Vaccination and Immunisation

Question 1

what is variolation

Answer 1

a method of inoculation first used to immunise individuals against smallpox by rubbing powdered smallpox scabs on skin or blowing powder up nostrils

Question 2

describe Jenners findings about how cowpox can protect against smallpox

Answer 2

1. first demonstration of cross protection using a related, live virus
2. antigens on cowpox induce memory B cells
3. on recall, these secrete antibodies that protect both cowpox and smallpox

Question 3

describe the role of Louis Pasteur

Answer 3

1. developed process of pasteurization
2. developed vaccines against anthrax and rabies

Question 4

outline Louis Pasteurs first study

Answer 4

1. noted that repeated cultures of Pasteurella lost ability to cause disease
2. bacteria had become weakened
3. immunised chickens with attenuated pasteurella were resistant to virulent strain
   - first lab developed vaccine

Question 5

outline Pasteurs second study

Answer 5

1. repeatedly cultured bacillus anthracis and immunised sheep with attenuated strain
2. immunised sheep became resistant to the virulent strain
3. attenuated bacillus anthracis also effective in humans

Question 6

outline Pasteurs third study

Answer 6

1. passaged rabies virus from dogs into brain of rabbits
2. immunised dogs and protected them against virulent rabies
3. created an inactivated vaccine

Question 7

what is the difference between attenuated and inactivated vaccines

Answer 7

• attenuated means live vaccine
• inactivated means dead vaccine

Question 8

define immunity

Answer 8

ability of the human body to protect itself from infectious disease

Question 9

what are the 2 main groups of defence mechanisms in the body

Answer 9

1. innate- non specific and non adaptive mechanisms
2. acquired- specific, adaptive mechanisms

Question 10

describe the strategy of immune defence

Answer 10

1. block infection by utilising barriers to entry- skin, tears, stomach acid, mucus
2. destroy invaders- initially by components of innate immune system (Natural killer cells, phagocytic cells)
3. if that fails, trigger adaptive immune system- antigen presenting cells activate T helper cells

Question 11

what are the 2 basic mechanisms for acquired immunity

Answer 11

1. active
2. passive

Question 12

what is active acquired immunity

Answer 12

1. produced by individuals own immune system- usually long lasting
2. involves cellular responses and humoral responses
3. can be acquired by natural disease or by vaccination

Question 13

what occurs in CD4 lineage in the adaptive immune system

Answer 13

1. bacterial pathogen is presented to antigen presenting cells
2. APCs present it as peptides with MHCII to naive CD4 T helper cells
3. which become effector T cells of 4 basic types

Question 14

what occurs in CD8 lineage in the adaptive immune system

Answer 14

1. APCs (dendritic cells) see antigen and present it with MHCI to naive CD8+ cells
2. CD8+ cells become cytotoxic T cells which produce cytotoxins or trigger apoptosis of the target cell
3. to continue cytotoxic T cell production and create memory cells, APC must interact with activated CD4 T helper cell

Question 15

what are humoral responses

Answer 15

antibody mediated immunity

Question 16

how does antibody provide immunity against infection

Answer 16

1. blocking binding of pathogen to cell surface receptors- neutralising antibodies
2. targeting CTLs to infected cells
3. coating pathogens and targeting them for phagocytosis
4. antibody antigen complexes activate classical complement cascade which leads to destruction of pathogens by phagocytosis or bacterial membrane attack

Question 17

what is cell mediated immunity provided by

Answer 17

effector lymphocytes (T cells) of T helper cells

Question 18

what are the 2 principle classes of cell mediated immunity

Answer 18

1. CD8+ T cells- recognise and destroy infected cells
2. CD4+ Th1 T cells- activate phagocytic macrophages to destroy and engulf bacteria

Question 19

how do Th1 cells activate macrophages

Answer 19

by cytokines

Question 20

what is the role of IgM

Answer 20

major role in complement activation
- limited role in neutralisation
- induced by vaccination

Question 21

what is the role of IgG

Answer 21

• systemic
• all major roles: neutralisation, ADCC, opsonisation and complement activation
• primarily induced by vaccination

Question 22

what is the role of IgA

Answer 22

• principle isotype in secretions at mucosa
• less potent opsonisation, weak activator of complement
• strong viral neutraliser
• can be induced by vaccination but needs specific adjuvant

Question 23

what is passive immunity

Answer 23

protection provided by transfer of antibodies from mother, most commonly across the placenta (IgG) and breast milk (IgA) to child

Question 24

which vaccines should pregnant women be offered and why

Answer 24

1. pertussis- most infant deaths from pertussis at less than 3 months old
2. rubella- can severely damage foetus, so mother offered MMR if not previously vaccinated
3. influenza- pregnant women have increased risk of death if not vaccinated

Question 25

how long does protection provided by MTC transfer last

Answer 25

temporary- few weeks or months
- neonate (1-28 days) is very vulnerable to disease and protected by maternal antibodies

Question 26

how do vaccines produce their protective effect

Answer 26

by inducing active acquired immunity and providing immunological memory

Question 27

what does immunological memory enable

Answer 27

enables the immune system to recognise and respond rapidly to exposure to natural infection at a later date
- to prevent or modify the disease

Question 28

what is the key to an effective vaccine

Answer 28

the ability for it to trigger proliferation of naive T cells
- success depends on whether T helper 1 and CTL responses are induced against intracellular organisms
- or T helper 2 antibody responses are induced against extracellular organisms

Question 29

describe how memory cells work

Answer 29

1. naive T cell proliferates in response to antigen
2. forms effector cells and memory cells which wait for subsequent infection
3. naive B cells do the same, with help from T cells form plasma cells to deal with current infection but also memory cells
4. so if same antigen returns, immune system can respond quickly and potently to destroy it

Question 30

what are adjuvants

Answer 30

compounds that enhance immunogenicity of protein antigens
- enhance the recipients immune response
- 2 broad groups: particulate vaccine delivery systems, immunostimulatory adjuvants

Question 31

what are particulate vaccine delivery systems

Answer 31

1. target antigen to APCs
2. convert soluble proteins into particles, eg. alum (absorbs proteins)

Question 32

what are immunostimulatory adjuvants

Answer 32

1. directly activate APCs through specific receptors (toll like receptors)
2. resulting in inflammatory responses that amplify the innate immune response

Question 33

give examples of adjuvants approved for human use

Answer 33

• aluminium based mineral salts (alum)
• virosomes
• MF59

Question 34

what are the principles of safe and effective vaccination

Answer 34

1. either search for attenuated organisms with reduced pathogenicity to stimulate protective immunity
2. or inactive organisms- will not cause lethal systemic infection in the immunosuppressed
3. use purified components of whole organisms containing only key antigens or nucleic acids that stimulate protective immunity

Question 35

outline the requirements for an effective vaccine

Answer 35

1. intracellular organisms usually need CTL and Ab
   - extracellular organisms usually need Abs
2. provides defence at point of entry
   - stimulation of mucosal immunity may be required at specific mucosa
3. pre existing antibody may be required
4. protection optimised when specific epitopes recognised
   - correct epitopes must be targeted
5. must be safe
6. must protect most vaccinees- rapid generation of herd immunity
7. must generate long lived immunity- repeated booster immunisations often impractical
8. cheap- will be administered to large populations

Question 36

describe the effect of optimising vaccination strategies

Answer 36

1. influences immunogenicity, efficacy and safety of a vaccine
   - including number and intervals between immunisations, use of boost regimens and vaccine modulators (adjuvants)
2. good vaccination schedule requires a minimal number of doses and optimal interval between immunisations
3. use green book for optimised strategies for NHS vaccines

Question 37

what is lifelong vaccination dependent on

Answer 37

immune status
- pregnancy, babies, children, teens, elderly, immunosuppressed or vulnerable patients

Question 38

compare the immunogenicity between the main parenteral vaccine routes of administration

Answer 38

1. intradermal immunisation generates greater immune response than IM injection
   - dermis contains more dendritic cells which facilitate the capture of antigens
   - but may be difficult to administer in children
2. sc or IM induce similar responses
3. less toxicity/anaphylaxis via IM and easier to do than sc or iD

Question 39

how can issues with IM injections be overcome

Answer 39

1. use oral or nasal route of administration
   - most pathogens enter via mucosa
   - adjuvants can play role in directing response to appropriate mucosa