1. Immunology, the HIV life cycle and stages of infection Anele Waters HIV Research Nurse North Middlesex Hospital, London

2. Objectives – To explain how the immune system works – To describe the role of the CD4 cells within the immune system – To discuss the life cycle of the HIV virus – To describe the stages of HIV infection

3. The healthy body Under attack everyday Viruses, bacteria, funghi, protozoa The body is protected by structures and processes that fight infection

4. The immune system Non-specific Immunity (Innate)Specific Immunity (Adaptive) Antigen-Independent responseAntigen-Dependent response Immediate maximal response Lag time between exposure and maximal response Not antigen-specificAntigen-specific No immunologic memoryImmunologic memory

5. Lymphocytes Type of Leukocyte (white blood cell) Contain B cells and T cells in addition to Natural Killer cells Part of the Adaptive immune system

6. B cells Humoral immune response Principal function to make antibodies for specific antigens Identify and neutralize foreign invaders Become memory B cells after activation by antigen interaction

7. T cells Cell mediated immune response Types of T cells T helper (AKA CD4 cells) Cytotoxic Memory Regulatory Natural Killer T cells

8. Function of T helper (CD4 cells) Directs immune system Signals maturation of B cells Activates cytotoxic T cells and macrophages

11. The Human Immunodeficiency Virus (HIV)

12. The virus Lentivirus type of Retrovirus Isolated in 1983 Called HIV in 1985 Related simian immunodeficieny virus (SIV) HIV-1 and HIV-2 Bushmeat or Hunter theory

13. Early history of HIV Two samples from Kinshasa, Congo, 1959 and 1960 16-year-old boy from Missouri USA who died in 1969 Norwegian sailor who had been to Cameroon in 60’s died in 1976 A Danish surgeon who travelled to Zaire in 1972, died in 1977 Children involved in research in Uganda 1973

16. Stages of HIV infection Primary HIV infection Asymptomatic HIV infection Symptomatic HIV infection AIDS diagnosis

18. Primary HIV infection Seroconversion illness Fever, rash, sore throat, similar to glandular fever Symptoms soon after exposure and usually lasts 2weeks 50-90% have some degree of symptoms

19. Primary HIV infection Inflammatory response HIV-specific CD4 cells are infected Antibody tests are negative Antigen positive HIV viral load elevated

20. HIV antibodies (within 6 wks but <3 mths) Window period High levels of HIV in blood, sexual fluids and/or breast milk. Highly infectious! Primary HIV infection

21. Asymptomatic HIV infection This stage lasts for an average of 7 to 10 years Free from major symptoms (lymphadenopathy) Viral load drops from seroconversion but remains infectious HIV antibody positive Not dormant, very active in the lymph nodes

22. Symptomatic HIV infection Over time immune system becomes severely damaged The lymph nodes and tissues become damaged HIV mutates and becomes more pathogenic CD4 cells become depleted Symptoms start mild and increase in severity Emergence of opportunistic infections

23. Symptomatic HIV infection Unexplained weight loss Recurrent respiratory tract infections Herpes zoster Recurrent oral ulceration Rashes Fungal nail Unexplained chronic diarrhoea Unexplained persistent fever Persistent oral candidiasis Oral hairy leukoplakia Severe bacterial infections Gingivitis or periodontitis Unexplained anaemia

24. Progression to AIDS 1993 European AIDS case definition (used by Europe, Canada, Australia and Japan)  HIV positive  One of the specified 28 Opportunistic illnesses (OIs)  Does not include CD4 <200 without an OI

25. Opportunistic infections Called “opportunistic” because they take advantage of the weakened immune system. With healthy immune systems exposure to certain viruses, bacteria, or parasites cause no problems. These same bacteria and viruses cause great damage to a weakened immune system.

26. AIDS defining Pneumocystis jirovecii pneumonia  Recurrent severe bacterial pneumonia  Chronic herpes simplex infection  Candidiasis: Esophageal, bronchi, trachea or lungs  Extra pulmonary, pulmonary, disseminated tuberculosis  Kaposi’s sarcoma  Cytomegalovirus, disease and retinitis  Encephalopathy, HIV related  Herpes simplex, bronchitis, pneumonitis, esophagitis, chronic>1mth  Disseminated mycosis (extrapulmonary histoplasmosis, coccidiomycosis)  Mycobacterium (avium complex, TB, kansasii, other)  Progressive multifocal leukoencephalopathy  Chronic cryptosporidiosis  Chronic isosporiasis  Lymphoma (cerebral, Burkitt’s, immunoblastic,non-Hodgkin)  Salmonella (sepsis, recurrent)  Toxoplasmosis (brain)  Wasting syndrome  Pneumonia (recurrent)  Cervical cancer (invasive)