Immunological Memory and Vaccination

Question 1

Goals of a Vaccination Programme:

Answer 1

To immunise people with a benign form of a pathogen in order to induce immunological memory and protect against infectious disease:

• Individual protection
• Herd immunity

Question 2

3 Mechanisms of Immunological Memory

Answer 2

1. Long-lived Plasma cells (Causes continual low level circulation of antigen-specific antibodies)
2. Generation of Memory B Cells
3. Generation of Memory T Cells (Memory Th cells and memory CTLs)

Question 3

Generation of Memory B cells and Generation of Memory T cells Respond quickly and robustly, Why?

Answer 3

a) An expanded population of Antigen-specific Memory B cell and T cells is generated during a Primary Immune response
b) These Memory cells are long-lived
c) Some Antigen-specific Memory T cells migrate out of secondary lymphoid tissues into the periphery
d) Memory B cells have already undergone Ig isotype switching and Somatic Hypermutation in the Germinal Centre
e) Only Memory B cells take part in Secondary Immune responses
f) Memory T cells are easier to activate

Question 4

Two types of memory T cells have been defined:

Answer 4

Central memory T cells
CD62L+, CD44+ and CCR7+ -> remain in secondary lymphoid tissues

Effector memory T cells
CCR7- and CD62L- -> migrate into peripheral tissues (mucosal sites, inflammed tissues)

Question 5

The Germinal Centre response:

Answer 5

Cytokine and CD40L ‘help’ from effector TFH cells ensures that B cells presenting peptide antigens:

• Undergo Ig class switching
• Undergo Somatic Hypermutation
• Differentiate into long-lived Plasma Cells
• Differentiate into Memory B cells

Question 6

Naïve B cells express the inhibitory receptor BLANK

Answer 6

Naïve B cells express the inhibitory receptor FcγRIIb (A low affinity receptor for IgG)

FcγRIIb expression is down-regulated on Memory B cells

Question 7

Memory T cells Switch CD45 isoform usage:

Answer 7

CD45 plays an important role in the positive regulation of antigen-receptor signaling in lymphocytes

Effector and Memory T cells express the CD45RO isoform, which is associated with increased TCR signalling strength (compared to CD45RA)

Consequently, memory T cells have a lower threshold for activation than that of naïve T cells:
Rely less on co-stimulation
More rapidly up-regulate CD40L

Question 8

Vaccination vs Immunisation:

Answer 8

Vaccination means having a vaccine – that is actually getting the injection.

Immunisation means both receiving a vaccine and becoming immune to a disease, as a result of being vaccinated

Question 9

Aim of an ideal vaccine:

Answer 9

To produce the same immune protection which usually follows natural infection but without causing disease
To generate long-lasting immunity
To interrupt spread of infection

A vaccine that sustains the Germinal Centre response is desirable
A vaccine that induces both T cell and B cells responses is desirable
A vaccine that induces long-lived immunological memory is desirable

Question 10

Types of Immunity:

Answer 10

Immunity -> Adapative or Innate Immunity

Adaptive Immunity -> Natural or Artificial Immunity

Natural Immunity -> Passive (Maternal) or Active (Infection)
Artificial Immunity -> Passive (Antibody Transfer) or Activate (Immunisation)

Question 11

Passive Immunity:

Answer 11

Natural:
Maternal transfer of antibodies to foetus/infant via placenta or colostrum

Artificial:
Administration of preformed substance to provide immediate but short-term protection (immunoglobulins, anti-toxins)

Question 12

Active Immunity:

Answer 12

Natural:
Following contact with the organism

Artificial:
Administration of agent to stimulate immune response (immunisation)

Question 13

Types of Vaccines:

Answer 13

1. Live attenuated vaccines (Attenuated (weakened) form of the “wild” virus or bacterium)
2. Inactivated vaccines
3. Toxoid vaccines (pathogen-derived toxins that have been inactivated and chemically modified)
4. Subunit vaccines (is a fragment of a pathogen, typically a surface protein, that is used to trigger an immune response and stimulate acquired immunity against the pathogen from which it is derived)

Question 14

Vaccine failures:

Answer 14

Primary failure:

• an individual fails to make an adequate immune response to the initial vaccination (e.g. in about 10% of measles and mumps vaccine recipients)
• Infection possible any time post-vaccination

Secondary failure:

• an individual makes an adequate immune response initially but then immunity wanes over time
• a feature of most inactivated vaccines, hence the need for boosters

Question 15

Adjuvants:

Answer 15

The immunologist’s dirty secret:

Mixture of inflammatory substances required to stimulate immune responses to co-administered peptides, proteins or carbohydrates

Enhances strength, speed, and duration of the immune response.