B cell Responses & Antibody Production Flashcards
What response are antibodies part of ?
The humoral immune response
What is meant by affinity in the case of an antibody-antigen interaction ?
Applies to only a single epitope binding to a single antigen binding site
What is meant by Avidity ?
The total strength
of the antibody-antigen interaction
What are the 2 contiguous exons of the heavy chain sequence ?
Membrane coding (MC) and secretion coding (SC) that can be alternately spliced
What are the five main mechanisms by which antibodies fight extracellular pathogens ?
- Opsonisation
- Complement activation: classical pathway
- Neutralisation
- Agglutination
- Antibody dependent cell-mediated cytotoxicity ADCC
What is meant by Isotype ? and what are the isotypes for L-chains and H-chains ?
- 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
What is Isotype switching ?
Mechanism that changes a B cell’s production of immunoglobulin from one isotype to another
When does Isotype switching occur ?
After activation by antigen in lymph node
How does each Isotype differ?
In hinge region, disulphide bonds, function
Explain T-dependent (TD) responses ?
- 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
Explain T-independent (TI) responses ?
- 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
TFH cells provide the B cell with:
- Anti-apoptotic signals via CD40
- Proliferations & differentiation
signals via IL-21 - Cytokines which regulate which isotype of antibody is produced
B cells migrate towards?
The boundary between the T&B cell zones
Activated B cells then migrate to ?
Follicles, proliferate & form
germinal centers
Antigen activated B cells create a germinal centres which facilitates :
- Clonal selection/expansion (proliferation) one B cell clone produces antibody of one
specificity - Somatic Hypermutation point mutations in V-region of antibody DNA to change affinitiy
& specificity - Class switch recombination from IgD, IgM to IgG, IgA or IgE
What is the Dark zone and the Light zone of the Germinal Centre Reaction ?
- Dark Zone = Proliferation, Class switching and Somatic mutation
- Light Zone = Apoptosis, Selective survival, Maturation
of surviving cells
What is Somatic Hypermutation?
Proliferating B cells in Germinal center subjected to mutational processes that change the sequence of their immunoglobulin genes
What is Affinity maturation ?
B cells with mutations that improve affinity for antigen are selected
What is Class Switch recombination ?
The process by which a B cell changes class of antibody
What does enzyme AID do ?
- Activation-induced cytadine deaminase
- Converts cytosine to uracil in single-stranded DNA
Explain function of antibody isotype: IgM ?
- 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
Explain function of antibody isotype: IgD ?
- 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
Explain function of antibody isotype: IgD ?
- IgG has 4 subclasses, all monomers: IgG1, IgG2, IgG3, IgG4
- Predominant class in blood & extracellular fluid (15%!)
- A longer lifetime than other Ig isotypes (23 days half life)
- Diffuses easily into tissues.
- All subclasses:
- neutralise pathogens/pathogen products
- block infectivity of bacteria and viruses
- diffuse into extracellular spaces
- opsonise - Some can activate complement, ADCC & activate mast cells
- IgG is the main Ab to cross the placenta via neonatal Fc Receptor
Explain function of antibody isotype: IgE ?
- 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)
