Memory and vaccination Flashcards
What are the actions of antibody
opsonisation, complement fixation, and neutralisation
Explain the memory B cell response in early and late
memory B cell retain IgM production, no class switched in early and memory cells leave GC and class switch to IgG, IgA and IgE
characteristics of memory B cell
low metabolic rate to respond more rapidly to activation signals than naive cells as they have more activating receptors
Why do low affinity IgM requires further affinity maturation
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
function of T stem cell memory cell
capable of differentiation into the various other types of memory T cell
function of central memory T cell
- 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
function of effector memory T cell
• respond to APCs (CD4+memory) or infected/cancerous cells (CD8+memory) in the blood or tissues.
function of effector T cell
- either to provide help (CD4+) or kill offending cells (CD8+)
- Memory cells can change into effector cells in response to stimulation
function of resident memory T cell
• 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.
How does immunological memory change the immune response
- 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
Describe the primary and secondary response
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)
what components of the memory response is needed to combat an extracellular bacterial infection
- 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
Which facets of the memory response are relevant to combating a virus infection?
- 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.
- Antibodies (from activated memory B cells
Which vaccines uses CTL response
only live attenuated vaccines
which vaccines use T helper response
LAV, inactivated, and maybe subunit and inactivated toxins
Which vaccines use antibody B cell response
All 4 kinds of vaccine
Explain to what extent will vaccine induce T helper cell response
- 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.
Explain live attenuated vaccines
- 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.
Explain inactivated vaccines
- 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
What are adjuvants in vaccine
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
what are subunit vaccines
• 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.
what are nucleic acid vaccines
• 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.
What are conjugate vaccines
- 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.
Nanoparticle vaccines
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.
