Clin. exp. Immunol. (1985) 60, 87-94.

Thymus dependency of induced immune responses against

Hymenolepis nana (cestode) using congenitally
athymic nude mice
A. ITO Department of Parasitology, Gifu University School of Medicine, Gifu, Japan

(Acceptedfor publication 30 October 1984)

SUMMARY
Anti-parasite antibody responses were compared among several strains of mice experi-
mentally infected with the dwarf tapeworm, Hymenolepis nana. The antibody titres were
highly variable among the mouse strains in addition to variation in worm fecundity and
longevity. The influence of the thymus on both infection and anti-parasite antibody
production (especially of IgE isotype) was studied by the use of congenitally athymic
(nu/nu) nude and their phenotypically normal (nu/ +) CD- I (ICR) mice infected with H.
nana. All nude (nu/nu) mice harboured fully mature 70 day old adult tapeworms of the
first generation derived from eggs initially given on day 0. In addition, they contained (a)
younger second generation adults derived from autoinfection and present in the intestinal
lumen, (b) a number of abnormally large (about 1-2 mm in diameter) balloon like, fluid
filled cysticercoids in not only the intestinal tissue but also parenteral tissues such as the
mesenteric lymph nodes, liver and lung, and (c) normal cysticercoids derived from
challenging eggs in the intestinal tissue. Infected nude mice produced no antibodies
detectable by PCA (IgE) and double diffusion (IgG) tests. In contrast, normal (nu/+)
mice and nude mice reconstituted with thymocytes expelled almost all luminal adults of
the primary infection by day 70 and produced antibodies to extracts of adult H. nana.
Neither autoinfection nor reinfection following egg challenge occurred in any of these
normal (nu/ +) and reconstituted nude mice. Therefore, acquired immune responsec
against H. nana (as assessed by resistance not only to the tissue phase measured by the
failure of tissue cysticercoid recovery from egg challenge, but also to the lumen phase
assessed by the failure of autoinfection adult recovery and 'worm expulsion' of the initially
established adults) are all thymus-dependent in mice. The antibody responses examined
are also thymus-dependent.

Keywords anti-parasite antibodies protective immunity nude mice Hymenolepis

nana

INTRODUCTION
The fact that mice initially given eggs of the dwarf tapeworm, Hymenolepis nana acquire complete
protective immunity to egg challenge has been well established (Hunninen, 1935). Mice infected
with H. nana produce protective antibody to egg challenge (Hearin, 1941; Ito, 1977; Patton, 1977;
Palmas, Wakelin & Gabriele, 1984). Isaak, Jacobson & Reed (1977) found that not only the
well known acquired immunity to egg challenge (Okamoto, 1968; Okamoto & Koizumi, 1972) but
also the longevity of the initially established adult tapeworms themselves, are thymus-dependent.
Correspondence: Dr Akira Ito, Department of Parasitology, Gifu University School of Medicine,
Tsukasa-Machi 40, Gifu 500, Japan.
87
88 A. Ito
These data strongly suggested that both the tissue and lumen phases of H. nana are immunogenic.
Ito (1980, 1982) revealed that mice initially given eggs acquire two different immune responses
against reinfection. One is an 'early' response directed against egg challenge or against the tissue
phase and assessed by the failure of tissue cysticercoid recovery 4 days after egg challenge. The other
is a 'late' response against cysticercoid challenge or against the lumen phase, assessed by the failure
of adult recovery 7 days after cysticercoid challenge. In these immunized mice, the initially
established adults do survive, at least for a short while. Ito (1980, 1984a, 1984b) has stressed that the
developmental stages of H. nana (oncosphere [target of the early response], luminal cysticercoid or
excysted juvenile [target of the late response] and luminal adult [target of the worm expulsion
response]) differ, at least phenotypically, in their immunogenicity from one another. These recent
advances on the immunology of adult cestode infections has been reviewed critically (Mitchell,
1979; Williams, 1979, 1982; Rickard & Williams, 1982; Rickard, 1983; Ito & Smyth, 1985).
There is, however, no report on the thymus dependency of antibody responses of mice specific to
this parasite infection, since we have had little information on how to detect specific antibody
responses to H. nana (Mitchell, 1982; Ito & Smyth, 1985). This applies to the natural mouse host
experimentally infected with H. nana eggs rather than the unnatural rabbit host artificially injected
with H. nana homogenates (Coleman, Carty & Graziadei, 1968). However, Ito (1984a) revealed that
mice infected with H. nana produce antibodies reacting with a crude extract of mature tapeworms
that are readily detectable with the rat skin PCA (IgE) and by double diffusion and immunoelectro-
phoresis which results in single precipitin band formation (IgG) (reviewed by Ito & Smyth, 1985).
In the present work, we have determined whether these antibody responses are thymus-depen-
dent, and whether acquisition of reinfection immunity to both the tissue and lumen phases of H.
nana is thymus-dependent.

MATERIALS AND METHODS

Previously uninfected, 5 week old male mice of nine strains were used for Expt 1. All the strains
other than the dd strain (bred in the present laboratory, Ito, 1981; Kano & Ito, 1983) were
purchased as specific pathogen free mice: CD-i (ICR) were purchased from Charles River Japan,
Kawasaki; C3H/He, C57BL/6 and DBA/1 from CLEA JAPAN, Tokyo, and BALB/c, DBA/2,
ddY and ICR from SCL, Shizuoka. In Expts 2 & 3, congenitally athymic nude (nu/nu) and their
phenotypically normal (nu/+) littermates of CD-1(ICR) mice, purchased from Charles River
Japan were used. All the mice were housed in 24 + 2C, 50 + 10% humidity, 12 h light and dark
conditions, with food (CA- 1, CLEA JAPAN) and water ad libitum. No antibiotics were added into
the drinking water, but the nude mice appeared to be healthy until the end of Expts 2 & 3. In Expt 3,
thymocyte donors were bred by mating nu/+ males and females. Thymocytes (5 x 108) obtained
from 7-10 day old phenotypically normal donors were injected i.p. into 3 week old nude mice each.
All the mice were used for Expts 2 & 3 at 6 week old.
Methods for detecting the parasites, adult tapeworms in the intestinal lumen and cysticercoids in
the intestinal tissue (Ito, 1982) and those for detecting antibodies (IgE and IgG (Ito, 1984a) have
been described previously.

EXPERIMENTAL DESIGNS AND RESULTS

Expt 1.
All the strains of mice summarized in Table 1 were each given 100 shell free eggs orally (day 0) and
killed 70 days later. During the course of the infection, partial bleedings from the tail vein into
heparinized haematocrit capillary tubes were carried out every 5 days from day 0 to day 20 and
thereafter every 10 days. Antibody responses were monitored using pooled plasma by the rat skin
PCA and double diffusion (DD) tests (Ito, 1984a): DD reactions became positive by day 40 in dd,
ddY and ICR mice, by day 60 in CD-I(ICR), C57BL/6 and C3H/He, but were negative throughout
in BALB/c, DBA/I and DBA/2 mice. PCA reactions became positive by day 30 in dd, ddY and
 Immunity against Hymenolepis nana in nude mice 89
Table 1. Strain variations in worm survival and antibody responses in mice infected with Hymenolepis nana

Maximum titre of
Number of mice 70 day serum
Mouse harbouring Average number of
strain 70 day old worms 70 day old worms IgG IgE
dd 25/25 19 8 1:16 1:5,120
ICR 6/10 24 1:16 1:640
ddY 11/20 12 1:8 1:640
CD-1 (ICR) 3/9 0-9 1:4 1:640
C57BL/6 1/6 02 1:4 1:320
C3H/He 1/6 03 1:1 1:160
BALB/c 2/10 0-4 undetected 1: 640
DBA/l 3/6 07 undetected 1:20
DBA/2 2/6 07 undetected 1:160

All mice were each given 100 shell free eggs (day 0) and killed 70 days later.
IgE and IgG isotypes detectable with crude extract of mature worms were
titrated by PCA test of rat skin and double diffusion test, respectively (Ito,
1984a).

ICR, by day 40 in BALB/c, C3H/He and C57BL/6, and by day 60 in CD-1 (ICR), DBA/1 and
DBA/2. Before autopsy on day 70, partial bleeding was done and fresh plasma samples of all mice
were each used for microtitration of DD reaction again. After the last partial bleeding, sera were
also obtained by cardiac puncture and used for titration of IgE antibody by the PCA test. The
results on day 70 sera are summarized in Table 1 with results of 70 day old adult recovery rates in all
strains of mice. As clearly shown in Table 1, all dd mice were exceptional in that they harboured
about 20 mature tapeworms on average (70-120 mm long) and showed exceptionally high responses
in both DD and PCA tests, whereas all other strains of mice expelled most tapeworms by day 70 and
showed lower responses.
Expt 2
Based on the results of Expt 1 (Table 1), congenitally athymic nude (nu/nu) and phenotypically
normal (nu/ +) mice of CD- I (ICR) were selected to determine whether these antibody responses
are thymus-dependent or not. All experimental groups of mice, either nu/nu or nu/ + initially given
100 shell free eggs on day 0, were challenged with 2,000 shell free eggs on day 66, killed on day 70 and
parasitological and serological examinations made. Experimental designs and results are summar-
ized in Tables 2 & 3. All nu/nu mice harboured small number of fully mature 70 day old adults,
60-100 mm long, and simultaneously, a number of younger (autoinfection) mature worms, 10-30
mm long, in the lumen. Furthermore, they were all highly susceptible to challenge eggs and
harboured cysticercoids in the intestinal tissue, whereas nu/+ mice rejected almost all luminal
adults by day 70 and neither autoinfection adults nor tissue cysticercoids derived from challenge
eggs were found. The number of tissue cysticercoids recovered from challenged nu/nu mice was five
times more than that from control groups either nu/nu or nu/+. Moreover, the majority of the
cysticercoids found in the experimental (reinfection) group of nu/nu mice were abnormally large
(about 1-2 mm in diameter), balloon like, fluid filled structures as previously reported by Lucas et
al. (1979, 1980) and Ito & Kamiyama (1984), and not derived from the eggs used for challenge on
day 66. Furthermore, the balloon like, abnormal cysticercoids were found in other parenteral
tissues especially in the mesenteric lymph nodes, liver and lung.
Antibody responses of these mice to H. nana extracted antigens are summarized in Table 3.
Almost all (five of six) of normal (nu/+) mice dosed with eggs produced (PCA positive) IgE
antibody, but only two of them showed low DD (IgG) responses. None of the nude (nu/nu) mice
given immunizing egg doses showed either PCA or DD responses.
90 A. Ito

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 Immunity against Hymenolepis nana in nude mice 9I
Table 3. Lack of Hymenolepis nana specific antibody responses in CD-I (ICR) congenitally athymic nude mice
70 days after immunizing egg inoculation

Egg doses for H. nana specific antibodies*

Genotype of
CD-1 (ICR) Immunizing Challenging No. of mice IgG titre No. of mice IgE titre
mice (day 0) (day 66) IgG positive (range) IgE positive (range)
Expt 2
nu/nu 100 2,000 0/6 undetected 0/6 undetected
nu/+ 100 2,000 2/6 1:1,1:2 5/6 1:40-640
nu/nu 0 2,000 0/4 undetected 0/4 undetected
nu/ + 0 2,000 0/5 undetected 0/5 undetected
Expt 3
nu/nu 100 2,000 0/5 undetected 0/5 undetected
TC-nu/nu 100 2,000 5/10 1:1-2 7/10 1:40-320
nu/+ 100 2,000 3/5 1:1-2 4/5 1:80-320

*
IgE and IgG isotypes were titrated by PCA test of rat skin and DD test, respectively with a
crude extract of mature worms (Ito, 1984a).

Expt 3
In order to ensure that these differences in antibody responses and the mode of H. nana infections
observed in Expt 2 are attributable exclusively to the thymus defect, the same experiment was
carried out by adding thymocyte reconstituted nude (TC-nu/nu) mice. The results are summarized
in Tables 2 & 3. TC-nu/nu as well as nu/+ mice were highly resistant to autoinfection and egg
challenge, and expelled almost all luminal adults of the primary infection by day 70. There were no
abnormal cysticercoid lesions except in one mouse which harboured both 16, 70 day old adults of
the first generation and 1,944 younger adults of the autoinfection second generation. Most of
TC-nu/nu mice produced IgE and IgG antibodies.

DISCUSSION
The present results clearly demonstrate that resistance to Hymenolepis nana infections, as well as
antibody responses, are all thymus-dependent. Responses occurred in immunologically competent
mice (either nu/ + or nu/nu reconstituted with thymocytes) infected with eggs of H. nana but did not
occur in congenitally athymic nude mice. In this system, resistance expressed against the tissue
phase is assessed by the failure of tissue cysticercoid recovery from egg challenge; resistance against
the lumen phase is assessed by the failure of autoinfection adult recovery and worm expulsion of the
initially established adult worms.
Experimental analyses of protective immunity to H. nana reinfections with eggs were carried out
by Okamoto using mice immunosuppressed with neonatal thymectomy (Okamoto, 1968), cortisone
acetate (Okamoto, 1969) and anti-thymocyte serum (Okamoto & Koizumi, 1972). Recently, Isaak
et al. (1977) using congenitally athymic nude BALB/c mice, observed the kinetics of H. nana
infection in normal and thymus deficient nude mice and found that in the nude mice, reinfection
either through autoinfection or coprophagy occurred in both intestinal tissue and lumen. Tissue
cysticercoids were found at any times of autopsy after patency and luminal adults increased greatly
in number. However, when the number of luminal adults increased up to about 1,500, a plateau
phase was established and slight decline in adult numbers followed. On the contrary, in normal mice
infected with H. nana, reinfection did not occur. Secondary adult recovery seldom occurred and
almost all luminal adults, even when secondary ones were established, were eliminated from the
host by day 35. From these results, they concluded that both tissue and luminal stages of H. nana are
immunogenic and the protective immunity is thymus-dependent. They did not, however,
92 A. Ito
distinguish the primary small population from secondary large ones. There was a possibility that
expulsion of the older adults might occur but that younger adults from autoinfection and/or
coprophagy continuously grow up to be rejected. Alternatively, the older adults that established at
the early time, and below the threshold of 'crowding' (Roberts, 1980), influenced the younger adults
and, being beyond the threshold, the latter adults are rejected. Thus, a plateau phase exists for
establishing luminal adults, about 1,500 in the BALB/c nude mice used by Isaak et al. (1977).
Based on our previous results distinguishing luminal adults of different ages (Ito, 1978), we have
differentiated in the present work between the primary, egg derived, fully mature, large adults and
the secondary, autoinfection, younger adults. There was no difference in luminal adult recovery
from the same batch of eggs between day 14 (about 15% of eggs administered, Ito & Kamiyama,
1984) and day 70 (16%, Expt 1). Therefore, we conclude that no worm expulsion (against adult
tapeworms) occurs in thymus deficient nude mice, at least by day 70, and support the same idea
proposed by Isaak et al. (1977).
Judging from such evidence described above (Table 2, Isaak et al., 1977) and our previous work
which strongly suggested that both the tissue and lumen phases of H. nana are highly immunogenic
(though immunogenicity clearly differs between the phases, Ito, 1980, 1982, 1984b), it is valid to
conclude that mice initially given eggs of H. nana become immune to egg challenge at first and then
to cysticercoid challenge. However, in such immunized mice, initially established immunogenic H.
nana (which have developed into adults) do survive until the worm expulsion response is expressed.
As clearly shown in the present results, these immune responses are all thymus-dependent (Isaak et
al., 1977; Ito & Kamiyama, 1984).
In the nude mice, a small proportion of the cysticercoids established in the intestinal tissue
remains there and becomes large (about 1 mm in diameter) and abnormal by day 14, although the
majority of them simultaneously escape from the tissue to the lumen and develop into mature
tapeworms by day 14 (Ito & Kamiyama, 1984). In the present work (Table 3), a great number of
such abnormal cysticercoids was formed in the intestinal wall and much fewer numbers in
parenteral tissues such as the mesenteric lymph nodes, liver and lung by day 70. Almost all of these
abnormal cysticercoids were derived from eggs released from the initially established mature
tapeworms. This abnormal development of cysticercoids was originally observed by Lucas et al.
(1979, 1980) using mice immunosuppressed by pre-adult thymectomy and antithymocyte serum.
In the immunologically competent mice (either nu/ + or reconstituted nu/nu) given eggs of H.
nana, there are usually no or few chances for oncospheral translocation from the intestinal tissue to
parenteral tissue such as liver. Even when a large number of eggs (such as 1 x 104 or more) was given,
fewer than 0- 1% of the eggs administered develop into cysticercoids in the liver (Astafiev, 1966;
Inoue, Furukawa & Miyazato, 1979). They were detectable with the naked eye as white spots on the
liver, but never detected as such large (about 1-2 mm in diameter) abnormal, fluid-filled, cysticercus
like cysticercoids unique in immunologically deficient mice (Lucas et al., 1979,1980) and in the nude
mice reported by Ito & Kamiyama (1984) and in the present paper. The mechanism of the
development of such abnormal cysticercoids is still unknown.
Antibodies against soluble extracted antigens of H. nana are detectable in infected mouse sera
using complement fixation test (Larsh, 1943; Coleman et al., 1968), indirect haemagglutination test
(Coleman & DeSa, 1964; Coleman et al., 1968) and gel diffusion tests such as DD and
immunoelectrophoresis (IEP) and heterologous passive cutaneous anaphylaxis (PCA) tests (Ito,
1984a). Antibody responses detected by DD (IgG) and PCA (IgE) in the present work were highly
variable among the mouse strains examined (Table 1). We could no detect IgG isotype (Ito, 1984a)
in immune sera of BALB/c, DBA/1 and DBA/2 mice by the relatively insensitive technique of DD,
but detected IgE isotype in all the strains of mice examined.
Ito (1984a) reported that there appeared to be a negative correlation between the timing of
worm loss and increase in antibody levels, although the increase in antibody levels was somewhat
preceded by a reduction in luminal adult load. The tendency appeared to be sound in all the strains
from which almost all luminal adults were rejected by day 70. However, all the dd mice harboured
fully mature large 70 day old adults. The fecundity of 70 day old adults recovered from dd mice
appeared somewhat better than that from the nude CD- I (ICR) mice, although not quantitatively
measured in this work (Ito & Kamiyama, 1984; Ito et al., unpublished observations). Thus, the dd
 Immunity against Hymenolepis nana in nude mice 93
mouse seems to be highly prone to H. nana, since mature adults survive for an exceptionally long
period; in other strains ofmice, adults are expelled within I or 2 months (Table 1; Kano & Ito, 1983).
Nevertheless, antibody (IgE and IgG) responses of dd mice are highest among all the strains of mice
examined (Table 1). At present, we have no critical information to explain this or which bears on the
function of such antibody responses. However, it is evident that these antibody responses are
thymus-dependent, since they were not detected in the nude mice but detected in nu/ + and
reconstituted nude mice (Table 3). Therefore, it is concluded that anti-parasite immune responses
during H. nana infections in mice, assessed in the present work, are all thymus-dependent.
In cyclophyllidean adult cestode infections of the definitive host, IgE responses specific to the
infected cestodes have been reported in the mouse/H. microstoma (Moss, 1971, 1972), the rat/H.
diminuta (Harris & Turton, 1973) and the dog/Echinococcus granulosus (Williams & Perez-Esandi,
1971). As demonstrated in this paper and our previous paper (Ito, 1984a; reviewed by Ito & Smyth,
1985), IgE responses are readily detected in mice infected with H. nana. Thus, H. nana may be
utilized as a useful model system for analysing the regulation of IgE production. Furthermore, it
would be interesting to know whether patients suffered from H. nana produce specific IgE or not.
This work was supported in part by Scientific Research Grant (56770230, 1981) from the Ministry of Education
of Japan. The author would like to thank Dr G. F. Mitchell, Head, Immunoparasitology Unit, The Walter and
Eliza Hall Institute of Medical Research, Melbourne, Australia, for his critical comments on this paper.

REFERENCES
ASTAFIEV, B.A. (1966) New data on the migration of
eggs and larvae of Hymenolepis nana in white mice.
Med. Parazitol. 35, 149.
COLEMAN, R.M. & DESA, L.M. (1964) Immunological
response to implanted adult dwarf tapeworms.
Nature, 204, 397.
COLEMAN, R.M., CARTY, F.X. & GRAZIADEI, W.D.
(1968) Immunogenicity and phylogenetic relation-
ship of tapeworm antigens produced by Hymeno-
lepis nana and Hymenolepis diminuta. Immunology,
115, 297.
HARRIS, W.G. & TURTON, J.A. (1973) Antibody
response to tapeworm (Hymenolepis diminuta) in
rat. Nature, 246, 521.
HEARIN, J.T. (1941) Studies on the acquired immunity
to the dwarf tapeworm Hymenolepis nana var.
fraterna in the mouse host. Am. J. Hyg. 33, 71.
HUNNINEN, A.V. (1935) Studies on the life history and
host-parasite relations of Hymenolepisfraterna (H.
nana var.fraterna Stiles) in white mice. Am. J. Hyg.
22, 414.
INOUE, T., FURUKAWA, T. & MIYAZATO, T. (1979)
Growth of Hymenolepis nana cysticercoids in the
mesenteric lymph nodes and livers of mice. Jpn. J.
Parasitol. 28, 309.
ISAAK, D.D., JACOBSON, R.H. & REED, N.D. (1977)
The course of Hymenolepis nana in thymus-defi-
cient mice. Int. Arch. Allergy Appl. Immunol. 55,
504.
ITO, A. (1977) The mode of passive protection against
Hymenolepis nana induced by serum transfer. Int. J.
Parasitol. 7, 67.
ITO, A. (1978) Hymenolepis nana: Protective immunity
against mouse-derived cysticercoids induced by
initial inoculation with eggs. Exp. Parasitol. 46, 12.
ITO, A. (1980) Hymenolepis nana: Survival in the
immunized mouse. Exp. Parasitol. 49, 248.
ITO, A. (1981) Comparison of the kinetics of infection
with Hymenolepis nana between BALB/c and dd
strains of mice. Jpn. J. Parasitol. 30, 439.
ITO, A. (1982) Hymenolepis nana: Immunogenicity of
a lumen phase of the direct cycle and failure of
autoinfection in BALB/c mice. Exp. Parasitol. 54,
113.
ITO, A. (1984a) IgG and IgE antibodies to Hymeno-
lepis nana detected in infected mouse sera by gel
diffusion and passive cutaneous anaphylaxis tests.
J. Parasitol. 70, 170.
ITO, A. (1984b) Stage specific immunogens of
Hymenolepis nana in mice. J. Helminthol. 58, 235.
ITO, A. & KAMIYAMA, T. (1984) Hymenolepis nana:
Comparison of worm recovery between congeni-
tally athymic nude and phenotypically normal rats
and mice. Exp. Parasitol. 58, 132.
ITO, A. & SMYTH, J.D. (1985) Adult cestodes. Immu-
nology of the lumen-dwelling cestode infections. In
Immunology, Immunopathology and Immunopro-
phylaxis of Parasitic Infections (ed. by E.J.L.
Soulsby) Vol. 2, CRC Press, Boca Raton. (In press.)
KANO, S. & ITO, A. (1983) Influence of the host
immune responses on the modes of primary infec-
tion and autoinfection with Hymenolepis nana in
mice. Jpn. J. Parasitol. 32, 183.
LARSH, J.E. (1943) Serological studies on the mouse
strain of the dwarf tapeworm, Hymenolepis nana
var. fraterna. Am. J. Hyg. 37, 289.
LUCAS, S.B., HASSOUNAH, O.A., DOENHOFF, M. &
MULLER, R. (1979) Aberrant form of Hymenolepis
nana: possible opportunistic infection in immuno-
suppressed patients. Lancet, ii, 1372.
LUCAS, S.B., HASSOUNAH, O.A., MULLER, R. & DOEN-
HOFF, M. (1980) Abnormal development of
Hymenolepis nana larvae in immunosuppressed
mice. J. Helminthol. 54, 75.
94
MITCHELL, G.F. (1979) Responses to infection with
metazoan and protozoan parasites in mice. Adv.
Immunol. 28, 451.
MITCHELL, G.F. (1982) The nude mouse in immuno-
parasitology. In The Nude Mouse in Experimental
and Clinical Research (ed. by J. Fogh & B.C.
Giovanella) Vol. II. p. 267. Academic Press, New
York.
Moss, G.D. (1971) The nature of the immune re-
sponse of the mouse to the bile duct cestode
Hymenolepis microstoma. Parasitology, 62, 285.
Moss, G.D. (1972) The effect of cortisone acetate
treatment on the growth of Hymenolepis Micros-
toma in mice. Parasitology, 64, 31 1.
OKAMOTO, K. (1968) Effect of neonatal thymectomy
on acquired resistance to Hymenolepis nana in mice.
Jpn. J. Parasitol. 17, 53.
OKAMOTO, K. (1969) Effect of cortisone acetate on
acquired resistance to Hymenolepis nana in mice.
Jpn. J. Parasitol. 18, 591.
OKAMOTO, K. & KOIZUMI, M. (1972) Hymenolepis
nana: Effect of antithymocyte serum on acquired
immunity in mice. Exp. Parasitol. 32, 56.
PALMAS, C., WAKELIN, D. & GABRIELE, F. (1984)
Transfer of immunity to Hymenolepis nana in mice
A. Ito
with lymphoid cells or serum from infected donors.
Parasitology, 89, 287.
PATTON, S. (1977) Studies on the passive transfer via
serum of immunity to Hymenolepis nana in the
mouse Mus musculus. Trans. Kentucky Acad. Sci.
38, 56.
RICKARD, M.D. (1983) Immunity. In Biology of the
Eucestoda (ed. by C. Arme & P.W. Pappas) Vol. 2,
chap. 14. Academic Press, London.
RICKARD, M.D. & WILLIAMS, J.F. (1982) Hydatido-
sis/cysticercosis: immune mechanisms and immuni-
zation against infection. Adv. Parasitol. 21, 229.
ROBERTS, L.S. (1980) Development of Hymenolepis
diminuta in its definitive host. In Biology of the
Tapeworm Hymenolepis diminuta (ed. by H.P.
Arai) p. 357. Academic Press, New York.
WILLIAMS, J.F. (1979) Recent advances in the immu-
nology of cestode infections. J. Parasitol. 65, 337.
WILLIAMS, J.F. (1982) Cestode infections. In Immuno-
logy of Parasitic Infections 2nd edn. (eds. by S.
Cohen & K.S. Warren) p. 676. Blackwell, Oxford.
WILLIAMS, J.F. & PEREz-ESANDI, M.V. (1971) Rea-
ginic antibodies in dogs infected with Echinococcus
granulosus. Immunology, 20, 451.