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Biology of disease > COVID > Flashcards

COVID Flashcards

1
Q

What is the mortality rate of SARS-COVID-2

A

3-4%

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2
Q

what are the 3 main spike proteins on covid?

A

S (spike), M(matrix) , E (envelope)

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3
Q

what does the S spike do?

A

binds membranes - target for antibodies

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4
Q

what does the E spike protein do?

A

responsible for infectivity

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5
Q

what does the M spike protein do?

A

helps E form the envelope and is the most abundant

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6
Q

whats the N protein?

A

Helical nucleocapsid - single strand + charge

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7
Q

what does covid bind to in lungs ?

A

pheumocyte, ACE2 receptor ( angiotensin converting enzyme)

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8
Q

whats TMPRSS2 ?

A

host cell serine protease - cuts off S protein and enables binding

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9
Q

what are the two ways covid can enter the cell?

A

engulfed or fusion

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10
Q

what ultimately gets released from host cell?

A

virions

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11
Q

what is triggered first in the immune response?

A

innate

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12
Q

what happens to interferons ?

A

they get suppressed or delayed

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13
Q

what causes the innate response to be unbalanced?

A

the cytokine storm - hyper reaction

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14
Q

whats lymphophenia ?

A

low levels of lymphocytes

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15
Q

why is lymphophenia common in covid?

A

reduces bone marrow production of immune cells

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16
Q

what do elisa tests do ?

A

see if there are any specific IgG or M antibodies

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17
Q

what happens to cd4/8 numbers in mild covid ?

A

numbers decrease

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18
Q

what happens in a mild covid response?

A

damaged epithelial cells send out cytokines which trigger macrophages to come

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19
Q

what happens in server covid ?

A

more inflammatory cytokines, increase of interleukin 6, decreases of interferon gamma which normally helps with viral infections

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20
Q

what is ARDS ?

A

acute respiratory disease syndrome

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21
Q

how do T cell precursors know what to differentiate into ?

A

due to the cytokines present which influence which one to turn into

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22
Q

what does a high amount of IL-6 AND TGF beta cause T cells to turn into?

A

TH17

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23
Q

what does TH17 produce?

A

IL-6 AND IL17

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24
Q

what does the low levels of TH - gamma do ?

A

reduce the chance of TH1 cells being produced

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25
Q

what does TH17 do ?

A

increases neutrophil production - unnecessary as it would be more beneficial to have CD8 cells

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26
Q

how does the IL6 signalling work ?

A

need both the IL6 and GPL30 subunits to be phosphorylated (JAK and STAT pathways ) in order to transduce signal

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27
Q

where is the IL6 found ?

A

in neutrophils and alveolar cells

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28
Q

what does anti IL6 receptor antibody do?

A

binds therefore blocks receptor

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29
Q

whats mass cytomometry ?

A

mix of flow cytonomy and mass spectrometry

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30
Q

what may explain why there is such a var in covid genes activated and responses

A

SNP - single nucleotide polymorphism’s - genetic , ethnic

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31
Q

what is dexamethasone ?

A

corticosteroid, anti inflammatory drug

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32
Q

how does dexamethasone work?

A

steroid is hydrophobic and passes through cell membrane, binds to steroid receptor. the steroid receptor is then free from the H chaperone protein to bind to specific gene regulatory seq. these can up/down regulate gene transcription

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33
Q

which down regulates gene expression of steroids ?

A

NFkB receptors bound to NFkB

34
Q

what is remdesivir ?

A

RNA dependant RNA polymerase inhibitor / pro inflammatory drug so not used currently

35
Q

what is remdesivir hydrolysed to?

A

nucleoside - phosophorlayted with 3pp

36
Q

how does remdesivir work ?

A

gets incorporated into viral RNA production , allows 3 other nucleotides to be added before steric clash occurs and transcription stopped

37
Q

what was chloroquine originally used for ?

A

malaria treatment

38
Q

how does chloroquine work?

A

causes ph changes in cellular compartments

autophagy, adaptive immunity and innate

39
Q

how does CQ work in autophagy ?

A

interfers with budding of the sporozoite from cell

40
Q

how does CQ work in adaptive immunity ?

A

changes the ph of antigen processing cellular compartments- MHC2 cannot be made properly

41
Q

how does CQ work in innate immunity?

A

TOL like receptors - TLR - are ph dependant and activity gets effected when ph is disrupted

42
Q

what structure is the S protein ?

A

trimer

43
Q

whats the normal function of ACE ?

A

regulate BP

44
Q

how does COVID effect ACE?

A

inhibits production

45
Q

What are the two types of immunisation ?

A

passive and active

46
Q

whats passive immunity ?

A

transfer of preformed immune factors- temporary can trigger immune responce as its not produced by the body

47
Q

whats active immunity?

A

invokes a protective immune responce in the recipient - long lasting

48
Q

what are the features that a vaccine must have?

A

safe, protective, sustained protection , induces neutralising antibody (stops virus from infecting cells such as neural ) , induces protective T cell response , practical considerations

49
Q

what happens to affinity of antibody to pathogen and somatic hypermutation in secondary response ?

A

it increases

50
Q

what do boosters do?

A

increases IgG an affinity of them

51
Q

what are the 3 main things which influence vac effectiveness ?

A

dose , immunogenicity and adjuvants

52
Q

how does does affect vaccine effectiveness ?

A

too much antigen present could trigger a apoptosis, too little not a strong enough immune response

53
Q

What are the factors within immunogenicity?

A

size of of antigen (large better), intermediate dose, route, infection better, composition - complex, form - particular and denatured , similarity to self cells- different, adjuvants - slow release , interaction with MHC - effective

54
Q

what are adjuvants?

A

enhance immune response by expressing a danger signal

55
Q

types of vaccines ?

A

killed , live , subunit , conjugate, synthetic , dendritic cell and nucleic acid

56
Q

whats the subunit vac?

A

only a certain part of the virus is used, antigen

57
Q

what conjugate vac?

A

polysaccharide plus virus allows engulf and then presentation

58
Q

whats synthetic vac?

A

surface antigen made by yeast

59
Q

whats the dendritic vac?

A

dendritic cells are removed injected with virus and then put back into the body

60
Q

whats nucleic acid vacs ?

A

mrna injected into via a plasmid host and host makes the viral proteins

61
Q

what is CQ?

A

serine portease inhibitor

62
Q

what is TMPRSS2?

A

anchored serine protease

63
Q

what does TMPRSS2 do ?

A

cleave ACE2 to improve viral binding or cleave S spike protein

64
Q

What are calu3 cells?

A

lung epithelial cells

65
Q

what does VIR on the end of drug names usually mean?

A

nuclease analog- stop transcription of RNA into proteins

66
Q

why were RNA vaccines not used up until recently ?

A

had issues with them being unstable and using an unspecific immune response - cytokine storm

67
Q

How can you improve the stability of the RNA ?

A

add different nucleotides to it -pseudouridine
5 cap
poly 3 tail

68
Q

What are the 5 normal nucleotides in RNA?

A

ATGCU

69
Q

How has the delivary mechanism for RNA vaccines improved ?

A

using liposomes

70
Q

what does the T7 allow ?

A

bacteriophage RNA polymerase

71
Q

what does luciferase do ?

A

cause light reactions

72
Q

what does an increase in TNFgamma do? (INTERFERON)

A

non specifc response activated - cytokine storm

73
Q

why does adding pseudouridine lower the risk of a non specific immune response ?

A

because human TOL like receptors havent evolved to recognise them

74
Q

what are the two vaccines from pfizer ?

A

BNT162B1/B2

75
Q

Why is the pfizer vaccine fused to trimer domain ?

A

mimics natural shape of the virus without including the whole pathogen

76
Q

what are the HCS in the trials ?

A

peeps who have recovered from covid

77
Q

how does an ELIspot assay work?

A

dish is coated with antibodies that recognise the cytokine - IFNG
incubate with cell thats producing INFG
wash cells away leaving an indent with secretions
INFG binds to antibodies on dish
add Biotinylated antibodies which also bind to INFG but also the detective reagent
colourful dots appear where cells where that made INFG

78
Q

what does neoantigen stand for ?

A

new antigen

79
Q

how do cancer cells stop T cells from attacking them ?

A

recognise the cytokines produced which cause genetic changes in which PD-L1 is up regualted and incerted into the surface of cancer cells. this bind with PD-L1 on the t cells and cause them to stop signalling

80
Q

how can you stop cancer cells fighting t cells?

A

use anti PD-L1 which block the PD-L1 binding site on the t cell so cancer cant stop it

Biology of disease (4 decks)

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