L19 Flashcards
How is the ab response to antigen different after immunisation?
Unimmunised donor primary response:
- frequency of antigen specific B cells 1x10^4
- isotype of ab produced IgM>IgM
- affinity of ab low
- somatic hyerpmutation low
Immunised donor secondary response:
- frequency of ag specific B cells 1x10^3
- isotype of ab produced IgG, IgA
- affinity of ab high
- somatic hypermutation high
What is the response like to T cell dependent vaccines?
Regular bump on graph after first, then taller and longer lasting bump on secondary vaccine.
What is the response like to T cell independent vaccines?
Regular bump to both vaccines. E.g. in capsular polysacch vaccines.
Why are T cells essential in relation to B cells?
they are NEEDED for:
- switching to IgG, IgA and IgE
- high affinity ab production
- essential for the longest lived ab responses
- for B cell memory
This is because T and B cells are needed for productive GCs.
What happens in T independent ab responses?
Shorter lived, less IgG, virtually no memory, no affinity maturation because there are no GCs.
Ab responses can develop through 2 pathways:
Extrafollicular giving modest affinity ab, memory? TD and TI
GC best boy, yes to all. TD response.
How do ab responses to protein antigens being? (DCs and B cells)
Ag specific B celsl binds ag, specific ag efficiently internalised by receptor mediated endocytosis.
DC aren’t specific in antigen uptake. They prime T cells.
B cells are highly specific in what antigen they take up. T cells license B cells.
Why and where is priming of T follicular helper cells by DC important?
Essential for T dependent ab responses.
Why are germinal centres important?
For long lived ab production (nearly all B cell memory) and CLASS SWITCHED and HIGH AFFINITY Ab
What does the B cells need to undergo in terms of recombination?
Further Ig V recombo but needs to be regulated to not recognise self
What is affinity maturation?
Process by which B cell produce Abs of increased affinity for Ag. Parts of affinity maturation include somatic hypermutation and clonal selection of the best B cell. B cells can undergo many rounds of GC to get the best one.
What is somatic hypermutation
The process used to achieve affinity maturation, involved mutations in the variable regions of the Ig
What happens in terms of competition of B cells and fDCs?
The best B cell with the strongest affinity for Ag that the fDC has will be selected, Other low affinity ones will be outcompeted or deleted
What happens in the dark zone of the GC?
Lots of proliferation of the centroblast and also somatic hypermutation
What B cells are in the light zone?
They leave dark zone as centrocytes having somatic hypermutated.
What do fDCs do? Where are they found?
They have intact Ag in its native conformation bound to their surface and CC has to compete to bind this Ag. In light zone.
What do follicular T helper cells do?
They give survival signals to CC after they come out of light and dark zone. they are GC involved T cells.
What is AID?
Activation induce cytidine deaminase when expressed in B cells allows class switch recombination and IgV hypermutation.
Why is CD4O/CD40L important?
CD40 on B cells and CD40L on T cells. It’s important to establish a germinal centre reaction. Important survival signal for B cells ‘licensing’
When can class switching occur?
After encountering Ag and only after activation by T cells
Where does class switching occur?
Both in primary foci in periphery and in GC
What 2; gene and CD are important for class switching?
AID and CD40
Why is IL-21 important?
For generation of T follicular helper cells
What is cognate interaction? What important cytokines are there?
CD4 T follicular helper cell are vital for efficient generation of Abs. They are primed by DCs. They then positively select B cells they recognise peptide presented on MHC2 by them. ICOSL (B cells) and ICOS (T cells) is also important. IL-6, IL-21, IL-4 and IFNγ.
