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PubMed1979

Diagnostic dilemma of a 13-month-old boy with 'late-onset' combined immunodeficiency.

A 13-month-old boy had a "late-onset" form of combined immunodeficiency and a fulminant Pneumocystis carinii pneumonia of one month's duration. There was no evidence of cutaneous-delayed hypersensitivity responses to diphtheria-tetanus toxoids, Candida albicans, or streptokinase-streptodornase, or of lymphocyte DNA synthesis after in vitro stimulation with the mitogens phytohemagglutinin and concanavalin A, and only 2% to 4% of peripheral blood E-rosetted T lymphocytes. The serum IgM level was normal (62 mg/dL), whereas the other immunoglobulins were markedly reduced. Despite an increased number of Ig-bearing lymphocytes, in vitro Ig secretion after pokeweed mitogen stimulation was substantially reduced. The thymus gland was dysplastic with no Hassalls' corpuscles or thymocytes, and other lymphoid organs showed depletion of T-dependent areas to a greater extent than the B-dependent areas.

B-Lymphocytes↗

PubMed1976

Cell-mediated immunity in patients with carcinoma: correlation between clinical stage and immunocompetence.

Cell-mediated immunity (CMI) was evaluated in 82 patients with non-lymphoid tumors by in vivo and in vitro methods. These included skin test with ubiquitous antigens, 2,4 dinitrochlorobenzene (DNCB) sensitization, determination of T and B peripheral blood lymphocytes, and lymphocyte response to phytohemagglutinin (PHA). The patients were divided into two groups: those with localized and those with disseminated disease (LD and DD). The patients with LD showed no significant differences in CMI when compared with normal controls. The patients with DD showed various defects in CMI when compared with controls and patients with LD. There were significant differences in the response to DNCB, and streptokinase-streptodornase (SK-SD) was the most discriminative of the skin-test antigens. The response to PHA was greatly depressed in patients with DD, whether in the presence of autologous or homologous plasma; in some patients a factor inhibiting to blastogenesis was detected in the serum. In patients with DD, a T-cell lymphopenia was observed. These data showed a correlation between immunocompetence and clinical stage.

Adult↗

PubMed1978

Immunological monitoring during chemotherapy for advanced Hodgkin's disease.

A study of some immunologic in vitro and in vivo changes during the course of chemotherapy in 17 cases of advanced Hodgkin's disease was made. Skin testing with PPD, candida albicans and streptodornase antigens was studied together with studies of B and T cell numbers in the blood and responses to migration inhibition testing for PPD and PHA. An excellent correlation was found between recovery of normal immunologic responses and clinical remission despite the use of immunosuppressive chemotherapy.

Adolescent↗

PubMed1980

Impaired cell-mediated immunity function in thyroid cancer.

Immunological parameters were studied in 31 patients with thyroid cancer. Serum immunoglobulin levels, T and B cell percentages in peripheral blood, showed no significant difference as compared with those of control group. The blastogenesis with phytohemagglutinin P (PHA) was significantly reduced, especially, in those having larger tumor size or metastasis or in those over age 60. The positive rate of skin test with purified-protein-derivative (PPD) and Streptokinase-Streptodornase (SK-SD) was also markedly reduced. The impaired blastogenesis of lymphocyte and reduced positive rate of skin test in those cancer patients suggested that the cell-mediated immunity function, in spite of adequate count of T-cells, was impaired.

Adult↗

PubMed1980

Lymphocyte cytotoxicity of patients developing multiple primary melanomas.

A study of cellular immunity was conducted, with particular attention to natural killer cell mediated in vitro cytotoxicity in 6 patients who had two or three primary melanomas (2 patients presenting synchronously with multiple primaries and additional melanomas subsequently developing in 4). All 6 patients were reactive to one or other recall skin test antigens (PPD, streptokinase streptodornase (SK-SD), monilia, mumps) and DNCB skin testing. All exhibited natural killing against melanoma and nomelanoma tumor target cells when examined in the 3H proline microcytotoxicity test with unfractionated as well as natural killer cell enriched (Fc receptor positive cells recovered as Fc receptor rosettes) lymphocyte fractions. None of the 4 patients who subsequently had additional primary tumors was found to lack in mature T or natural killer cell mediated cytotoxicity at the time of the development of additional primaries. Two melanoma cell lines were established from two separate primary tumors in 1 patient and in vitro cytotoxicity assays were performed with that patient's lymphocytes (unfractionated, T enriched, and natural killer cell enriched fractions) against these two lines. While the first melanoma cell line was consistently sensitive to lysis by all three lymphocyte fractions, the other cell line showed no sensitivity either for natural killing or for T enriched lymphocyte mediated lysis at any effector to target ratio. These results suggested that in vitro natural cytotoxicity was not translated into any substantive immunoprotective role in the development of multiple primary tumors and that the two separate melanoma cell lines from the same patient were antigenically hererogenous. Antigenic heterogeneity between different primary tumors may explain the lack of immunity against such development of multiple tumors of the same histology.

Antibody-Dependent Cell Cytotoxicity↗

PubMed1987

Zinc and anergy in pediatric Hodgkin's disease in Turkey.

Blood (serum, erythrocytes) and hair zinc levels were determined in 60 biopsy-proven pediatric Hodgkin's disease cases at diagnosis. Cellular immunity also was assessed through total lymphocyte counts, E-rosette formation, lymphoproliferative response (LP), and delayed cutaneous hypersensitivity tests to dinitrochlorobenzene, streptokinase-streptodornase, purified protein derivative and phytohemagglutinin (PHA) in some of these patients. Interestingly, anergic patients unresponsive to four antigens showed significantly more depressed serum zinc levels as well as decreased lymphoproliferative response to mitogen (PHA). A positive correlation could be shown between serum zinc level, cutaneous anergy and LP. A possible contributing role of zinc deficiency in defective cell mediated immunity in Hodgkin's disease was proposed, and administration of oral zinc, as a natural immunostimulant is considered in this lymphoma.

Adolescent↗

PubMed1996

Kinetics and functional implications of Th1 and Th2 cytokine production following activation of peripheral blood mononuclear cells in primary culture.

The importance of cytokine production in some disease processes is now widely recognized. To investigate temporal relationships between cytokines, we stimulated peripheral blood mononuclear cells (PBMC) in vitro using the T cell mitogen phytohemagglutinin (PHA) and various antigens chosen to induce predominantly Th1 (streptokinase: streptodornase or purified protein derivative) or Th2 (Dermatophagoides pteronyssinus, bee or wasp venom: allergens in sensitive subjects) responses. Cytokine production was measured by sensitive bioassays or enzyme-linked immunosorbent assays. Of the 30 subjects studied, 10 were normal and 20 individuals were allergic to either D. pteronyssinus (n = 10) or bee venom (n = 10) (examined before specific allergen immunotherapy). We examined the temporal profiles of a panel of cytokines produced in primary culture. In PHA-driven cultures, cytokines were found to be sequentially produced in the order interleukin (IL)-2, IL-4, IL-5, IL-3, interferon (IFN)-gamma, IL-10, IL-6, IL-12 and tumor necrosis factor (TNF)-alpha. The response to allergen in allergic patients was predominantly Th2 in nature, with the production of IL-4, IL-5, IL-6 and IL-10, but little or no IFN-gamma. IL-2, IL-3, TNF-alpha and IL-12 were also produced in low amounts. The response of both atopic and normal subjects to recall bacterial antigens was predominantly Th1, with high levels of IFN-gamma, IL-2 and TNF-alpha. The relevance of the order, amount and speed of production, characteristic kinetics (production, consumption, homeostatic regulation) and the cell source of the cytokines are discussed.

Allergens↗

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↗

PubMed1995

Prevention of postoperative adhesions by single intraperitoneal medication.

Postoperative adhesions account for a significant morbidity after abdominal, gynecological, or cardiac surgery. A large number of compounds have been suggested to prevent such adhesions, but none is generally accepted. We have compared eight different substances that could be beneficial for the prevention of postoperative adhesions in a new standardized rabbit model with measurement of the areas of adhesion. In 10 groups of 20 rabbits an area of abrasion of the serosa of the ileum, the appendix, and the abdominal wall measuring 10,000 mm2 was created by an emery piston during celiotomy. The controls received no medication. The treatment groups received a single intraperitoneal administration of 1 ml per 100 g body wt of normal saline (NaCl), 5 mg taurolidine (T), 0.5 U plasmin/300 U DNase (PD), 2000 IU streptokinase/500 IU streptodornase (SS), 7 mg phosphatidylcholine (PC), 4 mg hyaluronic acid (HA), 7 mg sphingolipid (SL), 7 mg galactolipid (GL), or 0.5 ml tetrachlorodecaoxide (TCDO), respectively. Ten days later the extent of adhesions was quantified by morphometry. The total area of adhesions (+/- SEM) was found to be 1998 +/- 124 mm2 in controls. The application of NaCl reduced the adhesions to 1368 +/- 58 mm2, of T to 1012 +/- 48 mm2, of PD to 673 +/- 33 mm2, of SS to 360 +/- 44 mm2, of PC to 335 +/- 84 mm2, of HA to 328 +/- 76 mm2, of SL to 278 +/- 80 mm2, of GL to 261 +/- 67 mm2, and of TCDO to 240 +/- 45 mm2. The effects of PD, SS, PC, HA, SL, GL, and TCDO were significant in comparison to controls and NaCl. Our experimental data suggest that the two new lipid substances, SL and GL, are the most likely candidates for routine clinical use in the prevention of postsurgical adhesions.

Abdominal Muscles↗

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↗

PubMed1999

Demonstration of a DNase-sensitive network associated with the nuclear pore complexes in rat liver nuclei.

Rat liver nuclei have been studied by transmission electron microscopy after resuspension in a phosphate-buffered salt solution containing SO2-4 as the quantitatively dominant anion. Owing to the high solubility of chromatin in the presence of SO2-4 instead of Cl- at isotonicity, nuclei are depleted for chromatin by DNase I digestion in this buffer, eliminating the need for high-salt extraction. This shows that at least 75% of the nuclear pore complexes are associated with fibrogranular structures, which ramify as a network throughout the nucleus, interconnecting the nuclear lamina, interchromatin granule clusters and nucleoli. Perichromatin granules are located in this material proximal to the nuclear pore complexes. Most of the chromatin is removed without major impact on the network, but below a level of 25% residual chromatin there is a considerable reduction of this material, and only about 15% of the connections to the nuclear pore complexes are resistant to digestion with DNase I or streptodornase A and B. The percentage of nuclear pore complexes connected to the network is further reduced by salt extraction and RNase treatment. These results suggest that DNA is an integral part of the network, which presumably plays a role in nucleo-cytoplasmic transport of RNA and protein.

Animals↗

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↗