Microbiota and Immunity Flashcards
what percentage of the variation in immune system is due to genetic factors
20-40%
what percentage of the variation in immune system is due to environmental factors
majority - 60-80%
what environmental component has the most significant influence on immune system development
co habitation
individuals that live together have 50% less variation in their immune system
what are two ways that lab mice can be altered to have a natural microbiota
wildling mice
co-housed mice
wildling mice
lab mice that have a controlled microbiota
normal lab mice: low microbiome diversity due to sterile environment
wildling mice: implanting lab mice embryos (to maintain inbred line) into a pseudopregnant wild type mouse that has high microbiome diversity to produce lab mice with natural microbiota
co-housing mice
housing an outbred/pathogen exposed mouse in a cage with an inbred/pathogen free (sterile) mouse to allow them to share their microbiota and produce inbred mice with natural microbiota
microbiota
community of microbes in the animal
controls the outcome of infection by a pathogen (does the animal get disease or not)
microbiome
genome of the microbiota
metagenome
genome of the microbiota + genome of the host
what is the easiest target for pathogens to enter into the body and why
mucosal surfaces
high surface area due to villi/microvilli –> greater space that the immune system must protect –> more opportunity for pathogens to cross
what are the two outcomes of immune recognition of an antigen
pathogen antigen –> stimulates immune response (inflammation)
self and food antigen –> stimulates tolerance (anti-inflammation)
how does the immune system respond to the microbiota
triggers an immune response that does NOT cause inflammation
does NOT induce tolerance
homeostatic immunity
immune response that does not cause inflammation
microbiota must be recognized by the immune system without initiating an inflammatory response
how can the immune system control the composition of the microbiota
“farming” the microbiota using homeostatic immunity
- regulates physiological responses (tissue repair)
allows animals to return their microbiome to normal after dysbiosis
what happens if an animal has a lack of homeostatic immunity
inability to generate proper immune responses
ex. germ free mice
gnotobiotic mice
defined microbiota gets added to a germ free mouse
results in the mouse being able to elicit specific immune responses depending on the type of microbiota added
how is the microbiota measured
sequencing of the 16s ribosomal RNA
has highly conserved segments and highly variable regions
can microbiota get cultured
no
can only be measuring using sequencing
how does the host sense the composition of the microbiota
innate receptors located on the surface of epithelial cells
constantly detect microbiota and elicit signals to avoid inflammation
where are TLRs located
apical surface of epithelial cells and paneth cells
how does the host “farm” the microbiota
cells in the mucosal surfaces that produce different substances to regulate bacteria
goblet cells
produce mucin to create an inner and outer layer of mucus that separates the microbiota from the epithelial cell surface
paneth cells
secretes antimicrobial peptides into the inner mucus layer to selectively kill off pathogenic bacteria and allow microbiota to survive
plasma cells
located in the lamina propria
secretes IgA to regulate bacterial metabolism
phagocytosis mechanisms in the intestines
ways to sample microbial antigen from intestinal lumen
- M cells
- apoptosis dependent transfer
- antigen capture
M cells
located over Peyer’s patches; sample antigen and transfer it to DCs underneath the enterocytes
apoptosis dependent transfer
as cells die, antigen gets released to the underlying DCs
antigen capture
cells (NOT DCs) extend processes through tight junctions between enterocytes to sample antigen from the intestinal lumen
what happens once DCs receive antigen
DCs migrate to LNs –> initiates local B cell response –> class switch to IgA –> generates IgA plasma cells –> relocates to the lamina propria
what are the main “farmers” of the microbiota
antimicrobial peptides and IgA
what are immune system characteristics of germ free animals
poor immune system:
- small LNs
- low serum igs
- low Th1 and Th17 responses
- few germinal centers
- low CD4 T cells and IgA plasma cells in intestines
how can immune function of germ free animals be restored
recolonizing with a proper microbiome –> will start eliciting normal immune responses
segmented filamentous bacteria (SFB)
candidates arthromitus
spore forming gram positive bacteria that colonize the intestines of many species
what is the function of SFB in immune responses
generates the Th17 immune response in the intestines
presence of this bacteria is required in order to generate a Th17 response
effect of antimicrobials on the immune system
clears the microbiome –> decreased colonization resistance –> increased intestinal inflammation and overgrowth of pathogenic species
creates an ecological niche for toxin producing bacteria
may not cause dysbiosis from one antibiotic course but can cause long term changes
how do previous intestinal infections affect the microbiota
previous infections elicit proper immune response –> may damage intestinal cells –> disrupts microbiota and causes inflammation
effect of probiotics on microbiota
has potential to be safe and effective at replacing need for antimicrobials but NOT enough studies and regulations to be considered effective
fecal microbiota transplant
treating the microbiota as an organ and replaces it to establish a “pre-disease” microbiota
ex. patients with C. diff infections normally require surgery to treat but can replace microbiome to treat instead
wolbachia
gram negative bacterial symbionts that commonly infect roundworms (heart worm) and are required for the reproduction of these worms
can treat heart worm by eliminating the wolbachia bacteria with doxycycline
