Apoptosis

Apoptosis

Infected CD4+ T cells may be killed when the regulation of cell function is distorted by HIV proteins, probably leading to cell suicide by a process known as programmed cell death or apoptosis. Recent reports indicate that apoptosis occurs to a greater extent in HIV-infected people, both in their bloodstreams and lymph nodes. Apoptosis is closely associated with the aberrant cellular activation seen in HIV disease.

Uninfected cells also may undergo apoptosis. Investigators have shown in cell cultures that the HIV envelope alone or bound to antibodies sends an inappropriate signal to CD4+ T cells causing them to undergo apoptosis, even if not infected by HIV.

Innocent bystanders

Uninfected cells may die in an innocent bystander scenario: HIV particles may bind to the cell surface, giving them the appearance of an infected cell and marking them for destruction by killer T cells after antibody attaches to the viral particle on the cell. This process is called antibody-dependent cellular cytotoxicity.

Killer T cells also may mistakenly destroy uninfected cells that have consumed HIV particles and that display HIV fragments on their surfaces. Alternatively, because HIV envelope proteins bear some resemblance to certain molecules that may appear on CD4+ T cells, the body's immune responses may mistakenly damage such cells as well.

Anergy

Researchers have shown in cell cultures that CD4+ T cells can be turned off by activation signals from HIV that leaves them unable to respond to further immune stimulation. This inactivated state is known as anergy.

Damage to precursor cells

Studies suggest that HIV also destroys precursor cells that mature to have special immune functions, as well as the microenvironment of the bone marrow and the thymus needed for developing such cells. These organs probably lose the ability to regenerate, further compounding the suppression of the immune system