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MIMM 314 > Lecture 3 aka lect 2 > Flashcards

Lecture 3 aka lect 2 Flashcards

1
Q

what are the costs of having sensitive host response systems

A

-autoimmune disease
-allergies
-very fast at controlling the damage but is non specific which means that it can be dangerous

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2
Q

can you name 3 was in which structure follows function in our immune system

A

-epithelial cells that try to cover the maximum
-dendritic cells that have dendrites that reach out to show off their antigens
-monocytes that get bigger once they differentiate into macrophages so that they can eat

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3
Q

the gut rapidely replenish itself and the … cells remake themselves rapidly

A

the gut rapidely replenish itself and the epithelial cells remake themselves rapidly

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4
Q

what is the reason why we are waterproof

A

our dead cells

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5
Q

what are vilis

A

it is in the gut and it covers the whole small intestinal tract they kinda protrude: they are these finger like protrusion that are covered by mucus and bacteria = increase the surface area

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6
Q

what is the crypt in the gut

A

the bottom cells of the gut, they are stem cells that are rapidly proliferating and they rise up so that they can differentiate

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7
Q

what is on the top of the gut like the type of cells

A

mostly made of enterocytes that help absorb nutrients from the lumen or water from the intestinal contents also goblet cells are at the top: they make mucus
-After the top cells, they will go through apoptosis and go into the tract, that fast replenishing is so that we don’t get cancer

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8
Q

true or false: the more differenciated you are the less you are proliferating

A

true

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9
Q

true or false: the gut regenerates slowly

A

false it regenerates fastly
because lots of stuff is in your gut like microbes, fungi, phages etc, we need to protect ourselves

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10
Q

what does Ki67 do

A

marks rapidly proliferating cells aka stem cells at the base of the vili

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11
Q

what are covering the villi

A

mucus and bacteria

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12
Q

what is epcam

A

it is a molecule that is expressed on the surface of epithelial cells that helps connect those epithelial cells along the surface of the vili

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13
Q

what does cd45 do

A

it marks all hematopoietic cells aka all immune cells express cd45 and they line up inside the vili under the epithelial layer and these are a lot of tissues resident cells, they will sense stuff that is inside the epithelial cells

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14
Q

why do we have intracellular and extracellulr receptors

A

because we have extracellular ad intracellular pathogens like viruses and bacteria

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15
Q

true or false: epithelial cells are phagocytic

A

false they absorb nutrients and they are not really phagocytic

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16
Q

what are the commonalities between all these pamps and TLRs

A

There are commonalities between all of these pamps like Toll like receptors and some alarmins: they all stimulate NFkB which is an important TF factor for driving an inflammatory response

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17
Q

what is TLR-4

A

TLR4 is a transmembrane receptor that activated through this adaptor receptor called MyD88

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18
Q

true or false: almost all tlr signaling gores through MyD88

A

true

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19
Q

what is the other type of signalling of TLR signalling

A

TRF dependant signalling

20
Q

what is one consequence of almost always using myd88 pathway

A
21
Q

what does myd88 pathway do q

A

it phosphorylated nfkb that will then travel to the nucleus on DNA to upregulate the transcription of mhc and costimulatory molecs

22
Q

what are nods

A

they are able to recognize intracellular peptidoglycans on intracellular bacteria which means that they are able to recognize both gram - and + bacteria and then turns on the immune system

23
Q

true or false: Myd88 is conserved in all tlrs

A

true
is conserved in all TLRs allows us to be highly responsive to different stimuli but what specifies that stimuli is all the other signals ij the context of an infection or tissue damage

24
Q

true or false: epithelial cells are considered sentinel cells

A

true

25
Q

true or false: TLR signalling promotes separation of the microbiota and the small intestinal surface

A

true

26
Q

16S is only expressed in ….

A

bacteria which we can use a dye to bind to that specific rna

27
Q

what does dapi stains for

A

all nucleated cells

28
Q

what did the scientists see after they stained using dapi and for 16s

A

they saw that there was this barrier/gap between the nucleated cells and the bacteria present

29
Q

what happened to the mouse when myd88 was ko

A

there was no gap

30
Q

which cells express myd88 and where are they

A

all immune cells
macrophages and innate immune cells and they are in the mucus

31
Q

true are false: the further away you get from the vili, the less there are bacteria

A

As you can see on the pic, as further as you get away from the villi tips, the more you get an increase in green fluorescence meaning that there ia s a gradient of bacteria

32
Q

How to test whether an epithelial cell can directly respond to a microbe through MyD88 dependent pathway?

A

cre lox

33
Q

how does cre lox work

A

-You generate LoxP sites which are very specific sequences of DNA and you engineer these 2 to flank a a gene of interest ex: MyD88 gene in one mouse
-You then cross that mouse that expresses CRE recombinase which is an enzyme that will cleave at LoXP sites
-In the case of the epithelium, there is a gene called Villin that all cells have
-So this mouse expresses CRE recombinase at anytime aka a cell expressing villin
-The 2 mouses described are breed
-You now generate a progeny that contains 1 allele of the Vilain Cre and is homozygote for the LoxP flank MyD88 target gene, so now only MyD88 will be KO in the epithelium since only epithelial cells that have the Cre recombinase attached to the Villain

34
Q

what happenend to the mouse once cre lox was used and what does it show

A

-The gap was kinda loss
Gene had a loss of function to show that myd88 was important in the gut
-Was a loss of function experiment because they deleted a gene to show that it was important for smth
-Shows that myd88 in the epithelium is necessary to maintain the gap but it does not show that it is sufficient

35
Q

gain of function with the myd88 cells

A

Gain of function experiment to show that MyD88 in epithelial cell is sufficient
-They took a KO mouse of MyD88 and they put in a transgene so that only Villain expressing cells are going to be the ones that express MyD88 and all the others are KO
-They showed that this restored the gao aka it is sufficient

36
Q

MyD88 is …. and …… for inducing a barrier between the epithelium and the commensal bacteria

A

MyD88 is necessary and sufficient for inducing a barrier between the epithelium and the commensal bacteria

37
Q

WHy does MyD88 signalling into the epithelium drives the formation of the gap?

A

Epithelial cells are good at making antimicrobial peptides that have direct bactericidal activity

38
Q

where is reg iii gama expressed

A

it is a protein that is highly expressed all around the intestinal epithelial so that they can kill bacteria

39
Q

true or false: in myd88 ko mouse regiii gamma was overexpressed

A

false, it was gove

40
Q

what happend to reg iii gamma when myd88 is overexpressed

A

too much regiiigamma

41
Q

Which experiment can you do to test that RegIII gamma is responsible for the whole MyD88 dependent gap thing

A

KO RegIII gamma, you KO the gap

42
Q

is the dmz good for us or is it good for the bacteria

A

-Both
-The mucus prevents the RegIII gamma from spreading to our intestines and kill everything; it provides a gradient
-Mucus is there to trap the RegIIIy so that the healthy bacteria to metabolize food and stuff, and can still be there and absorb nutrients

43
Q

what are sonme inducers of inflammation

A

-pamps ex: dr-rna
-damps
-allergens
-Injury detected by alarmins that are secreted by damaged or dead cells
-Sterile inflammation: inflammation induced in the absence of microbes

44
Q

does sterile inflammation show matzinger or janeway

A

janeway

45
Q

Perks and non perks of tissue resident

A

-Non perks: they are non specific, could lead to mount a response against a self antigen (could be a mistake of interpretation of self or non self due to the fact that the self and the non self are looking similar aka molecular mimick)
-Perk: the are fast acting

MIMM 314 (11 decks)

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