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
What is the cell lineage of the epithelium that is reverted into a fetal like state
revSC
26
Unraveling changes in cellular composition using single cell rna sequencing (scRNA seq), what did they use
They used FACS aka kinda like flow cytometry but we chan choose specific populations that we wanna study
27
scRNA seq advantages and limitations
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
Hpb induce the expansion of revSCs while suppressing ... cells
Hpb induce the expansion of revSCs while suppressing secretory cells
29
Fetal like reprogramming in the ISC niche in vibi following Hpb infection
-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
What constitutive a stem cells
-Proliferative -Multipotent
31
A type 2 immune response is dominant during the luminal stage of Hpb infection
-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
Type 2 immune signalling during helminth response :
-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
HES suppress type 2 induced differenciation of secretory cells
Use IL13 there is more epithelial differentiation but if there is hes it is completely suppressed in vitro and vivo
34
STAT 6 is the master regulator of type 2 cytokine signaling
-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
Type 2 signaling inhibits
revSC expansion
36
Stat 6 deficient mouse have increased
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
Why are revSCs expanded after infection? Do helminths promote tissue integrity/ barrier function?
yes
37
Why are revSCs expanded after infection? Do helminths promote tissue integrity/ barrier function?
yes