Ab formation

Hallmarks of the Immune Response Self/Non-self Discrimination Memory Specificity

Fate of the Immunogen Clearance after 1 o exposure –Equilibrium phase –Catabolic decay phase –Immune elimination phase Clearance after 2 o exposure – More rapid onset of immune elimination phase Immune Elimination Phase Days after Injection Amount of Circulating Ag (%) Equilibrium Phase Catabolic Decay Phase

Kinetics of the Ab Response T-dependent Ag; 1 o Response 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 LOGDECLINEPLATEAU

Kinetics of the Ab Response T-dependent Ag; 2 o Response * Specificity Lag phase Log phase Plateau phase Decline phase 1 o Ag 2 o 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

Qualitative Ab Changes during 1 o and 2 o Responses Class variation – 1 o - IgM – 2 o - IgG, IgA or IgE 1 o Ag 2 o 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

Qualitative Ab Changes during 1 o and 2 o Responses Class variation Affinity – Affinity Maturation 1 o 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 2 o Ag IgG Ab IgM Ab High Dose Low Dose

Qualitative Ab Changes during 1 o and 2 o Responses Class variation Affinity – Clonal selection – Somatic mutation High Ag Concentration Low Ag Concentration Moderate Affinity Ab High Affinity Ab

Qualitative Ab Changes during 1 o and 2 o Responses Class variation Affinity Avidity Cross reactivity

Cellular Events in 1 o Response to T-dependent Ags Lag –Clonal selection Log –IgM –Class switching Stationary Decline Memory Cell Pool IgM Memory Cells IgG 1 o Ag

Cellular Events in 2 o Response to T-dependent Ags Lag phase –Virgin cells –Memory cells Log phase –Pool size –IgG, IgA or IgE Stationary Decline –Sustained production IgM Memory Cells IgG Memory Cells Memory Pool Virgin B cell

Memory T cells Th Memory Cells Th Memory Cells Memory Pool Virgin cell T Cells –Virgin cells –Memory cells Th cells –Cytokines Long Term Memory

Kinetics of Ab Response to T-independent Ags 4 Phases IgM antibody No secondary response 1 o Ag 2 o 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

Class Switching DNA rearrangement –Antigen dependent –Switch site –Same VDJ –T H cytokines

Membrane vs Secreted Ig Differential pre-mRNA processing –Membrane exons –Alternate polyA sites –Same VDJ region used mRNA Primary Transcript H3H4 M M H3 H4 M M AAAA Membrane Bound H3H4 AAAA Secreted H3H4 AAAA H3H4 M M AAAA DNA Polyadenylation Sites