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PubMedDate not supplied

Disturbances of cellular immunity in rheumatic fever.

The alteration of cellular reactivity was investigated in 20 patients with rheumatic fever at the first rheumatic attack or in relapse with confirmed heart damage. The results obtained by studying in parallel ESR, the ASLO titer, IDR to streptococci and the degree of leukocyte migration inhibition proved that the onset of rheumatic attack was preceded by a deep disturbance of the cellular immunity. The migration inhibition values were between 50 and 60% (as compared with 10% in the normal controls) in over 85% of the patients investigated. It is emphasized that the selection of cases of streptococcal angina should be made very carefully and that sometimes it is necessary to use a more specific method for the detection of rheumatic fever in its preclinical stage.

Adolescent↗

PubMedDate not supplied

[Evaluation of the state of systemic and local cellular immunity using loading tests].

Local and systemic cellular immunity parameters of the blood and gastrointestinal mucosa were studied in 165 children suffering from chronic gastritis, duodenitis, celiac, secondary malabsorption syndrome, and phosphate diabetes by spontaneous E-RFC method with a number of loading tests in vitro. Thymalin, theophylline, cold incubation were used. Three types of T lymphocyte response were distinguished: the hypoergic, resistant, and hyperergic. To make the interpretation of the findings easier, coefficients were calculated for each type of response of the blood and gastrointestinal mucosa immunocompetent cells.

Adolescent↗

PubMed1999

Relation between pathologic findings and cellular immune responses in sheep with naturally acquired paratuberculosis.

OBJECTIVE: To investigate the relation between lesions and cellular immune response-based tests in sheep with naturally acquired paratuberculosis and to evaluate efficacy of an interferon-gamma (IFN-gamma) assay and the intradermal skin test. ANIMALS: 110 and 88 adult sheep were used to evaluate the IFN-gamma assay and skin test, respectively. PROCEDURE: Before euthanasia, heparinized blood was collected and incubated with avian purified protein derivative (PPD). Interferon-y production was assessed, using a commercial enzyme immunoassay. Skin testing in the caudal fold also was performed, using avian PPD. Sensitivity and specificity of these techniques were evaluated, using histopathologic findings as reference. RESULTS: Of the sheep examined, 61 (55.4%) had lesions that were classified in 5 categories, according to location, extension, cellular types, and presence of acid-fast bacilli. Regarding cellular immunity test results, 55.4% of sheep with and 6.1 % without pathologic changes had positive results of the IFN-gamma assay. Skin test sensitivity (55.6%) and specificity (100%) were slightly greater. CONCLUSION: Close association between pathologic findings and cellular immune response was apparent. Most sheep with focal (tuberculoid) and some with diffuse lesions (borderline tuberculoid), all with scant or no acid-fast bacilli in the intestine, had positive results of the IFN-gamma assay and skin test. Most sheep with diffuse lesions and high numbers of bacilli (borderline lepromatous) were test negative. CLINICAL RELEVANCE: Cellular immune response-based and serologic tests are useful tools for seeking evidence of paratuberculosis. Each technique detects different types of immune-reacting sheep, and their simultaneous use may detect most infected animals.

Animals↗

PubMed1982

Cellular immunity during follow-up of patients with sarcoidosis of varying duration.

Cellular immunity was followed up at 3 month intervals for 1 year in 43 patients with sarcoidosis representing three well defined categories of the disease viz acute (12), subacute (20) and chronic (11). Twelve apparently healthy individuals served as controls. Each follow-up included the following tests: total number of blood lymphocytes, T cells, B cells, leucocyte migration tests with PPD, BCG and Kveim test material and stimulation tests of lymphocytes in vitro in the presence of PHA, Con A, PPD and PWM. Statistically, the most abnormal initial findings in all the tests were noted in acute sarcoidosis, followed by the subacute group. The acute group showed the most marked changes also during the follow-up. The smallest changes during the follow-up were seen in the patients with the chronic form of the disease. However, the inter-individual variation was considerable and no definite conclusions could be drawn from findings in a given case. Alterations in cellular immunity occur in sarcoidosis. They differ between different subgroups of patients and vary differently in course of time. Well defined criteria for inclusion of patients in an investigation and repeated studies of included patients will increase the information available from investigations of cellular immunity in sarcoidosis.

Acute Disease↗

PubMed1992

Cellular immunity of patients with recurrent or refractory vulvovaginal moniliasis.

Cellular immunity was studied in 73 patients with recurrent vaginal moniliasis and 37 healthy controls, by skin testing with the multitest CMI kit and Candida antigen, with measurement of lymphoblastic transformation to phytohemagglutinin, antigens of Candida albicans, mumps, and streptokinase. Eighteen patients (24.7%) had a hypoergic or anergic response to Candida antigen on skin testing versus two controls (5.4%), p = 0.01. Overall, the patient's lymphoblastic proliferation to mitogen and various antigens was not significantly different from that of the controls. However, a subgroup of younger women (19 to 29 years old) had impaired responses to Candida antigen when compared with age-matched controls, 58% versus 17%, p less than 0.005. Most women with current vaginal moniliasis had normal cellular immunity.

Adult↗

PubMed1996

[Clinical usefulness of Multitest in the evaluation of cellular immunity].

The aim of this work was to assess cellular immunity using the Multitest CMI and relate its results with lymphocyte counts and lymphocyte subpopulations determined using monoclonal antibodies against CD4 and CD8 and fluorescence microscopy. We studied 51 patients (31 male), 20 infected with HIV, 18 recurring infections, 5 with cancer, 2 with tuberculosis and 6 with miscellaneous diagnoses. According to Multitest results, patients were classified as normal, hypoergic or anergic. Twenty five percent of patients were normal, 65% hypoergic and 10% anergic. Eighty percent of anergic patients were infected with HIV. No differences in total lymphocyte count were observed between the three groups. CD4 lymphocyte count was lower in anergic patients when compared with the other two groups. All patients with CD4 counts below 200 cells/mm3 were anergic. It is concluded that Multitest CMI is useful for the assessment of cellular immunity and complements the determination of lymphocyte subpopulations.

Adult↗

PubMed1975

Impaired anamnestic cellular immune response in patients with Crohn's disease.

The cellular immune system was studied in patients with Crohn's disease (CD), not receiving corticosteroids, or azathioprine, by means of in vitro and in vivo methods. It was found, that the in vitro lymphocyte reactivity of 54 CD patients after stimulation with a cocktail of antigens (varidase, trichophyton, candida, mumps, and PPD) was significantly depressed when compared with the response of 20 simultaneously cultured healthy controls (p less than 0-001) or a group of 54 separately cultured healthy controls, matched for age and sex (p less than 0-001). The lymphocyte response of a control group of 18 patients with malnutrition or malabsorption without any evidence of inflammatory bowel disease, was higher than the response of an equal number of CD cases, although the difference failed to reach significance. Intradermally injection of the same five antigens, as used in the antigen cocktail, showed a failure to react to any antigen in 13 out of 48 CD patients, in comparison with three of 48 matched healthy controls (p less than 0-01). In both CD patients, as well as in healthy controls a significant correlation could be demonstrated between the number of positive skin tests, the area of skin induration, and the in vitro lymphocyte responsiveness after stimulation with the antigen cocktail. In the CD group no correlation was found between in vitro responsiveness and disease activity, as defined by a score of clinical and biochemical parameters. The depressed skin reactivity and the hyporesponsiveness in the lymphocyte transformation test after stimulation by an antigen cocktail suggest that depression of the anamnestic cellular immune response is a basic feature in patients with Crohn's disease.

Adolescent↗

PubMed2005

Lysophosphatidylcholine is a natural adjuvant that initiates cellular immune responses.

The discovery of new adjuvants that can stimulate the immune response to protein antigens is a major issue for the development of subunit vaccines. Lipoprotein oxidation occurring during the acute phase response (APR) to aggression of the organism, provides signals of danger that are detected by dendritic cells (DC). Among other instructive molecules generated during the APR, lysophosphatidylcholine (LPC) promotes mature DC generation from differentiating human monocytes in vitro. It is shown here that LPC also controls the initiation of an adaptive immune response in vivo. LPC displays adjuvant properties when injected to mice in mixture with various antigens. Immunizations with LPC induced the production of antigen-specific antibodies with an efficiency similar to Alum, the reference adjuvant for human vaccination. Importantly, LPC also induced cytotoxic T cell responses, opening perspectives for vaccine development. Therefore, LPC is a natural adjuvant for the immune system, inducing humoral and cellular immune responses.

Adjuvants, Immunologic↗

PubMedDate not supplied

Immunosuppressive activity of an isoxazolo[5,4-e]triazepine--compound RM33. I. Effects on the humoral and cellular immune response in mice.

The aim of this investigation was to evaluate immunotropic properties of a new isoxazolotriazepine (compound RM33) in mice. We found that RM33 significantly inhibited induction of the humoral immune response to sheep red blood cells (SRBC), given 2 h prior to immunization. The development of the cellular immune response (delayed type hypersensitivity--DTH) to SRBC and to ovalbumin (OVA) was also suppressed, as well as the effector phase of the DTH to OVA. The compound was also effective when administered per os. The suppressive effects of RM33 on the immune response were comparable to those of cyclosporine A(CsA). We also showed that RM33 inhibited DTH to OVA if admixed with the sensitizing dose of an antigen and complete Freund's adjuvant (cFa) suggesting that the compound may affect initial events of antigen presentation. Such a hypothesis was supported by finding that RM33 significantly inhibited foot pad edema elicited by administration of cFa. The effects of RM33 on the activities of cytokines relevant to development and control of the immune response and inflammation such as: tumor necrosis factor alpha (TNF-alpha), interleukin 6 and 10 (IL-6 and IL-10) were also studied. The compound markedly (by 63%) inhibited lipopolysaccharide (LPS)-induced TNF-alpha serum level whereas IL-6 activity was lowered to a lesser extent (by 17%). The inducible IL-10 level in the splenocyte cultures was not affected at all. In summary, the presented results revealed immunosuppressive properties of RM33, which could be associated with its selective interference with co-stimulatory signals provided by adjuvant at initiation of the immune response.

Adjuvants, Immunologic↗

PubMed1998

Cellular immune responses to beta casein: elevated in but not specific for individuals with Type I diabetes mellitus.

Elevated cellular immune responses against the cows' milk protein beta casein have been reported in individuals with Type I diabetes mellitus, a finding supportive of the concept that cows' milk consumption may be causative for the disease. We analysed cellular immune reactivities against beta casein in newly-diagnosed Type I diabetic patients, their immediate autoantibody negative relatives, and unrelated healthy individuals in order to further elucidate the role of anti-beta casein immunity in the pathogenesis of Type I diabetes mellitus. Peripheral blood mononuclear cells were stimulated in vitro with various concentrations of three different beta casein preparations, control antigens (tetanus toxoid, mumps extract) and a mitogen (phytohemagglutinin). The frequency and/or mean simulation index of cellular proliferation against two of the beta casein preparations at high antigen concentrations (i.e. 10 or 50 microg/ml) were significantly higher in newly-diagnosed Type I diabetic subjects compared with autoantibody negative healthy control subjects. However, reactivities against beta casein in the Type I diabetic probands and their autoantibody negative relatives, individuals with a very low-rate of disease development, were almost identical. Cellular immune reactivities to other antigens were similar between the subject groups. In addition to indicating the need for appropriately matched subject populations (e.g. human leukocyte antigen (HLA) matched relatives) when analysing cellular immune responses, these findings support our previous contention that individuals genetically prone to autoimmunity may be deficient in forming tolerance to dietary antigens. However, the significance of anti-beta casein immunity as a specific causative factor in the pathogenesis of Type I diabetes mellitus remains unclear.

Adolescent↗

PubMed2004

Recombinant viruses as tools to induce protective cellular immunity against infectious diseases.

Infections by intracellular pathogens such as viruses, some bacteria and many parasites, are cleared in most cases after activation of specific T cellular immune responses that recognize foreign antigens and eliminate infected cells. Vaccines against those infectious organisms have been traditionally developed by administration of whole live attenuated or inactivated microorganisms. Nowadays, research is focused on the development of subunit vaccines, containing the most immunogenic antigens from the particular pathogen. However, when purified subunit vaccines are administered using traditional immunization protocols, the levels of cellular immunity induced are mostly low and not capable of eliciting complete protection against diseases caused by intracellular microbes. In this review, we present a promising alternative to those traditional protocols, which is the use of recombinant viruses encoding subunit vaccines as immunization tools. Recombinant viruses have several interesting features that make them extremely efficient at inducing immune responses mediated by T-lymphocytes. This cellular immunity has recently been demonstrated to be of key importance for protection against malaria and AIDS, both of which are major targets of the World Health Organization for vaccine development. Thus, this review will focus in particular on the development of new vaccination protocols against these diseases.

Adenoviridae↗

PubMed2001

Genetic immunization of wild-type and hepatitis C virus transgenic mice reveals a hierarchy of cellular immune response and tolerance induction against hepatitis C virus structural proteins.

To study the effect of genetic immunization on transgenic expression of hepatitis C virus (HCV) proteins, we evaluated the immunological response of HCV transgenic mice to HCV expression plasmids. FVB/n transgenic mice expressing HCV structural proteins (core, E1, and E2) and wild-type (WT) FVB/n mice were immunized intramuscularly with plasmids expressing core (pHCVcore) or core/E1/E2 (pHCVSt). After immunization, HCV-specific humoral and cellular immune response was studied. Both WT and transgenic mice immunized with either HCV construct produced antibodies and exhibited T-cell proliferative responses against core or envelope. In WT mice immunized with pHCVSt, cytotoxic T-lymphocyte (CTL) activities were detected against E2 but not against core or E1, whereas strong CTL activities against core could be detected in WT mice immunized with pHCVcore. In pHCVSt-immunized, transgenic mice, CTL activities against the core or envelope were completely absent, but core-specific CTL activities could be detected in pHCVcore-immunized transgenic mice. A similar pattern of immune responses was also observed in other mouse strains, including a transgenic line expressing human HLA-A2.1 molecules (AAD mice). Despite the presence of a peripheral cellular immunity against HCV, no liver pathology or lymphocytic infiltrate was observed in these transgenic mice. Our study suggests a hierarchy of CTL response against the HCV structural proteins (E2 > core > E1) in vivo when the proteins are expressed as a polyprotein. The HCV transgenic mice can be induced by DNA immunization to generate anti-HCV antibodies and anticore CTLs. However, they are tolerant at the CTL level against the E2 protein despite DNA immunization.

Adoptive Transfer↗

PubMed1987

Uveitis induced in primates by IRBP: humoral and cellular immune responses.

In a previous publication, we have reported that immunization with bovine interphotoreceptor retinoid-binding protein (IRBP) produces severe uveitis in monkeys. The present study further examined the uveitogenicity of IRBP and analysed the immune responses in the immunized monkeys. Uveitis developed in monkeys immunized with bovine IRBP at doses as low as 10 micrograms Kg-1 body wt. In contrast, no disease was detected in monkeys immunized with monkey IRBP at the total dose of 100 micrograms Kg-1. Serum antibodies were measured in the immunized monkeys by the enzyme-linked immunosorbent assay, while cellular immunity was determined by skin hypersensitivity and the lymphocyte mitotic reaction in culture. No humoral or cellular immune responses were detected in monkeys immunized with monkey IRBP. Monkeys immunized with bovine IRBP produced antibodies which cross-reacted well with monkey IRBP. On the other hand, these monkeys did not react with monkey IRBP by skin hypersensitivity and their lymphocytes responded in culture to this protein only when tested by a highly sensitive procedure. In contrast, significant responses of the same cells to bovine IRBP were obtained at all tested conditions. These data are interpreted to suggest that the pathogenic cellular immune responses in vivo detect cross-reactivity with this autologous ocular antigen more efficiently than most conventional laboratory tests.

Animals↗

PubMed1998

The cellular immune response to Bordetella pertussis in two children with whooping cough.

There is increasing evidence that the cellular immune response to Bordetella pertussis plays an important role in the immune protection. Particularly in animal models, Bordetella pertussis-specific T-cells have been shown to confer immunity. In this case report, we therefore investigated the cellular immune response to whole cell Bordetella pertussis bacteria, to the pertussis antigens filamentous hemagglutinin and pertussis toxoid defined by lymphoproliferation and cytokine secretion. Two children with whooping cough were compared to three individuals vaccinated against whooping cough with a whole cell pertussis vaccine. In contrast to the vaccinated controls, the cellular immune response to Bordetella pertussis in children with whooping cough was characterized by a strong proliferation of T cells to whole pertussis bacteria as well as to filamentous hemagglutinin and pertussis toxoid. This response was defined by a marked Th-1 type T cell response with IFN-gamma secretion to all Bordetella pertussis antigens. However, in the control individuals IFN-gamma was secreted only to whole cell Bordetella pertussis bacteria and filamentous hemagglutinin but not to pertussis toxoid. A Th-2 type cytokine response could not be detected in any condition. Our observations suggest that in the immune defense of a natural Bordetella pertussis infection, the Th-1 specific T cell response to filamentous hemagglutinin and particularly to pertussis toxoid may play a major role.

Adhesins, Bacterial↗

PubMed1975

Cellular immune responses to methylcholanthrene-induced fibrosarcoma in BALB/c mice.

Several in vitro parameters of cellular immunity were examined in BALB/c mice with an experimentally induced fibrosarcoma tumor. The results of capillary migration of spleen cells in high tumor cell dose inoculated mice show appearance of cellular immune response in the early stages of the tumor growth. As the tumor progresses, the cellular response declines and rapidly disappears, culminating in stimulation values near the time of the death of these mice. The blastogenic studies also show early cellular recognition of tumor antigen by mouse spleen cells and whole blood (Z24 h). After the 2nd day following tumor injection, no blast transformation is noted. However, the results obtained with a lower inoculating tumor cell dose demonstrate an initial cellular recognition on the 7th day. This response gradually disappears by the 19th day and remains negative up to the time of the death of these mice. This cellular immunity was confirmed by the cytotoxic experiments showing that the primary cells responsible for this cellular reactivity were the immune cells. An interesting finding was the presence of a factor(s) capable of blocking the cytotoxic effect. The nature and mechanism of this blocking factor(s) is now under investigation.

Animals↗

PubMed1978

Cellular immunity in Guamanians with amyotrophic lateral sclerosis and Parkinsonism-dementia.

To test the hypothesis that host resistance factors may be abnormal in Guamanians in whom amyotrophic lateral sclerosis and Parkinsonism-dementia develop, cellular immunity was evaluated in both diseases and compared to that of Guamanians with other nervous-system diseases, normal adult Guamanians and non-Guamanians with amyotrophic lateral sclerosis and Parkinsonism. Diminished responses to skin-test antigens, lymphopenia, diminished per cent and total T cells and, less frequently, decreased mitogen responses were seen in Guamanian patients with amytorophic lateral sclerosis and Parkinsonism-dementia but not in the other patient or normal groups. Guamanian patients with amyotrophic lateral sclerosis and diminished cellular immunity had an increased frequency of HLA-Bw35 (P less than 0.005) and shorter mean duration of disease (P less than 0.05) than those with normal cellular immunity. In Parkinsonism dementia diminished cellular immunity was less strongly associated with HLA-BW35 (P less than 0.05) and was not associated with differences in duration of disease. Normal Guamanians and those with other nervous-system diseases showed no association of diminished cellular immunity with HLA-Bw35. The association appeared disease-related, with onset concomitant with the neurologic expression of Guamanian amyotrophic lateral sclerosis and Parkinsonism-dementia.

Adult↗

PubMed2001

Dehydroepiandrosterone decreases mortality rate and improves cellular immune function during polymicrobial sepsis.

OBJECTIVE: Sepsis is associated with a marked depression of cellular immune function. The steroid hormone dehydroepiandrosterone (DHEA) is proposed to have immunoenhancing activities. We, therefore, investigated the effect of DHEA on the mortality rate and cellular immune functions in an experimental model of sepsis. DESIGN: Randomized animal study. SETTING: Level I trauma center, university research laboratory. SUBJECTS: Male NMRI mice. INTERVENTIONS: Mice were subjected to laparotomy (sham) or cecal ligation and puncture (CLP). Mice were treated with (sham/DHEA; CLP/DHEA) or without (sham; CLP) the steroid hormone DHEA (30 mg/kg sc). Animals were killed 48 hrs after the onset of sepsis. MEASUREMENTS AND MAIN RESULTS: The survival rate of septic mice was determined 24 and 48 hrs after onset of sepsis. Forty-eight hours after the septic challenge, a white blood cell count was performed and serum tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta concentrations were monitored using ELISA. Furthermore, the delayed type of hypersensitivity (DTH) reaction was evaluated on the basis of ear pinna swelling after dinitrofluorobenzene (DNFB) administration, and clinical variables (body weight, temperature, heart rate, fluid input/output, food intake) were monitored using metabolic cages. DHEA administration improved the survival rate (87% vs. 53% after 48 hrs; p <.001). This was accompanied by a restoration of the depressed DTH reaction and a reduction in TNF-alpha serum concentrations (20.7 +/- 1.4 pg/mL vs. 32.4 +/- 6.6 pg/mL). CONCLUSIONS: These results demonstrate that DHEA administration leads to an increased survival following a septic challenge. The immunoenhancing effect of DHEA is accompanied by a reduction of TNF-alpha release and an improved activity of T-cellular immunity. DHEA administration may, therefore, be beneficial in systemic inflammation.

Adjuvants, Immunologic↗

PubMed1991

Severe head injury: effect upon cellular immune function.

Infection is a major cause of morbidity following severe head injury. Although investigations have demonstrated central nervous system modulation of immune function, the effects of severe head injury on immune activity have not been well documented. This study prospectively investigated cellular immune function in 20 patients with isolated severe head injury. In vivo cellular immune status was determined by responses to delayed-type hypersensitivity (DTH) skin tests. In vitro studies included the effect of the lymphocyte mitogen, phytohaemagglutinin (PHA), on peripheral blood lymphocyte (PBL) phenotype expression and PBL blastogenesis. DTH skin testing demonstrated anergy to all antigens used during the first two weeks following head injury. Analysis of PBLs incubated with PHA demonstrated a decrease in the percent of PBL blastogenesis (p = 0.002), the percentage of cells marking as T-cells (p = 0.018), helper T-cells (p less than 0.001) and those expressing interleukin-2 receptors (p less than 0.001). There was a significant increase in the percentage of cells that marked as monocytes (p = 0.030), whereas there was no significant change in the percentage of B-cells, suppressor/cytotoxic T-cells, natural killer cells or in cells expressing the HLA-DR antigen. The infection rate was 55% with most occurring within 5 days of injury. The results of this study suggest that isolated severe head injury causes suppression of cellular immunity. The decrease in PHA stimulated PBL blastogenesis, helper T-cell phenotypic and interleukin-2 receptor expression, suggests suppression in early helper T-cell activation may be responsible for the high incidence of infection following severe head injury. The possible significance of increased monocyte phenotypic expression is discussed.

Adolescent↗