Immunodepression in Taenia crassiceps infection: restoration of the in vitro response to sheep erythrocytes by activated peritoneal cells.

The in vitro response to sheep erythrocytes of mesenteric lymph node cells from mice infected with the larval cestode Taenia crassiceps is significantly depressed and can be restored to control levels by addition of activated peritoneal cells depleted of functional T or B lymphocytes. Adherent mesenteric lymph node cells from infected mice are unable to reconstitute the in vitro response to sheep erythrocytes of normal nonadherent cells. The responses of mesenteric lymph node cells from infected mice to the T-lymphocyte mitogens concanavalin A and phytohemagglutinin and the B-lymphocyte mitogen lipopolysaccharide are normal. Mesenteric lymph node cells from infected mice do not suppress the in vitro response to sheep erythrocytes of normal mesenteric lymph node cells. These results suggest that the immunodepression in T. crassiceps-infected mice is primarily the result of alterations in functional accessory cells.     

Metabolic profile of the liver of mice infected with cysticerci of Taenia crassiceps

 Proton nuclear magnetic resonance (NMR) spectra of liver extracts from mice infected with cysticerci of Taenia crassiceps for 84 or 200 days showed differences in the concentrations of liver metabolites as compared with those of normal liver. The livers of mice infected for 84 days contained less glycogen and β-hydroxybutyrate but more glycine, taurine, betaine, phosphocholine (PC), choline, alanine and lactate. At 200 days post-infection (p.i.) the levels of hepatic glycogen and β-hydroxybutyrate remained lower and those of taurine, PC, choline, alanine and lactate were still elevated, but the concentration of glycine fell below that seen in the 84-day group and that of betaine assumed a value not statistically different from that of either the controls or the 84-day group. The concentrations of glucose, glycerophosphocholine, acylcarnitine, succinate and acetate stayed unchanged throughout the experiment. Received: 26 June 1995 / Accepted: 10 October 1995     

Dengue virus-induced cytotoxic factor suppresses immune response of mice to sheep erythrocytes.

The present study was undertaken to investigate if the suppressed cell-mediated immune responses observed in dengue type 2 virus (DV)-infected mice could be due to the cytotoxic factor (CF) produced in the spleens of DV-infected mice. We have observed that CF given intravenously (i.v.) kills splenic cells and reduces the total cells in the spleen. Mice treated with CF have a significantly depressed immune response to sheep erythrocytes, viz. delayed-type-hypersensitivity as measured by footpad swelling reaction at 24 hr; Jerne's antibody plaque-forming cells in the spleen; and migration inhibition of spleen cells in presence of antigen. These findings are similar to those seen earlier in DV-infected mice.     

Adjuvant effect of Taenia crassiceps glycans against leishmanial antigens in mice infected with Leishmania mexicana

Complex glycans derived from lipid, nucleic acid and protein free extracts of Taenia crassiceps metacestode larvae were found to have adjuvant effect against Leishmania mexicana antigens in BALB/c mice experimentally infected with L. mexicana. A single intraperitoneal or subcutaneous injection of Taenia glycans altered the Th-1/Th-2 balance in experimentally infected mice as determined by Western blot analysis of IgG 1 and IgG 2a antibodies to L. mexicana antigens. Leishmania antigens which were immunogenic in Taenia glycan vaccinated mice were different from those of non-vaccinated mice. Vaccination induced leishmania antigen specific IFN-γ expression in vitro culture by spleen cells from Taenia glycan vaccinated-leishmania infected mice and not from mock vaccinated-leishmania infected BALB/c mice. We conclude that T. crassiceps glycans have immunoadjuvant effects against leishmania and may be developed as adjuvants in anti-leishmania vaccines.     

Suppression of primary antibody response to sheep erythrocytes in susceptible and resistant mice infected with Giardia muris.

The kinetics of anti-sheep erythrocyte (SRBC) response were studied in susceptible (A/J) and resistant (B10.A) mice during infection with Giardia muris. Mice infected with G. muris were found to be less responsive to either intraperitoneally or intraduodenally administered SRBC. Immunodepression was of relatively short duration, occurring during the period of highest trophozoite density in the small intestine, and was present in both spleen and, in particular, mesenteric lymph node cell populations. The main difference in the kinetics of anti-SRBC responses between A/J and B10.A mice was that susceptible mice were significantly less responsive to SRBCs than were the resistant B10.A animals. The difference in the kinetics of the anti-SRBC response between A/J and B10.A mice was not due to T-suppressor cell activity. Mesenteric lymph node cell transfers but not spleen cell transfers from infected mice to syngeneic recipients caused depressed normal anti-SRBC response. Furthermore, administration of the soluble extract of the trophozoites to uninfected mice resulted in a depressed response against SRBCs. Pronounced immunodepression in gut-associated lymphoid tissues may be more relevant than systemic immunodepression to survival and reproduction of trophozoites in murine giardiasis.     

Effect of hydrazide cysteine on the humoral immune response of mice to sheep erythrocytes

Hydrazide of cysteine, introduced intraperitoneally or per os in three doses for three consecutive days after immunization of mice with SRBC, caused a stimulation or an inhibition of the humoral immune response, determined on day 4 as a number of cells in the spleen producing antibodies of 19S and 7S class. The stimulation of the humoral immune response was induced by the dose of 100 micrograms per mouse and was more significant in the case of the 7S response. High doses of HD, on the other hand (1 mg per mouse i.p. and 1-5 mg per mouse per os) caused an inhibition of the humoral immune response which was more pronounced in the case of the secondary immune response. The mechanism of action of HD in the course of the immune response and its possible application in therapy is discussed.     

The T cell-dependent period of the immune response to sheep erythrocytes.

To study the T cell-dependent period of the immune response of mouse spleen cells to sheep erythrocytes the co-operation between T and B cells was abrogated at different times during the in vivo or the in vitro response. The abrogation was performed by killing the T cells with anti-theta serum or anti-H-2 serum. The surviving cells were subsequently cultured in vitro and the number of IgM plaque-forming cells was determined each day. The results indicate that T cells play an important role during the first 3 days of the response in vivo. However, during the in vitro response the presence of the T cells is only required during the first 2 days. The difference between the response in vivo and in vitro is probably due to a synchronous start of the plasma cell development in vitro and a more asynchronous start of this process in vivo.     

Kinetics of the inflammatory response in subcutaneous cysticercosis induced in mice by Taenia crassiceps

The larval stage of Taenia crassiceps has been used to study human cysticercosis as these larvae have antigenic similarity to the cysticerci of Taenia solium. The aim of this study was to evaluate the histopathological and immunological changes that followed the inoculation of T. crassiceps cysticerci into the subcutaneous tissue of C57BL/6 mice. Microscopically, granulomas formed of neutrophils and macrophages developed at the sites of inoculation. The serum concentration of the cytokine interferon (IFN)-γ increased throughout the course of infection, while the serum concentration of interleukin-4 increased during the period of transition from the initial phase (7-30 days postinoculation [dpi]) to the late phase (60-90 dpi) of infection. Destruction of the parasite therefore appears to be associated with an increase in IFN-γ, suggesting that a type 1 immune response is important in the control of the parasite.     

Variation of the immune response to sheep erythrocytes in several strains of mice and their crosses

Summary There is a continuous variation in the immune response to sheep erythrocytes in inbred and outbred strains of mice. In animals of equal age strain-specific differences are the most important cause of the variation. Female animals are on the average superior to the male ones. Especially in the 7 S response the crossbreds showed positive deviations from the mid-parent values, thus suggesting the existence of non-additive gene effects. In one crossing experiment maternal influences could be shown.

---

Zusammenfassung Die Stärke der Immunantwort nach Injektion einer konstanten Dosis Schaferythrocyten variiert kontinuierlich in verschiedenen Mäusestämmen. Bei gleichaltrigen Tieren stellen stammbedingte Unterschiede eine wichtigere Varianzursache dar als das Geschlecht der Tiere. Trotzdem waren die weiblichen Tiere in der Mehrzahl der durchgeführten Tests den männlichen überlegen. Kreuzungstiere zeigten einen Hybrideffekt, der vor allem die Zahl der indirekten plaquebildenden Zellen in der Milz und den Titer der merkaptoäthanolresistenten Hämagglutinine im Serum betraf. In einem Kreuzungsexperiment konnte ein mütterlicher Effekt beobachtet werden.

---

---

This investigation was supported by the Deutsche Forschungsgemeinschaft.     

Depression of lymphocyte response to mitogens in sheep infected with tick-borne fever

Lymphocytes obtained from sheep experimentally infected with Cytoecetes phagocytophila, the causative agent of tick-borne fever, showed reduced blastogenesis induced by the mitogens phytohaemagglutinin and E. coli lipopolysaccharide. The period of reduced lymphocyte reactivity coincided with the period of parasitaemia and leucopenia.     

Modulation of the immune response to sheep erythrocytes by lipid-free glycerol teichoic acid.

The 4-day response of C3H/HeJ mice to sheep erythrocytes was suppressed by a lipid-free teichoic acid with an average molecular weight of 2,900 when it was administered by the intraperitoneal route. Enhancement was not observed at that time, and neither suppression nor enhancement could be demonstrated by the intravenous route. Either suppression or enhancement of background plaques could be induced, depending upon the timing. Dosage influenced the degree of suppression from 8 to 100 micrograms, whereas suppression of background plaques required only 1 microgram of lipid-free teichoic acid. The kinetics of the sheep erythrocyte response was altered by treatment of the mice with lipid-free teichoic acid, delaying the peak until day 5 and producing enhancement at that time. Although lipid-free teichoic acid was shown to be toxic for mouse splenocytes (50% lethal dose, ca. 200 micrograms) in vitro, no effect at the levels employed was observed in vivo. The data presented indicate that modulatory activity is influenced by route, timing, dosage, and apparently the number of antibody-secreting cells.     

Comparative serological reactivity of Taenia crassiceps, Taenia solium and Taenia saginata metacestode neutral glycolipids to infection serum from Taenia crassiceps-infected mice.

A comparative survey was undertaken of the neutral fraction glycolipids from the metacestodes of 3 taeniid species, Taenia crassiceps, Taenia solium and Taenia saginata, to determine their chemical and serological staining patterns on separation by thin-layer chromatography. The orcinol-positive patterns of T. solium and T. saginata metacestodes exhibited a closer superficial resemblance to each other than to T. crassiceps or T. saginata adults. A comparison of component migration properties against standards of known structure indicated the main oligosaccharide chains to be mono-, di-, tri- and tetrasaccharides; however, in T. solium this was extended to at least a heptasaccharide. The multiple banding characteristic of each component is a consequence of lipid moiety heterogeneity. Serologically, the patterns of the 3 taeniid species neutral fraction glycolipids showed virtually the same immunological reactivity towards mouse normal serum, infection serum and a monospecific, polyclonal antibody directed against the trisaccharide component of T. crassiceps. The latter antibody was isolated from mouse infection serum by affinity chromatography on a column of glycolipid-bound octyl-Sepharose CL-4B. Immunochemically, the major common epitope expressed by the neutral fraction glycolipids of the 3 taeniid species is the same or very similar to the glycosphingolipid, neogalatriaosyl ceramide derived from the marine mollusc Turbo cornutus (Gal(beta 1-6) Gal(beta 1-6) Gal(beta 1-1)Cer). Host tissue neutral fraction glycolipids, porcine muscle and bovine muscle, as well as human spleen, were not immunoreactive.     

Denervation and the immune response in mice infected with Trypanosoma cruzi.

C57B1 mice were infected with Trypanosoma cruzi Y strain trypomastigotes and showed a peak of parasitaemia 9 days after infection. Virtually all mice survived the acute stage of infection and were aparasitaemic thereafter. Coincident with the peak of parasitaemia, there was a progressive loss of cardiac neurones (up to the 20th day after infection) and an appearance of T. cruzi antigen on myofibres. Anti-parasite immunity, evidenced by a significant inhibition of macrophage migration in the presence of T. cruzi antigens (MIF test) and the deposition of complement and immunoglobulin in vivo around the nests of parasites, developed between days 7-10 after infection. Immunity to "self' components (MIF) test using neurone and heart antigens) was not detected until 15-20 days after infection. Although the MIF test detected a progressive increase in anti-neurone immunity between 20-90 days after infection, there was no additional loss of cardiac neurones during this period. In contrast to current hypotheses, these data suggest that the immunity to heart and neuronal antigens commonly detected in animals infected with T. cruzi is the result rather than the cause, of host cell destruction.     

The effect of antilymphocytic antibody on the humoral immune response in different strains of mice: II. The response to sheep erythrocytes

The effect of an horse anti-mouse thymocyte globulin (ALG) preparation on the primary and secondary immune responses to sheep erythrocytes (RBC) was studied in 2–3-month-old male A/HeJ, C57B1, BALB/c, DBA/1, CBA and C3H mice. A wide variation in the primary and secondary responses of the individual strains was noticed but in all cases these were significantly suppressed by ALG pretreatment. The capacity of the ALG to suppress the primary immune response was not overcome by increasing the antigen dose from 3 × 10⁷ to 3 × 10⁹ sheep RBC.     

Comparison of the immune response to sheep erythrocytes,tetanus toxoid and endotoxin in different strains of mice

The primary immune response in 7 inbred and 2 outbred mouse strains to SRBC, tetanus toxin and ‘E.coli’ endotoxin is compared. Significant variations are found in the different strains concerning their antibody response to these antigens. The differences in antibody production reached with SRBC (direct and indirect PFC) and tetanus toxin are on a quantitative level, those with endotoxin also on a qualitative level. The kinetic studies further indicate that course of antibody formation as well as peak of response may considerably vary between different strains.     

The effects of ALG on the murine immune response to sheep erythrocytes

Antilymphocyte globulin (ALG), and to a lesser extent normal rabbit globulin (NRG), when given to mice prior to immunization with sheep-RBC suppress both the γM and γG_2a responses. Globulin injected after the antigen suppresses the γG_2a response, augments the γG₁ response and has little effect on the γM response. These effects are also observed in mice partially paralysed to rabbit γ globulin. In another system—the response to hapten—protein conjugates precursors of antibody producing cells were found to be more resistant to ALS treatment in vivo than were helper cells. It is concluded that the suppressive effects of ALG treatment are largely due to the direct action of ALG on helper cells (T-cells). The mechanism of the adjuvant-like effect is unclear.     

Two epitopes shared by Taenia crassiceps and Taenia solium confer protection against murine T. crassiceps cysticercosis along with a prominent T1 response

Taenia crassiceps recombinant antigens KETc1 and KETc12 have been shown to induce high level of protection against experimental murine T. crassiceps cysticercosis, an experimental model successfully used to test candidate antigens for use in vaccination against porcine Taenia solium cysticercosis. Based on the deduced amino acid sequence, KETc1 and KETc12 were chemically synthesized in linear form. Immunization with KETc1 induced 66.7 to 100% protection against murine cysticercosis, and immunization with KETc12 induced 52.7 to 88.1% protection. The elicited immune response indicated that both peptides contain at least one B-cell epitope (as demonstrated by their ability to induce specific antibodies) and one T-cell epitope that strongly stimulated the proliferation of T cells primed with either the free peptide or total cysticercal T. crassiceps antigens. The high percentage of spleen cells expressing inflammatory cytokines points to the likelihood of a T1 response being involved in protection. The protective capacity of the peptides and their presence in all developmental stages of T. solium point to these two epitopes as strong candidates for inclusion in a polyepitopic synthetic vaccine against T. solium pig cysticercosis.