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Ab formation

Ab formation. Hallmarks of the Immune Response. Self/Non-self Discrimination Memory Specificity. Equilibrium Phase. 100. 75. Catabolic Decay Phase. Amount of Circulating Ag (%). 50. Immune Elimination Phase. 25. 8. 4. 2. 6. 10. 12. Days after Injection. Fate of the Immunogen.

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Ab formation

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  1. Ab formation

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

  3. Equilibrium Phase 100 75 Catabolic Decay Phase Amount of Circulating Ag (%) 50 Immune Elimination Phase 25 8 4 2 6 10 12 Days after Injection Fate of the Immunogen • Clearance after 1o exposure • Equilibrium phase • Catabolic decay phase • Immune elimination phase • Clearance after 2o exposure • More rapid onset of immune elimination phase

  4. LOG PLATEAU DECLINE LAG A b T i t e r Ag D a y s A f t e r I m m u n i z a t i o n Kinetics of the Ab ResponseT-dependent Ag; 1o Response • Lag phase • Log phase • Plateau phase • Decline phase

  5. 2o Ag 1o Ag A b T i t e r D a y s A f t e r I m m u n i z a t i o n Kinetics of the Ab ResponseT-dependent Ag; 2o Response • Lag phase • Log phase • Plateau phase • Decline phase * Specificity

  6. Total Ab IgG Ab IgM Ab 2o Ag 1o Ag A b T i t e r D a y s A f t e r I m m u n i z a t i o n Qualitative Ab Changes during 1o and 2o Responses • Class variation • 1o - IgM • 2o - IgG, IgA or IgE

  7. IgM Ab IgG Ab 2o Ag 1o Ag Low Dose A f f I n I t y High Dose D a y s A f t e r I m m u n i z a t i o n Qualitative Ab Changes during 1o and 2o Responses • Class variation • Affinity • Affinity Maturation

  8. High Ag Concentration 1010 109 108 107 106 105 Moderate Affinity Ab Low Ag Concentration 1010 109 108 High Affinity Ab 107 106 105 Qualitative Ab Changes during 1o and 2o Responses • Class variation • Affinity • Clonal selection • Somatic mutation

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

  10. 1o Ag IgM IgG Memory Cells Cellular Events in 1o Response to T-dependent Ags • Lag • Clonal selection • Log • IgM • Class switching • Stationary • Decline • Memory Cell Pool

  11. IgM Virgin B cell IgG Memory Cells Memory Pool IgG Memory Cells 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

  12. Virgin cell Th Th Memory Cells Memory Pool Th Memory Cells Memory T cells • T Cells • Virgin cells • Memory cells • Th cells • Cytokines • Long Term Memory

  13. IgM Ab 2o Ag 1o Ag A b T i t e r D a y s A f t e r I m m u n i z a t i o n Kinetics of Ab Response toT-independent Ags • 4 Phases • IgM antibody • No secondary response

  14. Class Switching DNA rearrangement Antigen dependent Switch site Same VDJ TH cytokines

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

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