HIV

1
HIV FIV - LCMV

• Immune system viruses
• Tricks of pers. VT deletion / escapenAb delay
  / escape
• Re-encountered / persistent antigen maintains nAb
  (successful vaccines) and act. T (infection
  immunity no vaccine) for protection

2
(No Transcript)
3
(No Transcript)
4
LCMV-viremia control or nAb escape
Ciurea, Hunziker et al.
5
(No Transcript)
6
(No Transcript)
7
(No Transcript)
8

• Prevent penetration IgA
• systemic neutr.-opson.IgM/G
• adoptive transferable IgG
• IgM 1-2d, regulated byAg-dose and structure(no
  negative selection)

B Ab

• Control-elim. intracell parasites also in solid
  organs
• regulate longterm IgG
• cause imunopathology(negative selection)

T
9
reverse genetic glycoprotein exchange between
LCMV and VSV Pinschewer, de la Torre et al.
rLCMV/INDG
rVSV/LCMV-GP
glycoprotein LCMV-GP
glycoproteinIND-G
LCMV
VSV-IND
glycoprotein LCMV-GP
glycoproteinIND-G
10
Only VSVG expressing viruses induce a
neutralizing antibody response
11
Neutralising Ab GP structure

• early TH independent IgM, germline high
  affinity / avidity
• late immunosuppression ? affinity maturation?

12
(No Transcript)
13
Hypergammaglobulinemia vs. neutralizing antibodies
Hypergammaglobulinemia
Neutralising antibodies
Neutralising antibodies
Recher, Lang, Hunziker 2004
14

• Conclusion
• Many nAb "specificities" control V, if "one" too
  slow/low V-escape!
• Hypergammaglobulinemia and polyclonal B cell
  activation compete with nAb responses and seem to
  depend upon amount of virus-specific CD4T cells.
  
• Mechanisms of B cell competition? (Cytokine
  receptor competition? Anatomic competition in
  germinal centers? Competition for anti-apoptotic
  cytokines?).

15
Why autoimmune disease inhumans mostly via
antibodies?
Memory vs. Protection
First infection kills hostno memory needed Host
survives first infectionmemory not necessary

• Why gtgt !Why all vaccines that function
  protect via neutr. antibodies?

16
No protection by Memory B cells but protection by
immune serum in IFN-aBR_/_ against VSV
VSVIND immune spleen cells TB LCMV
immune spleen cells VSVIND Ab
Anti-VSV neutr. AB lt 1 40 lt 1
40 lt 1 2500
Survivors 0 0 100
17
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

18
persistent virusfrom mother
19
Poliomyelitis age distribution in Massachusetts
1912 1952
20
(No Transcript)
21
Memory / Pregnant Female

• Academic earlier higher (AG )
• Immune against cytopathic infectionsotherwise
  abortions / malformations
• MHC-incompatibility offspring / mother
• 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

22
Conclusions

• Persistent infections numbers / variability
• T cell control immunopathology "tolerance"
• nAb essential (affinity maturation?) or escape
• antigen maintains nAb titers and act. T cells
  (but immunopathology!)
• All successful vaccines nAb not successful
  should (also) maintain act.T (not achieved yet)

23
H. Hengartner

• Battegay
• Ciurea
• Hunziker
• M. Recher
• U. Steinhoff

• Odermatt
• Th. Leist
• Lang
• Pinschewer
• J. de la Torre

24
(No Transcript)
25
(No Transcript)
26
IMMUNITY

• innate resistance gt 95
• Ab in eggs
• protective memory via Ab (vaccines)
• TB no vaccine
• autoimmunity gt 30 y, female gt male 5 1