Significant Increase In Antibodies Research Articles

Diagnosis of Pneumonia by Cultures, Bacterial and Viral Antigen Detection Tests, and Serology with Special Reference to Antibodies against Pneumococcal Antigens

In a prospective study of the etiology of pneumonia 196 adult patients were included. One of the following criteria was required for diagnosis of pneumococcal pneumonia: isolation of pneumococci from blood; isolation from transtracheal aspirate; isolation from sputum or nasopharynx or detection of capsular antigen in sputum in combination with a significant increase in antibodies against at least one pneumococcal antigen (type-specific capsular polysaccharide, C-polysaccharide, pneumolysin); or increase in antibodies against two pneumococcal antigens. Pneumococcal pneumonia was diagnosed in 63 patients (32%). Other diagnoses were nonencapsulated Haemophilus influenzae isolated from transtracheal aspirates, 9; Mycoplasma pneumoniae diagnosed by serology, 17; Chlamydia psittaci, 6; and viral infections, 42. Twenty-two patients (11%) had evidence of infection with more than one agent. The pathogen could not be determined in 70 (36%). Many patients were given antibiotics before admittance to the study, and in some cases a convalescent serum sample was not available.

Booster response to acellular pertussis vaccine in children primed with acellular or whole cell vaccines

Few data are available on the effect of a booster dose of acellular pertussis vaccine in children primed as infants with acellular vaccine. We administered acellular pertussis vaccine (ACV) at 19 months to children immunized in infancy with ACV or whole cell vaccine. Forty-one infants had been randomly assigned to receive either ACV or whole cell vaccine at 2, 4 and 6 months of age. Antibody titers to pertussis toxin and filamentous hemagglutinin were significantly higher in ACV than whole cell vaccine recipients at 7 months; at 15 months antibody to filamentous hemagglutinin (but not pertussis toxin) remained significantly higher among those receiving ACV. At 19 months all 41 children received an ACV booster. Local and systemic reactions were few and minor and were equally distributed between the two groups. All children responded to booster with significant increases in antibody; these increases tended to be greater for those having been primed with ACV. ACV booster immunization appears safe and immunogenic, regardless of the vaccine given for primary immunization.

Antibody response to outer membrane of noncapsulated Haemophilus influenzae isolated from the nasopharynx of children with pneumonia

In a prospective study aimed at determining the etiology of community-acquired pneumonia in children nasopharyngeal cultures and paired serum samples were obtained from 336 consecutive children ages 6 weeks to 15 years with pneumonia, 167 hospitalized and 169 outpatients. Results regarding Haemophilus influenzae are reported here. Blood cultures obtained from 127 of the hospitalized patients did not yield growth of H. influenzae. H. influenzae was isolated from the nasopharynx of 88 children. Seventy-three strains were noncapsulated, 2 were type b, 2 were type f and 11 were not serotyped. Paired serum samples were available from 38 children with growth of noncapsulated H. influenzae in the nasopharynx as the only potential pathogen. Sixteen of them responded with significant increases in serum antibodies against outer membrane preparations prepared from their own nasopharyngeal isolates. Thirty-eight age- and sex-matched control children with pneumonia without growth of H. influenzae in the nasopharynx served as controls. Sera from each control patient were tested for antibodies against two strains of noncapsulated H. influenzae. Of those, 4 had significant increases in antibodies against one or both outer membrane preparations. The increases in serum antibodies against the outer membrane of noncapsulated strains of H. influenzae indicate that this organism might be a cause of pneumonia in some children.

Haemophilus influenzae type b cellulitis of the lower extremity in a non-immunocompromised elderly patient.

An 83-year-old non-immunocompromised man who developed Haemophilus influenzae cellulitis on his lower left leg is described. H. influenzae type b was isolated by conventional bacteriological cultures from one blood culture and from a cutaneous blister fluid aspirate, and identified within the dermis by immunofluorescence on a punch biopsy of lesional skin. Evolution was characterized by a slow healing during appropriate systemic antibiotherapy, and absence of any significant increase in antibodies to the capsular polysaccharide of H. influenzae type b.

Increasing quantity of maternal immunoglobulin Gin trophoblastic tissue before the onset of normal labor

While levels of maternal immunoglobulin G (IgG) increase in the fetal circulation during the third trimester, actual trophoblastic concentrations have not been extensively studied. To investigate this process, placentas from 71 patients with gestational ages between 26 and 42 weeks were examined by means of a peroxidase-antiperoxidase immunostaining technique specific for IgG. Linear regression revealed a significant increase in antibody with advancing gestational age (r = 0.36, p less than 0.01). In addition, placentas from patients in spontaneous term labor revealed a significantly higher antibody level when compared with those of patients at term delivered electively before the onset of labor (mean +/- SEM 2.6 +/- 0.2 vs 1.7 +/- 0.3, p less than 0.02). Patients in premature labor failed to demonstrate this increase in antibody staining. One possible explanation for these findings is an enhanced recognition of the fetal trophoblastic tissue by the maternal immune system at term. It also suggests immunologic factors may play an important role in the initiation of normal labor.

Etiology of community-acquired pneumonia in children based on antibody responses to bacterial and viral antigens

The serologic responses to bacterial and viral antigens were determined in paired serum samples from 336 children, ages 1 month to 15 years, with roentgenographically verified community-acquired pneumonia. Significant increases in antibodies against one agent were found in 40% and against two or more agents in 8% of the children. There were significant increases in antibodies against respiratory syncytial virus in 20%, viruses of the influenza-parainfluenza group in 6% and adenovirus in 3%. A serologic response to one or more of the pneumococcal antigens used (type-specific capsular polysaccharide, C-polysaccharide and pneumolysin) was demonstrated in 13% of the patients. Ten percent of the children had significant increases in antibodies against Mycoplasma pneumoniae. Only three patients had increases against Haemophilus influenzae type b and one each against Legionella pneumophila and Chlamydia. Respiratory syncytial virus was the predominant etiologic agent in young children whereas M. pneumoniae was more frequent in the older age group.

Immunogenicity of synthetic peptides derived from the sequences of a Streptococcus mutans cell surface antigen in nonhuman primates.

The immunogenicity and antigenicity of synthetic peptides (SP) derived from the sequences of a cell surface Ag of Streptococcus mutans were investigated in macaque monkeys. Immunization with the free peptides of 11, 17, and 21 residues failed to elicit serum antibodies or T cell responses. However, immunization with the SP17 and SP21 linked to tetanus toxoid (TT) as a carrier elicited serum antibodies and proliferative responses of lymphocytes, not only to the SP but also to the native streptococcal Ag. In vivo recall of SP-TT immunized monkeys with suboptimal doses of the native streptococcal Ag resulted in a significant increase in antibodies, both to the SP and the streptococcal Ag, confirming that the SP shares antigenic epitopes with the native Ag. B and T cell epitopes were then determined and a B cell epitope was found in residues 8-13, whereas an overlapping T cell epitope was located in residues 7-15. The T cell epitope has an amino-terminal leucine and carboxy-terminal glycine and alanine added to residues 8-13 of the B cell epitope. In spite of the B and T cell epitopes being expressed in SP17 (residues 1-15), the monomer failed to induce serum antibodies without a carrier. However, immunization with a dimer of SP17 elicited both serum antibodies and proliferative responses of lymphocytes without a carrier. The results suggest that the monomeric SP17 is not immunogenic and needs to be dimerised in order to elicit antibodies and T cell responses, both to the SP and to the streptococcal Ag.

Serum antibody response to filamentous hemagglutinin in patients with clinical pertussis measured by an enzyme-linked immunosorbent assay.

Titers of antibodies to filamentous hemagglutinin (FHA) were determined by enzyme-linked immunosorbent assay in acute and convalescent phase serum samples from 158 patients with clinical symptoms typical of whooping-cough. In 96 of the patients the diagnosis was verified by culture. Significant changes in serum levels of IgG, IgM and/or IgA antibodies against FHA were demonstrated in 126 patients (80%). Thus, demonstration of significant changes in FHA antibody titers in serum can be used for serological diagnosis of pertussis. The results also show that high levels of IgG, IgM and/or IgA antibodies in a single serum sample suggest current pertussis infection, but if the diagnosis is based on determinations of FHA antibody titers in a single serum sample the sensitivity is low. The levels of antibody to FHA were compared with previously determined levels of antibodies to pertussis toxin. A significant antibody response against both FHA and pertussis toxin was seen in 111 patients (70%) while 147 patients (93%) developed a significant increase in antibodies against one or both antigens.

Stimulation of Antibody Following 51 Chromium Survival Studies

Abstract The survival of red blood cells (RBCs) radiolabeled with 51chromium (51Cr) is a reliable method for predicting transfusion compatibility. Approximately 1.0 ml of 51Cr tagged RBCs is infused into the patient and samples are drawn at predetermined intervals post in-fusion to determine RBC survival. Red cells used for the study are usually incompatible with the patient’s antibody. This antigenic rechallenge may stimulate further antibody production, which could contribute to accelerated destruction of RBCs during subsequent incompatible transfusions. To study this question, blood samples were collected from six patients with a single atypical doantibody, seven to nine months after 5lCr RBC survival studies had been performed in an unrelated protocol. Blood had not been transfused in the interim. The samples were tested in parallel with pre-survival samples for change in antibody titer and score. In addition, RBCs used for the 51Cr survival study, sensitized in vitro with pre- and postsurvival serum, were tested by the monocyte monolayer assay (MMA). Serum antibody titers showed a significant increase (>2 dilutions) in two of six patients and antibody score was significantly increased (> 10) in three of six patients. One of the two negative MMAs became weakly positive. This study suggests that 5lCr survival tests using small volumes of RBCs can stimulate significant increases in antibody in some patients, a factor that must be considered in performing these tests and in planning subsequent transfusions.

Immunization of carp ( [formula omitted]) with a [formula omitted] bacterin: Indications for a common mucosal immune system

Uptake and transport of formalin-killed Vibrio anguillarum bacteria were studied in the second gut segment of carp and the resulting reaction of the immune system was investigated. Within a few hours after anal administration antigenic determinants of bacteria were present in intraepithelial macrophages of the second gut segment. In gut and skin mucus and bile, immunoglobulins (Ig's) were detected, but the amount was much lower than found in serum. In mucus of the second gut segment, 4 times more Ig (per mg protein) was found than in the first segment. Upon oral or anal immunization, slightly enhanced antigen-specific Ig titers could be detected in skin mucus and bile, but only after a booster along the same route. The existence of a common mucosal immune system is discussed, with special reference to the significance of the second gut segment. After anal intubation an increase of antigen-specific Ig could also be observed in serum. Following a booster, an enhanced cal memory. After anal boosting equal levels of serum antibody were reached compared with two consecutive intramuscular injections. However, no significant antibody increase occurred in serum after oral immunization, not even when bacteria were administered daily with the food.

Type 1 pili (F1) of porcine enterotoxigenic Escherichia coli: vaccine trial and tests for production in the small intestine during disease

This study was performed to determine whether the F1 (type 1) pili of a porcine strain of enterotoxigenic Escherichia coli are protective antigens and whether they are produced in the pig small intestine during disease caused by an enterotoxigenic E. coli. Reciprocal cross-absorption experiments with antisera prepared against F1 pili purified from enterotoxigenic E. coli 431 (O101:K30,99:H-:F1) and P14 (O149:K91,88ac:8H+:F1) demonstrated that the F1 antigens of the two strains were closely related or identical. Pregnant swine vaccinated with a vaccine prepared from strain P14 (F1+) responded with a significant increase in antibody against F1 in their serum and colostrum. However, the vaccinated dams did not significantly protect their suckling pigs against fatal challenge with strain 431. There was no evidence of F1 pilus production in the strain 431-infected pigs, as determined by immunofluorescent staining of ileal sections, direct electron microscopic examination of bacteria from ilea, and titration of serum agglutinins in convalescent pigs. It was concluded that strain 431 did not produce F1 in the small intestine during disease and that F1 was not a protective antigen in this system.

BCG modulation of delayed type hypersensitivity, humoral response and acquired resistance after rabies vaccination

The immunopotentiating action of BCG was evaluated in rabies. The maximum enhancing effect on delayed type hypersensitivity (DTH) was obtained 14 days after rabies immunization when different BCG vaccination schedules were tested in mice. A stable form of specific sensitization to rabies antigen under the modulation of BCG pretreatment was obtained. High concentrations of rabies antigen were found to be inhibitory for the DTH reaction. Levels of protection were evaluated in rabies vaccination after BCG modulation. One single injection of rabies vaccine in BCG pretreated mice was as effective as two injections of rabies vaccine in normal mice. However, in the latter, increase of protection was correlated with the levels of neutralizing antibody. On the other hand, the BCG pretreated mice, protection was not associated with a significant increase in antibody. Pretreatment with BCG alone influenced the outcome of fixed rabies as well as street rabies by enhancing the natural resistance to rabies infection.

494 TOXOPLASMOSIS: MATERNAL AND PEDIATRIC FINDINGS IN 23,000 PREGNANCIES

We have studied approximately 23,000 pregnant women and their children from 14 institution located throughout the United States who participated in the Collaborative Perinatal Project. The children were followed for a period of 7 years. Serial serum specimens were available from the pregnant women and these were tested for antibody to toxoplasmosis using a micromodification of the indirect hemagglutination inhi-bition test (IHA). The patients with highest titers (≥1024) or fourfold rises to ≥ 256 by the IHA method were also tested for IgM antibody using indirect fluorescent test (IFA). Among the women tested, 38.6% had detectable antibody and a total of 2.2% of the women showed significant increases in antibody or were in the highest titer ranges. Based on this latter group and the IgM IFA tests, a “High Risk” group of 42 patients was identified. Two of the children had “probable” congenital toxoplasmosis and there were 3 stillbirths. Three other children had abnormalities including prematurity, hypotonia, or short leg which may or may not be related to toxoplasmosis. We also studied the entire population for evidence of abnormal findings which could be corelated with maternal antibody findings using a computer analysis. A total of approximately 240 first year and 300 seven year specific physical and developmental categories were considered. The only outcome indicated to be possibly important was an observed increase in micro-cephaly which was two-fold (.55% versus .24%) among the patients in the higher titer ranges.

Influence of preimmunization antibody levels on the specificity of the immune response to related polysaccharide antigens.

We studied the influence of preimmunization antibody level on the immune response of adults to one of two structurally related yet immunologically distinct type-specific polysaccharides from Type III Group B streptococcus and Type 14 pneumonococcus. Four weeks after immunization with multivalent pneumococcal vaccine, 20 subjects with low levels of antibody to Type III Group B streptococcus antigen had no significant increase in antibody to this antigen (P greater than 0.05), but all volunteers with moderate to high preimmunization antibody levels who were immunized with Pneumovax had significant increases (P less than 0.01). However, the streptococcal antibody response to pneumococcal Type 14 antigen was weaker and briefer than that in 10 adults given Type III Group B streptococcus vaccine(P less than 0.05). Preimmunization antibody levels influenced the immune response to a structurally similar polysaccharide antigen, but specific Type III polysaccharide antigen appeared necessary to induce a primary antibody response in "nonimmune" adults. We conclude that immunization of mothers with pneumococcal vaccine is not likely to prevent neonatal Type III Group B streptococcal infection, despite immunologic similarities between the two organisms.

The antibody responses to pneumococcal capsular polysaccharides in aged individuals.

AbstractA population of elderly individuals was studied following immunization with the pneumococcal capsular polysaccharides of types 3 and 8. The antibody responses, determined by indirect hemagglutination (IHA) and by radioimmunoassay (RIA), before and 2 weeks following immunization were compared to those in young adults. Immunoglobulin levels were measured prior to immunization. The numbers of individuals showing a significant increase in antibodies to the polysaccharides of pneumococcal types 3 and 8 were comparable in both age groups when assayed by IHA and RIA. In addition, the mean fold increases in levels of antibodies measured by IHA and by RIA were not significantly lower to either polysaccharide in the elderly group. Postimmunization levels of antibody in the elderly, determined by RIA, were lower to both polysaccharides studied than in young adults, but only those to pneumococcal polysaccharide type 3 differed at a stastically significant level. Comparison of immunoglobulin levels in elderly ...

Oyster-associated gastroenteritis in Australia: the detection of Norwalk virus and its antibody by immune electron microscopy and radioimmunoassay.

Following widespread outbreaks of oyster-associated gastroenteritis in Australia during 1978 in which Norwalk virus was implicated as the causative agent, collaborative studies were undertaken between laboratories in Australia and the United States to confirm the etiology. Immune electron microscopy (IEM) techniques were used in Australia and radioimmunoassay (RIA) methods in the United States. Norwalk virus was detected by IEM in seven of 15 faecal samples, and four were positive by RIA. A much better correlation was found with antibody determinations. Both methods demonstrated significant increases in antibody to Norwalk virus in 22 of 30 sets (73%) of "acute" and "convalescent" sera, confirming that Norwalk virus was responsible for the majority of cases. It is significant that the RIA serology was determined using Norwalk antigen originating in the United States and the IEM serology was determined using 27--30-nm particles originating in Australia.

Counterimmunoelectrophoresis of sputum and blood for the diagnosis of chest infections caused by pneumococci or Haemophilus influenzae.

In 107 patients with lower respiratory tract infections, counterimmunoelectrophoresis (CIE) of blood and sputum, bacterial cultures of blood, sputum and nasopharyngeal secretion, and enzyme-linked immunosorbent assay (ELISA) for antibody determination were performed, with special reference to pneumococci and Haemophilus influenzae. For pneumococci CIE of sputum was superior to culture especially in antibiotic-treated patients. The clinical significance of a positive CIE of sputum was supported by close correlation to significant antibody increase. The usefulness of CIE regarding H. influenzae was more difficult to evaluate.

Serological diagnosis of pneumococcal disease with enzyme-linked immunosorbent assay (ELISA).

Antibody response to pneumococcal type-specific polysaccharide was measured with enzyme-linked immunosorbent assay (ELISA). The test was shown to be up to 500 times more sensitive than indirect hemagglutination using chromic chloride-treated red blood cells. In 16/17 patients with pneumococcal pneumonia a significant antibody increase was seen as measured with ELISA. Only 6/23 patients with pneumonia caused by Mycoplasma pneumoniae gave a pneumococcal antibody rise and in those cases the increase was very slight. The authors consider ELISA a valuable contribution to the serological diagnosis of pneumococcal disease.

Immunoglobulin M antibody response against Mycoplasma pneumoniae lipid antigen in patients with acute pancreatitis.

Serial serum samples from patients with acute pancreatitis showed a significant increase in antibodies against methanol-chloroform-extracted lipid antigen from Mycoplasma pneumoniae when tested by complement fixation. The antibodies did not react with antigens prepared from other human mycoplasmas or from pancreatic tissue by lipid extraction. The antibodies were predominantly immunoglobulin M (IgM). No correlation with cold agglutinins or cardiolipid complement-fixing antibodies was found. The IgM antibody response seemed to be prolonged: after 3 to 4 weeks the antibodies were still in many cases exclusively IgM. Similar IgM responses were also found in certain cases of acute meningoencephalitis. We postulate that during the disease antigenic components identical or very similar to major determinants in the M. pneumoniae lipid antigen are revealed and elicit the IgM antibody response. Their resemblance to natural antibodies and their possible biological role is discussed.

HUMORAL AND CELLULAR IMMUNE RESPONSES TO PRP

Immune responses to Hemophilus influenzae, type b, polyribophosphate (PRP) were studied in 4 infants vaccinated at 6 months with 3 injections of PRP spaced 2 to 3 weeks apart. The injections totaled 1.6ugm of PRP mixed with 0.2ugm of cellular protein. Antibody to PRP was assayed by the Farr technique. Cellular responses were evaluated by incubating peripheral blood lymphocytes with several dilutions of pure PRP or PRP with protein and assaying for either protein or DNA synthesis. Generally significant increases in antibody to PRP were not seen as a result of this vaccination. No pre or post-vaccination lymphocyte cultures displayed increased DNA synthesis to the various dilutions and preparations of PRP tested. On the other hand, post-vaccination lymphocyte cultures from 2 infants displayed increased protein synthesis to pure PRP and one of these infants reacted similarly to PRP-protein. A third infant had significant pre-vaccination stimulation of protein synthesis and remained so following vaccination. The significance of cellular immune responses to PRP is unknown, however since antibody to PRP is not normally generated in the young infant, evaluation of both humoral and cellular immune responses may reveal additional mechanisms of immunity to infection with H. influenzae.