Evasion of the immune response: survival within low responder individuals of the host population

It is proposed that, for many species of parasites, evasion of the host immune response may be achieved passively through enhanced survival within host individuals that have a genetically determined low responsiveness to infection. Evasion by this means may contribute significantly to continued transmission of infection in man and domestic animals and influence the severity of pathology. Low responsiveness plays an important role in determining over-dispersion of parasites within host populations, and the common occurrence of this form of distribution is seen as supporting evidence for the proposition, although few of the examples available provide conclusive proof. The extensive individual and strain variation in response to parasitic infection in laboratory strains of mice is taken as a homologue of the natural situation and allows analysis of the mechanisms underlying low responsiveness. Two examples are considered in detail. In Leishmania infections both non-H-2 and H-2-linked genes influence resistance, but the primary expression of genetically determined low response is at the level of the macrophage. Genetic influences upon acquired immunity regulate macrophage-T-cell interactions. In Trichinella spiralis H-2-linked and non-H-2 genes influence development of the intestinal responses necessary for expulsion of the adult worm, the former through the response of helper T-cells to worm antigen and the amplification of this response through other T-cells, the latter through an effect upon the response of myeloid stem cells to T-cell signals. Modification of genetically determined low responsiveness is discussed in terms of improving host responsiveness through vaccination or non-specific immunostimulation and altering host genotype through selective breeding or the introduction of resistance alleles into a population.