The expulsion of worms from the gut is still not well understood in immunological terms and for some parasite species may be more difficult to manipulate with a vaccine. Although eosinophils are implicated as effectors in some murine models, there are clearly very capable alternative mechanisms available, and closer scrutiny of these is likely to teach us lessons more widely applicable in immunology. In a number of experimental models, we have yet to accurately track the migration of larvae and until this can be performed we will not be able to analyse the nature of immune responses the parasites encounter. An example of this is seen in N. brasiliensis see more infections, where resistance is most

potent in the pre-lung phase of infection and yet, larvae Tamoxifen manufacturer are virtually untraceable from the time they leave the skin 2 h pi., until the majority arrive in the lungs 24–48 h later. In this infection, larvae are being trapped both in and outside of subcutaneous tissues prior to the lung phase, but so far only the skin has been quantitatively surveyed with any degree accuracy. Eosinophils are quite numerous in the lamina propria

of the small intestine and increase in frequency after parasites localize to this compartment. Whilst eosinophils may make a contribution to expulsion of some species of worms, they are not essential and may offer little protection against other species. The role that eosinophils play in maintaining the integrity of the gut may turn out to be more important than

contributions made to worm expulsion. The complement system is another innate effector mechanism of importance in early resistance to nematode infection. Complement proteins can be involved in recruitment of leucocytes, attachment of effectors to larvae and at least to some degree, in retarding the migration of parasites. However, many parasitic helminths can upregulate mechanisms that interfere with the complement pathway. In addition, the absence of complement is compensated for in primary and secondary infections with pathogens that are at least partially sensitive to it. S. ratti and N. brasiliensis infections in mice may continue to prove useful in better understanding innate mechanisms Axenfeld syndrome that regulate the recruitment and behaviour of leucocytes soon after entry of the parasite and again, this is likely to have broader implications in immunology. Evidence of new or newly reconsidered innate effector mechanisms continue to emerge from murine models of nematode infections (23,24,71). We have yet to determine whether IL-4 and IL-13 are important in the pre-lung phase of infections with skin-invasive helminths other than N. brasiliensis. Nor do we understand how these cytokines function in N. brasiliensis infections, but they might have a combination of effects on leucocyte recruitment and function.