Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

204: The immune system > Vaccines and vaccine development > Flashcards

Vaccines and vaccine development Flashcards

1
Q

Immunisation

A

An artificial process by which an individual is rendered immune

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Historical background: variolation

A

Variola: smallpox virus

For variolation, fluid harvested from pustules of recovering individuals and injected under skin of recipient

Crude method of obtaining an inactivated vaccine

Documented practice in far east, middle east and south asia from 1000AD

Limited use in UK 1700s

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Historical background: Jenner

A

used fluid from cowpox lesions to protect against smallpox infections in 1796; recipient was James Phipps aged 8

First documented use of live attenuated vaccine and the birth of modern immunisation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Passive immunisation

A

Immunity conferred without an active host response on behalf of recipient

Passive vaccines are preparations of antibodies taken from hyperimmune donors, either human or animal

Protection is temporary

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

VZV exposure during pregnancy

A

Can cause fetal complications

In case of exposure, women should contact their GP, midwife or virology dept

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Active immunisation (vaccination)

A

Immunity conferred in recipient following the generation of an adaptive immune response

General principle is to stimulate an adaptive immune response without causing clinically apparent infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Most vaccines work by

A

Generating long lasting, high affinity IgG antibody response

Antibodies sufficient to prevent primary infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What goes into a vaccine?

A

Antigen
- to stimulate an antigen specific T and B cell response

Adjuvants
- immune potentiators to increase the immunogenicity of the vaccine

Excipients
- various diluents and additives required for vaccine integrity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Live attenuated vaccines

A

Prolonged culture ex vivo in non physiological conditions

This selects variants that are adapted to live in culture

These variants are viable in vivo but are no longer able to cause disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Pros of live vaccines

A

Replication within host, therefore produces highly effective and durable responses

In case of viral vaccine, intracellular infection leads to good CD8 response

Repeated boosting not required

In some diseases, may get secondary protection of unvaccinated individuals, who are infected with the live attenuated vaccine strain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Cons of live vaccines

A

Storage problems, short shelf life

May revert to wild type

Immunocompromised recipients may develop clinical disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Varicella zoster vaccine

A

Primary infection= chicken pox

Cellular and humoral immunity provide lifelong protection, but virus establishes permanent infection of sensory ganglia

Viral reactivation= zoster

Particularly elderly, fairly debilitating and may cause long term neuropathic pain

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Zoster vaccination

A

Similar VZV preparation, but much higher dose

Aims to boost memory T cell responses to VZV

In over 60s, 50% reduciton in zoster incidence after vaccination compared to controls, reduced severity and complications amongst vaccinated cases

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Poliomyelitis

A

Enterovirus establishes infection in oropharynx and GI tract

Spreads to peyers patches then disseminated via lymphatics

Haematogenous spread

1% of patients develop neurological phase: replication in motor neurones in spinal cord, brainstem and motor cortex, leading to denervation and flaccid paralysis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Sabin oral polio vaccine

A

Live attenuated

Viable virus can be recovered from stool after immunisation

Highly effective, and also establishes some protection in non-immunised population

1 in 750000 vaccine associated paralytic polio

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Salk injected polio vaccine

A

Inactivated

Effective but herd immunity inferior

17
Q

Tuberculosis

A

During primary infection, MTB establishes infection within phago-lysosome of macrophages

Macrophages present TB antigen to MTB specific CD4 T cells which secrete IFN-g

Activates macrophages to encase TB granuloma

May be visible as a calcified lesion on plain CXR

Most TB thought to be re-activation of this primary infection

18
Q

TB vaccination

A

Only licensed product is BCG

Produced by repeat passage of a non-tuberculus mycobacterium

Aims to increase Th1 cell responses to M bovis, thereby conferring protection against MTB

Given by intradermal injection

80% effective in preventing disseminated TB/ TB meningitis in children; little or no effect on pulmonary TB

19
Q

Killed (inactivated)

A

Entire organism used, but physical or chemical methods used to destroy viability

Stimulate B cells and taken up by antigen presenting cells to stimulate antigen specific CD4 T cells

Probably elicit minimal CD8 response as the vaccine cannot undergo intracellular replication

Responses less robust compared to live attenuated vaccines

20
Q

Pros of killed vaccines

A

No potential for reversion

Sage for immunocompromised

Stable in storage

21
Q

Cons of killed vaccines

A

Mainly DC4/ antibody response

Responses less durable than live vaccines

Higher uptake generally required to achieve herd immunity

22
Q

Structure of the influenza virus

A

Internal antigens are type specific proteins and are used to dteremine whether a particular virus is A, B or C

External antigens are subtype and strain specific antigens of influenza A virus: H1N1, H2N2 and H3N2

23
Q

Difficulties of influenza vaccination

A

Target antigens prone to mutation causing seasonal variation- therefore vaccine produced annually based on predictions

CDC provide candidate virus strains to manufacturer; injected into fertilised hens eggs and virus then harvested

More major changes occur when viral strains recombine

24
Q

Subunit vaccines

A

Uses only a critical part of the organism

Components may be:

  • purified from the organism or
  • generated by recombinant techniques

Protection depends on eliciting CD4 and antibody responses

25
Q

Subunit vaccines: toxoids

A

Many examples relate to toxin- producing bacteria

Toxins are chemically detoxified to toxoids

Retain immunogenicity

Work by stimulating antibody response, antibodies then neutralise the toxin

26
Q

Tetanus

A

Pre-formed high affinity IgG antibodies can neutralise the toxin molecules in the circulation; the immune complexes are then removed via the spleen

Anti-toxin can also be given in established cases (passive immunisation)

27
Q

Subunit vaccines: polysaccharide capsules

A

Thick polysaccharide coats of streptococcus pneumoniae and neisseria meningitidis make them resistant to phagocytosis

Vaccines for these organisms formed of purified polysaccharide coats

Vaccines formed of purified polysacchardies coats; aim to induce IgG antibodies that improve posonisation

Suboptimal as polysacchardies are weakly immunogenic

Latest vaccines utilise vaccine conjugation to boost responses: protein carrier attached to polysaccharide antigen

28
Q

Vaccine conjugation

A

Naive B cell expressing surface IgM recognises polysaccharide antigen

Antigen is internalised together with the protein conjugate

Conjugate is processed in the class II pathway

Naive B cell presents peptides from the conjugate to a helper T cell with the correct receptor

T cell helps the B cell to perform affinity maturation, but antibody is specific for the polysaccharide and not for the protein conjugate

29
Q

Recombinant protein subunit vaccine

A

Knowledge of key immunogenic proteins required

Proteins expressed in lower organisms

Purified to produce vaccine

  • hepatitis B surface antigen
  • HPV vaccine

This approach is increasingly employed in vaccine development

30
Q

Human papilloma virus vaccination

A

HPV subtypes 16 and 18 major causal factor in cervical carcinoma

Vaccine development problematic as HPV is difficult to culture

Subunit vaccines are ‘empty virus particles’ that prevent primary infection

Quadravalent vaccine covers additional HPV strains (genital warts, penile cancer)

31
Q

Pros of subunit vaccines

A

Extremely safe

Work well where primary infection may be prevented by an antibody response

Works when the virus cannot easily be cultured e.g. HPV and hep B

32
Q

Cons of subunit vaccines

A

Development requires detailed knowledge of virology, pathogenesis and immunology

Specialised and expensive production

Weaker immune responses- boosting often needed and response rate varies

33
Q

Adjuvants

A

Boost immune response to the antigen

Widely used, but mechanism understood only relatively recently

E.g. alum, lipopolysaccharide

Work by binding to pattern recognition receptors on antigen presenting cells
- this enhances co-stimulation and cytokine secretion, which ensures a robust T/B cell response

Important field for development in order to improve responses to subunit vaccines

Novel adjuvants are toll like receptor ligands e.g. CPG repeats

34
Q

Novel approaches: DNA vaccines

A

Plasmid DNA that encodes vaccine antigen of interest applied; taken up by cells, transcribed and translated

Elicits host immune response

Mainly performed in mice models

Poorly immunogenic to date in human trials

35
Q

Novel approaches: viral vector

A

Benign virus that can be easily grown in culture engineered to carry genes encoding immunogenic antigens

Altered virus used as a live attenuated vaccine

Use restricted to animals to date

204: The immune system (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions