B cells Flashcards
What components of the innate immune system recruit the adaptive system?
- dendritic cells
- complement cascade -macrophages
What do B cells do?
- make Abs that mark pathogens for destruction
- recruit other cells and molecules that destroy pathogens
Abs circulate as a component of _____ in blood and lymph.
plasma
Name 4 functions of Abs:
- neutralization of toxins/viruses/bacteria
- opsonization of bacteria
- activation of compliment cascade (classical pathway)
- help activate specialized cells in response to antigen
Describe IgG:
- major serum Ig (75%)
- small size i.e. diffuses easily from blood to tissues
- subclasses of IgG have diff roles: 1. opsonization 2. activation of compliment
Describe IgM:
- first Ab produced in immune response
- pentameric (binds strongly)
- BIG; doesn’t diffuse from blood (stays in circulation)
- no receptor for IgM Fc on phagocytes/leukocytes (doesn’t directly recruit these)
- IgM Fc can bind and activate compliment
Describe IgA:
- predominates in secretions
- dimeric; protects the surface of respiratory + intestinal tracts
- poor opsonin
- weak compliment activator
Describe IgE:
- trace amounts in serum
- mostly bound to surface of mast cells via Fc (beneath skin mucosa)
- binds Ag–> release of mast cell granules: inflammatory mediators–> trigger cough, sneezing, vomiting (all to expell pathogen)
The molecular process through which B cells are able to detect infinite, specific antigens and create specific antibodies is called _______.
somatic recombination
What order do the following happen?
immature B cell, heavy chain rearrangement, first checkpoint, second checkpoint, early pro-B cell, light chain gene rearrangement
which of these makes functional IgM??
order:
- early pro-B cell (committed)
- heavy chain gene rearrangement
- first checkpoint (selects functional heavy chains)
- light chain gene rearrangement
- second checkpoint (selects functional light chains)
- immature B cell (makes IgM)
What immunoglobulin serves as the receptor on new B cells?
IgM
Only B cells that do not recognize self-antigen are allowed to leave the bone marrow for the peripheral circulation. What regulatory process allows for this?
Tolerance (death by apoptosis, inactivation)
Where do B cells encounter antigen?
Secondary lymphoid tissue. Here they complete development/differentiation to plasma cells.
What is secondary lymphoid tissue?
- lymph nodes
- spleen
- gut-associated lymphoid tissue
What part of the lymph node is the ‘B cell area’ located?
The T cell area?
Cortex
Cortico-medullary area
What 3 things are necessary for B cell activation?
- cross-linking of surface Ig w specific Ag
- association of B cell receptor w B cell co-receptor (CDx)
- additional signals provided by CD4 helper T cells (Th); Th expresses CD40 ligand detected by B cell….Th secretes cytokines that activate B cell (plasma cells that secrete Ab)
What happens to B cells in the T cell zone?
- interact with Ag
- interact with Th cells of same Ag-specificity
- conjugate pairs form
- activation of B cells to plasma cells
Where is the primary focus for clonal expansion of Ah-activated B cells?
Medullary cords
Do all B cells require Th to differentiate into Ab-producing plasma cells?
No.
Where is the secondary focus for clonal expansion of Ag-activated B cells?
The germinal centre (cortex)
What is in the germinal centre?
- activated B cells
- Th cells
- Ag (carried by follicular dendritic cells- FDC)
What is the difference bw the roles of the primary focus and secondary focus?
Primary: leads to early secretion of specific Ab and provides early protection against infx.
Secondary (germinal centre): provides more effective, later response for persistent infx and re-infx. Dependent on Th cells to refine Ab response.
Mutations occurring in the B cell receptor gene during proliferation in the germinal centre can increase their affinity for Ag. What is this process called? What is allowing for rapid division?
Somatic hypermutation.
Cytokine microenvironment of the germinal centre.
Only B cells that have the highest affinity for Ag are given survival signals in the germinal centre. What is this called?
Affinity maturation.
When do germinal centres present in lymph nodes? What happens to the lymph nodes (seen clinically)?
~ 1 week post-infx
swelling of lymph nodes
What determines isotype switching (from IgM to other Igs: IgE, IgA, IgG)?
What region undergoes recombination during isotype switching?
- T cell interaction with B cell
- microenvironment
-C genes recombine (V regions stay the same)
What compounds result in centrocytes becoming 1. plasma cells versus 2. memory B cells?
IL-10 : plasma cells (make Ab, fight current infx)
IL-4: memory B cells (future)
List differences bw resting B cells and plasma cells.
B cell: has surface Ig, surface MHC II, lower rate Ig secretion, growth inducible, somatic hypermutation possible, isotype switching possible.
Name 2 types of B cell malignancies:
- multiple myeloma (arises from plasma cells in BM)
- leukemia (CLL-chronic lymphocytic leukemia)
List 2 B cell activation and survival factors.
- BAFF (excess in SLE, high Ab)
- APRIL
Name a Rx for lupus that relates to B cell survival factors:
Anti-BAFF antibody
APRIL, BAFF + TACI=
APRIL + BCMA=
BAFF + BR3 =
B cell activation
Bone marrow plasma cell survival
Naive B cell survival
Where is IgA secreted by plasma cells?
How does it get from the basal end of epithelial cells to the apical surface?
Just under the epithelial BM.
By binding to poly-Ig receptors.
What receptor on erythrocytes do C3b-Ab-Ag complexes bind to for clearance from circulation?
Where are the complexes taken>
CR1 receptor on erythrocytes.
Taken to; liver + spleen where pahgocytotic cells remove the immune complexes.
Immune complex mediated disease, due to circulating immune complexes that activate compliment in tissues/vessels, include
- vasculitis
- arthritis
- glomerulonephritis in the kidney
Low levels of C3 and C4 in serum indicates _________
compliment consumption (immune complex mediated disease)
What are the most effective Abs at activating compliment?
IgM and IgG3
