L06 Flashcards
when are B cells activated
when they bind an AG
what do activated B cells give rise to
Plasma cells and memory cells
what are the ways in which Ab work
neutralization, opsonization, compliment activation
what BCRs are always present in naive B cells
IgM and IgD
what provides signal 1 in BCR
Binding of Ag to BCR
what BCR-associated polypeptides involved in signal
Igα and Igβ
what is the role of compliment molecules in relation to signal one in B cells
they enhance it
what compliment molecule is involved in signal 1 of B cell
CR2
what are the types of antigens involved in B cell signal 2
T (thymus)-independent Ag (TI)
T (thymus)-dependent Ag (TD)
what is signal 2 provided by in T (thymus)-independent Ag (TI):
a) antigen itself or
b) extensive cross-linking of BCR
what is signal 2 provided by in T (thymus)-dependent Ag (TD)
CD4+ T cells
what class of Ab thro thymus independent signaling
IgM
what type of signaling allows Ab class switching
thymus dependent (TI)
give an example of a danger signal on dendritic cells
LPS
what do TI-1 Ag do
bind to other receptors on all B cells providing signal 2
give an example of TI-1 Ag
lipopolysaccharide from Gram -ve bacteria binds to TLR4 expressed by B cells
what are the types of thymus independent TI ag
TI-1
TI-2
what are the features of TI-2 Ag
contain repeated epitopes
will therefore cross-link many BCR molecules on same B cell surface
take longer (more Ag required) to induce B cell activation
Antibody responses to TI-2 Ag typically don’t develop until > 5 yrs. in humans
what are the features of the repeated epitopes in TI-2 Ag
often polysaccharides (same sugar repeated lots)
important in some bacterial infections (coated)
where does signal 2 in B cells come from
CD40
cytokines secreted by T cells
what plays a role in class switching of Ab
cytokines secreted by the T cells
what are the examples of a conjugate vaccine
Haemophilus influenzae type b when the protein tetanus toxoid is coupled
MenC
peneumococcal conjugate vaccine
what does the CD4 T cell do after binding to an MHC 2
expresses CD40 ligand (CD40)
secretes cytokines
what does CD40/CD40L binding do
sends signal 2 to B cell to proliferate
induces activation induced deaminase (AID)
what does activation induced deaminase (AID) do
required for class switching and somatic hypermutation
where in secondary lymphoid do B cells divide rapidly
form germinal centres (GC)
what do B cells that divide rapidly undergo
somatic hypermutation of Ig genes
isotype switching
what is the germinal centres (GC) within a B cell follicle formed of
conjugates of B lymphoblasts and T cells
B cells divide rapidly to form _______
centroblats
What other types of cells present in B cell germinal centre
Follicular dendritic cells, T cells
What is the role of T cells in the B cells germinal centre
Binds to B cells = signal 2
What type of T cell is present in the GC?
TFH
What is the role of TFH
continuous signal 2 in B cells
What cytokine is involved to allow the movement of T cells into GC?
IL6
What are the three fates of B cells once in the GC
- Differentiate into plasma cells
- form long lived memory cells
- die within lymphoid tissue
What does a B cell do after they differentiate into plasma cells
- secrete various isotypes
- high affinity antibodies
When would a B cell die within the lymphoid tissue
BCR ni longer binds antigen (due to unsuccessful v chain or somatic mutation
What do somatic hypermutations result in?
Point mutations into V regions, 1,000,000 times higher mutations.
What are the enzymes primarily involved in somatic hypermutations?
AID - activation induced deaminse and DNA repair gene
Are follicular dendritic cells bone marrow derived?
No
What is the role of the follicular dendritic cells?
APC
Describe B cell affinity maturation?
Centrocytes compete with e/o for Ag on FDC&signals from THC,
BCR with better affinity will present more efficiently and recieve CD40 signal from TFH cell
What happens if B cells fail to develop affinity maturation?
- apoptosis
- recycled to the dark zone
What sort of cytokines are produced by TFH?
Th1 or Th2
What cell produces CD40?
B cell
What are the roles of CD40?
- protects centrocytes from apoptosis
- induces isotype switching
How are different isotypes induced?
Different cytokines
Is isotype switching RAD mediated?
No
What is the initial BCR Ig class?
IgM
What is the role of cytokines in isotype switching?
Informs where to cut the DNA
