Immunity and Vaccines Immune system Virus persistence Immunity / memory / vaccines Neutr. Ab:...
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Transcript of Immunity and Vaccines Immune system Virus persistence Immunity / memory / vaccines Neutr. Ab:...
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)
• Control-elim. intracell parasites also in solid organs
• regulate longterm IgG• cause imunopathology
(negative selection)
T
BAb
IMMUNO-PATHOLOGY:
V known V
IMMUNOPROTECTION
IMMUNOPATHOLOGY
V
V
AUTOIMMUNITIY:
V not known unrecognized endogenous
VS.
glycoprotein: LCMV-GP glycoprotein:IND-G
rLCMV/INDG rVSV/LCMV-GP
reverse genetic glycoprotein exchange between LCMV and VSV
LCMV VSV-IND
glycoprotein: LCMV-GPglycoprotein:IND-G
Only VSVG expressing viruses induce a neutralizing antibody response
3 8 14 20
642
108
12
<1
time after infection (days)
642
108
12
<13 8 14 20
time after infection (days)
VSV-IND neutralization rLCMV/INDG neutralization
3 8 14 20time after infection (days)
642
108
12
<1
rVSV/LCMV-GP neutralization
3 8 14 20time after infection (days)
642
108
12
<1
LCMV-ARM neutralization
2x104 PFU rLCMV/INDG i.v.
2x104 PFU VSV-IND i.v.
2x104 PFU LCMV i.v.
2x104 PFU rVSV/LCMV-GP i.v.
2x107 PFU rVSV/LCMV-GP i.v.
total Ig IgG
LCMV HIS
WEN-3 mAb
Why autoimmune disease inhumans mostly via antibodies?
Why >> !Why all vaccines that function protect via neutr. antibodies?
First infection kills host:no memory needed
Host survives first infection:memory not necessary
persistent virusfrom mother
Poliomyelitis – age distribution in Massachusetts 1912 – 1952
Years Percent0 – 4 years
Percent5 – 9 years
Percent10+ years
1912-1916 70 18 121930-1934 28 38 341948-1952 18 27 55
Modified from: Nathanson,N. Am J Epidemiol 1979; 110:672-692.
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
Conclusions:
Persistent infections: numbers / variability
• T cell control – immunopathology – "tolerance"
• nAb essential (affinity maturation?) or escape
• All successful vaccines: nAbnot successful: should (also) maintainact.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
H. Hengartner A. AlthageM. Bachmann Th. KündigP. KlenermanA. CiureaU. KarrerTh. FehrL. HunzikerM. Recher
A. Ochsenbein B. LudewigM. PericinA. LamarreU. KalinkeHP. RoostC. LopezM. MartinicTh. Rülicke