Activating B cell Immunity Immunity Flashcards by Meghan May

What Ig’s are naive B cells + for?

Ig D and IgM

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What activates a naive B cell?

Antigens/foreign bodies and helper T cells

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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

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Two results of a high affinity Ig expressing B cell?

Affinity maturation and Memory B cells

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How do antiG’s get into the peripheral lymphoid tissues?

Via affernt lymphatic vessels

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Do all molecules get taken up by macrphages

no…some are delivered to follice via conduits

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Is there processing of the antiG before they are recognized by the BCR?

No!

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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

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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.

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If a protein antiG is presented to a B cell, what other lymphocyte do we need?

Thelper

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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

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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

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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

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What are the two options for second signal activation of B cell?

CD2/CD21 activated by C3d

TLR activated by PAMP

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CD19 is a …

marker for B cells

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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

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What is the role of ITAM?

immunoreceptor tyrosine-based ACTIVATION motif will activate a bunch of TFs for clonal expansion and differentiation

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Which TFs does ITAM turn on?

Myc and NFAT that tell the cell to proliferate and differentiation

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where are ITAMS localized?

in the Ig-alpha and Ig-Beta chains

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We can get 2 types of Effector B cells from a stimulating antiG:

T independent

T dependent

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Will cause differentiation in absense of T cell and is localized in ________

T independent

spleen, bone marrow, peritoeneal cavity and mucosal tissues

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What type of antiG is involved in T independent effector cell generation?

lipids or antiG w/ repetitive structutes

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During B cell activatin, we get proliferation of naive B cells in process called _______ which results in ________

Clonal expansion

clones!

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Causes differntiation when Thelps are around and the antiG is usually _______

T dependent

protein

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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

Activating B cell Immunity Immunity Flashcards

(79 cards)