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MIMM 314 > lecture 6 > Flashcards

lecture 6 Flashcards

1
Q

true or false: a majority of the parasites are poop transmitted

A

false they are soil transmitted

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2
Q

what are the 3 classes of parasited

A

-tapeworms
-flatworms
-roundworms

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3
Q

which proportion of the parasited do helminths infect

A

25%

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4
Q

true or false: there are no vaccines for parasites

A

true

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5
Q

new discoveries due helminths

A

-Type 2 immune responses
-New epithelial lineages
-New immune cells
-New subsets of immune cells

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6
Q

helminths regulate

A

-Inflammatory bowel diseases
-Allergy
-Autoimmunity
-Graft versus host disease

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7
Q

Heligmosomoides polygyrus bakeri aka Hpb

A

Model of human roundworm infection strictly enteric

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8
Q

how does Hpb work

A

Once inside it gets through the epithelial barrier into cell mucosa where they make granulomas=tissue invasion that will last a week after they are gonna cross back to get into intestinal lumen around the villi where they will lay their eggs lasts 3-4 months

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9
Q

why is the intestine epithelium a barrier

A

-Prevents the pathogens from getting intoi the intestines into the tissue
-Mucus

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10
Q

true or false intestinal epithelium senses pathogens, release alarmins and danger signals

A

true

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11
Q

how helminths fight infections

A

-Antimicrobials, antihelminths proteins
-Weep and sweep for helminths expulsion

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12
Q

intestine has two distinct epithelia, which are:

A

-The villus
-Crypt

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13
Q

what are the tyoes of cells in the villus

A

-enterocytes
-Enteroendocrine cells
-tuft cells
-goblet

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14
Q

what do enterocytes do

A

cells responsible for nutrient absorption

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15
Q

what do Enteroendocrine do

A

with are important for hormone secretion

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16
Q

what are tuft cells important for

A

which are important for sensing luminal content

17
Q

what do goblet cells do

A

they secrerte mucus

18
Q

type of cells in the crypt and what do they do

A

-Paneth cells: secrete antimicrobial peptides and growth factors to homeostatic stem cells marked by the Lgr5+ISCs that are responsible for the self renewal of the epithelial layer that will do that in 3-5 days
-They are always self vew and differentiate into all the different things
-When they get to the top they go through apoptosis

19
Q

to regenerate the pithelium tissues….

A

revert into a fetal like state following damage

20
Q

Following intestinal injury (DSS, irradiation)

A

-Homeostatic ISC are depleted
-Surviving cells of the crypts undergo a rapid, transient, proliferative boost that replenishes non-functional cells
-The epithelium is transiently reprogrammes into a fetal like state with de-novo expression of fetal jmarkers and suppression of adult stem cell markers

21
Q

Assesing global transcriptional changes using bulk RNAseq; advantages and disadvantages

A

Advantages:
o In-depth analysis of the full transcriptional landscape of a specific sample – all poly-A tailed mRNAs in all cells of the sample in a given time oHigh resolution – by choosing how many base-pairs to sequence we control the abundance of low-expressed genes we will detect

Limitations:
o A snapshot of a sample’s transcriptional landscape
o There is no distinction between different cells type in the sample

22
Q

what does gene set enrighment analysis do

A

identifies whether a predetermined list of genes is over represented in a large dataset pf genes
-it confirms a getal associated transcriptional signatures in he’s stimulated organoids

23
Q

Hpb secreted products induce a….

A

fetal like state on the ISC niche

24
Q

If you stimulate the cells with HES only then u can

A

see them express clu and very specific cells in the organoids were expressing them

25
Q

What is the cell lineage of the epithelium that is reverted into a fetal like state

A

revSC

26
Q

Unraveling changes in cellular composition using single cell rna sequencing (scRNA seq), what did they use

A

They used FACS aka kinda like flow cytometry but we chan choose specific populations that we wanna study

27
Q

scRNA seq advantages and limitations

A

Limitations:
-Technically complicated and expensive
Usually less high resolution, detection of low abundant genes is difficult
-Cell clusters are user determined and annotated

Advantages
-Can identify shifts/changes in cellular composition of a sample along with transcriptional changes within each cluster of cells

28
Q

Hpb induce the expansion of revSCs while suppressing … cells

A

Hpb induce the expansion of revSCs while suppressing secretory cells

29
Q

Fetal like reprogramming in the ISC niche in vibi following Hpb infection

A

-Can only identify it after 14 days of infection
-Must be occuring at the luminal Hpb infection
-DOES UP REGULATION OF FETAL ASSOCIATED genes necessarily means revSC expansion: nope if we want

30
Q

What constitutive a stem cells

A

-Proliferative
-Multipotent

31
Q

A type 2 immune response is dominant during the luminal stage of Hpb infection

A

-There will be secretion of il25
-That will stimulate ILC2 then activate Th2 that will secrete IL5 and IL13 and they have functionson the epithelial layer

32
Q

Type 2 immune signalling during helminth response :

A

-Responsible for secretory cell differentiation and function o Mucus production
o Antimicrobials/anthelmintics
o Epithelial turnover o Increased smooth muscle cell contractility
Promote worm expulsion

33
Q

HES suppress type 2 induced differenciation of secretory cells

A

Use IL13 there is more epithelial differentiation but if there is hes it is completely suppressed in vitro and vivo

34
Q

STAT 6 is the master regulator of type 2 cytokine signaling

A

-They dimerize
-Signal through either will make stat 6 phosphorylated anf go to nucleus
-If stat 6 is deletes then thet don’t respond to il-4 or 13 and there is no full type 2 immune response

35
Q

Type 2 signaling inhibits

A

revSC expansion

36
Q

Stat 6 deficient mouse have increased

A

Stat 6 deficient mouse have increased spheroid formation in their intestines and there is more clu= in no type 2 signalling there is expansion of revival stem cells (loss of function approach)

37
Q

Why are revSCs expanded after infection? Do helminths promote tissue integrity/ barrier function?

A

yes

37
Q

Why are revSCs expanded after infection? Do helminths promote tissue integrity/ barrier function?

A

yes

MIMM 314 (11 decks)

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