Memory and vaccination

Question 1

What are the actions of antibody

Answer 1

opsonisation, complement fixation, and neutralisation

Question 2

Explain the memory B cell response in early and late

Answer 2

memory B cell retain IgM production, no class switched in early and memory cells leave GC and class switch to IgG, IgA and IgE

Question 3

characteristics of memory B cell

Answer 3

low metabolic rate to respond more rapidly to activation signals than naive cells as they have more activating receptors

Question 4

Why do low affinity IgM requires further affinity maturation

Answer 4

Need to adapt to constantly changing epitopes in pathogen (antigenic drift)
• Keeping diverse Igs with low affinity as memory B cells making it more likely that some of those
will still be able to recognise a modestly mutated antigen
• act as a basis for producing new high affinity immunoglobulins against this modified strain of
pathogen

Question 5

function of T stem cell memory cell

Answer 5

capable of differentiation into the various other types of memory T cell

Question 6

function of central memory T cell

Answer 6

• found in both secondary lymphoid tissue and in the circulation
• most long-lived T cell type, and secrete relatively few cytokines at rest
• can give rise to both TEMand TRMcells

Question 7

function of effector memory T cell

Answer 7

• respond to APCs (CD4+memory) or infected/cancerous cells (CD8+memory) in the blood or tissues.

Question 8

function of effector T cell

Answer 8

• either to provide help (CD4+) or kill offending cells (CD8+)
• Memory cells can change into effector cells in response to stimulation

Question 9

function of resident memory T cell

Answer 9

• more mobile – actively patrolling tissues – and more metabolically active than other memory cells
Ø the first to come across antigen at a site of infection.

Question 10

How does immunological memory change the immune response

Answer 10

• Memory B cells need to be activated to differentiate into plasma cells to produce more antibodies/ cytotoxic T cells (TC) need to be activated to identify infected cells
  * Require T helper cells
  
  • strong response would come only once the antigen has been transported to the large collections of immune cells in the secondary lymphoid tissues
  • This response takes longer to mobilise than HIR - 4-7 days more
    
    • Need to bring T helper and B cells together
    • Need specific cells to proliferate into decent fighting force and differentiate into effector cells

Question 11

Describe the primary and secondary response

Answer 11

Lag phase

• Both T cells and B cells with receptors specific for the antigen must proliferate
• somatic hypermutation and clonal selection of the B cells for high affinity Ig takes place in the germinal centre.
• take 4-7 days or more to generate decent quantities of high affinity antibodies

Antibody phase

• B cells have been selected to make high affinity antibodies and they can differentiate into plasma cells that provide antibody at the site of infection
• rise while the B cells are stimulated by antigen, but stop rising when the infection is cleared

Peak antibody level

• New antibody is no longer being produced
• Antibody half life - 2-4 weeks

Primary response over

• level of antibodies against antigen A fall to a steady level.
• level is higher than it was before the first challenge, and the antibodies will probably have higher affinity and avidity
• new high affinity antibodies are continually produced by long lived plasma cells
• Level of antibody will fall if person does not encounter antigen again

Rapid secondary response

• production of antibodies against antigen A is triggered by the activation of memory B cells and their differentiation into plasma cells that secrete antibodies.
• process is supported by the activation of T helper cells specific for peptides from antigen A
• Shorter lag (1-2 days)

Question 12

what components of the memory response is needed to combat an extracellular bacterial infection

Answer 12

• Antibodies (from long lived plasma cells)
  
  • Antibodies (from activated memory B cells
  • Activation of CD4+ T cells
  • CD8+ cannot as TCR only respond to MHC class I which have an intracellular origin

Question 13

Which facets of the memory response are relevant to combating a virus infection?

Answer 13

• Antibodies (from long lived plasma cells)
  * Basal levels of antibodies could prevent virus infection or reduce scale of initial infection
  
  • Antibodies (from activated memory B cells
    
    • Surge of antibodies produced could reduce virus ability to spread
  • Activation of CD4+ T cells
  • Activation of Cd8+ T cells
  • CD8+T memory cells could identify and destroy infected cells;
  • CD4+T cells could help the rapid expansion and activation of both the CD8+T cells and B cells.

Question 14

Which vaccines uses CTL response

Answer 14

only live attenuated vaccines

Question 15

which vaccines use T helper response

Answer 15

LAV, inactivated, and maybe subunit and inactivated toxins

Question 16

Which vaccines use antibody B cell response

Answer 16

All 4 kinds of vaccine

Question 17

Explain to what extent will vaccine induce T helper cell response

Answer 17

• extent to which a response induces T helper cell responses will depend on the nature of the antigen:
  
  • A T-cell independent antigen (something repetitive, and/or with a strong PAMP) may elicit a B cell/antibody response without generating a CD4+ T cell response.
  • The diversity of antigens in a whole virus vaccine means inducing a CD4 T cell response is more likely, whereas a protein antigen may be less effective at establishing CD4+ T cell memory.

Question 18

Explain live attenuated vaccines

Answer 18

• attenuatedto reduce their potential to cause disease.
  
  • pathogen is grown and adapted to an environment different from what was normal for the virus
  • The resulting virus was able to grow in the gut of vaccinated people, but did not cause disease, and it appears unable to infect the nervous system.
  • The oral polio vaccine induces a strong lifelong immunity, including IgA production in the gut and specific CD8+T cells.

Question 19

Explain inactivated vaccines

Answer 19

• Virus is chemically inactivated, unable to replicate and amplify itself
  * Does not generate cytotoxic T cell response
  
  • the chemical inactivation needs to be stringent enough to kill any chance of a live pathogen surviving, but too much chemical modification runs the risk of changing the antigen so much that antibodies against it will not recognise the undamaged antigen.
  • vaccine should contain all the PAMPs and antigens to produce a decent antibody response, but not a cellular effector

Question 20

What are adjuvants in vaccine

Answer 20

were added to provoke a stronger response by some combination of prolonging the time that antigen survives to stimulate immunity and triggering the innate (PRR) responses of innate immunity.
But only used when assumed that specific antibody production correspond to protection against infection

Question 21

what are subunit vaccines

Answer 21

• consists only part derived from pathogen eg. Surface protein or viral glycoprotein
• may require booster vaccinations
•
requires that antibodies against that subunit correlate with protection from infection or disease: this approach will not work if the CD8+T cell response is essential for protection.

Question 22

what are nucleic acid vaccines

Answer 22

• In essence, DNA (or RNA) molecules are made that encode the antigen, and these molecules are delivered to cells.

the DNA is transcribed and translated into protein, which will be expressed on the cell membrane, while peptides will be presented by MHC class I, to allow both antibody and CTL responses to be induced.
• Most of the DNA/RNA will never makes it to be translated in the cells, and this will act as a PAMP to provide help for antigen presentation from the innate response.
• Often the DNA is engineered with increased frequencies of CpG dinucleotides to help trigger an innate response from TLR9.

Question 23

What are conjugate vaccines

Answer 23

• Some potential antigens are very poorly immunogenic, but if an immune response against them was raised, it would be protective.
• This is particularly true of non-protein antigens, such as bacterial surface polysaccharides that are joined to lipids (lipopolysaccharide – LPS).
• Conjugate vaccines join a non-immunogenic antigen to a protein, so that it becomes more easily identified by the immune system.

Question 24

Nanoparticle vaccines

Answer 24

engineer them into a more virus-like form
• This can use either an artificial bead, lipid droplet or can rely on the ability of (some) virus capsids to assemble spontaneously from their component parts.
• Different types have different properties, but having a small and repeating profile better resembles a pathogen surface, and may enhance antibody production through T-independent mechanisms.

Question 25

What is reproduction number

Answer 25

average number of times an infected individual transmits their pathogen to a new person if R0 below 1 then infection will not sustain continue spread and infection will burn out

Question 26

what is herd immunity

Answer 26

Having a level of immunity that means an infection cannot spread indefinitely

Question 27

what is passive immunisation

Answer 27

• Toxins tend to work more quickly than an adaptive response can develop
  
  • As an alternative, the patient can be injected with an antibody against the toxin (anti-toxin) to neutralise It

Question 28

Examples of passive immunisation

Answer 28

1. Tetanus infection
   • anti-tetanus toxin antibodies in patients where immunisation is incomplete or absent;
   
   2. Botulism
      • anti-botulinum toxin antibodies allows post-exposure prophylaxis
   3. Snake bites, jellyfish sting
      • Anti-venom antibodies prevent receptor binding and help clearance of the toxin
   4. Rabbis infection
      • anti-rabies virus polyclonal/monoclonal antibodies used to reduce/prevent infection after a bite
   5. Emerging infectious diseases
      • Serum from recovered patients given to patients or contacts to reduce illness or prevent spread of disease

Question 29

Why is passive immunisation not vaccination

Answer 29

antibodies do not last long in the circulation and cannot induce long term immunity leaving people vulnerable to re-infection on another bite