GI Immunology

Question 1

define microbiota

Answer 1

organisms in a defined environment

Question 2

define microbial-derived metabolite

Answer 2

molecules produced during microbial processing of ingredients (proteins, carbohydrates, lipids) available in the GI tract

Question 3

explain how microbial-derived metabolites in the GI system can help regulate inflammation

Answer 3

the presence of certain metabolites can direct cell differentiation, for example

short chain fatty acids are microbial-derived metabolites from microbial digestion of dietary fiber; one of these is butyrate that can translocate to the lamina propria and direct T cell differentiation to increase IL-10, an anti-inflammatory mediator (some other SCFAs can promote intestinal epithelial cell restitution, promoting intestinal barrier function)

Question 4

identify specialized immune cells and organs associated with the GI tract (paneth cells, M cells, GALT, etc.)

Answer 4

GALTs gut-associated lymphoid tissues, and include specialized cells such as paneth cells and M cells, and can be found in lymphatic follicles that are present throughout the GI tract, or in peyer’s patches, which are organized lymphatic tissue/follicles in the ileum

Question 5

describe paneth cells

Answer 5

immune cells that migrate to base of intestinal crypts and mature, developing acidophilic granules that contain
1. defensins
2. lysozymes
3. cytokines
4. IgA (but this comes from class-switched B cells, not the paneth cells themselves)

Question 6

describe paneth cells in the small intestine

Answer 6

these antimicrobial peptides provide a chemical barrier in the lumen of the small intestine between bacteria and epithelium; protection aided by a thin mucus layer

Question 7

describe the large intestinal barrier in terms of paneth cells, Lypd8, , and mucus

Answer 7

in the large intestine, there is less of a need for antimicrobial peptides from paneth cells, but they are still present in smaller numbers; an inner mucus layer that creates a physical barrier, and intestinal epithelial cells secrete Lypd8 that binds flagellated bacteria and inhibits invasion

Question 8

describe M cells

Answer 8

1. also called microfold cells due to structure, are specialized intestinal epithelial cells that are primarily found overlying GALT lymphoid follicles like peyer’s patches in the ileum
2. have blunted or absent microvilli
3. have paracellular junctions that keep the intestinal border intact, but M cells act as a functional opening and sample antigen and then contact macrophages and lymphocytes about it (more on this process in another card)

Question 9

describe the process of antigen sampling from the gastrointestinal lumen, noting cell types involved

Answer 9

M cells take up antigen via endocytosis, pinocytosis, and phagocytosis, and then directly contact macrophages and lymphocytes via their basolateral pocket, leading downstream, to local IgA production and secretion

Question 10

list the 5 ways that antigen can reach dendritic cells in the GI tract

Answer 10

1. dying epithelial cell internalized by DC
2. goblet cell-associated antigen passages
3. leakage between cells in cases of inflammation, hypoxia, cell damage
4. directly via M cells
5. specialized dendritic cell extends dendrite through pore in M cell