L11 Flashcards
What cells secrete IFN gamma?
CTL (cytotoxic t lymophocytes?) and other cells
What does IFN gamma do?
Enhance expression of MHCI (endogenous derived peptides ) (IFN gamma R on cell and then transcription
effects on MHC I locus)
Why is having more MHCI more likely to get a better immune response?
More Ag presentation by increased no. of MHCI molecules
What happens to cells that lack MHCI?
More likely to be killed by NK cells
What is the other role of IFN gamma?
Activate NK cells
What are the two types of immunity?
Active and passive
Give an example of the two types of active immunity and how it’s acquired?
Being exposed to a pathogen naturally, or getting a vaccine
Give an example of the two types of passive immunity and how it’s acquired?
Naturally acquired (breastfeeding) or artificially acquired (acquiring Ab from another person)
How do we achieve immunisation
Through vaccination
What is the half life for passive immunity?
Short (half-life of IgG about 3 weeks)
Give some examples of medical uses of passive immunity
Hypogammaglobulinaemia in infants as maternal IgG
declines
IVIgG every 2-4 weeks for immunodeficiency to maintain
protective levels
Tetanus antitoxin
What is hypogammaglobulinaemia
When maternal IgG is degraded
What is a characteristic of active immunity?
Memory
What is the most dominant Ig class in our circulation?
IgG
Compare secondary vs primary active immunity
faster, greater in magnitude, may be qualitatively better (higher affinity Ab)
Who can immunisation protect?
The individual and the population - the disease declines if the majority of the population is immune
How many people died from Measles in 2022?
136,000 people
What are some of the serious complications that can be caused by measles?
ear infection, pneumonia (esp in young children), sub-accute scloriding panencephalitis (SSPE) (rare but fatal complication involving the CNS)
When was the first vaccine introduced for measles?
1963
When was MMR introduced?
1988
What percentage of the population had to be immunised to prevent outbreaks?
83-94%
What impacted the uptake of vaccination of MMR?
A paper in 1998 linking MMR to autism
What are the requirements of an effective vaccine?
Safe
High level of protection
Long-lasting protection
Right type of response (local or systemic; antibody or cell-mediated immunity)
Low cost
Stable
Easy to administer
Minimal side-effects
What do vaccines contain?
Induce protective response to pathogen without causing disease
List the different types of vaccines
Inactivated, attenuated, subunit, toxoid, conjugate
What do inactivated vaccines contain?
dead organisms
Give an example of an inactivated vaccine
Salk polio vaccine
What are the points that need to be taken in consideration when making an inactivated organism
Important antigens must survive killing
May have side-effects
What do attenuated vaccines contain?
live but virulence disabled - contains live vaccine but is altered?
Give examples of live/attenuated vaccines
Vaccinia (smallpox), sabin (polio - drop on tongue w sugar), MMR or BCG
What are the pros of live vaccines?
Single dose effective
May be given by natural route
May induce local and systemic immunity
May induce right type of response
What are the cons of live vaccines?
Reversion to virulence
Possibility of contamination
Susceptible to inactivation
Causes disease in immunocompromised host
What is polio caused by?
enterovirus
What is the route through which polio is spread?
faeco-oral route
What is the main age group that contract polio
children under 5
What is the rate of patients that end up with paralysis
1/200 (0.05%)
What is polio a member of?
picornaviridae
What sort of RNA does polio have?
positive sense RNA
What happens to the RNA in polio?
translated into a large polypeptide which is cleaved post-translation
How many strains of polio are there?
3
Where is polio more common
Regions like Afghanistan and Pakistan
What do subunit vaccines contain?
Isolated antigens
Give examples of diseases that use subunit vaccines
Hep B, pneumococcal polysaccharide
What is tetanus toixoid
inactivated form of a protein exotoxin secreted by the bacteria
What do conjugate vaccines contain?
Capsular polysaccharide conjugated to a protein
Give examples of diseases that have conjugate vaccines
Hib, MenC, pneumococcal conjugate vaccines (prevnar 13),
How do conjugate vaccines alter the immune response?
TI-2 polysachharide antigen to a thymus dependent TD
What is reverse vaccinology
Screening of the whole genome to identify proteins that could be used as vaccines
Give an example of a disease that uses reverse vaccinology
Neisseria meningitidis group B
How many novel surface proteins were identified in Neisseria meningitidis group B
91
How many induced bacterial Ab in Neisseria meningitidis group B
28
How many components in the Neisseria meningitidis group B vaccine
4
What are some additional conditions that should be considered when developing a vaccine
Inducing the right type of immunity as the wrong type of immune response can do more harm than good
Give an example for vaccines causing more harm than good due to the wrong immune response type
1960 vaccine for resp. syncitial virus - vaccinated children suffered more serious infections with RSV
What are adjuvants?
A substance administered with an antigen to promote the immune response
Why do we no longer use oil adjuvants anymore in humans?
very stimulatory and can lead to necrotic regions
Why do we use adjuvants?
Pure antigens often elicit only weak immune responses
How do adjuvants enhance immune responses?
Providing a depot and by providing immunostimulatory properties
What are the ways adjuvants can act in?
Activate dendritic cells via TLRs or NLRs
Cause release of endogenous danger signals
Promote antigen uptake by dendritic cells
Stimulate release of chemokines/cytokines
Promote ‘cross-presentation’ of exogenous antigens by class I
What type of adjuvants are used in animals?
Freunds adjuvant: oil in water emulsion
Freunds complete adjuvant: also contains mycobacteria
What type of adjuvants are used in humans?
alum most commonly used
aluminium hydroxide or aluminium phosphate
Licensed in 1920s
Better for Ab responses than cell mediated immunity
What are the more recent clinical uses of newer adjuvants?
MF95 (novaritis_
ASO3 (GSK)
ASO4 (GSK)
MenB
Men ACWY
Influenza
Shingles
RSV
What vaccine has had the fastest rate of vaccine development globally
SARS-CoV-19
How many vaccines were ready at the clinical trial stage?
183