Further studies of competition of antigens. I. Variation in immunosuppression induced by alterations of dosage, route of injection, nature of antigen, and immunological status of host

1971 ◽  
Vol 17 (6) ◽  
pp. 803-812 ◽  
Author(s):  
D. Eidinger ◽  
H. F. Pross ◽  
R. S. Kerbel ◽  
M. G. Baines ◽  
A. Ackerman ◽  
...  

Several characteristics of antigenic competition were studied in mice using various pairs of antigens administered in sequence. Enhanced immunosuppression of the response to the second antigen was obtained by increasing the dose of the initial antigen relative to the dose of the test antigen. Diminished immunosuppression was elicited when the dose of the second antigen was increased to near maximum levels, corresponding to the plateau of immune responsiveness to this antigen when it was administered in equivalent dosage to normal control groups of animals. Induction of a primary immune response to the initial antigen was a more effective immunosuppressant than was induction of a secondary immune response to an equivalent dose of the same antigen. Antigenic competition was manifested when antigen was administered in differing sites in the animal such as in separate footpads. Administration of the antigens in the same site did not invariably result in antigenic competition, since a combination of two intraperitoneal injections of unrelated antigens in sequence was not associated with immunosuppression of response to the test antigen. Immunosuppression by antigenic competition did not alter the affinity of the antibody product to the test antigen.

1968 ◽  
Vol 128 (5) ◽  
pp. 1183-1200 ◽  
Author(s):  
David Eidinger ◽  
Salahuddin A. Khan ◽  
Kenneth G. Millar

The effect of antigenic competition on various parameters of humoral antibody formation and cellular immunity was studied in mice. Several pairs of antigens were employed in the investigation of the competitive aspects of induction of humoral antibody formation. Induction of a primary immune response to hemocyanin in Swiss white female mice moderately suppressed the induction of both 19S and 7S antibody formation to goose or rat erythrocytes. Suppression of 7S antibody formation was maximal when a time interval of 1–3 days separated the sequence of injections, although suppression was noted for intervals of up to 14 days. The induction of a primary immune response to rat RBC, the second of the two antigens in sequence, also suppressed The induction of both 19S and 7S antibody formation to goose RBC when appropriate intervals of 1–3 days were employed between injections. The induction of a secondary immune response to rat RBC totally suppressed the primary induction of both 19S and 7S antibody formation to goose RBC administered in the appropriate time sequence. Subsequently, it was shown that the secondary immune response to the suppressed antigen (goose RBC) elicited 30 days after induction of a primary immune response (5 days after secondary immunization with rat RBC) was characterized by deficient 19S and 7S antibody production. These levels were suppressed even in comparison with a normal primary immune response to this antigen. The results were interpreted in part on the basis of a deficiency of formation of primed cells associated with immunological memory. Alternatively, evidence was obtained for the development of a split type of immunological tolerance in 6 of 10 animals studied, since a total suppression of 7S antibody production was obtained in association with deficient 19S antibody synthesis (titers < 1/10). The induction of a primary immune response to several antigens in A/J female mice suppressed the processes of cellular immunity as manifested by prolonged survival of skin grafts from C57 BL/6J female donors. These results were interpreted as evidence for the existence and utilization of processing cells by the initial immune stimulus yielding a deficiency of cells available for processing the second antigen administered in sequence.


Author(s):  
Yiming Shao ◽  
Yifan Zhao ◽  
Tingting Zhu ◽  
Fen Zhang ◽  
Xiuli Chang ◽  
...  

Paraquat (PQ) is a toxic non-selective herbicide. To date, the effect of PQ on memory immune response is still unknown. We investigated the impact of PQ on memory immune response. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control every three days for two weeks. A single injection of keyhole limpet hemocyanin (KLH) at day four after the initial PQ treatment was used to induce a primary immune response; a second KLH challenge was performed at three months post the first KLH immunization to induce a secondary immune response. In steady state, treatment with 20 mg/kg PQ reduced the level of serum total IgG, but not that of IgM; treatment with 20 mg/kg PQ decreased the number of effector and memory lymphocytes, but not naïve or inactivated lymphocytes. During the primary immune response to KLH, treatment with 20 mg/kg PQ did not influence the proliferation of lymphocytes or expression of co-stimulatory molecules. Instead, treatment with 20 mg/kg PQ increased the apoptosis of lymphocytes at late stage, but not early stage of the primary immune response. During the secondary immune response to KLH, treatment with 20 mg/kg PQ reduced the serum anti-KLH IgG and KLH-responsive CD4 T cells and B cells. Moreover, effector or activated lymphocytes were more sensitive to PQ-induced apoptosis in vitro. Treatment with 2 mg/kg PQ did not impact memory immune response to KLH. Thus, treatment with 20 mg/kg PQ increased apoptosis of late stage effector cells to yield less memory cells and thereafter impair memory immune response, providing a novel understanding of the immunotoxicity of PQ.


2020 ◽  
Vol 10 (4) ◽  
pp. 717-728
Author(s):  
T. A. Mamaeva ◽  
N. V. Zheleznova ◽  
M. A. Bichurina ◽  
M. A. Naumova ◽  
M. V. Govoruhina ◽  
...  

In 2010—2016, blood serum samples were examined from 5539 patients, aged < 1—60 years, with clinically and laboratory confirmed measles. Primary or secondary type of immune response was determined for all measles cases. Studies were performed with children aged < 1—14 years (2381), adolescents, 15—17 years old (189), and adults aged 18—60 years (2969). Serum measles-specific IgM antibodies were measured by “VektoKor’ IgM” ELISA test system (Russia), concentration and avidity of specific IgG — by using “Anti-Measles Viruses ELISA/IgG” and “Avidity: Anti-Measles Viruses ELISA/ IgG” (Euroimmun, Germany). Primary immune response was identified based on the presence of serum measles-specific low avidity IgM and IgG antibodies, whereas secondary immune response was characterized by detecting high avidity IgM and IgG antibodies at concentration of ≥ 5.0 IU/ml. Analyzing measles-specific IgM antibodies in 2010—2016 demonstrated that measles morbidity was mainly due to children, aged 1—2 years reaching up to 39.9% of the total number of children with measles aged < 1—14 years as well as adults aged 18—40 years old comprising as high as 80.1% total number of patients aged 15—60 years. Serum measles-specific IgG testing showed that in 15.0% of cases they were detected at concentration of ≥ 5.0 IU/ml. Further serum dilution resulted in finding IgG titer ranging within 8.5—45.0 IU/ml (21.4+0.36) and high avidity antibodies in 80—100% (92.5+0.2) cases. The remaining 85.0% cases found low avidity measles-specific IgG antibodies (< 30%) at concentration of 0.2—3.46 IU/ml (1.73+0.03). An age-related analysis of our data demonstrated that all children under 14 with laboratory-confirmed measles developed primary immune response. Moreover, in 73.7% of measles patients aged 15—60 with primary immune response measles might be prevented by timely vaccination, whereas persons with “vaccine failure” comprised 26.3%. In 2010 (0.09 per 100,000 subjects) and 2016 (0.12 per 100,000 subjects), frequency of patients with “vaccine failure” during relative epidemic well-being was 35.3% and 18.2%, respectively, exceeding 9.9% (p < 0.001) serving as a hallmark 2014 high measles incidence rate (3.24 per 100,000 subjects).The data obtained indicate that measles virus circulate among people with “vaccine failure,” which may account for potential to spread and infect unprotected population cohorts as well as cause measles outbreaks during periods of epidemic well-being.


1970 ◽  
Vol 56 (5) ◽  
pp. 269-278 ◽  
Author(s):  
Carlo D. Baroni ◽  
Roberto Scelsi ◽  
Paolo C. Pesando ◽  
Pietro Mingazzini

It was previously reported that a neonatal injection of 7,12-dimethylbenz (a) anthracene (DMBA) in mice induces a reduction both of the primary immune response to sheep red blood cells (SRBC) and, later in life, of delayed hypersensitivity. In this study we investigated the secondary immune response to SRBC in Swiss mice injected at birth with 100 μg of DMBA. Groups of DMBA treated and control animals were sacrificed respectively 30, 50, 75, 100, 150 and 200 days after treatment with the carcinogen. They were given a priming i.p. injection of 4 × 108 SRBC in saline 20 days before sacrifice and a booster of SRBC 48 h before killing. The numbers of indirect spleen plaque forming cells and the hemagglutinin titers after reduction with 2-mercaptoethanol were determined at the time of sacrifice. It has been constantly found that animals given carcinogen at birth show a depressed secondary response, regardless of the presence of tumors. The present results fit well with our previously reported observations showing a constantly depressed immune response after neonatal DMBA treatment, and further suggest the existence of a relationship between immunodepression and the high rate of tumors that DMBA induces. The results are also discussed in relation to others studies indicating a direct action of leukemia viruses on undifferentiated B-lymphocytes of marrow origin, in view of the suggested activation of a latent lymphoma virus by DMBA.


2004 ◽  
Vol 11 (1) ◽  
pp. 119-122 ◽  
Author(s):  
Cláudio S. Pannuti ◽  
Ricardo José Morello ◽  
José Cássio de Moraes ◽  
Suely Pires Curti ◽  
Ana Maria S. Afonso ◽  
...  

ABSTRACT Despite almost universal use of measles vaccines in recent decades, epidemics of the disease continue to occur. Understanding the role of primary vaccine failure (failure to seroconvert after vaccination) and secondary vaccine failures (waning immunity after seroconversion) in measles epidemics is important for the evaluation of measles control programs in developing countries. After a measles epidemic in São Paulo, Brazil, 159 cases previously confirmed by detection of specific immunoglobulin M (IgM) antibodies were tested for IgG avidity, and a secondary immune response, defined by an IgG avidity index of at least 30%, was established in 30 of 159 (18.9%) patients. Among the 159 patients, 107 (67.3%) had not been vaccinated and 52 (32.7%) had received one or more doses of measles vaccine. Of the 107 unvaccinated patients, 104 (97.2%) showed a primary immune response, defined as an IgG avidity index of less than 30%. Among the 52 patients with documented vaccination, 25 (48.1%) showed a primary immune response and 27 (51.9%) showed a secondary immune response, thereby constituting a secondary vaccine failure. Primary vaccine failure was observed in 13 of 13 patients vaccinated prior to 1 year of age and in 43.5 and 12.5%, respectively, of patients receiving one or two doses after their first birthdays. These results provide evidence that measurement of IgG avidity can be used to distinguish between primary and secondary vaccine failures in vaccinated patients with measles; the method can also be a useful tool for the evaluation of measles control programs.


1971 ◽  
Vol 17 (7) ◽  
pp. 857-863 ◽  
Author(s):  
David Eidinger ◽  
Malcolm Baines

An indirect approach to the question of the role of a presumptive inhibitory factor or cell deficit to account for immunosuppression by antigenic competition was carried out in the present work.Several characteristics of antigenic competition were delineated. The response to PVP,* classed as a non-thymus dependent antigen, was capable of suppressing the response to a test antigen administered subsequently, and conversely, of being suppressed by unrelated antigens administered as initial antigens. Induction of immunological tolerance to RRBC* with cyclophosphamide did not prevent the capacity of the antigen to suppress the induction of humoral antibody formation to KLH* in a model of antigenic competition. Actinomycin-D in a dose of 0.60 mg/kg body weight abolished suppression by antigenic competition, although the drug suppressed the response to the suppressing antigen GRBC* and enhanced the response to RRBC, the test antigen, when administered to individual control groups of animals immunized with only the one antigen. Consequently, interpretation of the data in terms of antigenic competition was difficult.


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