Presence Of Type-specific Antibodies Research Articles

Epidemiology of Mycoplasma pneumoniae Infections in Japan and Therapeutic Strategies for Macrolide-Resistant M. pneumoniae.

Pneumonia caused by Mycoplasma pneumoniae (M. pneumoniae pneumonia) is a major cause of community-acquired pneumonia worldwide. The surveillance of M. pneumoniae pneumonia is important for etiological and epidemiological studies of acute respiratory infections. In Japan, nation-wide surveillance of M. pneumoniae pneumonia has been conducted as a part of the National Epidemiological Surveillance of Infectious Diseases (NESID) program. This surveillance started in 1981, and significant increases in the numbers of M. pneumoniae pneumonia patients were noted in 1984, 1988, 2006, 2010, 2011, 2012, and 2015. The epidemics in 2011 and 2012 were particularly widespread and motivated researchers to conduct detailed epidemiological studies, including genotyping and drug resistance analyses of M. pneumoniae isolates. The genotyping studies based on the p1 gene sequence suggested that the p1 gene type 1 lineage has been dominant in Japan since 2003, including the epidemic period during 2011–2012. However, more detailed p1 typing analysis is required to determine whether the type 2 lineages become more relevant after the dominance of the type 1 lineage. There has been extensive research interest in implications of the p1 gene types on the epidemiology of M. pneumoniae infections. Serological characterizations of sera from patients have provided a glimpse into these associations, showing the presence of type specific antibody in the patient sera. Another important epidemiological issue of M. pneumoniae pneumonia is the emergence of macrolide-resistant M. pneumoniae (MRMP). MRMPs were noted among clinical isolates in Japan after 2000. At present, the isolation rate of MRMPs from pediatric patients is estimated at 50–90% in Japan, depending on the specific location. In view of the situation, Japanese societies have issued guiding principles for treating M. pneumoniae pneumonia. In these guiding principles, macrolides are still recommended as the first-line drug, however, if the fever does not subside in 48–72 h from first-line drug administration, a change of antibiotics to second-line drugs is recommended.

Seroepidemiology of High-Risk HPV in HIV-Negative and HIV-Infected MSM: The H2M Study

Men who have sex with men (MSM), in particular HIV-infected MSM, are at increased risk for diseases related to human papilloma virus (HPV). Our goal was to assess the effect of HIV status on the presence of type-specific antibodies against seven high-risk HPV types in HPV-unvaccinated MSM. Moreover, we compared determinants of HPV seropositivity between HIV-negative and HIV-infected MSM. MSM ≥18 years of age were recruited from the Amsterdam Cohort Studies, a sexually transmitted infection clinic, and an HIV-treatment center in Amsterdam, the Netherlands. Participants completed a risk-factor questionnaire; serum samples were analyzed using a fluorescent bead-based multiplex assay. MSM (n = 795) were recruited in 2010 to 2011; 758 MSM were included in this analysis. Median age was 40.1 years (interquartile range 34.8-47.5) and 308 MSM (40.6%) were HIV-infected. Seroprevalence of HPV-16 was 37.1% in HIV-negative and 62.7% in HIV-infected MSM (P < 0.001); seroprevalence of HPV-18 was 29.1% in HIV-negative MSM and 42.5% in HIV-infected MSM (P < 0.001). Similar patterns of seroprevalence were observed for HPV types 31, 33, 45, 52, and 58. In multivariable analyses, HPV seropositivity was associated with HIV infection [adjusted OR = 2.1; 95% confidence interval, 1.6-2.6]. In multivariable analyses stratified by HIV status, increasing age and number of lifetime male sex partners were significantly associated with HPV seropositivity in HIV-negative, but not HIV-infected MSM. Seroprevalence of high-risk HPV types is high among unvaccinated MSM. HIV infection is a strong and independent determinant for HPV seropositivity, which we hypothesize is because of increased persistence of HPV infection in HIV-infected MSM.

Pyrogenicity of human adenoviruses.

High doses (>1.56x10(7) p.f.u.) of purified preparations of human adenovirus types 3, 5 and 8 exhibited definite pyrogenic activity when injected intravenously into rabbits. Complete pyrogenic tolerance was obtained not only with homologous types but also with heterologous types of adenovirus. No pyrogenic cross-tolerance was observed between each of these three adenovirus types and paramyxovirus pyrogen or bacterial lipopolysaccharide. Adenovirus pyrogenicity was retained after UV-inactivation, whereas it was inactivated by heating at 56 degrees C for 30 min. Adenovirus pyrogenicity was not neutralized by mixing with homologous type-specific antiserum but non-pyrogenic doses (10(7) p.f.u.) of adenovirus types 3, 5 and 8 became highly pyrogenic in the presence of type-specific antibodies at the optimal virus:antibody ratio. This enhanced pyrogenicity depended upon the virus-antibody complex. From these results, it is probable that the pyrogenic activity of the virus-antibody complex, rather than the pyrogenic activity of the virions, is the main contributor to fever in adenovirus infection under actual physiological conditions.

Type-specific immunity and pharyngeal acquisition of group A Streptococcus.

A prospective study of spread of M-type 1, 2, 13, 14, 25 and 60 group A Streptococcus in 64 families in Qalyub, Egypt, in 1972-1974 showed that type-specific serum bactericidal antibody does not protect against pharyngeal acquisition of homologous organisms. The presence of type-specific antibody also does not appear to affect duration of carriage of the organism. Type-specific immunity must be mediated in another way, such as by local antibody or trough prevention of infection (as evidenced by a host response) following acquisition. This study also confirms the observations of others that administration of penicillin lowers the probability that a person who acquires group A Streptococcus will develop type-specific antibody.

The role of complement in the localization of pneumococci in the splanchnic reticuloendothelial system during experimental bacteremia.

Pneumococci activate the alternative complement (C) pathway in the absence of demonstrable antibody in normal guinea pig serum. They also activate the classical C pathway in the presence of type-specific antibody and perhaps through other mechanisms as well. A quantitative examination was undertaken of the roles of these 2 pathways of C activation in the splanchnic sequestration of 125I-labeled pneumococci, using a-guinea pig model of pneumococcal bacteremia. Normal unimmunized guinea pigs (NIH-GP) localized more than 3 times as many pneumococci to the liver as the spleen during a period when exponential bloodstream clearance was occurring. C4-deficient guinea pigs (C4D-GP) and cobra venom factor-treated guinea pigs (CVF-GP) showed progressively fewer pneumococci cleared by the liver with concomitant increases in the extent of splenic uptake, demonstrating the important role of C in the clearance of bacteria in the unimmunized animal. Immunization of guinea pigs brought about an increase in pneumococcal sequestration by the liver in NIH and C4D-GP but did not affect the localization pattern of CVF-GP. A comparison of reticuloendothelial system (RES) localization patterns with the rate of removal of bacteria from the bloodstream showed a highly significant correlation between increases in splenic sequestration and persistence of bacteremia. Thus, opsonization by C is an important determinant of the RES clearance of pneumococci. Unlike RBC clearance, where C plus IgM leads to hepatic localization, and C plus IgG tends to produce splenic localization, C in the presence or absence of type-specific antibody tends to cause hepatic localization of pneumococci. When C-mediated opsonic activity is less than optimal, the slower clearance of bacteremia that results is accompanied by an increased dependence on splenic sequestration of pneumococci.

Comparison of the immunological properties of two canine adenoviruses.

By means of immunological methods, including neutralization (NT), neutralization-enhancement (NE), hemagglutination-inhibition (HI), as well as immunodiffusion experiments, the two known canine adenoviruses, infectious canine hepatitis (ICH) virus and infectious canine laryngotracheitis (ICL) virus, have been shown to be two distinct serotypes. The relationship between the two viruses was shown to be predominantly one-sided as ICH hexon antisera could neutralize ICL virus infectivity to a much higher extent than the reciprocal cross-reaction. The one-way cross-reaction was also found to involve the fiber components as demonstrated in HI tests with fiber-specific antisera and virions and soluble components as antigens. In contrast, NE tests with fiber-specific antisera were found to be type-specific. A HI test using virion antisera and soluble complete hemagglutinin as antigen was found to be a rapid and specific method for distinguishing between the two virus types. The specificity of this HI test was interpreted to be based on the presence of type-specific antibodies against the vertex capsomere (penton base). Immuno-diffusion precipitin analyses substantiated the data obtained in the preceding experiments, as spur formation in two directions was found when fiber antisera was tested against purified fiber. Precipitin patterns obtained with purified hexon and hexon antisera indicated a unique determinant associated with the ICL hexon, presumably the type specificity detected in the hexon antisera NT tests. On the basis of data obtained in this and previous studies on the relationship of the two canine adenoviruses, it is proposed that ICL virus be officially recognized as a distinct canine adenovirus serotype.

Studiey on the mechanism of the long chain phenomenon of group A streptococci.

The formation and destruction of long chains by growth of Group A streptococci in the presence of type-specific antibody have been studied with the fluorescent antibody technique. Long chain formation has been shown to depend on the presence of free antibody during the growth of the bacteria. Destruction of long chains has been shown to depend on the continued growth and division of the bacteria in the absence of free antibody. Univalent antibody fragments formed by proteolytic digestion of antibody globulin have been shown to have the combining properties of untreated antibody but do not result in the production of long chains. A model involving end-to-end agglutination during growth of Group A streptococci has been presented to explain the mechanism of production of long chains by growth of Group A streptococci in the presence of type-specific antibody.

Accessory plasma factors involved in the bactericidal test for type-specific antibody to group A streptococci. I. A typical behavior of some human and rabbit bloods.

The bloods of two apparently healthy human beings, of 25 studied, failed to produce a strong bactericidal test for type-specific antibody to the M protein of group A streptococci under in vitro conditions wherein most human blood leukocytes rapidly phagocytize and destroy virulent organisms in the presence of anti-M antibody and accessory plasma factors. The defect in bactericidal activity of these two individuals is associated with the plasma rather than with the blood leukocytes. Leukocytes suspended in these atypical plasmas showed a characteristic delay in the rate of activation of phagocytosis. Although previously the bloods of laboratory animals (except monkeys) had been reported to be much less active than human blood in this system, occasional exceptions were encountered in rabbits in this study. Two rabbits were found whose bloods were as strongly bactericidal against streptococci, in the presence of type-specific antibody, as the blood of the average "normal" human being. The atypical behavior of some human and rabbit bloods in the bactericidal test may be explained by variations in accessory plasma factors that are as yet unidentified and that influence the rate of phagocytosis of virulent streptococci in vitro in the presence of type-specific antibody.

CUTANEOUS REACTIONS TO THE POLYSACCHARIDES AND PROTEINS OF PNEUMOCOCCUS IN LOBAR PNEUMONIA

I. a. Pneumococcus polysaccharides, when injected intradermally into patients convalescent from pneumonia, are capable of eliciting a response. The polysaccharide inducing a cutaneous reaction was found always to be homologous in type to that of the pneumococcus causing the infection. b. The character of the reaction incited by the protein-free bacterial sugars is of the immediate wheal and erythema type. c. A patient's capacity to react was found to be intimately associated both with recovery from infection and with the presence of type specific antibodies in the circulating blood. II. a. The so-called nucleo-protein of pneumococcus, when injected intradermally, also causes a local cutaneous reaction in patients during convalescence from lobar pneumonia. b. The local lesion resulting from the injection of protein is tuberculin-like in character, and differs from that evoked by the type-specific polysaccharides in gross appearance, time of development, and duration. c. Individuals, acutely ill with and convalescent from pneumococcus pneumonia, possess in their circulating blood, precipitins reactive with pneumococcus protein. In the observations recorded, the concentration of anti-protein antibodies in the blood serum did not seem to influence the patient's capacity to react to intradermal injection of the protein.