Kinetics Of Antibody Production Research Articles

Changes in cell populations and immunoglobulin-producing cells in the spleens of mice infected with Trypanosoma cruzi: Correlations with parasite-specific antibody response

Infection of mice with Trypanosoma cruzi elicits the production of parasite-specific antibodies which reach high levels and remain elevated for at least 105 days of infection. The more susceptible C3H(He) mouse actually has a higher level of “natural” antibodies for T. cruzi but may show a greater lag time in the production of antibodies in response to infection than the more resistant C57BL/6 mouse. Comparison of the kinetics of antibody production against T. cruzi and the numbers of immunoglobulin-producing cells in the spleen during the course of infection suggests that a large number of the immunoglobulin-producing cells are probably producing antibodies directed against the parasite and are not the result of an exhaustive polyclonal B-cell activation. Cell numbers in the spleen change dramatically both in total numbers and in the percentage of different cell types during infection with T. cruzi.The percentage of T cells in the spleen remains relatively unchanged throughout infection in both mouse strains tested but numbers of Ig-positive cells decrease markedly during the acute phase of infection while macrophage numbers increase up to sixfold. Cell numbers and proportions of B cells, T cells, and macrophages return to near normal values by 105 days of infection in the C57BL/6 mouse.

The effect of a single dose of cyclophosphamide on the kinetics of antibody production in the guinea pig

Cyclophosphamide (CY) 250 mg/kg was given before, at the same time or after immunization with dinitrophenylated bovine gammaglobulin (DNP 47-BGG) in Freund's incomplete adjuvant (FIA). CY, given on day + 3 or + 7 strongly suppressed both IgG subclasses. CY, on the day of immunization, reduced the IgG 2 but not IgG 1 anti-DNP antibody synthesis. Carrier BGG, injected 42 days after initial immunization, caused a secondary anti-hapten IgG 1 response. This was not altered by CY treatment. The secondary anti-BGG response in animals pretreated with CY was also not affected. However, IgG 1 anti-BGG in the other groups given CY on day 0, + 3 or + 7 was delayed and reduced. IgG 2 anti-BGG was suppressed in guinea-pigs treated with CY, 3 or 7 days after primary immunization. DNP-BGG-specific IgE serum antibodies, not detectable in CY untreated animals, were found in guinea pigs given CY on days 0, + 3 or + 7. It is suggested that the kinetics of the IgG 1 and IgG 2 primary immune response differ, as does the development of IgG 1 and IgG 2 specific immunological memory.

Kinetics of antibody production to group A and group C meningococcal polysaccharide vaccines administered during the first six years of life: prospects for routine immunization of infants and children.

A cohort of infants, previously immunized once or twice between three and 12 months of age with vaccines containing polysaccharide of groups A and C Neisseria meningitidis, received boosters at two and five and one-half years of age with bivalent A/C vaccine. Antibody concentrations were measured by a radioactive antigen-binding assay. Concentrations of antibody to groups A and C N. meningitidis were 5.59 and 2.86 microgram/ml, respectively, by four years of age. After booster immunization at five and one-half years of age, concentrations of antibody to groups A and C N. meningitidis increased to 15.67 and 7.59 microgram/ml, respectively. Protective levels of antibody to group A meningococci may be achievable throughout early childhood by routine immunization with the A vaccine. Although the group C vaccine is effective in control of epidemics, the rapid decline in the concentration of antibody to group C meningococci following immunization of young children suggests that protection may not be long-lasting.

Induction of specific anti-actin antibodies and their measurement by ELISA technique

Using the ELISA technique we have been able to quantify antibodies directed against actin and to follow the kinetics of antibody production. Specific anti-actin antisera have been raised in rabbits by immunization with chemically modified white muscle rabbit actin. Two or three dinitrophenyl groups linked per actin molecule were sufficient to break natural tolerance, while linkage of three phosphorylcholine groups to actin was not.

The kinetics of IgG and IgM antibody-forming cells in ACI and F344 rats immunized with poly(glu52lys33tyr15).

The cellular kinetics of antibody production in high and low responder rats immunized with poly(Glu52Lys33Tyr15) or with poly(Glu52Lys33Tyr15)/MeBSA were characterized: serum antibody and IgG and IgM antibody-forming cells in the spleen and in selected lymph nodes were assayed in male and female rats following immunization by several routes. Aggregation of the antigen with MeBSA enabled the poorly responding F344 rats to produce antibody, which was almost exclusively IgG. High responder ACI rats, under the same conditions, produced antibody of both IgG AND IgM classes. These data suggest that in low responders one defect, possibly at the T-cell level, can be overcome by aggregation but that a second defect, involving the regulation of IgM production, still exists.

Kinetics of antibody formation and regulatory aspects of immunity.

This paper, which is to be read in conjunction with that of Dr. J.F.A.P. Miller earlier in this volume, addresses itself to the kinetics of antibody production and to the regulation of the immune response. It is divided into four main sections. The first examines the kinetics of antibody production to a single, strong challenge injection of antigen. The cellular events involved in the latent period and the subsequent exponential phase of antibody production are examined from the viewpoint of four key concepts: triggering, clonal expansion, IgM to IgG switch and affinity maturation. The second section examines the major regulatory influences and feedback loops in immunity. Antigen is discussed as an agent capable of causing tolerance as well as triggering. Antibody is considered an important regulator, and the mechanisms of IgM-positive feedback, IgG-negative feedback, and tolerance and blockade effects of immune complexes are outlined. Immunological memory, the opposite phenomenon to tolerance, is briefly described, as is the importance of genetic factors. The third sections looks at more complex models of the immune response, and in particular at the lessons to be learnt from tumour progression.

The Kinetics of Antibody Production and Affinity in Balb/c Mice Immune and Partially Tolerant to the 2,4-Dinitrophenyl Determinant

Abstract A study was undertaken of the kinetics of the immune responses to the 2,4-dinitrophenyl (DNP) determinant of immune and partially tolerant adult and neonate BALB/c mice. Neonate and adult mice were pretreated with multiple injections of soluble DNP-bovine serum albumin (DNP-BSA) to induce tolerance. The immune responses of pretreated mice were compared with those of nonpretreated controls following immunization with DNP-hemocyanin (DNP-HCY). The quantity of antibody was measured by radioimmunoassay and the affinity by equilibrium dialysis against ε-DNP-lysine. Maximum serum antibody levels were attained 4 weeks after the first and 1 week after the second immunizing injection of DNP-HCY in all groups. Mice made partially tolerant to the DNP determinant as either neonates or adults responded to primary and secondary immunization with DNP-HCY by producing less DNP-specific antibody which had lower average affinity for DNP-lysine than nontolerized controls. However, in all groups, antibody affinity increased with time so that by the 11th week after primary immunization tolerized mice were producing antibody within the range of affinities seen in controls. The implications of these data are discussed and interpreted in terms of an affinity-dependent selection of cell populations during tolerogenic and immunogenic stimulation.

The influence of Bordetella pertussis on the kinetics of antibody production to sheep red blood cells in NMRI mice.

Die simultane i.p. Injektion von 4 × 108 Schaferythrozyten und 2 × 109 Zellen vonB. pertussis fuhrt im Vergleich zur alleinigen Injektion des Erythrozytenantigens bei NMRI-Mausen zu einer gesteigerten und verlangerten Proliferation γM- und γG/γA-Antikorper produzierender Milzzellen.

Kinetics of cells producing antibodies to penicillin studied by plaque assay

The Jerne plaque assay technique was used for the detection and examination of the kinetics of antibody production to penicillin in mice. Potassium penicilln G (KPG) was linked to hemocyanin (KLH). Swiss mice were given KPG-KLH intravenously. Spleens were removed one to ten days after immunization. Sheep red blood cells (S.R.B.C.) were sensitized with KPG. The spleen cells and KPG-S.R.B.C. were mixed and plated as in Jerne's method. After incubation and overlaying with guinea pig complement, plaques of immune hemolysis were counted. Controls consisted of spleen cells from nonimmunized mice or from animals given KLH only. Peak numbers of plaques with KPG-S.R.B.C. occurred on the fourth day after immunization. There was a thirty- to fortyfold increase in numbers of plaque-forming cells (PFC) in KPG-KLH immunized animals compared with background PFC in nonimmunized mice. A four- to eightfold increase over background was observed in PFC in KLH immunized mice. With this method, it appears possible to study the kinetics of antibody formation to a haptenic allergen such as penicillin.

Biosynthesis of Intrinsically Labeled Antibodies in Vitro

Summary A tissue culture method is described for the production of intrinsically labeled antibodies with specific radioactivities of 1 to 2 × 107 cpm/mg antibody. The kinetics of antibody production in this system were examined. It was found that large changes in the specific radioactivity of the antibodies occurred where the amount of isotopically labeled amino acid precursor in the culture medium was kept constant. This variation in specific radioactivity was due to dilution of the labeled precursor by amino acid resulting from cell breakdown or protein release.