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HIV and the immune system: a complicated interplay

The immune system of vertebrates is traditionally divided into innate or nonspecific and specific.

The innate response includes the response of the cells of the mononuclear phagocyte system, dendritic cells, granulocytes and natural killer (NK) cells. All of them are activated on challenge by infectious organisms, without either the need for direct participation of the T-cell, or a previous sensitization. Because their response to pathogens is fast and immediate, the innate cellular response is considered to be at the forefront of the immune system and the initial step in the host response.

The cells of the innate response also interplay with the lymphocytes through two discrete processes. One is by presenting antigens to T and B lymphocytes in the form of peptide fragments through the major histocompatibility complex (MHC) system. The second process is by releasing molecules, specifically cytokines, which are able to modulate and influence the immune response (Unanue, 2000).

The adaptive immune response, in contrast to innate, requires the specific recognition of foreign antigens. These two responses are intimately connected and they are mutually influenced. In reality, the specific immune response executes several of its effector functions via the activation of elements of innate immunity.

The specific response can be divided into cell-mediated immune response that involves mainly T-cell activation and effector mechanisms, and humoral response, consisting of B-cell maturation and antibody production.

For infection with intracellular pathogens in particular, CD4 T lymphocytes dominate the scenario, and lead the response to pathogens.

CD4 T lymphocytes are sensitized and recognize peptides presented in the context of major histocompatibility class II molecules on the surface of specialized antigen-presenting-cells (APC), such as macrophages and dendritic cells. CD4+ T lymphocytes then undergo differentiation into effector cells, which are distinguished by their ability to produce the maximal level of cytokines.

HIV can be transmitted by means of sexual contact, parenteral exposure to blood products and vertical transmission during pregnancy or parturition (Curran et al., 1988). The most characteristic feature of AIDS is the depletion of the CD4+ T lymphocytes, causing severe immunosuppression, which paves the way for the presence of opportunistic infections and neoplasms (Fauci and Lane, 1991).

In clinical follow up, it has been observed that the level of CD4+ T lymphocytes progressively declines, suggesting that beyond a direct effect of circulating CD4+ T lymphocytes there is also a marked inability to effectively regenerate the CD4+ T cell pool (Fauci et al., 1991). This lack of regeneration of CD4 T lymphocytes, coupled with the haematological disorders that are frequent in HIV infection and AIDS (both in vivo and in vitro) may reflect HIV infection of bone marrow and other lymphoid progenitor cells. In fact, HIV has been shown to be able to infect human bone marrow cells in vitro and to be able to diminish the ability to proliferate and colonize (Steinberg, Crumpacker and Chatis, 1991).

The interaction of HIV and the immune system is a very complex topic because paradoxically, the cells devoted to control and destroy foreign molecules, in the case of diseases like AIDS, have been chosen by the pathogens themselves to represent the preferential site for multiplying. This relationship determines a particular scenario in which a balance between the protective mechanisms of host cells are opposed to those of viruses, allowing the establishment of a chronic infection with a progressive and fatal decline in CD4 + T lymphocytes.

The decline of CD4+ T lymphocytes weakens the immune system to the point that it is difficult to fight off certain "opportunistic" infections which are normally controlled by a healthy immune system, but may cause serious problems or may be life-threatening for people with AIDS.

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