IMMUNOGENETICS IN THE ANALYSIS OF RESISTANCE TO INTRACELLULAR PATHOGENS

Recent studies have identified genes involved in resistance to intrace llular pathogens. Such genes include the murine MHC class I gene, L(d) (toxoplasmosis), HLA-BW53, HLA DRB1 1302-DQ B10s01 and TNF2 (malaria ), murine Nramp (toxoplasmosis, leishmaniasis and tuberculosis), gene( s) modulating the T-helper type 1 and type 2 dichotomy (leishmaniasis, leprosy and HIV infection) and the natural killer cell complex (cytom egalovirus infection). There also have been other advances in immunoge netics that have led to a better understanding of resistance to intrac ellular pathogens. These include effector mechanisms of immune respons e genes and factors modulating genetic susceptibility. Identification of genes that determine resistance/susceptibility (and their effector mechanisms) has impacted on vaccine development. Immunogenetics has be en important in characterizing roles of TCR genes, superantigens, and host genes that play a role in molecular mimicry in disease pathogenes is. In addition, recent work with gene knockout, recombinant inbred or congenic, mutant, consomic, and transgenic mice, positional cloning, mouse/human gene homologies to identify candidate human resistance gen es, and the rapid expansion of the gene transcription maps of the huma n genome, have been important in analysis of resistance to intracellul ar pathogens.