Ab formation Hallmarks of the Immune Response Self/Non-self Discrimination Memory Specificity Fate of the Immunogen Clearance after 1o exposure Equilibrium phase Catabolic decay phase Immune elimination phase Kinetics of the Ab ResponseT-dependent Ag; 1o Response Kinetics of the Ab ResponseT-dependent Ag; 2o Response Qualitative Ab Changes during 1o and 2o Responses Qualitative Ab Changes during 1o and 2o Responses Qualitative Ab Changes during 1o and 2o Responses Qualitative Ab Changes during 1o and 2o Responses Cellular Events in 1o Response to T-dependent Ags Lag Clonal selection Log IgM Class switching Stationary Decline Cellular Events in 2o Response to T-dependent Ags Lag phase Virgin cells Memory cells Log phase Pool size IgG, IgA or IgE Stationary Decline Sustained production Memory T cells Kinetics of Ab Response toT-independent Ags 4 Phases IgM antibody No secondary response Class Switching DNA rearrangement Switch site Same VDJ TH cytokines Membrane vs Secreted Ig Differential pre-mRNA processing Membrane exons Alternate polyA sites Same VDJ region used * Clearance after 2o exposure More rapid onset of immune elimination phase Immune Elimination Phase Days after Injection 2 4 6 8 12 10 Amount of Circulating Ag (%) 25 75 100 50 Equilibrium Phase Catabolic Decay Phase Lag phase Log phase Plateau phase Decline phase Ag D a y s  A f t e r  I m m u n i z a t i o n A b T i t e r LAG LOG DECLINE PLATEAU * Specificity Lag phase Log phase Plateau phase Decline phase 1o Ag 2o Ag D a y s  A f t e r  I m m u n i z a t i o n A b T i t e r Class variation 1o - IgM 2o - IgG, IgA or IgE 1o Ag 2o Ag Total Ab IgM Ab IgG Ab D a y s  A f t e r  I m m u n i z a t i o n A b T i t e r Class variation Affinity Affinity Maturation 1o Ag D a y s  A f t e r  I m m u n i z a t i o n A f f I n I t y 2o Ag IgG Ab IgM Ab High Dose Low Dose Class variation Affinity Clonal selection Somatic mutation 10-10 10-8 10-6 10-5 10-9 10-7 High Ag Concentration 10-10 10-8 10-6 10-5 10-9 10-7 Low Ag Concentration Moderate Affinity Ab High Affinity Ab Class variation Affinity  Avidity Cross reactivity IgM Memory Cells IgG 1o Ag IgM Memory Cells IgG IgG Memory Cells Memory Pool Virgin B cell Th Memory Cells Th Th Memory Cells Memory Pool Virgin cell T Cells Virgin cells Memory cells Th cells Cytokines Long Term Memory 1o Ag 2o Ag D a y s  A f t e r  I m m u n i z a t i o n A b T i t e r IgM Ab L  3 2  1 4 1 2 P L V D J S S S S S S S S P L S 1 2 S S  Primary Transcript IgM or IgD Primary Transcript IgE RNA DNA DNA DNA Rearrangement L V D J V D J V D J mRNA Primary Transcript H3 H4 M M H3 H4 M M AAAA Membrane Bound H3 H4 AAAA Secreted H3 H4 AAAA H3 H4 M M AAAA DNA Polyadenylation Sites *