Humoral Immune Responses Flashcards
What is expressed on mature naive B cells?
BCR -- IgM, IgD, Ig-alpha, and Ig-beta Co-BCR -- CD19, CD81, and CR2 (CD21) MHC Class II CD40 CD20
B-2 cells can be divided into two major subsets, which are…
– Follicular B cells (recirculating B cells – majority)
– Marginal B cells (reside in spleen – blood borne polysaccharide Ags)
B-1 cells are located where?
Mucosa – have limited Ag specificity
Naive B cells travel to secondary lymphoid tissue. The primary lymphoid follicles are the spleen and lymph nodes. They enter the spleen through the ________ and lymph nodes via the _______.
Blood
Lymphatics
Activated (presented by DCs) T cells reduce expression of the chemokine receptor ________, which recognizes chemokines produced in T cell zones, and they increase expression of _______, which binds a chemokine produced in B cell follicles.
CCR7
CXCR5
Activated (antigen-stimulated) B cells decrease expression of _______ and increase expression of _______, exactly the opposite of T cells. As a result, antigen-stimulated T and B cells migrate toward one another and meet at the edges of the lymphoid follicles or in inter-follicular areas.
CXCR5
CCR7
When a B cell is not activated (no antigen) it uses _______ to migrate to the primary follicle.
CXCR5
What do B cells use to pass through the secondary lymphoid tissue?
HEV
Once B cells are in the primary follicle, they receive a signal to survive from ______.
FDCs (follicular DCs)
Within the primary follicle, there are too many B cells and not enough FDCs to provide survival signals. As B cells exit through the efferent lymphatic vessel, there is competition for the survival signals. What happens to naive B cells within weeks of not receiving survival signal/antigen?
They die
Antigen binds to membrane bound ______ on naive B cells and activates them.
Ig
Activation of B cells can occur in two ways, which are…
T-dependent
T-independent
How many signals are required to completely activate a B cell?
2 signals
In the first signal of BCRs, they must ________ 2 or more BCRs to create a strong signal. The signaling itself occurs through the ______ and ______ cytoplasmic tails that contain ITAMs.
Crosslink
Ig-alpha
Ig-beta
The intracellular signaling steps in B cell activation are identical to those of T cells except for the Src-family kinase used in the initial signaling step. B cells use _____, while T cells use ______.
Syk
ZAP-70
Cross-linking of BCR by antigen generates a signal that is necessary but NOT sufficient to activate naive B cells. Ag with bound ______ is recognized by membrane Ig and ______. ______ provides cross-linkage for signaling.
C3d
CR2
CR2
Signaling occurs through Ig-alpha and Ig-beta, CR2 and ______ cytoplasmic tails (BCR co-receptor complex).
CD19
If there is no C3d attached, the use of ______ can recognize PAMPs and develop a signal.
TLRs
After activation by Ag in the follicular area (lymph node), B cells change their chemokine receptor expression and migrate where?
Edge of the follicular zone
Activated B cells secrete low levels of _______ and increase expression of co-stimulatory molecules and cytokine receptors.
IgM
What are TI-1 (T-independent) microbial agents often called that can activate B cells in high concentrations?
Mitogen
The co-stimulatory signals are generated through the interactions of ______:______ and adhesion molecules.
CD40 (B cell)
CD40L (T cell)
Co-stimulatory signals induce cytokine modulated class switching, induce _______ enzyme, and affinity maturation (somatic hypermutation).
AID (activation-induced deaminase)
This enzyme is crucial to the diversification of the antibody repertoire via somatic hypermutation, class switching, and gene conversion. It is a cytidine deaminase and initiates these reactions by delaminating cytidine residues in single-stranded DNA in Ig genes.
AID (activation-induced deaminase)
After receiving T cell help, B cells change their chemokine receptor expression and migrate to the follicular area and establish _______ _______ in the follicles.
Germinal centers
Activated B cells begin cytokine modulated class switching and affinity maturation of receptors. Successful rearrangements are selected/supported by ______ and ______.
Tfh (follicular T helper cells)
FDCs
Cytokines released by Th cells promote two general functions, which are…
– Induce H chain class switching
– Augment B cell differentiation and proliferation
This is the term for the introduction of point mutations in the switch regions of the variable areas of the Ig genes resulting in expansion of the Ab repertoire to generate high-affinity antigen-specific Abs.
Somatic hypermutation