Activating B cell Immunity Immunity Flashcards
What Ig’s are naive B cells + for?
Ig D and IgM
What activates a naive B cell?
Antigens/foreign bodies and helper T cells
What are the three paths a B cell can take after differentiation?
Effector Cells: antiB secreting plasma cells
IgG expressing B cell
High Affinity Ig-expressing B cell
Two results of a high affinity Ig expressing B cell?
Affinity maturation and Memory B cells
How do antiG’s get into the peripheral lymphoid tissues?
Via affernt lymphatic vessels
Do all molecules get taken up by macrphages
no…some are delivered to follice via conduits
Is there processing of the antiG before they are recognized by the BCR?
No!
What is the difference between DC’s and follicular DC’s?
Follicular DC’s dont migrate, they will let antiG stick to their cell surface to present to the B cell but won’t process the antiG
If a B cell is responding to an antiG that is composed of protein, where is this going to happen and what type of B cell is involved?
will happen in the spleen or other lymphoid organ and is done with Follicular B cells.
If a protein antiG is presented to a B cell, what other lymphocyte do we need?
Thelper
What is the end result when an antiG is presented to a follicular B cell with a Thelper?
Isotype switching occurs, get high affinity antiBs and long lived plasma cells:
IgG, IgE, IgA
What type of antiG do marginal B Cells deal with?
What Ig do they express?
are they short or long lived?
lipids, polysachs
IgM recognizes these
they are short lived plasma cells
What signals are required for activation of naive B cells?
BCR binding to antiG
then CR2 or CD21 activated by C3d complenet protein or
TLR activated by PAMP
What are the two options for second signal activation of B cell?
CD2/CD21 activated by C3d
TLR activated by PAMP
CD19 is a …
marker for B cells
How does PAMP work?
its our 2nd signal that will activate a TLR receptor on the B cell surface
TLR then triggers proliferation and differentiation
What is the role of ITAM?
immunoreceptor tyrosine-based ACTIVATION motif will activate a bunch of TFs for clonal expansion and differentiation
Which TFs does ITAM turn on?
Myc and NFAT that tell the cell to proliferate and differentiation
where are ITAMS localized?
in the Ig-alpha and Ig-Beta chains
We can get 2 types of Effector B cells from a stimulating antiG:
T independent
T dependent
Will cause differentiation in absense of T cell and is localized in ________
T independent
spleen, bone marrow, peritoeneal cavity and mucosal tissues
What type of antiG is involved in T independent effector cell generation?
lipids or antiG w/ repetitive structutes
During B cell activatin, we get proliferation of naive B cells in process called _______ which results in ________
Clonal expansion
clones!
Causes differntiation when Thelps are around and the antiG is usually _______
T dependent
protein
What type of Ig makes a pentemeric sturcure?
IgM
IgM is involved in the early stages of what type of immune response?
Humoral
Three options a naive B cell does after activation?
Enters cell cylce mitosis
Increased expression of cytokine receptors
low level IgM secreation
During T dependent response, the initial B cell activation occurs in ________
While the Helper T cell is exposed to teh same antiG in the _______
follicle
extrafollicular space
What is going on during the Initial B-T interaction in T dependent responses?
B cell has moved to the extrafollicular space and is presenting the same antiG the Effector T cells were activated with: the B cell is acting as a specialized APC for the T cell
Result of T-B cell interaction
Get short lived plasma cells that then migrate to the Follicle
Once short lived plasma cells exit the extrafollicular space and enter the follicle what type of reaction do we get? (during T dependent response)
Get germinal center reaction: this is key for telling us we have a very large immune response
Steps of antiG presentation to T helper cells
B cell recognizes microbial protein antiG
Receptor mediate endocytosis
Antigen is processed and presented via a Class II-peptide complex
T cell recognition of antiG via : B7–CD28 to a CD4+ T ell
Once the B cell antiG presentation happens on it’s MHC II to a TCR, what occurs
TCR signals activation of cytokines and we upregulate expression of CD40 ligand
Why do T cells need to upregulate a CD40 ligand during T-cell mediated differentiation of activated B cells?
Because B cell will only be activate once it’s CD40 binds to a CD40L–> causes B cell proliferation, initial antiB production and germinal center rxn
Primary response has a lag of _____
Secondary response a lag of _______
5-10 days
1-3 days
which has a larger peak response, first or second response
second
What type of antiB’s are made during primary response
IgM more then IgG
What type of antiG are made during secondary response?
More IgG and depending on antiG:
Ig A or IgE via heavy chain isotype switching
Which has higher antiB affinity; primary or secondary
secondary (affinity maturation)
primary is less affinity and more variable
What is step 4 of B cell response?
Effector B cell differntation
What two types of Effector B cells do we differentiate into?
antiB secreting plasma cells
Memory B cells
Do memory B cells secreate antiB?
Nope, but retain ability to do so if exposed to their antiG
This process results in antiB’s with Fc region capable of diverse effector fnxs
Class switching
This produces antiB affinity with higher affinities for antiG binding and is triggered by repeated antiG stimulation (booster shots)
Affinity maturation
During secondary exposure, B cell antiB may have increased affinity maturation which d/t ________
will have _______ affinity
and the effector function will/will not change
somatic mutations of VARIABLE region
increased
no change
During secondary exposure, B cell antiB may switch from membrane to secreated form by a change in __________
The affinity will ______
and the effector function is now______
constant region changes so now its free to float around (in free form instead of membrane bound)
no change in affinity
no longer a BCR—> now we are in effector function
During secondary exposure, B cell antiB may do isotype switching which is a change in the ______ with ______change in affinity and the efftor function is specific to ______
change in heavy chain
no change in affinity
specific to each isotype
Three antiB mediated mechanisms for host defense
Complement activation
phagocytosis
Neutralization
Vh is first found on _______ and then is switched onto other _______ regions
IgM and IgD
Cheavy (which is originally Cmew)
What controlls isotype switching?
The switch region upstream of the constant region and is controlled by T helper cells and other cytokines
Why does antiG specificity remain the same during isotype switching?
Because the same LIGHT chain stays associated with the variable heavy chain
This Ig is secreated as a monomer or dimer and functions in mucosal immunity
Ig A–> VERY abundant in plasma
Ig A half life
6 days
This Ig fnxs as naive B cell antiG receptor and is found in trace amounts in plasma
IgD
This Ig is secreated as a monomer and functions in mast cell activation and as defense against helminthic parasites
IgE
This Ig is secreated as a momer and fnx in opsonization, complement activation, antiBdependent cell-mediated cytotoxicity, neonatal immunity
IgG
IgG has how many subtypes on it’s heavy chain?
4 dif subtypes
Half life of IgE
23 days
this Ig functions as naive B cell receptor and complement activation
IgM
What does the structure of an IgA secreated dimer look like?
has two Fc-alpha regions linked by a J-chain with the Fab regions on the outside
What does secreted IgM look like
pentermer structure with a J chain linking two of them and di-S bonds between the other Fc mew regions
This is a shared characteristic btwn a group of Ig molecules with shared antiG specificity adn Variable region Vh and Vl
Idiotype
Type of antiB defined as Constant Heavy region
Isotype
Switch regions are:
intronic genetic element
What is the difference btwn IgM membrane bound and Free?
IgM membrane bound still has the Smew in it’s DNA— has not yet been spliced out
IgM free had it’s Smew spliced out during transcription then is translated with the SAME VDJ
Does IgM get made during T dependent/independent?
T independent, doesn’t get signals from T help
What happens to DNA of naive B cell when it receives signals from Thelp
This signal from Thelp will drive the switch in our Constant region into a different Ig (maybe IgE or IgG depending on cytokine)
What enZ switches out Cmew for new constant region during heavy chain class switching?
AIDE
What Ig do we end up with if the Thelp presents IFN-gamma?
IgG (either IgG1 or IgG3)
This Ig is Fc receptor dependent phagocyte responses; complement activation, neonatoal immunity
IgG
What Ig do we end up with if make IL4 from Thelp?
IgE
What type of Thelper makes IL4?
Th2–> then induces IgE
Cytokines induce expression of which Ig from our B cell?
IgA
What are three modes of Affinity Maturation?
Somatic Hypermutation, High affinity Selection, and Follicular helper T cells
Proliferating/differentiating B cells accumulate mutations in genes encoding Vh and Vl regions
Somatic hypermutation
Maturing B cells undergo apop if don’t receive survival signal from Ag presented by follicular DC’s
High affinity selection
Provide survival signal to maturing B cells
Follicular T helpers (Tfh)
When does affinity maturation occur?
after B cells have been activated by PROTEIN antiG and have migrated into germinal center
What happens to the Vh and Vl regions as they are exposed to more antiGs?
They aquire more mutations
