Lecture 22 - S. pneumoniae Vaccination Flashcards Preview

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

Flashcards in Lecture 22 - S. pneumoniae Vaccination Deck (66):
0

What receptors do neutrophils have?

• FcR
• CR (complement receptors)

1

What receptors do neutrophils have?

• FcR
• CR (complement receptors)

2

What is the function of NETS?

Contain bacteria at the site of infection

3

What is the makeup of a NET?

• DNA
• Histoproteins
• Granule contents

4

What is the name for the production of NETS?

NETosis

5

What are cathelicidins?

Antimicrobial proteins in a neutrophil

6

Describe what is important about colonial selectin

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

Then expansion occurs

8

Describe the concentration of antibody in the blood over time

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

8

What is the central principle of vaccination?

Vaccination will be the first exposure

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

9

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

• Greater magnitude
• More rapid response

11

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

First: naive differentiates into:
• memory
• effector

Second:
• memory cells differentiate into many more effector cells

12

Which diseases are caused by S. pneumoniae

• Pneumonia

• Septicaemia
• Meningitis
• Otitis media

13

Why vaccinate against TB?

• Most important pathogen for children under 5

• Debilitating and permanent sequelae

• Disease occurs in the healthy as well as the immuno compromised

13

What is the primary site of replication of S. pneumonia

Nasopharynx

14

What we need to know when making a vaccine?

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

15

To where does S. pneumonia disseminate?

Ears
Lungs
Blood
Meninges

17

What does the S. pneumoniae vaccine need to protect?
How do we do this?

IgG:
• Blood
• Meninges
IgA:
• Mucosa

18

What are the virulence factors of S. pneumonia?

• Adhesins
• Pneumolysin
• Capsule (critical for virulence)

19

Describe the functions of pneumolysin

• cilia inhibition
• cytotoxic to alveolar / endothelial cells
• triggers C' cascade

19

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

Phagocytes
Spleen
PRRs (TLR2, NOD2)

20

Why is the capsule virulent?

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

21

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

Antibodies against capsule
--> opsonisation

23

Why is the spleen important in recovery?

Spleen receives antigens from the blood

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

23

What happens to people without spleens?

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

24

Describe how immune complexes are removed from the blood

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

RBCs + Immune Complexes circulate to spleen

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

25

What will the ideal prophylactic vaccine induce?

IgA (mucosa)
IgG (meninges and blood)

27

What will an ideal theraputic vaccine induce?

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

28

Describe the first pneumococcal vaccine

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

28

How was the whole killed vaccine improved upon?

The whole killed vaccine elicited undesirable reactions

They extracted just capsular antigens

29

Describe the vaccine in 1983

Pneumococcal polysaccharide vaccine
• just capsular polysaccharide antigens

Vaccine contains 23 of the most common serotypes

80% of infection prevented

30

Describe the structure of a native antigen

T cell determinant

B cell determinant

31

Describe the effects of vaccination with capsular antigens (1983)

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

Elderly, Children, immunocompromised:
• Variable / poor response

32

How are B cells activated to produce antibodies

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

What is required for isotype switching and high affinity antibodies?

T cell help
--> presentation of antigen on MHC II

35

What does T cell help bring about

Memory
High affinity antibody
Isotype switching

36

Can we launch an immune response against polysaccharide at all?

Yes

37

Describe how B cells respond to polysaccharide

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

NB not T cell help

38

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

IgM

A little IgG

39

Why are highly repetitive polysaccharides required?

Only repetitive sugars can cross link on the B cell receptors

Cross linking is required for activation

40

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

TD: protein
TI: polysaccharide, lipids, nucleic acids

41

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

TD: no
TI: yes

42

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

Explain this

TD: yes
TI: no

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

43

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

TD: yes
TI: no (some IgG)

44

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

TD: high
TI: low

45

Compare memory in T cell dependent and T cell independent antigens

TD: yes
TI: no

46

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

Chemically connect a protein antigen to a polysaccharide antigen

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

47

What is the connection of TD and TI called?

Conjugation

48

What does a B cell do to a conjugate antigen?

What is the significance of this?

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

What is the antigen specificity of the antibodies?

The capsular polysaccharide

Because the initial B cell receptor recognised the polysaccharide

50

What is the specificity of the T cell receptor?

The protein from the conjugated antigen

51

When were conjugated vaccines first licensed in Australia?

Which proteins are used?

2001

By 2005, on the national vaccination program

Tetanus toxoid or diphtheria toxoid

52

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

Heptavalent - 7 serotypes

Now, 13

53

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

Pros:
- response in children

Cons:
- expensive

54

What is the result of the conjugate vaccine?

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

What is serotype replacement?

Give an example

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

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

Dramatic decrease in IPD

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

57

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

The children were no longer transmitting the bacteria to their grandparents

HERD IMMUNITY

58

What is herd immunity?

This is when vaccinating one group has effects on another group

59

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

Increase in incidence

Due to serotype replacement

60

Why did the vaccine elicit such a poor response?

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

WHat are some possibilities of new vaccines?

1/ Less antigenic variation
- pneumolysin

2/ Protein antigens

62

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

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

What does H. influenzae cause in children?

Meningitis

64

Describe the mode of action of the Hib vaccine

(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

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

Big decrease in incidence of childhood H. influenzae infection

66

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

A toxoid:
• Diphtheria
• Tetanus