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Altered Monocyte or Macrophage Functions

Decreased chemotaxis and phagocytosis

Decreased HLA class II antigen expression

Diminished capacity to present antigen to T cells

Increased spontaneous secretion of IL-1, TNF, IL-6

HIV infection of macrophages has three important implications. First, monocytes and macrophages represent a veritable virus factory and reservoir, whose output remains largely protected

from host defenses. Second, macrophages provide a safe vehicle for HIV to be transported to various parts of the body, including the nervous system. Third, in late stages of HIV infection,

when the CD4+ T-cell numbers decline greatly, macrophages may be an important site of continued viral replication.[135]

In contrast to tissue macrophages, the number of monocytes in circulation infected by HIV is low, yet there are unexplained functional defects that have important consequences for host

defense. These defects include impaired microbicidal activity, decreased chemotaxis, decreased secretion of IL-1, inappropriate secretion of TNF, and, most important, poor capacity to

present antigens to T cells.

Studies have documented that, in addition to macrophages, two types of dendritic cells are also important targets for the initiation and maintenance of HIV infection: mucosal and follicular

dendritic cells. It is thought that mucosal dendritic cells are infected by the virus and transport it to regional lymph

nodes, where CD4+ T cells are infected.[136] Dendritic cells also express a lectin-like receptor that specifically binds HIV and displays it in an intact, infectious form to T cells, thus

promoting infection of the T cells.[137] Follicular dendritic cells in the germinal centers of lymph nodes are, similar to macrophages, important reservoirs of HIV.[138] Although some

follicular dendritic cells may be susceptible to HIV infection, most virus particles are found on the surface of their dendritic processes. Follicular dendritic cells have receptors for the Fc

portion of immunoglobulins, and hence they trap HIV virions coated with anti-HIV antibodies. The antibody-coated virions localized to follicular dendritic cells retain the ability to infect

CD4+ T cells as they traverse the intricate meshwork formed by the dendritic processes of the follicular dendritic cells. To summarize, CD4+ T cells, macrophages, and follicular dendritic

cells contained in the lymphoid tissues are the major sites of HIV infection and persistence.

Although much attention has been focused on T cells, macrophages, and dendritic cells because they can be infected by HIV, patients with AIDS also display profound abnormalities of Bcell

function. Paradoxically, these patients have hypergammaglobulinemia and circulating immune complexes owing to polyclonal B-cell activation. This may result from multiple

interacting factors: reactivation of or reinfection with cytomegalovirus and EBV, both of which are polyclonal B-cell activators, can occur; gp41 itself can promote B-cell growth and



differentiation; and HIV-infected macrophages produce increased amounts of IL-6, which stimulates proliferation of B cells. Despite the presence of spontaneously activated B cells,

patients with AIDS are unable to mount antibody responses to new antigens. This could be due, in part, to lack of T-cell help, but antibody responses against T-independent antigens are

also suppressed, and hence there may be other defects in B cells as well. Impaired humoral immunity renders these patients prey to disseminated infections caused by encapsulated bacteria,

such as S. pneumoniae and H. influenzae, both of which require antibodies for effective opsonization and clearance.


Date: 2016-04-22; view: 895


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