L14 - Immune memory and vaccines Flashcards
Immunological Memory
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.
Protective Immunity and Memory
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)
Features of Immunological Memory
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)
Immune cells: the changes associated with memory
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
Generation of Memory B cells: what have they already done, what can they do, and how do they differ from plasma cells?
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
Maintenance of Memory T cells: why and how do they survive?
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)
Memory T cells: what do they express and where are they located?
- 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)
Features of Naïve versus Memory B Cells
Membrane Markers:
Immunoglobulin
Complement Receptor
Where are they?
Life Span?
Recirculation
Receptor Affinity
Adhesion Molecules
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
Immunisation/vaccination
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
Vaccine design: what are their two components
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
Types of modern vaccines
- Live Attenuated Infection
- Killed or Inactivated Infection
- Protein Subunit Vaccines (purified or recombinant components)
- Recombinant viral-vectored vaccines
- Virus-like particles
- Nucleic acid-based (mRNA) vaccines
Live Attenuated Infection: what types are there, what do they do, and what strengths/weaknesses do they have?
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
Killed or Inactivated Infection: what is it and what are its strengths/weaknesses?
In the name lol
- Lower risk of disease but can occur due to improper activation
- May need boosters
Protein Subunit Vaccines (purified or recombinant components): what is it and what are its strengths/weaknesses?
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
Recombinant viral-vectored vaccines: what is it and what are its strengths/weaknesses?
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
Virus-like particles: what is it and what are its strengths/weaknesses?
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.
Nucleic acid-based (mRNA) vaccines: what is it and what are its strengths/weaknesses?
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.
Inactivating pathogens for use in vaccines
- Chemically inactivated (formaldehyde etc)
- Heated
Adjuvants: what are they, what do they do, what examples of them are there, and what may go wrong?
“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
How can we improve vaccines?
- 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
Mucosal vaccines: what are they, how are they delivered, and what are the strengths of this vaccine?
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
Why do so many diseases lack vaccines?
- 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
MMR vaccine
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.
Herd immunity: what is it and what is it determined by?
The immunity of an entire population after a certain percentage is immunised to it
Depends on virulence of pathogen or susceptibility of population
Vaccine Hesitancy: The themes
- Control: the idea that we can take back control of our own bodies through alternative means.
- Parenting style: philosophies that shun mainstream medicine, opting for “natural” remedies.
- The Past: previous bad healthcare experiences or a bad experience around vaccination shapes perceptions.
- Risk: misunderstandings about the risks of vaccination versus the risks of disease.
- Fear of chemicals: the fear that the vaccine will introduce toxic chemicals.
- Distrust of government agencies and corporations.
Misinformation vs disinformation
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
