Vaccine 2 Flashcards

1
Q

subunit vaccines are

A

isolated components of microorganisms e.g. individual proteins or polysaccharides

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2
Q

Subunit vaccine primarily provoke which response

A

antibody response

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3
Q

antibody response (6)

A

1) agglutination
2) opsonisation
3) neutralisation
4) activation of complement
5) inflammation
6) antibody-dependent cell-mediated cytotoxicity

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4
Q

protein processing pathways

A

CD5 T response- MHC2

CD8 T response-MHC I

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5
Q

CD4 T cell response

A

proteins processed via endosomal pathway, which causes inflammation, macrophage activation and antibody production

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6
Q

CD8 T cell response

A

proteins processes via cytosolic pathways

  • kills infected cell
  • cytotoxic T cell
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7
Q

polysaccharide sub-unit vaccines are based on the fact

A

that all bacteria are coated in sugar

- different bacteria have very specific sugars- which makes them good vaccines

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8
Q

the different combinations of polysaccharides make up

A

unique cell surface structures

- antibodies can be are again

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9
Q

the different combinations give arise to

A

immunologically distinct polysaccharides

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10
Q

Streptococcal pneumoniae is the

A

Major cause worldwide of community acquired pneumonia, bacterial meningitis, bacteraemia and otitis media
- causes systemic infections which are hard to treat due to the time of diagnosis being to late

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11
Q

Streptococcal pneumoniae is a bacteria

A

that had an abundance of polysaccharide on its outer layer

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12
Q

how are antibodies protective against streptococcal pneumoniae

A

opsonising- mostly

complement fixing

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13
Q

issues with developing streptococcal polysaccharide vaccines

A

different strains have different polysaccharides on their surgave

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14
Q

how many serotypes of pstreptococcal polysaccharide

A

90

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15
Q

how do you develop a vaccine which has a potential of 90 different strains

A

o focus on the most abundant serotypes (the ones most likely to cause disease)
o especially meningitis and bacteraemia

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16
Q

currently how many serotypes in vaccines against streptococcal pneumoniae

A

23

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17
Q

Although the very group we want to protect against are the you and elderly do not respond well to polysaccharide vaccine

A

no memory, weak immune system

- adaptive immune system is weak

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18
Q

why do polysaccharides provide weak immunity in the young and elderly?

A

polysaccharides are not processed i the same way as proteins e.g. - through the CD4/CD8 pathways- so don’t get protective responses such as cytokines, which cause inflammation, antibody production, macrophage activation

  • cannot stimulate CD4/CD8
  • immature antibody response
19
Q

immature antibody response with Streptococcal pneumonia vaccines

A

very few IgG- dominated by IgM- directly interact with b cells
- clonal proliferation of B cells

20
Q

how can we get around the issues surrounding streptococcal polysaccharide infections

A
  • link the polysaccharide to a protein carrier
  • means that it behaves more similarly to proteins
  • turning o T cell activation
  • MHC class 2 see the peptide and polysaccharide fragment
  • more IgG
21
Q

example of a protein that can be tagged to the strecptoccal vaccine

A

diphtheria CRM197 toxin ( which is genetically modified- activate site region mutated to abolish toxicity)

22
Q

conjugate vaccines

A

are predominately used against streptococcal disease mix between polysaccharides linked to a protein carrier)

23
Q

streptococcal disease is a massive killer

A

in developing countries

24
Q

23-valent vaccine

A

¥ Pick the serotypes most likely to cause disease.
¥ Isolate polysaccharides from these serotypes (1, 2, 3, 4, 5, 6b, 7F, 8,9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F and 33F)

25
Q

what type of antigen are polysaccharides

A

T cell independent antigens

26
Q

Polysaccharides are t cel idnepdnent antigens

A

no involvement of antigens presenting cell, CD4+/8+ T cells.

- polysaccharides interact directly with B-cells

27
Q

Polysaccharides interact directly with

A

B cells

  • clonal proliferation of B cell
  • production of IgM antibody
    - poor antibody response in children and elderly
    - no memory
28
Q

conjugate vaccine

A

chemically couple protein- polysaccharide vaccine

29
Q

example of polysaccharide vaccines

A
¥	Streptococcus pneumoniae - pneumonia
¥	Haemophilus influenzae - pneumonia
¥	Neisseria meningitidis - meningitis
¥	Salmonella typhi – typhoid fever
¥	Burkholderia pseudomallei - melioidosis
30
Q

mechanisms of T-cell activation by glyconjugate vaccine

A

1) glycoconjugate vaccine is internalised into an endosome of theB cell and processed into glycansaccharides and glycanpeptides
2) MHC II presentation of glycol peptide by MHC II to the ab receptor of CD4+ T cells
4) activation of the T cell by the carbohydrate/MHCII results in T-cell production o cytokines which mature the b cell to become a memory B cell

31
Q

vaccines which induce CD8+ T cell responses

A
  • subunit vaccines evoke CD4= endosome

- we need a vaccine which gets into the cytosol

32
Q

which diseases required CD8+T cell response to clear infections

A
TB
Salmonellosis
Meliondosis
Viral infection- yellow fever, influenza, measles
Cancer vaccines
33
Q

CD8 T cell response is required anytime

A

where killing of host cell is required

34
Q

pathogens which growth within infected cell

A

require a response where the whole cell is destroyed

35
Q

it is difficult to develop vaccines

A

which induce CD8+ T cell responses

36
Q

CD8 T cells

A

kill via cytotoxicity

37
Q

approaches which induce a CD8 T cell response from vaccines

A

1) use live attenuated microbes

2) using naked DNA vaccines

38
Q

Using live attenuated microbes to induce a CD8 T cell response

A

capable of replicating inside the cytosol- presenting protein antigens to the immune system via CD8 T cell responses

  • can survive long enough to establish an immune response
  • balance between over and under attenuation
39
Q

issues with live vaccines

A

may not be able to control infection by attenuated strain

40
Q

Using naked DNA vaccines to evoke a CD8 T cell response

A
  • identify and produce gene coding for vaccine compoenent- protein
  • DNA is taken up into cytoplasm (muscle cells( and transcribed and translated
  • generate specific antigenic proteins
  • an immune response develops
  • cytosol response stimulates CD8 T cell responses
41
Q

issues with DNA vaccines

A
  • difficult to control duration of exposure- how long the DNA will survive
  • works well in animals but not humans
42
Q

in theory DNA vaccines

A

combine the advantage of live and sub-unit vaccines
e.g. West Nile Fever vaccine licensed for use in hordes – vaccines encode coat proteins

e.g. Infectious hematopoietic necrosis vaccine licensed for use in fish- vaccine encode surface glycoprotein

43
Q

summary

A
  • polysaccharides are often included in vaccines
  • to improve the response to the vaccine they are linked to a protein
  • developing vaccines which induce CD8 T cell responses is difficult