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Immunology, infection and inflammation > Vaccines > Flashcards

Vaccines Flashcards

1
Q

before Edward Jenners discovery (cow pox for small pox) what was used for small pox inoculation in asia in the 1500s

A

ground up small pox scabs blown into the nostril or scratching matter from a sore

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2
Q

what did Thucydides notice in 430BC Athens

A

that survivors of the plague were resistant to further attacks of the plague but not to other diseases

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3
Q

what is immunisation

A

the process of eliciting a state of protective immunity against a disease causing pathogen

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4
Q

how was the covid-19 vaccine developed so fast

A

was tested on other types of sars
many years already contributing to platform (mRNA tech)
cost not a problem bcos every country contributed
no shortage of viable patients
phases were overlapped
didn’t wait to develop a batch method

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5
Q

give features of the ideal vaccine

A
  • give lifelong immunity
  • broadly protective against variants
  • prevent disease transmission
  • induce effective immunity rapidly
  • be effective in all vaccinated subjects
  • transmit maternal protection to foetus
  • require few immunisation to induce protection
  • not administered by injection
  • affordable world wide
  • stable (temp, no cold chain)
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6
Q

what 3 ways can passive immunity be acquired

A

naturally when maternal IgG crosses placenta
maternally produces IgA in breast milk
injection with preformed antibodies (antiserum)

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7
Q

what is passive immunity

A

immunity acquired without activation of hosts natural immune response

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8
Q

what is active immunity

A

immunity in which the hosts immune system plays an active role through antigen specific T and B cell activation and formation of protective memory cells

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9
Q

what two ways can active immunity be acquired

A

natural infection

and vaccinations

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10
Q

when is passive immunity used in treatments

A
  • babies born with congenital immune deficiencies
  • unvaccinated individual exposed to botulism tetanus diphtheria measles rabies (things that will have immediate effect if not treated)
  • antiserum provides antidote against poisonous venom
  • exposure to pathogen that causes death faster than immune response
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11
Q

what are the possible risks of passive immunity

A

host immune system can mount an anti isotype response if antibody is from another species - systemic anaphylaxis

activation of complement immune complexes through IgM or IgG - type 3 hypersensitivity reactions

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12
Q

what drug induced passive immunity against ebola

A

Zmapp (made of three humanised monoclonal antibodies harvested from mice exposed to ebola virus proteins)

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13
Q

what is the primary goal of vaccination

A

to offer long term protection by inducing a memory response

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14
Q

what is the principle of vaccination

A

to mimic infection in a way that activates host immune response in order to induce long lasting immunological memory

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15
Q

what cells are involved in the innate immune response

A

NK cells, mast cells, eosinophils, basophils, macrophages, neutrophils, dendritic cells

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16
Q

what are the steps to generating an immune response from vaccination

A

1 uptake of vaccine by phagocytes
2 activation and migration of APCs from infected tissue to peripheral lymphoid organs (closest to vac site)
3 antigen presentation to T and B cells
4 activation of T and B cells
5 long lasting protection through memory cell development

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17
Q

where does t cell activation occur

A

in secondary lymphoid organs (lymph nodes, spleen, peyers patches, mucosal tissues (adenoids and tonsils))

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18
Q

what 3 things are required for t cell activation

A

1 recognition of antigen by TCR
2 costimulatory signal between CD28 (on t cell) and CD80/86 (on apc)
3 cytokine mediated differentiation and expansion

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19
Q

what are the 4 types of memory t cell

A

stem cell memory t cells - in secondary lymphoid organs, give rise to central memory t cells
central - reside in 2ndary lymphoids
effector - circulate among tissues
resident - settle in peripheral tissues for a long time, first cells to respond to reinfection

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20
Q

what is immunological memory

A

the ability of the immune system to respond with greater vigour upon re ecounter with the same pathogen

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21
Q

why would vaccination not be 100% effective

A

incomplete uptake of boosters
small percentage may not respond
immune deficiency
poor uptake due to health scares

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22
Q

what is measles

A

a respiratory system infection caused by paramyxovirus via aerosol transmission

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23
Q

what is the MMR vaccine

A

a combined vaccine of measle mumps and rubella - live attenuated vaccine

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24
Q

what is herd immunity and when is it effective

A

immunity developed by a group of vaccinated individuals- immunised majority allow few unimmunised to be protected - effected when 80-95% are vaccinated (depends on disease)

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25
Q

what are the barriers to widespread coverage (herd immunity) in the developed world?

A

access and cost issues among certain populations
language barriers
failure to obtain booster shots/complete series
fears concerning vaccination

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26
Q

what are the barriers to widespread coverage (herd immunity) in the developing countries?

A 
storage requirements
poor infrastructure 
lack of roads
personnel issues
conflict
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27
Q

what components make up the newly film based vaccine

A

attenuated virus, methylcellulose, sugar alcohol and surfactant

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28
Q

what does the SARS-CoV2 virus bind to on the host target cell - what other protein is involved

A

ACE2 (binding to RBD motif of spike)

TMPRSS2 cleaves the spike to allow viral entry

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29
Q

what are the two main influenza antigens

A

Hemagglutinin (binds to host cell receptor)

Neuraminidase (clips polysaccharide chains from host cell surface, facilitate new viral particle release)

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30
Q

what are the types of influenza virus

A 
Influenza A and B (related to seasonal epidemics)
Influenza C (mild symptoms)
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31
Q

what mechanisms cause variations in influenza

A 
antigenic drift (seasonal flus)
antigenic shift (pandemics)
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32
Q

what is antigenic shift

A

re assortment of entire ssRNA between human and animal virons infecting the same cell - human antibodies have no recognition- drives pandemics

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33
Q

what is antigenic drift

A

accumulation of point mutations entail ly yielding a variant protein no longer recognised by the antibody to the original antigen - causes seasonal flu and covid variants

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34
Q

what is sterilising immunity? give example

A

a unique immune status which prevent effective virus infection into the host
sterilising immunity for influenza infection can be created by a vaccine that maintains high levels of neutralising serum antibodies

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35
Q

how does the incubation period of a pathogen effect immune response

A

short incubation doesn’t give time for memory cell activation
long incubation gives sufficient time so memory b cells can produce serum antibodies to clear the virus

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36
Q

what are the 7(9) types of vaccines

A 
live attenuated virus
inactivated or killed virus 
subunit: toxoid and bacterial capsular polysaccharide 
conjugate 
multitalented subunit
nucleic acid: plasmid DNA and mRNA
therapeutic
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37
Q

what is the target for the newly developed breast cancer vaccine

A

Mammaglobin-A secretory protein

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38
Q

how is the mammaglobinA breast cancer vaccine administered, why?

A

delivered by electroporation injection into muscle (accompanied by a small electrical charge to help delivery - opens muscle channels so muscle cells express protein)

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39
Q

why are cancer vaccines hard to develop

A

cancer originates from self, need to avoid problems tolerance

40
Q

what are therapeutic vaccines

A

vaccines to treat already established vaccines

41
Q

give some examples of live attenuated vaccines

A

oral polio
mmr
tuberculosis (BCG-bacilli calmette guerin)
vaccina (cowpox)

42
Q

how is attenuation achieved

A

natural
serial passage and selection of mutants with reduced virulence or toxicity (repeated subculture by growing in bulk and growing sample from it)
chemical mutagenesis

43
Q

what are the advantages of live attenuated vaccines

A

can replicate in host similar to pathogenic bro
larger more sustained dose of antigen
results in increased immunogenicity and more efficient production of highly efficient memory cells
gives long lasting and cell mediated immunity
fewer and lower doses required

44
Q

what are the disadvantages of live attenuated vaccines

A

requires cold storage
may develop symptoms of natural disease
can’t be used in immune deficient people (causes serious complications)
reversion to virulent form possible

45
Q

what are the two polio vaccines developed in 1950s/60s

A

Salk developed inactivated poliovirus vaccine

Sabin developed a live attenuated oral vaccine

46
Q

what was the major issue with sabins polio vaccine

A

it was made from live attenuated virus that random mutagenesis caused reversion to virulent form causing the paralytic disease paralytic poliomyelitis

47
Q

how were live attenuated vaccines made safer

A

recombinant dna technology - can now change large blocks of dna that’s harder to reverse

48
Q

what genes are deleted in the attenuated malaria vaccine

A

p52 and p36

49
Q

give five features of the sabin polio vaccine

A

works be colonising the intestine with three attenuated serotypes of polio virus (so they outcompete each other in gut)
requires three doses
only diff to virulent strain by 9 nucleotides
induces IgA IgM and IgG response

50
Q

how are inactivated/killed vaccines made

A

by using either chemical reagents (formaldyhyde, glutaraldehyde) or heat to destroy the nucleic acid inside the pathogen so it can no longer replicate

51
Q

give examples or inactivated or killed vaccines

A

Pertussis (whooping cough), cholera, typhoid fever, inactivated polio vaccines (Salk), influenza and zika.

52
Q

what is critically important when inactivating a virus for vaccination

A

Critically important to maintain structure of key epitopes on surface antigens

53
Q

what are the advantages of inactivated or killed vaccines

A
  • Inactivated vaccines tend to be safer than live vaccines - can’t revert to virulent form.
  • More stable and don’t require refrigeration – easier storage and transportation.
  • Some may be freeze-dried.
  • Commonly used against both viral and bacterial diseases.
54
Q

what are the disadvantages of inactivated or killed vaccines

A
  • Failure to inactivate pathogen (quality control important)
  • Exposure of virulent pathogen to those making the vaccine.
  • Need to be administered by injection.
  • Produce a weaker immune response than live vaccines – generally requires boosters to illicit immune response.
  • Generally only induce humoral immunity and NOT cell-mediated responses as organisms don’t replicate in host. (no good t cell response)
55
Q

what are subunit vaccines

A

a specific purified macromolecule from pathogen.

56
Q

what vaccine can be given to immunodeficent individuals

A

subunit vaccines/polysaccharide vaccines

57
Q

what are the three main strategies/ types of subunit vaccines

A

toxoids, isolated capsular polysaccharides and purified key recombinant protein antigens.

58
Q

give examples of subunit vaccines

A

Hepatitis B, Streptococcus pneumonia, diphtheria and tetanus.

59
Q

what is a toxoid vaccine

A

exotoxins produced by pathogens are purified and inactivate to eliminate toxicity while maintaining immunogenicity

60
Q

what is the host response to exotoxins

A

anti toxoid antibodies bind to and neutralise effect of exotoxin

61
Q

what pathogens can toxoid vaccines be used for

A

diptheria and tetanus

62
Q

what are bacterial capsular polysaccharide vaccines

A

type of subunit vaccine that involves a polysaccharide capsule coated in antibodies and/or complement increasing the ability of macrophages and neurophils to phagocytose

63
Q

what two current vaccines use capsular polysaccharide vaccines

A

Current vaccine for Streptococcus pneumoniae consists of 13 antigenically distinct polysaccharides.
Neisseria meningitidis vaccine, cause of bacterial meningitis, consists of purified capsular polysaccharides

64
Q

what are the advantages of subunit vaccines

A
  • They are relatively easy to produce and are stable.
  • Generally safer and better tolerated than whole organism vaccines.
  • Can be given safely to immuno-suppressed people.
65
Q

what are the disadvantages of subunit vaccines

A
  • Generally requires strong adjuvants which can often induce a tissue reaction.
  • Duration of immunity is generally shorter than live vaccines.
  • They often need to be linked to carriers to enhance immunogenicity.
  • Several doses must be given for proper life-long immunity.
  • Induce little cell-mediated immunity
66
Q

what are adjuvants, how do they act to this function?

A

: any material that can increase the humoral and cellular immune response against an antigen. - stimulate the innate immune system directly by acting on dendritic cells, macrophages, and neutrophils (improve antigen presentation) – leads to activation of adaptive immune system

67
Q

what is the depot effect induced by adjuvants

A

at site of injection, adjuvants act by slowing the antigen release contain within the vaccine, prolonging the time they’re presented to the body (because they are oily)

68
Q

what 4 mechanisms are used by adjuvants to augment and modulate immunogenicity

A

depot effect
attraction and stimulation of antigen-presenting cells
inflammasome activation
improve the delivery of the antigen

69
Q

how do adjuvants cause attraction and stimulation of APCs

A

can cause local tissue damage to draw in APC stimulating them via pattern recognition receptors on the apcs.

70
Q

describe the inflammasome activation caused by adjuvants

A

a multicomplex protein that forms intracellular complex, detects pathogenic organisms and causes inflammation, release of cytokines to surrounding area recruiting other innate cells. Responsible for redness on arm.

71
Q

how do adjuvants improve the delivery of the antigen

A

improve delivery to the regional lymph nodes and the presentation of the antigen by improving uptake to apcs.

72
Q

what are the advantageous characteristics of adjuvants

A

makes vaccines more cost effective (fewer doses needed)
effective innate immune signals including danger signals
goof immunomodulatory capacity
high specific antibody production
antigen specific clonal expansion
generation of cytotoxic t cells
long lasting adaptive immune response
makes antigen more potent (less dose required
)

73
Q

what are the side effects of adjuvants

A

local reactions: redness, swelling, pain at injection site

systemic reactions: fever, chills, body aches

74
Q

give 4 examples of adjuvants and what vaccines they accompany

A

aluminium based mineral salts - for anthrax and hep A
MF59 - for influenza
Monophophoryl lipid A - for hep B
virosomes - for hep A and influenza

75
Q

what are conjugate vaccines

A

fusion of a highly immunogenic protein to a weak vaccine

76
Q

what vaccine uses a conjugate

A

Haemophilus influenza type b (Hib) vaccine for Hib disease, tetanus, diphtheria, whooping cough, and polio

77
Q

what major part of the immune repsonse do conjugate vaccines not induce

A

does NOT induce memory T cells specific for pathogen

78
Q

what are multivalent subunit vaccines

A

incorporation of antigens into lipid vesicles (intracellular delivery) - designed to increase uptake and presentation of the antigens

79
Q

give an example of a multivalents subunit vaccine, and describe its benefits

A

Immunostimulating complexes (ISCOM); antigenic proteins contained inside phospholipid monolayer.- good at fusing with cell surface of APC so good at delivery for loading onto MHC molecules to induce adaptive immune system response

80
Q

why were recombinant viral vector vaccines developed?

A

Developed to overcome the reversion but retain the sustained antigen exposure

81
Q

how are recombinant viral vector vaccines formed

A

take virulent pathogen, isolate antigen gene/s, get rid of all the other genes (no way of reversion). Then insert gene encoding antigen into an expression vector and put inside a different virus (completely nonvirulent) this construct is injected into the muscle and delivers dna encoding the antigen into the host cell.

82
Q

what bacterial and viral diseases now used recombinant viral vectors

A

hiv, rabies, measles, covid

83
Q

give examples of viruses that are used as vectors in recombinant vaccines

A

modified vaccinia virus Ankara (MVA), adenovirus (Ad) & adeno-associated virus (AAV).

84
Q

how are recombinant viral vector vaccines administered

A

• Administered simply by scratching the skin causing a localised infection.

85
Q

what plasmid gene is commonly used in recombinant viral vector vaccines - and how do you test the success of antigen gene insertion?

A

Thymidine Kinase gene.
To test, add thymidine analogue called BrDU.- in cells with intact TK gene (unsuccessful implant) thymidine kinase converts nucleotide into nucleoside which is then incorporated into the viral genome. – this kills all the viral particles

86
Q

how does the Astrazeneca/Oxford Uni ChAdOx1 nCoV-19 vaccine work

A

Adenovirus vector-based, (tough coat, no cold storage)
Encodes codon optimised full length spike protein into modified chimp adenovirus. Deliver antigen coding gene into cells but cannot replicate.
Host cell machinery produces spike protein, some expressed on cells surface other loaded onto mhc molecule and put on the surface
Helps activate helper t and cd8 t cells. Give good humoral (neutralising antibodies) and cell mediated (cytotoxic t-cell activation) response

87
Q

what are nucleic acid vaccines

A

vaccines that involves the administration of genetic material encoding the desired antigen. in the form of either plasmid containing DNA or a lipid encapsulating mRNA so the encoded antigen is made and expressed by the host cell itself

88
Q

why are most DNA vaccines administered via intramusclular injection

A
  • muscle avidly takes up DNA.

- relatively low turnover rate of muscle cells prevents dispersion in dividing cells – prolonged exposure

89
Q

give examples of DNA vaccines

A

Hepatitis B, malaria, HIV, Influenza, Zika, Dengue fever, HPV, cancer, and Coronavirus.

90
Q

what are the two main routes of DNA vaccines

A

Direct: DNA taken up directly by antigen presenting cells at point of injection, these express antigen and load onto MHC molecules to display on surface
Indirect: DNA taken up by non APCs (keratinocytes and myocytes), express antigen or released ectracellularly. at some point transfer to APCs where expressed on MHCs on surface

91
Q

what are the advantages of DNA vaccines

A
  • Low intrinsic immunogenicity of nucleic acids
  • Induction of long-term immune responses
  • Induction of both humoral and cellular immune responses
  • Possibility of constructing multiple epitope plasmids
  • Heat stability
  • Ease of large-scale production
92
Q

what are the disadvantages of DNA vaccines

A
  • Effects of long-term expression unknown
  • Formation of antinucleic acid antibodies possible
  • Possible integration of the vaccine DNA into the host genome
  • Concept restricted to peptide and protein antigens
  • Poor delivery
  • Poorly immunogenic in man
93
Q

what are the basic structural elements of mRNA vaccines

A
  • 5’ cap: helps achieve superior translational performance by stabilizing the mRNA molecule and directing the immune response.
  • 5’ and 3’ untranslated region (UTR): contain various regulatory sequences associated with the stability of mRNA, recognition of mRNA by ribosomes, interaction with the components in translational Machinery.
  • Coding region
  • Poly(A) tail: maximises the translational performance of mRNA vaccines.
94
Q

what are the advantages of mRNA vaccines vs DNA vaccines

A
  • mRNA vaccines appear to perform better.
  • Does not need to enter nucleus.
  • Safer – no possibility of integration into host genome.
95
Q

what are the disadvantages of mRNA vaccines

A

• Stability – requires storage at -80 °C or -20°C

96
Q

what are antiidiotypic vaccines

A

A vaccine made of antibodies that see other antibodies as the antigen and bind to it. Can stimulate the body to produce antibodies against tumor cells.

comprise antibodies that have three-dimensional immunogenic regions, designated idiotopes, that consist of protein sequences that bind to cell receptors. Idiotopes are aggregated into idiotypes specific of their target antigen. An example of anti-idiotype antibody is Racotumomab.
mainly used for high risk cancer patients

Immunology, infection and inflammation (8 decks)

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