B-2 follicular cells
-re-circulating B cells: Majority
B-2 marginal B cells
-reside in the spleen: blood-borne polysaccharide Ags
B-1 cells
-mucosa-limited Ag specificty
Migration of Naive B cells
- passage through SLT, enter through HEV
- No antigen, migrate to primary follicle (CXCR5)
- recieve signal to survive (FDCs)
- Exit through efferent lymphatic vessel competition for survival signals
- naive B cells will die within weeks in absence of antigen
First Signal of B cell activation
- Ag recognition by mlgs
- must crosslink 2 or more BCR
- Ag with bound C3d recognized by mlgs and CR2 (Ag is now more immunogenic)
- Syk-B cell phosphorylation
Migration of Activated B cells
- after activation by Ag in the follicular area, B cells change their chemokine receptor expression and migrate to the edge of the follicular zone
- activated B cells secrete low levels of IgM and increase expression of co-stimulatory molecules and cytokine receptors
T-dependent Immune Synapse
- co-stimulatory signals are generated through the interactions of CD40:CD40L and adhesion molecules
- Cytokine modulated class switching
- Induced expression of activation-induced deaminase enzyme
Somatic Hypermutation
10^3 to 10^4 times higher than normal spontaneous mutation rates
Tfh
- CD4+, low levels of CD25 expression
- secrete IL-21
T-independent Ag B cell activation
- B-1 cells respond to T-independent responses
- marginal zone B cells (B-2) in spleen recognize blood-borne polysaccharides
- Mainly igM, low-affinity antibodies, short-lived plasma cells
Memory B cells
- survival for long periods of time without additional Ag stimulation
- express high levels of anti-apoptotic protein Bcl-2
- capable of mounting a rapid response to subsequent exposure to same Ag (secondary immune response)
Antibody feedback
- control mechanism triggered by secreted Ab that blocks further Ab production
- IgG only, has ITIMS
Humoral Immunity
- Branch of adaptive immunity mediated by antibodies produced by B cells and plasma cells
- principle defense against extracellular pathogens
- Abs are produced by plasma cells in the lymphoid tissues/organs
- effector function of Abs are mediated by the Fc region, all functions are triggered by the binding of Ag to the Fab (V) region
Primary response
- within 5-10 days
- peak response is small
- mostly IgM
- mower average affinity
Secondary response
- within 1-3 days
- Larger response
- increase in IgG, under certain situations, IgA or IgE (heavy chain isotype switching)
- higher average affinity
Fc region
- Deliver antibody to inaccessible anatomical sites
- link bound antigen to molecules/cells that effect destruction
Neutralization
- many microbes bind to the surface of cells to gain entry
- Ab neutralize the infectivity and potential effects of infection
- Abs may sterically hinder binding of microbes
Opsonization and Phagocytosis
- Fc receptors on immune cell populations promote phagocytosis and deliver signals
1. Opsonization of microbe by IgG
2. Binding of opsonized microbes to phagocyte Fc receptors
3. Fc receptor signals activate phagocyte
4. phagocytosis of microbe
ADCC (Antibody-dependent cellular toxicity)
- NK bind to antibody-coated cells by Fc receptors and destroy infected cell
Natural Antibodies
- Mainly IgM, some IgG
- produced by B-1 and marginal zone B cells
- All blood group have IgG and IgM except for AB
IgE mediated reactions
- IgE binds to Fcę receptors on present mast cells
- Ag binding causes degranulation of cell
Neonatal immunity
- IgG from maternal circulation, FcRn transports it across placental barrier
- IgA secreted in breast milk
Vaccination
- mimics a natural infection
- normal immune response is invoked to destroy and clear components of the vaccine
Passive immunization
- immediate immunity but transient
- prevent disease after a known exposure
- protect immunosuppressed patients
- block action of bacterial toxins and prevent diseases that they cause
- Ex: snake bite anti-venom, passive transfer of Ig from mother to child
