Pathogenesis of AIDS
المؤلف:
Abbas, A. K., Lichtman, A. H., & Pillai, S
المصدر:
Basic Immunology : Function and disorders of immune system
الجزء والصفحة:
6th ed , page 246-248
2025-06-21
518
AIDS develops over many years as latent HIV becomes activated and destroys cells of the immune system. Virus production leads to death of infected cells, as well as to death of uninfected lymphocytes, subsequent immune deficiencies, and clinical AIDS (Fig. 1). HIV infection is acquired by sexual intercourse, sharing contaminated needles used by intravenous drug users, transplacental transfer, or transfusion of infected blood or blood products. After infection there may be a brief acute viremia, when the virus is detected in the blood, and the host may respond as in any mild viral infection and present with nonspecific symptoms such as fever, body aches, and malaise. The virus primarily infects CD4+ T cells at sites of entry through mucosal epithelia, in lymphoid organs such as lymph nodes, and in the circulation. In mucosal tissues at the sites of entry, there may be considerable destruction of infected T cells. Because a large fraction of the body’s lymphocytes, and especially memory T cells, reside in these tissues, the result of the local destruction may be a significant functional deficit that is not reflected in the presence of infected cells in the blood or the depletion of circulating T cells. Dendritic cells may capture the virus as it enters through mucosal epithelia and transport it to peripheral lymphoid organs, where it infects T cells. The integrated provirus may be activated in infected cells, as described previously, leading to production of viral particles and spread of the infection. During the course of HIV infection, the major source of infectious viral particles is activated CD4+ T cells. As mentioned earlier, follicular helper T cells and macrophages may become reservoirs of infection, wherein the virus may lie dormant and be reactivated months or years later.
Fig1. Pathogenesis of disease caused by human immunodeficiency virus (HIV). The development of HIV disease is associated with the spread of HIV from the initial site of infection to lymphoid tissues throughout the body. The immune response of the host temporarily controls acute infection but does not prevent establishment of chronic infection of cells in lymphoid tissues. Cytokines produced in response to HIV and other microbes serve to enhance HIV production and progression to acquired immunodeficiency syndrome (AIDS). CTLs, Cytotoxic T lymphocytes.
The depletion of CD4+ T cells after HIV infection is caused by a cytopathic effect of the virus resulting from production of viral particles in infected cells, as well as death of uninfected cells. Active viral gene expression and protein production may interfere with the synthetic machinery of the infected T cells. Therefore, T cells in which the virus is replicating are killed during this process. The number of T cells lost during the progression to AIDS appears to be greater than the number of infected cells. The mechanism of this T cell loss remains poorly defined.
Other infected cells, such as dendritic cells and macrophages, may also die, resulting in destruction of the architecture of lymphoid organs. Many studies have suggested that immune deficiency results not only from depletion of T cells but also from various functional abnormalities in T lymphocytes and other immune cells (dendritic cells and macrophages). The significance of these functional defects has not been established, however, and loss of T cells (followed by a fall in the blood CD4+ T cell count) remains the most reliable indicator of disease progression.
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