1. AIDS-Acquired ImmunoDeficiency Syndrome
Lecturer: Adelheid Cerwenka, PhD, D080, Innate Immunity
Sources: Janeway: Immunobiology, 5th edition

2. AIDS Definition: AIDS is the end-stage disease caused by infection
with the
Human Immunodeficiency
Virus (HIV)
First recognized in 1981

3. AIDS-Acquired ImmunoDeficiency Syndrome
General mechanisms for recognition of viruses by the immune system
Groupwork
History of AIDS, Epidemiology
Structure of HIV
The Immune system and HIV
AIDS and other diseases (Karposi Sarcoma)
Treatment of AIDS
Perspectives

4. The course of a typical acute infection

5. The time-course of infection of normal and immuno-deficient mice and humans

6. A.) Direct recognition and
Innate immune response
A.) Direct recognition and
elimination of
virus infected cells
B.) Cross-talk with adaptive
immunity
Virus infected cell
Cell-cell contact
Natural Killers
Macrophages
Dendritic Cells
T cells
Cytokines

7. Immune response to invading viruses

8. History Since 1981 the syndrome known
Los Angeles: 5 people in hospital with Pneumocystis Pneumonia.
1983 Virus identified HIV-1 (NIH: Robert Gallo, Luc Montagnier, Pasteur), HIV-2

9. Group work 1.) How many people in the world are infected with HIV?
2.) In which part of the world is the highest incidence?
3.) How does transmission of HIV take place?
4.) What goes wrong with the immune system?
5.) Ideas for prevention and cure?

10. 16 mio died
3.4 mio people alive
with AIDS
Sahara Africa: 7% inf
Botswana: 30% inf
6 mio newly infected
newly each day
Course of inf:
10% 2-3 years AIDS
80% progress in 10 years

12. Routes of transmission/risk groups
Hemophiliac
Intravenous drug abusers
Homosexuals
Heterosexuals
Babies of infected mothers

13. Routes of transmission/risk groups

14. Most HIV Infected people progress over a period of time

15. Typical course of untreated infection with HIV

16. The virion of HIV

17. 2 strains of HIV-1

18. Coreceptors for HIV
CCR5: (ligands RANTES, MIP1a, MIP1b): DC, Macrophages
CXCR4 (SDF-1): activ. T cells
DC-Sign (possibly traps virus before encounter of susceptible cells)

19. The infection of CD4 T cells with AIDS

20. Genes and proteins of HIV

21. Only activated cells become infected

22. The immuneresponse to HIV

23. Immune response against HIV
Problems: virus mutates, virus is hiding in storage sited (in mucosa, brain).
CD4 T cells: help is missing
CD8 T cells: Good in the beginning, later they can’t see the mutated virus,
B cells: good, but Ab is directed against the initial virus

24. Organs affected with AIDS
Lymphoid tissue
Nervous system
Gastrointestinal tract
Cancer: Karposi Sarcoma

25. Organs affected with AIDS-lymphoid tissue

26. HIV in the nervous system AIDS dementia

27. Karposi Sarkoma
First reported by Hungarian physician: Moritz Karposi in 1872
Multifocal cancer: dominant type is called spindle cells: endothelial origin
Typically in older man in Mediterranian rim
In HIV-1: very aggressive: occurs in 20% of infected homosexual man, only 2% in others
Evidence that Herpes virus (HHV8) is necessary is strong

28. Karposi Sarkoma

29. Karposi Sarkoma

30. Treatment of AIDS
HAART: highly efficient triple combination therapy: (2x anti-reverse transcriptase, 1xprotease inhib.)

31. Viral decay on drug treatment

32. Viral decay on drug treatment

33. HIV Infection is spreading over all continents

34. Immune Therapies/Prophylactic vaccine development
Difficulties:
Rapid mutations in virus
Danger to cause an inappropriate immune response
Necessity to target privileged sites (mucosa, brain)
Small animal models not available
Ethical issues of vaccination: people should adjust behaviour

35. Perspectives
Prevention!!!!!
Multiple steps in viral replication offer new targets