Autoantibodies, FunctionaL Loss of CD8 CTL and Cytokines, Growth Factors and Cancers

Autoantibodies,

This then is the intricate attack of the virus of AIDS which, from the beginning, has been posing a challenge to scientists. At first, a simplistic view was taken to explain the virus armament. It was thought that immunity is affected because of the direct effect of HIV on the crucial CD4 cell. This was also the explanation given for the marked depletion of this cell which coincided with the progression of HIV to AIDS.

That things were not as simple as believed at first, became obvious when more studies were undertaken. It appeared that there were qualitative changes during the early phase which went unnoticed. Later studies led some scientists to hypothesise that AIDS pathogenesis was not due to a lack of immune response but probably resulted from too much of a (certain kind of) response. It was shown that B cells of the infected individuals produced antibodies not only to the 'non-self' viral proteins but, in the process to overcome these produced antibodies also to certain 'self', i.e. autoantibodies against the body's own cellular antigens. Antibodies to lymphocytes and even against histocompatibility antigens have been found in AIDS patients. This has been attributed to the similarity in a fragment of HIV envelope antigens (gp 120 and gp 41) with a part of the human HLA. It has been realised that much greater complexity is involved in the immune response to HIV. Not only the disturbance in CD4 functions, but in the functions of antigen presenting cells (macrophages and dendritic cells) were noted. Although the virus does not seem to damage these cells directly, the functional ability of these cells appears to be impaired.

FunctionaL Loss of CD8 Cytotoxic Lymphocytes (CTL) :

Another feature that came to light concerned the CD8 cells called cytotoxic/suppressor cells. Using specialised markers, a defect has been found specifically in the killing function. Although there is not much of a quantitative change, i.e. the absolute number of CD8 cells may not be affected, a qualitative change is noted. These CD8 cells are incapable of CTL function of killing the virus-infected cells; instead, the majority of these cells act as 'suppresor' cells, further diminishing the immune system. Marked reduction is also noted in the number of NK cells which perform a very important function of killing cells which are cancerous or are infected with HIV.

Cytokines, Growth Factors and Cancers :

Investigations on the soluble chemical messengers (cytokines) also revealed changs, which could be pathogenic, i.e. disease producing. It has been recently realised that HIV-associated cancers like Kaposi's sarcoma was probably due to chronic activation of the system, and the release of a cytokine that could act as a growth factor. Thus, the cells would keep on growing in an unregulated manner leading to cancers.
Similarly, cancers of B cells, called B cell lymphomas, have also been attributed to a cytokine that acts as a growth factor. NK cells, which in normal circumstances kill cancer cells, are themselves depleted and functionally almost defunct. This in brief and simple terms is how HIV may cause AIDS; or, in other words, HIV pathogenesis.