Immunopathogenic Mechanisms in Human Immunodeficiency Virus (HIV) Infections

Infection with HIV can result in a complex array of immunopathogenic effects. HIV infection involves both a direct quantitative depletion of T4 lymphocytes as well as an indirect qualitative effect on the function of several types of immune effector cells. The combination of T4-cell destruction and functional abnormalities contributes to the broad scope of immunologic aberrations and opportunistic diseases seen in HIV-infected individuals. In addition, HIV infection of monocyte/macrophages may play an important role as a reservoir or sanctuary of infection in the host and contribute to the characteristically long incubation period between HIV infection and disease. The activation of HIV from latent or chronically infected cells in vitro by mitogens, antigens, heterologous viruses, and cytokines represents a potential mechanism whereby HIV infection in individuals progresses from an asymptomatic carrier state to clinical AIDS. The release of virus from activated cells can lead to the spread of the virus to other target cells and result in both a qualitative or quantitative defect in immunocompetent cells and subsequent immunosuppression. It is also clear that HIV infection can result in the modulation of expression of certain cellular genes, thereby potentially compounding immunoregulatory abnormalities. Further knowledge of the complex relation between HIV and its target cells will be essential to our understanding of the myriad of potential pathogenic mechanisms of HIV infection and may lead to ways of interrupting the progression of HIV-induced disease.