IM2 03: Vaccination - Manipulation of the Immune System
Physician Assistant Pa 2013 Session 1 with Tsai at Touro University (NV)
About this deck
By: John Yaw-Jong Tsai
Created: 2011-09-24
Size: 46 flashcards
Views: 15
Created: 2011-09-24
Size: 46 flashcards
Views: 15
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What is the difference between passive and active immunization?
passive immunization
introduction of protective immune cells or molecules generated by active immunization in another organism
active immunization
introduction of antigen that generates active immune response that leads to protective immunity and memory
introduction of protective immune cells or molecules generated by active immunization in another organism
active immunization
introduction of antigen that generates active immune response that leads to protective immunity and memory
What are adjuvants?
a prerequisite for a good immune response is inflammation
adjuvants are combined with vaccines to aid in the immune response to vaccine
adjuvants are combined with vaccines to aid in the immune response to vaccine
How do adjuvants work?
adjuvants work by
concentrating vaccine at site of introduction to limit spread - easier to attack if all in one place
(except with live-attenuated)
non-specifically induces inflammation at site of introduction
(antigen-independent inflammation)
concentrating vaccine at site of introduction to limit spread - easier to attack if all in one place
(except with live-attenuated)
non-specifically induces inflammation at site of introduction
(antigen-independent inflammation)
What is Freund's complete?
Freund's complete is an emulsion of killed mycobacteria and mineral oil
a very strong adjuvant and can be fatal (by septic shock; LPS)
a very strong adjuvant and can be fatal (by septic shock; LPS)
What adjuvants are used for humans?
adjuvants used for humans are
alum
a form of aluminum hydroxide
MF59
emulsion of squalene, oil and water
weaker than Freund's complete, but safer without side effects of death
alum
a form of aluminum hydroxide
MF59
emulsion of squalene, oil and water
weaker than Freund's complete, but safer without side effects of death
What are the 4 normal forms/types of vaccines?
4 types of vaccines
killed or inactivated vaccines
live-attenuated vaccines
subunit vaccines
conjugate vaccines
killed or inactivated vaccines
live-attenuated vaccines
subunit vaccines
conjugate vaccines
What are killed or inactivated vaccines?
pathogen is killed or has had its virulence factors removed
bacteria is killed
virus is inactivated
still can stimulate immune system
bacteria is killed
virus is inactivated
still can stimulate immune system
How are killed or inactivated vaccines made?
killed or virulence factors removed by
chemical treatment with formalin
heat killing by autoclave
irradiation to create unrepairable nucleic acid damage
safer than live-attenuated vaccines
chemical treatment with formalin
heat killing by autoclave
irradiation to create unrepairable nucleic acid damage
safer than live-attenuated vaccines
What are some common examples of killed or inactivated vaccines?
some examples of killed or inactivated vaccines
influenza vaccines
rabies vaccine
Salk polio vaccines
influenza vaccines
rabies vaccine
Salk polio vaccines
What are some problems with killed or inactivated vaccines?
problems with killed or inactivated vaccines
large quantities of inactivated pathogen needed
suitability of genome for irradiation (large genomes are difficult to break)
health hazards of chemicals used in killing or inactivation process
large quantities of inactivated pathogen needed
suitability of genome for irradiation (large genomes are difficult to break)
health hazards of chemicals used in killing or inactivation process
What are live-attenuated vaccines?
pathogen virulence factor removed by manipulation of its genome
forced evolution of a virus in culture of non-human cells
direct manipulation of viral or bacterial genome using molecular biological techniques
(genetic re-sequencing)
forced evolution of a virus in culture of non-human cells
direct manipulation of viral or bacterial genome using molecular biological techniques
(genetic re-sequencing)
forced evolution o fa virus in culture of non-human cells
first grown in human cells
then grown in non-human cells
virus acquires mutations that adapt it for non-human cells
until virus no longer infects human cells efficiently ⇒ can be used as a vaccine
first grown in human cells
then grown in non-human cells
virus acquires mutations that adapt it for non-human cells
until virus no longer infects human cells efficiently ⇒ can be used as a vaccine
Describe recombinant techniques to attenuate viruses or bacteria
all genes involved in virulence but not required for growth are removed
same technique for bacteria
bacteria have many virulence genes located in a plasmid
same technique for bacteria
bacteria have many virulence genes located in a plasmid
What are the pros and cons of using live-attenuated vaccines?
live-attenuated vaccines
pros
best at inducing an immune response
cons
safety - very small chance of reversion into full pathogenicity
e.g. Sabin polio vaccine
mutated at 6 bases, but only takes 1 base to mutate back to become full pathogen again
pros
best at inducing an immune response
cons
safety - very small chance of reversion into full pathogenicity
e.g. Sabin polio vaccine
mutated at 6 bases, but only takes 1 base to mutate back to become full pathogen again
What are subunit vaccines?
subunit vaccines are parts of proteins, lipids or polysaccharides present on exterior of viral particles or bacterial capsules
isolated and purified as a vaccine
humoral immune response are made against these 'pieces of pathogens'
isolated and purified as a vaccine
humoral immune response are made against these 'pieces of pathogens'
What are the different types of subunit vaccines?
different types of subunit vaccines
protein subunit
polysaccharide subunit
toxoid subunit
DNA vaccines
viral vectors
protein subunit
polysaccharide subunit
toxoid subunit
DNA vaccines
viral vectors
Differentiate between protein and polysaccharide subunit vaccines
protein subunit vaccines
genes for proteins produced in large quantities by recombinant techniques
polysaccharide subunit vaccines
capsules of bacteria are purified and used as subunit vaccine
genes for proteins produced in large quantities by recombinant techniques
polysaccharide subunit vaccines
capsules of bacteria are purified and used as subunit vaccine
Give one common example of a subunit vaccine
(the first licensed vaccine produced in US by recombinant DNA technology)
(the first licensed vaccine produced in US by recombinant DNA technology)
HBV vaccine (HBsAg) protein subunit
hepatitis B virus vaccine
produced by recombinant DNA techniques and grown in yeast
hepatitis B virus vaccine
produced by recombinant DNA techniques and grown in yeast
Why are polysaccharide subunit vaccines not generally given to children under 18 months old?
polysaccharide subunit vaccines elicit a T-cell independent response that is poor in children under 18 months old
What is the most successful of bacterial subunit vaccines developed?
toxoid subunit vaccines are the most successful of bacterial subunit vaccines developed
bacterial toxins are inactivated by treatment with formalin
toxin loses its pathogenicity but still elicits immune response
bacterial toxins are inactivated by treatment with formalin
toxin loses its pathogenicity but still elicits immune response
Give some examples of toxoid vaccines
tetanus toxoid and diphtheria toxoid
DTP: combination of diphtheria and tetanus toxoid
along with killed Bordetella pertussis
DTaP: combination of diphtheria and tetanus toxoids
along with acellular pertussis (aP) component
(inactivated pertussis toxin)
DTP: combination of diphtheria and tetanus toxoid
along with killed Bordetella pertussis
DTaP: combination of diphtheria and tetanus toxoids
along with acellular pertussis (aP) component
(inactivated pertussis toxin)
What are the different types of acellular pertussis (aP) components used in DTaP vaccines?
inactivated pertussis toxins
hemagglutinin
pertactin
fimbrillar
combined with diphtheria and tetanus toxoids to make DTaP vaccines
hemagglutinin
pertactin
fimbrillar
combined with diphtheria and tetanus toxoids to make DTaP vaccines
What are DNA vaccines?
DNA vaccines count as subunit vaccines
patient inoculated with plasmids that have a complementary DNA (cDNA) that codes for protein antigen
host cells take up cDNA and express protein
protein presented to T-cells to elicit an immune response
patient inoculated with plasmids that have a complementary DNA (cDNA) that codes for protein antigen
host cells take up cDNA and express protein
protein presented to T-cells to elicit an immune response
For DNA vaccines, how would growing plasmids in bacteria that are rich in unmethylated CpG nucleotides enhance the immune response against it?
unmethylated CpG nucleotides are recognized by TLR9 (a PRR) on macrophages and other cells
enhancing innate immune response (macrophages) will enhance adaptive immune response
enhancing innate immune response (macrophages) will enhance adaptive immune response
How can DNA vaccines work by transfecting dendritic cells in vitro with cDNA plasmid?
dendritic cells are removed and transfected with cDNA plasmid
take up cDNA and express the protein
dendritic cells then introduced back into host
present expressed protein from plasmid
take up cDNA and express the protein
dendritic cells then introduced back into host
present expressed protein from plasmid
DNA complete with promoter
encodes a single protein from a pathogen
it can be introduced into whole organism
or into dendritic cells that are removed and then returned to host
in use as trial for tumor vaccine
encodes a single protein from a pathogen
it can be introduced into whole organism
or into dendritic cells that are removed and then returned to host
in use as trial for tumor vaccine
viral genomes modified to include protein from a pathogen to be vaccinated against
recombinant virus acts as a live-attenuated vaccine and elicits better immune response against both virus and pathogen proteins of interest
recombinant virus acts as a live-attenuated vaccine and elicits better immune response against both virus and pathogen proteins of interest
How does 'incidence of preexisting immunity' affect viral vector vaccines?
important when choosing which viral vector to use
if the incidence or preexisting immunity against a viral vector is high in a population, then the host will destroy the viral vector before the pathogen proteins are expressed
affects vector reusability
if the incidence or preexisting immunity against a viral vector is high in a population, then the host will destroy the viral vector before the pathogen proteins are expressed
affects vector reusability
What types of DNA subunit vaccines are there?
types of DNA subunit vaccines
cDNA subunit vaccine
complete plasmid DNA subunit vaccine
viral vector subunit vaccine
cDNA subunit vaccine
complete plasmid DNA subunit vaccine
viral vector subunit vaccine
What are conjugate vaccines?
viral or bacterial target antigen is fused or conjugated to a harmless but immunogenic protein that elicits a T-cell dependent response
it is a method for making a T-cell independent subunit vaccine into a T-cell dependent subunit vaccine
it is a method for making a T-cell independent subunit vaccine into a T-cell dependent subunit vaccine
B-cell receptor (Ig) recognizes polysaccharide, which is linked to an immunogenic protein
immunogenic protein presented to T-cell to elicit immune response and activates B-cell
Ig is made against polysaccharide
(original molecule recognized by B-cell)
immunogenic protein presented to T-cell to elicit immune response and activates B-cell
Ig is made against polysaccharide
(original molecule recognized by B-cell)
What is a common conjugate vaccine?
Are there any problems in production of this vaccine?
Are there any problems in production of this vaccine?
H. influenza-B vaccine is a common conjugate vaccine
common problems: none
common problems: none
How would the route of vaccination affect the immune response?
intestines and eye, ear, nose (ENT) regions often provide local response and memory
pathogen entry through skin and blood more likely to induce systemic response and memory - which may not protect against entry from intestines or eye, ear, nose (ENT)
pathogen entry through skin and blood more likely to induce systemic response and memory - which may not protect against entry from intestines or eye, ear, nose (ENT)
Why are newer vaccines moving towards nasal sprays?
nasal spray vaccines induce local response and memory at route of most infection
most infections enter body through eating or breathing (ENT) but intramuscular vaccinations not efficient at producing response at intestines, or ENT
most infections enter body through eating or breathing (ENT) but intramuscular vaccinations not efficient at producing response at intestines, or ENT
What are some difficulties in immunizing infants?
difficulties in immunizing infants due to
poor T-independent Ig production
lower Ig responses to T-dependent protein vaccines
short-lived Ig responses to vaccines
inhibitory effect of maternal Ig
altered T-cell responses
poor T-independent Ig production
lower Ig responses to T-dependent protein vaccines
short-lived Ig responses to vaccines
inhibitory effect of maternal Ig
altered T-cell responses
What is meant by poor T-independent Ig production?
prior to age of 2 yrs, there is low response to T-cell independent (polysaccharide) antigens due to lack of marginal zone (spleen) B-cells
spleen marginal zone not developed until near 2 yrs old
spleen marginal zone not developed until near 2 yrs old
What is meant by lower Ig responses to T-dependent protein vaccines?
germinal centers in lymph nodes are delayed in appearance in infants
unknown reason
unknown reason
What is meant by short-lived Ig responses to vaccines?
B-cells differentiate into plasma cells (plasmablasts) but fail to survive as long in infants as they do in older children or adults
What is meant by inhibitory effect of maternal Ig?
maternal Ig will inhibit (by outcompeting) infant Ig production, but not T-cell responses
the effect of vaccines becomes diminished, but still exists
which is why vaccines are still given since there are no negative effects
e.g. measles vaccine
the effect of vaccines becomes diminished, but still exists
which is why vaccines are still given since there are no negative effects
e.g. measles vaccine
What is meant by altered T-cell responses?
infants show skewered TH2-cell responses
neonatal dendritic cells produce different cytokines than adult dendritic cells to the same antigen
neonatal dendritic cells produce different cytokines than adult dendritic cells to the same antigen
The many potential barriers to infant vaccination lead to the use of multiple doses and boosters. T/F?
true
poor T-independent Ig production
lower Ig responses to T-dependent protein vaccines
short-lived Ig responses to vaccines
inhibitory effect of maternal Ig
altered T-cell responses
poor T-independent Ig production
lower Ig responses to T-dependent protein vaccines
short-lived Ig responses to vaccines
inhibitory effect of maternal Ig
altered T-cell responses
Which type of vaccine induces the best response in infants compared to other vaccine types?
live-attenuated vaccines
pathogen virulence factor removed by genetic manipulation
forced evolution of a virus in culture of non-human cells
direct manipulation of viral or bacterial genome using molecular biological techniques
(genetic re-sequencing)
pathogen virulence factor removed by genetic manipulation
forced evolution of a virus in culture of non-human cells
direct manipulation of viral or bacterial genome using molecular biological techniques
(genetic re-sequencing)
What are the pros and cons of live-attenuated vaccines?
live-attenuated vaccines
pros
best at inducing an immune response
cons
safety - very small chance of reversion into full pathogenicity
e.g. Sabin polio vaccine
mutated at 6 bases, but only takes 1 base to mutate back to become full pathogen again
pros
best at inducing an immune response
cons
safety - very small chance of reversion into full pathogenicity
e.g. Sabin polio vaccine
mutated at 6 bases, but only takes 1 base to mutate back to become full pathogen again
What is herd immunity?
herd immunity
if vast majority of population is vaccinated or immune to a pathogen, there are fewer individuals that can become infected and expose those that are also not immune
declining vaccination rates lead to increase in measles, whopping cough
if vast majority of population is vaccinated or immune to a pathogen, there are fewer individuals that can become infected and expose those that are also not immune
declining vaccination rates lead to increase in measles, whopping cough
BCG is similar to Mycobacterium tuberculosis such that an immune response to shared epitopes allows some protection. T/F?
true
US does not vaccinate using BCG because BCG causes a full infection and is not attenuated
instead, performs surveillance and containment of TB infections (skin test, X-rays)
US does not vaccinate using BCG because BCG causes a full infection and is not attenuated
instead, performs surveillance and containment of TB infections (skin test, X-rays)
What are some common side effects of DTaP?
inflammation at site of injection, within 2 days, usually after 4th or 5th injection
up to 5% may get a fever over 101°F
1 in 3,000 may get fever over 104ºF
only 1 in 14000 may have convulsions from fever
fever caused by reaction to vaccine/adjuvant only
up to 5% may get a fever over 101°F
1 in 3,000 may get fever over 104ºF
only 1 in 14000 may have convulsions from fever
fever caused by reaction to vaccine/adjuvant only
About this deck
By: John Yaw-Jong Tsai
Created: 2011-09-24
Size: 46 flashcards
Views: 15
Created: 2011-09-24
Size: 46 flashcards
Views: 15
About StudyBlue
STUDYBLUE makes things that make you better at school.
Things like online flashcards with photos and audio.
Things like personalized quizzes and friendly reminders about when (and what) to study next.
Think of it as a digital backpack™: access to all of your study materials online and on your phone.
STUDYBLUE exists to make studying efficient and effective for every student, for free. Join us.
“I have used this website for three exams, and I see a huge difference in my test results.”
Naj
Naj