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AIDS-Acquired ImmunoDeficiency Syndrome
Lecturer: Adelheid Cerwenka, PhD, D080, Innate Immunity
Sources: Janeway: Immunobiology, 5th edition
AIDS
Definition:
AIDS is the end-stage
disease caused by infection
with the
Human Immunodeficiency
Virus (HIV)
First recognized in 1981
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Annelies Verbrugge
Innate Immunity / D080
AIDS-Acquired ImmunoDeficiency Syndrome
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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
Annelies Verbrugge
Innate Immunity / D080
The course of a typical acute infection
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Innate Immunity / D080
The time-course of infection of normal and immunodeficient mice and humans
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Innate Immunity / D080
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
T cells
Dendritic Cells
Cytokines
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Innate Immunity / D080
Immune response to invading viruses
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Innate Immunity / D080
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
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Annelies Verbrugge
Innate Immunity / D080
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?
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Innate Immunity / D080
16 mio died
3.4 mio people alive
with AIDS
Sahara Africa: 7% inf
Botswana: 30% inf
6 mio newly infected
16 000 newly each day
Course of inf:
10% 2-3 years AIDS
80% progress in 10 years
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Innate Immunity / D080
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Innate Immunity / D080
Routes of transmission/risk groups
Hemophiliac
Intravenous drug abusers
Homosexuals
Heterosexuals
Babies of infected mothers
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Innate Immunity / D080
Routes of transmission/risk groups
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Innate Immunity / D080
Most HIV Infected people progress over a period of time
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Innate Immunity / D080
Typical course of untreated infection with HIV
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Innate Immunity / D080
The virion of HIV
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Innate Immunity / D080
2 strains of HIV-1
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Innate Immunity / D080
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)
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Innate Immunity / D080
The infection of CD4 T cells with AIDS
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Innate Immunity / D080
Genes and proteins of HIV
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Innate Immunity / D080
Only activated cells become infected
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Innate Immunity / D080
The immuneresponse to HIV
The immuneresponse to HIV
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Innate Immunity / D080
Immune response against HIV
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Problems: virus mutates, virus is hiding in storage sited (in
mucosa, brain).
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CD4 T cells: help is missing
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CD8 T cells: Good in the beginning, later they can’t see the
mutated virus,
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B cells: good, but Ab is directed against the initial virus
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Innate Immunity / D080
Organs affected with AIDS
 Lymphoid tissue
 Nervous system
 Gastrointestinal tract
 Cancer: Karposi Sarcoma
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Innate Immunity / D080
Organs affected with AIDS-lymphoid tissue
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Innate Immunity / D080
HIV in the nervous system AIDS dementia
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Innate Immunity / D080
Karposi Sarkoma
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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
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Innate Immunity / D080
Karposi Sarkoma
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Innate Immunity / D080
Karposi Sarkoma
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Innate Immunity / D080
Treatment of AIDS
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HAART: highly efficient triple
combination therapy: (2x antireverse transcriptase,
1xprotease inhib.)
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Innate Immunity / D080
Viral decay on drug treatment
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Innate Immunity / D080
Viral decay on drug treatment
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Innate Immunity / D080
HIV Infection is spreading over all continents
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Innate Immunity / D080
Immune Therapies/Prophylactic vaccine development
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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
Annelies Verbrugge
Innate Immunity / D080
Perspectives
 Prevention!!!!!
 Multiple steps in viral replication offer new targets
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Innate Immunity / D080