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Effect of Crotalus venom on the humoral and cellular immune response.

The effect of venom of South American rattlesnake Crotalus durissus terrificus (cdt) on the humoral and cellular immune response was studied in BALB/c mice that were immunized with soluble antigens [human serum albumin (HSA) or chicken ovoalbumin (OVA)] or sensitized to DNFB 1 hr after venom injection. Pretreatment of the animals with cdt venom induced a significant reduction in the level of anti-OVA and anti-HSA IgG antibodies. The effect of crotoxin, a major neurotoxic component of cdt venom, its acidic non-toxic subunit (CA) and its basic phospholipase A2 subunit (CB) was also studied. The whole crotoxin molecule was as able as cdt venom to induce a significant decrease in the level of anti-OVA and anti-HSA IgG antibodies. However, the CA and CB subunits of crotoxin did not change the antibody level to either antigen, suggesting that the suppressive effect of crotoxin requires the intact molecule. Both cdt venom and the whole crotoxin molecule were able to induce a significant decrease in the level of anti-HSA IgG1 antibodies. The levels of other IgG isotypes and IgE were barely detectable and could not be estimated. In spite of their suppressive effect on the humoral immune response neither cdt venom nor crotoxin had any effect on the cellular immune response as estimated by contact sensitivity reaction to DNFB. It is suggested that cdt venom and its crotoxin component have an inhibitory effect on the humoral but not on the cellular immune response.

Animals↗

Impaired cellular immune response in harbour seals (Phoca vitulina) feeding on environmentally contaminated herring.

In a 2.5-year immunotoxicological study, two groups of captive harbour seals (Phoca vitulina) were fed herring from the heavily polluted Baltic Sea or from the relatively uncontaminated Atlantic Ocean. Blood samples were collected at regular intervals, and functional immunological parameters were monitored. T cell mitogen and mixed lymphocyte-induced proliferative responses of peripheral blood mononuclear cells (PBMC) obtained from seals fed Baltic herring were significantly reduced over the course of experiment. Upon immunization with rabies virus antigen (RV) and tetanus toxoid (TT), specific proliferative responses of PBMC from the seals fed Baltic herring were also significantly reduced. Impairment of T cell-mediated immune responses became especially apparent during the second year on the respective diets, and correlated significantly to 2,3,7,8-tetrachloro-dibenzo-p-dioxin toxic equivalent levels in blubber biopsies taken from the seals after 2 years on the respective diets. Humoral immune responses, including lipopolysaccharide (LPS)-induced lymphoproliferative responses, in vitro immunoglobulin production by PBMC, as well as RV-, TT-and poliovirus-specific serum antibody responses following immunization, remained largely unaffected. We conclude that suppression of the cellular immune response in the seals fed Baltic herring was induced by the chronic exposure to immunotoxic environmental contaminants accumulated through the food chain. Since cellular immune responses are known to be of crucial importance in the clearance of morbillivirus infections, these results suggest that environmental pollution-related immunosuppression may have contributed to the severity and extent of recent morbillivirus-related mass mortalities among marine mammals.

Animals↗

Cellular immunity and IgE levels in asthmatic children.

Several reports have suggested that asthmatic children may be particularly vulnerable to viral respiratory infections, in addition to this, abnormal cellular regulation has been suggested as an explanation for the increased IgE levels in atopy. Despite such evidence there have been few studies evaluating cellular immune function in asthmatic children. This study has examined in vivo and in vitro aspects of cellular immune function in twenty-six atopic asthmatic children and compared them with nineteen age-matched non-atopic control subjects. In vivo cellular immunity was assessed by quantitating the cutaneous delayed hypersensitivity (CDH) response to four ubiquitous antigens. Lymphocyte responsiveness to three polyclonal mitogens was measured in vitro. The serum IgE level was determined in all study subjects. The results indicate that CDH to Candida antigen is significantly diminished among the asthmatic subjects and lessened to streptokinase/streptodornase. Lymphocyte mitogen response did not differ significantly between the study groups. No correlation could be shown between in vitro lymphocyte responsiveness and IgE level. These studies suggest that a subtle cellular immune defect may exist in asthmatic children and support the need for further studies of this question.

Adolescent↗

Inhibition of the cellular immune response to simian virus 40 tumor cells in tumor-bearing and tumor-immune mice by concanavalin A.

The effects of in vivo-administered concanavalin A (Con A) on the kinetics of the primary and secondary cellular immune responses to simian virus 40-transformed tumor cells were investigated in BALB/c mice. Either a single initial dose of 400 mug Con A or daily doses of 50 mug depressed the cell-mediated immune response to tumor cells during the progressive growth of tumors, as determined by a radioisotopic foot-pad assay. The immune depression correlated with an increase in ultimate tumor weight. Similarly, Con A suppressed the antitumor cellular immune response in tumor-immune animals. Immune reactivity returned within 6 days after a single injection of 400 mug Con. Continuous administration 50 mug Con A resulted in a gradual decline in antitumor cellular immune responsiveness, which reached a plateau by the 5th day. Splenic lymphocytes from Con A-treated, immune mice failed to elicit a local adoptive transfer reaction; their immune responsiveness tended to return after incubation with alpha-methyl-D-pyranosyl sugars.

Animals↗

External biliary drainage plus bile acid feeding is not equal to internal drainage in preserving the cellular immunity following prolonged obstructive jaundice.

This study investigates the importance of intestinal bile flow in cellular immunity. Sprague-Dawley rats undergoing bile duct ligation (BDL) and sham ceiliotomy (Sham) for 14 and 21 days were investigated. Experimental animals following BDL were further divided into an external drainage (ED) group, an ED group with rat chow mixed with 2:2:1 cholic acid, chenodeoxycholic acid, and deoxycholic acid (ED + BF), and an internal drainage (ID) group. Fourteen days later, they were killed and analyzed for spleen lymphocytic [3H] thymidine uptake (LHU) under mitogen stimulation with phytohemagglutinin, blood biochemistry, hemogram, and liver pathology. In the 14-day BDL experiment, LHU and serum albumin level were decreased in the BDL group (P < 0.05). After drainage, they were not significantly different among sham, ED, ED + BF, and ID groups. In the 21-day BDL experiment, the red cell volume was decreased (P < 0.05). After drainage, the ED, ED + BF, and ID groups still had a significantly lower LHU than the sham group (P < 0.05). However, the ID group had higher LHU than the ED and ED + BF groups (P < 0.05). The ED + BF group had a slightly higher LHU than the ED group but not statistically significant. Liver pathology returned to normal after drainage in the 14-day BDL model. In contrast, the 21-day BDL group had prominent periportal necrosis and developed periportal fibrosis after drainage. The present study reveals the duration of BDL determines the severity of hepatic damage. In the 14-day BDL groups, all kinds of drainage completely reverse the impaired liver function and cellular immunity. In the 21-day BDL group, 14-day drainage is inadequate for recovery because irreversible pathological changes are found. The reversal of cellular immunity in ID is better and faster, because it provides a better hepatic functional, nutritional, and hematological recovery besides the presence of primarily secreted bile acids.

Animals↗

Potent, persistent cellular immune responses elicited by sequential immunization of rhesus macaques with Ad5 host range mutant recombinants encoding SIV Rev and SIV Nef.

Vaccines incorporating multiple HIV components should elicit broad immunity and protection against a spectrum of HIV strains. Early regulatory and accessory gene products are attractive candidates for such vaccines. Here, immunogenicity studies on SIV Rev and Nef expressed in replication competent Adenovirus type 5 host range mutant vectors (Ad5hr) are summarized. Interferon-gamma (IFN-gamma)-secreting cells in response to Env and Rev peptides were enumerated by ELISPOT after two sequential immunizations of 55 macaques with Ad5hr-SIVenv/rev. Responses to SIV Nef were assessed in 16 macaques also immunized with Ad5hr-SIVnef. Potent cellular immunity to both Rev and Nef was induced following the second Ad-recombinant immunization and persisted for at least 30 weeks. Persistent cellular immunity to SIV Env was also seen, with a mean of 700 IFN-gamma-secreting cells per million PBMC. Rev and Env responses were positively correlated. While greater responses to early gene products occur in natural infection, as immunogens Rev and Nef elicited the same number of IFN-gamma secreting cells as Env, after adjusting for differences in protein size. The same percentage of macaques also responded to Rev, Nef, and Env: 59, 63, and 64%, respectively. Overall, Ad5hrSIVenv/rev and -SIVnef were highly effective immunogens. Their contribution to protective efficacy will be addressed in future studies.

AIDS Vaccines↗

Cellular immunity during pregnancy. I. Proliferative and cytotoxic reactivity of paraaortic lymph nodes.

The possibility of changes in immune reactivity during pregnancy was studied by measuring cellular immunity in vitro of the paraaortic (PA) lymph nodes, which drain the uterus in pregnant mice. The proliferation of PA lymph node cells from primiparous pregnant C57Bl/6J mice, in mixed lymphocyte cultures (MLC) against alloantigens, was lower in magnitude, but had the same kinetics, as the response of virgins. This was observed in syngeneic and allogeneic (to DBA/2J) pregnancies, and using the paternal as well as third party allogeneic stimulators. The response was depressed by day 8 of gestation and returned to normal two days after delivery. The decrease was not due to an active suppressor mechanism, as assayed by mixing experiments. Irradiation (1500R) of the lymphocytes from pregnant mice, prior to mixing with cells from virgins, did not reveal the presence of a radioresistant suppressor cell. In contrast to the MLC results, no differences were found between lymphocytes from pregnant and virgin mice in their ability to develop MLC-generated cell-mediated lympholysis (CML) against alloantigens, as measured in a chromium release assay. The PA lymph node cells from pregnant animals bearing allogeneic fetuses also did not show evidence of in vivo sensitization to the paternal alloantigens. Therefore, the local nodes draining the uterus from primiparous pregnant animals bearing syngeneic or allogeneic fetuses show a nonspecific decrease of MLC proliferation while retaining the capacity to generate normal CML activity.

Animals↗

Cellular immunity and memory to respiratory virus infections.

Respiratory virus infections, such as those caused by influenza and parainfluenza viruses, are a major cause of morbidity and mortality worldwide. Current vaccines against these pathogens rely on the induction of humoral immune responses that target viral coat proteins. Although this type of immunity provides solid protection against homologous virus strains, it is ineffective against heterologous virus strains that express serologically distinct coat proteins. In contrast, cellular immune responses can target internal antigens that are shared between heterologous viral strains. This form of immunity, sometimes referred to as heterosubtypic immunity, can mediate a substantial degree of protection. Thus, vaccines that emphasize cellular immune responses would be a valuable complement to available humoral vaccines. However, we only have a rudimentary understanding of which T cell subsets mediate protective immunity, how T cell memory is established and maintained, how that memory is recalled in a secondary infection, and why cellular immunity wanes rapidly with time. Here we review the role of CD4+ and CD8+ T cells in the recall response to influenza and parainfluenza viruses. In particular we focus on the recent observation that substantial numbers of memory T cells are established in the lung tissues and discuss the potential role of these cells in mediating a recall response. A thorough understanding of the cellular immune response to infection in the lungs is essential for future vaccine development.

Animals↗

Cellular immune reactivity in patients with rheumatoid arthritis and effects of levamisole.

Cellular immune reactivity was examined in control subjects and in 16 patients with rheumatoid arthritis before and after administration of levamisole. Prior to levamisole treatment, this population of patients with rheumatoid arthritis had diminished cellular immunity as measured by skin test reactivity, lymphocyte stimulation by antigen and by PHA, lymphocyte count and percentage and absolute numbers of long-incubation rosette-forming cells (RFC). Administration of levamisole caused enhancement of skin test reactivity and flares at dinitrochlorobenzene (DNCB) test sites which were not paralleled by an increase in lymphocyte stimulation by the same antigens in vitro or enhancement in the PHA response. The increase in lymphocyte count and RFC was borderline (p = .06). Of the 16 patients who received levamisole for three months, nine patients showed at least one physical sign of improvement, five patients remained unchanged, and two patients experienced progression of their disease.

Adult↗

Prolonged oviposition decreases the ability of the parasitoid Leptopilina boulardi to suppress the cellular immune response of its host Drosophila melanogaster.

The cellular immune response of Drosophila against metazoan parasites is characterized by the production of melanotic capsules comprised mostly of host blood cells (hemocytes). During the latter part of the ovipositional period of the cynipid wasp parasitoid Leptopilina boulardi, eggs are deposited into host larvae of Drosophila melanogaster that are more susceptible to destruction by melanotic encapsulation than are eggs laid earlier. The increase in parasitoid mortality is attributed to a decline in the wasp's ability to suppress the host immune response. The decrease in active immune suppression is dependent on the reproductive physiology of the wasp, and this correlates with the extent of her prior ovipositional experience and not on her chronological age nor on the number of eggs remaining in the ovarioles. Such females with prior ovipositional experience which lack the ability to immune suppress infect far fewer hosts than females with no prior ovipositional experience. The reluctance of experienced wasps to infect hosts is not due to egg depletion, but instead is attributed to a depletion in immune suppressive substances. Perhaps by ovipositional restraints, retaining eggs that would otherwise become encapsulated reduces selection pressure in host populations for specific immune reactivity.

Analysis of Variance↗

Cellular immune response following thermal injury in human patients.

Cellular immune response was studied longitudinally for a period of 1 month in a group of 51 patients sustaining burns between 20 and 55 per cent of their body surface area. The results indicated lymphocytopenia and significant depression in the total T cells in all the patients. T cells showed a significant rise in their levels in those patients who showed clinical improvement. Further, the loss of expression of 'E' receptor correlated with the lowering of the protein-synthesizing capacity of the mononuclear cells. The functional integrity of the lymphocytes also showed an inability to recognize and stimulate normal alloantigens in an MLR reaction. Investigation of the mechanisms responsible for immunosuppression revealed the generation of T suppressor activity.

Adolescent↗

Humoral and cellular immunity in atopic eczema.

Parameters of humoral and cellular immunity were measured in thirty-five patients with atopic eczema. The mean serum IgE level was raised but levels of the other major immunoglobulin classes were normal. Ten per cent of patients failed to respond to tetanus immunization. All patients responded to S. typhi H antigen. Fourteen per cent of patients failed to mount delayed hypersensitivity reactions to a battery of three intradermal antigens. The phytohaemagglutinin-stimulated uptake of 3H thymidine by lymphocytes was normal in the presence of autologous or of fetal calf serum, as was the spontaneous lymphocyte uptake. T and B lymphocyte numbers in the peripheral blood were normal. These results are similar to those found in asthmatic patients and support the hypothesis that, in some patients, atopic eczema is associated with an immunodeficiency state.

Adolescent↗

Some aspects of cellular immunity in untreated and maintenance hemodialysis patients.

The cellular pattern of skin exudate in untreated uremic patients differed from that in healthy persons. The skin exudate composition in patients on maintenance hemodialysis approached normal values. Such normalization was, however, static: after sensitization with dinitrochlorobenzene--contrary to the control--both treated and untreated patients exhibited no changes in the cellular pattern of exudate. The activity of acid phosphatase in the cells of exudate was highly positive in control, almost normal in dialyzed, but weak in untreated uremic patients. Our investigations confirmed that cellular immunity in untreated and in maintenance hemodialysis patients is suppressed.

Acid Phosphatase↗

Cellular immune responses and lymphocyte populations in chronic hepatitis.

Cellular immune responsiveness was examined in chronic persistent hepatitis, chronic active hepatitis and alcoholic liver disease by the use of the lymphocyte transformation test in response to PHA and to allogenic liver mitochondria, inhibition of leukocyte migration, delayed-type skin tests and non-immunospecific granulocyte function tests. Lymphocyte markers, E and EAC rosette forming cells were used for the study of lymphocyte populations. The results have confirmed that the T-cell borne cell-mediated immune function is impaired in chronic active hepatitis, as also in a number of cases of chronic persistent hepatitis.

Adolescent↗

[The evaluation of cellular immunity in the aged by skin tests].

UNLABELLED: Cellular immunity of persons over 60 years of age was evaluated by intradermal testing with ubiquitous antigens, such as PPD, Trichophytin, Candidine and Varidase (SK, SD-40-10 U/ml) and by skin sensitization with DNCB. The group consisted of 290 individuals, 95 men and 195 women, without any signs of disease other than the usual geriatric disturbances, such as osteoporosis, ostearthritis and mild systolic hypertension. No medication was used that could interfere with the results of the tests. The patients were divided into 2 groups, group I, 190 cases between 60 and 75 years of age, and group II, 100 cases over 75. RESULTS: Intradermal tests with all ubiquitous antigens were negative in 7,4% of group I and 13% of group II, while in a control of younger adults each had at least had 2 positive tests. This difference was mainly due to a lower sensitivity to PPD in the elder persons. 16% of group I and 23% of group II did not sensitize with DNCB. All skin tests, intradermal and DNCB, were negative in 1,1% of group I and 4% of group II. Our results suggest a decreasing immunological activity according age which could explain the higher incidence of infections, neoplasms and autoimmune diseases in old people. Also periodical repetition of the test in elderly people could evaluate immunological competence and, consequently, susceptibility to these diseases. Patients with negative tests or only one positive test, should be carefully investigated in order to exclude the existence of pathology. Our results and considerations also suggest the possibility that, by increasing immunological reactivity, the occurrence of certain diseases could the prevented.

Age Factors↗

[In vivo evaluation of cellular immunity in melanoma patients against melanoma].

Evaluation of cellular immunity against human melanoma was performed in an in vivo model using Balb/c nude mice bearing the human melanoma. Intraperitoneal injection of 1 X 10(7) melanoma cells produced peritonitis carcinomatosa which lead to death of the mice at 23.8 +/- 2.6 days (N = 12). Peripheral blood lymphocytes (PBL) from healthy donors and the melanoma cells cultured on the back of the nude mouse were given to nude mice intraperitoneally, and survival times of 22.0 +/- 2.3 days were observed (N = 8). PBL from four of the five healthy donors which have been presensitized on monolayers of the melanoma tissue culture cells in flask failed to prolong host survival times. In contrast, PBL from 15 of 20 melanoma patients were found to prolong the survival of the tumor bearing nude mice. Of these 15 patients, 8 were treated with specific active immunotherapy, but 7 had not been sensitized except by the disease process. The ability of PBL from patients to prolong survival of the melanoma bearing nude mice did not seem to correlate with either the stage of the disease or the clinical course. The possible mechanisms for the prolonged survival and the usefulness of this in vivo model were discussed.

Animals↗

Age-dependent cellular immune responses to Plasmodium vivax Duffy binding protein in humans.

The Plasmodium vivax merozoite Duffy binding protein (DBP) contains a cysteine-rich region II (DBPII) that binds to the Duffy Ag receptor for chemokines on erythrocytes, which is essential for parasite invasion. Cellular immune responses to DBPII have not been reported in P. vivax endemic populations, although they may contribute to partial acquired immunity. To examine host cellular immunity to DBPII and identify major T cell epitopes, PBMCs from 107 individuals (2-68 years old) were examined for cytokine production by ELISPOT and/or ELISA to rDBP and overlapping peptides (displaced by 2 aa spanning a 170-aa region of DBPII corresponding to the critical binding motif to the Duffy Ag receptor for chemokines). In P. vivax-exposed subjects, 60 and 71% generated significant rDBP-induced IFN-gamma and IL-10 production, respectively, 11% stimulated IL-2, and IL-5 and IL-13 were not detected. Children <5 years of age had reduced levels and frequency of rDBP-induced IL-10 and IFN-gamma production compared with partially immune older children and adults (p < 0.01). Five major T cell epitopes were identified. Three of these T cell epitopes contained polymorphic residues present in the population. Peptides synthesized corresponding to these variants induced IFN-gamma and IL-10 production to one variant and little response to the other variant in the same individual. These results demonstrate age-dependent and variant-specific cellular immune responses to DBPII and implicate this molecule in partial acquired immunity to P. vivax in endemic populations.

Adolescent↗

Stress-induced suppression of the cellular immune reactions: on the neuroendocrine control of the immune system.

Immune competence is considered as a state of equilibrium between humoral and cellular immunity. This notion fits well with the functionally antagonistic cytokine profiles in cell groups of CD4(+)-helper cells as described by Mosmann and Coffman. The Th-1 cells release mainly IL-2, IL-12 and IFN gamma and thereby stimulate the cellular immune reactions. Conversely, the Th-2 cells produce predominantly IL-4, IL-6 and IL-10, thus enhancing humoral immune reactions. Recently, it has been shown that the lymphokine profiles in Th-2 are linked to changes of the humoral balance between cortisol and dehydroepiandrosterone. These studies show that there exist states of equilibrium between T- and B-cell-mediated immune reactions, which may selectively be altered to the disadvantage of the T-cellular immunity by a stress-induced enhancement of cortisol release. In an attempt to restitute stress-induced immunosuppression, a dampening of the cortisol release hormone in the hypothalamus should, therefore, be of primary importance.

Animals↗