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Microbiology > Defence against bacteria > Flashcards

Defence against bacteria Flashcards

1
Q

What are the properties of a good vaccine?

A
  • Stimulates an effective immune response
  • Safe and does not cause adverse reactions
  • Inexpensive
  • Stable
  • Easy to administer
  • Simple for both manufacturer and regulatory authorities to control
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2
Q

What happens in phase 1 vaccine trials?

A
  • for safety
  • used to assess immunogenicity (ability to induce immune response)
  • small number of adults
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3
Q

What happens in phase 2 vaccine trials?

A
  • to assess immune response and safety

- all groups of people

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4
Q

What happens in phase 3 vaccine trials?

A
  • placebo controlled double blind studies
  • data needed for licensure
  • requires good disease surveillance
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5
Q

How is vaccine efficacy calculated?

A

Done in phase 3 trials

vaccine efficacy= 1-(attack rate in vaccinated/attack rate in unvaccinated)

usually a %

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6
Q

What is the definition of vaccine efficacy?

A

The reduction in the incidence of disease among people who have received a vaccine compared to the incidence in unvaccinated people.

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7
Q

What is the definition of herd immunity?

A

Form of immunity that occurs when the vaccination of a significant portion of the population provides a measure of protection for individuals who have not yet developed immunity.

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8
Q

When is the herd effect determined?

A

post vaccine introduction

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9
Q

How is the herd effect calculated?

A

1-(attack rate unvaccinated post introduction/attack rate unvaccinated pre introduction)

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10
Q

What are the three main elements that vaccines contain and what are their roles?

A
  • Antigen
    To stimulate immune response to the target disease
  • Adjuvant
    To enhance and modulate the immune response
  • Excipients
    Buffer, salts, saccharides and proteins to maintain the pH, osmolarity and stability of the vaccine
    Preservative
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11
Q

What vaccines do children have around 2 months of age?

A
  • DTaP Hib IPV

- pneumonccocal conjugate

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12
Q

What vaccines do children have around 3 months of age?

A
  • MenC conjugate

- DTaP Hib IPV

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13
Q

What vaccines do children have around 4 months of age?

A
  • DTaP Hib IPV
  • pneumonccocal conjugate
  • MenC conjugate
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14
Q

What vaccines do children have around 1 years old?

A
  • Hib booster
  • pneumonccocal conjugate
  • MenC booster
  • MMR
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15
Q

From 3 years 4 months onwards which vaccines do children recieve?

A
  • before primary school: DTaP-IPV and MMR booster
  • girls aged 12-13 get HPV
  • during secondary school DT-IPV
  • ages 10-14 or sometimes neonatal BCG
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16
Q

What does DTaP-Hib-IPV mean?

A
  • Tetanus and Diptheria Toxoids
  • Bordatella pertussis - whooping cough
  • Haemophilus influenzae type b
  • Polio
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17
Q

What are conjugate vaccines?

A
  • Carbohydrate chemically linked to immunogenic protein (usually protein is conjugate and carbohydrate is the antigen)
  • T cell recognition of protein carriers enhances B cell activation
  • Promotes efficient antibody response to polysaccharide capsule
18
Q

How do pathogenic bacteria avoid host defences?

A

Resist Complement

  • Having thick cell wall (Mycobacterium tuberculosis)
  • Capsule (Neisseria meningitidis)

Resist Antibodies

  • Antibody protease (Streptococcus pneumoniae)
  • Antigenic variation (Neisseria gonorrhoeae)

Resist Phagocytosis

  • Polysaccharide capsule (Neisseria meningitidis)
  • Debilitate phagocytes (Yersinia pestis)
  • Hide inside other cells (Chlamydia)

Inhibit Intracellular Killing

  • Escape from phagosome (Listeria monocytogenes)
  • Block phagosome maturation (Mycobacterium tuberculosis)
19
Q

What are the types of vaccines?

A
  • toxoids
  • conjugates
  • live attenutated
  • killed whole cell
20
Q

How do you calculate the vaccine coverage needed to achieve the herd effect?

A

(1-1/R0)/effectiveness

21
Q

For pathogens with complex, multiple ill defined antigens, which vaccines are required?

A
  • live attenuated

- killed whole organisms

22
Q

For pathogens with small number of wee defined antigens, which vaccines are required?

A
  • toxoids
  • polysaccharide conjugates
  • purified component vaccines
23
Q

Explanation of herd immunity with S, q and R0

A

In an endemic state R0=1/S
S=1-q

in herd immunity
q>=1-1/R0 and disease will die out

24
Q

Active vs passive immunity

A
  • Active immunity is elicited in the host in response to an antigen
  • Passive immunity is the acquisition of protection from another immune person through transfer of
    antibodies of activated T-lymphocytes
25
Q

Give an example of live attenuated vaccine

A
  • BCG
  • Typhoid
  • Ones for salmonella typhi being developed
26
Q

What are the advantages of DT vaccine?

A
  • simple to produce
  • relatively pure
  • safe
  • high protective efficacy (very immunogenic and appropriate immune response)
27
Q

What do the tetanus and diptheria toxins do?

A
  • Tetanus toxin is a neurotoxin causing muscle spasm.

- Diphtheria toxin like tetanus toxin is an exotoxin. Affects nose, throat and skin

28
Q

Whooping cough

A
  • aP part of vaccine
  • caused by Bordetella pertussis infecting ciliated epithelium and releasing toxins
  • characterized by convulsive cough
29
Q

Acceptibility of whole cell pertussis vaccine

A
  • Whole cell pertussis vaccine is effective
  • It has been associated with a number of adverse reactions e.g. anaphylaxis,
    prolonged crying, febrile seizures
  • Development of acellular (component) vaccine driven by poor acceptance of the whole cell vaccine
30
Q

B. pertussis components contributing to virulence

A
  • Attachment to ciliated epithelium
  • Adherence and complement resistance
  • Toxins
    pertussis toxin (PT)
    adenylate cyclase
31
Q

The whooping cough problem

A

The acellular vaccine was introduced in the UK in 2004. The vaccine was initially very effective but by eight years later their was an increase in cases and deaths caused by whooping cough. This was addressed in 2013 by the introduction of maternal immunisation but leaves questions about the different immunobiology of the two types of vaccine and how to improve the acellular product.

32
Q

Why did the aP vaccine not provide herd immunity?

A

Acellular pertussis vaccine induces an immune response that is different from natural infection or vaccination with whole cell vaccine. This may explain the resurgence of whooping cough where aP has been widely used. It suggests that aP vaccines need further development.

33
Q

Hib

A
  • H. influenzae type b causes meningitis and septicaemia in the young.
  • Bacterial surface covered by a polyribosyl-ribitol phosphate capsule.
  • Polysaccharides are poorly immunogenic
    The Hib component is a conjugate vaccine
34
Q

Examples of DTaP-Hib-IPV and what is contained

A
  • pediacel
  • infranrix

contain tetanus toxiud, diptheria toxoid, pertussis components (pertussis toxid, pertactin, filamentous haemoaglutinin), Hib PRP conjugate and inactivated polio virus type 1/2/3 and adjuvant (aluminium phosphate)

35
Q

What are the 3 types of conjugate vaccines prepared?

A
  • Random activation of polysaccharide
  • Degradation of the polysaccharide to form active functional groups at both terminals
  • Degradation of the polysaccharide to form active functional group at only one terminal
36
Q

Examples of conjugate vaccines

A
  • Hib
  • Pneumococcal conjugates
  • Men C
  • Men ACYW
37
Q

Vaccine against group B meningoccocal disease

A
  • OMVs (outer membrane vescicles) are released spontaneously by meningococci in vivo and in culture
  • They contain all the protein antigens usually associated with the OM
  • Vaccines are produced by extraction and by reducing the endotoxin content
38
Q

Does BCG work?

A
  • Cannot be answered definitively
  • Generally accepted that it prevents severe childhood TB and leprosy
  • Variation in field trials of BCG: methodology, vaccine variation (strain, dose, potency)
  • Regional differences in TB strains
39
Q

What are the two types of adjuvants?

A
  • Serve to potentiate the right immune response
  • Might be used to enhance/strengthen the immune response, to determine whether the humoral or CMI arms of the immune system are stimulated, to direct the Th cell response, or to favour antibody subclasses
  • Adjuvants broadly fall into two groups: delivery systems and immune potentiators
  • Adjuvants create a depot of antigen that can be released over a period to maximise the immune response.
  • Potentiators specifically stimulate the immune system to obtain the desired response
40
Q

Give examples of adjuvants

A 
Delivery systems:
mineral salts
surface active agents
synthetic microparticles
oil-water emulsions
liposomes
Immune potentiators:
Toxins and lipids
Nucleic acids
Peptidoglycan
Carbohydrates
Peptides
Cytokines and hormones
41
Q

Polysaccharide antigens are usually large, not easily degraded and highly repetitive, what does this mean for the immune response?

A
  • poorly immunogenic because they are t cell independent antigens
  • can cross link immunoglobulins on B cells without T cells
  • immune response is predominantly IgM , poor memory effect and low avidity anitbody

Microbiology (8 decks)

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