L14 - Immune memory and vaccines

Question 1

Immunological Memory

Answer 1

Specific antigen recognition is retained by the adaptive immune system

Adaptive immune cells that have recognised a foreign antigen survive in case the same infection occurs again.

Question 2

Protective Immunity and Memory

Answer 2

Increased protection against pathogens that are encountered more than once:

Initial adaptive immune response

Then protective immunity.

Then memory responses

(effector cells fall below threshold for protection)

Question 3

Features of Immunological Memory

Answer 3

Primary adaptive response to infection-often slow and weak.

Secondary exposure to same pathogen: greater response

Secondary exposure is more rapid.

better (has higher affinity)

Question 4

Immune cells: the changes associated with memory

Answer 4

Expansion of “clones” of cells with re-arranged antigen receptor genes specific for the primary antigen encountered:

• T cells with antigen-specific TcR
• B cells with antigen-specific BcR / Ig
• Enhanced migration & re-stimulation properties
• Adhesion molecules, rapid effector function
• Survival maintenance of those clones
• Responsive to growth/survival cytokine signals

Question 5

Generation of Memory B cells: what have they already done, what can they do, and how do they differ from plasma cells?

Answer 5

Already undergone antibody class switch and affinity maturation

Can re-enter germinal centres during secondary immune responses to undergo additional somatic hypermutation and affinity maturation

Not yet differentiated into a plasma cell

Require help from CD4+ Th cells for secretion of Ab

Question 6

Maintenance of Memory T cells: why and how do they survive?

Answer 6

Most activated (effector) T cells are programmed to die - activation-induced cell death (AICD)

Memory cell survival and maintenance is mediated by e.g. IL15 & IL7 (homeostatic proliferation)

Question 7

Memory T cells: what do they express and where are they located?

Answer 7

• Express high levels cytokine receptors e.g. IL7R –for survival and genes such as bcl2
• High adhesion molecules e.g. CD44
• Lower expression markers associated with effector cells e.g. CD69

Can be tissue-resident or adapted for recirculation through lymphoid (central memory) or adapted to rapidly re-enter inflamed tissues (effector memory)

Question 8

Features of Naïve versus Memory B Cells
Membrane Markers:
Immunoglobulin
Complement Receptor
Where are they?
Life Span?
Recirculation
Receptor Affinity
Adhesion Molecules

Answer 8

IgM, IgD
Low
Spleen
Short-lived
Yes
Higher average
High ICAM-1

IgM, IgD (?), IgG, IgA or IgE
High
Bone Marrow, Lymph node, spleen
Long-lived
Yes
Lower average
Low ICAM-1

Question 9

Immunisation/vaccination

Answer 9

If we can acquire immunity to a pathogen before naturally encountering it, we can bypass the risk taken when building up the primary adaptive response and only do the secondary safer response

Immunisation/vaccination

Question 10

Vaccine design: what are their two components

Answer 10

Vaccines require two components:

• Antigens from the target pathogen that are provided to/ or generated by the vaccine recipient - potentially by heating/chemical inactivation (formaldehyde, radiation, etc)
• An infection signal (that alerts and activates the host immune system) - adjuvant

Live and attenuated vaccines naturally provide both but other vaccine platforms may need multiple boosters

Question 11

Types of modern vaccines

Answer 11

1. Live Attenuated Infection
2. Killed or Inactivated Infection
3. Protein Subunit Vaccines (purified or recombinant components)
4. Recombinant viral-vectored vaccines
5. Virus-like particles
6. Nucleic acid-based (mRNA) vaccines

Question 12

Live Attenuated Infection: what types are there, what do they do, and what strengths/weaknesses do they have?

Answer 12

Two forms:
* Related, less harmful infection
* Live, attenuated pathogen

1- Related pathogen that causes immunity against the target pathogen can be used

• Highly effective, rarely found in nature
• Dangerous to immuno-compromised patients.

2 - Weakened form of the pathogen

• Highly effective
• Some risk of disease in immuno-compromised patients

Question 13

Killed or Inactivated Infection: what is it and what are its strengths/weaknesses?

Answer 13

In the name lol

• Lower risk of disease but can occur due to improper activation
• May need boosters

Question 14

Protein Subunit Vaccines (purified or recombinant components): what is it and what are its strengths/weaknesses?

Answer 14

Use antigens that best stimulate the immune system

May be linked to e.g. boosting mechanism such as a bacterial stimuli e.g. HiB meningitis

Question 15

Recombinant viral-vectored vaccines: what is it and what are its strengths/weaknesses?

Answer 15

Bioengineered virus to express target pathogen antigens in vivo - widely investigated with good safety

Often use non-human virus as carrier

• Can cause reactivity to carrier virus so cannot use same carrier repeatedly

Question 16

Virus-like particles: what is it and what are its strengths/weaknesses?

Answer 16

Particle that acts in the same manner as viruses without causing viral infections

• Highly effective - closely resembles live virus but non-infectious
• can contain multiple antigenic components.

Question 17

Nucleic acid-based (mRNA) vaccines: what is it and what are its strengths/weaknesses?

Answer 17

Administering the mRNA of antigens into cells for production using carriers like lipid nanoparticles

• Can encode many antigens (even whole genome of pathogens)
• Non-infectious and quick to manufacture and bulk up
• Can be tricky to store as requires cold chain

e.g. SARsCoV-2 vaccine made by Moderna and Pfizer.

Question 18

Inactivating pathogens for use in vaccines

Answer 18

• Chemically inactivated (formaldehyde etc)
• Heated

Question 19

Adjuvants: what are they, what do they do, what examples of them are there, and what may go wrong?

Answer 19

“Helper” chemicals that boost immune responses to antigen

Stimulate inflammation and antigen presentation to activate antigen-specific T cells

e.g. Oil/Water emulsion, Alum (Aluminium Hydroxide), TLR ligands, liposomes

Can cause adverse immune pathology, including organ damage, septic shock, and autoimmunity if immune system stimulated too much

Question 20

How can we improve vaccines?

Answer 20

• The efficacy of a vaccine depends on factors such as an individual’s MHC type - not all antigens are immunogenic in all people
• Some pathogens mutate rapidly/multiple life cycle stages

Deliver a variety of antigen epitopes (multivalent vaccines) with an adjuvant to trigger a range of protective immune responses may overcome these issues - may also be useful for infections that mutate rapidly e.g. flu, cold, COVID 19, etc

Question 21

Mucosal vaccines: what are they, how are they delivered, and what are the strengths of this vaccine?

Answer 21

Using vaccines to give resident memory cells in locations where pathogens attack - lungs, etc

Usually delivered in your nose or throat, as sniffable or inhalable formulations

• Potential virus blocking for e.g. respiratory viruses using Igs
• Potentially more durable i.e. long-term memory

Question 22

Why do so many diseases lack vaccines?

Answer 22

• Lack of understanding of infection life cycle
• Complex life cycle with stage specific immune response e.g. malaria
• Lack of understanding of immune response to pathogen e.g. major antigens
• Pathogen antigen variability
• Lack of good lab models
• Physical lacking of costs to store and deliver them to those requiring them

Question 23

MMR vaccine

Answer 23

Andrew Wakefield, hypothesised in 1998 that MMR was linked to autism.

His work was proved fraudulent, unethical, the work was retracted and he was disbarred

His legacy persists and the rise of vaccine hesitancy and the anti-vax movement has lead to a reduction in vaccine uptake

Multiple studies been conducted since with a study in 2019, the largest ever study to dispel Wakefield’s theory. No study has replicated his findings

Measles cases in Europe have risen 30 fold and there have been alarms about growing numbers of cases in England

1 in 5 children currently unprotected against measles

The World Health Organization has said vaccine hesitancy is one of the 10 biggest global threats to health.

Question 24

Herd immunity: what is it and what is it determined by?

Answer 24

The immunity of an entire population after a certain percentage is immunised to it

Depends on virulence of pathogen or susceptibility of population

Question 25

Vaccine Hesitancy: The themes

Answer 25

1. Control: the idea that we can take back control of our own bodies through alternative means.
2. Parenting style: philosophies that shun mainstream medicine, opting for “natural” remedies.
3. The Past: previous bad healthcare experiences or a bad experience around vaccination shapes perceptions.
4. Risk: misunderstandings about the risks of vaccination versus the risks of disease.
5. Fear of chemicals: the fear that the vaccine will introduce toxic chemicals.
6. Distrust of government agencies and corporations.

Question 26

Misinformation vs disinformation

Answer 26

Misinformation is false or inaccurate information—getting the facts wrong.

Disinformation is false information which is deliberately intended to mislead—intentionally making the misstating facts - This can be a VERY lucrative initiative