Limited humoral immunity in hepatitis C virus infection

BACKGROUND & AIMS: The extremely high rate of chronicity to hepatitis C virus (HVC) infection suggests an inefficient immune response. The humoral immune response to HCV was evaluated in 60 patients with chronic HCV infection and in 12 patients acutely infected with HCV. METHODS: A number of recombinant HCV antigens including the core, envelope 2 (E2), nonstructural (NS) 3, NS4, and NS5 proteins, and NS4a and E2-HVR-1 peptides were used in enzyme-linked immunoassays. RESULTS: Immunoglobulin (Ig) G antibody responses to these viral antigens, except for the HCV core, were highly restricted to the IgG1 isotype. The prevalence of antibodies of the IgG1 isotype specific for the HCV core, E2, E2-HVR1, NS3 (helicase domain), NS4, and NS5 antigens was 97%, 98%, 28%, 88%, 33%, and 68%, respectively. Antibodies of the IgG3 isotype specific for E2, E2-HVR-1, NS3, NS4, and NS5 were detected in a minority of serum samples. The IgG2 and IgG4 isotypes were rarely if ever detected. Furthermore, antibody responses to HCV viral antigens were of relatively low titer and, with the exception of anti-HCV core, were delayed in appearance until the chronic phase of infection. CONCLUSIONS: The IgG1 restriction, low titer, and delayed appearance of antibody responses elicited during HCV infection suggest that the immunogenicity of HCV proteins is limited in the context of natural infection. Inasmuch as recombinant HCV viral antigens perform as relatively normal immunogens in small animals, we suggest that the defective humoral immune responses during HCV infection may be attributable to an "immune avoidance" strategy.     

Conditioned suppression of humoral immunity in the rat.

180 Charles River rats were conditioned by pairing consumption of a novel sodium saccharin drinking solution with the effects of an ip injection of 75 mg/kg cyclophosphamide, an immunosuppressive drug. Five and 10 days after conditioning, an experimental group (Group CS) was reexposed to the saccharin drinking solution. Control Ss (Group CSo) were conditioned but were not reexposed to saccharin. On Days 10, 15, or 25 after conditioning, Ss were injected ip with sheep erythrocytes, and independent subgroups were sampled for hemagglutinating antibody titer 4, 6, or 8 days later. Antibody titers 4 days after immunization were lower than values observed 6 and 8 days after immunization, and CS Ss had an attenuated antibody response. There were no significant differences between Group CSo and a group of placebo-treated Ss, but CS Ss had lower antibody titers than placebo-treated animals 4, 6, and 8 days after antigenic stimulation. Results suggest that reexposure to a CS may have long-lasting effects, and provide further documentation of conditioned immunopharmacologic effects and the impact of behavioral factors in modifying immunologic reactivity. (16 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Raised agalactosyl IgG and antimycobacterial humoral immunity in Takayasu's arteritis

OBJECTIVE: Takayasu's arteritis is an inflammatory occlusive disease of the aorta and its main branches of unknown etiology. Some suggested causes include inapparent infection with Mycobacterium tuberculosis, or autoimmunity evoked by this organism. We have therefore sought links with mycobacterial disease. METHODS: We assayed the % agalactosyl IgG, antibody to a tuberculosis-specific 38 kDa protein, and antibody to the mycobacterial 65 kDa heat shock protein (HSP), in patients with active or inactive Takayasu's arteritis, in whom the diagnosis of tuberculosis was excluded. The results were compared with findings in tuberculosis (positive controls), normal donors and patients with Wegener's granulomatosis. RESULTS: The % agalactosyl IgG in patients with active arteritis was in the range previously seen only in rheumatoid arthritis, Crohn's disease, and the mycobacterioses. Similarly, significantly raised antibody to the purified 38-kDa protein of M. tuberculosis, and to the 65-kDa HSP of M. leprae, was found in 78% of patients with Takayasu's arteritis, and the levels were higher in those with active disease. CONCLUSION: These results suggest that Takayasu's arteritis particularly clearly illustrates the occasional relationship between mycobacteria and diseases of superficially autoimmune pathogenesis.     

Stress-induced alteration of T-lymphocyte subsets and humoral immunity in mice.

Effects of acute rotational stress on the tissue distribution of lymphocyte subpopulations, and the capacity to mount a humoral immune response were examined in normal and adrenalectomized mice. The splenic lymphocyte population showed a significant alteration in its content of T lymphocytes in normal, but not adrenalectomized animals subjected to rotational stress. Thus adrenal steroids may influence lymphocyte subpopulations in animals responding to stress. Humoral immune responsiveness of splenic lymphocytes was assessed by a direct lymphocyte plaque forming cell assay following immunization with sheep erythrocytes. The peak number of lymphocytes forming antibody to sheep erythrocytes found in spleens of animals subjected to stress begun 24 hours after antigen inoculation was 50% of the number observed in animals immunized and stressed simultaneously (p?     

Specific and nonspecific factors in the effectiveness of a treatment system.

The paradox of the placebo concept is used to evaluate both specific and nonspecific treatment components responsible for the effectiveness of North Carolina's statewide program for the Treatment and Education of Autistic and related Communication Handicapped Children (Division {teacch}). Empirical studies used to demonstrate specific treatment procedures of structured teaching and parent training are reviewed. The use of extended field trials to avoid negative side effects and short-lived fads characteristic of many specific treatment techniques is discussed. The enthusiastic response of the program's constituency, or the nonspecific effects of the {teacch} system, are evaluated from personal observation, to reduce their vagueness and potential for misunderstanding. Central program concepts and structures that generate and support this nonspecific response of enthusiasm are discussed. It is concluded that empirical research demonstrating specific treatment techniques must be evaluated in the broader context of nonspecific treatment effects. Implications for other service programs are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Local humoral immunity in women with combined forms of infertility

An evaluation was done of the immunity status in 100 women presenting with infertility of associated genesis. An immunologic investigation into blood serum, follicular fluid (FF) and peritoneal fluid (PF) was carried out at day 14-16 and 18-23 of the menstrual cycle. The functional status of spermatozoa was characterized with the aid of the index of their survival in FF and PF. Local humoral immunity of FF and PF differs from the indices in blood serum, which fact was manifested by a striking reduction of Igs G, A, M. Sperm-immobilizing antibodies (SIAB) have been identified in blood serum, FF, and PF in 14, 4%, 22.4%, and 25% of women. SIAB production is associated with inadequacy of local immunity, such as low levels of SIgA, IgA, and lysozyme. Occurrence of SIAB in PF and FF worsens general motility of spermatozoa by agglutination of the latter, which fact undoubtedly affects conception.     

Features of humoral antibacterial immunity in patients with HIV infections and AIDS

The level of antibodies to some bacterial antigens, their affinity and relationship to the level of CD4+ T-lymphocytes in persons at different stages of HIV infection was studied. The study revealed that at early stages of the development of HIV infection a decrease in the levels of antibodies to Streptococcus pneumoniae protein somatic antigen in comparison with those in HIV-negative donors occurred. In the process of the development of HIV infection an increase in the level of Staphylococcus aureus peptidoglycan and some S.aureus antigenic determinants, as well as to S.pneumoniae protein somatic antigen, took place. Patients with HIV infection who had non-specific pulmonary diseases exhibited an increased level of antibodies to Branhamella catarrhalis complex ultrasonic antigen. In patients with HIV infection having an amount of CD4+ T-lymphocytes below 200/1 the level of antibodies to bacterial antigen was higher than in patients with an amount of CD4+ T-lymphocytes varying within 200-400/1. In addition, at all stages of HIV infection and in all kinds of its complications an increase in the titer of antibodies to N-acetylglycosoaminylmuramyl dipeptide, an antigenic determinant of peptidoglycan with immunostimulating and adjuvant activity.     

Development of humoral immunity system of the small bowel

The study was performed in 24 children aged 2 months to 6 years, without intestinal or immunological diseases. Intestinal biopsies were obtained by a Crosby's capsule, pediatric size. The number of immunoglobulin forming cells of lamina propria was measured by planimetry. Under 12 months of age there are increased levels of IgM forming cells and a low IgA forming cells/IgM forming cells quotient, but over 1 year the difference disappears. This suggests that the maturity process is very rapid. There are no correlation between serum IgA, IgM, and IgG levels and its respective forming cells number of lamina propria. It seems to support that the participation of intestinal lymphoid tissue in serum pool of immunoglobulin is very poor and that systemic and intestinal immunity maturation are completely independent.     

Effects of leuzea tincture and leveton on humoral immunity of athletes

The effect of 20-day administration of ectisten-containing tincture of leuzea and leveton on humoral immunity of track and field runners for distances of 5,000 and 10,000 m was studied. Intensive cyclic physical activity induced significant decrease of IgG and IgA in blood serum of the athletes as well as the complement C3 component on the 10th and 20th days. Both drugs contributed to restoration of the lowered IgG, IgA, and C3 concentration. The effect of leveton was more pronounced. The working capacity of the athletes grew by 10 to 15% in this case.     

Observation and discrimination learning in the rat: Specific and nonspecific effects.

After watching the performance of a model rat (N = 10), 48 Os (naive male hooded rats) were trained on a visual pattern discrimination. Results show that the observational experience facilitated discrimination learning if the same cue pattern was positive for the model and the O; it retarded learning in Ss trained on the reversal of the observed discrimination. These results depend on the viewing of a model contiguous with the cue pattern. A 2nd type of facilitating effect followed visual exposure to the cue patterns presented without a model S. When such an observational condition involved stimulus change, discrimination learning was facilitated regardless of the cue to be approached. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Vaccination of racing greyhounds: effects on humoral and cellular immunity

Greyhound kennel owners frequently employ multiple vaccination schedules in an attempt to reduce financial losses incurred as a result of infectious diseases. In order to determine the effects of multiple vaccination schedules on the immune system of racing greyhounds, three litters of greyhound pups raised in laboratory conditions were divided into two groups and subjected to either a maximum or a minimum vaccination schedule. Blood samples were collected biweekly for 6 months beginning at 2 weeks of age and analyzed to establish 'baseline' values for the lymphatic system of greyhounds. Lymphocyte transformation, total and differential leukocyte counts, and flow cytometry were used to evaluate cellular immunity. Humoral immunity was evaluated using serum neutralization and hemagglutination inhibition tests. Proliferation of peripheral blood lymphocytes in response to the mitogen concanavalin A (Con A) was higher for the maximum vaccination groups. The frequency distribution of circulating CD4 and IgG labeled lymphocytes was higher in the minimum vaccination groups. A significant treatment by time interaction in CD4, IgG, and IgM labeled cells was observed, This interaction, however, was not significant at any point in time for CD4 and IgG labeled cells. The percentage of lymphocytes expressing surface IgM was significantly higher in the minimum vaccination groups at 10 and 14 weeks of age. No significant differences were detected in humoral immunity between the maximum and minimum groups of each litter. Results of this study indicate that maximum vaccination schedules do not appear to be more effective or more immunosuppressive than minimum vaccination schedules.     

Influence of subchronic exposure to lindane on humoral immunity in mice

Lindane suppressed both primary and secondary antibody responses to sheep red blood cell (SRBC) in albino mice, the effects being more pronounced on the secondary than the primary response. However, a longer duration of pesticide exposure induced similar degrees of immunosuppression on both responses. The sequential study of plaque forming cells (PFC) kinetics revealed that suppression of plaque formation not only occurred at peak days but also on pre and post peak days, and there was no delay in peak antibody formation. Moreover, reduction in the primary PFC was not associated with decrease in the antibody response to SRBC. The results indicate that lindane suppresses both primary and secondary humoral immune responses in a time and dose dependent manner, and suggest a threshold susceptibility to exposure.     

The effect of ascorbate on cellular humoral immunity in asthmatic children

Ten White children with bronchial asthma and exercise-induced bronchoconstriction were assessed immunologically before and 1, 3 and 6 months after the commencement of standard therapy supplemented with ascorbate 1 g/d. The tests of cellular immune function were neutrophil chemotaxis, phagocytosis and resting and stimulated nitroblue tetrazolium reduction, and lymphocyte mitogen-induced transformation. Humoral functions measured were secretory IgA, serum immunoglobulins, alpha 1-antitrypsin, C3, C4 and total haemolytic complement, antistreptolysin O (ASO) and C-reactive protein. Radio-allergosorbent testing to the common allergens Cynodon dactylon (grass), Dermatophagoides pteronyssinus (mite), house dust and cat epithelium was performed on each child before and 3 and 6 months after treatment. Two children had depressed neutrophil motility, 4 had depressed lymphocyte transformation, and 7 had elevated levels of ASO. These functions normalized after 6 months of ascorbate-supplemented therapy. Serum total IgE levels but not specific IgE levels were likewise reduced after 6 months of therapy. Reduced levels of serum alpha 1-antitrypsin were observed in 2 children, and remained unchanged throughout the study.