Cellular immunity in chronic Chagas'' disease.

The cellular immune response was assessed in 20 patients with chronic Chagas' disease (American trypanosomiasis). Thymus-derived lymphocyte function was determined in vivo by cutaneous reactivity to several antigens including a soluble preparation derived from Trypanosoma cruzi and sensitization to 2,4-dinitrochlorobenzene. The in vitro T-cell reactivity was investigated by the proliferative response to phytohemagglutinin and to T. cruzi antigen and by inhibition of leukocyte migration with the specific antigen. In addition, the proportion and absolute numbers of peripheral blood T and B-lymphocytes were determined by rosette formation. This research indicates that the general and specific cellular immune response, evaluated by the tests herein mentioned, is well preserved in patients, with Chagas' disease. We conclude that chronic Chagas' disease is not associated with deficiency in cellular immunity, nor does it lead to it. Conceivably, the active participation of delayed hypersensitivity may play an important role in the expression of the human chagasic lesions.     

Cellular immunity in patients with psoriasis

The angiotensin converting enzyme activity was determined in a dog's plasma in the course of an irreversible hemorrhagic shock development. A statistically significant increase of the angiotensin converting enzyme activity in the plasma was found after one hour and two hours' duration of posthemorrhagic hypotension. After one hour and two hours' duration of posthemorrhagic hypotension the plasma angiotensin converting activity was higher by 29% and 33%, respectively, compared with the control levels determined in the normotensive period. After three hours' duration of posthemorrhagic hypotension the plasma activity of the angiotension converting activity was even more evident. In these conditions the plasma enzyme activity was increased by 71% compared to the control levels. The results obtained indicate the possibility that certain changes occur at the endothelial level of pulmonary blood vessels during the hemorrhagic shock development. These changes suggest an intense angiotensin converting enzyme release into the systemic circulation. The results of this investigation are a contribution to a better understanding of the renin-angiotensin system in shock conditions.     

Studies of cellular and humoral immunity in typhoid fever and TAB vaccinated subjects.

An assessment of both humoral and cell-mediated immune responses to Salmonella typhi antigens in patients with acute typhoid infection, TAB inoculated subjects and in healthy controls is reported. Cell-mediated immunity as assessed by the leucocyte migration inhibition test (LMI), and developed in all cases with typhoid fever. Positive LMI was evident in the first week of the illness and was maintained during the evolution of disease and in some patients was still present after a year. It also developed at the end of 3 weeks in five out of nine TAB vaccinated subjects. Weakly positive LMI was noticed in only two of twenty asian and caucasian controls. Antibodies, determined by the standard Widal test, were significantly raised in both patients with typhoid fever and TAB inoculated subjects. The antibodies and cellular reactivity developed almost simultaneously but there was no correlation between the agglutination titres and LMI positivity, implying that they are independent of each other. Typhoid patients also showed significantly raised serum IgM and IgA levels and increased concentrations of secretory IgA in their saliva.     

Protection against meningococcal serogroup ACYW disease in complement-deficient individuals vaccinated with the tetravalent meningococcal capsular polysaccharide vaccine

Individuals with properdin, C3 or late complement component deficiency (LCCD) frequently develop meningococcal disease. Vaccination of these persons has been recommended, although reports on efficacy are scarce and not conclusive. We immunized 53 complement-deficient persons, of whom 19 had properdin deficiency, seven a C3 deficiency syndrome and 27 had LCCD with the tetravalent (ACYW) meningococcal capsular polysaccharide vaccine. Serological studies were performed in 43 of them. As controls 25 non-complement-deficient relatives of the complement-deficient vaccinees and 21 healthy non-related controls were vaccinated. Post-vaccination, complement-deficient individuals and controls developed a significant immunoglobulin-specific antibody response to capsular polysaccharides group A, C, Y, W135, but a great individual variation was noticed. Also, the proportion of vaccinees of the various vaccinated groups with a significant increase in bactericidal titre (assayed with heterologous complement) was similar. Opsonization of meningococci A and W135 with sera of the 20 LCCD individuals yielded in 11 (55%) and eight (40%) sera a significant increase of phagocytic activity after vaccination, respectively. Despite vaccination, four complement-deficient patients experienced six episodes of meningococcal disease in the 6 years post-vaccination. Four episodes were due to serogroup B, not included in the vaccine. Despite good response to serogroup Y upon vaccination, disease due to serogroup Y occurred in two C8β-deficient patients, 3.5 and 5 years post-vaccination. These results support the recommendation to vaccinate complement-deficient individuals and to revaccinate them every 3 years.     

Cross-reacting serum opsonins in patients with meningococcal disease.

We have examined the opsonic activity of sera from patients with Neisseria meningitidis (B:15:P1.16) infections against different meningococcal strains, using flow cytometry and luminol-enhanced chemiluminescence. A marked increase in the phagocytosis of ethanol-fixed meningococcal strains of different serogroups, serotypes, and serosubtypes was demonstrated in the presence of convalescence sera compared with acute sera. Convalescence sera also caused a significant increase of leukocyte oxidative metabolism during phagocytosis, as measured by luminol-enhanced chemiluminescence. The sera contained a broad range of opsonins cross-reacting with serogroup A, B, C, W-135, and Y meningococci of different serotypes and serosubtypes, indicating that the cross-reacting opsonins recognized surface epitopes other than those determined by current serotyping schemes.     

Cellular immunity and herpesvirus infections in cardiac-transplant patients.

We observed severe infection with herpes simplex virus in cardiac-transplant patients despite their high serum antibody levels to this virus. Therefore, we sought to correlate clinical susceptibility to two herpesvirus (simplex and zoster) infections with specific cellular immunity, assessed by the transformation and interferon responses of peripheral blood mononuclear cells to heat-inactivated antigens. Transformation and interferon response to herps simplex virus was maximally depressed immediately after transplantation, the time when severe and prolonged infection with herps simplex virus occurred. Six months to six years after transplantation, both clinical susceptibility and cellular immunity to herpes simplex virus were normal. Herpes zoster infections were more frequent than normal at all times after cardiac transplantation; depressed or absent cellular responses to the varicella zoster virus paralleled that susceptibility. In these patients the risk of severe herpesvirus infections correlated with depressed cellular immune responses to the specific viral agent involved.     

Cellular immunity in SSPE patients

In vivo andin vitro tests were performed to detect any immunological abnormalities in SSPE patients (n=15). An unexpected high incidence of skin test anergy (about 40%) against 5 common skin test antigens was observed (candidin, streptokinase-streptodornase, mumps, PPD, trichophytin). All of these patients could, however, be successfully sensitized to 2,4-dinitrochlorbenzene (DNCB).Other screening tests suggest that SSPE patients have normal subpopulations of lymphocytes in peripheral blood.Specific cellular immunity was demonstrated by lymphocyte-mediated cytotoxicity against [⁵¹Cr]-labelled target cells persistently infected with measle virus. Lymphocytes from all SSPE patients gave a vigorous response.These results do not confirm Burnet's theory (Burnet, 1968) that SSPE patients have a specific defect of cell-mediated immunity against measles virus.Supported by the Deutsche Forschungsgemeinschaft, AZ Me 270/10.Presented at the workshop on molecular and pathogenetic aspects of measles virus, 9./11. April 1974, Belfast, Northern Ireland.     

Cellular immunity in patients with systemic juvenile rheumatoid arthritis

We studied the cellular immune responses in 10 patients with systemic form of juvenile rheumatoid arthritis. The numbers of peripheral T lymphocytes and their helper/inducer and cytotoxic/suppressor subpopulation were within normal levels. Activated T lymphocytes (DR+) were slightly increased but not at statistically significant levels. In contrast to the T cells, B lymphocytes were increased; both the percentage of B cells (B1+) and the number of cells spontaneously secreting IgG, IgA, and IgM were increased. Stimulation of peripheral mononuclear cells in vitro with pokeweed mitogen induced poor plaque-forming cell responses, which were partially improved upon removal of monocytes. The presence of concanavalin A in the cultures led to complete suppression. We conclude that patients with systemic JRA are characterized primarily by B-cell rather than T-cell abnormalities.     

Colostral immunity in piglets from sows vaccinated with inactivated Aujeszky disease virus vaccine

Neutralizing antibodies against ADV were transmitted from sows, vaccinated with inactivated ADV adjuvanted with DEAE dextran, to their offspring via colostrum. The suckling piglets were protected by colostral immunity against contact infection with ADV at week 1 p.p., however, they were not protected against i.n. infection (10(8) TCD50). At 2 and 3 weeks p.p. all the piglets were protected against both contact infection and i.n. infection. At 4 weeks p.p. 50 per cent of the litter were protected against i.n. infection, in spite of very low antibody titres (1:2--1:4). The colostral antibodies did not interfere with active antibody response when the piglets were vaccinated with the inactivated vaccine from 2 weeks p.p. onward. Lymphocytes from suckling piglets of a vaccinated sow showed in vitro reactivity (enhanced 3H-thymidine incorporation) against ADV and BHK antigen, both contained in the vaccine used for the immunization of the sow.     

Cellular immunity in asbestosis.

A highly statistically significant correlation was found between asbestosis and impaired responsiveness in skin reaction to intermediate and second strength tuberculin and SK-SD. Considering ANA incidence these antibodies were found with higher frequency in asbestos workers who lacked a cutaneous response to the recall antigens. In asbestosis cases peripheral blood lymphocyte profiles are also abnormal demonstrating low proportions of E-RFC. Moreover, MIF test results showed the impairment of this cytokine generation when lymphocytes were stimulated with SK-SD, PPD and PHA in asbestosis cases. The lymphocyte transformation study documents an impaired response mainly to a lower dose of PHA and ConA in asbestosis cases and in asbestos workers with ANA.     

Cell-mediated immunity in mice vaccinated against malaria.

Mice vaccinated with a formalin-fixed preparation of either Plasmodium berghei or P. yoelli exhibited delayed type hypersensitivity (DTH) to the homologous antigen. This manifested itself in increased delayed thickening of antigen-challenged pinnae of the vaccinated mice as compared to the non-vaccinated controls. DTH was also evident in the vaccinated mice using the homing of radio-labelled bone marrow cells (BMC) to the delayed lesion as a criterion of reactivity. When P. yoelii vaccinated mice were given a live infection P. yoelii, a marked migration of BMC into the spleen occurred, with a peak at 48 hr, and it is suggested that this was a systemic response of DTH. The splenic T-cells of P. yoelii-vaccinated animals transformed in vitro with a soluble extract of the homologous parasite. The potential function of cell-mediated mechanisms in immunity to malarial infections is discussed.     

Cellular immunity and IgE levels in atopic patients

Twenty young adult atopic patients and their matched controls were studied. Spontaneously generated and Con-A-induced suppressor T cell functions as well as Natural Killer (NK) activity against K-562 target cells, measured in a short-time 3H-thymidine uptake, were evaluated. Suppressor T cell activity in the patients was more than 2 SD lower than that found in the controls and there was, contrary to expectation, a direct correlation between suppressor function and serum IgE levels. Atopic patients showed a statistically significant lower NK activity than normal controls when related to a low IL-2 production. Both facts inversely correlated with the concentration of IgE in serum. We concluded that atopic patients' vulnerability to viral infections may be due to defective NK activity. Suppressor T cell function is abnormal in these patients. Both defects could be due to a faulty immunoregulatory helper function.     

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.     

Cell-mediated immunity in patients with chronic fatigue syndrome, healthy control subjects and patients with major depression.

The chronic fatigue syndrome (CFS) is characterized by severe persistent fatigue and neuropsychiatric symptoms. It has been proposed that the abnormalities in cell-mediated immunity which have been documented in patients with CFS may be attributable to a clinical depression, prevalent in patients with this disorder. Cell-mediated immune status was evaluated in patients with carefully defined CFS and compared with that of matched subjects with major depression (non-melancholic, non-psychotic) as well as healthy control subjects. Patients with CFS demonstrated impaired lymphocyte responses to phytohaemagglutinin (PHA) stimulation, and reduced or absent delayed-type hypersensitivity (DTH) skin responses when compared either with subjects with major depression or with healthy control subjects (P less than 0.05 for each analysis). Although depression is common in patients with CFS, the disturbances of cell-mediated immunity in this disorder differ in prevalence and magnitude from those associated with major depression. These observations strengthen the likelihood of a direct relationship between abnormal cell-mediated immunity and the etiology of CFS.     

Dynamics of PCR-based diagnosis in patients with invasive meningococcal disease

Invasive meningococcal disease continues to be a life-threatening condition and rapid diagnosis is important for the administration of appropriate treatment. This study focused on the use of PCR for the diagnosis of meningococcal aetiology and the dynamics of PCR-based diagnosis over time in various biological samples. Sixty cerebrospinal fluid (CSF) and 144 serum samples collected during the first week of hospitalisation from 37 patients with laboratory-confirmed invasive meningococcal disease were investigated. Overall, 91.9% of CSF samples and 45.9% of serum samples were PCR-positive, while culture of CSF and blood was positive for only 35% and 39% samples, respectively. Positive PCR results were obtained until day 7 with CSF and until day 5 with serum. It is therefore recommended that samples for molecular diagnosis should be collected early in the course of suspected invasive meningococcal disease.     

Cellular immunity in pediatric uveitis.

To evaluate cellular immunity in children with uveitis, we used the flow cytometry method to study the T lymphocyte subpopulation in peripheral blood. Cytometric analysis of peripheral blood lymphocytes using fluorochrome-marked monoclonal antibodies was carried out in 29 children aged 6-18 years with parasitic uveitis (group A) and with uveitis of another etiology (group B). The control group consisted of 28 healthy children aged 6-15 years. A substantially higher percentage of B lymphocytes (19.0 +/- 6.03) was observed in the children with parasitic uveitis than was observed in the healthy children. Moreover, the absolute values were higher in groups A (1.60 +/- 0.53) and B (1.81 +/- 0.40) than in controls (1.50 +/- 0.38). The lowest percentage of CD4+ lymphocytes (34.25 +/- 6.06) and the highest percentage of CD8+ lymphocytes (31.14 +/- 6.50) was found in children with parasitic uveitis. The lowest index CD4+/CD8+ (1.29 +/- 0.53) in the group of children with parasitic uveitis reflected severe disorders in response regulation. However, the percentage values of natural killer cells was lower in the two groups of patients than in controls. These results suggest that quantitative changes in the subpopulation of peripheral blood lymphocytes are more pronounced in parasitic uveitis.