B lymphocytes activation Flashcards
(41 cards)
What are the 3 Ag independent B cell development in bone marrow?
1) DNA somatic rearrangements - create diversity in repertoire
2) Allelic exclusion - ensure each clone expresses single Ab specificity
3) Negative selection of self-reactive clones - to prevent autoimmunity
What are the 3 Ag independent B cell development in the periphery?
1) Somatic hypermutation - allow for increased binding affinity of Abs to Ags (affinity maturation)
2) Isotype switching - deliver Abs effector functions
3) Development of plasma cells - secrete Abs and memory cells (reactivate in secondary response)
What are the 2 types of B cell Ags?
1) Thymus-independent Ags - Weaker but faster response, no memory cell formation, IgM predominant Ab secreted (low level class switching)
2) Thymus-dependent Ags - response to TD Ags requires direct contact with Th cells, slower but stronger response, isotype switch, Ab affinity maturation, memory
What are the 2 types of thymus-independent Ags?
1) Type 1 - bacterial cell wall components as LPS and bacterial DNA, at high concs. can bind to BCRs and TLRs on B cells leading to polyclonal activation - mitogens
2) Type 2 - multivalent highly repetitious molecules (e.g., bacterial flagellin, cell wall polysaccharides), extensive direct cross-linking of BRC activates B cell
What is unique about thymus-dependent (TD) Ags?
1) Contain protein component necessary for T cell activation
2) B cells and Th cells must recognise epitopes of same molecular complex in order to interact - LINKED RECOGNITION
3) Only TD Ags can induce Germinal Centre responses
What is the linked recognition between T cells and B cells?
1) Th cell activated by same Ag (can sometimes not be same epitope)
2) Recognised by B cell and provides ‘help’ to B cell activation
Where does Ag-specific B cell manage to encounter a Th cell with same Ag specificity?
Ag-specific trapping of migrating lymphocytes in secondary lymphoid
How do peripheral lymphoid tissues promote cell-cell contact?
Trap Ag-containing phagocytic cells and concentrate cells together
What is the process for an Ag transported to local lymphoid organ?
1) Ag entry inro skin, GI or respiratory tract
2) Ag captured by DCs and either travel to lymph node/circulation and spleen
3) Ag transported to local lymphoid organ (collects Ag from tissue)
4) If transported to circulation/spleen, blood-borne Ags captured by Ag presenting cells in spleen
What is immune surveillance?
Where T cells recirculate throughout body searching for Ag they are specific for
Where is B cell proliferation and differentiation found in the lymph node?
Cortex (follicle) - B-cell zone
What is the role of the germinal centre for lymph node?
B-cell proliferation and differentiation
What is the role of the paracortex in the lymph node?
Initial T-cell and B-cell activation
What is the role of the medulla in the lymph node?
Plasma-cell secretion of Ab
How do lymphocytes cross from blood into the lymph node?
Via high endothelial venules (HEV)
How are recirculating B cells trapped by foreign Ags in lymphoid organs (short version)?
1) Ags enter node in afferent lymphatic
2) B cells proliferate rapidly
3) B cells enter lymph node from blood via HEVs
4) Short lived B cells secrete Abs and provide immediate defence against infections
How are recirculating B cells trapped by foreign Ags in lymphoid organs (long version)?
1) Ag loaded dendritic cells migrate from tissues into T cell area (paracortex) of local lymph nodes
2) Ag-specific naive T cells migrate in lymph node through HEV, in lymph node they recognise Ags presented by DC: T cell activation
3) Primed T cells proliferate
4) B cells migrate through HEV, trapped by interaction with Ag-specific primed Th cells in T cell area: B cell receive activation signals (cytokines and co-stimulatory signals) and proliferate
5) Activated B cells and cognate T cells migrate to medullary cords where they proliferate to form primary focus (i.e., cluster of Ag specific B cells) - some of these B cells differentiate into short-lived plasma cells that start producing Abs immediately
6) From primary focus, some activated B cells migrate to B cell area follicles to form Germinal Centres (cortex) - B cells interact with follicular dendritic cells and T follicular helper (TFH) cells
What are the 3 things that B cells undergo in germinal centres?
1) Somatic hypermutations
2) Affinity maturation
3) Isotype switching
What is the germinal centre?
1) Split into light and dark zones
2) Where activated B cells (centroblasts) downregulate surface Ig, proliferate, somatically hypermutate their Ig V genes - affinity maturation
3) B cells (centrocytes) upregulate surface Ig, stop dividing and receive co-stimulatory signals from TFH cells and FDC
4) FDCs select useful B cells and follicular T cells are primed by TFH cells
What is affinity maturation?
1) Somatic hypermutation of heavy and light chain variable-region genes (introduction of random somatic point mutations, deletions, insertions in rearranged Ig genes at a rate of around 1bp:10^3 cell divisions) in dividing centroblasts
2) Selection of B cells with affinity surface Ig through Follicular dendritic cells
How are mutations are targeted to Ig Ag binding region?
1) Affinity maturation improves ‘fit’ of Ab for inducing Ag, increasing binding affinity
2) CDR = complementarity determining region or hypervariable region
What is the function of follicular DC?
1) Origin - non-haematopoietic stem cell derived, MHCII-, no presentation of Ags to CD4+ T cells
2) Express DCs express complement receptors CR1, CR2, CR3 and FcR: holding of Ab/complement associated intact Ags
3) Trap and store immune complexes for long periods of time
4) FDCs bind immune complex on cell surface, but do not internalise and process it
What happens after somatic hypermutation of follicular dendritic cells?
1) The mIg of centrocytes might bind the Ag either better/worse than Ig expressed on its precursor
2) Somatic hypermutation of IgV genes produces B cells with diverse range of affinities
What does centrocytes with low affinity surface Ig lead to?
1) Fail to bind Ag held by FDC
2) Leads to apoptosis
