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PubMed2004

APRIL-deficient mice have normal immune system development.

APRIL (a proliferation-inducing ligand) is a member of the tumor necrosis factor (TNF) superfamily. APRIL mRNA shows high levels of expression in tumors of different origin and a low level of expression in normal cells. APRIL shares two TNF receptor family members, TACI and BCMA, with another TNF homolog, BLyS/BAFF. BLyS is involved in regulation of B-cell activation and survival and also binds to a third receptor, BR3/BAFF-R, which is not shared with APRIL. Recombinant APRIL and BLyS induce accumulation of B cells in mice, while BLyS deficiency results in severe B-cell dysfunction. To investigate the physiological role of APRIL, we generated mice that are deficient in its encoding gene. APRIL(-/-) mice were viable and fertile and lacked any gross abnormality. Detailed histological analysis did not reveal any defects in major tissues and organs, including the primary and secondary immune organs. T- and B-cell development and in vitro function were normal as well, as were T-cell-dependent and -independent in vivo humoral responses to antigenic challenge. These data indicate that APRIL is dispensable in the mouse for proper development. Thus, BLyS may be capable of fulfilling APRIL's main functions.

Animals↗
PubMed1990

Obtention of monoclonal antibodies against human IgG4 using two different immunization strategies: development of a biotin-based ELISA for IgG4 quantitation.

Several monoclonal antibodies (MAbs) against human IgG4 have been produced in two fusion experiments. In fusion I, Balb/c mice were conventionally immunized and most of the antibodies obtained recognized IgG class-specific epitope(s). Therefore, a second fusion experiment was performed using IgG4-immunized mice that had been made tolerant to epitopes shared by the four IgG subclasses, and most of the hybridomas derived from this second fusion secreted antibodies specific for IgG4. Five MAbs which were found to be specific for both IgG4 isoallotypes (4a and 4b) were selected from the two fusion experiments. These antibodies define at least two non-overlapping epitopes located on the Fab and Fc regions of IgG4 molecule, respectively. Two MAbs were used to develop a two-site ELISA for IgG4 quantitation, in which one MAb (anti-Fab) was immobilized in the solid phase and the other one (anti-Fc) was biotin-labeled. The assay had a detection limit below 1 ng/ml and a practical working range between 4 and 200 ng/ml. The use of these MAbs should improve our understanding of the role of IgG4 in different clinical conditions.

Antibodies, Monoclonal↗
PubMed1993

Non-efficacy of low-dose intradermal vaccination against hepatitis B in Down's syndrome.

Persons with Down's syndrome (DS) constitute a risk group for hepatitis B (HB) and are recommended to be immunized. Of 123 persons with DS in Orebro county screened for markers of HB, 31% had such markers; 16% were potentially contagious. 83 persons without markers participated in a comparative trial of the immunogenicity of a recombinant HB vaccine given either intramuscularly (IM) or in a lower dose intradermally (ID). Immunity developed in 73% after IM vaccination as compared to 29% of those given ID vaccination (p < 0.005). At 3-year follow-up half and two-thirds of the immune persons, respectively, had lost their immunity. Those > 30 years had a poor immunization response compared to the younger ones (p < 0.01). Only 19% of the non-responders developed immunity after an IM booster dose given 10 months after the third injection. Intradermal vaccination is not warranted in persons with DS, especially not in middle aged and older persons. A booster dose of vaccine does not ascertain immunity in those who do not respond with immunity to the ordinary immunization schedule. Post-vaccination immunity should therefore be controlled.

Adolescent↗
PubMed2005

Bacteriocins: developing innate immunity for food.

Bacteriocins are bacterially produced antimicrobial peptides with narrow or broad host ranges. Many bacteriocins are produced by food-grade lactic acid bacteria, a phenomenon which offers food scientists the possibility of directing or preventing the development of specific bacterial species in food. This can be particularly useful in preservation or food safety applications, but also has implications for the development of desirable flora in fermented food. In this sense, bacteriocins can be used to confer a rudimentary form of innate immunity to foodstuffs, helping processors extend their control over the food flora long after manufacture.

Amino Acid Sequence↗
PubMed1995

Safety, effectiveness and ease of use of a non-reusable syringe in a developing country immunization programme.

Unsterile needles and syringes may transmit blood-borne infectious agents such as HIV and hepatitis B virus. The emergence of these diseases as major public health concerns and the risk of nosocomial transmission has heightened interest in the development of single-use injection devices. WHO and UNICEF embarked on a programme to develop and introduce these devices in 1987. We report on a field trial in Karachi, Pakistan, of the SoloShot (SS) plastic disposable syringe, which has a metal clip in the syringe barrel to prevent second-time withdrawal of the plunger. A conventional disposable syringe (CS) was used as a comparison. We observed 48 vaccinators giving 2400 injections with the SS and 1440 with the CS; 98.7% of SS performed as designed. The average volume required per delivered dose was comparable for the two syringes and was delivered more quickly with SS. Training and experience had a small but statistically significant effect on several aspects of SS use. Vaccinators who indicated a syringe preference preferred SS on 7 out of 9 indicators. SS is safe and effective in preventing reuse and is easier and quicker to use than the CS. Vaccinators require little, if any, special training. It could directly replace disposable syringes in expanded programmes on immunization (EPI) in countries where use of unsterile disposable devices occurs or when sterilization is not practical.

Allied Health Personnel↗
PubMed1989

[Characteristics of the development of immunity in healthy children during the first year of life].

Studies of the levels of serum IgA, IgG, and IgM, of B and T lymphocyte function in 20 neonates of days 7-8 of life (funic blood) and their mothers, in children aged 1,3,6,9 and 12 months made it possible to define the characteristic features of the establishment of humoral and cellular immunity during the first year of the child's life. The children placed under observation were normal as regards their physical and psychomotor development and had no infectious or inflammatory diseases. The neonates were characterized by high activity of T lymphocytes, the lack of IgA and traces of IgM, and the high level of IgG in blood serum. The least IgG concentration was seen at an age of 1 month. The data obtained will permit a proper assessment of the changes occurring in the child's immune status during different diseases. The changes should be taken into consideration in carrying out preventive and treatment measures during the first year of the child's life.

Age Factors↗
PubMed1967

The ultrastructure and function of the cells in lymph following antigenic stimulation.

When a lymph node receives an antigenic stimulus the cell population in the efferent lymph changes and large basophilic cells appear. During a secondary immune response cells of this type may account for over 50% of the cells present in lymph. When examined by electron microscopy, many of these cells were found to be primitive undifferentiated blast cells with many free ribosomes in their cytoplasm and only an occasional piece of endoplasmic reticulum. Their nuclear chromatin was sparse and the nuclei contained several nucleoli. Many other cells which were judged to be more differentiated had large numbers of ribosomes arranged in clusters which took the form of rosettes or spirals. These cells also had more ergastoplasm but this occurred usually in the form of short pieces of disorganized endoplasmic reticulum. No cells with the ultrastructure of classical plasma cells were found in efferent lymph although these cells were abundant in the stimulated lymph nodes. It was shown that when the lymph which contained these cells was collected quantitatively no systemic immunity developed even though a vigorous immune response took place in the lymph node with the formation of many plasma cells. Failure of the systemic immune response to develop could not be explained merely in terms of the loss of antibody. It was concluded that these basophilic cells rather than antigen are responsible for propagating the immune response throughout the body and that they depend on an intact lymphatic pathway for their immediate transport. This view was supported by experiments which showed that these cells are capable of initiating immune responses in other lymph nodes of the same animal and of transferring active immunity between chimeric twins. The most likely explanation of these results is that the basophilic lymphoid cells carry out their messenger function by developing into plasma cells at sites remote from the site at which antigen is localized. However this has yet to be proven and the possibility remains that these mobile, highly motile, RNA-rich cells may express their messenger function by transferring information to other effector cells.

Animals↗
PubMed2003

The value of perinatal immune responses in predicting allergic disease at 6 years of age.

BACKGROUND: Characterizing early abnormalities in immune development of allergic individuals provides an important basis for defining disease pathogenesis and future prevention strategies. This study compares patterns of early immune responses in an established cohort based on allergic outcomes and allergen skin prick test (SPT) reactions at 6 years of age. METHODS: Children from an original birth cohort (n = 60) consisting of 44 high risk (HR) (family history of allergy) and 16 low risk (LR) (no family history) were reassessed at 6 years of age. Detailed clinical information about allergic disease was obtained (n = 53) and a subgroup (n = 31) consented to have allergen SPT to common food and inhalant allergens. Data from previous immunological assessments performed at birth, 1 and 2 years of age, including lymphoproliferation and cytokine [interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13 and interferon (IFN)-gamma] responses to ovalbumin (OVA), house dust mite (HDM), cat allergen (Fel d 1), phytohaemaglutinin (PHA) and tetanus toxoid, were re-analysed based on the 6-year clinical outcomes. RESULTS: Twenty-eight HR and three LR children had a clinical history of allergic disease at 6 years of age including doctor diagnosed asthma (n = 17) and/or eczema (n = 24). Most children (78%) with atopy at 6 years had positive SPT to the allergens tested, and 70% had symptoms within the last year. Children at genetic risk (family history) of allergy had weaker (P = 0.017) polyclonal T helper 1 (Th1) IFN-gamma responses in the neonatal period compared with LR children. Although children with allergic disease at 6 years also tended to have weaker neonatal IFN-gamma responses compared to those with no symptoms, but this was not quite significant (P = 0.05). A positive SPT to HDM at 6 years was associated with higher IL-13 responses to HDM at 1 year (P = 0.02), whereas allergic disease at 6 years was associated with higher IL-5 messenger RNA (mRNA) responses to HDM at 1 year (P = 0.01). Despite these associations, regression analysis demonstrated that the only significant early predictors of allergic sensitization at 6 years of age were a family history of allergic disease, and atopic symptoms at 2 years. Importantly, none of the early immunological parameters measured were significantly predictive of allergic disease or allergic sensitization in these 6-year-olds. CONCLUSIONS: Although our observations suggest that subtle differential alterations in cytokine responses during early immune development are associated with different aspects of subsequent atopy, there are still no early predictive biomarkers of disease. A positive family history of allergy remains the dominant predictive factor.

Allergens↗
PubMed1984

Development of specific immunity in patients with pulmonary or extrapulmonary blastomycosis.

The development of specific cellular-immune mechanisms has not been reported in human blastomycosis. We have examined lymphocyte stimulation to a fungal antigen before and during antifungal therapy in 16 patients with blastomycosis. Patients with pulmonary infection only did not have increased 3H-thymidine uptake on initial testing, but all 8 had vigorous lymphocyte stimulation as an indicator of cellular immunity after at least 2 wk of therapy. Patients with extrapulmonary blastomycosis had higher counts in response to the Blastomyces antigen before therapy. These tests differentiated between those with blastomycosis after therapy was started and normal persons or those with a nonfungal infection. Because of the delayed appearance, lymphocyte stimulation does not appear helpful for diagnosis of persons with untreated pulmonary blastomycosis, but in vitro correlates of cellular immunity developed in these patients in a similar time course as with other chronic infections.

Adult↗
PubMed1993

The integrin alpha 4 beta 1 and its counter receptor VCAM-1 in development and immune function.

The integrin alpha 4 beta 1 and its counter receptor vascular cell adhesion molecule-1 (VCAM-1) mediate well-described cell-cell interactions that are critical for immune function. However, these receptors also mediate cell-cell interactions that are important for skeletal muscle differentiation. We have found that contrasting transcriptional mechanisms control their patterns of expression in the immune system and in muscle. Recent studies indicate that alpha 4 beta 1 and VCAM-1 are also expressed in a number of developing tissues, implying that these receptors have a general role in facilitating cell-cell interactions during development.

Animals↗
PubMed1991

Genetic control of immunopathology induced by Mycobacterium leprae.

The pathogenesis of leprosy is almost totally attributable to the immune response of the host towards Mycobacterium leprae, a virtually non-toxic intra-cellular parasite. At one end of the leprosy spectrum are tuberculoid leprosy patients, who develop immunity but also delayed-type hypersensitivity towards M. leprae; at the other end are lepromatous leprosy patients, who lack helper T cell activity and therefore do not develop immunity, but who can nevertheless produce antibodies that may cause immunopathology due to immune complexes. A range of immunopathology is seen between these poles.

Antigens, Bacterial↗
PubMed2006

Anthrax toxins: A paradigm of bacterial immune suppression.

Several species of microorganism have developed immune evasion and/or immunosuppression strategies. Bacillus anthracis secretes two toxins, edema toxin and lethal toxin, that enter the cytosol of almost every cell type, including the cells of the innate and adaptive immune systems, and subvert cell signaling. Edema toxin causes a consistent elevation of cyclic adenosine monophosphate, whereas lethal toxin cleaves most isoforms of mitogen-activated protein kinase kinases. In a concerted manner, these toxins alter major signaling pathways involved in the development of immune-cell effector functions, with the inhibition of bacterial clearance by phagocytes and of B. anthracis-specific responses. Thus, B. anthracis can invade the host, with ensuing massive bacteremia and toxemia. Here, we review the specific effects of B. anthracis on neutrophils, macrophages, dendritic cells, T- and B-lymphocytes.

Animals↗
PubMed2002

Toll receptors in Drosophila: a family of molecules regulating development and immunity.

In recent years, Toll-like receptors (TLRs) have emerged as key receptors which detect microbes and initiate an inflammatory response. The Toll receptor was originally identified and characterized 14 years ago for its role in the embryonic development of the fruit-fly Drosophila melanogaster. Subsequently, it was also shown to be an essential component of the signaling pathway mediating the anti-fungal host defense in this model organism. New factors involved in the activation of the Toll receptor or in intracytoplasmic signaling during the immune response in Drosophila have recently been identified. The existence of significant functional differences between mammalian TLRs and Drosophila Toll receptors is also becoming apparent.

Animals↗
PubMed1991

Inability of Plasmodium vinckei-immune spleen cells to transfer protection to recipient mice exposed to vaccine 'vectors' or heterologous species of plasmodium.

Mice can be immunized to Plasmodium vinckei by repeated infections followed by cure. Such immunity is dependent on CD4 T cells and an architecturally modified spleen, but has little requirement for antibody. Thus, athymic mice can be exposed to P. vinckei and cured, but do not develop immunity. They are resistant to challenge with parasites, however, if they are then given spleen cells from euthymic immunized animals. Such immune spleen cells, however, cannot transfer resistance to normal mice which have been exposed to BCG, Salmonella typhimurium, or vaccinia virus, and are only partially effective in transferring resistance to mice which have been previously immunized with heterologous plasmodia, P. yoelii, P. chabaudi and P. berghei. Mice exposed to varying numbers of irradiated P. vinckei-pRBC do not develop immunity and nor are such animals protected following adoptive transfer of immune spleen cells. Cellular immunity to malaria may not only be dependent on a population of immune CD4 T cells, but may require a specifically architecturally modified spleen which may not occur following either exposure to candidate vaccine vectors, heterologous plasmodia or non-viable homologous plasmodia.

Animals↗
PubMed1975

Clinical trials of hepatitis B immune globulin. Development of policies and materials for the 1972-1975 studies sponsored by the National Heart and Lung Institute.

Plasma from persons with high titers of hepatitis B antibody (anti-HBs) was used to manufacture one lot of hepatitis B "immune" globulin sufficient for four interlocking clinical trials of prevention or modification of hepatitis B infections. The trials were carried out in renal dialysis units, in medical personnel with accidental exposures to hepatitis B, in transfused patients, and in patients with fulminant hepatitis. A single policy board developed protocols that allowed comparisons among the four studies while respecting the unique requirements of each.

Antibodies↗
PubMed1991

Cancer promotion in a mouse-skin model by a 60-Hz magnetic field: II. Tumor development and immune response.

This paper describes preliminary findings on the influence of 60-Hz (2-mT) magnetic fields on tumor promotion and co-promotion in the skins of mice. The effect of magnetic fields on natural killer (NK) cell activity in spleen and blood was also examined. Groups of 32 juvenile female mice were exposed to the magnetic field as described in part I. The dorsal skin of all animals was treated with a subthreshold dose of the carcinogen 7,12-dimethyl-benz(a)anthracene (DMBA). One week after the treatment, two groups were sham exposed (group A) or field exposed at 2 mT (group B) 6 h/day for 21 weeks, to test whether the field would act as a tumor promoter. No tumors developed in these two groups of mice. To test whether the magnetic field would modify tumor development by directly affecting tumor growth or by suppressing immune surveillance, two additional groups of mice were treated weekly with the tumor promoter 12-0-tetradecanoylphorbol-13-acetate (TPA) and then either sham exposed (group C) or field exposed (group D). The time to appearance of tumors was shorter (but not statistically so) in the group exposed to magnetic fields and TPA. Some differences in NK cell activity and spleen size were observed between the sham- and field-exposed groups.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1992

The effects of parental immunoreactivity on pregnancy, birth, and cognitive development: maternal immune attack on the fetus?

The effects of parental immunoreactivity were tested in two ways on questionnaire data collected from 468 children and their families. (1) It was found that the presence of learning difficulties in boys was associated with pregnancy and birth complications, as well as with maternal immunoreactivity. Paternal immunoreactivity did not appear to be related to any of the variables in question. (2) The antecedent brother effect, that children, particularly males, with older brothers have higher rates of the same set of variables, was not found. Maternal immunoreactivity emerges as a risk factor for pregnancy, birth, and cognitive development, but not exclusively by the proposed mechanism of maternal immune attack on the fetus.

Adolescent↗