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MIIM20002 - Microbes, Infections, Responses > Lecture 22 - S. pneumoniae Vaccination > Flashcards

Lecture 22 - S. pneumoniae Vaccination Flashcards

0
Q

What receptors do neutrophils have?

A
  • FcR

* CR (complement receptors)

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1
Q

What receptors do neutrophils have?

A
  • FcR

* CR (complement receptors)

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2
Q

What is the function of NETS?

A

Contain bacteria at the site of infection

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3
Q

What is the makeup of a NET?

A
  • DNA
  • Histoproteins
  • Granule contents
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4
Q

What is the name for the production of NETS?

A

NETosis

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5
Q

What are cathelicidins?

A

Antimicrobial proteins in a neutrophil

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6
Q

Describe what is important about colonial selectin

A

Only the B lymphocyte that has the specific TCR appropriate for the antigen will be selected

Then expansion occurs

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8
Q

Describe the concentration of antibody in the blood over time

A
  • Before immunisation: none
  • First immunisation: rapid increase, then decline to a low number
  • Interim: low number (memory)
  • Second immunisation: more antibody made, more quickly
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8
Q

What is the central principle of vaccination?

A

Vaccination will be the first exposure

When we are exposed to the antigen again, the immune response will be heightened and rapid

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9
Q

Describe the magnitude of e response the second time we are exposed to an antigen

A
  • Greater magnitude

* More rapid response

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11
Q

Describe the differentiation of naive cells after exposure to antigen:
• first immunisation
• second immunisation

A

First: naive differentiates into:
• memory
• effector

Second:
• memory cells differentiate into many more effector cells

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12
Q

Which diseases are caused by S. pneumoniae

A

• Pneumonia

  • Septicaemia
  • Meningitis
  • Otitis media
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13
Q

Why vaccinate against TB?

A
  • Most important pathogen for children under 5
  • Debilitating and permanent sequelae
  • Disease occurs in the healthy as well as the immuno compromised
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13
Q

What is the primary site of replication of S. pneumonia

A

Nasopharynx

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14
Q

What we need to know when making a vaccine?

A
  • Pathogenesis of bacterium
  • Nature of immune response which will give protection (B cell, CD4+, CD8+, IgA?)
  • Ensuring response to antigen is immunogenic, not pathogenic
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15
Q

To where does S. pneumonia disseminate?

A

Ears
Lungs
Blood
Meninges

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17
Q

What does the S. pneumoniae vaccine need to protect?

How do we do this?

A 
IgG:
• Blood
• Meninges
IgA:
• Mucosa
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18
Q

What are the virulence factors of S. pneumonia?

A
  • Adhesins
  • Pneumolysin
  • Capsule (critical for virulence)
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19
Q

Describe the functions of pneumolysin

A
  • cilia inhibition
  • cytotoxic to alveolar / endothelial cells
  • triggers C’ cascade
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19
Q

What are the innate immune functions that allow us to recover from infection?

A

Phagocytes
Spleen
PRRs (TLR2, NOD2)

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20
Q

Why is the capsule virulent?

A
  • Allows the bacterium to survive in the blood
  • Masks underlying structures
  • Reduces efficiency of phagocytosis
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21
Q

What are the adaptive immune responses that lead to recovery from infection

A

Antibodies against capsule

–> opsonisation

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23
Q

Why is the spleen important in recovery?

A

Spleen receives antigens from the blood

It is thus a major site of:
• antibody production
• removal of old cells
• removal of antigens

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23
Q

What happens to people without spleens?

A

Suffer from overwhelming infections, due to lack of antigen and immune complex removal

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24
Q

Describe how immune complexes are removed from the blood

A
  1. In tissue, circulation:
    • Red blood cells have C3bR which bind complement in the immune complexes

RBCs + Immune Complexes circulate to spleen

  1. In spleen:
    • Splenic macrophages express C3bR and FcR
    • Endocytosis of complexes; removal
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25
Q

What will the ideal prophylactic vaccine induce?

A

IgA (mucosa)

IgG (meninges and blood)

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27
Q

What will an ideal theraputic vaccine induce?

A

Innate and adaptive responses:
• splenic macrophages
• antibody against capsule

28
Q

Describe the first pneumococcal vaccine

A
  • Whole killed vaccine
  • Sir Almroth Wright
  • South African miners
  • Success questioned
28
Q

How was the whole killed vaccine improved upon?

A

The whole killed vaccine elicited undesirable reactions

They extracted just capsular antigens

29
Q

Describe the vaccine in 1983

A

Pneumococcal polysaccharide vaccine
• just capsular polysaccharide antigens

Vaccine contains 23 of the most common serotypes

80% of infection prevented

30
Q

Describe the structure of a native antigen

A

T cell determinant

B cell determinant

31
Q

Describe the effects of vaccination with capsular antigens (1983)

A

Adults:
• 80% effective in immunocompetent
• Short lived response (no memory)

Elderly, Children, immunocompromised:
• Variable / poor response

32
Q

How are B cells activated to produce antibodies

A
  1. Take up, process antigen, present on MHC II
  2. Th cell activated by macrophage
  3. Th cell activates B cell with presentation of antigen, costimulation and cytokines
  4. B cell makes antibodies
33
Q

What is required for isotype switching and high affinity antibodies?

A

T cell help

–> presentation of antigen on MHC II

35
Q

What does T cell help bring about

A

Memory
High affinity antibody
Isotype switching

36
Q

Can we launch an immune response against polysaccharide at all?

A

Yes

37
Q

Describe how B cells respond to polysaccharide

A
  1. Repetitive antigens
  2. Cross linking to receptors on B cells
  3. B cells activated

NB not T cell help

38
Q

What is produced by B cells that are activated by polysaccharide?

A

IgM

A little IgG

39
Q

Why are highly repetitive polysaccharides required?

A

Only repetitive sugars can cross link on the B cell receptors

Cross linking is required for activation

40
Q

Compare the type of molecule in T cell dependent and T cell independent antigen

A

TD: protein
TI: polysaccharide, lipids, nucleic acids

41
Q

Compare repeating epitopes in T cell dependent and T cell independent antigen

A

TD: no
TI: yes

42
Q

Compare response in infants in T cell dependent and T cell independent antigen

Explain this

A

TD: yes
TI: no

In infants, the immune system has not yet developed to be able to response to TI antigen

43
Q

Compare isotype switching in T cell dependent and T cell independent antigen

A

TD: yes
TI: no (some IgG)

44
Q

Compare antibody affinity in T cell dependent and T cell independent antigen

A

TD: high
TI: low

45
Q

Compare memory in T cell dependent and T cell independent antigens

A

TD: yes
TI: no

46
Q

How do we change our antigens so that the vaccine is more effective?

A

Chemically connect a protein antigen to a polysaccharide antigen

Perform conjugation, because
T cell reacts to protein
B cells react to polysaccharide

47
Q

What is the connection of TD and TI called?

A

Conjugation

48
Q

What does a B cell do to a conjugate antigen?

What is the significance of this?

A

BCR recognises polysaccharides

Takes it up whole thing up

Presents the protein on MHC II

Now, Th cells can recognise this B cell
–> isotype switching, affinity, memory

49
Q

What is the antigen specificity of the antibodies?

A

The capsular polysaccharide

Because the initial B cell receptor recognised the polysaccharide

50
Q

What is the specificity of the T cell receptor?

A

The protein from the conjugated antigen

51
Q

When were conjugated vaccines first licensed in Australia?

Which proteins are used?

A

2001

By 2005, on the national vaccination program

Tetanus toxoid or diphtheria toxoid

52
Q

How many serotypes in the new generation conjugate S. pneumoniae vaccine?

A

Heptavalent - 7 serotypes

Now, 13

53
Q

What are the pros and cons of conjugate S. pneumoniae vaccine?

A

Pros:
- response in children

Cons:
- expensive

54
Q

What is the result of the conjugate vaccine?

A

Children:
72% efficacy against IPD

Adults:
Reduced incidence of pneumonia –> if children don’t have it, their parents won’t

New disease, serotype 19A:
From serotypes that aren’t in the vaccine, esp. 19A

55
Q

What is serotype replacement?

Give an example

A

This is when a non-vaccinated serotype starts to cause the majority of infections

For example:
19A infection rate has increased since vaccination was brought in, because it was not in the vaccine

56
Q

Describe the effect of the vaccine on under 2s from 2001 to 2006

A

Dramatic decrease in IPD

Indigenous communities: still have a higher rate of infection than other groups

57
Q

Why was there also a decrease in IPD in elderly when the children were infected?

A

The children were no longer transmitting the bacteria to their grandparents

HERD IMMUNITY

58
Q

What is herd immunity?

A

This is when vaccinating one group has effects on another group

59
Q

What happened to incidence of IPD due to non 7vPCV serotypes after vaccination?

A

Increase in incidence

Due to serotype replacement

60
Q

Why did the vaccine elicit such a poor response?

A

The vaccine contained only polysaccharide, not protein.

Since there was no antigen presented on MHC, no T cells were activated.

Low affinity antibodies, no isotype switching, no memory

61
Q

WHat are some possibilities of new vaccines?

A

1/ Less antigenic variation
- pneumolysin

2/ Protein antigens

62
Q

How is it that B cells can be helped by T cells that recognise an internal part of the antigen?

A

B cells take up the antigen, degrade it and express the internal antigen on their MHC II.
Th cells recognise this with their TCR

63
Q

What does H. influenzae cause in children?

A

Meningitis

64
Q

Describe the mode of action of the Hib vaccine

A

(vaccine against H. influenzae type b)
• Conjugate vaccine: polysaccharide antigen + toxoid protein
• BCR binds polysaccharide
• TCT recognises toxoid protein
• B cell present toxoid on BCR –> T cell help
• high affinity, isotype switching, memory

65
Q

What have been the outcomes in the community since the use of the Hib conjugate vaccine?

A

Big decrease in incidence of childhood H. influenzae infection

66
Q

What is the protein that is conjugated onto the polysaccharide antigens?

A

A toxoid:
• Diphtheria
• Tetanus

MIIM20002 - Microbes, Infections, Responses (32 decks)

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