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Malnutrition and humoral immunity: long-term protein deprivation.

The effect of long-term protein deprivation and refeeding on delayed-type hypersensitivity (DTH) and humoral immune function was investigated in rats. Animals previously sensitized to keyhole limpet hemocyanin (KLH) were placed on a 2% protein diet ad lib for 8 weeks, after which some groups of animals were refed for up to 4 weeks. Control rats received normal rat chow. Recall skin testing with KLH, and immunization with tetanus toxoid (TT) were used to assess DTH and humoral immune responses. Weight, DTH, and antibody responses declined progressively with protein deprivation. Refeeding restored skin test responses and humoral immunity. There was a direct correlation between degree of malnutrition as reflected by weight and antibody responses as well as between DTH and antibody responses. The data demonstrate that chronic protein deprivation modulates both DTH skin testing and humoral immune responses and show that under conditions of altered immune function, there is a correlation between DTH responses and humoral immune function.

Animals↗

CSF proteogenomics implicates novel proteins and humoral immunity in Alzheimer's disease risk.

We profiled 2,961 cerebrospinal fluid (CSF) proteins in 1,005 participants of the Alzheimer's Disease Neuroimaging Initiative (ADNI), including 1,066 proteins not measured in prior studies, using mass spectrometry (MS). We mapped protein quantitative trait loci (pQTLs) in CSF, compared them with brain and plasma pQTLs, and integrated them with Alzheimer's disease (AD) genome-wide association study (GWAS) data. We identified 1,417 index cis pQTLs for 654 unique genes and 130 index trans pQTLs for 94 unique genes. Cross-tissue and cross-proteomic-platform comparisons show broad consistency between MS-based CSF pQTLs and MS-based brain pQTLs as well as affinity-based CSF and plasma pQTLs. Lastly, through integrating CSF pQTLs with the largest AD GWAS, we identified 24 candidate AD causal proteins in CSF, including 10 novel and 14 previously identified in either brain, CSF, or plasma using similar approaches. These CSF AD candidate causal proteins are involved in immune response - notably humoral immunity (3 of 24) - that expands the role of the immune system in AD beyond innate immunity, as well as lysosomal function and neurovascular growth and remodeling. Together, our findings provide novel insights into AD biology and new targets for biomarker and therapeutic development.

Journal Article↗

The role and mechanism of cobra venom factor-induced suppression of the humoral immune response in guinea pigs.

The cobra venom factor (CVF)-mediated suppression of the humoral immune response to bacteriophage phi X 174, a T cell-dependent antigen, was investigated in guinea pigs. The suppression was markedly dependent on the amount of antigen used: decomplementation of animals diminished the humoral immune response when immunizing with low doses of antigen, whereas increasing the antigenic dose resulted in little or no diminution by CVF. In contrast to the results with normal animals, CVF had no influence on the humoral immune response of genetically C2-deficient guinea pigs; i.e., no suppression occurred above that due to the inherited complement deficiency state alone. We therefore postulate that CVF suppresses the humoral immune response by the depletion of C3, with no measurable role for complement split products under these experimental conditions.

Animals↗

CpG immuno-stimulatory motifs enhance humoral immune responses against hepatitis C virus core protein after DNA-based immunization.

Chronic HCV infection is associated with a high morbidity and mortality rate, and currently a prophylactic or therapeutic vaccine is not available. DNA-based immunization is a powerful method to generate cellular and humoral immune responses. However, DNA immunization against HCV core results only in a weak humoral immune response demonstrated in several studies. Therefore, co-immunization with a novel adjuvant may enhance such potentially important immune responses. We examined whether unmethylated CpG motifs in the form of oligodeoxynucleotides (ODN) or E. coli DNA can act as adjuvants for a DNA vaccination approach, since CpG motifs have been shown to stimulate the innate immune system as well as B and T cell immune reactivity. The present study demonstrates that CpG motifs enhance in vivo antibody levels after DNA immunization against HCV core. However, despite some in vitro activity of CpG motifs, no enhancement of T cell responses in vivo was observed after immunization with HCV plasmid DNA and CpG motifs in mice. Our results suggest that co-immunization with CpG-ODN may strengthen humoral immune responses but show no potential effect as an adjuvant to induce cellular immunity against HCV core.

Adjuvants, Immunologic↗

[Cellular and humoral immunity in atopic dermatitis].

In vitro tests of cellular and humoral immunity were analysed by: T and B lymphocytes, T4 and T8 lymphocyte subsets, lymphocyte blast transformation tests with unspecified mitogenom--phytohemaglutinin, C3 and C4 components of the complement and circulating immune complexes at patients from 6 to 54 years old who suffered from atopic dermatitis without any other clinical symptom of atopy (so called "pure" atopic dermatitis). Parameters of cellular and humoral immunity were analysed in the active and quiescent phase of illness. The results were statistically analyzed by Student's "t" test and compared with results of the control group. In the active phase of illness IgE level in serum was statistically and significantly increased while other parameters of humoral and cellular immunity did not significantly differ in relation to control group. In certain percentage in the active phase of illness decreased values of serum's IgA, C3 component of the complement, number of T8 lymphocytes and lymphocytes transformation test were found as well as the increase of circulating immune complexes IgG, IgM and B lymphocyte. All laboratory tests were repeated in the quiescent phase of illness, when patients had no changes on the skin in at least one month period. It was found that some increased values of serum's IgE were normalised in the quiescent phase of illness. Besides increased serum's IgE in the active phase of illness, it was not possible to determine cellular and humoral immunity defect by tests in vitro at "pure" atopic dermatitis.

Adolescent↗

Differences in intestinal humoral immunity between healthy volunteers from UK and Bangladesh.

BACKGROUND/AIMS: Intestinal morphology has been shown to vary geographically. The impact of this variation on gut mucosal humoral immunity is not well-studied. The technique of peroral whole-gut lavage (WGL) with nonabsorbable cleansing fluid can be utilized for the study of gut immune responses in health and disease. In this study, the WGL technique was employed to compare various gut humoral immune parameters in healthy volunteers from Dhaka in Bangladesh and Edinburgh, UK. METHODS: Eleven healthy individuals (all male, age range 18-32) from Dhaka and 12 healthy individuals (4 male and 8 female, age range 23-48) from Edinburgh underwent WGL with a polyethylene glycol electrolyte-based solution drunk at a rate of 1 l/h. The first clear effluent was collected and processed. An ELISA technique was used to measure total immunoglobulins (A, M and G) and antibodies to bacterial lipopolysaccharide (LPS: endotoxin) ovalbumin and eotaxin. Immunoturbimetry and radioimmunoassy techniques were used to measure protein (albumin and alpha-1 antitrypsin) and eosinophil cationic protein (ECP), respectively, in WGL fluid (WGLF). RESULTS: The total IgA, ECP and eotaxin concentrations in WGLF from the Dhaka group were significantly higher than those of the Edinburgh group (P < 0.03, P < 0.002 and P< 0.005 respectively). The IgA antibody level against the core oligosaccharide of bacterial LPS from several Gram-negative species was significantly higher in the Dhaka group compared to the Edinburgh group (P< 0.0001). Similarly, there was generally higher level of IgA antibody response against the various different LPS core structures of Escherichia coli in the Dhaka group, in particular significantly higher against R1, R3 and R4 LPS cores (P< 0.02, P< 0.03 and P< 0.01 respectively) compared to the Edinburgh group. In contrast to antibacterial antibodies, the IgA and IgM antibodies against ovalbumin were significantly lower in the Dhaka group (P< 0.001 and P< 0.003, respectively) compared to the Edinburgh group. CONCLUSIONS: This study on gut mucosal humoral immunity from two geographically distinct populations suggests that place of residence influences gut mucosal humoral immunity. This difference in stimulation of humoral immunity of the gut might explain different rates of inflammatory bowel diseases in developing and developed countries, and also provides a major challenge for the development of mucosally presented vaccine worldwide.

Adult↗

Human male genital tract secretions: both mucosal and systemic immune compartments contribute to the humoral immunity.

In contrast to numerous studies of female genital tract secretions, the molecular properties of Abs and the magnitude of humoral responses in human male genital tract secretions to naturally occurring Ags and to mucosal and systemic immunizations have not been extensively investigated. Therefore, seminal plasma (SP) collected from healthy individuals was analyzed with respect to Ig levels, their isotypes, molecular forms of IgA, and for the presence of Abs to naturally occurring Ags, or induced by systemic or mucosal immunizations with viral and bacterial vaccines. The results indicated that in SP, IgG and not IgA, is the dominant Ig isotype, and that IgM is present at low levels. IgA is represented by secretory IgA, polymeric IgA, and monomeric IgA. In contrast to the female genital tract secretions in which IgA2 occurs in slight excess, the distribution of IgA subclasses in SP resembles that in plasma with a pronounced preponderance of IgA1. The IgG subclass profiles in SP are also similar to those in serum. Thus, SP is an external secretion that shares common features with both typical external secretions and plasma. Specifically, SP contains naturally occurring secretory IgA Abs to environmental Ags of microbial origin and to an orally administered bacterial vaccine, and plasma-derived IgG Abs to systemically injected vaccines. Therefore, both mucosal and systemic immunization with various types of Ags can induce humoral responses in SP. These findings should be considered in immunization strategies to induce humoral responses against sexually transmitted infections, including HIV-1.

Antibodies↗

Cellular and humoral immunity in subacute sclerosing panencephalitis.

Cellular and humoral immunity was studied in 26 patients with subacute sclerosing panencephalitis. Results were compared with those of 14 normal controls and 11 patients suffering from other neurological disorders. It was shown that cellular and humoral immune responses are adequate in subacute sclerosing panencephalitis. The persistently elevated levels of serum immunoglobulin G (IgG) and IgA indicated a persistent infection, and their progressive rise in later stages correlated with the progressive nature of the illness. IgG progressively increased with the clinical stage in the cerebrospinal fluid unaccompanied by a corresponding rise in the measles antibody titer. This suggests that antigenic determinants other than those tested play a role in the production of IgG in the cerebrospinal fluid. The progressive increase in the ratio of cerebrospinal fluid to serum IgG with the advance of the disease suggests synthesis of IgG locally in the central nervous system. Elevated measles antibody titer in serum and cerebrospinal fluid is a consistent aid in the diagnosis of subacute sclerosing panencephalitis. It is more specific in cerebrospinal fluid than in serum. Its level did not vary significantly with the clinical stages or duration of illness. Depressed serum complement activity has been detected in some subacute sclerosing panencephalitis patients in whom serum levels of the third and fourth components of the complement were normal.

Antibodies, Viral↗

Oral immunization with recombinant BCG induces cellular and humoral immune responses against the foreign antigen.

It has been shown recently that BCG can be used as a live recombinant vaccine to stimulate immune responses. Proliferative or cytotoxic T-cell responses against several viral proteins such as HIV Gag, Env or Nef were obtained after parenteral immunization with BCG expressing these proteins. Antibody responses were also obtained after immunization of mice with recombinant BCG strain which expressed lac Z under the control of a promoter sequence isolated from Mycobacterium paratuberculosis. We have used this recombinant vaccine in guinea-pigs to investigate the influence of various routes of immunization on the immunogenicity of a foreign antigen expressed by recombinant BCG. Guinea-pigs were immunized by oral, respiratory or intradermal routes and proliferative responses, delayed-type hypersensitivity and antibody responses specific for beta-galactosidase were followed for 16 weeks. Results demonstrated that humoral and cellular immune responses specific for beta-galactosidase can be produced in all groups of guinea-pigs. However, the respiratory and especially the oral route of administration induced higher local and systemic immune responses than the intradermal route of immunization. Moreover, the oral immunization of mice with this recombinant BCG induced IgA responses which could be detected in both sera and intestinal secretions. Therefore, this study demonstrates for the first time that oral immunization with recombinant BCG can induce strong cellular and humoral immune responses.

Administration, Inhalation↗

Salivary specific IgG is a sensitive indicator of the humoral immune response to Helicobacter pylori.

In humans, salivary antibodies are secreted during humoral immune response. Helicobacter pylori infection is associated with systemic humoral immune response reflected by raised serum levels of specific IgG. The present study was aimed at exploring whether salivary concentrations of specific H. pylori IgG are a reliable indicator of H. pylori infection. Serum and salivary samples were obtained from 291 subjects attending the GI clinic and tested for H. pylori-specific IgG by a direct ELISA (94% sensitivity, 95% specificity for serum determinations) using a crude H. pylori sonicate as antigen. Data are given as optical density (mean +/- S.D.). Levels of salivary H. pylori IgG paralleled those of circulating specific IgG in the 291 subjects studied (0.981 +/- 0.431 vs. 0.777 +/- 0.682, respectively). A significant positive correlation was found between specific H. pylori IgG in sera and saliva samples (r = 0.981, P < 0.0001). An overall concordance between circulating and salivary H. pylori IgG was observed in 238 out of the 291 (81.7%) subjects. Salivary H. pylori IgG represent a sensitive marker of specific humoral immune response and they may substitute circulating H. pylori IgG measurement when sera samples are not available.

Adult↗

Cell-mediated and humoral immune responses in immunized and/or Dermatobia hominis infested rabbits.

The cell-mediated and humoral immune response of rabbits to antigens from larvae of Dermatobia hominis were analyzed by leucocyte migration inhibition factor assay (MIF), immunodiffusion (ID) and passive hemagglutination (PH) test in rabbits immunized with D. hominis extract, in rabbits immunized and infested with the parasite and rabbits infested with D. hominis. Twenty rabbits were divided into five groups: Group 1, rabbits immunized with a crude antigen extract, evaluated for 40 weeks at 4 week intervals; Group 2, rabbits immunized and infested with newly hatched larvae at 14 weeks post immunization (PI) and evaluated as Group 1; Group 3, rabbits immunized, evaluated for 28 weeks at 2 week intervals; Group 4, rabbits immunized and infested at 4 weeks PI and evaluated as Group 3; Group 5, rabbits infested and evaluated for 24 weeks at 2 week intervals. Different patterns of reactivity were observed in the infested and immunized animals: immunized rabbits developed antibodies and cellular immune responses earlier and at higher levels during immunization than the infested rabbits; the infestation at 14 weeks PI, when the cell-mediated and humoral immune response began to decrease, or at 4 weeks PI when these parameters were at higher levels, elicited an anamnestic response. After the spontaneous elimination of larvae by the host, from the 4th week PI onwards, high titers of antibodies and migration inhibition indices were maintained for a long period. These results suggest that the onset of cellular and humoral immune responses after immunization may be important as a biological control of myiasis and contribute to better understanding of the immune defense mechanism of the host against D. hominis.

Animals↗

[Changes in the parameters of humoral immunity due to surgical operations or trauma].

Humoral immunity (immunoglobulins and C3) as well as nutritional conditions (serum albumin, transferrin) have been investigated in 23 patients in the acute phase after surgery and/or trauma. Immunoglobulin deficiency, well correlated with the severity of trauma, was observed in the most critically ill patients in the very early phase, followed by a rapid rise to near to normal values and typical immunologic response. There is no evidence that this depression of humoral immunity may enhance the risk of infectious complications in the postoperative period. Very different immunological patterns were observed in surgical patients with chronic sepsis.

Antibody Formation↗

Immune response to Mycobacterium lepraemurium: assessment of the humoral immune response in mice.

Intraperitoneal infection of mice with Mycobacterium lepraemurium produced a primary immune response as represented by direct (IgM) plaque-forming cells at the splenic level within a short period after infection. This response was enhanced when animals were administered a second infection fifteen days after the first one. An identical situation was observed with the developed (IgG) plaques, although the magnitude of these plaques in animals given the second challenge was of a higher order than those given only one infection. In both instances, the number of plaques declined within a very short time after reaching a peak. Higher levels of both direct and developed plaques in animals given second infection was a consequence of the dual effect of antigenic stimulus offerred through the extracellular organisms in the second challenge and intracellular organisms from the previous challenge. The rapid decline, indicated a dampening of the immune response through restricted antigenic stimulus, not only due to all organisms becoming intracellular during the course of infection but also due to structural alterations in the spleens, caused by extensive proliferation of the infecting pathogen. Comparative analysis of the humoral immune response in animals infected with M. leprae, M. marinum and M. lepraemurium indicated similarities in terms of the latent period of induction and decline of the immune response and some very distinct differences in other respects. These differences could be attributed to various factors, such as the site and dose of infection, nature of the disease induced in the animal hose and the ability of the respective organisms to become intracellular. Based on these observations, it is suggested that neither the M. lepraemurium nor the M. marinum models can fully satisfy the requirements, at least immunologically, needed to consider these models as possible substitutes for evaluation of the host-parasite interactions in M. leprae infection of mice, although such a concept has been proposed previously, especially in regard to the M. marinum model.

Animals↗

Association of HLA with humoral immune responses.

The association of HLA with humoral immune responsiveness to various common antigens was studied. Increased frequencies of HLA-A2 in the higher cold agglutinin group and of B5 in the lower heterophil antibody group were observed. But these increases were not statistically significant. Although simple phenotype frequency of neither A9 nor B5 was associated with any group studied, the positive linkage disequilibrium for haplotype of A9-B5 was observed in the higher antibody titer groups of anti-streptolysin O, cold agglutinin and heterophil antibody and in the anti-HBs antigen negative group as well as in the general Japanese population. These results suggest that there may be humoral immune response and/or suppressive genes linked to the chromosomal area where the genes coding A9-B5 exist.

Antibody Formation↗

Dissociation between systemic and mucosal humoral immune responses in coeliac disease.

We examined humoral immunity in coeliac disease as expressed in serum (systemic immunity), and in saliva, jejunal aspirate, and whole gut lavage fluid (mucosal immunity). The aims were to define features of the secretory immune response (IgA and IgM concentrations and antibody values to gliadin and other food proteins measured by enzyme linked immunosorbent assay (ELISA)) in active disease and remission, and to establish whether secretions obtained by relatively non-invasive techniques (saliva and gut lavage fluid) can be used for indirect measurements of events in the jejunum. Serum, saliva, and jejunal aspirate from 26 adults with untreated coeliac disease, 22 treated patients, and 28 immunologically normal control subjects were studied, together with intestinal secretions obtained by gut lavage from 15 untreated and 19 treated patients with coeliac disease and 25 control subjects. Jejunal aspirate IgA and IgM and gut lavage fluid IgM concentrations were significantly raised in patients with untreated coeliac disease; the lavage fluid IgM concentration remained higher in patients with treated coeliac disease than in controls. Serum and salivary immunoglobulin concentrations were similar in the three groups. Patients with untreated coeliac disease had higher values of antibodies to gliadin compared with treated patients and control subjects in all body fluids tested; these were predominantly of IgA and IgG classes in serum, and of IgA and IgM classes in jejunal aspirate and gut lavage fluid. Values of salivary IgA antibodies to gliadin were significantly higher in untreated coeliacs, though antibody values were generally low, with a large overlap between coeliac disease patients and control subjects. In treated patients, with proved histological recovery on gluten free diet, serum IgA antigliadin antibody values fell to control values, though serum IgG antigliadin antibody values remained moderately raised. In contrast, there was persistence of secretory antigliadin antibodies in treated patients (particularly IgM antibody) in both jejunal aspirate and gut lavage fluid. Antibody responses to betalactoglobulin and ovalbumin were similar to those for gliadin, including persistence of high intestinal antibody values in patients with treated coeliac disease. There was a positive correlation between antibody values in jejunal aspirate and gut lavage fluid, but not between saliva and jejunal aspirate; thus salivary antibodies do not reflect intestinal humoral immunity.

Adolescent↗

Studies on specific humoral immunity in leukemia.

The paper concerns some results in studies on humoral immunity in human and animal leukemia obtained in author's laboratory (1970-1974). The data presented here disclose immunological mechanisms of mice viral leukemogenesis (cytotoxic and blocking antibodies interrelations). The existence of specific humoral immune response in acute leukemia patients was established (immunoglobulins with the properties of antibodies were revealed in 42.6% of patients). Different forms of specific humoral immunity manifestations in different types of leukemia were distinguished (areactive, nonspecific, cytotoxic, blocking and mixed forms.

Animals↗

Differential cellular and humoral immune responses to HCV core and HBV envelope proteins after genetic immunizations using chimeric constructs.

Development of a broad based cellular and humoral immune response to hepatitis C virus (HCV) structural proteins may be important for eradication of viral infection. In previous studies in mice we demonstrated that facilitated DNA-based immunization with an HCV core DNA-expression construct stimulated the generation of weak cytotoxic T lymphocyte (CTL), helper T cell (Th), and humoral immune responses against HCV core related epitopes. To enhance the immunogenicity of this non-secreted viral structural protein at both the B- and T-cell level, several chimeric HBV-HCV constructs were prepared which were designed to express and secrete HCV core protein along with various regions of the hepatitis B envelope protein. No secretion of the chimeric proteins into the culture supernatant was detected using sensitive radioimmunoassays. However, such chimeric proteins were capable of generating CD4+ inflammatory T cell and CD8+ CTL activity against both HBV and HCV components of the fusion proteins. It was determined that the proliferative activity of T cells as well as the humoral immune responses to HCV core protein were substantially enhanced by some chimeric fusion proteins as compared to the HCV core protein alone. The strength of the immune responses appeared directly related to the level of Th1 cytokines produced by CD4+ T cells obtained from immunized animals. Further characterization of the immune responses stimulated by these DNA constructs studied helped to define some of the most immunogenic regions of the chimeric proteins that they encode.

Animals↗

Androgen-sensitive period of humoral immune reactivity development in male mice.

The influence of androgens on the humoral immune reactivity development was investigated in male CBA mice. Positive correlation was found to exist between the plasma androgen level and the primary immune response throughout the pubertal period. The androgen-sensitive period of the humoral immune reactivity development coincided with the early stages of sexual maturation (from the 18th to the 30th day of life). In mice orchidectomized on the 18th day of life (18 ORx) the immune response followed the pattern of that in intact males up to 3 months of age but did not reach its peak at 4 months of age. On the contrary, in mice orchidectomized on the 30th day of life (30 ORx) the immune response was maximal at 2 months of age and remained high thereafter. Ten-day treatment of 18 ORx mice with daily injections of testosterone propionate at a dose of 0.1 or 1 mg/kg b.w. was ineffective in making their immune reactivity pattern similar to that in 30 ORx mice, while daily injections of 5 alpha-dihydrotestosterone (DHT, 1 mg/kg b.w.) was effective. The results suggest that the stimulating influence of testes on the humoral immune reactivity development in maturing mice is effected via DHT.

Androgens↗