Immunological unresponsiveness to helminth parasites: III. Challenge of rats previously infected at an early age with Nippostrongylus brasiliensis

Abstract

We have previously shown that when rats are infected when young with 500 N. brasiliensis larvae worm expulsion does not occur as in adult rats; instead rats so infected remain unresponsive to their intestinal worm burdens well into adult life. It was subsequently shown that this state is to a certain extent dose dependent in that infections of a greater size do result in a measure of worm expulsion but that this ceases when a burden of approximately 200 is reached; this also persists into the adult life of the rats. In this paper the response of rats infected when young to a subsequent challenge infection has been studied. Three factors have been found to be of importance in determining the type of response elicited: 1. (1) The size of the first infection given when young. Young rats initially infected with a small dose of larvae (500) respond to a challenge of 1000 larvae in adult life by a pattern of worm expulsion similar to rats experiencing a primary infection of N. brasiliensis, whereas rats initially infected with a large dose (3200) show a secondary type of response. 2. (2) The size of the challenge infection. Whereas removal of the original worm population by thiabendazole and its replacement with a similar small number of new worms (either by infection with larvae or by adult worm transplant) results in a primary type of worm expulsion, a large challenge infection (3000) larvae is capable of eliciting a secondary type of expulsion response despite an initial small infection. 3. (3) The age of the rats at the challenge infection. The superimposition of a challenge infection on a primary infection where both occur during the original unresponsive period (i.e. up to 7 weeks) results merely in a continuation of the unresponsive state into adult life although the worm burden is again adjusted to bring it down to a level of around 200 worms. It was concluded on several grounds that immune tolerance in the classical sense is not responsible for the persistence into adult life of the relatively large worm burdens acquired from infection during the immunologically unresponsive period. Alternative explanations and the significance of the phenomenon are discussed.