Ab Formation 2001

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Ab Formation 2001

  1. 1. Ab formation
  2. 2. Hallmarks of the Immune Response <ul><li>Self/Non-self Discrimination </li></ul><ul><li>Memory </li></ul><ul><li>Specificity </li></ul>
  3. 3. Fate of the Immunogen <ul><li>Clearance after 1 o exposure </li></ul><ul><ul><li>Equilibrium phase </li></ul></ul><ul><ul><li>Catabolic decay phase </li></ul></ul><ul><ul><li>Immune elimination phase </li></ul></ul><ul><li>Clearance after 2 o exposure </li></ul><ul><ul><li>More rapid onset of immune elimination phase </li></ul></ul>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
  4. 4. Kinetics of the Ab Response T-dependent Ag; 1 o Response <ul><li>Lag phase </li></ul><ul><li>Log phase </li></ul><ul><li>Plateau phase </li></ul><ul><li>Decline phase </li></ul>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
  5. 5. Kinetics of the Ab Response T-dependent Ag; 2 o Response * Specificity <ul><li>Lag phase </li></ul><ul><li>Log phase </li></ul><ul><li>Plateau phase </li></ul><ul><li>Decline phase </li></ul>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
  6. 6. Qualitative Ab Changes during 1 o and 2 o Responses <ul><li>Class variation </li></ul><ul><ul><li>1 o - IgM </li></ul></ul><ul><ul><li>2 o - IgG, IgA or IgE </li></ul></ul>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
  7. 7. Qualitative Ab Changes during 1 o and 2 o Responses <ul><li>Class variation </li></ul><ul><li>Affinity </li></ul><ul><ul><li>Affinity Maturation </li></ul></ul>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
  8. 8. Qualitative Ab Changes during 1 o and 2 o Responses <ul><li>Class variation </li></ul><ul><li>Affinity </li></ul><ul><ul><li>Clonal selection </li></ul></ul><ul><ul><li>Somatic mutation </li></ul></ul>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
  9. 9. Qualitative Ab Changes during 1 o and 2 o Responses <ul><li>Class variation </li></ul><ul><li>Affinity </li></ul><ul><li>Avidity </li></ul><ul><li>Cross reactivity </li></ul>
  10. 10. Cellular Events in 1 o Response to T-dependent Ags <ul><li>Lag </li></ul><ul><ul><li>Clonal selection </li></ul></ul><ul><li>Log </li></ul><ul><ul><li>IgM </li></ul></ul><ul><ul><li>Class switching </li></ul></ul><ul><li>Stationary </li></ul><ul><li>Decline </li></ul><ul><li>Memory Cell Pool </li></ul>IgM Memory Cells IgG 1 o Ag
  11. 11. Cellular Events in 2 o Response to T-dependent Ags <ul><li>Lag phase </li></ul><ul><ul><li>Virgin cells </li></ul></ul><ul><ul><li>Memory cells </li></ul></ul><ul><li>Log phase </li></ul><ul><ul><li>Pool size </li></ul></ul><ul><ul><li>IgG, IgA or IgE </li></ul></ul><ul><li>Stationary </li></ul><ul><li>Decline </li></ul><ul><ul><li>Sustained production </li></ul></ul>IgM Memory Cells IgG IgG Memory Cells Memory Pool Virgin B cell
  12. 12. Memory T cells <ul><li>T Cells </li></ul><ul><ul><li>Virgin cells </li></ul></ul><ul><ul><li>Memory cells </li></ul></ul><ul><li>Th cells </li></ul><ul><ul><li>Cytokines </li></ul></ul><ul><li>Long Term Memory </li></ul>Th Memory Cells Th Th Memory Cells Memory Pool Virgin cell
  13. 13. Kinetics of Ab Response to T-independent Ags <ul><li>4 Phases </li></ul><ul><li>IgM antibody </li></ul><ul><li>No secondary response </li></ul>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
  14. 14. Class Switching <ul><li>DNA rearrangement </li></ul><ul><ul><li>Antigen dependent </li></ul></ul><ul><ul><li>Switch site </li></ul></ul><ul><ul><li>Same VDJ </li></ul></ul><ul><ul><li>T H cytokines </li></ul></ul>  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
  15. 15. Membrane vs Secreted Ig <ul><li>Differential pre-mRNA processing </li></ul><ul><ul><li>Membrane exons </li></ul></ul><ul><ul><li>Alternate polyA sites </li></ul></ul><ul><ul><li>Same VDJ region used </li></ul></ul>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

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