B cell response Flashcards
BCR signalling
BCR = antibody (IgM and IgD in naive)
Ig-alpha and Ig-beta transduce signals
Co-receptors - increase signal (promote activation if weak signal)
- CD21 (complement receptor 2)
- CD19
- CD81
B cell activation
Antigen:BCR (IgM or IgD + Igalpha + Igbeta) ->
Receptor-mediated endocytosis ->
MHC II presentation to T cells -> stimulatory signals ->
Return to follicle and create germinal center
BCR activation effects
- initial proliferation
- B7/CD80 expression
- cytokine receptors, downregulate chemokine receptors -> migration from follicle to T-cell area
- MHC II production and presentation
T cell -> B cell help
CD40 stimulation is required for survival
Some Th2 cells migrate to germinal center to deliver signals
Also:
- affinity maturation via somatic mutation
- Ig class switching (via chromatin remodeling?)
Other cytokines help - ex IL-4
Primary humoral response
Within a week -> proliferation -> plasma cells ->
IgM, IgG -> form complexes -> phagocytosis
Serum concentrations and timeline vary with Ab production, route, catabolism
Secondary humoral response
Memory T and B cells recognize -> Faster and stronger proliferation -> - high Ab concentration - only IgG (high avidity) - clonal selection - highest affinity survive
Serum memory
Long-lived (years) plasma cells (vs short-lived, high production)
In bone marrow
Replaced by higher affinity plasma cells -> refined response
Class switching
Naive express IgM, IgD
Switch requires CD40, differential cytokine signals (IL-4, IL-F, IFN-g, TNF-a)
- ex mucosal surfaces -> TNF-a -> induces IgA production
DNA recombination - places VDJ next to new constant region
- intervening constant regions (mu, delta) are removed
RNA transcript further refined by splicing
Hyper IgM syndrome
Lack of CD40/CD154 signalling to B cells
Can’t class switch ->
Continue to produce IgM, can’t produce other antibodies
Affinity maturation
Somatic mutations in variable regions -> higher affinity of Fab:antigen (better amino acid residues)
- both H and L chains
Occurs in both plasma and memory cells
Competition for antigen binding between and within germinal center -> more proliferation signals
- antigen binding facilitated by follicular dendritic cells
- signals from follicular Th
T-cell independent activation
Antigens that can’t activate T cells (LPS, capsule, dextrans -> can’t be turned into peptide for MHC)
- > repeating epitopes -> bind to multiple BCR’s -> crosslinking -> signal
- > primary IgM response
- no class switching
- no memory (secondary response is the same)
Infant immune function
Normal/high levels of B and T lymphocytes but
Lower immune response overall
- genetic expression of receptors (TCR, Ig’s)
- immature T, B, or APCs
We still try to vaccinate early - HepB, DPT
Newborn antibodies
IgM - produced at birth
IgG -
- passive through placenta (binds to neonatal FcR)
- produced during first year - exposure to GI flora, env’t, pathogens, vaccines
IgA -
- passive through colostrum/breastmilk
- produced at 1-2 months
Immune-exclusion
sIgA binds to pathogens and prevents any interaction with other cells
Ex: Maternal sIgA coats GI tract of newborn
Protective but also decreases vaccine effectiveness (ex RSV)
Antibody function (alone)
Can neutralize viruses and toxins by direct binding
- bind to functional sites
- must have high affinity to outcompete binding by cell receptors, etc
Bacteria - similar binding -> blocks adherence and colonization
Special cases:
Immuno-exclusion = sIgA binding to protect mucosal surface
Tumor therapy - design antibodies for apoptosis receptors
