TH2-MEDIATED HOST PROTECTIVE IMMUNITY TO INTESTINAL NEMATODE INFECTIONS

Despite many years of study, relatively little is known about the effe ctor mechanims that operate against intestine-dwelling nematodes. Most of the current understanding comes from studies of laboratory model s ystems in rodents. It is clear that when an intestinal helminth infect ion takes place the immune system generates a strong Th2-mediated resp onse, which regulates a variety of responses characteristic of helmint h infections such as eosinophilia, intestinal mastocytosis and elevate d IgE production. The ability to modulate the host's immune response i n vivo with cytokine-specific monoclonal antibodies and recombinant cy tokines, together with the use of animals with disruption of key genes involved in the immune response, have provided powerful tools with wh ich to dissect the potential effector mechanisms operating. In the abs ence of a T-cell compartment the host is unable to expel the parasite. If a Th1-dominated response is generated, protective immunity is almo st universally compromised. Thus, it would appear that some aspect of a Th2-mediated response controls effector mechanisms. Although it is c lear that for some infections the mast cell appears to be involved in protection, probably through the generation of a non-specific inflamma tory response, how these cells become activated remains unclear. Data from infections in transgenic animals suggest that activation is not t hrough the high-affinity receptor for IgE. Such studies also call into doubt the importance of conventional interactions between effector le ucocytes and antibody. There is little evidence to support a protectiv e role for eosinophilia in any system. New data also imply that, altho ugh interleukin 4 (IL-4) is generally important (and can exert effects independent of an adaptive immune response), it is not always suffici ent to mediate protection; other Th2 cytokines (e.g. IL-13) may warran t closer investigation. It is apparent that a number of potential Th2- controlled effector mechanisms (some of which may be particularly impo rtant at mucosal surfaces) remain to be explored. Overall, it is likel y that worm expulsion is the result of a combination of multiple mecha nisms, some of which are more critical to some species of parasite tha n to others.