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Microbiota On Mucosal > LA10- Viruses At Mucosal Surface > Flashcards

LA10- Viruses At Mucosal Surface Flashcards

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1
Q

Give 3 gut Mucosal viruses present , 2 respiratory, 3 ugt

A

Polio, rotavirus, norocirus

Influenza, covid

Hiv, hpv, trichamonasvirus

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2
Q

Which vaccines have been effective for mucosal viruses

A

Covid, hpv, polio (eradicated)

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3
Q

Which has variable responses

A

Influenza and rotavirus

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4
Q

Why is it so important hiv develop a vaccine in future

A

Kills 700,000 people per year

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5
Q

Why has it been difficult

A

Live attenuated too risky as hiv inserrts into host dna
Inactivated do not havee strong enough immune response

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6
Q

Which type of vaccine is ideally whag you want to tackle mucosal viruses (BECAUSE OF SPECIFIC EFFECTOR HOMING PROGRAMS)

A

Topical/local/mucosal
Eg because pearwnteral is not effective for gut immune response and you want to evoke strong Siga and cell responses

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7
Q

Are mucosal successful as parentedal

A

No, still weakly immunogenic compared to parentedal
Plus parentedal can be used for resp tract and ugt response because they get 50% igG from systemic sources

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8
Q

Give 4 modes of mucosal vaccination and what effect they have

A

Orally - suga mammary, gi tract and salivary

Intranasal- ugt, urt and lrt Siga and igG

Rectal - local Siga

Vaginal - local response

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9
Q

Since ugt have no malt where do their local immune responses come from

A

Associated lymphoid tissue eg inguinal lymph nodes

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10
Q

Which type of vaccine route needs an adjuvant and why

A

Oral

Gi tract tolerance because of constant Microbiota and food means need stronger evoking

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11
Q

What do adjuvants aim to induce

A

Release of things like baff, april

Cosrimulatory molecules like b7 on main target dc

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12
Q

What type of b and T cells can be induced by nasal vaccines

A

Memory

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13
Q

What would both nasal and intramuscular vaccines in future help with covid

A

Tackle both urt cia nalt to stop flu symptoms and then also lrt protection

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14
Q

What’s the difference between live attenuated and inactivated

A

Attenuated is where purified virus incubates with eg monkey cells and adapts to infect those cells so not as easy infecting human cells

Inactivated means they are killed

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15
Q

Give an example of a purified subunit vaccine

A

Ha influenza

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16
Q

What type of cloning subunit vaccine is hpv

A

L1 capsid protein is cloned (using yeast cell expression)
and attached to a vlp which is then inserted

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17
Q

What we’re viral vector vaccines originally used for before covid use of adenovirus

A

Ebola

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18
Q

How does the mrna covid vaccine work

A

Contained in liposome vesicles which can fuse with a cell membrane and it’s translated so cell presents spike to induce immune response

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19
Q

What are 3 viral vaccines licensed that are mucosal

A

Polio , rotavirus, influenza (flumist)

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20
Q

Explain the features of polio virus

A

Non enveloped ssrna with icosahedral capsid

4 capsid proteins line inside v1-4

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21
Q

How is it transmitted

A

Faecal oral route

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22
Q

Where can it go in some cases of people

A

Through draining lymph node to bbb and cause paralytic poliomyelitis where paralysis ef of the legs can occur (1%)

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23
Q

Which 2 vaccines are there for polio and whcih is better and why

A

Inactivated parenteral IPV
Oral live attenuated OPV

OPV is better as it induces both Siga and systemic igG responses eventually

IPV induces only igG systemically which can help only if it spreads through draining lymph node

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24
Q

What is the only drawback of the OPV vaccine which means it is rarely used

A

Small risk of vaccine associated paralytic polio since it isn’t inactivated

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25
Which is more expensive
Ipv
26
Explain the lifecycle of most enteroviruses but more specifically polio
Cd155 receptor for polio induced endocytosis Uncoatinf in acidic endosome causes +ve rna to be released Rna then translated to form polyprotein processed and capsid proteins start to assembly The rna is replicated via the newly translated rep machinery eg protein polio 3A by rna dep rna pol = replication Then assembles and lyric or non lyric release
27
Which protein binds to rna when it’s released crucial to prime for replication
VpG
28
What is the importance of neutralising antibodies
Stop attachment, endocytosis and uncoating
29
What genome does triple capsid icosahedral non enveloped rv have
11 piece segmented ds rna
30
Why is this viral so important
Biggest diarrhoea death of kids under 2 Kills 450k a year
31
Where do 90% of death occur
Africa or Asia (where vaccine is less effective)
32
Which 3 antibodies help with initial infection
Anti-vp4 and 7(outer capsid proteins for attachment) Anti-vp6 (important in endosomal attachment and assembly)
33
Why is cell mediated response good for rotavirus but limited
Doesn’t work effectively without Siga too Works through iec cd8 recognition of mhc1 and killing via FAs, perforin and granzymes Also the cell response has limited memory
34
Which 2 oral vaccines are licensed for rotavirus and what are they specific for
Rotateq (cattle-human hybrid reassortment vaccine) Rotarix (live attenuated) For vp 4 and 7
35
How variable are they in effectiveness
Varies between 70-90% effective and lowest in countries in Africa like Ghana
36
Why could this be
Sanitation, malnutrition, birth mode, breastfeeding , antibiotics Ie Microbiota and dysbiosis If malnutritioned you’re likely having a lower diversity which affects your immune maturation (shown from gf mice)
37
Why could Microbiota be involved
They shape the immune system and also the barrier to rv Eg if you have persistent infections, not breastfed, antibiotic use this can all disrupt the barrier eg thin mucus,Amps , cell permeability etc Plasma cell survival induced by TSLP- baff and April These are the first line of defence = poor vaccine performance
38
Where is iga acquired from which could affect effectiveness
Breast milk
39
Which bacteria was showed to effective in inducing iga and th1 responses for RV oral vaccine efficacy
Lactobacillus GG and bifido bb12
40
Which ssrna icosahedral gut virus has no vaccine
Norovirus
41
Why is this bad
Leading cause of non bacterial gastroenteritis (with diarrhoea)
42
Who gets worse symptoms/ chronic with norocirus
Immunocompromised
43
What else can you think of that will allow better vaccine response/infection response
Pigr upregulation through the nfkb pathway via il17/ other cytokines Baff/April which are induced by adjuvants can be induced by tslp- mediated Microbiota release
44
Which bacterial product was found to give polio better adherence and which bacteria in particular
Lps Bacillus cereus upreg infectivity by 500%
45
How else were Microbiota in mouse models seen to permit polio infection
Increased replicativity and infectivity eg by 500% in b.cereus colonised nice
46
Mmtv retrovirus binding to tlr4 with lps on dc induced what
Induced il6 induced il10 (via th2 responses) release which is immunosuppressive so lack of response to virus = way that Microbiota increase infective
47
Which murine virus was investigated as a stimulator of crohns-like disease with what common snp by cadwell in 2010
Norovirus Atg16L1 (autophagy snp common) Causes abnorma autophagy, villus blunting and packaging of paneth cells with reduced amp release
48
In presence of just the snp whag Happened
No crohns-like pathologies occurred unless virus was present
49
What sort of paneth cell issues were seen with the mice atg16L1 snp and norovirus present
reduced granule number and size, altered paneth gene exp
50
What sort of crohns-like pathologies were seen (only with c6 persistent strain)
Deep inflammation into the muscularis and local blood vessels Blunted villi
51
Which cytokines response induced by this combination induced rhe villus blunting
TNFa and infy
52
When antibiotics were given to mice what happened
All the pathologies disappeared Reduced inflammatory cytokines like ifny and TNFa too
53
What does this indicate
Dysbiosis induced by Norovirus / Microbiota is responsible for crohns symptoms
54
What is influenza a structure
Segmented ssrna 8x enveloped
55
How is it transmitted
Human to human or zooanthroponosis
56
What 2 events can occur for it to escape immunological memory
Antigenic drift - mutational changes in ag eg HA Antigenic shift - reassortment of genes majorly in a vector where 2 strains combine
57
Wht 2 vaccines are there (1 is mucosal) - both provide 3:4 strains
Purified subunit (many strain ag) Live attenuated flumist nasal spray
58
How many cases does it prevent
About 50% not so effective
59
Which secondary bacterial infection can occur with influenza virus which is an issue
Strep pneumoniae
60
What type of coronavirus is covid 19
Beta
61
What do normally except 3 a or b coronaviruses cause
Self limiting urt infections
62
What do the severe ones cause
Severe lrt issues like ards and extra pulmonary problems like diarrhoea
63
Which is most deadly
Mers (35% death rate)
64
What is the death rate of covid 19
1%
65
What are some common comorbidities in people who died with Covid-19
Cvd Diabetes Hypertension
66
Why is diabetes a risk factor
Increased ace2 expression and low ifn response
67
What happens in old age which could influence inflam state and therefore death widh covid
Dysbiosis (loss of diversity) Increased proteo bacteria known for inflammatory states - gut lung axis increasing lps??
68
What sort of inflam states are associated with covid
Low tregs, increased th17,
69
Which antibody treatment been developed which only works for severe covid
Anti-il6R eg tocilizumab
70
Where has a nasal vaccine recently been approved but still long to go for mucosal vaccines to covid
China
71
Which antiinflam given to severe cases
Dexamethasone
72
Why is il6 significant in ards
Promotes the th17 imbalance and nutrpohilic damage
73
What marker do iga + cells have which make them impossible to get from iv response
Ccr10 specific to mucosal
74
Explain the nasal effect on ugt/resp working similar to systemic in that it induced systemic igG and also siga mucosal
Siga mucosal- produces cells with ccr10 and a4b1 which are mucosal specific eg iga only has ccr10 and a4b1 can bind vcam on bronchi Systemic receptors also induced in nalt eg l-selectin and ccr7 to provide systemic igG (ugt and resp tract)
75
What is the success of polio vaccination
Massively eradicated except for places like afghanistan
76
Explain rotavirus pathogenesis
Attachment through vp4 protein and endocytosis Subsequent release from infected absorptive cell causes cell death Villus atrophy Malabsorption means drexreased water and electrolyte absorption = diarrhoea
77
Loss of which immunomodulatory bacteria phyla was associated with ghanaian reduction of rotavirus efficacy and why do you think (vs high proteobac)
Bacteroidetes were much lower - this reduces beneficial scfa effects for strengthening epi barriers etc Also drive expansion of th1 cells via tbet hyperacetylarion but then not too overwhelming as they induce tregs too - help with the progression of infection
78
What types of cell are deficient in mice that are scfa deficient
Plasma cells (they induce class switching eg via aid expression)
79
What did lei 2019 find about Norovirus and dysbiosis in gnotobiotic pigs infected with human Norovirus
Reduced levels of bifido bacteria and firmicutes which is likely to cause inflammatory effects
80
How is nlrc4/tlr5 Microbiota interactions important for rotavirus protection showing benefits of commensals - mouse model studied this and found induction was able to prevent or eliminate infection.
Recognition of flagellin Induced caspases-1 Il1b and il18 maturation Il1b important for il22 production and release for barrier runctjons
81
What is ards
Respiratory condition in which an inflammatory state plus cytokines storms will occur - infiltration and destruction of the alveolar-capolly membrane and subsequent pulmonary oedema

Microbiota On Mucosal (22 decks)

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