Immunological studies on Nippostrongylus brasiliensis infection in the rat

Neilson, John Taylor McLaren (1966) Immunological studies on Nippostrongylus brasiliensis infection in the rat. PhD thesis, University of Glasgow.

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The object of the work described in this thesis was to study certain aspects of the "self cure" of N. brasdiliensis infections la the rat, with a view to throwing some light on the mechanism of immunity to gastro-intestinal parasites generally. The starting point for the investigation was the immune expulsion of the adult parasites at the terminal phase of a primary infection this was investigated in a more quantitative fashion than formerly and its rapidity and extent clearly demonstrated. It vas shown that between days 10 and 20 following a primary larval infection almost the entire adult worm population was expelled from the host's small intestine. In order to study this reaction between host and adult parasite in an uncomplicated way, a reliable quantitative method had to be developed for the introduction of adult worms into the test animal. A surgical technique was evolved which was safe and reliable and gave "takes" which were no less uniform than those resulting from infections with larva. Using the adult transfer method, the fate of parasites transferred to rate of different immunological status was studied and the "half-lifes" of those introduced populations measured. It was found that the pattern and kinetics of the expulsion of adult worms between actively and passively immunised rats varied considerably. There was also a distinct difference in the rate of expulsion of adult worms by rate possessing differing degrees of acquired immunity, i.e. it was more rapid with hyperinfected rats than with rats which had had only one previous infection. The most important question to be answered for this system is the mechanism of the immune expulsion. Parallel work by other colleagues in the department had indicated that local anaphylactic reactions in the gut might give rise to conditions which were "unsuitable" for the worms and thus lead to their elimination. It seemed to the author that the local anaphylaxis might only be one component in the expulsion mechanism and that the associated increased capillary permeability might allow plasma and, therefore, antibody, in quantity to come in contact with the parasite, and that the main effect might be due to "antibody v. parasite". In order to try and assess the importance of any direct effect of antibody upon the adult worm in this system two parallel studies were conducted. The first was aimed at examining some of the ways in which antibody might come in contact with the worm in vivo. Experiments with red cells labelled with 51Cr showed the extent to which this might occur due to blood sucking by the parasite or haemorrhage caused by it. Infected rats suffered a loss into the gut of about 100 mul blood per 24 hours due to the presence of a population of about 1,000 adult worms. The worms, however, did not ingest any significant amount of this blood. Other studies using a macromolecule, polyvinylpyrrolidone labelled with 131I, indicated an increased gut permeability to large molecules in infected rats just before and during the time of self cure. This work showed that in an infected rat, conditions exist whereby greater than normal amounts of plasma protein and hence antibody can move from the vascular system into the gut. The second part of the "antibody v. parasites" approach depends upon demonstrating that, if antibody does come in contact with the worm in quantity, it can do some harm. Again this was investigated in two ways. Firstly by incubating adult worms in immune serum before introducing them to the host, and secondly by studying the effects of immune serum on the in vitro metabolism of the worms. Broadly speaking it appeared that adult worms, after 20 hours exposure to immune serum, consumed less oxygen and incorporated more inorganic phosphate than did worms exposed in a similar fashion to normal serum. A variety of different ways for producing immune serum was included in this study. The possible significance of cell-fixed or reagin-like antibodies in immunity to N. brasiliensis and the participation and importance of such antibodies in the passive transfer of resistance was studied. Attempts were made to demonstrate the presence of cell bound antibody in the mucose of the small intestine and other tissues of resistant rats by in vitro incubation of viable cell suspensions of these tissues with a crude aqueous adult worm extract labelled with 131I.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Parasitology, Immunology
Date of Award: 1966
Depositing User: Enlighten Team
Unique ID: glathesis:1966-72729
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jun 2019 11:06
Last Modified: 11 Jun 2019 11:06

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