Date of download: 5/31/2016 From: Immunopathogenic Mechanisms of HIV Infection Ann Intern Med. 1996;124(7): doi: / Typical course of human immunodeficiency virus (HIV) infection.The New England Journal of MedicineThe complex, multifactorial, multiphasic, and overlapping factors of the immunopathogenic mechanisms of HIV disease are shown. Throughout the course of HIV infection, virus replicates and immunodeficiency progresses steadily, despite the absence of observed disease during the so-called clinical latency period. Immune activation and cytokine secretion vary among HIV-infected persons, sometimes increasing dramatically as disease progresses. Immune activation and cytokine secretion play a major role in pathogenesis. Adapted from reference 2 by permission of. Pantaleo et al. 1993; 328: Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

Date of download: 5/31/2016 From: Immunopathogenic Mechanisms of HIV Infection Ann Intern Med. 1996;124(7): doi: / Perturbation of T-cell subsets during primary human immunodeficiency virus (HIV) infection: patient 1.Analysis of the T-cell antigen receptor repertoire during primary HIV infection by a semiquantitative polymerase chain reaction assay showing a transient but marked increase in the number of circulating Vβ19+ cells acutely after HIV infection. Adapted from reference 27 by permission of Nature. 1994; 270: Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

Date of download: 5/31/2016 From: Immunopathogenic Mechanisms of HIV Infection Ann Intern Med. 1996;124(7): doi: / Infection of the SCID-hu thymus with human immunodeficiency virus (HIV).Human fetal thymus and liver are implanted under the renal capsule of the SCID (severe combined immunodeficient) mouse and allowed to mature over 3 to 4 months (original magnification × 15). A. Uninfected, normalappearing thymus with distinct lobes, well-defined corticomedullary junctions, and Hassall corpuscles. B. HIV-infected thymus. A primary isolate of HIV was injected intrathymically, and the tissue was harvested 3 weeks later. Note the marked thymocyte depletion, fibrosis, and infiltration with adipose tissue (original magnification × 15). C. Electron microscopic image of HIV-infected thymus showed marked dropout of thymocytes, leaving behind the network of interdigitating thymic epithelial cells (original magnification × 2300). D. Destruction of thymic epithelial cells. The thymocytes in this area of an HIV-infected thymus appear healthy, but the thymic epithelial cells are degenerating, appearing to undergo a toxic insult with resultant cell death. No HIV is visible (original magnification × 6000). Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

Date of download: 5/31/2016 From: Immunopathogenic Mechanisms of HIV Infection Ann Intern Med. 1996;124(7): doi: / Analysis of dendritic cells from human peripheral blood.[38-41]Dendritic cells purified from peripheral blood by standard methods showed two populations with similar structure. Dendritic cells were isolated from peripheral blood mononuclear cells by density gradient centrifugation through 12.5% (weight/volume) metrizamide (Sigma, St. Louis, Missouri). The low-density cells were shown to be depleted of T, B, natural killer, and monocytic cells by specific staining with monoclonal antibodies and flow cytometry. A. Light microscopy showed that more than 90% of the cells had lobulated nuclei and multiple long cytoplasmic extensions (veils) (original magnification × 400). B. Transmission electron microscopy showed cells with long veiled processes, extensive Golgi regions, and lobulated nuclei. The individual cells shown in panels A and B morphologically represent the entire population (original magnification × 5500). Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

Date of download: 5/31/2016 From: Immunopathogenic Mechanisms of HIV Infection Ann Intern Med. 1996;124(7): doi: / Human immunodeficiency virus (HIV)-pulsed CD83+ dendritic cells can bind virus to their surfaces and transmit virus to unstimulated, autologous CD4+ T cells.IIIB6Top.closed circleBottom.IIIB6The CD83+ population of cells with dendritic structure were purified by flow cytometry using HLA-DR brightness. Monocytes were purified by adherence to plastic for 24 hours. B cells and CD4+T cells were isolated with CD19 and CD4 magnetic beads (Dynal, Lake Success, New York) and were detached from the beads as per the manufacturer's instructions. Cells were pulsed with HIV at various concentrations for 1.5 hours at 37 °C and then washed three times. The HIV-pulsed cells were added to CD4+T cells (2 × 10 /well) and followed for released reverse transcriptase activity. CD4+ T cells and HIV-pulsed cells were mixed at a ratio of 1:10 and were followed for infection. Dendritic cells were pulsed with HIV at a multiplicity of infection of 0.01 □, (open diamond), and ○. Monocytes ( ▵ ) and B cells ( ) were pulsed with HIV at a multiplicity of infection of Cells were pulsed with HIV at an multiplicity of infection of 0.01 and were added in decreasing numbers to 2 × 10 CD4+ T cells. Peak reverse transcriptase activity of the infection is shown. RT CPM = referse transcriptase counts per minute. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians

Date of download: 5/31/2016 From: Immunopathogenic Mechanisms of HIV Infection Ann Intern Med. 1996;124(7): doi: / Human immunodeficiency virus (HIV) disease in progressors compared with long-term nonprogressors.closed circlesopen circles56The course of HIV disease varies dramatically between typical HIV disease progressors ( ) and long term nonprogressors ( ). Both groups may have an initial decrease in CD4+ T-lymphocyte counts during primary infection, but long-term nonprogressors do not have continued progressive loss of CD4+ T lymphocytes during the course of HIV disease. Adapted from reference by permission of Blackwell Science, Inc., from Fauci AS. Newer concepts in the immunopathogenesis of HIV disease. Proceedings of the Association of American Physicians. 1995; 107:1-7. Figure Legend: Copyright © American College of Physicians. All rights reserved.American College of Physicians