Pantaleo G; International Conference on AIDS.
Int Conf AIDS. 1996 Jul 7-12; 11: 208 (abstract no.Th.20).
Laboratory of Immunoregulation, NIAID, NIH, Bethesda, MD, USA.
Recent studies have clearly indicated that host factors play a crucial role on the course of both bacterial and virus infections. In this regard, several genes have been identified in mice that are involved in resistance to intracellular pathogens. Most of the genes identified influence the resistance to pathogens by modulating the immune response. Modulation of the immune response may occur a) during the early phase of induction of the immune response, i.e. antigen presentation and processing; b) during the phase of selection and maturation of the immune response, i.e. selection for T cell receptor (TCR) repertoire specific for certain antigen(s)/superantigen(s); and c) during the effector phase of the immune response, i.e. influence on microbicidal mechanisms and cytotoxic T lymphocytes (CTL) function. Major histocompatibility complex (MHC) class I and II, transport associated protein (TAP), LMP and Bcg/lty/Lsh genes modulate the phase of induction of the immune response; TCR and cytokine genes the phase of selection and maturation of the immune response; NOS2, nuclear resistance associated macrophage protein (Nramp) I, pfp, FasL and Fas influence the effector phase of the immune response. Furthermore, other genetic factors may confer resistance to pathogens either by creating unfavorable conditions for the growth of pathogens or by altering the expression of receptor molecules crucial for entry. Similar to these studies performed in mice, several observations have clearly indicated that host factors influence resistance to pathogens also in humans. With regard to HIV infection it has been shown that different HLA (MHC genes) profiles are associated with different courses of HIV infection and with different courses of HIV infection and with different rates of progression to AIDS. Furthermore, the degree of immune activation significantly influences the levels of virus replication. Of interest, resistance to infection may be dependent upon the levels of production of soluble factors, i.e. chemokines, with antiviral activity, and abnormal surface expression of co-receptor molecules for HIV. Finally, the qualitative nature of the immune response observed during primary infection but not the levels of viremia, is a strong predictor of the rate of progression of HIV disease. In conclusion, although the persistence of the pathogen is the primary mechanism of disease, host factors are critical determinants of the resistance to pathogens and of the subsequent clinical outcome.
Publication Types:
Keywords:
- Acquired Immunodeficiency Syndrome
- Animals
- Cytoplasm
- Disease Progression
- HIV
- HIV Antigens
- HIV Infections
- HIV Seropositivity
- HLA Antigens
- Histocompatibility Antigens Class II
- Humans
- I-E-antigen
- Infection
- Integration Host Factors
- Major Histocompatibility Complex
- Mice
- Receptors, Antigen, T-Cell
- Receptors, HIV
- T-Lymphocytes, Cytotoxic
- Viremia
- Virus Replication
- genetics
- immunology
- virology
Other ID:
UI: 102220098
From Meeting Abstracts