Immune memory and vaccination

Question 1

Action of antibody

Answer 1

Opsonization Mark a pathogen for phagocytosis
Complement fixation Promote the rupturing of membranes
neutralisation Prevent the successful invasion of cells by the pathogen

Question 2

Compare the antibodies produced in early response and late response

Answer 2

In early response, memory B cell retain IgM produced which has not class-switched. IN late response, memory cells leave GC will have class-switched to IgG, IgA and IgE depending on nature of signals provoked by pathogen

Question 3

characteristics of memory B cells

Answer 3

lower metabolic rate and respond more rapidly to activation signals than naive cells due to more activating receptors on surface
they require T cell helper, BCR binding to trigger activation and proliferation

Question 4

Why is further maturation needed for low affinity IgM

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 differentiating into other types of memory T cell and is constantly replenished in blood

Question 6

function of central memory T cell

Answer 6

most long lived T cell type and can give rise to effector memory T cell and resident memory T cell. It is activated for helper functions in lymphoid tissues

Question 7

function of effector memory T cell

Answer 7

found in tissues or in circulation, respond to APCs or infected cells via CD4+ or CD8+

Question 8

Function of effector T cells

Answer 8

• either to provide help (CD4+) or kill offending cells (CD8+)
• Memory cells can change into effector cells in response to stimulation
• CD4 memory T cell can become any one of the various subsets of cells (TH1, TH2, TH17, Tregetc) that are effector T cells
  
  • Depending on nature of response and cytokine environment

Question 9

function of resident memory T cell

Answer 9

present in tissues and is actively patrolling tissues and more metabolically active than other memory cells. They are the first to come across antigens at site of infection

Question 10

Describe the primary response and secondary response

Answer 10

Primary response begins with lag phase where T cells and B cells proliferate and somatic hypermutation and clonal selection of B cells for high affinity occur in GC

During the antibody phase, B cells have been selected to make high affinity antibodies and differentiate into plasma cells that produce antibodies

At peak antibody level, new antibody is no longer produced
Then primary response is over and levels of antibodies fall to a steady level but higher than at first. new high affinity antibodies are continuous produced by long lived plasma cells

During a secondary response, memory B cells will be activated and differentiate into plasma cells that secrete antibodies. Process is supported by activation of T helper cells specific for peptides from antigen A with a shorter lag

Question 11

Which facets of the memory response can help combat an extracellular bacterial infection?

Answer 11

• Antibodies (from long lived plasma cells)
  
  • Antibodies (from activated memory B cells
  • Activation of CD4+ T cells

Question 12

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

Answer 12

• 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 13

Which vaccines activate CTL response

Answer 13

only live attenuated vaccines

Question 14

which vaccines activate antibody B cell response

Answer 14

live attenuated, inactivated, subunit, toxoid vaccines

Question 15

which vaccines activate T helper cell vaccines

Answer 15

live attenuated vaccines, inactivated and maybe subunit and toxoid

Question 16

Which vaccine will induce T helper cell response ?

Answer 16

• 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 17

Describe live attenuated vaccines

Answer 17

attenuated to reduce their potential to cause disease and the vaccine will not cause disease. It induce a strong lifelong immunity, producing IgA production and specific Cd8+ T cells

Question 18

Describe inactivated vaccines

Answer 18

virus is chemically inactivated and unable to replicate, however too much chemical modification runs the risk of changing antigen so much antibodies cannot target. vaccine contained all the PAMPs and antigens but no cellular effector, produce IgG

Question 19

Problems about inactivated vaccines

Answer 19

roblem
• the virus has reversed some of its attenuating mutations, meaning that the vaccine-derived polio has evolved to again be able to cause disease.
• Once polio is eradicated, we will need to stop vaccinating, but if the vaccine strain is still circulating, then it has the potential to spread into unvaccinated youngsters.

Solution
• switch to the IPV, but this is both much more expensive to manufacture and deliver, and may not even be able to prevent the circulation of polio, because it fails to induce gut immunity.

Question 20

What are good adjuvants

Answer 20

adjuvants added to vaccines to provoke a stronger response assuming that specific antibody production would correspond to protection against infection or disease. Good adjuvants work by combining of prolonging the time that antigen survives to stimulate immunity and triggering the innate(PRR) responses of innate immunity

Question 21

What are subunit vaccines

Answer 21

• consists only part derived from pathogen eg. Surface protein or viral glycoprotein
• may require booster vaccinations
equires 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.
• these vaccines still show limited immunogenicity, and need multiple administrations, or combination with a subunit vaccine to get effective immunity.

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

What are 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.
• The human papilloma virus vaccine is made from its capsid protein, which self-assembles into a virus-like particle.

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

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

transfer of ready-made antibodies against the toxin to neutralise

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