B cell Responses & Antibody Production

Question 1

What response are antibodies part of ?

Answer 1

The humoral immune response

Question 2

What is meant by affinity in the case of an antibody-antigen interaction ?

Answer 2

Applies to only a single epitope binding to a single antigen binding site

Question 3

What is meant by Avidity ?

Answer 3

The total strength

of the antibody-antigen interaction

Question 4

What are the 2 contiguous exons of the heavy chain sequence ?

Answer 4

Membrane coding (MC) and 
secretion coding (SC) that can be alternately spliced

Question 5

What are the five main mechanisms by which antibodies fight extracellular pathogens ?

Answer 5

1. Opsonisation
2. Complement activation: classical pathway
3. Neutralisation
4. Agglutination
5. Antibody dependent cell-mediated cytotoxicity ADCC

Question 6

What is meant by Isotype ? and what are the isotypes for L-chains and H-chains ?

Answer 6

• Variation in antibody constant regions
• L chains can be either κ or λ
• H-chains can express the μ, δ, γ, α, or ε gene segments

Question 7

What is Isotype switching ?

Answer 7

Mechanism that changes a B cell’s production of immunoglobulin from one isotype to another

Question 8

When does Isotype switching occur ?

Answer 8

After activation by antigen in lymph node

Question 9

How does each Isotype differ?

Answer 9

In hinge region, disulphide bonds, function

Question 10

Explain T-dependent (TD) responses ?

Answer 10

• Require help from T cells
• Are typically generated upon recognition of protein Ag
• Interactions with T helper cells provides correct conditions for Isotype switching, somatic hypermutation and memory cell production

Question 11

Explain T-independent (TI) responses ?

Answer 11

• Do not require T-cell help
• Generated upon exposure to multivalent/polymerised antigens that B cells recognise through pattern recognition receptors and their surface immunoglobulin

Question 12

TFH cells provide the B cell with:

Answer 12

• Anti-apoptotic signals via CD40
• Proliferations & differentiation
  signals via IL-21
• Cytokines which regulate which isotype of antibody is produced

Question 13

B cells migrate towards?

Answer 13

The boundary between the T&B cell zones

Question 14

Activated B cells then migrate to ?

Answer 14

Follicles, proliferate & form

germinal centers

Question 15

Antigen activated B cells create a germinal centres which facilitates :

Answer 15

1. Clonal selection/expansion (proliferation) one B cell clone produces antibody of one
   specificity
2. Somatic Hypermutation point mutations in V-region of antibody DNA to change affinitiy
   & specificity
3. Class switch recombination from IgD, IgM to IgG, IgA or IgE

Question 16

What is the Dark zone and the Light zone of the Germinal Centre Reaction ?

Answer 16

• Dark Zone = Proliferation, Class switching and Somatic mutation
• Light Zone = Apoptosis, Selective survival, Maturation
  of surviving cells

Question 17

What is Somatic Hypermutation?

Answer 17

Proliferating B cells in Germinal center subjected to mutational processes that change the sequence of their immunoglobulin genes

Question 18

What is Affinity maturation ?

Answer 18

B cells with mutations that improve affinity for antigen are selected

Question 19

What is Class Switch recombination ?

Answer 19

The process by which a B cell changes class of antibody

Question 20

What does enzyme AID do ?

Answer 20

• Activation-induced cytadine deaminase

- Converts cytosine to uracil in single-stranded DNA

Question 21

Explain function of antibody isotype: IgM ?

Answer 21

• First antibody secreted by B cells
• IgM forms a flexible pentamer by interacting with the J-chain
  enabling strong antigen binding via 10 antigen binding sites
• The major function of IgM is
  complement activation
• Neutralisation, opsonisation and antigen transport are also functions of IgM
• IgM & IgD are derived from the same pre-mRNA transcript

Question 22

Explain function of antibody isotype: IgD ?

Answer 22

• Unique functions of IgD are still unclear
• IgM & IgD are co-expressed on the surface of almost all mature B cells and binds to antigen
• But IgD is only secreted in small amounts at any time
• The hinge region of IgD is more flexible than IgM
  suggestive of an auxillary receptor function to facilitate antigen binding by naive B cells
• B cells expressing IgM and IgD have not undergone
  class switching

Question 23

Explain function of antibody isotype: IgD ?

Answer 23

1. IgG has 4 subclasses, all monomers: IgG1, IgG2, IgG3, IgG4
2. Predominant class in blood & extracellular fluid (15%!)
3. A longer lifetime than other Ig isotypes (23 days half life)
4. Diffuses easily into tissues.
5. All subclasses:
   - neutralise pathogens/pathogen products
   - block infectivity of bacteria and viruses
   - diffuse into extracellular spaces
   - opsonise
6. Some can activate complement, ADCC & activate mast cells
7. IgG is the main Ab to cross the placenta via neonatal Fc Receptor

Question 24

Explain function of antibody isotype: IgE ?

Answer 24

• Mediator of allergic reactions
• Contributes to a small but important part of the immune response: anti-parasite responses & allergy
• IgE functions as a cell surface receptor and sensitises mast cells & basophils (increased its half-life when bound)

Question 25

Explain function of antibody isotype: IgA ?

Answer 25

• Primary function is transport across the mucosal epithelium (dimeric form)
• Monomeric form diffuses into extravascular sites
• Involved in pathogen neutralisation & is transferred to neonates in breastmilk

Question 26

Agglutination forms ?

Answer 26

Precipitate of soluble antigen ‘clumps’ for easy detection & removal

Question 27

Explain Antibody dependent cell cytotoxicity (ADCC) ?

Answer 27

An immune mechanism through which Fc receptor-bearing effector cells can recognise and kill antibody-coated target cells expressing tumour- or pathogen-derived antigens on their surface