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Reticuloendothelial Fc receptor function in SLE patients. II. Associations with humoral immune response parameters in vivo and in vitro.

We studied the relationship between reticuloendothelial Fc receptor function and some parameters of the humoral immune response in vivo and in vitro in 18 SLE patients. Fc receptor-mediated immune clearance correlated remarkably well with (a) a decrease of antigen specific IgG after immunization with a primary test antigen (alpha-Helix pomatia haemocyanin) (P less than 0.01) and (b) the spontaneous IgG release in vitro of B cells obtained from peripheral blood (P less than 0.01). These two parameters were significantly interrelated. Reticuloendothelial Fc receptor function was not related to serum IgG levels. The study provides evidence for an association between polyclonal B cell activation and Fc receptor-mediated immune clearance in SLE patients. The possible nature of this association is discussed.

Adult↗

Suppression of the anti-erythrocyte immune response in mice by the C5b--9 complex of complement.

The C5b--9 complex of complement associated with sheep erythrocyte membranes suppresses the immune response of mice to sheep erythrocytes as measured with the Jerne plaque technique. This type of immune suppression is independent of early complement components and antibody, and is mediated by both human and guinea-pig complement components. The degree of immune suppression correlates with the number of C5b--9 complexes per cell used for immunization: 21,000 C5b--9 complexes per erythrocyte lead to a 97% inhibition of the immune response in comparison to untreated erythrocytes. Inhibition requires the full assembly of the C5b--9 complex including C8 and C9. Virtually no inhibition was observed by the C5b--7 complex. C5b--9 and IgG-mediated immune suppression do not function additively. From dose-response experiments it is concluded that separate and mutually independent sites mediate suppression by C5b--9 and IgG, respectively.

Animals↗

Differential patterns of serum biomarkers of immune activation in human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis, and adult T-cell leukemia/lymphoma.

Adult T-cell leukemia/lymphoma (ATL) and human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) are associated with differing patterns of immune dysfunction. Biomarkers of immune activation may correlate with perturbations of immune function associated with these diseases. We conducted a pilot cross-sectional study to assess four candidate biomarkers of immune activation. beta 2-microglobulin, neopterin, tryptophan, and kynurenine levels were assayed in stored sera from asymptomatic, human T-cell leukemia virus type I (HTL V-I)-seronegative (HTLV-I-) and HTLV-I-seropositive (HTLV-I+) individuals, and ATL and HAM/TSP patients previously enrolled in seroepidemiological studies in Jamaica. Mean levels of beta 2-microglobulin, neopterin, and kynurenine were significantly elevated among ATL patients compared to the other study groups. Mean tryptophan levels were significantly lower among ATL and HAM/TSP patients than HTLV-I- and HTLV-I+ groups. No significant differences in biomarkers were found between the HTLV-I- and HTLV-I+ groups. Among HAM/TSP patients, a significant association was found between elevated neopterin levels and symptoms of less than 4 years duration. In Cox proportional hazards regression modeling, neopterin and tryptophan were found to be independent predictors of survival among ATL patients. This study demonstrates a differential pattern of biomarkers of immune activation among ATL and HAM/TSP patients compared to HTLV-I- and HTLV-I+ individuals. Neopterin and tryptophan may be useful clinical indicators of disease severity and prognosis among HAM/TSP and ATL patients.

Adult↗

Rhythms of immunity.

Rhythms of daily activity are found in all vertebrate species, some of them being diurnal (like humans, dogs, pigeons), others--nocturnal (like mice, rats and bats). Some species undergo very pronounced seasonal changes, as they hibernate in the winter or mate only at the specific seasons. The main regulator (a clock and a calendar) for daily and seasonal rhythms is the periodicity of the external light-darkness, reflected by the periodicity of melatonin secretion from the pineal gland, which is inhibited by light and induced during the darkness. In contrast to melatonin which peaks during the night both in diurnal and noctural species, the cyclicity of other hormones and several immune parameters correlates with the pattern of the animal locomotor activity-resting. The immune parameter that peaks at one time of day for a diurnal species peaks about 12 h later for a nocturnal one. Various immune parameters peak at various time points, anticipating an encounter with pathogens during the period of activity while energetically expensive resolution of the immune response during the resting. Daily and seasonal cyclicity of the immune functions are temporally integrated with other physiologic and behavioral processes and all of them are regulated and coordinated with daily and seasonal changes of an external environment by the neuroendocrine homeostatic system.

Animals↗

The correlation between insulin antibodies and circulating immune complexes in diabetics with and without microangiopathy.

The relationship between immune complexes and insulin antibodies was evaluated in 237 insulin treated subjects with a duration of diabetes of more than 1 year. Ninety-seven diabetics were selected at random (group 1) whereas 140 according to the presence of diabetic microangiopathy (group 2). Immune complexes were evaluated by the solid phase C1q binding test in all patients and by conglutinin radioimmune assay in most of them. Insulin antibodies were determined by Christiansen's and Anderson's methods. Immune complexes as detected by the solid phase C1q method were found increased in group 1 and there was an inverse correlation between these complexes and insulin antibody levels. In group 2 patients with microangiopathy the amount of this kind of complex was significantly greater than in those without microvascular lesions and there was no correlation with insulin antibodies. Immune complexes as detected by conglutinin were found increased in group 2 patients and these were significantly correlated with the level of insulin antibodies. No increase in these immune complexes was found in patients with microangiopathy when compared with patients without microangiopathy. Insulin antibodies were not correlated with the presence of complications. Overall, immune complexes detected by C1q binding were significantly correlated with the presence of microangiopathy. In patients with high insulin antibody levels the complexes formed were not detected by C1q binding. The immune complexes detected by conglutinin are correlated with insulin antibodies, but not with the presence of microangiopathy.

Adolescent↗

Comparison of immune parameters in patients with one or two primary malignant neoplasms.

The purpose of this study was to correlate cellular immune responses and cytokine production in vitro between patients with one or two primary malignant neoplasms. One hundred and ninety-three patients (110 patients with one primary malignant neoplasm (group I), and 83 patients with two primary tumors (group II), entered this study. Mononuclear cells isolated from peripheral blood were tested in the following tests: (a) proliferative responses in the autologous and allogeneic mixed lymphocyte reaction (auto- and allo-MLR respectively): (b) natural killer cell activity; (c) production of interleukin-2 during the allo-MLR, and (d) interleukin-1 beta production by lipopolysaccharide-stimulated monocytes. All these parameters were found to be decreased in cancer patients as compared to normal donors (p < 10(-3)). In addition, we were able to detect significant differences between the values obtained from patients in groups I and II (p < 10(-2)). These data suggest a further impairment in cancer patients' immune status after the diagnosis of a second malignancy.

Cytotoxicity, Immunologic↗

Epidermal cis-urocanic acid levels correlate with lower specific cellular immune responses after hepatitis B vaccination of ultraviolet B-exposed humans.

Urocanic acid (UCA) is a major UV-absorbing chromophore in the epidermis and has been suggested to act as one of the initiators of UV-induced immunosuppression. cis-UCA, the isomer from UCA that is formed upon UV exposure, has been shown to impair some cellular immune responses. cis-UCA levels were determined in a study in which the influence of ultraviolet B (UVB) exposure on immune responses after hepatitis B vaccination in human volunteers was established. A significant increase in cis-UCA levels was found in the skin of UVB-exposed volunteers compared with controls. cis-UCA levels, calculated as the percentage of the total UCA amount, in UVB-exposed volunteers correlated significantly with the cumulative UVB dose received in 5 consecutive days, i.e. the higher the UVB dose (J/m2), the higher the cis-UCA levels (until a cis-UCA plateau was reached in the so-called photostationary state). Correlations between skin cis-UCA levels and immune responses were determined, and they revealed no statistically significant correlations among lymphocyte proliferation responses after either mitogenic stimulation or stimulation with recall antigens. No correlation was found between cis-UCA levels and hepatitis B-specific antibody titers. However, we found a statistically significant negative correlation between cis-UCA levels and hepatitis B-specific lymphocyte proliferation responses when volunteers were irradiated with UVB before hepatitis B vaccination. In other words, volunteers with high cis-UCA levels caused by UVB exposure showed lower cellular immune responses against hepatitis B antigen after hepatitis B vaccination.

Adult↗

Interstitial lung disease in scleroderma. Immune complexes in sera and bronchoalveolar lavage fluid.

Interstitial lung disease is a common feature of scleroderma (systemic sclerosis), and it may be a major determinant of morbidity and mortality. Analysis of bronchoalveolar lavage fluid from patients with scleroderma has shown evidence of inflammation in the lower respiratory tract of many patients. We have analyzed sera and bronchoalveolar lavage fluid from scleroderma patients for the presence of immune complexes, which may play a role in the inflammatory process. Using a solid-phase C1q enzyme-linked immunosorbent assay, we detected immune complexes in the sera of 6 of 23 patients (26%) and in none of 32 controls (P less than 0.01). All 6 patients with serum immune complexes had inflammatory cells in bronchoalveolar lavage fluid, and the presence of serum immune complexes correlated with the percentage of neutrophils in lavage fluid (P less than 0.02). Immune complexes were detected in lavage fluid of 11 of 21 patients (52%) compared with 1 of 7 normal controls (14%). Subjects having immune complexes in lavage fluid had a lower forced vital capacity than did those without lavage fluid immune complexes (P less than 0.05). The levels of immune complexes in bronchoalveolar lavage fluid exceeded those in serum by a mean of 45-fold, suggesting either local formation or selective deposition of immune complexes in the lower respiratory tract of some scleroderma patients.

Adult↗

Circulating immune complexes in experimental filariasis.

Circulating immune complexes have been investigated in jirds (Meriones unguiculatus) infected with the filarial nematode Brugia pahangi. Two-month-old male jirds were inoculated with seventy-five B. pahangi infective larvae into the left groin. At 8 months post-infection, sera of individual animals from a group of seventeen infecteds and seventeen age-matched controls were analysed for immune complexes by (1) a solid-phase C1q binding assay (Clq-SP) and (2) precipitation with 3.5% polyethylene glycol followed by binding of 125I-labelled rabbit anti-jird Ig antiserum (PEG). A significant increase in the level of circulating immune complexes was shown in the infected group as compared with the controls for both assays, with a P value = 0.005 for PEG and P = 0.001 for Clq-SP. Using the mean of the control group +/- 2 s.d. as the upper limit of the normal range, 24% of the infected group had elevated immune complex levels by the PEG assay, and 41% were elevated in the C1q-SP assay. A high degree of variability was noted in the levels of immune complexes among individual animals in the infected group by each test. No correlation between immune complex levels and numbers of circulating microfilariae was found in either assay.

Animals↗

[Cellular immunity: in vitro leukocyte migration inhibition does not correlate with the tuberculin skin test].

The leukocyte migration inhibition test (LMIT) is said to be an in-vitro correlate of cell mediated immunity in vivo. The authors' series of experiments, however, in which they compared skin tests and LMIT (taking the same tuberculin for both tests), showed wed no correlation between the two tests. The discrepancy between these results and those of other authors may be due to the fact that the authors worked under sterile conditions. It is known that contamination even by minute amounts of endotoxin may alter the results of in-vitro tests of cell mediated immunity. The authors therefore question the value of the LMIT as an in-vitro counterpart of the skin test.

Blood Sedimentation↗

Passive immunization against experimental pseudomonas infection: correlation of protection to verder and evans "o" serotypes.

Passive-protection tests were conducted in mice with antisera from rabbits immunized with formalinized or heat-killed cells or with an alcohol-precipitated fraction from the slime layer. Protection was conferred by antisera against the heatstable antigens and correlated well with agglutinin levels. Specificity was found to relate closely to the heat-stable "O" serotypes as defined by Verder and Evans.

Journal Article↗

Sequential evaluation of general immune competence in cancer patients: correlation with clinical course.

An evaluation of general immunologic reactivity was performed in 116 patients with malignant melanoma and in 40 patients with skeletal and soft tissue sarcoma who received adjunctive immunotherapy. An excellent correlation was observed between delayed cutaneous hypersensitivity to DNCB and the clinical extent of malignancy. Eighty percent of patients with Stage I disease were DNCB positive, whereas only 37% of Stage III patients were reactive on initial testing. A method for sequential evaluation of DNCB response was established, and revealed that variations in immune reactivity occurred that also correlated with the patient's clinical course. Persistence of nonreactivity to DNCB or conversion from a reactive to an anergic status was associated with postoperative recurrence in more than 80% of the patients. Conversely, conversion from an anergic to a reactive status was observed if tumor control was achieved. These results indicate that the defect in systemic immunity is closely associated with tumor cell burden, and that sequential evaluation of DNCB reactivity is a clinically useful monitor of disease progression.

Adolescent↗

Vaccination against chlamydial genital tract infection after immunization with dendritic cells pulsed ex vivo with nonviable Chlamydiae.

Chlamydia trachomatis, an obligate intracellular bacterial pathogen of mucosal surfaces, is a major cause of preventable blindness and sexually transmitted diseases for which vaccines are badly needed. Despite considerable effort, antichlamydial vaccines have proven to be elusive using conventional immunization strategies. We report the use of murine bone marrow-derived dendritic cells (DC) pulsed ex vivo with killed chlamydiae as a novel approach to vaccination against chlamydial infection. Our results show that DC efficiently phagocytose chlamydiae, secrete IL-12 p40, and present chlamydial antigen(s) to infection sensitized CD4(+) T cells. Mice immunized intravenously with chlamydial-pulsed DC produce protective immunity against chlamydial infection of the female genital tract equal to that obtained after infection with live organisms. Immunized mice shed approximately 3 logs fewer infectious chlamydiae and are protected from genital tract inflammatory and obstructive disease. Protective immunity is correlated with a chlamydial-specific Th1-biased response that closely mimics the immune response produced after chlamydial infection. Thus, ex vivo antigen-pulsed DC represent a powerful tool for the study of protective immunity to chlamydial mucosal infection and for the identification of chlamydial protective antigens through reconstitution experiments. Moreover, these findings might impact the design of vaccine strategies against other medically important sexually transmitted diseases for which vaccines are sought but which have proven difficult to develop.

Adoptive Transfer↗

HIV-specific CD8 T-cell activity in uninfected injection drug users is associated with maintenance of seronegativity.

OBJECTIVES: To determine whether HIV-exposed, uninfected subjects (EUs) having HIV-specific effector activity are at a reduced risk for seroconverting compared with EUs with no HIV-specific effector responses. DESIGN: Twenty-eight intravenous drug users (IVDU) with documented risk for HIV infection over a 1-year period were screened for the presence of HIV-specific CD8+ effector cell activity. Group I included 18 IVDUs who remained seronegative despite exposure to HIV through needle sharing with partner(s) known to be HIV infected. Group II included 10 IVDUs who seroconverted after similar HIV exposure. METHODS: The enzyme-linked immunospot (ELIspot; Mabtech AB, Nacka, Sweden) assay was used to measure the frequency of HIV-specific interferon-gamma secreting cells. Peripheral blood mononuclear cells (PBMC) were stimulated with a panel of synthetic HIV peptides in a major histocompatibility complex class I antigen-restricted fashion. PBMC from group II were obtained from timepoints 7 months or less before seroconversion. RESULTS: Twelve of 18 (66.7%) persistently seronegative subjects versus none of 10 seroconverters exhibited detectable HIV-specific effector responses at the sampling date (P < 0.001; Fisher's exact test). This represents an odds ratio of 40.38 (95% confidence intervals 2.95 to > 3000). CONCLUSION: EUs who have developed HIV-specific effector responses are at a reduced risk for seroconversion compared with EUs who do not develop this type of immunity. This observation supports the hypothesis that HIV-specific effector responses are a correlate of immune protection from HIV infection.

CD8-Positive T-Lymphocytes↗

Immunogenicity of purified Habu snake-venom toxoid in guinea pigs and monkeys with special reference to HR1 component.

Purity of the parent toxin influenced greatly the immunogenicity in guinea pigs of HR1 component of Habu-venom toxoid. The potency of HR1 toxoid in terms of the immunizing unit (ImU) appeared to be related to the antigen and aluminum contents. The immune response of the animals differed depending on the purity of the toxoid when the dose-response curve was examined over a wide range of the antigen dosage. Anti-HR1 titers of the guinea pigs immunized with crude toxoid (adsorbed) reached a plateau at about 10-20 U/ml ane further rise was not remarkable even when the amout of the antigen was increased several times, while 200 U/ml (maximum 400 U/ml or higher) of annti-HR1 was produced with a large amount of highly purified HR1 toxoid. Purified toxoid showed an excellent immunogenicity also in monkeys. The amounts of antigens necessary for the basic immunization to resist the challenge with a certainly lethal dose of crude venom were 18 and 0.5 mg as protein, for a crude and a highly purified toxoid, respectively. The total amount of aluminum was also reduced from 8.1 (crude toxoid) to 0.5 mg (purified toxoid). Multiple injections for the primary immunization enhanced early production of anti-HR1 in monkeys. However, at later stage of immunization, significant correlation was observed between the amount of HR1 toxoid (in ImU) for the primary immunization and the circulating anti-HR1 titer irrespective of the schedule of immunization. Anti-HR2 higher than 10 U/ml was produced consistently in monkeys with HR2 toxoid of 1.0 ImU for the basic immunization. However, excess HR2 toxoid of more than 10 ImU seemed rather unfavorable for anti-HR2 production.

Aluminum↗

[Neuroimmune interactions in normal aging and in Alzheimer disease].

The study was undertaken to examine nerve-immune processes and the specific visual and limbic-reticular-cortical systems by analysing visual evoked potentials (VEP), as well as nerve-immune relationships in 21 patients aged 62.2ë1.3 years who had Alzheimer's disease and in 15 healthy individuals of the same age. AD patients were found to have lower lymphocyte count, enhanced proliferative activity of T lymphocytes and to tend to have increased production of interleukin (IL-1) as compared to that in healthy individuals. In AD, latent periods of late EVP components are higher than normal age-specific ones. The relationship between VEP and immunity parameters differ in normal ageing and AD. In health, there is a negative correlation between the latencies of N1, P2, N2 VEP components and the lymphocyte count and between the amplitude of a N1 VEP component and the production of IL-1. There is a prevalent correlation of immune parameters with VEP parameters in the right hemisphere. In AD, the higher proliferative activity of T lymphocytes is associated with more prolonged latent periods of N3 VEP components, suggesting that there are abnormal changes in the limbic-reticular-cortical systems of the brain.

Aging↗

Cellular immunity to encephalitogenic protein in multiple sclerosis. Correlations with other laboratory characteristics at different disease courses.

A very suggestive, although non-significant, correlation was found between cellular immunity to encephalitogenic protein in multiple sclerosis and the genetic marker HLA-B7 in patients with no disease activity during at least the past 5 years and in those with a chronic progressive disease course during recent years, but not in patients studied longitudinally after a relapse. Only the latter group showed a significant correlation with parameters indicating intrathecal synthesis of immunoglobulin. No correlation was demonstrable with a parameter indicating intrathecal synthesis of measles antibodies.

Antibodies, Viral↗

Immunomorphological lymph node changes in patients with operable bronchogenic squamous cell carcinoma.

Histological changes in tracheobronchial and bronchopulmonary lymph nodes of patients with operable (i.e. stages T1/2, N0/1, M0) bronchogenic squamous cell carcinoma were examined histometrically. Out of 29 patients, 10 survived less than 12 months and 19 lived longer than two years after surgery. Quantitative methods were employed for measuring structural changes in lymph node sections at the histological and cellular level. The following parameters reflecting both cellular and humoral immune responses correlated with survival: relative numbers of large lymphoid cells and mitotic figures in the paracortical ("thymus-dependent") area; volume of the follicular (predominantly B-cell) cortex; and volume of germinal centers. Pronounced accumulation of histiocytes or dust-loaded macrophages in the paracortex and presence of "empty" lymph sinusoids (i.e. without sinuhistiocytosis) correlated inversely with survival. In addition to the theoretical importance and considerations of a documented immune response, such data could help in identifying high risk groups within the same stage of bronchogenic carcinoma of a given type.

Carcinoma, Bronchogenic↗