B cell response

What are antibodies?

Plasma proteins that bind specific antigens

What type of bond mediates antigen-antibody interaction?

Non-covalent

What receptor do antibodies form on B cells?

BCR

Where are antibodies found?

Plasma and secretions

What is the basic structure of an immunoglobulin?

L2H2 tetramer

What holds immunoglobulin chains together?

Disulfide bonds

What are the 5 heavy chain types?

α γ ε μ δ

Which heavy chain is found in IgA?

α

Which heavy chain is found in IgG?

γ

Which heavy chain is found in IgE?

ε

Which heavy chain is found in IgM?

μ

Which heavy chain is found in IgD?

δ

Which end of the heavy chain is variable?

Amino terminal

Which end of the heavy chain is constant?

Carboxy terminal

What are the two light chain types?

κ and λ

Can one antibody contain both κ and λ chains?

No

What part of antibody binds antigen?

Fab

What enzyme cleaves Ig into 2 Fab and 1 Fc?

Papain

What does Fc stand for?

Fragment crystallizable

What are Fc functions?

Complement fixation and Fc receptor binding

Which antibody region mediates placental transfer?

Fc region

What enzyme produces F(ab’)2 fragments?

Pepsin

Is F(ab’)2 monovalent or divalent?

Divalent

Does F(ab’)2 mediate effector functions?

No

What forms the antigen-binding site?

VH and VL regions

How many antigen-binding sites does an antibody have?

2

What are hypervariable regions also called?

CDRs

Which CDR has greatest variability?

CDR3

Which CDR contributes most to antigen binding?

CDR3

Which antibodies serve as BCRs on mature B cells?

IgM and IgD

Which antibody is produced first in primary response?

IgM

What is class switching?

Change in isotype without specificity change

Do variable regions change in class switching?

No

What determines antibody isotype?

Heavy chain type

What determines antibody idiotype?

Variable region

Can antibodies recognize conformational epitopes?

Yes

Define antibody affinity.

Strength of one epitope-antibody interaction

Define antibody avidity.

Total binding strength

What increases with repeated antigen exposure?

Affinity maturation

What type of antigens are T-dependent?

Proteins

What type of antigens are T-independent?

Polysaccharides and lipids

Do protein antigens require T-cell help?

Yes

Do polysaccharides require T-cell help?

No

What happens when polysaccharide is conjugated to protein?

Becomes T-dependent

Which B cells mediate T-dependent responses?

Follicular B cells

What type of antibodies do follicular B cells produce?

High-affinity class-switched antibodies

What do follicular B cells become?

Long-lived plasma cells

Where are marginal-zone B cells located?

Splenic white pulp

What antigens activate marginal-zone B cells?

Blood-borne polysaccharides and lipids

Where are B-1 cells found?

Mucosa and peritoneum

What type of response do B-1 cells produce?

T-independent IgM

What are natural antibodies?

Spontaneous IgM antibodies

Function of natural antibodies?

Clear apoptotic cells

How are B cells activated by antigen?

BCR cross-linking

What receptor on B cells binds C3d?

CR2/CD21

What innate signals activate B cells?

Microbial PRRs

What is first antibody secreted after B-cell activation?

IgM

Which antigens strongly cross-link BCRs?

T-independent antigens

How do B cells present protein antigens?

MHC II presentation

Where are naïve CD4 T cells activated?

T-cell zones

Where are naïve B cells activated?

Follicles

Where do activated T and B cells meet?

Follicle edges

Where do germinal centers form?

Follicles

Which receptor decreases on activated T cells?

CCR7

Which receptor increases on activated T cells?

CXCR5

What does CXCR5 promote?

Migration into follicles

What happens to activated B-cell chemokine receptors?

Opposite of T cells

Do B and T cells recognize same epitope?

No

What allows antigen-specific T-B interaction?

Same protein antigen recognition

Define hapten.

Small antigen needing carrier protein

What do helper T cells recognize in conjugate vaccines?

Carrier peptides

What antibody class is promoted by conjugate vaccines?

IgG

Which bacteria are targeted by conjugate vaccines?

H. influenzae and S. pneumoniae

What ligand on T cells activates B cells?

CD40L

What receptor on B cells binds CD40L?

CD40

Functions of CD40 signaling?

Proliferation and class switching

What do T-cell cytokines stimulate in B cells?

Ig production

What helper T-cell subset enters follicles?

Tfh cells

What receptor is highly expressed on Tfh cells?

CXCR5

What costimulatory molecule is on Tfh cells?

ICOS

What cytokine is secreted by Tfh cells?

IL-21

What cells are selected in germinal centers?

Highest-affinity B cells

What do high-affinity B cells become?

Memory and plasma cells

What induces IgE class switching?

IL-4

What induces IgA class switching?

TGF-β and IL-21

What induces IgG switching?

IL-21 and IFN-γ

What enzyme mediates class switch recombination?

AID

What does AID do?

Alters switch regions

Does class switching alter antigen specificity?

No

Where does affinity maturation occur?

Germinal centers

What causes affinity maturation?

Somatic hypermutation

What type of mutations occur in affinity maturation?

Point mutations

What happens to low-affinity B cells in germinal centers?

Apoptosis

Which cells display antigen in germinal centers?

FDCs

What rescues B cells from apoptosis?

Antigen and T-cell help

Most abundant serum immunoglobulin?

IgG

Structure of IgG?

Monomer

Half-life of IgG?

23 days

Main role of IgG?

Secondary immune response

Can IgG cross placenta?

Yes