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Ab formation
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Hallmarks of the Immune Response Self/Non-self Discrimination Memory Specificity
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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 2 4 6 8 1210 Amount of Circulating Ag (%) 25 75 100 50 Equilibrium Phase Catabolic Decay Phase
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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
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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
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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
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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
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Qualitative Ab Changes during 1 o and 2 o Responses 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
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Qualitative Ab Changes during 1 o and 2 o Responses Class variation Affinity Avidity Cross reactivity
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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
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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
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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
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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
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Class Switching DNA rearrangement –Antigen dependent –Switch site –Same VDJ –T H cytokines
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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
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