Gene M. Shearer

Are Some People Protected Against HIV Infection

Human populations are known to differ in their susceptibility to infectious pathogens. These differences can be associated with genetic factors, prior exposure to the infectious agent, and/or the general status of the immune system. More than 20 years ago, independent discoveries were made demonstrating that multiple sexual exposures to HIV did not necessarily result in HIV infection in all individuals, and that these non-infectious exposures could result in HIV-specific cellular but not humoral immunity. Many AIDS researchers were surprised and skeptical of these HIV epidemiologic and immunologic findings. However, during the past two decades independent evidence has been collected by several laboratories indicating that each cohort of HIV-exposed individuals contains a small percentage of individuals who do not become infected, despite repeated HIV exposure. As the result of two recent workshops, this phenomenon is being more broadly supported and investigated, and is now termed “HIV-exposed seronegatives” (HESN).

The Relationships Between Cytokines, Complement and HIV Infection

Publisher Summary The immunologic hallmark of successful infection with the Human Immunodeficiency Virus (HIV) is a progressive decline in CD4 T cell count, which ultimately results in the appearance of infections characteristic of acquired immune deficiency syndrome (AIDS). However, prior to this decline in CD4 + T cell number, impairment of T helper cell (Th) function is observed. Alterations in cytokine production could contribute to HIV disease progression by modulating antigen induced cell death (AICD), which has recently been reported to occur preferentially in Th1 cells. This chapter summarizes the evidence that cytokines influence the progression of HIV disease, as well as protection against HIV infection. Cytokines also appear to have an effect on AICD, a model for HIV immunopathogenesis, and on the production of cell generated anti-HIV factors. It remains to be determined whether cytokine-driven immune-based therapies and cytokine-directed prophylactic immunization against HIV and AIDS can be effectively achieved without creating new problems of immune dysregulation. The immunologic components considered likely to contribute to protection against HIV infection and progression to AIDS is listed in chapter. It remains to be determined whether all of these factors of potential immune protection can be optimized simultaneously.

TH1 and TH2 Type Responses in HIV Infection

The most dramatic and well known immunologic consequence of infection with the human immunodeficiency virus type-1 (HIV) is the severe depletion of CD4+ T cells in the progression toward the acquired immunodeficiency syndrome (AIDS) (reviewed by Fauci, 1988). The ultimate outcome of this loss of helper cells is susceptibility to opportunistic infections and the development of neoplastic conditions such as generalized Kaposi’s sarcoma and non-Hodgkin’s lymphoma. Most immunologic studies of HIV infection and AIDS have focused on this CD4-deficient state. However, to understand the complex series of events that ultimately results in AIDS and the extreme immune deficient state that is its hallmark, it is necessary to investigate the earlier events of immune dysregulation that result from HIV infection.