Vaccination Flashcards

1
Q

What is a vaccine?

A

A substance used to stimulate the production of antibodies, and provide immunity against one or multiple diseases, prepared from the causative agent of a disease, products or a synthetic substitute, treated to behave as an antigen without inducing pathology

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2
Q

What is the principal aim of immunization?

A

To provoke immunological memory to protect the individual against a particular disease

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3
Q

What is an ideal vaccine?

A

Safe, easy to administer single dose, needle-free, cheap, stable, active against all variants and provides long-life protection

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4
Q

What is immune memory?

A

Improves the efficacy of the innate immune response. Focuses a response on the site of infection and the organism responsible, involves memory cells.

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5
Q

Where are memory cells stored?

A

Lymphoid organs or within the circulation

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6
Q

What does the primary response involve in terms of T & B cells?

A

Primary response requires differentiation and proliferation of naive T & B cells to facilitate appropriate TCRs & BCRs in addition to the production of specific antibodies complementary to particular antigen epitope

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7
Q

What is the main difference between a primary & secondary immune response?

A

The secondary immunological response is relatively quickly due to the presence of memory cells, thus grater production of antibodies (secondary expansion)

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8
Q

What are the correlates of protection?

A

Measurable signs that an individual or potential host is immune regarding protection against infection or developing disease

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9
Q

What is an example of a correlate of immunity?

A

Antibodies

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10
Q

What does the correlate of protection enable, clinically?

A

Enables smarter vaccine design, anti-F RSV antibody has driven the vaccine drive in RSV
Small efficacy studies (season flu vaccine roll out)

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11
Q

What are the two selection processes for b cells?

A

positive selection and negative selection

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12
Q

How does the negative selection of B cells occur?

A

Eliminates self-reacting B cells (apoptosis or induction of anergy in the B cell).

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13
Q

What does a BCR contain?

A

Light and heavy chains encoded by an individual gene.

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14
Q

How does mRNA splicing occur in terms of BCR recombination?

A

The primary RNA transcript is complimentary to the exons and introns present in the base sequence of the template strand. Intron sections removed from pre-mRNA transcript, and the exons undergo mRNA splicing
The recombination of exons results in various polypeptide sequences encoding for multiple immunoglobulin proteins. Regions shuffle and rearrange via recombination cell maturation, variable units are removed. VDJ recombinase enzymes involved

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15
Q

Which enzyme enables DNA recombination?

A

VDJ recombinase enzymes

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16
Q

Which VJD proteins are involved in light chain?

A

V & J

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17
Q

Which VJD proteins are involved in heavy chains?

A

V, J & D

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18
Q

Which region of the antibody determines the type of immunoglobulin?

A

Constant(Fc) region

Alpha region = IgA

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19
Q

Where does BCR selection occur?

A

Bone marrow

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20
Q

Linked recognition caused which type of Th to be released upon activation?

A

Th2 secretes cytokines activate B cells and causes proliferation into clonal daughter cells

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21
Q

What role do Th2 cells have in terms of B cells?

A

Secretes cytokines and causes proliferation into clonal daughter cells - rounds of proliferation stimulates differentiation of activated B-cell clones into memory B cells and plasma cells

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22
Q

Which immunoglobulin is initially secreted by plasma cells?

A

IgM

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23
Q

What effect do Th2 cells have on plasma cells?

A

Stimulates plasma cells to switch from IgM production to IgG, IgA, IgE. Process of class switching or isotype switching - allows plasma cells cloned from same activated b cells to produce a variety of antibody classes

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24
Q

Which regions of the antibody are changed during isotype switching?

A

Genetic rearrangement of gene segments encoding the constant region (determines class)
The variable region not changed, class retains original epitope specificity

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25
Q

Where does affinity maturation of b cells occur?

A

Germinal centers

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26
Q

What is the purpose of affinity maturation of B cells?

A

It generates high-affinity antibodies. Mutations resulting in gin alterations in the variable region to produce greater affinity antibodies

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27
Q

Which enzymes are involved in class switch recombination?

A

Activation-induced cytidine deaminase

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28
Q

What is R0?

A

The basic reproduction number of infection can be considered as the number of cases one case generates on average over the course of its infectious period, in an otherwise uninfected population

29
Q

If R0 <1 what will happen to the infection?

A

The infection will die out in the long run,

30
Q

What will happen if R0 >1?

A

The infection will be able to spread in a population

31
Q

What equation is given to determine the proportion of the population that needs to be vaccinated to stimulate herd immunity?

A

1 - 1/R0

32
Q

What is the basic reproduction number influenced by?

A

Influenced by the duration of infectivity of affected patients.

The infectiousness of the pathogen

Number of susceptible hosts within the population that has affected patients are in contact with

33
Q

What is herd immunity?

A

The resistance to the spread of a contagious disease within a population, resulting if a sufficiently high proportion of individuals are immune to the disease, predominantly through prophylactic treatment (Vaccinations)

34
Q

What are inactivated toxoid vaccines?

A

Toxoids are inactivated toxins whose toxicity has been suppressed either through heat or chemical treatment; while immunogenetics is maintained.
Toxins are secreted by bacteria, however, toxoids are altered variants of toxins (not bacteria secreted)

35
Q

How are toxoids used?

A

Chemically inactivated toxins can be formulated in a vaccine preparation to stimulate the production of antibodies which serve to effectively disarm the bacterium

36
Q

What is the main example of a toxoid vaccine?

A

Tetanus toxoid

37
Q

How do toxoids work?

A

Toxoid enables the immunoglobulin antibody to bind onto toxoid, interfering with the normal interaction of the toxoid with the human tissue, preventing toxoid invasion of the nervous system, and protecting from producing painful muscle spasms as well as autonomic dysfunction.

38
Q

How is the immunoglobulin bound toxoid destroyed?

A

Hydrolyzed by phagocytes

39
Q

What are the advantages of toxoid vaccines?

A

Cheap, well-characterized, safe

40
Q

What are the disadvantages of toxoid vaccines?

A

Requires understanding of biological infection, not all organisms encode toxins, minor risk of failure of inactivated impurities.

41
Q

What are recombinant protein vaccines?

A

Genes encoding for antigenic surface protein is extracted from bacterial genome to and inserted into a plasmid, increasing antigenic protein production which are inserted into vaccine

42
Q

How are recombinant protein vaccines formed?

A

Bacterial structural gene encoding for antigenic surface protein is extracted from bacterial genome through restriction endonucleases, cleaving the DNA at specific restriction sites; resulting a staggered cut, hence exposing a particular sequence of nucleotides (Sticky ends).
Restriction endonucleases applied onto bacterial plasmid to remove a section of DNA, formation of complimentary staggered ends, enable the formation of hydrogen bonds with the sticky ends of extracted gene. Ligases form phosphodiester bonds between adjacent DNA nucleotides to produce recombinant plasmid. Recombinant protein can thereby be synthesised and purified.

43
Q

What are the main examples of recombinant protein vaccines?

A

Hep B surface antigen (HbSAg). Antigen induces classic neutralising antibodies; stimulates immunological memory through B clonal selection.

44
Q

What are the advantages of recombinant protein vaccines?

A

Pure, safe, because low strain variation and human only host highly protective

45
Q

What are the disadvantages of recombinant protein vaccines?

A

Relatively expensive, has not proved to be answer to all pathogens

46
Q

What do conjugate vaccines include?

A

The polysaccharide coat component is coupled to an immunogenic carrier protein. Polysaccharide components present on pathogens are independently insufficient to elicit a strong immune response, a conjugate vaccine is used in order to invoke an immune system response against a weak antigen

47
Q

How do conjugate vaccines work?

A

The weak antigen is covalently attached to an immunogenic carrier protein

48
Q

Which cells are enlisted by the s.pneumonine conjugate vaccine?

A

CD4+ T helper cells in order to stimulate clonal selection of B cells in response to immunogen polysaccharide.

49
Q

Upon BCR antigen recognition what happens to the antigen?

A

The antigen is internalised through endocytosis, processing of antigenic fragments at the endoplasmic reticulum. Peptides associated with MHC-II molecules on B cell surface membrane.

50
Q

What happens during linked recognition?

A

T cell/b cell linked recognition and secretion of cytokines enables B cells to differentiate into plasma cells and secrete specific IgG antibodies

51
Q

What is the main advantage of using conjugate vaccines?

A

Improves immunogenicity, effective at controlling bacterial infection

52
Q

What is the main disadvantage of conjugate vaccines?

A

Cost, carrier protein interferences, strain-specific, polysaccharide alone is poorly immunogenic

53
Q

What are dead pathogen vaccines?

A

Pathogen can be subjected to chemical treatment and killed. This induces antibody and T cell responses to the presented antigenic proteins on the pathogenic surface.

54
Q

What is an example of a dead pathogen vaccine?

A

Influenza split vaccine

55
Q

What are the disadvantages of a dead pathogen vaccine?

A

Disadvantages: Fixing can alter the chemical structure of antigen, requires the capacity to grow the pathogen (H5N1), vaccine-induced pathogenicity a risk, risk of contamination with the live pathogen

56
Q

What are the advantages of a dead pathogen?

A

Advantages: Leaves antigenic components intact and in context of other antigen. Immunogenic due to inclusion of pathogen entirety.

57
Q

What are live attenuated vaccines?

A

Pathogens are attenuated by serial passage, in order to reduce and limit the presence of virulence factors. In situ replication triggers the innate response, in addition to stimulating the adaptive immune system to develop immunological memory against the particular pathogen. Clonal selection of B cells, and T-cell activation (Humoral and cell mediated responses) are activated.

58
Q

What is an example of a live attenuated vaccine?

A

BCG, LAIV, OPV

59
Q

What is the advantage of a live attenuated vaccine?

A

Induce a strong immune response. Induces local immune response in the site of potential infection.

60
Q

What is the disadvantage of a live attenuated vaccine?

A

Reversion to virulence, infection immunosuppressed (BCG/HIV); attenuation may distort and lose fundamental antigens; can be outcompeted by other infections.

61
Q

What is an adjuvant in terms of vaccine?

A

Adjuvants are designed to improve immunogenic vaccines; are substances used in combination with a specific antigen that produced a more robust immune response than the antigen exclusively.

62
Q

How do adjuvants affect the immune response?

A

Adjuvants affect the immune response: Increases immunogenicity of weak antigens; enhances speed and duration of immune response; stimulates and modulated humoral response, including antibody isotype; stimulate cell-mediated immunity; improve induction of mucosal immunity; enhance immune response; decreased dose of antigen required (reduces need for boosters).

63
Q

Name an example of an adjuvant?

A

Mineral compounds (Alum), emulsions and synthetic natural toxins in bacteria

64
Q

Which receptors engage with adjuvants?

A

Pattern recognition receptors

65
Q

What is the overall aim of adjuvants?

A

Activates innate immune system to respond more rapidly to infection, and for adaptive immune response to become more specific

66
Q

Which cells are activated by adjuvants?

A

Adjuvant stimulates dendritic cells
DC uptakes antigen and moves to lymph node
Upregulated stimulatory signaling and cytokines

67
Q

How are B cells affected in conjugate vaccines?

A

B cells are turned from T independent to T-cell dependent

68
Q

Give 5 barriers to new vaccines being produced

A

Scientific Challenges
Injection Safety
Logistics/ Cold Chain
Development Issues
:
Time: 8 yrs in 1960s; 15 yrs now
Cost of vaccine development high
Cost of the product
Public expectation of risk-free vaccines

69
Q

How do vaccines enter the UK schedule(6 steps)?

A

Licensure
Recommendations
Policy decision
Vaccine purchase
Control of vaccine
Post-licensure assessment