Immunological Experience Research Articles

Immunité chez le foetus et le nouveau-né : modèle porcin

An efficient placental barrier protects the pig fetus from all exogenous antigenic stimulation. The results of studies on different subpopulations of lymphocytes, histological localization, and stimulation as well as immunization in utero with allogeneic lymphocytes have confirmed that the pig fetus becomes immunocompetent at around 80 days of fetal life (total length of gestation: 115 days). Because the newborn piglet has had no "immunological experience" in utero, it can only elaborate a primary response which is often advantageous to pathogenic microorganisms. Under natural conditions, immune protection is provided by the mother in the form of colostrum. This colostrum provides systemic immunity and is followed by milk which insures local immunity in the piglet gastrointestinal tract. However, the great disadvantage of maternal antibodies is that they suppress the active synthesis of new antibodies in young pig. Thus, the beginning of active immunity in the piglet is a function of the ratio of maternal antibody level to the level of antigenic stimulation.

Clinical and immunologic evaluation of trimellitic anhydride workers in multiple industrial settings

This article describes our clinical and immunologic experience in assessing workers exposed to trimellitic anhydride (TMA) in three industrial settings. Since 1977 we have been engaged in a prospective study of workers involved at the site of manufacture of TMA. These studies demonstrate that serologic measurements of total antibody to trimellityl human serum albumin (TM-HSA) and IgE antibody to TM-HSA are predictive of the development of an immunologically mediated respiratory illness and are useful in monitoring workers removed from TMA exposure, in identifying asymptomatic workers who may be at risk in the future, and in defining the nature of sensitization of the workforce. In a different industrial setting, we have been able to study workers who mixed previously manufactured TMA powder with epoxy resins. This study indicated that clinical assessments by a plant physician with a standardized questionnaire, along with serologic tests, could establish the presence or absence of an immunologic respiratory illness caused by the inhalation of TMA dust. In a third industrial situation, workers were exposed to both TMA and phthalic anhydride (PA). Here workers were interviewed by a local physician with minimal experience with TMA-related respiratory illness. In this situation a more detailed questionnaire was utilized, along with serologic tests utilizing the enzyme-linked immunosorbent assay to establish the presence of a TMA- or PA-related syndrome. Immunologic studies demonstrated in workers exposed to both TMA and PA that the antibody responses elicited showed little crossreactivity between antibodies directed against TM-HSA or PA-HSA.

Limitations of the complement-fixation test for distinguishing naturally acquired from vaccine-induced yellow fever infection in flavivirus-hyperendemic areas.

On the basis of previous studies, it has long been stated that 17D yellow fever (YF) vaccine generally does not induce complement-fixing (CF) antibodies, and that the presence of CF antibodies could be used in epidemiological studies to distinguish individuals infected with wild YF virus from vaccinated persons. In January 1979, seroepidemiological investigations were conducted during a YF epidemic in The Gambia, West Africa. Since a mass vaccination campaign was also in progress, it was important to confirm that the CF test could be used for serodiagnosis and determination of the incidence of natural YF infections. The serological responses of 58 individuals who received 17D YF vaccine were studied. The vaccinees fell into three gorups: 1) those with prevaccination YF neutralizing (N) antibodies; 2) immunological virgins without prevaccination YF-N antibody or hemagglutination-inhibiting (HI) antibodies to heterologous flaviviruses (Zika, West Nile, dengue 1, Uganda S, Spondweni, or Ntaya; and 3) those without prevaccination YF-N antibodies but with heterologous flaviviral HI antibodies. Vaccination of persons without prior flaviviral immunological experience resulted in monotypic YF HI and/or N antibody seroconversions, but no CF antibody response. The presence of prevaccination YF N antibodies blocked serological response to the vaccine in a high proportion of the cases; however, 24% of vaccinees in this group had a marked rise in log2 YF CF antibody titer (mean increase of 3.9). Thirteen (46%) of 28 persons without prevaccination YF N, but with heterologous flaviviral HI antibodies demonstrated YF CF antibody seroconversion or increase in titer following vaccination; in this group the mean increase in log2/ YF CF antibody titer was 2.1. The CF antibody response was generally broadly cross-reactive; but in a few individuals, the YF CF antibody response was homotypic. Nine different patterns of HI and CF homologous and heterologous antibody responses were defined and are discussed. The practical significance of these studies is that they demonstrate that in a high percentage of persons with prior flavivirus exposure, anamnestic serological responses to YF vaccine result in CF antibodies similar to those induced by natural YF virus infection. In Africa and tropical America, where the background of flaviviral immunity is high, it is imperative that seroepidemiologic investigations during or after YF outbreaks be conducted prior to vaccination.

The Effect of Climate on Experimental Infection of Bovine Skin with Dermatophilus Congolensis

Studies of the effects of experimental infection with D. congolensis on the skin surface ecosystem of cattle indicate that changes in environmental temperature and humidity alone have no significant action on susceptibility. Other environmental factors such as heavy rainfall which cause epidermal damage, may, however, be involved. Following damage to the epidermis, either by mild trauma or moderate to severe maceration, marked infection occurs. However, a high degree of resistance to such infection develops within 24 h. This resistance seems to be independent of the level of damage to the skin surface and appears to be related to the re-establishment of an impermeable surface barrier, which may result from the hardening of freshly secreted sebum in the follicle infundibula and between the superficial squames of the interfollicular region. Differences in reaction to infection observed between animals did not seem to be due to previous immunological experience of D. congolensis.

Serologic response to whole, split and subunit influenza vaccines of persons with and without immunological experience towards influenza A/U.S.S.R.90/77 virus

The present work is concerned with the ability of three commercial vaccines (A=whole; B=split; S=subunit) and an experimental vaccine (A-EV=low content of antigen) to induce in 304 persons with and without immunological experience towards influenza A/U.S.S.R.90/77 (N 2N 1) virus, antibodies against influenza hemagglutinin and neuraminidase. The data from this randomised double blind trial confirm that the response to influenza vaccines is strongly influenced by the previous contact of the population with influenza viruses of the past years. An age related seroconversion response to all vaccines has been observed: lower in the 25 yr of age group, higher in the group over 25 yr of age. As far as the H 1N 1 antibodies in unprimed persons are concerned the whole virus vaccines induced a higher GMT titer (1 : 52 and 1 : 48 (A-EV)), respectively as the split (1: 33) or the subunit vaccine (1: 10). All the vaccines produced a satisfactory NI seroconversion factor. The experimental vaccine (A-EV) gave good results comparable with those induced by the commercial vaccines.

A sensitive plaque inhibition technique for assay of antibodies to influenza virus: Use to detect previous antigenic priming with influenza viruses

Plaque reduction test performed in MDCK cells was found to be a more sensitive assay than hemagglutination inhibition, for revealing previous immunological experience with influenza A virus in the population. Based on the preimmunization antibody levels, determined by plaque reduction tests, it was possible to distinguish between previously primed and unprimed subjects among vaccinees.

Primary in vivo Immunization of F1 (2 × 13) Guinea Pigs by Parental Macrophages Bearing Multideterminant and Genetically Restricted Antigens

Abstract An objection has been raised to the concept of macrophage Ir gene function by the in vivo experiments of Pierce et al. in which nonresponder murine macrophages (Mϕ) primed responder mice, thus suggesting Ir gene function at the level of the T cell. Both to examine this issue in the guinea pig and to determine whether in vitro secondary responses are solely reflections of the animal's initial immunologic experience, inbred strain 2 and 13 guinea pigs were immunized in vivo with syngeneic or allogeneic antigen bearing Mϕ. Monolayer purified Mϕ were pulsed with oxidized B chain of insulin and dinitrophenylated ovalbumin (DNP-OVA) for 60 minutes, washed and 2 × 107 injected intradermally into recipient animals. Fourteen days later, in vitro antigen induced specific T cell proliferation was assessed. When strain 13 guinea pigs, high responder to both antigens, were immunized by antigen pulsed strain 13 Mϕ, T cells proliferated in vitro to both antigens.

Alterations in antigen-induced DNA synthesis by specifically localizing cells and other lymphoid cells as a function of immunological memory

The effect of prior immunological experience on the antigen-induced DNA synthesis by specifically localizing cells (SLC) and other cells capable of migrating into lymph nodes (nonspecific cells, NSC) has been studied. Prior immunization with a homologous red cell antigen (sheep red blood cells, SRBC) results in enhanced DNA synthesis, relative to controls pretreated with saline, by NSC but not SLC for the first 48 hr following secondary immunization. By 72 hr both SLC and NSC show markedly reduced DNA synthesis, the SLC showing the greater reduction. Prior immunization with the strongly cross-reacting antigen, ox red blood cells (ORBC), shows a similar but milder effect; prior immunization with the non-cross-reacting antigen chicken red blood cells (CRBC) is without effect, though a similar depression of DNA synthesis by both SLC and NSC occurs 72 hr after secondary immunization with CRBC. In the presence of a concomitant secondary reaction to a non-cross-reacting (CRBC) or very weakly cross-reacting (horse red blood cells, HRBC) antigen, DNA syntheses by SLC-SRBC and NSC are depressed to approximately the same extent, suggesting that the greater depression of DNA synthesis by SLC seen in homologous secondary reactions reflects the additive effects of clonally specific and nonspecific suppressive factors. A comparison of the DNA synthesis by cross-reacting (ORBC) and non-cross-reacting (SRBC) SLC in mice given SRBC following preimmunization with ORBC suggests that “educated” SLC are considerably more resistant to the effects of nonspecific suppressors than “naive” SLC. Passively administered antibody, in concentrations that markedly reduced the numbers of direct plaque-forming cells appearing 72 hr after primary immunization, had no significant effect on DNA synthesis by SLC or NSC.

Colostral Cell-Mediated Immunity and the Concept of a Common Secretory Immune System

Historically colostrum and milk have been thought to confer immunity on the neonate only by virtue of their immunoglobulin content. Recently we have observed that colostrum also contains viable T lymphocytes capable of expressing cell-mediated immunity in vitro and have employed techniques of lymphocyte culture to elucidate the local nature of mammary tissue immunity at the T-cell level. The results indicate that the activity of colostral lymphocytes appears not to represent the total immunological experience of the mother but that they may contain reactive clones beneficial for the suckling. Colostral immunity appears to depend upon sensitizing events within the intestine and respiratory tract, followed by the migration of lymphoid precursors to the breast, suggesting a relationship between the expression of immunity at various secretory surfaces.

Relationships between rheumatoid cells in culture.

Rheumatoid synovial fluid macrophages are compatible with synovial membrane fibroblasts in mixed cell culture. They do not appear to have had any immunological experience recognized by homologous rheumatoid blood lymphocytes. The fusion between macrophages which often takes place in cultures of rheumatoid synovial fluid cells seems to be the result of a cell membrane change between contiguous cells rather than to the release of of a 'fusion factor'. Other combinations and manipulations of the rheumatoid cell population may yet prove fruitful in the search for cell-associated phenomena important in the pathogenesis of rheumatoid disease.

The potential role of immunological adjuvants in influenza vaccines.

SummaryAqueous influenza vaccines seldom induce long-persistent protection against epidemic risk, and often fail to immunize up to one-third of the recipients, especially when there has been no previous immunological experience of the serotype of virus contained in the vaccine. Attempts to improve the situation by increasing the size or number of doses are limited by expense, toxicity and the time available in face of an oncoming epidemic. The future use of isolated viral antigens as vaccines may be limited by similar disadvantages.Immunological adjuvants may make a valuable contribution in decreasing the minimum effective dose of antigen, thereby reducing the toxicity and expense of the vaccine, and increasing its availability. Adjuvant vaccines used in the past have been shown to induce higher mean titres of circulating virus-neutralizing or HI antibody in a higher proportion of the population than have aqueous vaccines, and the duration of immunity has been prolonged. The choice of adjuvants and the avoidance of untoward side-effects are discussed in this review.

Cutaneous responses to cholera skin toxin in man. I. Responses in unimmunized American males.

Graded doses of the vascular-permeability factor, or skin toxin, of Vibrio cholerae and of heated control material were injected intracutaneously in a group of 93 normal males from the United States, who had no history of exposure to cholera antigens. In all 93 subjects, 0.025 limit-of-blueing dose of unheated toxin elicited readily palpable, firm swellings which reached maximal diameters of 5–14 mm on the third day. The same dose of heated toxin caused comparable skin response in only one out of 93 subjects. In the doses used, cholera skin toxin did not produce necrosis, hemorrhage, ulceration, or systemic reactions in any of the subjects. The lesions of the skin disappeared slowly but completely over a period of six months. Since circulating antitoxin to permeability factor suppresses the response to skin toxin in animals, the present study suggests that a skin test with cholera toxin in man could be safely used as an indicator of previous immunologic experience with cholera toxin and perhaps as a test for susceptibility to cholera.

Chronic oxidant exposure and epidemic influenza

The effect of oxidant air pollution upon epidemic A 2/Hong Kong/68 influenza incidence and duration was studied retrospectively during 1968–1969 among 3500 elementary school children from five Southern California communities selected to represent a chronic exposure gradient. No difference in community oxidant exposure was present just prior to and during the epidemic. Information from school absenteeism, questionnaires, and hemagglutination-inhibition titers revealed no statistically significant morbidity differences corresponding to the pollution dose gradient. Only 27.2% of the children remained well; 37.4% reported nonspecific illness without fever: 13.9% had a febrile illness not clinically typical of influenza; and 21.5% had febrile clinical influenza. Overall, 24.6% had diagnostically elevated convalescent hemagglutination-inhibition titers, ≥ 1:32. Females reported more illness but this excess was not serologically confirmed. Second graders reported more illness but exhibited lower III titers, probably because they lacked the immunologic experience of older children. An index of subclinical influenza, a hemagglutination inhibition titer ≥ 1:32 without illness, was observed in 10.3% of the population. The clinical to subclinical ratio ranged from 2.3 to 6.3 depending on the definition of clinical illness. Influenza was associated with school absences averaging 3.3 days, and periods of restricted activity averaging 6.3–7.4 days.

Functional Asplenia in Sickle Cell Anemia—A Reversible Defect

Functional Asplenia in Sickle Cell Anemia—A Reversible Defect

MYCOPLASMAS (PPLO) AND DISEASE: SERUM ANTIBODY TITERS IN A HOSPITAL POPULATION OF ELDERLY PATIENTS

Abstract:In a random sample of sera from a predominantly male group of hospital patients with an average age of 67, complement‐fixing antibodies were found in 20 per cent to M. hominis type 1, in 16 per cent to Unknown Strain CE 5, in 1 per cent to M. pharyngis and in 2 per cent to M. pneumoniae.These percentages are lower than those reported in the literature for younger populations of patients. Thus the immunological experience with mycoplasmas (pleuropneumonia‐like organisms) varies from one population to another. In general, however, the incidence of mycoplasmal infection seems to be lower in older than in younger populations.The findings also indicate that the mere isolation of these organisms from the sera of patients who manifest a disease process does not constitute evidence of an etiological relationship unless other correlates can be established.

Immunological Studies with Group B Arthropod-Borne Viruses

SummaryHemagglutination-inhibiting antibody responses with selected Group B arthropod-borne virus antigens were studied following administration of living attenuated 17D strain yellow fever vaccine to human subjects who had (a) no previous Group B arbovirus experience, (b) only 17D strain vaccine previously, (c) previous inapparent natural Japanese encephalitis virus infection and (d) complex Group B arbovirus experience previously. The results indicate the following: 1. Previous homologous or heterologous immunological experience did not suppress the yellow fever HI response to the living vaccine. On the contrary, the response was sometimes enhanced. 2. Heterologous HI responses depended upon the nature of the previous Group B arbovirus experience. (a) Subjects with no prevaccination Group B arbovirus experience developed a limited array of low-titered heterologous antibodies. (b) Subjects previously vaccinated with the 17D strain but with no other Group B arbovirus experience exhibited limited intensification and broadening of heterologous HI antibodies. (c) Subjects who had experienced some other Group B virus infection prior to yellow fever vaccination displayed a broad heterologous antibody response producing at times significantly higher HI antibody titers to other viruses. 3. Subjects with relatively low, but not with high, yellow fever neutralization indices prior to revaccination tended to show a significant increase in neutralizing antibody level in response to the vaccines.

Challenge of Hamsters with Japanese B, St. Louis and Murray Valley Encephalitis Viruses after Immunization by West Nile Infection Plus Specific Vaccine

Summary and Conclusions Groups of hamsters were basically immunized with active WN virus following administration of WN inactivated vaccine. Most of these animals were given 1 or 2 supplementary injections of formalin inactivated vaccines of JBE, SLE or MVE viruses. Others were given 1 to 3 injections of vaccine without the preceding WN immunization. Groups of animals with these various immunization schedules were then challenged subcutaneously in a quantitative manner with JBE, SLE or MVE virus, depending on the virus vaccine used. For JBE and SLE virus challenge the animals were treated with cortisone to render them susceptible to peripheral inoculation. Quantitative neutrahzation and complement fixation tests against WN and one or more other viruses were made on sera drawn from animals of the various groups just prior to virus challenge. In general, the character of challenge and serological responses was similar with all viruses. WN infection plus 1 injection of vaccine always afforded better protection than 1 injection of vaccine alone and usually gave protection equal to or better than that obtained after 3 injections of vaccine. Neutralizing antibody titers showed an association with protection as afforded by inactivated virus vaccine of homologous type when used alone. Occasionally, however, those animals with WN virus plus vaccine, the group which was most resistant, did not have the highest neutralization index. Complement-fixing antibodies were never detected after vaccine alone, but appeared only in animals which had had a preceding infection with active WN virus. Detectable complement-fixing antibody response to the virus of the type represented by the vaccine appeared to correlate best with maximum protection. Among the 3 viruses used, the most striking difference observed in protection against challenge occurred between the groups tested with JBE or SLE viruses and those with MVE. The latter resisted challenge to a much greater extent after all types of immunizing procedures. This was attributed in large part to the fact that cortisone was not used during challenge with MVE virus. It was suggested that cortisone interfered with the booster response ordinarily associated with infection in a partially immunized animal. Immunity in a naturally susceptible host, such as man, it was predicted, would probably be of a higher order for JBE and SLE than that observed in cortisone treated hamsters. Results should parallel those of hamsters challenged with MVE—a situation in which cortisone was not needed. Parallels have been pointed out between the serological responses occurring in hamsters and man after a variety of immunological experiences with hve and inactivated agents of Group B, singly and in combination. It is concluded that when and if a suitably benign or attenuated strain of WN virus becomes available for safe administration to man as a basic immunizing procedure to these Group B viruses, one or more subsequent injections of inactivated vaccine of the virus type against which protection is desired should provide better immunity than vaccine alone.