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PoM - Principles of Medicine Week 3 > Vaccinations > Flashcards

Vaccinations Flashcards

1
Q

What is a vaccine?

A

Something that stimulates the immune system, without causing serious harm or side effects

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2
Q

What is the aim of immunisation?

A

Provoke immunological memory to protect individual against a particular disease / pathogen if later encountered

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3
Q

What are the 7 main features for an ideal vaccine?

A
  1. Completely safe - population preventative medication, more likely to be used if they are safe
  2. Easy to administer - for mass distribution
  3. Single dose, needle-free - needles may infect others / can get an infection
  4. Cheap - for mass production
  5. Stable - temperature especially, so they do not get denatured as it changes the shape of the antigens
  6. Active against all variants - so only need to get immunised once (unlike the flu jab, new every year)
  7. Life-long protection
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4
Q

Why are vaccines important?

A

Improve life expectancy - preventative measure

Instance of disease instantly goes towards zero when vaccines are introduced

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5
Q

Why are vaccines economically profitable?

A

It is more cost effective to prevent infections / disease, than to treat / cure people once they have it
The money invested in the vaccine every year can be re-invested once the disease has been eradicated

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6
Q

Which disease was eradicated by the use of vaccines?

A

Small pox

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7
Q

What disease is the next aim for eradication?

A

Polio (2 out of 3 polio viruses have now been officially eradicated)

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8
Q

Why is polio harder to eradicate?

A

Even once a person has been vaccinated, they can sill pass on polio to someone not vaccinated

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9
Q

What is the first step to making a vaccine?

A

To understand the vaccine - e.g. there is a gap between the development of viral vaccines and bacterial vaccines because bacteriology and viral biology are different

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10
Q

Is bacteriology or viral biology easier to understand and why?

A

Bacteriology is perhaps easier than viral biology

Viruses need to be grown in cells, whereas bacteria can be grown in agar plates

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11
Q

How do technological advancements help manufacture more vaccines?

A

e.g. Men B vaccine - The genome of the bacteria responsible was sequenced, and every single protein was synthesised from it to find the best combination to include in the vaccine

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12
Q

Describe a broad overview of the immune response (e.g. for a virus):

A

Pathogen invades host cell
Triggers innate immune response - recognises blunt structures
Early inflammatory mediators released - e.g. cytokines, chemokines
Recruits innate effector neutrophils, NK cells, macrophages (non-specific)
Antigens are released from the infected cells, taken up by antigen presenting cells, and presented as fragments on the MHC II receptor on the surface
This activates specific T cells and B cells - as they see their cognate antigen on the antigen presenting cell
They expand by clonal expansion, once the infection is cleared, the number of cells go back down
Immune memory cells are made

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13
Q

Which part of the immune response does the immunisation programme focus on?

A

Immune memory
Once the primary immune response is initiated by the vaccine and memory cells are made
Secondary infections with the same pathogen produce a faster and more powerful immune response

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14
Q

What is the process of expose, expand, contract and memory?

A

Naive T cells / B cells - antigen stimuli causes them to expand to be effector cells
The antigen source is removed
Leads to Contraction phase where immune cells are made
When the same antigen is encountered again, the immune cells expand more rapidly into effector cells and fight off the pathogen before it causes harm

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15
Q

How do vaccines improve the immune response?

A

Prevent entry of the pathogen into the host cell
Enable killing of the infected cell
Boost the immune response - protected during subsequent exposures

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16
Q

What are the 2 things Abs do?

A
  1. Covers receptors on the surface of the pathogen so it can no longer communicate with the host cells to enter them
  2. Opsonisation - when the Abs cover the pathogen, the Fc receptor part binds to immune cells e.g. macrophages for phagocytosis
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17
Q

How do vaccines help boost the T cell response upon secondary encounter to the same pathogen?

A

CD8 killer cells - recognise pathogen infected cells i.e. viral proteins on MHC I receptor
Vaccine induces T cell response producing memory cells - so upon reinfection, T cells kill the infected cells

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18
Q

How do vaccines boost the immune response overall?

A

Engages CD4 T cells - responsible for the consequent immune responses
Vaccine boosters often work by increasing CD4 T cell count for a specific pathogen

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19
Q

What is a correlate of protection?

A

A measurable sign that a person is immune - in sense of being protected against becoming infected and/or developing the disease

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20
Q

What is commonly used as a correlate of protection?

A

Antibody count - take a sample of blood and use the ELISA test (antibody binding assay) to measure the levels of a specific antibody in the blood

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21
Q

How can the antibody count be used to determine whether a person is immune or not to a specific disease?

A

If their antibody count is higher than a specific minimum level

22
Q

How were the minimum levels for immunity determined?

A

Using human challenge studies from the 1950s/60s - volunteers had their antibody count measured, and then deliberately infected
Cut off point to antibody count and chance of infection was determined using these studies
These results are used as the base for all vaccine licensing

23
Q

As the influenza virus vaccine needs to be generated every year, how is the efficacy measured?

A

There is insufficient time to do large scale trials to see if the vaccines produce a strong enough immune response for long term immunity
Instead, antibody levels are measured to see if the meet the minimum standard for immunity using the values from the human challenge studies in 1950s/60s

24
Q

What else do correlates of protection help with for vaccines?

A

Vaccine design - target the production of a specific antibody

25
Q

How and where are mature B cells generated and what does this produce?

A

From stem cells in the bone marrow, which generate the unique B cell receptor (BCR) by undergoing VDJ recombination - segments of different genes are combined to produce a unique cell receptor that can recognise one specific antigen
Pre-set variety of different BCRs generated

26
Q

What triggers B cells to divide during an infection?

A

The one B cell that recognises its specific antigen then divides (clonal expansion)

27
Q

What are the 3 main pathways for B cells after recognition?

A
  1. Divide to become plasma cells, which produce Abs until the infection is cleared (plasma cells have a short half life)
  2. Memory cells are made to prevent / reduce harm during future infections with this same pathogen
  3. Affinity maturation
28
Q

What is affinity maturation?

A

A selective pressure on the B cells that make the BCR / Ab more specific to the antigen
Use the BCR gene and force it to undergo a series of point mutations - each producing a slightly different BCR shape
The BCRs better at binding to the Ab survive, and those that are not, die / killed off

29
Q

Why is affinity maturation useful and how is this concept used during immunisation programmes?

A

Makes the BCR and Ab more specific to the antigen, so there is a higher affinity for them to bind to the antigen
More efficient in clearing the infection
Vaccination programmes deliver multiple shots / booster jabs to give multiple exposures to the same pathogen, partly so this process can occur

30
Q

Do T cells also undergo affinity maturation?

A

No

31
Q

What does R0 stand for? (pronounced ‘R’ nought)

A

The basic reproduction number

32
Q

What is R0?

A

Measure of spread (of disease)
The number of cases one case generates on average e.g. if R0 = 2, one person with the disease will infect 2 other people, whom move on to infect 4 more people (together) etc.

33
Q

What is the point of vaccines in terms of R0 / spread?

A

Slows down the spread of disease due to the concept of herd immunity
Brings down the R0 value from above 1 to below 1

34
Q

What does herd immunity do / provide?

A

Break the chains of transmission, hence protect those who are unable to get the vaccine as the disease is not being passed around the community
Those vaccinated / immunised act as a barrier to indirectly protect those susceptible / vulnerable

35
Q

What is in a vaccine?

A

Some form of the antigen
Adjuvant e.g. alum
Stabilising components e.g. buffers
Water

36
Q

What are the 5 forms of antigen that can be in a vaccine?

A
  1. Inactivated Protein / toxin e.g. Tetanus toxoid2
  2. Recombinant protein e.g. Hep B
  3. Live Attenuated Pathogen e.g. Polio/ BCG
  4. Dead Pathogen e.g. Split Flu vaccine
  5. Carbohydrate e.g. S. pneumoniae
37
Q

What is an inactivate toxoid vaccine and how does it work?

A

Chemically inactivated form of toxin - keeps the original shape of the toxin, however, no longer performs the harmful function it did in its active form
Induces antibody, antibody blocks the toxin from binding the nerves
e.g. tetanus produces a toxin that binds to the nerves, causing harm. This requires ATP to change shape and carry out that process, so if this toxin is treated with a chemical such as formalin, it locks it into shape (inactivating it)

38
Q

What are the advantages and disadvantages of an inactivate toxoid vaccine?

A

Advantages: Cheap, well characterised, safe, in use for many decades
Disadvantages: Requires good understanding of biology of infection, not all organisms encode toxins - only works for pathogens that secrete agents, tiny risk of failure to inactivate/ impurities

39
Q

What is a recombinant protein vaccine and how does it work?

A

Identify antigenic protein from the pathogen, and take the gene responsible
Insert into another organism and express it
Not infectious as it is not part of the pathogen, but looks the same - induces classic neutralising antibodies
e.g. for Hep B, take the gene coding for the surface antigen and express it in yeast

40
Q

What are the advantages and disadvantages of a advantages and disadvantages of a recombinant protein vaccine?

A

Advantages: Pure, safe, because low strain variation and human only host highly protective
Disadvantages: Relatively expensive, has not proved to be answer to all pathogens as expression of the viral protein does not necessarily mean the folding and structure of the recombinant protein is the same as on the original pathogen

41
Q

Why is protein structure so critical?

A

If the vaccine contains the wrong structure, the person will make Abs against this, however, these Abs will not be useful when encountering the actual pathogen as the Abs produced during the vaccination are not complementary to the structure of the antigens on the actual pathogen

42
Q

How is protein structure maintained primarily?

A

Temperature stability - high temperatures can cause proteins to denature, which changes their structure and so induces Abs to be produced against the ‘wrong’ structure

43
Q

What are conjugate vaccines and why are they used?

A

Many bacteria have a capsule, so their outer layer is made of polysaccharides, which often only induces a T cell response independent to B cells
In a vaccine, to provide better / longer lasting immunity, the polysaccharides on the capsule are attached to a carrier protein to induce a B cell response as well

44
Q

How does the conjugate vaccine work and improve the B cell response?

A

Tricks the immune response
The vaccine has a protein part and a polysaccharide part - the B cell’s BCR recognises the polysaccharide portion, but takes up the whole component, including the protein section; and the dendritic cell recognises the carrier protein portion, and also takes up it up
Both process the protein section of the vaccine and present it on the MHC II surface receptor
This activates the CD4 T helper cells, which can now communicate with the B cells to further activate them

Normally, without the protein portion, the B cells get little to no help from the T cells during the immune response

45
Q

What are the advantages and disadvantages of the conjugate vaccine?

A

Advantages: Improves immunogenicity, highly effective at controlling bacterial infection
Disadvantages: Cost, carrier protein interference, very strain specific, polysaccharide alone is poorly immunogenic

46
Q

What are dead pathogen vaccines and how do they work?

A

Rather than using a component of the pathogen, it can be chemically killed
Induces antibody and T cell responses
e.g. influenza virus - embryonated chicken eggs injected with virus, they grow, purify out the surface components

47
Q

What are the advantages and disadvantages of usinf the dead pathogen vaccine?

A

Advantages: Leaves antigenic components intact and in context of other antigen, immunogenic because of the inclusion of other components
Disadvantages: Fixing/ killing can alter chemical structure of antigen (loses efficacy), quite “dirty”, requires the capacity to grow the pathogen (H5N1), vaccine induced pathogenicity a risk, risk of contamination with live pathogen (Polio)

48
Q

What are live attenuated vaccines and how do they work?

A

Pathogens selected for the vaccine are ones that replicate, but do not cause sickness
The are attenuated by serial passage (growing the pathogens in one environment, then moving them to another)
Leads to a loss of virulence (harmful) factors
They replicate in situ so they trigger the innate response and boost the immune response
e.g. BCG, LAIV

49
Q

What are the advantages and disadvantages of live attenuated vaccines?

A

Advantages: Induce a strong immune response, can induce a local immune response in the site where infection might occur (e.g. LAIV)
Disadvantages: Can revert to virulence, can infect immunocompromised (BCG is not given to children with HIV), attenuation may lose key antigens, can be competed out by other infections

50
Q

What are adjuvants and why are they used?

A

Substances used in combination with a specific antigen that produced a more robust immune response than the antigen alone
Engage and activate the dendritic cells using molecules like PAMPs and DAMPs
Dendritic cells (DCs) then move from the site of immunisation to the lymphnodes
DC produces 3 things needed for the activation of T cells: cognate antigen recognition (antigen MHC II complexes), surface co-stimulation (stimulatory signalling), and production of cytokines

51
Q

What vaccines do people get and when?

A

Many vaccines, over the years there is an increase in the number of vaccines the average person gets
Many vaccines given after birth / before pre-school, many booster jabs given during school

52
Q

Why is it difficult to just make more vaccines to more pathogens?

A

Many pathogens are diverse, so multiple strains / subtypes in just one area - difficult to develop a vaccine for all the strains and the Ab response will be less effective due to the huge variety
Strain replacement - there is a niche for bacteria and other pathogens, so if one strain is contained, it will be replaced by a new strain as there is less competition, so more resources for the new strain to expand

PoM - Principles of Medicine Week 3 (9 decks)

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