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AIDS and the Immune System

General Overview of how AIDS effects ones Immune System

Contrary to popular belief AIDS is not a fatal disease all and by itself. AIDS is an acronym, which stands for (Acquired Immune Deficiency Syndrome.) The actual syndrome is caused by the onset of a virus called HIV (human immunodeficiency virus) which attacks and cripples the immune system by attacking a certain class of cells known as helper T cells. Consequently one may find themselves more susceptible to common diseases or illnesses such as colds, bacteria, viruses which they may have previously been protected. Illnesses such as these in the end may lead to more serious complications and even death. This is all attributed to the fact that your immune system has become weaker and no longer has the ability to carry out its original function of protecting the body against dangerous pathogens.

Chemical Mechanism of AIDS

Part I Human Immunodeficiency virus (HIV)

The human immunodeficiency virus, often referred to as HIV, is a retrovirus from the lentivirus family. Characteristic of retroviruses HIV is unable to replicate itself outside of a living cell because they only contain RNA (ribonucleic acid) and not DNA (deoxynucleic acid.) The variant of HIV, which is the largest cause for most infections, is that of HIV 1.

Part II Mechanism of Infection

The human immunodeficiency virus primarily infects cells with CD4 cell-surface molecules. The virus attaches to the cell membrane by fusion or by endocytosis. The virus contains a certain gene called gp120 which allows it to attach to the CD4 recptor molecule and tricks the CD4 molecule it into letting it enter the cell. It is by way of these cell-surface molecules that the virus gains entry . Many neighboring cells share similar epitopes with this particular protein. The HIV may also gain entry via Fc receptor sites or a complement receptor. Fc receptor sites may be commonly found on macrophages and in some other cells, which may lack CD4 cell-surface molecules. The primary targets of HIV infection include tissue macrophages, T lymphocytes, B-lymphocytes, hematopoietic stem cells, endothelial cells, and cells of the mononuclearphagocyte system.

The probability of infection is based on two factors:

1. Number of infective HIV virions in the body fluid which contacts the host.

2. Number of cells available at the site of contact that have appropriate CD4 receptors.

Once inside the cell the viral particle uncoats from the envelope of the virus to release its RNA. Once released the enzyme reverse transcriptase , which is the enzyme product of the pol gene allows for the reverse transcription of RNA to proviral DNA . It is this proviral DNA that is inserted into the genomic DNA of the host cell by the integrase enzyme. Once encoded the viral DNA neither be destroyed nor eliminated without killing the host cell. The host cell then replicates the HIV provirus. The newly formed virions are then released into the cellular environment by means of either budding at the cells surface or lysis.

Dynamics of HIV Infection

After the initial infection of the human immunodeficiency virus, replication may at first only occur within inflammatory cells at the site of infection or possibly within the mononuclear cells within the peripheral blood. However, the site of replication will eventually shift to that of the lymphoid tissues of the body.
Macrophages and Langerhans cells in the epithelia are important as vectors and reservoirs for the virions of HIV. For instance Langerhans cells (a subset of blood dendritic cells) act as antigen presenting cells for CD4 lymphocytes. One interesting note is that although Langerhan and macrophage cells are infected they are not destroyed. Replication is stimulated by various forms of cytokines such as intrleukin and tumor necrosis factor, which are what activate CD4 lymphocytes and make them more susceptible to HIV infection. Once replication is complete in a particular host cell, it is followed by the host cell erupting and the new virions pouring out into the peripheral blood. In periods of latency, the presence of virions in peripheral blood is low but it actively continues in lymphoid tissues.

Onset of AIDS

After the initial onset of HIV a mild disease may occur or it may go along unnoticed, followed by a long clinical "latent" period lasting years. Various symptoms include fever, lymphadenopathy, pharyngitis, diffuse erythematous rash, trtharalgia/malgia, diarrhea, and headaches. After about three weeks to three months a decline in HIV viremia occurs. The number of CD4 lymphocytes rebound in number but not to pre-infection levels. This immune response is usually accompanied by seroconversion however it is a extremely rare event.
AIDS is characterized by a very long latent period before any signs of its presence may be detected. During this period there is no viral replication able to be detected in the peripheral blood mononuclear cells and no cultivable virus in peripheral blood. The lymphocyte count remains to be moderately low. However viral replication does continue to occur in lymphoid tissues. Therefore, although the immune system has recovered enough to prevent replication in certain areas it is unable to rid the body of the virus completely. As viral replication continues and the destruction of CD4 lymphocytes continues the immune system gradually is destroyed. People who are infected with the HIV are often have an unusual incidence of cancer. Such cancers as Pneumocystis carinii pneumonia and Kaposi's sarcoma are two common ones that may be found in AIDS patients. Once the production of CD4 lymphocytes can no longer match the number of lymphocytes being destroyed then the failure of the immune system leads to appearance of clinical AIDS.

Immunoresponse to Aids

The method by which our body responds to the presence of HIV and eventually to AIDS is no different than the way that it would repond to any other disease or virus that our body may encounter. Through a complex system of humoral and cell mediated responses our body goes about the task of destroying the virus. Upon initial infection T lymphocytes or T4 helper cells recognize the foreign molecule and stimulate all of the other cells and molecules which are involved in immune protection. Those of which include B lympohocytes , the cells which produce antibodies to fight infection; cytotoxic T lymphocytes, which destroy cells infected with virus; and macrophages and other effector cells, which attack invading pathogens. All of these molecules work together to try to rid the body of the virus. However, since the primary target of HIV is the immune system no matter how hard it works at destroying the virus it is at the same time being directly effected. As this war wages on the body begins to develop a wasting type of syndrome, usually a direct result of the relentless attack of pathogens which ones body comes into contact day after day. However, now in its weakened state the immune system is no longer capable and the body beging to show signs of fatigue.

Questions

1) What is it specifically about T lymphocytes and cells of the immune system that make them targets of HIV besides the fact that they have CD4 receptor sites that make entry for them into the host cell easier?

2) Can HIV attack other cells which do not have CD4 or Fc receptor sites?

3) Since HIV does have such and an affinity for cells that have these receptors is it possible that there is a closer relation between HIV and immune system molecules than what is known presently?

Project Related Links

Main Page -- AIDS Overview
The Physiological Effects of AIDS
Current and Future Treatments
Q The Life Cycle of AIDS

Email: rld9881@garnet.fsu.edu