In vitro effects of 2-tert-butyl-benzothiazole derivatives on microfilariae of Litomosoides carinii, Brugia malayi and Acanthocheilonema viteae.

Six 2-tert-butyl-benzothiazole derivatives (2-tert-butyl-6-iso-thiocyanato-5-methyl-benzothiazole CGP 21306); 3-[(2-tert-butyl-5-methyl-benzothiazole-6-yl) aminothiocarbonylthiol] propionic acid (CGP 21835); 2-tert-butyl-5-methyl-6-(N-methyl-piperazinyl-thiocarbonylamino)-b enzothiazole (CGP 21833); 2-tert-butyl-5-methyl-6-(4-dimethylamino-piperid-1-yl-thiocarbo nylamino)- benzothiazole (CGP 26702); CGP 20376, the 5-methoxy analogue to CGP 21835 and CGP 20309, the 5-methoxy analogue to CGP 21833) with known, high filaricidal activity in vivo were tested for in vitro efficacy against microfilariae of L. carinii (Lc), B. malayi (Bm) and A. viteae (Av) in order to study intrinsic antifilarial activities. All drugs affected the motility of the microfilariae of the three species in a species, dose and time dependent fashion. Lc was the most sensitive, Av the most resistant species. CGP 20376 and 21835 were the most effective compounds followed by CGP 21306. Complete immobilization of microfilariae was observed after 20 h in protein-free medium RPMI 1640 at drug concentrations of 0.1 to 10 nmol/ml. Effects were still marked 2 when graded on a 4 (full motility) to 0 (immobile) scale at concentrations of 0.01-0.1 nmol/ml. In the case of the thiourea derivatives CGP 21833, 26702 and 20309 concentrations had to be increased 10-100 fold to obtain similar effects. When proteins were present in the incubation medium (10% foetal calf serum, 100% normal serum) the efficacy of the compounds was reduced, i.e. drug concentrations had to be increased up to 100 fold to produce similar effects as in protein-free medium.(ABSTRACT TRUNCATED AT 250 WORDS)

Lead and immunity: II. Suppression of humoral immune response to Hymenolepis nana in mice.

Serum protein changes in mice treated for varying durations with lead nitrate and subsequently infected with 1000 H. nana eggs were compared with their counterpart controls, only treated and only infected groups. Decreased values of beta and gamma globulins in all the experimental groups along with higher worm recoveries indicate suppression of humoral immune response by lead in association with higher worm recoveries indicate suppression of humoral immune response by lead in association with the cellular components since these globulins are known to contain antibodies. Lead treatment for a duration of 45 days proved to be most effective in suppressing the immune response.

Serum protein changes in lead exposed mice infected with Hymenolepis nana.

Significant decrease in serum globulin took place in Hymenolepis nana mouse model treated with lead prior to infection. Decrease of alpha, beta and gamma globulins was maximum on day 4 in comparison to that of control, gradually tapering off by day 100 when suppression was minimum with the experimental values almost reaching the same level as those of the control. Thus, suppression of globulins was neither total nor permanent.

Increased susceptibility of lead exposed chickens to experimental infection of Ascaridia galli.

Two sets of one day old, white leghorn (Victoria Strain) chickens were each orally exposed to 1.0 mg lead nitrate daily for 7 days and subsequently infected with 15 and 30 A. galli eggs. These experimental chickens exposed to lead harboured significantly greater worm burden when compared to unexposed controls leading strong support to the view that lead exposure significantly suppressed their immune response to A. galli infection. It also indicated that exposure of lead prior to infection greatly impaired weakened the immune capability of such chickens.

Cell mediated immunity during experimental ancylostomiasis: a review.

Cell-mediated immunity is usually recognized only in a very small number of infections caused by helminths. The present review is engaged with some aspects of the cell-mediated immunity in infections caused by Ancylostoma caninum. Special attention is paid to the role of passive transfer of sensitized cells and serum. The paper is based on a series of own original investigations of the authors.

Experimental infection of Ancylostoma caninum in chickens: immunization through transfer of sensitized bursal cells.

An attempt has been made to demonstrate the immune response in chickens to infection by the dog hookworm Ancylostoma caninum following transfer of sensitized bursal cells from infected donor chickens. Recipients were challenged with a dose of 500 larvae each, 1, 3 and 5 days after cell transfer. The immune response was found to be more pronounced in recipients challenged 5 days after cell transfer than in those challenged 1 or 3 days after transfer and those which received non-sensitized bursal cells.

Effect of spleen extracts on the immune response in chickens to Ancylostoma caninum larvae.

Spleen extracts from WLH chickens nonsensitized and sensitized by repeated infections of Ancylostoma caninum larvae were injected separately into isologous recipients. Extracts from donors infected with repeated high dose (250 + 250 + 500) and low dose (125 + 125 + 250) of larvae induced a significant acquired protective immune response when compared to controls which received normal extracts. No significant difference was observed between the two experimental groups. The filariform Ancylostoma caninum larvae which can cause cutaneous larva migrans in man are found to be carried by a variety of paratenic hosts. Several studies from this lab have shown that the white leg horn (WLH) chicken successfully sustains and also responds immunologically to this parasite. The present authors have also shown that extracts of bursae of Fabricius and spleens of immunized chickens can induce immunity in syngeneic recipients. Here an attempt has been made to investigate whether repeatedly sensitized extracts of A. caninum infected chickens can cause expulsion of a challenge dose from the recipients.

Nematospiroides dubius: adoptive transfer of immunity through peritoneal exudate cells and extent of immunosuppression in recipient Swiss albino mice.

Adoptively immunized female Swiss albino mice responded better to HcA when treated before cell transfer than those treated after cell transfer and also from treated donors during the course of experimental infection of Nematospiroides dubius. Immunosuppression in recipients treated after cell transfer gave an overall considerably better expression of immunosuppression and those treated before cell transfer exhibited better retention capacity on day 1 only.

A possible explanation for the synergism between mixed T- and B- cell populations in mice adoptively immunized with Ancylostoma caninum.

Ancylostoma caninum--mouse model was employed to study the cellular cooperation in the adoptive immune response. The syngeneic recipient mice were intraperitoneally injected once or twice with mixtures of thymus and bone marrow cells from infected (with 500 or 2000 larvae) and uninfected donors. The experimental recipients expelled and/or destroyed the challenge larval burden more readily and at a greater rate than the controls with unsensitized cells. The cooperation between sensitized thymus and bone marrow cells was, thus, found to be exposed in a better manifestation of adoptive immune response than either of these two alone. The cellular elements of delayed hypersensitivity after combining with the antibodies of humoral system could elicit a much better response in these recipients.

Rapid expulsion of Ancylostoma caninum larvae due to previous infection with Hymenolepis nana deshelled eggs.

Mice initially infected with single and repeated doses of Hymenolepis nana deshelled eggs produced rapid and significant expulsion of challenged Ancylostoma caninum larvae. Absolute protective response was observed 8 days after initial infection (at 96 hours after challenge) in both singly and repeatedly infected groups probably due to high titres of heterologous reacting antibodies.

Pattern of immune response in recipients after transfer of mesenteric lymph node cells sensitized with low and high doses of Ancylostoma caninum.

Cellular immune response was detected in female Swiss albino mice with mesenteric lymph node cells during Ancylostoma caninum infection. Sensitized lymphocytes responded vigorously to A. caninum antigens and it was found that the cells (singly or repeatedly) sensitized with either low or high doses could confer adoptive protective immunity in recipients later challenged with a single dose of 500 A. caninum larvae.

Transfer of delayed hypersensitivity through repeatedly sensitized peritoneal exudate cells during experimental ancylostomiasis in mice.

Current investigations using sensitized peritoneal exudate cells from mice infected repeatedly with Ancylostoma caninum larvae supply the evidence that these cells have the capability to transfer passive immunity to isogeneic recipients in contrast to normal cells from uninfected donors. High doses of sensitization to donors and a lapse of time between the expansion and proliferation of cells in the recipients provide a rather strong immunological readiness to expel/destroy the worm burden. The larvae bore through the gut reaching the peritoneal cavity but cannot enter the liver and/or lungs; they are thus misled (in the absence of normal guiding influences) to muscles where they undergo allergic death.

Experimental infection of Nematospiroides dubius in Swiss albino mice. IX. Effect of dose break up on the serum protein patterns.

The present study concerns with the effects of larval inoculation with either a single dose or two or more spaced doses of 200 larvae on the serum protein profiles. No significant difference occurred in the various fractions among the three groups indicating that the total quantity of antigenic stimulation in the most important factor in eliciting such changes, no matter whether the dose is given once or spaced in two or three small doses. Serum protein fractions of Swiss albino mice undergoing experimental infection of Nematospiroides dubius do not tend to rise further due to repeated exposures in comparison to those that received a challenge dose only (1). Hence, experiments were designed to ascertain whether there is any difference in serum protein patterns due to breaking up of the infective dose into two or three spaced doses of N. dubius larvae.

Ancylostoma caninum: a report on the peripheral eosinophilia in naive and immunized Swiss albino mice.

The number of peripheral eosinophils was counted in female Swiss albino mice on 1, 4, 9, 16 and 30 days after infection with various single (500, 1000 and 2000) and weekly repeated (500 + + 500 + 1000, 1000 + 1000 and 1000 + 1000 + 2000) doses of filariform Ancylostoma caninum larvae. The eosinophil response was significantly higher in infected than in uninfected mice and reached a peak on day 16 in naive and day 4 and 9 in immunized mice. Immunized mice were significantly more eosinophilic than the naive mice. An attempt has been made to correlate eosinophilia with immunity of mice to A. caninum larvae.

Experimental infection of Nematospiroides dubius in Swiss albino mice. VII. Worm burdens and serum protein fractions.

The paper deals with the alterations in serum protein profiles and its possible correlation with the worm burden in Swiss white mice infected with single and repeated doses of N. dubius infective larvae. Marked changes observed in serum protein fractions in all the groups were found to be further raised with increase in dose levels. However, maximum (optimal) changes of different fractions depend on the total number of larvae inoculated irrespective of the number of inoculations given. Percentage of worm retention was found to be inversely proportional to the number of larvae inoculated. Worm expulsion during repeated infections was attributed to the therefore, participation of increased amount of immunoglobulins and, humoral immunity (immediate type) has been suggested to play a major role in the immune mechanism of this model.

Experimental infection with Ancylostoma caninum larvae in mice. VII. Role of promethazine hydrochloride in the rejection of worm burden from the intestine.

Acquired resistance of female swiss albino mice (6 to 8 weeks old) to Ancylostoma caninum infection was demonstrated by the transfer of mesenteric lymph node cells (MLNC) from resistant (sensitised and promethazine treated), sensitised and untreated and non-sensitised and untreated donors to normal recipients of the same isogeneic strain. MLNC from sensitised and promethazine treated donors were more effective in suppressing the rejection mechanism of worm burden in recipients in comparison to the cells obtained from other donor groups; the drug may be exerting an inhibitory action at either the specific lymphoid level (reducing antibodies effect) and at the non-specific amine level.