Immunology of IBD Flashcards

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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
Q

High carb diet effect on microbiota

A

increased bacteroidetes, firmicutes, and actinobacteria

26
Q

What infection has an inverse relationship to incidence of IBd?

A

helminth colonization

27
Q

What microbe infections might be implicated in dev of IBD?

A

M paratuberculosis

persistent measles

listeria

salmonella and campylobacter

28
Q

What is the role of genetic factors in IBD?

A

a bunch of different loci that encode for immuno-inflammatory components

certain SNPs associated more w/ IBD

(more CD genes than UC)

29
Q

What is the role of IBD-1 in Crohns?

A

IBD-1 on chr 16 –> encodes CARD15/NOD2

MDP from bacteria (peptidoglycan) –> CARD15 on macrophages/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
Q

What are the possible mechanisms of CD caused by NOD2 mutations

A

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
Q

How do microbiota affect the intestinal mucosal barrier?

A

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
Q

How are SCFAs produced and why are they good?

A

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
Q

What receptor on Treg cells recognizes SCFAs?

A

GPR43

34
Q

What are segmented filamentous bacteria and what do they do in gut immunity?

A

bacteroides, clostridium spp.

induce Treg cells in lamina propria

play role in basal activation of Th17 = integrity of barrier

35
Q

What happens in the absence of commensial bacteroides?

What about in the presence?

A

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
Q

What immune things predominate in crohn’s Dz?

UC?

A

Crohns: Th1 and Th17 –> IFNgamma, TNF, IL-17

UC: Th2 –> IL-4, 5, and 13

37
Q

What cytokines drive Th1 an 17 response?

A

IL-12, IL-6, IL-23

38
Q

How might Tregs be involved in IBD?

A

Tregs actively suppress immune response to commensals in normal ppl

might have breakdown in IBD

39
Q

How do Tregs generally work?

A

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