L9- B cell effector function Flashcards
What happens to immature B cells recognising self cell surface antibodies in the bone marrow?
They can be rescued by receptor editing or apoptosis.
What happens to immature B cells recognising soluble antibodies in the bone marrow?
They down regulate the B cell receptor expression and become anergic when they migrate to the periphery.
What happens to immature B cells that recognise low affinity non crosslinking self molecules in the bone marrow?
These B cells undergo apoptosis in the periphery.
What happens to immature B cells that have no self reaction?
They encounter antibodies with T cell help in the periphery and are activated successfully.
How are B cells activated?
B cells recognising antigen stop in the T cell zone of peripheral lymphoid tissues.
If an exogenous antigen is present there will be a B-T cell interaction and activation will occur.
What are the 3 signals needed to activate the B cell?
- Antigen
- Activated T helper cell or PRR’s or APC’s - prevents inappropriate activation.
- Cytokines stimulate differentiation of B cells into plasma or memory cells.
What are the types of antigen that can activate B cells?
- T cell dependent
- T cell independent 1
- T cell independent 2
What are the receptors and costimulatory molecules involved in T cell dependent antigens?
B cell receptor, cytokines
CD40 molecule from Th cells
What are the receptors and costimulatory molecules involved in the T cell independent antigens?
B cell receptor, cytokines
Innate immune receptors (TLRs)
BAFF from dendritic cells (type 2)
How does T cell dependent activation of B cells occur?
- B cells process the a antigens from pathogens and presents them on its surface with MHC class 2 molecules.
- Activated CD4+ T cells are recruited and bind to activate the B cells. Helped by CD40.
- B cells activate and differentiate into plasma and memory cells with the help of cytokines.
Which adhesion molecules are involved in B-T contact?
Integrin adhesion molecules
T CELL- LFA1/VLA4—–>
What does CD40 do?
CD40 is a costimulatory molecule expressed on the surface of T cells which binds to its ligand on B cells.
It stimulates B cell differentiation/class switching/proliferation.
Causes release of cytokines from T cell which guide the B cell in its development (tell it what cell to become/what isotype. It also stimulates the development of the germinal centre.
How does TI-1 activation of B cells occur in low concentration?
- B cell recognises antigen on surface of pathogen via BCR (usually bacteria).
- Bacteria normally contain PAMPs on surface which are recognised by PRR’s on B cell surface e.g LPS(bacteria, virus, fungi, protozoan)-TLR4(B cell)
- Produces a monoclonal B cell line.
How does TI-1 activation of B cells occur in high concentration?
- PAMPs on pathogens are recognised by PRR’ s on B cell surface. No signal from BCR is needed.
- Polyclonal B cell line produced.
How does TI-2 activation of B cells occur?
Large repeating molecules (H. influenzae) bind multiple BCR’s on their cell surface causing cross linking and activation.
This signal is strong enough to activate the B cell but it is a short response so no memory cells.
How can dendritic cells help the TI-2 response?
- Dendritic cells that become an APC for that pathogen can bind to B cells and produce the second signal.
- They can also release BAFF cytokine to increase production of Ab against antigen and induce class switching (IgG produced not just IgM).
What are germinal centre reactions?
Transient structures formed in lymph nodes, spleen, GALT/MALT. Formed at the boundary between B/T cell zones.
Site of second round of Immunoglobulin diversification after detection of antigen by b cell. Induce class switching by AID enzyme.
What is somatic hypermutation and selection?
Ig gene is mutated (by AID enzyme help) and the best suited clone is selected for the antigen.
What does AID do?
Switch regions found after each heavy chain gene have target sequences for AID.
AID is recruited and initiates DNA strand breakage, looping and recombination.
What does the heavy chain (Fc region) determine?
Antibody structure
Complement activation
Isotype
Different cells express receptors for different Fc regions
