B lymphocyte mediated immunity Flashcards
(43 cards)
what are the 2 roles of BCRs
- initiate signalling cascade upon Ag binding
- deliver Ag to intracellular sites for antigen processing & presentation to T-helper cells
what are the 2 types of B cell activation
thymus-dependent: via T-helper cells
thymus-independent: via BCR clustering
thymus-dependent B cell activation
- needs the help of T cells
- presents protein antigens
- CD40:CD40L is the signal for survival
- T cell secretes IL-21 for proliferation and differentiation
thymus-independent B cell activation
- 2 types: TI-1 antigen (clustering of BCRs, TLR) TI-2 antigen (BCR + C3d and CR2)
- BCR clustering leads to signalling
- presents multivalent antigens (carbohydrates)
what is linked recognition
how B cells and T cells work together in B lymphocyte mediated immunity -to mount an immune response against the same pathogen
- present in B cell mediated immunity
what is the second signal required for B-cell activation by thymus-dependent antigens
- from helper TCR:MHC II
- NFkB pathway
what is the second signal required for B-cell activation by thymus-independent antigens
- TLR binds LPS
- myD88 and IKKy activate NFkB pathway
what is the first signal required for B-cell activation
- BCR binding antigens
- PI-3 kinase activates Ras/MAPK pathway to activate AP1 and NFAT TF’s
what is Mcl1
anti-apoptotic gene which is transcribed in the thymus-dependent pathway of B-cell activation
what are the different cytokines that T-helper cells provide to activate B cells and control their differentiation
IL-6
TGF-B
IFN-y
IL-4
how do T-helper cells provided help to B cells that recognize a linked epitope
- T cells are activated to antigens that may reside within the viral particle
- B cell that recognizes a surface epitope of a virus can process and present other antigen epitopes
how do antigen-binding B cells meet T cells at the border between T-cell area and B-cell follicle in SLO’s
(give step by step)
- before activation resting B cells express CXCR5 and reside in follicles, T cells express CCR7 and reside in T-cell zones
- activated B cells induce CCR7 and EBI and T cells induce CXCR5
- both cells migrate to follicular and inter-follicular regions
- B and T cells aggregate at the periphery of follicles
what is the fate of B and T cells after they aggregate in periphery of follicles
- some B cells migrate to form a primary focus and differentiate into plasmablasts
- some T cells induce Bcl-6 and become T-FH cells
what are the 2 possible differentiation steps that B cells which receive T cell help can undergo
- T-FH interaction, remain in follicle: form plasma blast (primary focus) + plasma cell
- no T-FH interaction, outside follicle: form germinal center
what is the difference between a primary and secondary focus?
primary = B cell with no TH interaction, early and rapid Ab production - short-lived
secondary = B cell with strong TH connection, sustain and long-term Ab production, long-lived
when inside lymphoid follicles, activated B cells form…
germinal centers: site for refining B-cell responses (affinity maturation + somatic hyper mutation, class switching)
when B cells form germinal centres inside lymphoid follicles, how do the plasma cells get to bone marrow?
- when B cell encounters antigen in the follicle it forms a primary focus
- some proliferating B cells migrate into the follicle to form a germinal centre
- plasma cells migrate to the medullary cords or leave via efferent lymphatics
- plasma cells migrate to the bone marrow
what are the different zones of germinal centers
- mantle zone
- Dark zone
- Light zone
The dark zone of a germinal center
- contains rapid proliferating B cells (centroblasts) that express CXCR4
- CXCR4 is attracted to CXCL12 produced in dark zone
- densely packed with proliferating cells
- somatic hypermutation of Ig genes happens here
The light zone of a germinal center
- contains T-FH cells
- contains slower proliferating B cells (centrocytes) that express CXCR5
- CXCR5 is attracted to CXCL13 by follicular DCs in light zone
- affinity maturation where B and T-FH test reactivity to new Ig happens here
- cells can return to dark zone for additional rounds of Ig mutation if needed
which area of the germinal centre does class switching happen in
the dark zone
centrocyte vs centroblast B-cell make-up
centrocyte: CXCR5, CD83, CD86
centroblast: CXCR5, CXCR4
where does the primary antibody become diversified
centroblasts (dark zone)
includes somatic hypermutation and class switch
what is the difference between affinity maturation and somatic hypermutation
- IgM is the first antibody made but does not have high affinity
- somatic hypermutation introduces mutations into the rearranged Ig V regions to produce a diverse pool of B cells
- affinity maturation ensures only B cells producing high-affinity antibodies survive and expand
