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Immunity and Vaccines

Immunity and Vaccines. Immune system Virus persistence Immunity / memory / vaccines Neutr. Ab: successful vaccines!. Prevent penetration IgA systemic neutr.-opson.IgM/G adoptive transferable IgG IgM 1-2d, regulated by Ag-dose and structure (no negative selection). B Ab. T.

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Immunity and Vaccines

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  1. Immunity and Vaccines • Immune system • Virus persistence • Immunity / memory / vaccines • Neutr. Ab: successful vaccines!

  2. Prevent penetration IgA • systemic neutr.-opson.IgM/G • adoptive transferable IgG • IgM 1-2d, regulated byAg-dose and structure(no negative selection) B Ab T • Control-elim. intracell parasites also in solid organs • regulate longterm IgG • cause imunopathology(negative selection)

  3. IMMUNOPROTECTION IMMUNOPATHOLOGY V V IMMUNO-PATHOLOGY: V known V AUTOIMMUNITIY: V not known unrecognized endogenous VS.

  4. reverse genetic glycoprotein exchange between LCMV and VSV rLCMV/INDG rVSV/LCMV-GP glycoprotein:IND-G glycoprotein: LCMV-GP LCMV VSV-IND glycoprotein: LCMV-GP glycoprotein:IND-G

  5. Only VSVG expressing viruses induce a neutralizing antibody response

  6. First infection kills host:no memory needed Host survives first infection:memory not necessary Why autoimmune disease inhumans mostly via antibodies? Why >> !Why all vaccines that function protect via neutr. antibodies?

  7. persistent virusfrom mother

  8. Poliomyelitis – age distribution in Massachusetts 1912 – 1952

  9. Maintenance of protection 1. Agent persists: TB, leprosy, HIV, HCV, LCMV Herpes viruses crippled: measles 2. Repetitive inf.: polio, bact. toxins 3. Antibody-antigen complex depots in lymph nodes and spleens

  10. Conclusions: Persistent infections: numbers / variability • T cell control – immunopathology – "tolerance" • nAb essential (affinity maturation?) or escape • All successful vaccines: nAb not successful: should (also) maintain act.T (not achieved yet, TB!) • Maternal antibodies attenuate acute infectionsphysiological vaccinations (incl. malaria, eggs) • Non-cytophatic infections transferred via placenta / at birth / after birth (LCMV, HCV, Herpes) • Resistance via T cells: HIV, HTV, TB Lepr. slow • "Emerging" infections

  11. A. Althage M. Bachmann Th. Kündig P. Klenerman A. Ciurea U. Karrer Th. Fehr Hunziker M. Recher H. Hengartner A. Ochsenbein B. Ludewig M. Pericin A. Lamarre U. Kalinke HP. Roost C. Lopez M. Martinic Th. Rülicke

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