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Evaluation of various methods of maternal placental blood collection for immunology studies.

The collection of maternal placental intervillous blood (IVB), without contamination of fetal blood and with an accurate mononuclear cell profile, is essential for immunological studies of placental malaria and other infectious diseases of the placenta. We have compared five documented methods of IVB collection: perfusion, incision, biopsy, tissue grinding, and puncture (prick) for fetal blood contamination and mononuclear cell profiles using flow cytometry. Twenty-five placentas were obtained from Plasmodium falciparum and human immunodeficiency virus-negative primigravid and secundigravid women delivering at Nyanza Provincial Hospital in Kisumu, western Kenya. Each of the five methods was performed on the same placenta. Fetal red blood cell contamination was significantly lower for the prick and perfusion methods (4.1% and 8.3%, respectively) than for incision (59.5%), biopsy (42.6%), and tissue grinding (19.9%). Significant variation was noted among the five methods in the percentages of monocytes, total T cells, CD4+ and CD8+ T cells, B cells, and NK cells. Further, a pairwise comparison of prick and perfusion, the two methods with low fetal blood contamination, showed that they were not different for fetal red blood cell contamination levels; however, prick yielded significantly higher percentages of CD4 T cells and CD4 memory T cells than perfusion. Collection by prick was determined to be the best method of intervillous blood collection for immunology studies, and perfusion represented the next best method of choice due to high sample volume yield. Overall, in considering the advantages/disadvantages of the two methods with low fetal cell contamination, we conclude that a combination of prick and perfusion is most suitable for immunology studies.

B-Lymphocytes↗

Structural and immunological relationships of isoferritins in normal and malignant cells.

Ferritins from normal adult human liver and heart were compared with ferritins from a lung carcinoma metastatic to liver and from HeLa cells on the basis of their isoferritin profiles, subunit composition, and immunological relationships. Each ferritin preparation gave different isoferritin profiles, but several contained common isoferritins. All of the tumor isoferritins had counterparts in the normal tissues. All ferritins contained similar subunits but in different proportions. Qualitative differences were demonstrable in some ferritins with antibodies to different tissue ferritins. These differences correlated with the subunit composition of the ferritins. By appropriate absorption, an antibody population was obtained that was apparently specific for one subunit type. Heart ferritin gave lines of apparent identity with the tumor ferritins with these antibodies. It is concluded that tumor ferritins are not tumor-specific antigens but correspond to isoferritins in normal adult heart.

Antibodies↗

DNA arrays in allergy and immunology.

The DNA array technique allows the simultaneous analysis of multiple genes. This makes it an interesting tool for studies of gene expression in various diseases that are caused by or depend on multiple genes. DNA arrays are particularly applied to define certain immunological conditions such as allergic diseases. We summarize strategies on gene expression profiling of inflammatory disease and immunologically relevant cells using DNA array technology. Using DNA arrays, gene expression analysis of CD4+ T cells of allergy patients revealed interesting differences compared to healthy individuals, but also between different allergic conditions. This comparison demonstrated that T cells differed in their capacity to regulate peripheral tolerance, neuronal innervation, chemotaxis, neovascularization and epidermal growth. On the basis of these findings the DNA array technique appears to be especially interesting for the development of powerful diagnostic tools allowing fine specification and subtyping of allergic conditions, monitoring of therapy and of tailored therapy concepts.

CD4-Positive T-Lymphocytes↗

Biological and immunological characterization of human luteinizing hormone: I. Biological profile in pituitary and plasma samples after electrofocusing.

Pituitary and plasma pools from postmenopausal women and plasma pools from women at midcycle were fractionated by electrofocusing in sucrose density gradients. The biological LH activity was determined in each of the electrofocusing fractions by the use of an in vitro bioassay method. A heterogeneous profile of LH activity was found in both pituitary and plasma samples with a large proportion present within the pH range 6.5-10. In a total of 11 electrofocusing runs 7 main regions of high LH activity were found within this range with mean pI values (+/- SD) of 6.75 +/- 0.08 (n = 6), 7.33 +/- 0.08 (11), 7.80 +/- 0.09 (11), 8.23 +/- 0.10 (11), 8.81 +/- 0.04 (7), 9.17 +/- 0.05 (6) and 9.55 (2). A significantly higher proportion of LH activity was found in the midcycle plasma samples (36%) in the pH regions with mean pI values of 8.81, 9.17 and 9.55 than in postmenopausal plasma (7%) and pituitary extracts (5%). This indicates that the profile of biologically active LH in women in the fertile age is different from that present in postmenopausal women. By detailed fractionation based on narrow pH range studies and the refocusing of specific peak fractions it was shown that each of the regions studied consisted of several peaks of LH activity indicating the presence of a large number of molecular species exhibiting varying degrees of LH activity. The relative proportions of these species showed considerable differences between sources but also between samples from the same source.

Animals↗

Abnormalities in apolipoprotein and lipid levels in an HIV-infected Brazilian population under different treatment profiles: the relevance of apolipoprotein E genotypes and immunological status.

HIV infection is associated with disturbances in lipid metabolism due to a host's response mechanism and the current antiretroviral therapy. The pathological appearance and progression of atherosclerosis is dependent on the presence of injurious agents in the vascular endothelium and variations in different subsets of candidate genes. Therefore, the Hha I polymorphism in the apolipoprotein E gene was evaluated in addition to triglycerides, total cholesterol, very low-density lipoprotein (VLDL), LDL, high-density lipoprotein (HDL), and apolipoprotein (apo) Al, B and E levels in 86 Brazilian HIV-infected patients and 29 healthy controls. The allele frequency for apoE in the HIV-infected group and controls was in agreement with data on the Brazilian population. Dyslipidemia was observed in the HIV group and verified by increased levels of triglycerides, VLDL and apoE, and decreased levels of HDL and apoAl. The greatest abnormalities in these biochemical variables were shown in the HIV-infected individuals whose immune function was more compromised. The effect of the genetic variation at the APOE gene on biochemical variables was more pronounced in the HIV-infected individuals who carried the apoE2/3 genotype. The highly active anti-retroviral therapy (HAART)-receiving group presented increased levels of total cholesterol and apoE. Dyslipidemia was a predictable consequence of HIV infection and the protease inhibitors intensified the increase in apoE values.

Adult↗

Immunologic complexity of lymphoblastic lymphoma.

Twelve patients with a histologic diagnosis of lymphoblastic lymphoma (LBL) were studied immunologically using the methodologic refinement of comparative serial section immunochemistry. By this means, we demonstrate complex LBL phenotypic profiles, revealing 3 major immunologic subtypes: immature T cell, 7 cases; intermediate or mature T cell, 3 cases; immature B cell (pre-pre-B), 2 cases. This phenotypic diversity challenges the basic belief that all LBL are the same. Our immature T-cell cases with frequent simultaneous Leu 2/3/6/9/CALLA/Tdt expression correspond to cortical thymic phenotypes; our mature T-cell phenotypes with Leu 9/la expression and absent L6/Tdt correspond either to medullary thymocytes or post-thymic T cells; our pre-pre-B phenotypes with simultaneous Tdt/CALLA/B4 expression correspond to common acute lymphocytic leukemia (ALL) phenotypes. Mature T-LBL phenotypes are similar to "novel" peripheral T-cell lymphoma phenotypes. Scant or absent Tdt expression in mature LBL is not an isolated antigenic change but a complete phenotypic profile difference from immature T-LBL. The major T- and B-cell phenotypes of LBL might have therapeutic significance. Treatment among LBL phenotypes may need to vary as with acute lymphocytic leukemia phenotypes. Further study is needed; in the meantime, comparative serial section immunotyping promises substantial utility in revealing the immunologic complexity of the lymphomas.

Adolescent↗

Delayed disease progression after allogeneic cell vaccination in hormone-resistant prostate cancer and correlation with immunologic variables.

PURPOSE: There are a significant number of patients with asymptomatic hormone-resistant prostate cancer who have increasing prostate-specific antigen (PSA) levels but little or no evaluable disease. The immunogenicity and minimal toxicity associated with cell-based vaccine therapy makes this approach attractive for these patients. EXPERIMENTAL DESIGN: We have evaluated a vaccine comprising monthly intradermal injection of three irradiated allogeneic prostate cell lines (8 x 10(6) cells each) over 1 year. The first two doses were supplemented with bacille Calmette-Guérin as vaccine adjuvant. Twenty-eight hormone-resistant prostate cancer patients were enrolled. Patients were assessed clinically and PSA levels were measured monthly. Radiologic scans (X-ray, computed tomography, and bone scan) were taken at baseline and at intervals throughout the treatment period. Comprehensive monthly immunologic monitoring was undertaken including proliferation studies, activation markers, cytokine protein expression, and gene copy number. This longitudinal data was analyzed through predictive modeling using artificial neural network feed-forward/back-propagation algorithms with multilayer perceptron architecture. RESULTS: Eleven of the 26 patients showed statistically significant, prolonged decreases in their PSA velocity (PSAV). None experienced any significant toxicity. Median time to disease progression was 58 weeks, compared with recent studies of other agents and historical control values of around 28 weeks. PSAV-responding patients showed a titratable T(H)1 cytokine release profile in response to restimulation with a vaccine lysate, while nonresponders showed a mixed T(H)1 and T(H)2 response. Furthermore, immunologic profile correlated with PSAV response by artificial neural network analysis. We found predictive power not only in expression of cytokines after maximal stimulation with phorbol 12-myristate 13-acetate, but also the method of analysis (qPCR measurement of IFN-gamma > qPCR measurement tumor necrosis factor-alpha > protein expression of IFN-gamma > protein expression of interleukin 2). CONCLUSIONS: Whole cell allogeneic vaccination in hormone-resistant prostate cancer is nontoxic and improves the natural history of the disease. Longitudinal changes in immunologic function in vaccinated patients may be better interpreted through predictive modeling using tools such as the artificial neural network rather than periodic "snapshot" readouts.

Aged↗

Use of immunomodulatory therapy (other than interferon) for the treatment of chronic hepatitis B virus infection.

Chronic hepatitis B virus (HBV) infection is a major health threat in Asia. In order to design a better therapeutic regimen, the underlying mechanism of HBV viral persistence must be understood. Immunological studies have found that impaired HBV virus-specific T cell reactivity is the major cause of chronic infection, whereas strong and multispecific T cell responses to HBV are associated with long-term control, but not elimination of the virus. Furthermore, in the serological clearance of hepatitis B surface antigen (HBsAg) in allogeneic haematopoietic cell transplantation, HBsAg seroconversion is associated with activation of the donor's hepatitis B core antigen-specific CD4+ T lymphocytes. This suggests that the donor's hepatitis B core antigen-specific CD4+ T cells provide 'intermolecular T cell help' for the HBsAg seroconversion. These findings are relevant to the future development of therapeutic vaccines or DNA vaccine as immunotherapy for chronic hepatitis B. Apart from interferon-alpha, thymosin alpha1 (Talpha1) has been investigated for treatment of chronic hepatitis B. Meta-analysis of 4 randomized controlled studies investigating the safety and efficacy of Talpha1 monotherapy for the treatment of chronic hepatitis B showed that 6 months treatment with Talpha1 (1.6 mg twice weekly) almost doubles the sustained response rate (36%) compared with controls (19%; P=0.04). However, more specific immunological approaches are being developed; notably, hepatitis B core antigen-based therapeutic vaccine was found to induce T cell proliferative responses in chronically infected hepatitis B patients to the T helper epitope included in the construct. However, the cytokine profile observed suggested the induction of a T helper 0/T helper 2 CD4+ T cell response rather than T helper 1 response. Thus, its combination with interferon-gamma or interleukin-12, which might reverse the CD4+T cell response, should be considered. In the future, it is likely that different types of combination therapy may have to be tailor-made for chronic HBV infection with different virological and immunological profiles and different degrees of liver damage.

Adjuvants, Immunologic↗

Allergic bronchopulmonary aspergillosis: an Indian perspective.

PURPOSE OF REVIEW: Allergic bronchopulmonary aspergillosis is an immunologically mediated lung disease that is caused by hypersensitivity to antigens of the genus Aspergillus. This review summarizes the clinical presentation, radiologic profile, lung functions and immunologic studies on allergic bronchopulmonary aspergillosis from India. Data regarding Aspergillus sensitization in asthmatics are presented. The association of allergic bronchopulmonary aspergillosis with allergic Aspergillus sinusitis and aspergilloma is also highlighted. RECENT FINDINGS: Allergic bronchopulmonary aspergillosis is now an emerging disease in India. Sensitization to Aspergillus antigens is not uncommon in our patients with asthma. Although asthma commenced in these subjects in their early 20s, allergic bronchopulmonary aspergillosis was recognized more than a decade later. Allergic bronchopulmonary aspergillosis can also occur in patients without clinical asthma. Radiology is crucial to the diagnosis of allergic bronchopulmonary aspergillosis. The remarkable radiological similarity to pulmonary tuberculosis has important clinical implications in our country as patients with allergic bronchopulmonary aspergillosis often receive antituberculous therapy for a long time. Although oral corticosteroids still remain the cornerstone for management, itraconazole has emerged as an adjunct therapy in appropriate situations. Concomitant occurrence of allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis is now being increasingly recognized. SUMMARY: All asthmatic subjects with a positive skin prick test to Aspergillus antigens must be evaluated for allergic bronchopulmonary aspergillosis and allergic Aspergillus sinusitis should be excluded.

Adrenal Cortex Hormones↗

A pilot trial of tumor lysate-loaded dendritic cells for the treatment of metastatic renal cell carcinoma.

Cultured tumor lysate-loaded dendritic cells (TuLy-DC) have been demonstrated in vitro to stimulate potent immune modulations and generate significant antitumor response. We report the results of a pilot trial of TuLy-DC vaccine for patients with metastatic renal cell carcinoma (mRCC). Fourteen mRCC patients underwent nephrectomy to obtain autologous TuLy prepared by subjecting tumor cells to 3 freeze/thaw cycles. Dendritic cells were generated from peripheral blood CD14+ precursors cultured in the presence of GM-CSF, IL-4, and 10% autologous serum. Patients received one vaccination of TuLy alone as an immunologic control, followed by 3 weekly vaccinations of DC-TuLy injected intradermally in the midaxillary region. Peripheral blood lymphocytes were collected before and after weekly vaccines and were assessed for changes in phenotype, cytotoxicity, and cytokine profile. The TuLy-DC vaccine was successfully prepared and administered to 12 patients, whereas 2 patients did not receive vaccine treatment due to declines in postoperative performance status. The vaccines were well tolerated, with only grade 1 toxicities noted. One patient had a partial response to treatment that did not correspond to any significant change in immunologic profile. This pilot trial demonstrated both the safety and feasibility of reliably preparing a DC-based vaccine for mRCC patients. Our data suggest that autologous TuLy-DC vaccines generate only limited clinical response. Further clinical studies are needed to identify the most potent treatment regimen that can consistently mediate an antitumor immune response in vivo.

Adult↗

Effects of interferon and ribavirin combination therapy on CD4+ proliferation, lymphocyte activation, and Th1 and Th2 cytokine profiles in chronic hepatitis C.

We studied the relationship between immunological markers such as CD4+ proliferation, cytokines profile and lymphocyte activation markers in patients with chronic hepatitis C, having different responses to interferon (IFN) and ribavirin (RBV) treatment. A prospective study of 20 patients was conducted, six had received IFN-alpha-2b alone and 14 IFN in combination with RBV. The proliferative immune responses of peripheral blood mononuclear cells to hepatitis C virus peptides and the lymphocyte activation markers (CD25+, CD38+ and CD69+) were assessed before treatment, at 1 week, and 1, 3 and 6 months of treatment. Cytokines interleukin (IL)-2, IFN-gamma, IL-4 and IL-10 were determined in supernatants before onset of treatment and at 1 and 6 months thereafter. Stimulation indices (SI) were higher in the sustained responders (SR), in comparison with those with no response (NR), before treatment (5.2 +/- 3.7 to 3.3 +/- 1.9, P = 0.028) and also at 6 months (7.8 +/- 1.9 to 4.1 +/- 1.2, P = 0.021). Patients with SR also had high SI to NS3 when compared with those with transitory response or no response (NR) (4.9 +/- 2.5 and 3.3 +/- 1.1, P = 0.033). At 1 month, SR had higher supernatant IL-2 than those with NR (133.8 +/- 119.2 to 56.0 +/- 89.3 pg/mL, P = 0.023) and lower levels of IL-10 (13.8 +/- 10.1 and 167.1 +/- 272.0 pg/mL, P = 0.023) in response to NS3. Combination therapy induced a higher percentage of the lymphocyte activation markers CD69+ and CD38+. In conclusion, we found that SR is associated with higher CD4+ proliferation particularly in response to the NS3 region, promoting a T-helper (Th)1/Th0 profile of cytokines, and that combination therapy induced a higher percentage of lymphocyte activation than therapy with IFN alone.

Adult↗

Defining protective responses to pathogens: cytokine profiles in leprosy lesions.

The immunological mechanisms required to engender resistance have been defined in few infectious diseases of man, and the role of specific cytokines is unclear. Leprosy presents clinically as a spectrum in which resistance correlates with cell-mediated immunity to the pathogen. To assess in situ cytokine patterns, messenger RNA extracted from leprosy skin biopsy specimens was amplified by the polymerase chain reaction with 14 cytokine-specific primers. In lesions of the resistant form of the disease, messenger RNAs coding for interleukin-2 and interferon-gamma were most evident. In contrast, messenger RNAs for interleukin-4, interleukin-5, and interleukin-10 predominated in the multibacillary form. Thus, resistance and susceptibility were correlated with distinct patterns of cytokine production.

Base Sequence↗

Intracerebral cytokine profiles in adult rats grafted with neural tissue of different immunological disparity.

To understand graft rejection in cell based therapies for brain repair we have quantified IL-1beta, IL-2, IL-4, IL-10, IL-12p40, IFN-gamma and TNF-alpha mRNA levels using real-time PCR, at days 4, 14, and 42 post-transplantation, in rats engrafted with syngeneic, allogeneic, concordant and discordant xenogeneic neural tissues. In addition, in the discordant xenografts immunohistochemistry and in situ hybridization were applied to detect local expression of IFN-gamma, TNF-alpha, IL-10 and TGF-beta. Allografts remained non-rejected but expressed IL-1beta, TNF-alpha and IL-4 transcripts but not IL-12p40 and IFN-gamma. Xenografts demonstrated distinct cytokine profiles that differed from syngeneic and allogeneic grafts. Non-rejected discordant xenografts contained higher levels of TNF-alpha transcripts and lower levels of IL-2 transcripts than the rejected ones at day 42. Discordant xenografts displayed a stronger and earlier expression of IL-1beta and TNF-alpha, followed by T-helper 1 and T-helper 2 associated cytokine expression. The number of cells expressing mRNA encoding TNF-alpha and TGF-beta was significantly increased over time in the discordant group. In conclusion, the immunological disparity of the implanted tissue explains survival rates and is associated with different cytokine profiles. In allografts, a chronic inflammatory reaction was detected and in xenogeneic grafts a delayed hypersensitivity like reaction may be involved in rejection.

Animals↗

Plasma glutathione concentrations in children infected with human immunodeficiency virus.

BACKGROUND: Glutathione (GSH) is the principal intracellular defense against oxidants, and HIV-infected individuals tend to have subnormal concentrations in plasma. This GSH deficiency may contribute to the pathogenesis of disease progression. In the pediatric population correlations between GSH concentrations with clinical, immunologic and virologic disease profiles are scarce. OBJECTIVES: The main objectives of this study were (1) to compare plasma GSH concentrations of HIV-infected children and healthy controls and (2) to correlate GSH values with clinical, immunologic and virologic disease indices. METHODS: Twenty-four HIV-infected and 24 healthy control children entered the study. Plasma concentrations of total glutathione and related thiols were determined. RESULTS: The difference in mean plasma GSH concentrations between HIV-infected (2.96 +/- 0.31 microM) and control (6.62 +/- 0.58 microM) groups was highly significant (P < 0.0001). Linear regression analyses in HIV-infected patients revealed significant correlations between GSH and both absolute CD4+ cell counts (r = 0.56, P = 0.004) and viral load measured as log HIV-RNA PCR (r = -0.49, P = 0.018). GSH concentrations did not significantly correlate with CDC clinical stage but were lower in HIV-infected patients with growth failure (1.60 +/- 0.54 microM) vs. non-growth failure (3.23 +/- 0.33 microM); P = 0.05. CONCLUSIONS: This study confirmed that HIV-infected children are deficient in plasma GSH concentrations compared with healthy controls. We documented that low GSH concentrations in HIV-infected children are directly correlated with CD4+ cell counts and inversely correlated with viral loads. These findings support a possible role of GSH in the pathogenesis of HIV disease progression.

CD4 Lymphocyte Count↗

Clonal plasma cells from monoclonal gammopathy of undetermined significance, multiple myeloma and plasma cell leukemia show different expression profiles of molecules involved in the interaction with the immunological bone marrow microenvironment.

The immunological bone marrow (BM) microenvironment plays a major role in controlling growth and survival of clonal plasma cells (PC); this might translate into different patterns of expression of molecules involved in immune responses on PC from different types of monoclonal gammopathies (MG). We have studied the expression of a group of nine such molecules on both BMPC and the plasma of 61 newly diagnosed MG patients (30 MG of undetermined significance (MGUS), 27 multiple myeloma (MM) and four plasma cell leukemia (PCL)) and five normal individuals. Clonal PC from all MG displayed significantly increased levels of CD56, CD86 and CD126, and decreased amounts of CD38 (P<0.001). Additionally, HLA-I and beta2-microglobulin were abnormally highly expressed in MGUS, while CD40 expression was decreased in MM and PCL (P<0.05). Interestingly, a progressive increase in the soluble levels of beta2-microglobulin was found from MGUS to MM and PCL patients (P=0.03). In contrast, all groups showed similar surface and soluble amounts of CD126, CD130 and CD95, except for increased soluble levels of CD95 observed in PCL. Overall, those phenotypic differences are consistent with increased antigen presentation and costimulatory capacities in MGUS, which progressively deteriorate in malignant MG (MM and PCL).

Aged↗

Suberosis and bird fancier's disease: a comparative study of radiological, functional and bronchoalveolar lavage profiles.

Hypersensitivity Pneumonitis (HP) is an immunologically mediated interstitial lung disease that may result from repeated inhalation of many different environmental agents. Heterogeneity of the clinical presentation and bronchoalveolar lavage profiles have been described, possibly related to different occupational exposures. The aim of our study was to compare bronchoalveolar lavage fluid (BALF), clinical, functional and radiological characteristics of the two most frequent forms of HP seen in our practice: Suberosis (an HP related to moldy cork dust exposure) and bird fancier's disease (BFD). We included 81 patients with Suberosis, with a mean age of 38.8 +/- 11.3 years and a mean exposure of 20.0 +/- 10.5 years and 32 patients with BFD, with a mean age of 46.3 +/- 11.8 years and mean exposure of 10.5 +/- 1.0 years. Patients with BFD had more acute forms, while subacute and chronic presentations predominated in Suberosis. Restrictive defect was the most frequent pattern of lung function impairment, and more severe in BFD. Ground glass opacities were the most frequent pattern in high-resolution computed tomography. A normal chest x-ray was more frequently seen in Suberosis. Both types of HP had lymphocytic alveolitis in BALF: Suberosis - 6.6 +/- 5.7 x 10(5) ml-l cells, 58.8 +/- 18.9% lymphocytes; bird fancier's disease - 9.0 +/- 6.5 x 105 ml-l cells, 61.7 +/- 22.2% lymphocytes. Although BALF CD8+ lymphocytes predominated in both diseases, the proportion of CD4+ and CD4/CD8 ratios were significantly higher in bird fancier's disease (Suberosis: 0.47 +/- 0.33 versus BFD: 1.1 +/- 1.5; p < 0.005). Moreover, BALF cellularity and mast cell counts were also significantly higher in BFD. In conclusion, Suberosis and bird fancier's disease are HP with different clinical and laboratory profiles, suggesting that despite their pathophysiological similarities, different antigenic exposures may cause different immune and inflammatory response dynamics in the lung.

Adult↗

Immunological changes in peripheral blood mononuclear cells of patients with metastatic renal cell carcinoma after low doses of subcutaneous immunotherapy with IFN-alpha-2b and IL-2.

To elucidate the immunologic changes induced by low doses of subcutaneous interferon (IFN)-alpha-2b plus interleukin-2 (IL-2) in patients with metastatic renal cell cancer, we have studied a group of eight patients undergoing two cycles of immunotherapy after radical nephrectomy. Natural killer (NK) cytotoxic activity, proliferative response to T-lymphocyte mitogens, and phenotypic profile of T and NK cells were determined in peripheral blood mononuclear cells (PBMCs) before and after each cycle. No significant differences were found in either of the studies realized between untreated patients and their counterpart healthy controls. However, after the first cycle, there was a significant increase in NK-cytotoxic activity and in the number of CD16+/CD56+ cells that parallelled a significant decrease in the percentage of CD3+ and CD4+ lymphocytes with no changes in the proliferative response to T-cell mitogenic signals. Individual analysis of each patient on the basis of their clinical response to treatment showed that after the first cycle of immunotherapy there were no significant differences in the immunological profiles analyzed between patients with complete or partial responses and those who did not respond to treatment, whereas, at the end of the second cycle, patients who achieved complete or partial clinical responses had higher NK-cytotoxic activity that those who remained in disease progression. We conclude that subcutaneous immunotherapy with IFN-alpha-2b and IL-2 induces a systemic immunomodulatory effect on PBMCs, manifested preferentially in a systemic NK activation and expansion that is related to the clinical outcome.

Aged↗

Immunologic studies in Holstein-Friesian cattle: an immunocompetence profile.

An immunocompetence profile has been developed for Holstein-Friesian cattle. In vitro and in vivo immunoassays were used to determine (1) the percentage of peripheral blood lymphocyte (PBL) subpopulations bearing surface-membrane receptors for sheep erythrocytes, complement, or surface immunoglobulin; (2) the PBL blastogenic response to leukoagglutinin, concanavalin A, or pokeweed mitogen, (3) the serum immunoglobulin concentrations of IgG, IgM, and IgA, (4) the humoral antibody response to keyhole limpet hemocyanin, and (5) the in vitro blastogenic response and in vivo delayed hypersensitivity skin reaction to purified protein derivative in cattle immunized with BCG.

Animals↗