How HIV Causes AIDS
How HIV Causes AIDS
Studies suggest that HIV also destroys precursor cells that mature to have special immune functions, as well as the parts of the bone marrow and the thymus needed for the development of such cells. These organs probably lose the ability to regenerate, further compounding the suppression of the immune system.
Although monocytes and macrophages can be infected by HIV, they appear to be relatively resistant to killing. However, these cells travel throughout the body and carry HIV to various organs, especially the lungs and brain. People infected with HIV often experience abnormalities in the central nervous system. Neurologic manifestations of HIV disease, seen in 40 to 50 percent of HIV-infected people, are the subject of many research projects. Investigators have hypothesized that an accumulation of HIV in brain and nerve cells, or the inappropriate release of cytokines or toxic byproducts by these cells, may be to blame.
During a normal immune response, many components of the immune system are mobilized to fight an invader. CD4+ T cells, for instance, may quickly proliferate and increase their cytokine secretion, thereby signalling 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 disease 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 may also result in a massive stimulation of a person's 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 may not only 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 individuals.
The persistence of HIV and HIV replication probably 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.
In this article
- Overview
- Scope of the HIV Epidemic
- HIV Is a Retrovirus
- Slow viruses
- Organization of the HIV-1 Virion
- The viral envelope
- The viral core
- Life Cylce of HIV
- Entry of HIV into cells
- Reverse transcription
- Integration
- Transcription
- Translation
- Assembly and budding
- Transmission of HIV
- Early Events in HIV Infection
- Course of HIV Infection
- HIV co-receptors and disease progression
- Viral burden predicts disease progression
- HIV Is Active in the Lymph Nodes
- Breakdown of FDC networks
- Role of CD8+ T Cells
- Rapid Replication and Mutation of HIV
- Theories of Immune System Cell Loss in HIV Infection
- Direct cell killing
- Syncytia formation
- Apoptosis
- Innocent bystanders
- Anergy
- Superantigens
- Damage to Precursor Cells
- Central Nervous System Damage
- Role of Immune Activation in HIV Disease
- NIAID Research on the Pathogenesis of AIDS
- Glossary
Damage to Precursor Cells
Studies suggest that HIV also destroys precursor cells that mature to have special immune functions, as well as the parts of the bone marrow and the thymus needed for the development of such cells. These organs probably lose the ability to regenerate, further compounding the suppression of the immune system.
Central Nervous System Damage
Although monocytes and macrophages can be infected by HIV, they appear to be relatively resistant to killing. However, these cells travel throughout the body and carry HIV to various organs, especially the lungs and brain. People infected with HIV often experience abnormalities in the central nervous system. Neurologic manifestations of HIV disease, seen in 40 to 50 percent of HIV-infected people, are the subject of many research projects. Investigators have hypothesized that an accumulation of HIV in brain and nerve cells, or the inappropriate release of cytokines or toxic byproducts by these cells, may be to blame.
Role of Immune Activation in HIV Disease
During a normal immune response, many components of the immune system are mobilized to fight an invader. CD4+ T cells, for instance, may quickly proliferate and increase their cytokine secretion, thereby signalling 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 disease 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 may also result in a massive stimulation of a person's 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 may not only 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 individuals.
The persistence of HIV and HIV replication probably 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.
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