L12 - Immunisation

Question 1

What is passive immunity?

Answer 1

Immunity produced by the transfer to one person of antibodies that were produced by another person. Protection from passive immunity diminishes in a relatively short time, usually a few weeks or months

Question 2

What is active immunity?

Answer 2

The immunity which results from the production of antibodies by the immune system in response to the presence of an antigen

Exploits “immunological memory”

Question 3

Secondary vs. primary response

Answer 3

Faster to develop

Greater in magnitude

May be qualitatively better (e.g higher affinity antibody)

Question 4

What is the most effective antibody?

Answer 4

IgG

Question 5

What is herd immunity?

Answer 5

Immunisation can protect:
• The individual
• The population – disease declines in majority of population is immune

Question 6

Thresholds for different diseases

Answer 6

RO is the number of people in an unprotected population an infected person can transmit the disease to

Threshold is the percentage of the population that needs to be vaccinated in order to protect the entire population

Measles is extremely contagious and can spread through the air so has a high RO so needs a high threshold

Question 7

Measles

Answer 7

A highly infectious viral disease; patients develop a rash and a fever

Serious complications can occur:
– Ear infection, which can lead to hearing loss
– Pneumonia, particularly in young children
– Sub-acute sclerosing panencephalitis (SSPE): a rare but fatal complication involving the CNS

Question 8

Herd immunity & measles

Answer 8

MMR vaccine introduced in 1988

Need 83-94% of population immune to prevent outbreaks

1998 paper from Wakefield and colleagues linked MMR vaccine to autism

The paper was subsequently retracted but bad publicity resulted in a decline in uptake of vaccination and outbreaks are occurring

Question 9

When has a country eliminated a disease?

Answer 9

A country has ‘eliminated’ the disease when it has stopped it freely circulating for at least three years

Question 10

Requirements for an effective vaccine

Answer 10

• Safe
• High level of protection
• Long-lasting protection
• Right type of response
• Low cost
• Stable
• Easy to administer
• Minimal side-effects

Question 11

What are the 5 types of vaccine?

Answer 11

Inactivated

Attenuated

Subunit

Toxoid

Conjugate

Question 12

Inactivated vaccines

Answer 12

Dead/inactivated organisms

Have lost disease producing capacity

e.g. Salk polio vaccine (parenteral injection)

Question 13

Attenuated vaccines

Answer 13

Live but virulence disabled

Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent

Examples:
• Vaccinia (smallpox)
• Sabin (polio)
• MMR (measles, mumps & rubella)
• BCG (tuberculosis)

Question 14

Pros of live vaccines

Answer 14

• Single dose effective
• May be given by natural route
• May induce local and systemic immunity
• May induce right type of response

Question 15

Cons of live vaccines

Answer 15

• Reversion to virulence
• Possibility of contamination
• Susceptible to inactivation
• Causes disease in immunocompromised host

Question 16

The global polio eradication initiative

Answer 16

In 1988, the World Health Assembly (WHA) voted to launch a global goal to eradicate polio via high routine coverage with 3 doses of oral polio vaccine

• 1988: Endemic in >125 countries
• 2016: Endemic in 3 countries: Afghanistan, Pakistan and Nigeria
• Children affected by polio reduced from 1000 per day in 1988 to about 5 per day in 2006
• 99% eradicated

Question 17

What is polio caused by?

Answer 17

Caused by an enterovirus, spread through faeco-oral route

Member of the picornaviridae: positive sense RNA, translated into a large polypeptide which is cleaved post-translation

Question 18

What is a subunit vaccine?

Answer 18

A fragment of a pathogen, typically a surface protein, that is used to trigger an immune response and stimulate acquired immunity against the pathogen from which it is derived

Subunit vaccines need to have an antigen otherwise the B cells cannot recognise the infection

Examples:
• Hepatitis B 
• Diptheria 
• Tetanus 
• Pneumococcal

Question 19

What is a toxoid vaccine?

Answer 19

Toxoid vaccines contain a toxin or chemical made by the bacteria or virus. They make you immune to the harmful effects of the infection, instead of to the infection itself

Examples:
• Diphtheria
• Tetanus

Question 20

What are conjugate vaccines?

Answer 20

Conjugate vaccines combine a weak antigen (polysaccharide) with a strong antigen (proteins) as a carrier so that the immune system has a stronger response to the weak antigen

Converts TI-2 polysaccharide antigen to a TD form

Allows young children to respond

Examples:
• Hib (Haemophilus influenzae type b)
• MenC (meningococcus type C)
• Pneumococcal conjugate vaccines (Prevnar 13®)

Question 21

What is reverse vaccinology?

Answer 21

Whole genome screening to identify proteins that could be used as vaccines

Approach used to develop vaccine against Neisseria meningitidis group B

Question 22

What are adjuvants?

Answer 22

Immunology’s ‘dirty little secret’

A substance administered with an antigen to promote the immune response

Question 23

How do adjuvants enhance the immune response?

Answer 23

By providing a “depot”

By immunostimulatory properties

Question 24

How do adjuvants act?

Answer 24

• 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