Immunology of IBD Flashcards

1
Q

What is the hygiene hypothesis?

A

theory that not getting exposure to germs early causes incr risk of allergic and autoimmune dz –> increased incidence of IBD

*note: not due to genetic drift, all environmental caused

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2
Q

What can be altered in the epithelial barrier in IBD?

A

impaired formation of tight jxns –> increased permiability of barrier

bacteria can cross mucosal barrier –> induce innate and adaptive responses

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3
Q

What type of bacteria does the GI react to in IBD?

A

normal intestinal microbiota –> self sustained mucosal inflammation

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4
Q

Microbiome

A

combined genomes of all organisms that constitue the mcirobiota

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5
Q

mycobiota

A

subset of microbiota that includes fungi alone

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6
Q

Virome

A

collection of all viruses, including viruses integrated into the human genome, found in or on humans

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7
Q

dysbiosis

A

condition in which there is disequilibrium of the microbial communities that constitute the microbiota at a given body site

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8
Q

gnotobiotic

A

“known life”

describes animals in which the full complement of colonizing microbes is known

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9
Q

Which component of the pathogenesis of IBD (barrier or microbe sensing) is more prominent in UC and CD respectively?

A

UC = mainly disruption of barrier function

CD = dysfunction of microbe sensing more prominent

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10
Q

Which ANCA/ASCAs are positive in UC and crohns dz respectively?

A

CD: + ASCA

UC: + pANCA

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11
Q

microbial Ags act as ______ that stimulate immune responses

A

adjuvants

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12
Q

Where does IBD develop?

A

in areas of high bacterial concentration

(terminal ileum and colon)

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13
Q

What is the colonization environment of the colon and cecum like?

A

low pH

SCFAs abundant

most microbes

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14
Q

Where are lactobacilli found?

A

duodenum and jejunum

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15
Q

Where in the GI tract are ther more anti-microbial peptides (AMPs)?

A

farther up - duodenum

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16
Q

What type of bacteria grow in the ileum and colon?

What of note do they produce?

A

obligate anaerobes

produce SCFAs, actate, propionate, and butyrate

17
Q

What are firmicutes?

A

normal gut microbiome

clostridium and lactobacillus most impt

18
Q

What are bacteroidetes?

A

normal gut flora

bacteroides, prevotella xylanibacte

19
Q

What does a healthy microbiota look like?

UC?

CD?

A

healthy: high bacteroidetes > firmicutes > others

UC: more proteobacteria, less normal ones

CD: more actinobacteria and firmicutes, wayy less bacteriodetes

20
Q

When does spontaneous IBD develop in the lab?

A

not in germ-free environment

develops rapidly when these mice are colonized by commensals

get exacerbated disease if GFM colonized w/ microbiotas from IBD donors

21
Q

What happens to babies born of IBD women?

A

babies have diff microbiota and altered adaptive immune system

22
Q

High fiber diet effect on microbiota

A

increased bacteriodetes, firmicutes, and actinobacteria

less proteo

23
Q

High protein diet effect of microbiota

A

increased bacteroidetes, firmicutes, and proteos

24
Q

High fat diet effect on microbiota

A

decreased bacteroidetes, firmicutes, and proteo

25
High carb diet effect on microbiota
increased bacteroidetes, firmicutes, and actinobacteria
26
What infection has an inverse relationship to incidence of IBd?
helminth colonization
27
What microbe infections might be implicated in dev of IBD?
M paratuberculosis persistent measles listeria salmonella and campylobacter
28
What is the role of genetic factors in IBD?
a bunch of different loci that encode for immuno-inflammatory components certain SNPs associated more w/ IBD (more CD genes than UC)
29
What is the role of IBD-1 in Crohns?
IBD-1 on chr 16 --\> encodes CARD15/NOD2 **MDP** from bacteria (peptidoglycan) --\> **CARD15** on macro**phages**/DCs recognize --\> triggers **NF-KB** activation defects in CARD15 found in 17-27% of CD homozygous for susceptible variant --\> 20x more likely to develop CD
30
What are the possible mechanisms of CD caused by NOD2 mutations
defective function of macrophages --\> chronic T cell response bc persistent intracelular infection defective phages --\> defective epithelial barrier inappropriate activation of APCs and loss of balance
31
How do microbiota affect the intestinal mucosal barrier?
colonization --\> GALT microbiota maintain basal level of Th17 and th1 cells beneficial bacteria increase Tregs and IL-10 good bacteria, Tregs and IL-10 inhibit bad bacteria
32
How are SCFAs produced and why are they good?
commensal bacterial ferment nondigestible polysaccharides --\> SCFAs have anti-inflammatory properties in macrophages, DCs, CD4+ Tcells and intestinal epithelial cells induce IgA and mucus secretion
33
What receptor on Treg cells recognizes SCFAs?
GPR43
34
What are segmented filamentous bacteria and what do they do in gut immunity?
bacteroides, clostridium spp. induce Treg cells in lamina propria play role in basal activation of Th17 = integrity of barrier
35
What happens in the absence of commensial bacteroides? What about in the presence?
absence: salmonella flagellin binds TLR5 --\> activates IKK --\> NF-kB activation and proinflammation presence: proinflammatory response is attenuated, induction of PPAR exports activated NF-kB from the nucleus
36
What immune things predominate in crohn's Dz? UC?
Crohns: Th1 and Th17 --\> IFNgamma, TNF, IL-17 UC: Th2 --\> IL-4, 5, and 13
37
What cytokines drive Th1 an 17 response?
IL-12, IL-6, IL-23
38
How might Tregs be involved in IBD?
Tregs actively suppress immune response to commensals in normal ppl might have breakdown in IBD
39
How do Tregs generally work?
activated by APC presenting auto-Ag express CTLA-4 and IL-2R (CD25) --\> can deprive T cells of IL-2 so there aren't as many of them directly suppress APCs via cell-cell contact