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VET 413: Infectious Disease/Immunology > Microbiota and Immunity > Flashcards

Microbiota and Immunity Flashcards

1
Q

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

A

20-40%

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2
Q

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

A

majority - 60-80%

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3
Q

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

A

co habitation

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

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4
Q

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

A

wildling mice

co-housed mice

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5
Q

wildling mice

A

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

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6
Q

co-housing mice

A

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

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7
Q

microbiota

A

community of microbes in the animal

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

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8
Q

microbiome

A

genome of the microbiota

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9
Q

metagenome

A

genome of the microbiota + genome of the host

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10
Q

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

A

mucosal surfaces

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

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11
Q

what are the two outcomes of immune recognition of an antigen

A

pathogen antigen –> stimulates immune response (inflammation)

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

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12
Q

how does the immune system respond to the microbiota

A

triggers an immune response that does NOT cause inflammation

does NOT induce tolerance

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13
Q

homeostatic immunity

A

immune response that does not cause inflammation

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

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14
Q

how can the immune system control the composition of the microbiota

A

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

allows animals to return their microbiome to normal after dysbiosis

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15
Q

what happens if an animal has a lack of homeostatic immunity

A

inability to generate proper immune responses

ex. germ free mice

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16
Q

gnotobiotic mice

A

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

17
Q

how is the microbiota measured

A

sequencing of the 16s ribosomal RNA

has highly conserved segments and highly variable regions

18
Q

can microbiota get cultured

A

no

can only be measuring using sequencing

19
Q

how does the host sense the composition of the microbiota

A

innate receptors located on the surface of epithelial cells

constantly detect microbiota and elicit signals to avoid inflammation

20
Q

where are TLRs located

A

apical surface of epithelial cells and paneth cells

21
Q

how does the host “farm” the microbiota

A

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

22
Q

goblet cells

A

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

23
Q

paneth cells

A

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

24
Q

plasma cells

A

located in the lamina propria

secretes IgA to regulate bacterial metabolism

25
Q

phagocytosis mechanisms in the intestines

A

ways to sample microbial antigen from intestinal lumen

  • M cells
  • apoptosis dependent transfer
  • antigen capture
26
Q

M cells

A

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

27
Q

apoptosis dependent transfer

A

as cells die, antigen gets released to the underlying DCs

28
Q

antigen capture

A

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

29
Q

what happens once DCs receive antigen

A

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

30
Q

what are the main “farmers” of the microbiota

A

antimicrobial peptides and IgA

31
Q

what are immune system characteristics of germ free animals

A

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

32
Q

how can immune function of germ free animals be restored

A

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

33
Q

segmented filamentous bacteria (SFB)

A

candidates arthromitus

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

34
Q

what is the function of SFB in immune responses

A

generates the Th17 immune response in the intestines

presence of this bacteria is required in order to generate a Th17 response

35
Q

effect of antimicrobials on the immune system

A

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

36
Q

how do previous intestinal infections affect the microbiota

A

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

37
Q

effect of probiotics on microbiota

A

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

38
Q

fecal microbiota transplant

A

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

39
Q

wolbachia

A

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

VET 413: Infectious Disease/Immunology (38 decks)

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