Role of Immune Activation in HIV Disease

Role of Immune Activation in HIV Disease

During a normal immune response, many parts of the immune system are mobilized to fight an invader. CD4+ T cells, for instance, may quickly multiply and increase their cytokine secretion, thereby signaling other cells to perform their special functions. Scavenger cells called macrophages may double in size and develop numerous organelles, including lysosomes that contain digestive enzymes used to process ingested pathogens. Once the immune system clears the foreign antigen, it returns to a relative state of quiescence.

Paradoxically, although it ultimately causes immune deficiency, HIV infecton for most of its course is characterized by immune system hyperactivation, which has negative consequences. As noted above, HIV replication and spread are much more efficient in activated CD4+ cells. Chronic immune system activation during HIV disease also may result in a massive stimulation of B cells, impairing the ability of these cells to make antibodies against other pathogens.

Chronic immune activation also can result in apoptosis, and an increased production of cytokines that not only may increase HIV replication but also have other deleterious effects. Increased levels of TNF-alpha, for example, may be at least partly responsible for the severe weight loss or wasting syndrome seen in many HIV-infected people.

The persistence of HIV and HIV replication plays an important role in the chronic state of immune activation seen in HIV-infected people. In addition, researchers have shown that infections with other organisms activate immune system cells and increase production of the virus in HIV-infected people. Chronic immune activation due to persistent infections, or the cumulative effects of multiple episodes of immune activation and bursts of virus production, likely contribute to the progression of HIV disease.