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PubMed1976

Capillary tube leukocyte adherence inhibition: an assay for cell-mediated immunity in cancer patients.

The leukocyte adherence inhibition (LAI) assay has been modified and automated in order to facilitate its clinical application. This new assay-the capillary tube LAI test-correlated with delayed cutaneous hypersensitivity using streptokinase-streptodornase antigen in 83% of the cases. When tested with a 3 M KC1 lung carcinoma antigen, lung carcinoma patients' leukocytes were more frequently inhibited (55%) than those of controls (normals 6%, other tumors 20%).

Antibodies, Neoplasm↗
PubMed1976

An examination of the immunology of cancer patients.

We have examined 111 cancer patients and 111 control individuals for general immunocompetence (haematological values, "recall" antigen skin tests, PHA and PPD induced lymphocyte transformation, serum Ig levels and lymphocyte subpopulations), for evidence of sensitisation to tumour-associated antigens (leucocyte migration test, serum inhibition of autologous leucocyte migration, lymphocytotoxicity, membrane immunofluorescence and immune adherence) and for evidence of continuing immune reactions (alterations of complement components and anticomplementary activity). Major differences between the cancer patients and controls were demonstrated by several tests of sensitisation and these also detected differences between patients with and without metastases. The only differences detected between cancer patients and controls by the tests of general immunocompetence were in serum IgG and IgA (higher in the cancer patients) and lymphocyte subpopulations ("active" T, autorosetting lymphocytes and lymphocytes forming "super-rosettes" increased in cancer patients). In a comparison of cancer patients with and without metastases, patients with metastases were less often reactive to the Candida DHS and streptokinase-streptodornase antigens and had raised circulating Fc positive cells. Abnormalities of the individual components of complement occurred in about half the cancer patients, but were equally common in those with and without metastases. Serum anti-complementary activity was very rarely detected. The tests of specific sensitisation correlated reasonably well but correlations of tests of general immunocompetence were infrequent.

Adolescent↗
PubMed1992

Delayed hypersensitivity skin tests in prognosis of human immunodeficiency virus infection.

Delayed hypersensitivity skin tests (DHST) with recall antigens were investigated as prognostic markers in five different approaches. In the first study, 42 acquired immunodeficiency syndrome (AIDS) patients (IVb, IVcl, IVd, and IVe; MMWR 35:334-339, 1986) 26 AIDS-related complex (ARC) patients (IVa and IVc2), and 98 asymptomatic patients (II and III) were evaluated with candidin, tricophytin, PPD and streptokinase-streptodornase. In the second study, 10 patients (II and III) were evaluated sequentially with the same antigens. In the third, 45 patients with at least two positive skin tests ("reactors") were followed for one year and evaluated every 6 months with the same antigens. In the fourth, 16 "reactors" were followed and evaluated every 3 months with the same antigens. We measured the interval from the time at which patients first presented with only one or no positive DHST until the development of ARC or AIDS. In the last study, the correlation between absolute number of CD4+ lymphocytes and the number of DHST was studied in 151 patients. We found that the decrease in reactiveness to DHST correlated directly with the progression to AIDS, demonstrating the usefulness of this simple procedure as a valid prognostic marker.

AIDS-Related Complex↗
PubMed1979

The absence of differences in cellular immunity in elderly individuals with and without delayed local cutaneous reactions to influenza vaccine.

Two groups of elderly subjects who received bivalent influenza virus vaccine were identified. Those in Group I manifested marked local reactions, suggestive of delayed hypersensitivity reactions, whereas those in Group II, matched with Group I for vaccine preparation, had no cutaneous reactions. In vitro assays of immune function were performed on pairs of subjects from the two groups and included serum immunoglobulin and complement levels, antibody response to vaccine, lymphocyte transformation to mitogens (phytohemagglutinin, pokeweed mitogen and concanavalin A) and antigens (streptokinase-streptodornase, influenza virus vaccine antigens and multiple mixed lymphocytes), and polymorphonuclear leukocyte chemotactic responsiveness. There was no demonstrable correlation between delayed local cutaneous reaction and preservation of in vitro cell-mediated immune function in these elderly individuals.

Age Factors↗
PubMed1986

Functional heterogeneity of human antigen-presenting cells: presentation of soluble antigen but not self-Ia by monocytes.

These studies were undertaken to examine the phenotype of the antigen-presenting cells (APC) circulating in human peripheral blood. Cells adherent to glass were found to be efficient APC, restoring antigen-induced 3H-thymidine incorporation to T4-positive T cells that had been rigorously depleted of contaminating APC. In order to identify the APC within the glass-adherent cells (AC), these cells were stained with a number of monocyte-specific monoclonal antibodies (Mo-Mab) including 3C10, 63D3, and 61D3, and the Mo-Mab-positive and -negative cells were separated with the fluorescence-activated cell sorter. This method of preparation yielded Mo-Mab(+) AC populations that were more than 98% positive for the relevant Mab when reanalyzed with the fluorescence-activated cell sorter. Less than 1% of the Mo-Mab(-) AC populations were positive when reanalyzed with the Mab used for the separation. However, each Mo-Mab(-) AC population was contaminated with variable numbers (4-60%) of Mo as detected by morphologic criteria, histochemical analysis for esterase activity, or staining with a different Mo-Mab. Both Mo-Mab(+) and (-) AC populations were found to be similarly effective APC, with as few as 500 cells/well supporting responses to streptokinase-streptodornase, tetanus toxoid, and Candida albicans antigen. In the absence of antigen, only 3C10(-), 63D3(-), or 61D3(-) AC consistently stimulated 3H-thymidine incorporation of autologous T4 cells; large numbers (greater than 5 X 10(3)/well) of APC were necessary to induce this response. These results support the conclusion that cells identified by Mo-specific Mab are capable of functioning as APC, inducing 3H-thymidine incorporation in response to exogenous antigens. However, Mo-Mab(+) AC are not unique in this activity since Mo-Mab(-) AC also appeared to be able to present antigen. These Mo-Mab(-) AC appear to contain the majority of cells inducing autologous T4-cell reactivity.

Antibodies, Monoclonal↗
PubMed1990

Depressed T-cell reactivity to recall antigens in rheumatoid arthritis.

Reactivity toward soluble recall antigens (Candida albicans, cytomegalovirus, herpes simplex, streptokinase-streptodornase, and influenza) was determined in cultures of peripheral blood mononuclear cells from 41 rheumatoid arthritis patients (with clinically active as well as inactive disease) and from 28 controls. In the group with clinically active rheumatoid arthritis we found an increased incidence of "anergy," defined as nonreactivity to three or more antigens. In an attempt to explain this decreased antigen reactivity, the latter was correlated with peripheral blood lymphocyte subsets, as defined by two-color immunofluorescence with a panel of eight monoclonal antibodies. We found a significantly lower number of memory T4 cells (CD4+CD45RA-) and a significantly higher number of the CD3-CD57+ (nonspecific suppressor) cells and of CD3-CD56+/CD16+ (natural killer) cells in anergic RA patients. In the total group of rheumatoid arthritis patients, the antigen reactivity correlated positively with the percentage of memory T4 cells. Antigen reactivity was negatively correlated with the percentage of CD3-CD57+ cells and of the CD3- natural killer cells in peripheral blood. Our data suggest that a decrease in memory T4 cells and an increase in nonspecific suppressor cells may contribute to the impaired cellular immune function in peripheral blood of rheumatoid arthritis patients.

Aged↗
PubMed1978

Skin test reactivity in inflammatory bowel disease in the United States and Czechoslovakia.

Inflammatory bowel disease (IBD) patients in the United States of America (USA) and Czechoslovakia (CSSR) were categorized by clinical, pathological, and radiological criteria as having Crohn's disease (CD) or ulcerative colitis (UC) and were tested with five skin test antigens [Candida, mumps, purified protein derivative (PPD), streptokinase-streptodornase (SK-SD), and trichophytin] at two different dilutions in an attempt to elicit some evidence of anergy. No significant differences were encountered between the USA and CSSR populations or between any patient group and its controls.

Allergens↗
PubMed1979

[The immune competence of patients with Crohn's disease (author's transl)].

The cell-mediated and humoral immune responses were assessed in 15 patients with Crohn's disease and in 28 age-matched control subjects by means of several in vivo and in vitro methods. The disease activity in most patients was absent or moderate. Studying cellular immunocompetence we investigated the skin reactivity to various recall antigens (Candida, Trichophytin, Mumpsantigen, Streptokinase-Streptodornase, PPD), the primary immune response to Dinitrochlorobenzene (DNCB) and Keyhole Limpet Hemocyanin (KLH), and the lymphocyte transformation induced by mitogens (Phytohemagglutinin, Concanavaline A, Pokeweed Mitogen) and specific antigens. Humoral immunity was studied by measuring immunoglobulins, isohemagglutinins, and the antibody response to KLH. In addition, complement components and (in 10 patients) the proportions of T- and B-lymphocytes in the peripheral blood were evaluated. Cutaneous responsiveness to Candida, Mumps-antigen, SK-SD, and DNCB as well as the cellular immune response to KLH were impaired in patients with Crohn's disease (significance was reached for SK-SD, DNCB, and the mean area of induration). The lymphocyte transformation test with PHA, ConA, and PWM revealed normal results. For specific antigens (PPD, SK-SD, KLH) a good correlation could be demonstrated between delayed hypersensitivity and the in vitro lymphocyte responsiveness. Humoral immunity was not unequivocally impaired in Crohn's disease. Five patients with Crohn's disease proved constantly decreased total absolute lymphocyte counts in peripheral blood. The proportions of T- and B-lymphocytes and the complement-levels were corresponding to those in normal controls. No correlation was found between immunological and clinical parameters. In conclusion, patients with Crohn's disease exhibited a partial impairment of the cellular immune response, whereas humoral immunity was not affected. However, it remains to be elucidated whether this immune defect represents a basic pathogenetic factor in the onset of the disease.

Adolescent↗
PubMed1975

Impaired cell-mediated immunity in systemic lupus erythematosus (SLE). A controlled study of 23 untreated patients.

Cell-mediated immunity was evaluated in 23 patients with systemic lupus erythematosus (SLE) prior to therapy and in 23 control subjects. The patients with SLE who had moderate to severe disease activity had significantly fewer positive delayed skin tests to streptokinase-streptodornase (SK-SD) and Candida than the control subjects, and a higher frequency of anergy than either the control subjects or the patients with mild SLE. Significant impairment of lymphocyte transformation to all common antigens tested was found in patients with SLE as compared to both normal subjects and control subjects with disease. Phytohemagglutinin response was reduced in patients with SLE as compared to normal subjects but not to the control subjects with disease. Lymphocyte transformation responses to SK-SD and Candida were also significantly lower in patients with moderate to severe SLE as compared to patients with mildly active SLE. Primary immune response to keyhole limpet hemocyanin (KLH) was impaired in patients with SLE as measured by lymphocyte transformation and total KLH antibody, but not 2-mercaptoethanol resistant antibody. The data indicate defective T-cell function in SLE, and suggest that the impairment relates in part to disease activity.

Adolescent↗
PubMed1981

Beneficial effects of oral zinc supplementation on the immune response of old people.

Zinc is known to have beneficial effects on the immune response. In an attempt to modify age-associated immune dysfunction, supplemental zinc was administered to 15 subjects over 70 years of age (220 mg zinc sulfate twice daily for a month). As compared to 15 controls, matched for age and sex, there was a significant improvement in the following immune parameters in the treated group: (1) number of circulating T lymphocytes; (2) delayed cutaneous hypersensitivity reactions to purified protein derivative, Candidin and streptokinase-streptodornase; (3) immunoglobulin G (IgG) antibody response to tetanus vaccine. Zinc treatment had no influence on the number of total circulating leukocytes or lymphocytes, or on the in vitro lymphocyte response to three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). The data suggest that the addition of zinc to the diet of old persons could be an effective and simple way to improve their immune function.

Adult↗
PubMed1984

Capping of the surface OKT3 binding molecule prevents the T-cell proliferative response to antigens: evidence that this molecule conveys the activation signal.

The human T-lymphocyte receptor for antigen appears to have been localized to a cluster of associated surface glycoprotein molecules, among which is the OKT3 binding molecule. We have tested the hypothesis that selective removal of the OKT3 binding molecule eliminates the cellular immune response to antigens by clearing the surface of the molecule that conveys the activation signal. Enriched T cells were obtained from donors immune to purified protein derivative (PPD), streptokinase-streptodornase (SK-SD), or keyhole limpet hemocyanin (KLH). T-3 molecules were cleared from the cell surface by capping with OKT3 and F(ab')2 goat anti-mouse IgG. Regeneration of surface molecules was prevented by culturing the T-3 capped cells with OKT3 625 ng/ml. The capacity of capped T cells to proliferate in culture with antibody in response to antigens, alloantigens, and the mitogens, PHA and ionophore A23187, was compared to uncapped cells pretreated with media and to capped cells permitted to regenerate the OKT3 binding molecule. T-3 capped cells cultured in the presence of antibody failed to proliferate to antigens or alloantigens. However, T-3 capped cells cocultured with antibody also did not significantly proliferate to PHA, but did respond to A23187. In contrast, both media-treated T cells and cells which had regenerated the OKT3 binding molecule proliferated to mitogens, antigens, or alloantigens. The requirement for the OKT3 binding molecule was determined by utilizing T-1, T-4, and T-8 capped cells. T-1, T-4, or T-8 capped cells cultured in the presence of OKT1, OKT4, or OKT8 proliferated in response to antigens, alloantigens, and mitogens. These results demonstrate that in the absence of the OKT3 binding molecule, antigens, alloantigens, and PHA failed to induce a significant cellular proliferative response. In the absence of this molecule, PHA cannot bind to its carbohydrate moiety, and therefore cannot activate T cells to proliferate. These data support the concept that the molecule binding OKT3 conveys the transmembrane signal resulting in cellular activation.

Adult↗
PubMed1983

Prolonged impairment of cell-mediated immunity after major abdominal surgery in malnourished patients.

The effect of the nutritional status on postoperative impairment of the immune response was studied in adults undergoing major abdominal surgery. The immune function was evaluated by measuring in vitro the lymphocytic response to phytohaemagglutinin (PHA), concanavalin A (Con A) and the purified protein derivative of tuberculin (PPD) in whole blood cultures, and in vivo delayed skin hypersensitivity to candida, mumps, streptokinase-streptodornase and PPD. Nutritional assessment was carried out by evaluating recent weight loss, the weight for height index and by measuring the arm muscle circumference (AMC), triceps skinfold thickness (TSF), the creatinine-height index (CHI) and the serum concentration of albumin and prealbumin. The patient was considered malnourished, if at least three of these criteria were abnormal. The immune parameters were measured preoperatively, at the end of the surgery and five days after operation. Before the operation both malnourished and well-nourished patients had normal lymphocytic responses, but the malnourished patients had a slower recovery of immune responses after the operation and they had an increased number of postoperative complications. No significant differences in the incidence of anergy were observed between the well and malnourished patients pre or postoperatively.

Journal Article↗
PubMed1986

Outcome of asbestos exposure (lung fibrosis and antinuclear antibodies) with respect to skin reactivity: an 8-year longitudinal study.

Two hundred seventy asbestos workers were examined during an 8-year period. During this time five consecutive surveys were completed. Skin tests with streptokinase-streptodornase (SK-SD), tuberculin (PPD), and phytohemagglutinin (PHA) were performed in the middle of this period. The results of these tests were related to X-ray chest film results and the appearance of antinuclear antibodies (ANA). In all surveys, except the first, X-ray films with small irregular opacities with a profusion greater than or equal to 1/1 belonged more frequently to asbestos workers who did not respond to SK-SD or PHA. Thirty-one cases of asbestosis were diagnosed at that time, 23 of them became asbestotic after the skin tests were performed. Asbestotic cases contributed more frequently to the group with anergy as compared to asbestos workers lacking asbestosis. Furthermore, asbestosis was correlated with lack of response to second strength of SK-SD in males and PHA in both sexes. Lack of response to these activators was predictive of asbestosis. Asbestos workers with ANA frequently displayed a lack of response to the first strength of SK-SD, PPD, and PHA. This was partly due to the presence of asbestotic cases in the group. However, low responders to all these activators were found more frequently in the group with ANA independent of the presence of asbestosis.

Adult↗
PubMedDate not supplied

Antigen-specific suppressor cells in subclinical leprosy infection.

A two-stage in-vitro culture system was used to assay cells which suppress the lympho-proliferative response to Mycobacterium leprae (ML). Responses to ML, purified protein derivative of tuberculin, and streptokinase-streptodornase were preferentially suppressed by mitomycin-treated cells which had been primed with the same antigen in a 7-day primary culture. Healthy subjects exposed to leprosy for more than 3 years showed strong suppression of the response to ML antigens (11 of 12 showed more than 40% suppression), whereas those exposed for 3 months to 3 years showed much less suppression (12 of 15 showed less than 40% suppression). The in-vitro generation of strong ML-specific suppression may reflect the maturation of a well-regulated and protective immune response. However, premature induction and in-vivo activation of these suppressor cells could predispose to disseminated (lepromatous) forms of leprosy. With this assay it would be possible to assess the ability of proposed leprosy vaccines to engage strongly the regulatory network controlling the immune response to ML in the same way as long-term exposure to the natural infection.

Adolescent↗
PubMed1984

Effects of preoperative parenteral nutrition on cell-mediated immunity in malnourished patients.

Cell-mediated immunity was studied in 19 malnourished patients admitted for major abdominal surgery. Nine of them received total parenteral nutrition (TPN) before operation (the TPN group), while ten (the control group) were operated on without a period of TPN. In vitro lymphocyte proliferative responses to phytohaemagglutinin (PHA), concanavalin A (Con A) and purified protein derivative of tuberculin (PPD), were measured in whole blood cultures preoperatively, at the end of surgery and 5 days after operation. In vivo delayed skin hypersensitivity to candida, mumps, streptokinase-streptodornase and PPD was studied preoperatively and 5 days after operation. Complications in both groups were observed and recorded. Nutritional assessment was carried out by evaluating the extent of recent weight loss, the weight for height index and by measuring the arm muscle circumference (AMC), triceps skinfold thickness (TSF), the creatinine-height index (CHI) and serum albumin and prealbumin concentrations. The patient was considered to be malnourished and was included in the study, if at least three of these criteria were abnormal. In the TPN group changes in mitogen induced lymphocyte proliferative responses caused by surgery were not significant. By contrast, responses in the control group decreased significantly (P < 0.01) during surgery and most of these responses differed from the preoperative values even at the fifth postoperative day. Anergy was equally common in both groups before and after surgery. The number of infectious complications was lower in the TPN group.

Journal Article↗
PubMed1997

Immunodeficiency in non-tuberculous mycobacterial disease.

T-cell immunity was investigated in eight patients with non-tuberculous mycobacterial disease, to see whether impaired immune function might be the explanation for their infection. Cellular immune function was evaluated in vitro by measuring the proliferation of peripheral blood mononuclear cells in response to both non-specific mitogens (phytohaemagglutinin and pokeweed mitogen) and specific recall antigens (streptokinase-streptodornase and purified protein derivative from Mycobacterium tuberculosis), and in vivo, by measuring the skin test response to a panel of recall antigens. Functionally relevant T-lymphocyte sub-populations (CD4, CD8, activated CD3 and gamma/delta T-cells) were enumerated by two-colour flow cytometry. The results were compared with those for a group of patients with pulmonary tuberculosis, with groups of controls matched for age and smoking habit, and with a patient group receiving steroid treatment. The patients with non-tuberculous mycobacterial disease had poor or absent skin test responses; in vitro, their response to recall antigens was depressed, although their response to mitogens was normal. The patients had significantly raised levels of CD8 lymphocytes and activated T-cells, but lacked any circulating gamma/delta T-cells. There were also differences between the various control groups. In conclusion, this study demonstrates a deficiency in the cellular immune system of these patients, which is most readily detectable by skin testing, or by measuring lymphocyte proliferative responses to recall antigens. However, the study also shows changes in cellular immune responses in controls matched for age and smoking and in patients on steroid treatment, and underscores the need for matched controls. Further work needs to be done to ascertain whether the cellular immune deficiency is a cause of, or is caused by, the mycobacterial infections, and also to investigate the pathological significance of the alterations in T-cell sub-populations.

Adult↗
PubMed1989

An investigation of the general immune status and specific immune responsiveness to retinal-(S)-antigen in patients with chronic posterior uveitis.

Immunological abnormalities in endogenous posterior uveitis are widely reported but difficult to verify. We have therefore studied several immunological parameters in 14 patients with chronic posterior uveitis and compared the results with 14 healthy controls. Both the general immune status and the specific immune responsiveness to retinal S-antigen have been investigated. Results for the patient group as a whole were not significantly different from the control group. However the patients with severe eye disease (n = 4) had a reduced proliferative response to streptokinase-streptodornase antigen and two further individuals showed a general deficiency in functional cell mediated immunity. Circulating T-helper cells were marginally but not significantly reduced in patients. Responsiveness to bovine retinal S-antigen varied to a similar degree in both the patient and control groups. These findings indicate that, although severe uveitis may be associated with functional defects in cellular immunity in certain cases, in general the measurement of immune responsiveness of peripheral blood lymphocytes is unlikely to aid in the diagnosis or management of chronic posterior uveitis.

Adolescent↗