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Hiv's Immune-system Impairment Mechanism

One of the most disastrous effects of HIV infection is the loss of the immune system's CD4 T cells. These cells are responsible for recognizing foreign invaders to a person's body and initiating antibody production to ward off the infection. Without them, people are susceptible to a variety of diseases. HIV destroys the T cells slowly, sometimes taking a decade to destroy a person's immunity. However, in all the time before an HIV-infected individual shows any symptoms, the virus has been reproducing rapidly. The lymph tissue, the resting place for CD4 T cells, macrophages, and dendritic cells, becomes increasingly full of HIV, and viral particles are also released into the bloodstream.

HIV's main target is the population of CD4 T cells within a host's body. HIV kills them in one of three ways. It kills them directly by reproducing within them, then breaking them upon exit; it kills them indirectly by causing the cells to "commit suicide" by inducing apoptosis; or it kills them indirectly by triggering other immune cells to recognize the infected T cell and kill it as part of the immune system's normal function.

As infected T cells die, the immune system generates more to take their place. As new T cells become infected, they are either actively killed or induced to commit suicide. Meanwhile, the HIV virus is not completely HIV binds to CD4 and CCR-5 or CXCR4 on the surface of the target cell, allowing the virus coat to fuse with the cell membrane and virus contents to enter the cell. (2) Reverse transcriptase (RT) enzyme transcribes viral RNA into single-strand viral DNA, a step blocked by RT inhibitors (AZT, ddi, d4t, ddc). Single-strand DNA is converted to double-strand DNA which then enters the nucleus and integrates into the host chromosome. (3) Upon activation of the cell, viral RNA triggers manufacture of viral proteins. In the absence of protease inhibitors, proteins are processed into shorter lengths. Protease inhibitors (saquinavir, ritonavir, indinavir, nelfinavir) prevent this step, interrupting the viral life cycle. (4) After all components are present in the cell, HIV particles assemble and bud from the cell. Adapted from Stine, 1997. hidden from the immune system. As with any infectious agent, HIV presents its proteins to the immune system, which develops antibodies against it. This antibody production, however, is hampered by the fact that HIV mutates rapidly, changing the proteins it displays to the immune system. With each new protein, the immune system must generate new antibodies to fight the infection. Thus, an HIV infection is a dramatic balance between a replicating, ever changing virus and the replenishing stores of T cells that are fighting it. Unfortunately, the immune system, without therapeutic intervention, eventually loses the battle.

Once the CD4 T cells are depleted, the immune system can no longer ward off the daily bombardment of pathogens that all human organisms experience. Common infectious agents thus overwhelm the system, and HIV patients become susceptible to a variety of "opportunistic" diseases that take advantage of the body's reduced ability to fight them off. AIDS doctors report at least twenty-six different opportunistic diseases specific to HIV infection. These include unusual fungal infections such as thrush. The chickenpox virus may come out of dormancy, manifesting itself as the painful disease known as shingles. An obscure form of pneumonia, called pneumocystis pneumonia, is also common in AIDS patients. In addition, patients can acquire cancers such as B-cell lymphoma, which is a cancer of the immune system. Doctors generally consider patients with fewer than 200 CD4 T cells per cubic milliliter of blood as having AIDS. (In contrast, a healthy person counts more than 1,000.)

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Medicine EncyclopediaGenetics in Medicine - Part 2HIV - Hiv And Aids, Hiv Life Cycle: Entering Cells, Hiv Life Cycle: Reproduction, Hiv's Immune-system Impairment Mechanism