer of cells that renews every 5-6 days and are joined by tight junctions. Work to keep pathogens from leaving GI tract. Not perfect barrier, so other defense mechanisms are needed.
How do goblet cells and mucin contribute to GI immunity?
Produce and secrete new, thick layer of mucin every 6-12 hours. Mucin has many glycosylated proteins in it, so when in the presence of water it forms a hydrated gel that prevents bacterial attachment to the epithelia of the gut.
Describe how M cells execute their antigen sampling function.
The M cells sit above the peyer’s patches. When they come in contact with bacteria in the mucous layer of the gut, they are able to attach to the bacteria using short microvilli and then they bring them into their cytoplasm via large fenestrations in their membranes. They pass them through the M cell to the basolateral surface where the bacteria are moved into a Peyer’s patch. From there, the bacteria can be taken up by dendritic cells in the peyer’s patch for anitgen presentation. M cells do not present antigen.
Describe how the dendritic cells in the GI system peyer’s patches function in GI immunity.
There are several mechanisms by which dendritic cells can be exposed to antigen:
- Dendritic cells can take up bacteria brought into the peyer’s patch by the M cell. They process the bacteria and present antigens on their surface. They present these antigens to the lymphocytes in the peyer’s patches.
- Dendritic cells can also have processes that extend between epithelial cells of the GI tract which allows them to sample antigen directly from the lumen of the gut.
- Dendritic cells can also be present in the lamina propria just below the basement membrane of the epithelial cells and sample any antigens that make it through the tight junctions between epithelial cells.
What is the GALT?
Discretely organized collections of immune cells closely associated with the mucosal epithelial barrier and are sits of priming adaptive immune responses.
What is a peyer’s patch? Is it a lymph node?
Most predominant in small intestine. Similar to a lymph node but is NOT a lymph node (not encapsulated). Promotes adaptive immune response, high ratio of B:T cells.
What are isolated lymphoid follicles?
Scattered throughout the lamina propria, another way that we can have immune function (mostly b cells)
What are mesenteric lymph nodes? Are they part of GALT?
Sites of adaptive immune response. Not considered part of GALT b/c they’re encapuslated lymph nodes –> part of lymphatic system.
What are the 3 main structural components to the GI immune system?
Peyer’s patches (GALT)
Isolated lymphoid follicles (GALT)
Mesenteric lymph nodes (Not GALT)
The major form of adaptive immunity in the gut is […] immunity directed at microbes in the lumen.
Humoral
[…] is produced in the gut in larger amounts than any other antibody isotype.
IgA
Plasma cells are generated in […] and […] in the GI immune system.
Peyer’s patches
Mesenteric lymph nodes
Let’s say that antigen has entered the peyer’s patch through an M cell. Describe what the immune response of the peyer’s patch will be in response to the antigen.
It will be taken into dendritic cell, processed, expressed on dendritic cell, which will present it to naive CD4+ t cell. This will activate the t cell to become one of the types of helper t cells, which can then activate b cells to undergo class-switching to become a plasma cell that secretes IgA. The plasma cells remain in the lamina propria.
Let’s say that NO antigen has entered the peyer’s patch. Describe what the immune response of the peyer’s patch will be in response to lack of antigen.
In the absence of antigen, dendritic cells secrete nitric oxide and TGF-Beta which stimulates B cells to undergo class switching to become plasma cells that secrete IgA.
Describe the structure of IgA.
Dimer joined by disulfide bonds. Since the Fc region is not exposed, it cannot bind to Fc receptors or activate complement. This allows it to execute mostly a function of binding to pathogens to limit their motility and enhance clearance.
Describe how the dimeric IgA that is produced by Plasma cells in the peyer’s patches actually get secreted into the lumen of the GI tract.
- Which of the t-helper cells do we see the most in the gut?
- What stimulates the formation of this t-helper cell compared to the other types?
- What do they respond to and how?
- Th -17
- TGF-Beta from dendritic cells
- Respond to extracellular pathogens
- Produce mucins and defensins to help maintain barrier integrity and combat microbes, also stimulate inflammatory response (recruitment of neutrophils)
What are the other kinds of T helper cells you might see in the gut and what are their roles in GI immunity?
What is an intraepithelial cytotoxic lymphocyte? What is their role in GI immunity?
How do Treg cells exert their function?
In response to SCFA metabolites and TGF-beta, immature Treg cells in lymphatics become activated to regulatory T cells, which secrete IL-10, TGF-beta, express CTLA-4. These factors allow them to inhibit Th17 cells in GI system so that we don’t have an immune response to unecessary antigens.
What is oral tolerance?
