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Effects of essential fatty acid deficiency, and various levels of dietary polyunsaturated fatty acids, on humoral immunity in mice.

Six experiments were conducted to determine the influence of an essential fatty acid deficient diet (EFAD), and various levels of dietary polyunsaturated fatty acids, on humoral immunity in mice. The results indicated that: 1) Consumption of diets deficient in essential fatty acids (0% corn oil) significantly reduced the humoral response. This reduction was demonstrated after feeding the essential fatty acid deficient diet for only 28 days; and preceded the effects of essential fatty acid deficiency on growth or appearance. 2) Reduced antibody response was demonstrated against T-cell dependent and T-cell independent antigens, and in both primary and secondary responses of mice fed the essential fatty acid deficient diet. 3) After 56 days of feeding the EFAD diet (0% corn oil), mice switched to the control diet (13% corn oil) for 7 days demonstrated full recovery of the humoral response. 4) Diets containing various levels of polyunsaturated fatty acids (from 2 to 70% of energy from corn oil) did not adversely affect the humoral response. The results support the hypothesis that essential fatty acids play a crucial role in maintaining the functional integrity of humoral immunity.

Animals↗

[Indicators of humoral immunity in the surgical treatment of toxic goiter].

Changes in the content of gammaglobulins, immunoglobulins of all classes, and circulating immune complexes were revealed in 70 patients with toxic goiter given thyrostatic therapy, which may be evidence of disturbed humoral immunity. These disorders were most manifest in unstable compensation of toxicosis and in patients with ophthalmopathy. In patients with developed postoperative toxic reactions no specific changes in the immune status were detected in the preoperative period and no regularities allowing the prognostication of the development of a toxic reaction were revealed. Essential changes in humoral immunity values did not occur on the eighth postoperative day.

Adult↗

[Comparison of tumor-associated cellular and nonspecific humoral immune parameters in immunologic monitoring of breast cancer].

In 119 patients with breast cancer states pT1-4 N0-3 M0 the following parameters of tumor-associated cellular and unspecific humoral immunity were determined: (1) leukocyte-migration-inhibition test against preparations of the autologous and homologous tumor tissue; (2) determination of the immunosuppressive activity of the serum on the PHA-, Con A- and PWM-induced lymphocyte transformation; and (3) determination of the alpha-2 pregnancy-associated globulin (alpha-2-PAG) serum level. In both groups of lymph node negative and positive breast cancer patients, half of the patients showed a significant reaction in the LMI test in the form of a reduced or enhanced migration of the macrophages (enhancement). In lymph node negative breast cancer patients the immunosuppressive activity of the serum on the PHA- and CON A-induced lymphocyte reactivity was decreased, whereby we found a positive correlation between the immunosuppressive activity of the serum and the LMI reactivity against autologous tumor tissue. We found no differences in the alpha-2-PAG serum level between lymph node negative and positive breast cancer patients, but there were greatly increased alpha-2-PAG levels in LMI-reactive patients compared to those showing an enhancement in the LMI test. A tumor-associated cellular immunity could be shown in the LMI test in breast cancer patients, which can be correlated with other humoral immune parameters. Especially the demonstration of an immunological enhancement in the LMI test could possibly be used for the definition of high-risk groups.

Breast Neoplasms↗

Cell-mediated and humoral immune responses in children infected with human immunodeficiency virus during the first four years of life.

OBJECTIVES: To determine whether cell-mediated and humoral immune responses to recall antigens develop in children infected with the human immunodeficiency virus (HIV) and, if so, whether these responses are retained. METHODS: Children infected with HIV and uninfected children born to mothers infected with HIV were compared with respect to lymphoproliferative responses to recall antigens and protective levels of antibody to bacterial toxoids during the first 4 years of life. RESULTS: Children infected with HIV who were enrolled in a prospective study of the natural history of the infection were relatively normal (1) in their lymphoproliferative responses to diphtheria toxoid, tetanus toxoid, and Candida, and (2) in their ability to make protective diphtheria and tetanus antitoxins during the first 2 years of life. During the next 2 years, attrition was noted in both lymphoproliferative and humoral responses. Attrition in response was not necessarily correlated with declining numbers of helper T cells. CONCLUSIONS: These results suggest that both cellular and humoral immune responses develop early in life in most children infected with HIV, while they remain relatively well both clinically and immunologically. Previously reported severe immune deficits in these children were probably attributable to advanced clinical disease when they were first studied.

Age Factors↗

[Study of the humoral immune suppression of recombinant human collagen type II peptide 250-270].

AIM: To investigate the modulation of rhC II 250-270 peptide on special humoral immune response in the course of oral administration. METHODS: ELISA was used to determine antigen-specific antibodies in mice sera. The frequency of anti-C II and anti-C II (250-270) antibody-forming spleen cells was measured by ELISPOT. RESULTS: The level of C II- and C II (250-270)- specific IgG in serum from the mice fed with rhC II (250-270) were (0.82+/-0.02) and (0.84+/-0.04) respectively, and lower significantly than those of collagen-induced arthritis (CIA) control group. The anti-C II (250-270) antibody responses were suppressed obviously (P<0.01). The frequency of antibody-forming cells in the spleen from rhC II (250-270)-fed mice were (158+/-9 counts/well) and (181+/-10 counts/well) respectively, and also were reduced significantly when compared with that in CIA control group (247+/-16 counts/well)(P<0.05). CONCLUSION: Oral rhC II (250-270) could induce specific suppression of humoral responds in CIA. These findings together with a better understanding of the mechanisms of oral tolerance and regulation of humoral immune response in CIA, will help the development of innovative therapeutic intervention for rheumatoid arthritis.

Animals↗

[Humoral immune response in humans and animals infected and immunized with Mycobacteria of the MAIS complex].

Hyperimmunization of mice and rabbits with surface (whole cells) and complex (ultrasound disintegrants) with the MAIS complex Mycobacterium antigens induced a humoral immune response which was largely aimed against cross-reacting than "unique" Mycobacterium antigens. Infection of BALB/c mice and rabbits with M. avium induced a humoral immune response which was chiefly against cross-antigenic Mycobacterium determinants. A series of consecutive immunochemical procedures were used to isolate from M. avium antiserum the antibody reacting with the antigenic determinants 18, 20, 24, 27, 39, 68, 94, kDa. Mab to the antigenic determinant 79 kDa of M. avium, which belong to the IgG class and unreacting with antigens of other Mycobacterium types were obtained. The antibodies isolated from hyperimmune serum and Mabs were used in the competitive EIA to determine antimycobacterial antibodies in man, mice, and rabbits. With Mab, positive results were obtained in 75% of M. avium-infected mice, 63.6% of rabbits and 63.6% of patients with M. avium infection (with 5.0% false positive results in humans). With antiserum, 83.3% of positive results were obtained in mice (with 10.0% of false positive results), 81.8 in rabbits (with 25% of false positive results) and 90.9% in M. avium-infected persons (with 30% of false positive results).

Animals↗

IL-4-producing CD8+ T cells with a CD62L++(bright) phenotype accumulate in a subgroup of older adults and are associated with the maintenance of intact humoral immunity in old age.

An increased production of proinflammatory cytokines occurs in a high percentage of elderly persons and is associated with an impaired humoral immune response. However, high IL-4 production has also been observed in old age. We now demonstrate an IL-4-producing subpopulation of CD8+ T cells in a subgroup of healthy older adults. This T cell subset is substantial in size and has a characteristic phenotype expressing CD45RO, CD28, CD62L, and CD25. IL-4-producing CD8+ T cells produce large amounts of IL-2 but not IFN-gamma or perforin, and these cells do not have a regulatory suppressive effect on other T cells. In vivo IL-4-producing CD8+ T cells can be stably detected over a year. When put into culture they also have a stable cytokine production pattern but fail to produce perforin even in the presence of IL-12. This special T cell type does not occur in persons under the age of 40, but is present in 36% of the persons >60 years of age. In this age group, IL-4-producing CD8+ T cells are more frequent in persons who are still capable of raising a humoral immune response following immunization than in others who fail to produce protective Abs after vaccination. Our results suggest that CD8+ T cells with a CD62L++(bright) phenotype accumulate in a subgroup of older adults. Due to their phenotype that enables them to migrate into lymphoid tissues and to their capacity to produce IL-4, these cells may counterbalance the overproduction of proinflammatory cytokines in old age.

Adult↗

Association of humoral immunity to human Hsp60 with the IL-6 gene polymorphism C-174G in patients with type 2 diabetes and controls.

The relationship between humoral immunity to hsp60 and type 2 diabetes along with other relevant metabolic, inflammatory and immunogenetic variables was studied in 76 non-diabetic and 74 diabetic persons aged 55-74 years selected from the population-based KORA Survey 2000. Antibodies to human hsp60 were measured in serum samples by ELISA. Hsp60 antibodies were detected in all but two individuals in a considerable range of titres (22-1,856 AU/ml). There was no significant association to age and sex, or to key clinical or metabolic parameters (BMI, WHR, HbA1c, total cholesterol, LDL cholesterol, HDL cholesterol, systolic and diastolic blood pressure, albumin, uric acid) or immunological parameters (CRP, IL-6, sIL-6R, TNFalpha, sTNFalpha R60, sTNFalpha R80). Analysis of antibody-positive individuals revealed an association between hsp60 antibodies and diabetes at borderline significance (p = 0.047), which was lost when the two antibody-negative individuals were included. Genetic analyses indicated that this association was significant in carriers of the C allele of the IL-6 promoter region polymorphism at nucleotide -174 (p = 0.02), but not in GG genotype carriers. We conclude that humoral immunity to human hsp60 may be enhanced in those diabetic patients carrying the -174C allele of the IL-6 gene. This finding may contribute to an understanding of the relationship between the -174C allele and increased risk of atherosclerosis.

Aged↗

Characterization of the humoral immune response in alpacas (Lama pacos) experimentally infected with Fasciola hepatica against cysteine proteinases Fas1 and Fas2 and histopathological findings.

A characterization of the humoral immune response of alpacas to Fasciola hepatica Fas1 and Fas2 antigens, two abundant cysteine proteinases in the excretory/secretory (E/S) products, was performed over the course of 6 months of experimental infection. Six adult alpacas aged 1-2 years old received a single dose of 200 F. hepatica metacercariae; two non-infected alpacas were kept as control group. All infected animals shed eggs 8 weeks post-infection (PI) and the number of flukes recovered at necropsy averaged 41+/-4. The livers of infected animals showed regions with chronic inflammation, granuloma containing parasite eggs, necrosis and cirrhosis. Peripheral eosinophilia in infected animals was greatly enhanced 6 weeks post-infection and later. A single peak of serum glutamic piruvic transaminase (SGPT) was observed 4 weeks PI and serum glutamic oxalacetic transaminase (SGOT) elevated 3 weeks PI and later. Circulating IgG Abs against Fas1 and Fas2 were measured by enzyme-linked immunosorbent assay (ELISA). Fas2-ELISA detected the infection 10 days PI reaching to highest titer on 7-8 weeks PI and kept elevated, until the end of infection. Fas1-ELISA detected the infection 2 weeks PI and followed the same pattern as Fas2-ELISA. Anti Fas2 IgG Abs were in higher titers and showed stronger avidity than anti Fas1 IgG Abs. In addition, rabbit IgG antibodies raised against cysteine proteinase Fas2 showed infiltration of this parasite antigen associated to the degradation of bile ducts and liver parenchyma of infected alpacas. In the present study we have established a F. hepatica experimental infection of alpacas, Fas2 appears to have a role in the pathogenesis of the liver damage in alpacas caused by the liver fluke. Infected alpacas elicited a strong humoral immune response against fluke cysteine proteinases Fas1 and Fas2, which might be considered as candidates for immunodiagnosis and vaccine development against fasciolosis in alpacas.

Animals↗

Complex humoral immune response against a benign tumor: frequent antibody response against specific antigens as diagnostic targets.

There are numerous studies on the immune response against malignant human tumors. This study was aimed to address the complexity and specificity of humoral immune response against a benign human tumor. We assembled a panel of 62 meningioma-expressed antigens that show reactivity with serum antibodies of meningioma patients, including 41 previously uncharacterized antigens by screening of a fetal brain expression library. We tested the panel for reactivity with 48 sera, including sera of patients with common-type, atypical, and anaplastic meningioma, respectively. Meningioma sera detected an average of 14.6 antigens per serum and normal sera an average of 7.8 antigens per serum (P = 0.0001). We found a decline of seroreactivity with malignancy with a statistical significant difference between common-type and anaplastic meningioma (P < 0.05). We detected 17 antigens exclusively with patient sera, including 12 sera that were reactive against KIAA1344, 9 against natural killer tumor recognition (NKTR), and 7 against SRY (sex determining region Y)-box2 (SOX2). More than 80% of meningioma patients had antibodies against at least one of the antigens KIAA1344, SC65, SOX2, and C6orf153. Our results show a highly complex but specific humoral immune response against a benign tumor with a distinct serum reactivity pattern and a decline of complexity with malignancy. The frequent antibody response against specific antigens offers new diagnostic and therapeutic targets for meningioma. We developed a statistical learning method to differentiate sera of meningioma patients from sera of healthy donors.

Antibodies, Neoplasm↗

Cell-mediated and humoral immune response to non-viable Mycoplasma pulmonis in mice enhanced by cross-linked ricin.

The enhancing effect of cross-linked ricin (CL-ricin) on the cell-mediated and humoral immune response of mice to non-viable Mycoplasma pulmonis was studied. The cell-mediated immune response was evaluated by means of the delayed-type footpad swelling, and the humoral immune response by means of the indirect hemagglutination test. Mice pre-treated subcutaneously with non-viable M. pulmonis and CL-ricin showed significantly increased delayed-type footpad swelling when they were injected in the footpad with the same antigen 7 days later. Delayed-type footpad swelling was not detected in mice pre-treated only with non-viable M. pulmonis or CL-ricin followed by footpad injection with non-viable M. pulmonis. Injection of non-viable M. pulmonis in the footpad on Days 3, 7, 14, 21, 28, 35 and 42 after pre-treatment with non-viable M. pulmonis and CL-ricin resulted in significant footpad swelling. Delayed-type footpad swelling was transferred by intravenous injection of spleen cells from mice which had been pre-treated 7 days previously with non-viable M. pulmonis and CL-ricin into non-treated recipient mice. Intravenous injection of anti-mouse thymus cell serum into mice previously pre-treated with non-viable M. pulmonis and CL-ricin reduced the delayed-type footpad swelling significantly. Mice pre-treated subcutaneously with non-viable M. pulmonis and CL-ricin showed a marked increase in serum antibody titers compared with those that received non-viable M. pulmonis alone.

Adjuvants, Immunologic↗

Comparison of effects of smoking and smokeless tobacco "Maras powder" use on humoral immune system parameters.

BACKGROUND: The aim of this study is to assess the impacts of "Maras powder" and cigarette smoking on the parameters of the humoral immune system. MATERIAL AND METHODS: One hundred seventy seven subjects were included in the study. The IgA, IgG, IgM, C3 and C4 levels were detected via nephelometric method. RESULTS: In 1.4% of the control group IgM levels were below normal where it was 10.8% and 18.6% in Maras powder group and in cigarette smoking group respectively. The IgM levels of both groups were significantly lower compared to the control group (P < .05). Nonetheless, the IgE levels of Maras powder group and smoking group were found to be remarkably higher compared to the control group (P < .01). CONCLUSION: Effects of Maras powder on humoral immune response were found to be similar to that of smoking.

Adult↗

The effect of Plantago ovata on humoral immune responses in experimental animals.

The effect of the aqueous extract of Plantago ovata (PO) (Plantaginaceae) consisting of a mixture of polysaccharides and glycoside on humoral immune responses was studied. In rabbits, after oral administration of PO (0.5 g/kg) a significant decrease in anti-HD antibody titre was observed in primary response. Intraperitoneal injection of 0.25 g/kg of PO in mice prior to immunisation with sheep red blood cells (SRBC) resulted in a significant decrease in hemagglutinating antibody (HD) titre. Oral administration and intraperitoneal injection of 0.25 and 0.5 g/kg of PO resulted in a significant increase in white blood cells (WBC) and spleen leukocytes counts. The spleen weight also increased with intraperitoneal injection (0.25 and 0.5 g/kg) and oral administration of 0.5 g/kg of PO. Present results indicate that PO can suppress the humoral immune responses, especially in primary immune response.

Animals↗

Effect of fresh frozen plasma and gammaglobulin on humoral immunity in neonatal sepsis.

Fresh frozen plasma and intravenous immunoglobulin are used as prophylaxis against, and for the treatment of, neonatal infection. It is assumed that any beneficial effect is mediated through the humoral immune factors contained in each preparation. The effect of fresh frozen plasma and intravenous immunoglobulin on humoral immune markers (immunoglobulins and IgG subclasses, complement components and activation products, and C reactive protein) was investigated over a 24 hour period after their randomised administration to 67 infants with suspected infection. Thirty infants without suspicion of infection were studied as controls. Compared with control infants, infants with suspected infection had increased concentrations of C reactive protein, reduced concentrations of fibronectin, and increased concentrations of the complement activation marker C3d, but similar concentrations of IgG, IgG subclasses, IgA, and IgM. After intravenous immunoglobulin treatment (500 mg/kg) concentrations of total IgG and all IgG subclasses increased, as did IgA and complement component C4. Concentrations of C reactive protein decreased after intravenous immunoglobulin treatment and were significantly lower than baseline after 24 hours. In contrast, no change in IgG or IgG subclass concentrations occurred after fresh frozen plasma administration. At 24 hours after fresh frozen plasma administration, concentrations of IgA, IgM, and C4 were significantly higher than baseline and serum IgA was significantly higher than in infants tested 24 hours after intravenous immunoglobulin treatment. These results confirm the rational basis for intravenous immunoglobulin treatment but question the value of fresh frozen plasma, particularly in the light of its attendant problems as an untreated blood product.

Antibody Formation↗

Humoral immune responses to Porphyromonas gingivalis before and following therapy in rapidly progressive periodontitis patients.

We have performed studies aimed at elucidating the nature of the humoral immune response in rapidly progressive periodontitis (RPP). We analyzed the sera of 36 periodontally normal subjects and 36 RPP patients for titers and avidities of IgG antibodies reactive with the antigens of Porphyromonas gingivalis using ELISA, prior to and following treatment. We used whole-cell sonicate, purified lipopolysaccharide (LPS), and total extractable protein as plate antigens. Twelve of the patients had antibody titers at least 2-fold greater than the median of the controls and were designated as seropositive. The remaining 24 patients had titers that did not exceed twice the median titer of the controls and were designated as seronegative. For both patient groups, antibody titers were highest when whole-cell antigen was used, intermediate for LPS, and lowest for the protein fraction. Following treatment, median titer for seropositive patients decreased from pretreatment values of 241.7 to 76.5, while median titer for seronegative patients increased from 39.5 to 80.1. Avidities of pretreatment sera from both patient groups for all 3 antigen preparations were lower than the median avidities of the control sera. Avidity significantly increased following treatment to levels greater than those for control sera in both patient groups. Thus, some young adults with severe periodontitis mount a humoral immune response and produce high levels of serum IgG antibodies reactive with antigens of P. gingivalis, while others do not. The antibodies produced are of relatively low avidity, and may therefore be relatively ineffective biologically. Therapy, which greatly reduces antigen load, appears to stimulate production of higher avidity IgG antibodies in both patient groups; in the seropositive group, low avidity antibodies appear to be replaced by antibodies of higher avidity. Both the purified LPS and protein fractions contain reactive antigen(s), although LPS binds more antibody. Our data are consistent with the idea that many RPP patients do not produce protective levels of biologically functional antibody during the course of their natural infection, but they may be stimulated to do so by treatment.

Adult↗

Organochlorine contaminant exposure and associations with hematological and humoral immune functional assays with dam age as a factor in free-ranging northern fur seal pups (Callorhinus ursinus).

Potential effects of organochlorine contaminant (OC) exposure on humoral immune function and health of free-ranging northern fur seals were investigated. Forty-two "neonates" were captured for blood sample collection and re-sampled as "pups" 29-51 days later. OCs were extracted from whole blood to identify polychlorinated biphenyl congeners and chlorinated pesticides by high performance liquid chromatography. Humoral immune function was assessed by antibody responses to vaccination and immunoglobulin concentrations. Additional health status indicators included leukocyte counts and haptoglobin concentrations. Mean OC concentrations were higher in neonates than at recapture. Neonates of young dams had higher mean OC concentrations than neonates of older dams. A higher proportion of old dam's pups developed a twofold or greater increase in antigen-specific antibodies compared to young dam's pups. Higher OC exposure and poor immune responses in first-born pups may indicate a higher risk of secondary morbidity and mortality than pups of multiparous dams.

Age Factors↗

Humoral immune responses to human lymphoma cell heterotransplants in the central nervous system of athymic, nude mice.

Human malignant lymphoma cells may be readily heterotransplanted into the brains of athymic nude mice. We have examined humoral immune responses to these lymphoma cells and have found a primary cytotoxic IgM and a late cytotoxic IgG response. Nude mice with tumors growing intracerebrally were injected intravenously with fractionated IgM or IgG anti-lymphoma cell antibody obtained from heterozygous immunocompetent animals. Frozen brain sections from these mice stained with fluoresceinated antibodies to mouse IgG and IgM revealed the presence of IgG but no IgM. Thus, IgM could not cross the blood-brain barrier to react with the heterotransplanted lymphoma cells. It is proposed that xenogeneic tumor cells grow readily within the brains of nude mice because these cells are protected from a primary host cytotoxic IgM response by the blood-brain barrier. The blood-brain barrier renders the brain an immune sanctuary within which the impaired cell-mediated immune responses of nude mice are further compromised by the exclusion of a major component of the humoral immune response.

Animals↗

In vivo manipulation of endogenous metallothionein with a monoclonal antibody enhances a T-dependent humoral immune response.

Metallothionein (MT) is a small stress response protein that can be induced by exposure to heavy metal cations, oxidative stressors, and acute phase cytokines that mediate inflammation. In previous experiments, we have shown that exogenous MT can affect cell proliferation, macrophage and cytotoxic T lymphocyte function, and humoral immunity to T-dependent antigens. In the studies described here, we have explored the effect of a monoclonal anti-MT antibody (clone UC1MT) on the role that endogenous MT plays in the humoral immune response. In vivo injection of UC1MT significantly increased the humoral response to simultaneous challenge with ovalbumin (OVA). In contrast, mice immunized with OVA in the presence of an isotype-matched antibody control (MOPC 21) showed no change in the anti-OVA humoral response. The predominant anti-OVA response that was enhanced by UC1MT treatment was the IgG(1) response; the IgG(2a) anti-OVA response was not altered by UC1MT treatment. UC1MT treatment increased the numbers of IgG anti-OVA secreting cells as measured by ELISPOT assay, suggesting that blocking the effects of MT synthesized during the immune response augments the differentiation of antigen-specific plasma cells. The percentages of T and B cells in the spleens of animals from each treatment group were not significantly different, suggesting that this regimen of UC1MT treatment does not significantly affect hematopoiesis, but rather alters antigen-induced differentiation of lymphocytes. These observations are compatible with previous results from our laboratory that suggest that endogenous MT synthesized during the normal immune response or as a consequence of toxicant exposure suppresses in vivo immune function. In light of the fact that significant amounts of MT can be synthesized during toxicant exposure, manipulation of MT levels with an anti-MT antibody may ultimately represent an important therapeutic approach to the treatment of immune dysfunctions that result from toxicant exposure.

Animals↗