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

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

The course of a typical acute infection

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

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

Immune response to invading viruses

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

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?

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

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

Routes of transmission/risk groups

Most HIV Infected people progress over a period of time

Typical course of untreated infection with HIV

The virion of HIV

2 strains of HIV-1

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)

The infection of CD4 T cells with AIDS

Genes and proteins of HIV

Only activated cells become infected

The immuneresponse to HIV

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

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

Organs affected with AIDS-lymphoid tissue

HIV in the nervous system AIDS dementia

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

Karposi Sarkoma

Karposi Sarkoma

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

Viral decay on drug treatment

Viral decay on drug treatment

HIV Infection is spreading over all continents

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

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