(L25) Humoral (B cell) Immune Response

Question 1

What surface molecules do B cells have?

L24 S9

Answer 1

• BCR (IgM/IgD)
• Igα and Igβ
• CD19, CD81, and CD21 (CR2)
• MHC class II
• CD40
• CD20

Question 2

What are the types of B cells and where are they found?

L25 S7

Answer 2

B-1 cells:

• found in mucosa
• limited Ag specificity

B-2 cells:
-follicular B cells (majority)
—circulating B cells
-marginal B cells
—found in marginal zone of spleen
—secrete Abs for polysaccharides

Question 3

What causes B cells to migrate to the lymph follicles?

L25 S8

Answer 3

CXCR5 expressed on B cells which is a receptor for CXCL13, a chemotactic factor produced by the spleen and lymph nodes.

Question 4

What responses do B cells have to binding of Ag to BCRs?

L25 S12

Answer 4

Increased survival and proliferation signals

Expression of B7 (CD80/86) for interaction with T helper cells

Expression of cytokine receptors

Expression of CCR7 for migration to follicle

Secretion of IgM

Question 5

What signals are involved in T-dependent B cell activation?

L25 S15

Answer 5

Binding of Ag to BCR results in generation of signals for B cell activation and internalization of Ag/presentation on MHC class II

Interaction upregulates expression of CD80/86 (B7) on B cell

CD80/86 binds CD28 (constitutive) on T cells, upregulating expression of CD40L and release of cytokines

Binding of CD40L to CD40 (constitutive) on B cells generates remaining signals needed for activation

Cytokine receptors and CD40 generate signals needed for somatic hypermutation and class switching

Question 6

What is somatic hypermutation and by what process does it occur?

L25 S20

Answer 6

T-dependent activation causes expression of (activation-induced cytidine deaminase)

AID causes deamination of cytosine to uracil

Native enzyme cleave the uracil base from the DNA backbone.

Apurinic endonuclease (APE) causes a double-stranded break.

Double-stranded break is repaired and possible change is DNA sequence occurs that could change the affinity of the Ab produced.

Question 7

How does class switching occur?

L25 S19

Answer 7

T-dependent activation causes expression of (activation-induced cytidine deaminase)

AID causes deamination of cytosine to uracil

Native enzyme cleave the uracil base from the DNA backbone.

Apurinic endonuclease (APE) causes a double-stranded break.

These double stranded breaks are made at the ends of VDJ segment and in C region of desired heavy chain isotype.

Double stranded breaks are ligated together with desired heavy chain isotype next to VDJ segment. Intervening DNA is deleted

Question 8

What selection occurs following somatic hypermutation?
Why and how does it happen?

L25 S25

Answer 8

B cells have changed their affinity follow somatic hypermutation.

Follicular DCs and Tfh cells test B cell for affinity with Ag.

Only B cells with high affinity are given survival signals and proceed to become antigen secreting plasma cells.

Question 9

What signals are involved in T-independent B cell activation?

L25 S27

Answer 9

Extensive cross linking of BCRs to polysaccharide Ag

Can be be supplemented with binding of bacterial PAMPs to B cell TLRs

Activation mechanism of marginal zone B cells and B-1 cells

Question 10

What causes contraction of B cell response?

L25 S31

Answer 10

Binding of IgG to FcγRIIB (IgG specific) on B cells prevents PIP3 formation attenuating B cell activation signals

Question 11

What are the characteristics of primary and secondary antibody responses? (timing, strength of response, Ab type, affinity)

L25 S35

Answer 11

Primary:

• slow response time (5-10 days)
• weaker response
• mostly IgM
• lower affinity

Secondary:

• fast response time (1-3 days)
• larger response
• mostly IgG or class switched
• higher affinity

Question 12

What are the effector mechanisms of Abs?

L25 S36

Answer 12

• neutralization
• opsonization via Fc region
• antibody-dependent cellular cytotoxicity (ADCC)
• inflammation
• opsonization via complement (C3b)
• lysis via MAC

Question 13

How do Abs neutralize microbes and toxins?
What Abs are capable of this?

L25 S43

Answer 13

Works with any Ab

Microbes:

• coats microbe preventing penetration of epithelium
• coats microbe preventing binding/infection of cells

Toxins:
-binds toxins preventing effector mechanism

Question 14

How do Abs opsonize microbes?
What Abs are capable of this?

L25 S44

Answer 14

Fc region of IgG binds FcγRI (CD64) of phagocytes, activating them

Question 15

What is ADCC and how do Abs regulate it?
What Abs are capable of this?

L25 S46

Answer 15

Antibody-dependent cellular cytotoxicity, effector mechanism of NK cells, caused by binding of IgG to NK cell FcγRIII (CD16)

Question 16

What Ab protection does an individual have before and in the first year of life?

L25 S54

Answer 16

Initially protected as a fetus via maternal IgG which crosses the placenta. This supply ends at birth and is out of the system before the age of 1.

Low levels of produced IgM as a fetus that drastically increased during the first year.

Maternal IgA from breast milk.

Sufficient IgG and IgA produced starting at 6-12 months of age.

Question 17

How does maternal IgG cross the placenta?

L25 S53

Answer 17

Endothelial FcRn binds maternal IgG and transports it across the placenta.

FcRn is recycled.

Question 18

Differentiate between passive and active immunization.

L25 S56;59-60

Answer 18

Passive immunization:

• immunization consists of antibodies or antiserum which are transferred to recipient
• faster protection
• no memory generated

Active immunization:

• immunization from exposure to pathogens or components of pathogen (either through natural exposure or via vaccination)
• delayed protection
• memory is generated