Cell-mediated Immune Responses In Rats Research Articles

Augmented primary humoral immune response and decreased cell-mediated immunity by Murraya koenigii in rats

Murraya koenigii (Rutaceae) (curry patta: Hindi) of the family Rutaceae is used in the traditional Indian system of medicine for its immunomodulatory properties. The essential oil of the leaves of M. koenigii possesses antimicrobial, antifungal, and pesticidal activities and is used for the treatment of amebiasis, diabetes, and hepatitis. The present study was performed to evaluate the effect of M. koenigii on humoral and cell-mediated immune responses in rats. Aqueous extract of M. koenigii leaves was administered orally in a dose of 350 mg/kg. Cell-mediated immunity was assessed by measuring foot pad thickness following sensitization by injection of keyhole limpet hemocyanin and subsequent challenge by the same. Humoral immunity was assessed by measurement of hemagglutination titer to sheep red blood cells (SRBCs). In the humoral immune response, the administration of M. koenigii [350 mg/kg per os (p.o.)] from day 1 to day 7 after sensitization with SRBC on day 0 caused a significant increase in the primary anti-SRBC titer. However, the secondary immune response was decreased significantly (p<0.05) as shown by a decrease in secondary anti-SRBC titer measured on day 11 following a booster dose of antigen on day 8. In the delayed-type hypersensitivity test, M. koenigii (350 mg/kg, p.o.), when administered for 14 days, produced a significant (p<0.05) decrease in foot pad thickness when compared with the control group. Thus, these results suggest that oral administration of M. koenigii augments primary humoral immune response and decreases cell-mediated immunity.

Effect of Triphala on oxidative stress and on cell-mediated immune response against noise stress in rats

Stress is one of the basic factors in the etiology of number of diseases. The present study was aimed to investigate the effect of Triphala (Terminalia chebula, Terminalia belerica and Emblica officinalis) on noise-stress induced alterations in the antioxidant status and on the cell-mediated immune response in Wistar strain male albino rats. Noise-stress employed in this study was 100 dB for 4 h/d/15 days and Triphala was used at a dose of 1 g/kg/b.w/48 days. Eight different groups of rats namely, non-immunized: control, Triphala, noise-stress, Triphala with noise-stress, and corresponding immunized groups were used. Sheep red blood cells (5 x 10(9) cells/ml) were used to immunize the animals. Biochemical indicators of oxidative stress namely lipid peroxidation, antioxidants superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), ascorbic acid in plasma and tissues (thymus and spleen) and SOD, GPx and corticosterone level in plasma were estimated. Cell-mediated immune response namely foot pad thickness (FPT) and leukocyte migration inhibition (LMI) test were performed only in immunized groups. Results showed that noise-stress significantly increased the lipid peroxidation and corticosterone level with concomitant depletion of antioxidants in plasma and tissues of both non-immunized and immunized rats. Noise-stress significantly suppressed the cell-mediated immune response by decreased FPT with an enhanced LMI test. The supplementation with Triphala prevents the noise-stress induced changes in the antioxidant as well as cell-mediated immune response in rats. This study concludes that Triphala restores the noise-stress induced changes may be due to its antioxidant properties.

Effect of l-arginine on restraint stress induced modulation of immune responses in rats and mice

The present study investigates the role of nitric oxide (NO) on restraint stress (RS)-induced modulation of humoral and cell-mediated immune responses in rats and mice. RS produced suppression of humoral immune response, i.e., anti-SRBC antibody titre (7.38±0.32 versus 4.13±0.30; mean±S.E.M., P<0.001). In case of cell-mediated immunity, in delayed type hypersensitivity (DTH) response the change in paw volume decreased from 0.069±0.003 mm (mean±S.E.M.) in control non-stressed group to 0.038±0.002 mm in the stressed group ( P<0.001) while percentage leucocyte migration inhibition (% LMI) decreased from 39.7±1.95 in control non-stressed animals to 15.2±1.07 in animals subjected to stress ( P<0.01). Pretreating the animals with an NO precursor, l-arginine (1000 mg kg −1, i.p.) antagonized the effect of RS on humoral (anti-SRBC antibody titre 6.50±0.27 versus 4.13±0.30, P<0.001) and cell-mediated (DTH response 0.066±0.002 mm versus 0.038±0.002 mm, P<0.001; % LMI 41.5±1.46 versus 15.2±1.07, P<0.01) immune responses. Administration of 7-nitroindazole (7-NI, 50 mg kg −1, i.p.), an inhibitor of neuronal NO synthase, alone further enhanced the immunosuppressive effect of RS (anti-SRBC antibody titre 2.75±0.25 versus 4.13±0.30, P<0.001; DTH response 0.019±0.002 mm versus 0.038±0.002 mm, P<0.001; % LMI 5.0±1.08 versus 15.2±1.07, P<0.01). However, when given before l-arginine treatment, 7-NI reversed the effect of the latter drug on stress-induced immunomodulation (anti-SRBC antibody titre 3.00±0.27 versus 6.5±0.27, P<0.001; DTH response 0.043±0.003 mm versus 0.066±0.002 mm, P<0.001; % LMI 12.0±0.93 versus 41.5±1.46, P<0.01). Unlike its effect on RS-induced immune responsiveness, l-arginine (250, 500, 1000 mg kg −1) when given for 5–7 days to naive non-stressed animals produced dose dependent suppression of both humoral (anti-SRBC antibody titre 6.4±0.32 versus 5.4±0.32, 4.0±0.27, 3.1±0.30, respectively) and cell-mediated (DTH 0.065±0.003 mm versus 0.064±0.004 mm, 0.039±0.003 mm, 0.020±0.002 mm, respectively and % LMI 37.52±1.58 versus 30.48±1.07, 28.18±1.22, 19.76±0.83, respectively) immune responses. 7-NI significantly blocked these immunosuppressive effects of l-arginine (anti-SRBC antibody titre 6.0±0.38 versus 3.1±0.030, P<0.001; DTH response 0.056±0.004 mm versus 0.020±0.002 mm, P<0.001; % LMI 34.76±1.31 versus 19.76±0.83, P<0.01). However, 7-NI when given to non-stressed animals failed to modulate immune responsiveness. Thus, NO appears to play an important role in RS-induced immunomodulation and these effects are different from its effect on immune responsiveness in non-stressed animals.

Efficacy of individual measles virus structural proteins in the protection of rats from measles encephalitis

Lewis rats were immunized with recombinant vaccinia virus (VV) expressing the nucleocapsid (N), phospho (P), matrix (M), fusion (F), and haemagglutinin (H) proteins of measles virus (MV). Animals developed humoral as well as cell-mediated immune (CMI) responses to the corresponding MV proteins. Rats immunized with recombinants VVN, VVF or VVH survived a MV challenge infection whereas VVP- and VVM-immunized rats were only partially protected. In vivo depletion of CD8+ T lymphocytes did not prevent the protective effect of the N, F or H protein-specific CMI response in rats. VVH and VVF immunization induced neutralizing antibodies, but no such antibodies were detected after VVN immunization. Further investigation of the temporal occurrence of the antiviral antibodies indicated that the observed protection provided by VVN and VVF immunization depends on CD4+ N- or F-specific T cells in the absence of neutralizing antibodies and CD8+ T cells. A role for neutralizing antibodies induced by VVH cannot be ruled out.

Measles virus nucleocapsid protein protects rats from encephalitis

Lewis rats immunized with recombinant vaccinia virus expressing the nucleocapsid (N) protein of measles virus were protected from encephalitis when subsequently challenged by intracerebral infection with neurotropic measles virus. Immunized rats revealed polyvalent antibodies to the N protein of measles virus in the absence of any neutralizing antibodies as well as an N protein-specific proliferative lymphocyte response. Depletion of CD8+ T lymphocytes did not abrogate the protective potential of the N protein-specific cell-mediated immune response in rats, while protection could be adoptively transferred with N protein-specific CD4+ T lymphocytes. These results indicate that a CD4+ cell-mediated immune response specific for the N protein of measles virus is sufficient to control measles virus infections of the central nervous system.

Magnetic fields, brain and immunity: Effect on humoral and cell-mediated immune responses

Magnetic fields (MF) can influence biological systems in a wide range of animal species and humans. We report here on the influence of static MF, locally applied to the brain area, on immune system performances in the rat. In the first series of experiments two AKMA micromagnets (M) with the influx density of 600 Gauss were bilaterally implanted (with "N" polarity facing the cranial bones) and fixed to the skull posterior to the fronto-parietal suture (parietal brain exposure). Rats implanted with iron beads (I) and sham-operated (SO) rats served as controls. Animals were exposed to MF or I during different periods of time before and after immunization with several soluble or cellular antigens. We report here on the in vivo immunoregulating effects of centrally applied MF on plaque-forming cell (PFC) response, local hypersensitivity skin reactions and experimental allergic encephalomyelitis. The selective influence of MF applied to different brain regions on PFC response was evaluated, as well. For this purpose, two M were bilaterally implanted in the area of (a) frontal, (b) parietal and (c) occipital brain regions. Rats were under the influence of MF for 20 days before and 4 days after immunization with sheep red blood cells. Groups of nonimmunized rats were exposed for 14, 24 and 34 days to parietally implanted M or I, and the number of peripheral blood CD4+ and CD8+ cells determined by mouse anti-rat W3/25 and MRC OX 8 monoclonal antibodies. The results show an overall in vivo immunopotentiation of humoral and cell-mediated immune responses in rats exposed to MF. Furthermore, these immunomodulating effects of centrally applied MF depend on at least two basic parameters, time of exposure and brain region exposed. The highest immune performance was obtained after exposure of the occipital brain region for a total period of 24 days. The results provide further evidence of the complex interrelationship between the environment, the central nervous system and the immune system.

Effects of sub-chronic DDT exposure on humoral and cell-mediated immune responses in albino rats.

The present study was designed to evaluate the effect of sub-chronic doses of endosulfan on humoral and cell-mediated immune (CMI) responses in albino rats. Male albino rats were given a diet containing 5, 10 or 20 ppm endosulfan for 8–22 weeks and immunized with tetanus toxoid in Freund's complete adjuvant subcutaneously 20 days before terminating the exposure. The humoral immune response was studied by serum globulin level, immunoglobulin (IgM and IgG) concentration and antibody titre against tetanus toxoid. The CMI response was studied by leucocyte migration inhibition (LMI) and macrophage migration inhibition (MMI) factors. The antigen-induced increases in serum globulin fraction and immunoglobulin level were reduced at high doses of the endosulfan after 12 weeks of exposure. Antibody titre was significantly decreased in endosulfan-exposed rats at 10 and 20 ppm levels and a consistent trend was observed. Rats in the 10 and 20 ppm dose groups had significantly depressed LMI and MMI responses. Results obtained in this study revealed marked suppression of the humoral and CMI responses in rats administered with sub-chronic doses of endosulfan. Both cellular and humoral immune responses were decreased in a dose-time dependent pattern. Suppression of immune responses by endosulfan is clearly an important aspect of its toxicology.

Effects of endosulfan on humoral and cell-mediated immune responses in rats

Endosulfan (6,7,8,9,10,10a-hexa-chloro-1,5,5a,6,9,9a-hexahydro, 6,9-methano-2,4,3-benzodioxathiepin-3-oxide), a polycyclic chlorinated hydrocarbon of cyclodien group, is a well known insecticide. Food is the main source of exposure of the general population to endosulfan. The physical, chemical as well as toxicological effects of endosulfan in experimental animals have been reported by various workers. However, the reports regarding the effect of endosulfan on immune system are not available. In view of its widespread use there is an urgent need to investigate the immunotoxicological effect of endosulfan in mammals for the safety evaluation of this insecticide. This has, therefore, prompted the authors to investigate the effect of endosulfan on immune system employing albino rats as the experimental animals. Included in this report are their preliminary findings on humoral and cell-mediated immune responses in rats exposed to sub-chronic doses of endosulfan.

Effect of sub-chronic endosulfan exposure on humoral and cell-mediated immune responses in albino rats.

The present study was designed to evaluate the effect of sub-chronic doses of endosulfan on humoral and cell-mediated immune (CMI) responses in albino rats. Male albino rats were given a diet containing 5, 10 or 20 ppm endosulfan for 8-22 weeks and immunized with tetanus toxoid in Freund's complete adjuvant subcutaneously 20 days before terminating the exposure. The humoral immune response was studied by serum globulin level, immunoglobulin (IgM and IgG) concentration and antibody titre against tetanus toxoid. The CMI response was studied by leucocyte migration inhibition (LMI) and macrophage migration inhibition (MMI) factors. The antigen-induced increases in serum globulin fraction and immunoglobulin level were reduced at high doses of the endosulfan after 12 weeks of exposure. Antibody titre was significantly decreased in endosulfan-exposed rats at 10 and 20 ppm levels and a consistent trend was observed. Rats in the 10 and 20 ppm dose groups had significantly depressed LMI and MMI responses. Results obtained in this study revealed marked suppression of the humoral and CMI responses in rats administered with sub-chronic doses of endosulfan. Both cellular and humoral immune responses were decreased in a dose-time dependent pattern. Suppression of immune responses by endosulfan is clearly an important aspect of its toxicology.

Immunogenicities of haemocyanins from the giant African snail ( Achatina fulica) and the keyhole limpet ( Megathura crenulata)

1. 1. The immunogenicities of the giant African snail ( Achatina fulica) haemocyanin (AFH) and the keyhole limpet ( Megathura crenulata) haemocyanin (KLH) were compared by determining their capacities to induce humoral and cell-mediated immune response in rats. 2. 2. KLH was found to be more immunogenic than AFH, and this was attributed to the fact that KLH contains more moieties, and probably more antigenic determinants than AFH. 3. 3. Since AFH was found capable of stimulating both humoral and cell-mediated immunity, it was suggested that it could be used as an antigen for the investigation of immune responses.

Adjuvant activity for alkylamines of immune responses to ovalbumin, myelin basic protein and a tumor.

Emulsions of ovalbumin in alkylamines, particularly octadecylamine, were compared with an emulsion of ovalbumin in complete Freund’s adjuvant for ability to induce humoral and cell-mediated immune responses in rats. Under defined conditions alkylamine emulsions induced significantly higher IgG immune responses to ovalbumin, but cell-mediated immunity was not significantly different from that induced with complete Freund’s adjuvant. Emulsions of syngeneic myelin basic protein in octadecylamine failed to induce either humoral or cell-mediated immunity to basic protein and neither clinical nor histologic signs of experimental allergic encephalomyelitis ensued. An intranodular injection of octadecylamine into a solid tumor caused significantly enhanced growth of the tumor despite marked necrosis of tumor tissue at the site of injection.