Review Articles On Immunogenetics

Studies of twins and adoptees have indicated that genetic factors in the host are major determinants of susceptibility to infectious diseases in humans. Twin studies have also revealed high heritabilities for many humoral and cellular immune responses to pathogenic antigens, with most genetic components mapped outside the main histocompatibility complex. Candidate gene studies have implicated several immunogenetic polymorphisms in human infectious diseases. Variation in HLA has been associated with susceptibility or resistance to malaria, tuberculosis, leprosy, AIDS and persistence of the hepatitis virus. Variation in the promoter of the tumor necrosis factor gene has also been associated with several infectious diseases. Chemokine receptor polymorphism affects both susceptibility to HIV-1 infection and the rate of progression to AIDS. The inactivation of mutations in the interferon γ receptor leads to increased sensitivity to atypical mycobacteria and to disseminated BCG infection in homozygous children. The active form of vitamin D has immunomodulatory effects and the allelic variants of the vitamin D receptor appear to be associated with differential susceptibility to several infectious diseases. NRAMP1, a macrophage gene identified by positional cloning of its murine counterpart, has been implicated in susceptibility to tuberculosis in Africans. Whole genome linkage analysis of multi-case families is now used to map and identify new loci affecting susceptibility to infectious diseases. Susceptibility to most microorganisms is likely to be determined by a large number of polymorphic genes, and their identification should provide information on the protective and pathogenic mechanisms of infectious diseases.