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Semester 4 > case 4 - immunology of the gut > Flashcards

case 4 - immunology of the gut Flashcards

1
Q

what type of surface does the GI tract have

A

an undulating surface, which increases surface area for absorption and secretion

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2
Q

what is mucus secreted by

A

goblet cells

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3
Q

what does this mucus do

A

lubricant
Prevents mechanical stress on epithelium
Thick layer provided stable microenvironment
Prevents invasion
Essential environment for microflora

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4
Q

what helps to maintain the acidic environment in the stomach

A

the gastric glands and gastric pits

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5
Q

what is the protection of the gastric epithelium carried out by

A

mucus and secretion of neutralising bicarbonate by specialised epithelial cells

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6
Q

what does the mucus provide

A

a pH gradient - lumen pH is around 1-2 and the mucus pH is around 7

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7
Q

what is this pH gradient due to

A

the bicarbonate

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8
Q

what is the strongest known risk for gastric cancer

A

h pylori

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9
Q

what is the upper layer of mucus colonised by

A

bacteria

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10
Q

what does the absence of gut bacteria affect

A

behaviour
Gut homeostasis
Immune response under stress
Body weight
Brain development and gene expression

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11
Q

what is the clostridium difficile infection

A

a spore forming gram positive bacillus which is part of normal healthy flora in 4% of healthy indivudals

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12
Q

what does this infection lead to

A

pseudomembranous ulcerative colitis

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13
Q

what can it result in and what is the mortaility rate

A

can result in organ failure and the mortality rate it 35-80%

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14
Q

how does one fix this infection

A

infusion of donor faeces

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15
Q

how do we maintain a healthy microbiome

A

antimicrobial peptides
Alpha and beta defensins that are secreted by the paneth cells
there is good experimental evidence that gut bacteria actually stimulate secretion of antimicrobial peptides maintaining homeostasis

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16
Q

what is the specific antibody responsible for the primary defence against bacteria

A

IgA

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17
Q

what coats colitogenic bacteria with high affinity

A

SIgA

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18
Q

what do the paneth cells do to the crypt

A

keep it sterile

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19
Q

what happens in coeliac disease

A

the villi get smaller and no epithelium

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20
Q

what is in the sub epithelial layer

A

antigen specific responses
Macrophages and dendritic cells
T cells and innate lymphoid cells

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21
Q

features of dendritic cells

A

distinct yet complimentary function
Migratory
Excellent primers of T cells via antigen presentation
Discrete subsets with different function
CD11b+/-CD103+/-
Derive from a committed progenitor

22
Q

features of macrophages

A

Non-migratory
Express CD64, CD11b, CD11c, CX3CR1
Replenished by blood monocytes
phagocytes

23
Q

what are resident macrophages

A

in mice, CX3CR1 macrophages control translocation of luminal bacteria to the draining lymph ode

front line cells that clean up any bacteria that gets though

24
Q

what does Th1 do

A

defence against intracellular parasites

25
Q

what does Th2 do

A

allergy, asthma, controls parasite and extracellular pathogens

26
Q

what does Th17 do

A

defence against pathogens, autoimmunity, transplantation rejection and cancer

27
Q

what does Treg do

A

immune homeostasis and maintains tolerance

28
Q

what does Tfh do

A

help germinal centre B cells to make antibodies, affinity maturation and antibody class switching

29
Q

what are innate lymphoid cells and some features of them

A

derived from common lymphoid progenitor
Rely on IL2R signalling (as do T cells)
INNATE lymphocytes i.e no T cell receptor
Stimulated by cytokines or microbes - probably directly
Present at very low number in steady state
Characterised as ILC1,2, or 3

30
Q

what is ILC1, what does it produce and what does it expres

A

produces IFN gamma
includes natural killer cells
it expresses T-bet

31
Q

what is ILC2, what does it express and what does it produce

A

IL5/IL13 producers
Express RORalpha and GATA3
Seen in allergy
Respond to IL25 and IL33
Also called nuocytes, natural helper cells

32
Q

what is ILC3 and what does it express and produce

A

contribute to mucosal homeostasis
IL17A&F and IL22 producers
Express RORgammaT
Respond to IL23
Important in fetal lymphoid organogenesis
Important for GALT formation
Important in mucosal homeostasis
Loss of ILC3 has been associated with HIV+ progression in aids

33
Q

what can all ILCs be

A

both pro and anti tumorgenic

34
Q

what happens in cancer with ILC2 and ILC3

A

ILC3s are lost and ILC2 go up and ILC3 can potentially help with anti tumour response and if they are lost they lose the help it provides to keep the barrier in tact

35
Q

what is Treg, what are the key factors

A

the two key factors are TGFbeta and IL10
T cell populations contribute to homeostasis
Helps to keep everything happen particularly the ILC3s
If the dendritic cells pick up something pathogenic, it triggers the production of inflammatory cytokines which drive inflammation
To resolve the inflammation you need to produce more Treg

36
Q

what cell surface receptors also put a break on inflammation

A

PD-1/PD-L1
CTLA4/B71 or 2

37
Q

what interaction stops T cell activation

A

CTLA4/B7 interaction between T cell and antigen presenting cell stops T cell activation

38
Q

what activates T cells

A

CD28 on T cell binds to B7 on dendritic cells to activate T cell

39
Q

what is engaged to stop T cells working

A

By engaging CTLA4, it binds to B7 and stops T cells working

40
Q

what is PT1

A

an off switch

41
Q

what interaction reduces T cell activation

A

PD1/PD-L1 interaction

42
Q

features of PD1/PD-L1

A

PD1 is an immune suppressive molecule to avoid over activation
Expressed by infected cells - prevents efficient immunity to virally infected cells
Expressed on APCs and tissue - prevents immune recognition of self
Expressed on tumour cells - tumour evasion mechanism

43
Q

what is sporadic colorectal cancer

A

in non-IBD patients, it usually begins as a non-cancerous polyp

44
Q

what are the chancers of developing it

A

Man has a 1 in 17 chance
Woman has a 1 in 18 chance

45
Q

what is the main thing about Crohn’s disease

A

dysregulation of host flora contributes to disease

46
Q

what are the paneth cell defects in Crohn’s disease

A

reduced secretion of HD5

47
Q

what are the other paneth cell defects

A

NOD2 polymorphisms potentially affecting microbiome and response to commensal flora

48
Q

that is the cancer inflammation parafgm

A

Intrinsic pathway to inflammation (in tumour cells)
And balanced with:
Extrinsic pathway driven by chronic inflammation e.g IBD, dysbiosis

49
Q

what is the intrinsic pathway to inflammation

A

normal tissue homeostasis disrupted

sequential mutations

epigenetic alterations

oxidative stress - Bcl2, p53

proliferation / apoptosis dysregulation

50
Q

what is the extrinsic pathway driven by chronic inflammation

A

inflammatory tumour microenvironment

inflammatory cytokines (TNF alpha, IFN gamma, IL1)

reduced regulatory cytokines - IL10, TGF

disrupted homeostasis

proliferation and apoptosis disregulation

Semester 4 (80 decks)

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