Chapter 7 a) B cell activation Flashcards
Describe the cycle of B cells
B cells grow in BM and thymus
they mature and are activated by secondary lymphoid organs like LN and spleen before entering circulation and traveling to site of infection
how are B cells diverse?
combinatorial diversity
- v x j or v xd xj
junctional diversity
-flexible joining at RSS sequences
- P and N nucleotide addition
the combinatorial pairing of heavy and light chains
how do we ensure that only one Ab per B cell is expressed?
productive rearrangement and allelic exclusions
2 chnaces for heavy cahin
4 chances for light chain
B cell deveopment when we are in periphery and antigen dependent
naive B ceel - mature b cell - then exposed to an antigen whihc it consumes inorder to produce antibodies
when travling to LN and spleen describe the antigen
soluble antigen
travel to Ln or spine via what?
subcapsular sinus macrophages (SCSM)
where in the LN or spleen are Ag transferred to?
follicular DC
how are B cells activated from the APC
B cells can be activated via antigen-presenting cell or soluble antigen (tho this is unlikely)
when activated by APC extracts antigen from it so B cell comsumes it through the help of actin, myosin and clathrin
what is the APC for B cells?
Follicular DC
how does B cell recognition of cell-bound Ag reuslt in membrane spreading?
interactions induce a cluster of BCRS and their cognate antigens
the B cells rapidly spread over the traget membrane before contracting back
explain the B cell and APC immunologic synapse
the central supramolecule activation cluster (cSMAC) is surrounded by the peripherial surpamolcule activation cluster (pSMAC) and the distal supramolceule activation cluster (dSMAC)
cSMAC - signaling
pSMAC - integration molecules
dSMAC - like a fence
explai the cytoplasmic protion of B cells
other moleculess associet with them for signal transduction
the Ig alpha and Ig beta units whihc have the ITAMs
what is the fucntion of ITAMs
immunoreceptor tyrosine actiavtion motif (ITAMs) have Ig alpha/beta phosphorylated on them
phospho-Tyr serve as docking points for adapter molcules
B cell activation when tyrosine phosphorlaytion occurs many things happening in the signaling cascade explain them
early steps (0-30mins)
intermediate steps (30 min - 48 hr)
last steps (>48 hrs)
what happens is Btk is produced so that there can be an increase in calcium production
end goal is : generation of many genetically identical effector B cells
what do B cells need help from to be actiavted?
help from CD4+ T helper cells
how do t-dependent responses require help from T-cells
typically generation upon recognition of proetin Ag
in a T-dependent B cell reponse where do animals have to recieve grafts from inorder to produce antibodies??
the thymus and BM
because we need Tcell and B cells
describe the steps of a T-dependent B -cell response
- B cell binds Ag via BCR and this induces intial activation and proliferation events
- interation with helper T cells provides condition for differntiaition and memory cell proudtcion
describe the steps of a T-dependent B -cell response with relation to two signals produced
- recognition of Ag by multiple Ab cross-linking of Abs is the first signal
- upregulation of MHC II and B7
-endocytosis of Ag, presentation on MHC 11 - MHC II binds peptide on TCR
B7 : CD28
upregulation od CD40L - recognition of CD40 by CD40L is 2nd signal
-co-actiavtion of T cell causes T-cell to release cytokines
B cell epitopes
B cells bind Ag via Abs, recognixe and bind free antigen in slution
epitopes can be liner or confrontational, must be accessible and on external surface of antigen
what is an epitope?
specific protion of an antigen that binds to BCR or TCR
what is linked recognition
both the T help cell and B ceel can recognixe the same or different epitopes from the same protein and bind to them
what provides the first signal to B cells, what provides the second signal?
1 - Ag
2 - CD40 L
where does B cell activation in the LN occur?
the GC