Microbiota and Immunity

Question 1

what percentage of the variation in immune system is due to genetic factors

Answer 1

20-40%

Question 2

what percentage of the variation in immune system is due to environmental factors

Answer 2

majority - 60-80%

Question 3

what environmental component has the most significant influence on immune system development

Answer 3

co habitation

individuals that live together have 50% less variation in their immune system

Question 4

what are two ways that lab mice can be altered to have a natural microbiota

Answer 4

wildling mice

co-housed mice

Question 5

wildling mice

Answer 5

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

Question 6

co-housing mice

Answer 6

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

Question 7

microbiota

Answer 7

community of microbes in the animal

controls the outcome of infection by a pathogen (does the animal get disease or not)

Question 8

microbiome

Answer 8

genome of the microbiota

Question 9

metagenome

Answer 9

genome of the microbiota + genome of the host

Question 10

what is the easiest target for pathogens to enter into the body and why

Answer 10

mucosal surfaces

high surface area due to villi/microvilli –> greater space that the immune system must protect –> more opportunity for pathogens to cross

Question 11

what are the two outcomes of immune recognition of an antigen

Answer 11

pathogen antigen –> stimulates immune response (inflammation)

self and food antigen –> stimulates tolerance (anti-inflammation)

Question 12

how does the immune system respond to the microbiota

Answer 12

triggers an immune response that does NOT cause inflammation

does NOT induce tolerance

Question 13

homeostatic immunity

Answer 13

immune response that does not cause inflammation

microbiota must be recognized by the immune system without initiating an inflammatory response

Question 14

how can the immune system control the composition of the microbiota

Answer 14

“farming” the microbiota using homeostatic immunity
- regulates physiological responses (tissue repair)

allows animals to return their microbiome to normal after dysbiosis

Question 15

what happens if an animal has a lack of homeostatic immunity

Answer 15

inability to generate proper immune responses

ex. germ free mice

Question 16

gnotobiotic mice

Answer 16

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

Question 17

how is the microbiota measured

Answer 17

sequencing of the 16s ribosomal RNA

has highly conserved segments and highly variable regions

Question 18

can microbiota get cultured

Answer 18

no

can only be measuring using sequencing

Question 19

how does the host sense the composition of the microbiota

Answer 19

innate receptors located on the surface of epithelial cells

constantly detect microbiota and elicit signals to avoid inflammation

Question 20

where are TLRs located

Answer 20

apical surface of epithelial cells and paneth cells

Question 21

how does the host “farm” the microbiota

Answer 21

cells in the mucosal surfaces that produce different substances to regulate bacteria

Question 22

goblet cells

Answer 22

produce mucin to create an inner and outer layer of mucus that separates the microbiota from the epithelial cell surface

Question 23

paneth cells

Answer 23

secretes antimicrobial peptides into the inner mucus layer to selectively kill off pathogenic bacteria and allow microbiota to survive

Question 24

plasma cells

Answer 24

located in the lamina propria

secretes IgA to regulate bacterial metabolism

Question 25

phagocytosis mechanisms in the intestines

Answer 25

ways to sample microbial antigen from intestinal lumen - M cells - apoptosis dependent transfer - antigen capture

Question 26

M cells

Answer 26

located over Peyer's patches; sample antigen and transfer it to DCs underneath the enterocytes

Question 27

apoptosis dependent transfer

Answer 27

as cells die, antigen gets released to the underlying DCs

Question 28

antigen capture

Answer 28

cells (NOT DCs) extend processes through tight junctions between enterocytes to sample antigen from the intestinal lumen

Question 29

what happens once DCs receive antigen

Answer 29

DCs migrate to LNs --> initiates local B cell response --> class switch to IgA --> generates IgA plasma cells --> relocates to the lamina propria

Question 30

what are the main "farmers" of the microbiota

Answer 30

antimicrobial peptides and IgA

Question 31

what are immune system characteristics of germ free animals

Answer 31

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

Question 32

how can immune function of germ free animals be restored

Answer 32

recolonizing with a proper microbiome --> will start eliciting normal immune responses

Question 33

segmented filamentous bacteria (SFB)

Answer 33

candidates arthromitus spore forming gram positive bacteria that colonize the intestines of many species

Question 34

what is the function of SFB in immune responses

Answer 34

generates the Th17 immune response in the intestines presence of this bacteria is required in order to generate a Th17 response

Question 35

effect of antimicrobials on the immune system

Answer 35

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

Question 36

how do previous intestinal infections affect the microbiota

Answer 36

previous infections elicit proper immune response --> may damage intestinal cells --> disrupts microbiota and causes inflammation

Question 37

effect of probiotics on microbiota

Answer 37

has potential to be safe and effective at replacing need for antimicrobials but NOT enough studies and regulations to be considered effective

Question 38

fecal microbiota transplant

Answer 38

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

Question 39

wolbachia

Answer 39

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