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Ch19 Disorders Associated with the Immune System: AIDS

Ch19 Disorders Associated with the Immune System: AIDS. Student Learning Outcomes. Explain the attachment of HIV to a host cell List two ways in which HIV avoids the host’s antibodies Describe the stages of HIV infection Describe the effects of HIV infection on the immune system

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Ch19 Disorders Associated with the Immune System: AIDS

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  1. Ch19Disorders Associated with the Immune System: AIDS

  2. Student Learning Outcomes • Explain the attachment of HIV to a host cell • List two ways in which HIV avoids the host’s antibodies • Describe the stages of HIV infection • Describe the effects of HIV infection on the immune system • Describe how HIV infection is diagnosed • List the routes of HIV transmission • Identify geographic patterns of HIV transmission • List the current methods of preventing and treating HIV infection

  3. Acquired Immunodeficiency Syndrome (AIDS) Origin and History • 1981: In US, cluster of Pneumocystis pneumonia and Kaposi's sarcoma in young homosexual men discovered. The men showed loss of immune function. • 1983: Discovery of virus causing loss of immune function. • 1986: Scientists started to identify the virus with "HIV" abbreviation. • HIV is thought to have crossed the species barrier into humans in central Africa about 1908. • Patient who died in 1959 in Congo is the oldest known case. • Virus spread in Africa as result of urbanization. World-wide spread through modern transportation and unsafe sex. • Norwegian sailor who died in 1976 is the first known case in Western world.

  4. Human Immunodeficiency Virus Fig1.1e

  5. HIV Infection – Review from Ch 13 Fig13.19

  6. Pathogenesis: HIV cellular targets : Th cells APCs brain cell intestinal epithelium

  7. HIV Infection – AIDS is Final stage of HIV Infection HIV: Retrovirus with ssRNA, RT, and envelope with gp120 spikes. Gp120 attach to CD4on ________ cells, M, dendritic cells. Function of RT? Provirus latent or directs active virion synthesis HIV evades IS via latency, vacuoles, antigenic change Fig 19.13

  8. HIV Attachment, Fusion, and Entry Fig 19.13

  9. Latent vs. Active HIV Infection in CD4+ T Cells Fig19.14b

  10. Active HIV Infection in Macrophages Fig19.15

  11. The Stages of HIV Infection • Phase 1: Asymptomatic or chronic lymphadenopathy • Phase 2: Symptomatic; early indications of immune failure • Phase 3 is AIDS: Characterized by indicator conditions, such as: CMV, TB, Pneumocystis, toxoplasmosis, and Kaposi's sarcoma (see Table 19.5) • Phases 1 and 2 are reported as AIDS if CD4+ T cells <200 cells/µl; Phase 3 always reported as AIDS • Progression from HIV infection to AIDS:  10 y • The life of an AIDS patient can be prolonged by the proper treatment of opportunistic infections • People lacking CCR5 are resistant to HIV infection

  12. The Progression of HIV Infection Foundation Fig19.16

  13. Exposed, but not infected • 1 – 3% of Caucasians • No CCR5 gene Survival with HIV Infection • Long-term nonprogressors • 1 in 300 • Measurable PVL, CD4 count slightly  • Highly effective CTLs

  14. Some Diseases Commonly Associated with AIDS See Table 19.5 Pneumocystis jirovecii

  15. Diagnostic Methods • Seroconversion takes up to 3 months • Standard test: ELISA to detect___________ • Confirm by Western blot • Alternative: APTIMA HIV-1 RNA Qualitative Assay (combination of target amplification, hybridization and magnetic capture) • Conventional PLV is determined by PCR or NA hybridization

  16. To be conclusive (HIV-positive), a Western Blot must have 5 horizontal stripes.

  17. HIV Transmission HIV survives 6 h outside a cell and > 1.5 d inside a cell Infected body fluids transmit HIV via • Sexual contact • Breast milk • Transplacental infection of fetus • Blood-contaminated needles • Organ transplants • Artificial insemination • Blood transfusion • In developed countries, blood transfusions are not a likely source of infection anymore

  18. AIDS Worldwide • Heterosexual intercourse (85%) • Injected drug use (IDU) • Women comprise 42% of infected 1.5 mio Fig 19.17 10th ed.

  19. AIDS Prevention • Condoms and sterile needles! • Health care workers use Universal Precautions: • Wear gloves, gowns, masks, and goggles • Do not recap needles • Risk of infection from infected needle stick injury is 0.3% • Vaccine difficulties due to • Mutations • Geographical clades • Quick integration into DNA • Need to also stimulate CTLs (Many failed vaccines. 2009 last phase III trial in Thailand)

  20. AIDS Chemotherapy Treatment has much improved with HAARTHighly Active Anti-Retroviral Therapy - cocktail) • Reverse transcriptase inhibitors (most are nucleoside /-tide analogs, e.g.: AZT) • Fusion inhibitors / Cell entry inhibitors • Protease inhibitors • Integrase inhibitors HIV protease cleaves viral polypeptide into functional proteins Protease inhibition  HIV cannot mature and noninfectious viruses are produced. The End

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