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Serum immune complexes and rheumatoid factors in superficial bladder tumours.

Serum immune complex (IC) and rheumatoid factor (RF) levels of 39 patients with a transitional cell tumour of the bladder were analyzed using 4 different IC and 2 RF assays. Elevated serum immune complex and rheumatoid factor levels were observed in the majority of the patients (95%). Conglutinin-binding (KgB), C1q-binding (C1qB), platelet iodinated protein A test (PIPA) and RF-enzyme immunoassay (RF-EIA) gave positive results in 31%, 62%, 23% and 31% of the cases, respectively and separated cancer sera from normal blood donors (p less than 0.001). Elevated titers were also observed with platelet aggregation test (PAT) and latex agglutination for RF in 23% and 67% of the cases, respectively. A negative correlation (p less than 0.01) was observed with the stage of the disease and RF-values. Other IC tests did not correlate significantly with stage, histological grade or progression of the disease. The best prognostic marker was the histological grade of the tumour. Males had more undifferentiated tumours than females. Multivariate analysis was carried out to correlate several laboratory parameters simultaneously with clinical variables and it revealed that elevated IC tests values (KgB, C1qB and PIPA) and low RF-values correlated to stage (p = 0.009) but not to histological grade or progressive course of the disease.

Antigen-Antibody Complex↗

Effect of human immune serum globulin on infectivity of hepatitis A virus.

A standard preparation of immune serum globulin containing a titer of immune adherence hemagglutination hepatitis A antibody of 1:3,200 neutralized the infectivity of MS-1 serum. An inoculation of MS-1 serum was followed by the following evidence of hepatitis A infection in eight of 14 seronegative recipients: (1) abnormal values for serum aspartate aminotransferase after an incubation period of 29-42 days, and (2) no detectable immune adherence hemagglutination hepatitis A antibody (less than 1:5) before exposure, and an eightfold or greater increase in antibody titer during convalescence. In contrast, inoculation of the mixture of MS-1 serum and immune serum globulin was followed by (1) normal values for aspartate aminotransferase in all eight seronegative recipients, and (2) evidence of an antibody response (indicating subclinical infection) in two of the eight. Under the conditions of this study, the use of the preparation of immune serum globulin described prevented or modified hepatitis A infection.

Antibodies, Viral↗

Antigen-specific augmentation of delayed-type hypersensitivity by immune serum factor in mice.

The serum from C3H/He mice immunized with chicken erythrocytes (CRBC) in complete Freund's adjuvant contained a factor able to augment delayed-type hypersensitivity (DTH) antigen specifically, when transferred into naive syngeneic recipient mice before their sensitization with CRBC. This activity in immune serum appeared on Day 4 and reached a peak on Day 8 after immunization, and was enhanced when donor mice were treated with cyclophosphamide (CY) 2 days before immunization. The ability of recipient mice to respond to this factor was enhanced by CY treatment of these mice 4 days before being transferred. This factor could be discriminated from conventional antibodies. Production of this factor in the serum donor and the expression of its activity in transferred recipient was mediated by a T-cell subset which showed a low degree of thymus dependency in ontogenic development.

Animals↗

Immunity to syphilis: passive transfer in rabbits using serial doses of immune serum.

The influence of prolonged treatment with serial doses of immune serum initiated either 2 or 48 h before intracutaneous challenge with Treponema pallidum on the subsequent appearance and development of lesions was studied. Whereas treatment with large doses of immune serum initiated 48 h before treponemal challenge caused a delay of 9 to 20 days in the onset of lesions and marked suppression of lesion development. Treatment initiated 2 h before treponemal challenge failed to delay the onset of lesions and only moderately suppressed their development. Lesion development was suppressed as long as treatment was continued. The significance of the results is discussed.

Animals↗

Plasmodium falciparum: passive immunization of Aotus lemurinus griseimembra with immune serum.

Owl monkeys (Aotus lemurinus griseimembra) were immunized against Plasmodium falciparum by infection and drug cure. After challenge, 3 of 4 monkeys developed extended prepatent periods and low grade parasitemias followed by self cure. The fourth monkey did not develop a patent infection. Immune monkey serum passively transferred at the time of challenge conferred immunity to 20 naive monkeys. Immunity was characterized by extended prepatent periods in 19 monkeys, low levels of parasitemia (< or = 1%) followed by self cure in 12 animals, and lack of detectable infection in 3 recipient monkeys. Immune serum collected from monkeys undergoing repeated challenges afforded more protection than serum from singly infected monkeys. However, single doses of hyperimmune serum appeared to be as effective as multiple doses. Normal serum had no effect on the course of infection in 12 monkeys. These studies confirm that owl monkeys can be immunized by infection and cure and demonstrate that this immunity can, in large part, be transferred to nonimmune recipients with serum from immune donors.

Animals↗

The effect of immune serum and complement on the in vitro phagocytosis of Babesia rodhaini.

The effect of immune serum and complement on the in vitro phagocytosis of Babesia rodhaini was investigated. Infected erythrocytes and parasites released from erythrocytes by lysis were phagocytosed by mouse peritoneal macrophages in vitro when the infected erythrocytes or parasites were exposed to hyperimmune B. rodhaini serum. Complement, in the presence of immune serum, did not reproducibly enhance phagocytosis of infected erythrocytes or parasites alone. When adjusted for its effect on normal erythrocytes and normal serum, complement generally inhibited rather than enhanced phagocytosis. When coupled with other published data, our data suggest that the activation of the immune system in vivo against this species of Babesia involves a series of mechanisms of which phagocytosis is but one.

Animals↗

Complement consumption by Photobacterium damselae subsp. piscicida in seabream, red porgy and seabass normal and immune serum. Effect of the capsule on the bactericidal effect.

A virulent strain of Photobacterium damselae subsp. piscicida (Pdp) was grown without (C form) or with (C+ form) glucose supplementation, the latter to enhance capsule formation. Both forms were resistant to killing by normal serum of seabream, red porgy and seabass. However, the C form was killed by immune serum of all three fish species while the C+ form was killed only by seabream and red porgy sera and to a lesser extent than the C form. Both C and C+ forms consumed complement in normal serum and this consumption was enhanced by precoating the bacteria in specific fish antibody. Complement consumption was greatest in seabass serum, especially with antibody-coated C+ form yet in this case the bacteria were not killed. The killing of the C form in immune serum of all three fish species was completely inhibited by EGTA/Mg(2+), indicating that the mechanism of complement activation leading to killing of the bacteria was by the classical pathway. The results suggest that immune serum killing by the classical complement pathway may provide some degree of protection against pasteurellosis, but enhanced expression of the capsule by Pdp in vivo may restrict complement-mediated killing, especially in immunised seabass.

Animals↗

Effect of immune serum on infectivity of Rickettsia tsutsugamushi.

Hyperimmune antirickettsial serum was shown to prevent the attachment/penetration stage of Rickettsia tsutsugamushi infection of suspended chicken cells. The extent of the inhibition depended on the serum concentration but not on the presence of complement. The neutralizing activity was reduced by prior adsorption of immune serum with staphylococcal protein A or with intact rickettsiae but was not affected by adsorption with target cells. In the neutralization tests, there was no cross-reactivity between the Karp and Gilliam strains of R. tsutsugamushi. Incubation of rickettsiae with immune serum did not alter their capacity to metabolize glutamate nor grossly damage the permeability barrier function of their cytoplasmic membranes. Although the assay method had the capacity to detect some aggregated infectious organisms, none were found in immune serum-treated suspensions. It was concluded that immune serum may inhibit rickettsial infection by blocking a surface component(s) whose function is necessary for attachment to and/or penetration of target cells.

Animals↗

Corticosteroids for prevention of adverse reactions to intravenous immune serum globulin infusions in hypogammaglobulinemic patients.

Severe adverse reactions to intravenous immune serum globulin occurred repeatedly in four of 10 hypogammaglobulinemic patients. Treatment-limiting symptoms included fever, chills, headache, hypertension, and chest pain. Pretreatment of patients with hydrocortisone immediately prior to infusion prevented subsequent adverse reactions and permitted these patients to receive immune serum globulin intravenously.

Adult↗

Varicella zoster antibody titers after the administration of intravenous immune serum globulin or varicella zoster immune globulin.

Varicella is a serious infection in the immunocompromised patient. Prophylaxis with varicella zoster immune globulin is known to decrease the incidence of severe varicella infection. The titers of antibody to varicella zoster virus were compared in patients who received either varicella zoster immune globulin or intravenous immune globulin, 4 ml or 6 ml/kg per dose. The titers of antibody to varicella zoster virus were comparable in each group.

Adolescent↗

Sensitization of circulating basophils in guinea pig recipients of passive transfer of cutaneous basophil hypersensitivity (CBH) with immune serum: antigen-specific histamine release in vitro.

An in vitro histamine release assay was used to test the hypothesis that passive sensitization of circulating basophils is associated with the activity of immune serum that transfer the ability to elicit cutaneous basophil hypersensitivity (CBH) reactions. Systemic i.v. transfer of several types of immune sera that mediate CBH also led to passive sensitization of circulating basophils for antigen-specific release of histamine in vitro. In addition, we found that immune serum passively sensitizes basophils in vitro. Thus immune sera had three activities that are probably interconnected: sera will 1) passively transfer CBH in vivo, 2) passively sensitize basophils in vivo, and 3) passively sensitize basophils in vitro. These results suggest that passive sensitization of circulating basophils by immune serum contributes to the mechanism by which antibodies transfer the ability to elicit CBH reactions.

Animals↗

A clinical and laboratory evaluation of immune serum globulin from donors with a history of hepatitis: attempted prevention of post-transfusion hepatitis.

A controlled trial of passive immunization for prevention of post-transfusion viral hepatitis was carried out in order to determine whether effective levels of antibody were present in the "convalescent" immune serum globulin used in the study. This globulin was prepared selectively from plasma of donors giving a history of overt viral hepatitis two or more years earlier. The proportion of contributors to the globulin who had B hepatitis was unknown but the final product contained a low titer of antibody to the surface antigen of hepatitis B virus (anti-HBs). The failure of 20 ml of immune serum globulin to reduce the incidence of type B post-transfusion hepatitis (7/93) below that of placebo-treated controls (8/102) was not unexpected in view of the globulin's low titer of anti-HBs. However, more than two thirds of the post-transfusion cases were not type B and were as plentiful among globulin recipients (17/93) as among controls (17/102). Although some of the donors from whom the immune serum globulin was obtained may once have had the same type(s) of hepatitis as the non-B cases currently observed in transfusion recipients, the globulin apparently did not contain enough specific antibody to confer protection in the dose schedule tested.

Antibodies, Viral↗

Immune serum transfer of cutaneous basophil-associated resistance to ticks: mediation by 7SIgG1 antibodies.

Guinea pigs acquired resistance to Amblyomma americanum larval ticks after one infestation, resulting in 46% tick rejection when challenged. Intravenous transfer of immune serum from twice-infested hosts to naive animals conferred a significant level of immunity resulting in 18 to 30% tick rejection. The minimum effective dose of serum was 3 ml per recipient, and heating the serum at 56 degrees C for 4 hr had no effect on serum activity. Fractionation of whole immune serum by gel filtration chromatography (Sephadex G-200) and ion -exchange chromatography (DEAE) demonstrated resistance activity to be in the IgG- and IgG1-containing fractions, respectively. Passage of whole immune serum through a heavy chain-specific rabbit anti-guinea pig IgG1 affinity column removed anti-tick activity and decreased the cutaneous basophil response to tick feeding by 70% in recipients. The ability to transfer both resistance to tick feeding and a significant cutaneous basophil response was eluted from the affinity column with 0.2 M Na2CO3, pH 11.5. In addition, immune serum raised against larval Ixodes dammini ticks, but not larval Rhipicephalus sanguineus ticks, was also effective at reducing feeding by larval Amblyomma americanum ticks, indicating that antibodies mediating resistance can be cross-reactive with antigens of different tick species and genera. This study demonstrates that IgG1 antibodies are responsible for the ability of immune serum to transfer cutaneous basophil-associated immune resistance against tick feeding in guinea pigs.

Animals↗

Efficacy of orally administered immune serum globulin against type III group B streptococcal colonization and systemic disease in an infant rat model.

We established an experimental animal model of the gastrointestinal colonization and systemic disease following oral challenge of type III group B streptococcal strain in 3-day-old newborn rats. Two type III group B streptococcal strains isolated from the cerebrospinal fluid of septic newborn infants produced colonization in 57-87% of the challenged animals and 13-31% of these colonized animals developed systemic disease. Using this new animal model, we evaluated the effect of orally administered human immune serum globulin on the colonization and systemic disease. This antiserum contained 21 micrograms/ml of type III group B streptococcal antibody of human IgG class. Animals fed with immune serum globulin developed significantly lower rates of colonization and systemic disease than those of control (albumin or saline) (23 versus 71%, p less than 0.001 for colonization; 7 versus 31%, p less than 0.05 for systemic disease). However, rates of the development of systemic disease among the colonized animals were not significantly different between the two groups (33 versus 43%, p greater than 0.1). These findings suggest that orally administered immune serum globulin is beneficial in the prevention of colonization and systemic disease in this rat model and that this protective effect of oral immune serum globulin occurs primarily at the mucosal level.

Administration, Oral↗

Decreased protective efficacy of reduced and alkylated human immune serum globulin in experimental infection with Haemophilus influenzae type b.

Conventionally prepared immune serum globulin frequently produces severe side effects when administered intravenously. A modified preparation in which 4 to 5 interchain disulfide bonds have been reduced and alkylated has been made for intravenous use. However, reduction and alkylation may affect Fc-mediated functions of immunoglobulin G, particularly its ability to fix complement by the classical pathway. To determine whether reduction and alkylation alters the protective activity of immune serum globulin in vivo we compared it with two less harshly prepared globulins (pH 4 treated or ultrafiltered) in an infant rat model of Haemophilus influenzae b infection. Antibody binding to the capsular and noncapsular components of H. influenzae b and in vitro bactericidal activity were similar in the globulin preparations. Infant rats were treated with various doses of globulins adjusted to provide identical concentrations of anticapsular antibodies as measured by the Farr radioactive antigen binding assay. At high doses of anticapsular antibody (greater than 1,500 ng per pup), all preparations protected well. At marginal doses (750 ng per pup), however, rats given reduced and alkylated globulin had a significantly greater incidence of bacteremia (P less than 0.05), meningitis (P less than 0.01), and death (P less than 0.05) and a higher magnitude of bacteremia (P less than 0.02) than rats who received pH4-treated or ultrafiltered globulins. These differences were not due to differences in anticapsular antibody concentrations achieved in the serum. The 50% protective serum concentrations of anticapsular antibody in this model were 200 to 300 ng/ml for reduced and alkylated globulin and 100 to 200 ng/ml for acid-treated globulin. Absorption of the globulins with purified H. influenzae b capsule reduced in vitro bactericidal activity and rat protective activity. However, the magnitude of bacteremia was lower in rats receiving absorbed pH 4-treated globulin than in those receiving absorbed reduced and alkylated globulin (P less than 0.05). We conclude that reduced and alkylated immunoglobulin G provides significantly less protective activity against H. influenzae b infection in this model than globulins not so modified, and we suggest that the altered Fc function of the immunoglobulin G, such as the decreased ability to fix complement by the classical pathway or decreased Fc-mediated opsonization, may be responsible for this impairment.

Alkylation↗

Mechanisms of immunity in typhus infections. 3. Influence of human immune serum and complement on the fate of Rickettsia mooseri within the human macrophages.

Preincubation of Rickettsia mooseri with human typhus convalescent serum, which is not rickettsiacidal but which confers passive protection to animals, opsonizes the rickettsiae for enhanced phagocytosis by monocyte-derived human macrophages in cell culture and renders them susceptible to destruction within the macrophages. Nonspecific opsonization by preincubation of the rickettsia with methylated bovine serum albumin enhances phagocytosis, but the rickettsiae are not prepared for intracellular destruction. Instead, they grow within the macrophages and eventually destroy these cells. Thus, immune serum and macrophages, neither of which is capable of killing these rickettsiae alone, act in concert to destroy the virulent organisms. In this system, immune serum appears to exert two distinct, possibly dissociable, actions on the rickettsiae: enhancement of phagocytosis and preparation for intracellular destruction. Complement is not required for this action but, when present with immune serum, markedly enhances phagocytosis of the rickettsiae, often leading to rapid destruction of the macrophage.

Animals↗

Induction of interleukin 2 from a murine B cell tumor by a factor found in immune serum.

The murine B cell tumor line 2 PK-3 secretes T cell growth factor activity after incubation for 6 to 48 hr with a factor present in heterologous immune serum. T cell growth factor derived from 2 PK-3 was compared with IL 2 produced by the Con A-induced T lymphoma cell line EL-4 G12. These studies indicated that T cell growth factor activities derived from both cell lines were similar with respect to m.w., pI values, and the ability to support growth of two IL 2-dependent T cell clones. Three preparations of immune sera were found to be active in the induction of IL 2 activity from 2 PK-3 cells, including rabbit anti-mouse brain, rabbit anti-complete Freund's adjuvant, and goat anti-mouse Ig. None of these preparations, however, induced IL 2 from EL-4 G12 cells. It was also observed that LPS synergized with immune serum to produce enhanced activity. Normal sera prepared from unimmunized animals were not active in the induction of IL 2 activity. Fractionation of immune serum on protein A Sepharose suggested that the IL 2-inducing agent is not IgG.

Animals↗