Presentation on theme: "Ch19 Disorders Associated with the Immune System: AIDS"— Presentation transcript:
1 Ch19 Disorders Associated with the Immune System: AIDS
2 LEARNING OBJECTIVES Explain the attachment of HIV to a host cell List two ways in which HIV avoids the host’s antibodiesDescribe the stages of HIV infectionDescribe the effects of HIV infection on the immune systemDescribe how HIV infection is diagnosedList the routes of HIV transmissionIdentify geographic patterns of HIV transmissionList the current methods of preventing and treating HIV infection
3 Acquired Immunodeficiency Syndrome (AIDS) Origin and History1981: 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 in the 1930s.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.
5 Pathogenesis: HIV cellular targets Th cellsAPCsbrain cellintestinal epithelium
6 HIV Infection – AIDS is Final stage of HIV Infection HIV: Retrovirus with ssRNA, RT, and envelope with gp120 spikes.Gp120 attach to CD4 on ________ cells, M, dendritic cells.Function of RT?Provirus latent or directs active viron synthesisHIV evades IS via latency, vacuoles, antigenic changeFig 19.13
10 The Stages of HIV Infection Phase 1: Asymptomatic or chroniclymphadenopathyPhase 2: Symptomatic; early indications of immune failurePhase 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 AIDSProgression from HIV infection to AIDS: 10 yThe life of an AIDS patient can be prolonged by the proper treatment of opportunistic infectionsPeople lacking CCR5 are resistant to HIV infectionCCR5, short for chemokine (C-C motif) receptor 5 is a protein which in humans is encoded by the CCR5 gene which is located on chromosome 3 on the short (p) arm at position 21. CCR5 has also recently been designated CD195 (cluster of differentiation 195).The CCR5 protein functions as a chemokine receptor. The natural chemokine ligands that bind to this receptor are RANTES, MIP-1α and MIP-1β. CCR5 is predominantly expressed on T cells, macrophages, dendritic cells and microglia. It is likely that CCR5 plays a role in inflammatory responses to infection, though its exact role in normal immune function is unclear. HIV uses CCR5 or another protein, CXCR4, as a co-receptor to enter its target cells. Several chemokine receptors can function as viral coreceptors, but CCR5 is likely the most physiologically important coreceptor during natural infection. A number of new experimental HIV drugs, called entry inhibitors, have been designed to interfere with the interaction between CCR5 and HIV, including PRO140 (), Vicriviroc (Schering Plough), Aplaviroc (GW ) (GlaxoSmithKline) and Maraviroc (UK ) (Pfizer). A potential problem of this approach is that, while CCR5 is the major co-receptor by which HIV infects cells, it is not the only such co-receptor. It is possible that under selective pressure HIV will evolve to use another co-receptor.
11 Several chemokine receptors can function as viral coreceptors, but CCR5 is likely the most physiologically important. new experimental HIV drugs, called entry inhibitors
12 The Progression of HIV Infection Foundation Fig19.16
13 Exposed, but not infected Survival with HIV Infection CCR5 mutationEffective CTLsSurvival with HIV InfectionLong-term nonprogressorsMechanism not known
15 Diagnostic Methods Seroconversion takes up to 3 months HIV antibodies detected by ELISAHIV antigens detected by Western blottingHIV antigens detection for diagnosis of congenital HIV infection, needle stick accidents and to monitor drug therapy: Plasma viral load tests (PCR or Western blot)Plasma viral load (PVL) is determined by PCR or nucleic acid hybridization
16 To be conclusive (HIV-positive), a Western Blot must have 5 horizontal stripes.
17 Below is a photograph of a Western Blot tests Below is a photograph of a Western Blot tests. This series of tests illustrates how an HIV test result can change during the window period from HIV-negative to HIV-positive. Each column is one Western Blot test. On the left side of the image there are two columns to be used as points of comparison. The column marked "PC" is an HIV-positive test result and the column marked "NC" is an HIV-negative test result. Column 3 to Column 10 are tests performed on a single person beginning with the day when the person was first exposed to HIV (Column 3, Day 0) to when the person had a full-blown HIV infection (Column 10, Day 30). An HIV infection is not the same as an AIDS diagnosis. This series records the process during which a person's immune system produces a response to an HIV infection. Each black or dark grey horizontal stripe is representative of the presence of a different antibody against a protein found in HIV. To be conclusive (HIV-positive), a Western Blot must have 5 horizontal stripes.
18 HIV TransmissionHIV survives 6 h outside a cell and < 1.5 d inside a cellInfected body fluids transmit HIV viaSexual contactBreast milkTransplacental infection of fetusBlood-contaminated needlesOrgan transplantsArtificial inseminationBlood transfusionIn developed countries, blood transfusions are not a likely source of infection anymore
19 AIDS Worldwide Heterosexual intercourse (85%) Injected drug use (IDU) Women comprise 42% of infectedFig 19.17
20 AIDS Prevention Condoms and sterile needles! Health care workers use Universal Precautions:Wear gloves, gowns, masks, and gogglesDo not recap needlesRisk of infection from infected needlestick injury is 0.3%Vaccine difficulties due toMutationsGeographical cladesAntibody-binding sites “hidden”Infected cells not susceptible to CTLsProvirusesLatent viruses(2099 last phase III trial in Thailand)See Table 19.6
21 AIDS Chemotherapy The End Treatment has much improved with HAART Highly Active Anti-Retroviral Therapy - cocktail)Nucleoside reverse transcriptase inhibitors(mostly nucleoside analogs, e.g.: AZT)Non-nucleoside reverse transcriptase inhibitorsProtease inhibitorsFusion inhibitorsThe End