scholarly journals Effect of colchicine on the antibody response. I. Enhancement of antibody formation in mice.

1978 ◽  
Vol 147 (4) ◽  
pp. 1213-1227 ◽  
Author(s):  
P N Shek ◽  
A H Coons
Keyword(s):  
Antibody Response ◽  
Antibody Formation ◽  
Suppressor Cells ◽  
Optimal Dose ◽  
Primary Response ◽  
Secondary Response ◽  
Structural Isomer ◽  
Protein Antigens ◽  
Critical Timing ◽  
Circulating Antibody

Colchicine (CC) enhances the antibody response in mice to protein antigens, like diphtheria toxoid and human gamma globulin, as well as to the 2,4,6-trinitrophenyl hapten. Maximal enhancement was observed when CC was administered to animals on the same day as the injection of antigen. The optimal dose of CC was in the range of 1.0-1.5 mg/kg body weight. The enhanced antibody formation was evident from elevated circulating antibody titers and from an increased number of antibody plaque-forming cells (PFC) of the spleen. The circulating antibody titer of CC-treated animals was higher than that of control animals by a factor of about 3-7 in the primary response, and by a factor of at least 15 in the secondary response. In terms of the number of antibody forming cells, CC enhanced the primary PFC response by approximately equal to 100%, and the secondary PFC response by as high as fivefold. The enhancing effect of CC seemed to be related to its mitosis-blocking capacity since (a) vinblastine another antimitotic drug, was found to be as effective as CC and (b) lumicolchicine, the non-anti-mitotic structural isomer of CC, was ineffective in potentiating antibody responses. The critical timing in the administration of CC on the same day as antigen suggests that most likely, the mitotic poison was acting on antigen-stimulated early dividing suppressor cells.

scholarly journals BIOLOGICAL CHARACTERIZATION OF AN IMMUNOSUPPRESSANT FROM GROUP A STREPTOCOCCI

1971 ◽  
Vol 134 (5) ◽  
pp. 1253-1265 ◽  
Author(s):  
Artin H. Malakian ◽  
John H. Schwab
Keyword(s):  
Antibody Formation ◽  
Memory Cell ◽  
Primary Response ◽  
Repeated Injection ◽  
Group A Streptococci ◽  
Biological Characterization ◽  
Protein Antigens ◽  
Immunosuppressive Action ◽  
Group A

A component in extracts of Group A streptococci suppresses antibody formation in mice against heterologous erythrocyte and protein antigens. Large doses are not toxic and repeated injection does not change its effectiveness. It is most effective when injected 1 or 2 days before antigen and it is not suppressive when given after antigen. The active factor occurs as a large polydisperse complex and activity can be increased 10- to 25-fold by filtration through Sepharose 2B. Both direct (γM) and indirect (γG) antibody-forming cells are suppressed in primary and secondary responses. Injection before a primary response does not reduce memory cell development. It increases rather than depresses the "background" antibody-forming cells to sheep erythrocytes, and is equally effective if injected intraperitoneally or intravenously. Ribonuclease increases activity while deoxyribonuclease has no effect. Proteases destroy immunosuppressive action.

scholarly journals HOMEOSTASIS OF ANTIBODY FORMATION IN THE ADULT RAT

1964 ◽  
Vol 120 (6) ◽  
pp. 987-1005 ◽  
Author(s):  
Donald A. Rowley ◽  
Frank W. Fitch
Keyword(s):  
Antibody Response ◽  
Specific Antibody ◽  
Antibody Formation ◽  
Sheep Erythrocyte ◽  
Passive Immunization ◽  
Primary Antibody ◽  
Secondary Response ◽  
Primary Antibody Response

Passive immunization of rats with homologous anti-sheep erythrocyte serum markedly inhibited the primary antibody response to various doses of sheep erythrocytes. Inhibition was "specific" and apparently produced by either "19S" or "7S" antibody to the antigen. Passive immunization inhibited splenic hyperplasia associated with the primary antibody response. Passive immunization 24 hours after active immunization effectively inhibited the primary antibody response. The markedly suppressive effect of specific antibody on the primary antibody response contrasted sharply with the absence of this effect on the secondary response. Antigen-antibody complexes formed in vitro elicited no measurable primary antibody response but did elicit a high secondary response. Exposure of normal spleen cells to the antibody in vivo or in vitro suppressed their response to the antigen in x-irradiated recipients. In contrast, cells from previously immunized animals transferred to x-irradiated animals produced antibody in the presence of passively given antibody. Thus, "potential antibody-forming cells" from normal animals were unresponsive to the antigen in the presence of specific antibody, while "antibody-forming cells" from previously immunized animals responded to the antigen in the presence of antibody. Presumably, antibody actively produced in small quantities by a few antibody-forming cells might inhibit antibody formation by potential antibody-forming cells. Confirmation of this suggestion was obtained by showing that some animals initially injected with small doses of antigen failed to produce measurable antibody to subsequent injections of larger doses of the antigen. Low doses of antigen capable of inducing unresponsiveness produced no measurable circulating antibody, but these doses did produce increased numbers of plaque-forming (antibody-releasing) cells in spleens of rats. Thus, the formation of specific antibody may provide a homeostatic or "feed-back" mechanism which controls or limits production of specific antibody to the portion of the antibody-forming system previously stimulated by the antigen. This mechanism may account in part for immunological unresponsiveness produced in certain other related experimental systems.

scholarly journals THE X-Y-Z SCHEME OF IMMUNOCYTE MATURATION

1968 ◽  
Vol 128 (4) ◽  
pp. 715-728 ◽  
Author(s):  
Vera S. Byers ◽  
Eli E. Sercarz
Keyword(s):  
Bovine Serum Albumin ◽  
Antibody Response ◽  
Serum Albumin ◽  
Lymph Nodes ◽  
Bovine Serum ◽  
Antibody Formation ◽  
Memory Cell ◽  
Secondary Response ◽  
Antigen Concentration

A concentration of 5 mg/ml bovine serum albumin (BSA) prevents the in vitro elicitation of a secondary response in primed rabbit popliteal lymph nodes, if it is left in contact with the node fragments for the first 6 days of culture. No antibody formation can be detected at any time during the culture period in most cases, although occasional fragments are resistant to inhibition. Reducing the exposure time to the first 3 days of culture delays the peak of the antibody response. The inhibition is antigen specific. Reconstruction experiments demonstrate that the inhibition is not due to antigen masking of the antibody. Even shortly after optimal stimulation, the addition of 5 mg/ml BSA to the fragments was not able to prevent a normal antibody response. The implications of these findings are that (a) a high antigen concentration suspends the memory cell in a reversibly paralyzed state, (b) memory cells have a heterogeneous susceptibility to inhibition, (c) once induced, the antibody response cannot be inhibited by antigen overloading, (d) unresponsiveness in a primed animal can be due to either exhaustion of the memory cell population or paralysis of the memory cell.

scholarly journals EFFECT OF 6-MERCAPTOPURINE (6-MP) ON DIFFERENT CLASSES OF ANTIBODY

1965 ◽  
Vol 122 (2) ◽  
pp. 263-275 ◽  
Author(s):  
Yves Borel ◽  
Marthe Fauconnet ◽  
Peter A. Miescher
Keyword(s):  
Antibody Formation ◽  
Primary Response ◽  
Red Cells ◽  
Secondary Response ◽  
Anamnestic Response ◽  
Small Doses ◽  
Antibody Pattern

In the primary response of mice and rabbits immunized with foreign red cells, 6-MP administration prolonged the formation of 19S antibody. 7S antibody formation was delayed and reduced in these animals. Animals treated with 6-MP during primary response exhibited a preferential 19S response when challenged in the anamnestic response. Animals immunized with small doses of antigen and treated with 6-MP only during the secondary response, reversed the usual antibody pattern and responded with preferential 19S antibody formation.

scholarly journals ANTIBODY FORMATION

1962 ◽  
Vol 115 (3) ◽  
pp. 655-670 ◽  
Author(s):  
Jonathan W. Uhr ◽  
Martin S. Finkelstein ◽  
Joyce B. Baumann
Keyword(s):  
Antibody Response ◽  
Rate Constant ◽  
Guinea Pigs ◽  
Antibody Formation ◽  
Relative Rate ◽  
Serum Antibody ◽  
Similar Rate ◽  
Cellular Level ◽  
Secondary Response ◽  
Whole Body

Injection of a small bacteriophage ϕX 174 into guinea pigs results in an accelerated elimination of phage detectable as early as 24 hours after injection. The immune nature of the accelerated elimination is indicated by its specificity, by the appearance of excess specific serum antibody after phage elimination, and by the prevention of accelerated elimination by 400 r whole body x-irradiation of guinea pigs prior to injection of phage. The early antibody response is considered to be a primary one since an analogous response occurs in newborn guinea pigs, antibody is not detectable in the sera of non-immunized animals, and the second challenge with ϕX stimulates a serum antibody response 100-fold greater than that after primary immunization. The early detection of immune elimination appears to be due, in part, to the small amounts of phage employed, since larger doses of phage delay the time of onset of detectable immune elimination. The early rise of serum antibody in the primary and secondary response appears exponential with a similar rate constant of antibody formation. The rate constant is also independent of dose. These findings have led to the suggestion that during this exponential phase, the relative rate of antibody formation at a cellular level may be constant for a given antigen.

scholarly journals THE TRANSFER OF LYMPH NODE CELLS IN THE STUDY OF THE IMMUNE RESPONSE TO FOREIGN PROTEINS

1955 ◽  
Vol 102 (4) ◽  
pp. 379-392 ◽  
Author(s):  
James C. Roberts ◽  
Frank J. Dixon
Keyword(s):  
Immune Response ◽  
Lymph Node ◽  
Plasma Cells ◽  
Primary Response ◽  
Secondary Response ◽  
Foreign Protein ◽  
Protein Antigens ◽  
Foreign Proteins ◽  
Lymph Node Cells ◽  
Wet Weight

A secondary immune response to the soluble foreign protein antigens I*BSA and I*BGG has been demonstrated when lymph node cells, largely lymphocytes with a few reticulo-endothelial and plasma cells, from previously immunized rabbits were transferred to x-radiated recipient rabbits, and the recipients then challenged with antigen. The total specific antibody synthesized by the transferred cells during the first 8 days of the secondary response amounted to approximately ⅔ of the wet weight of the transferred cells. In an attempt to elicit a primary response, lymph node cells were obtained from normal, non-immunized donors, and transferred to x-radiated recipients. No immune response was observed upon antigenic stimulation. When normal or previously immunized lymph node cells were incubated with antigen for periods up to 1 hour, washed and injected into recipients, no antibody production was observed.

scholarly journals Genetic control of immune response. The dose of antigen given in aqueous solution is critical in determining which mouse strain is high responder to poly(LTyr, LGlu)-poly(LPro)--poly(LLys).

1975 ◽  
Vol 141 (5) ◽  
pp. 1057-1072 ◽  
Author(s):  
S Jormalainen ◽  
E Mozes ◽  
M Sela
Keyword(s):  
Aqueous Solution ◽  
Serum Antibody ◽  
Optimal Dose ◽  
Primary Response ◽  
High Responder ◽  
Secondary Response ◽  
Similar Proportion ◽  
Major Histocompatibility Locus ◽  
Low Responder ◽  
Higher Doses

Antibody response to different doses of (T,G)-Pro--L, given in aqueous solution, was investigated in the high responder SJL and low responder DBA/1 strains by measuring hemolytic plaque-forming cells (PFC) in the spleens as well as hemagglutination titers in the sera. The gene responsible for the difference between the two strains in the response to this antigen, given in complete Freund's adjuvant, has been previously denoted Ir-3. This gene is not linked to the major histocompatibility locus. In the response to the optimal dose (1 mug) of antigen, no difference could be shown between the strains. The peak of the response and the numbers of direct and indirect PFC were similar in both strains in the primary and secondary response. After injection of higher doses (10-100 mug) of antigen, both the direct and indirect PFC responses were lower in the low responder than in the high responder strain. Moreover, the peak of the response occurred earlier in the high responder strain in the primary response to the 10 mu dose of antigen. After administration of a suboptimal dose (0.02 mug) of antigen, the low responder strain produced in the primary response 4-20 times more indirect plaques than the high responder strain. Also the number of direct plaques was higher in the low responder than in the high responder strain. The serum antibody responses to the optimal and higher doses of antigen were parallel to the PFC responses. From inhibition of PFC with free antigen, it was concluded that a similar proportion of cells was producing high and low affinity antibodies to (T,G)-Pro--L in both strains. High and low zone tolerance could be induced in the two strains with (T,G)-Pro--L, but no difference could be shown between the strains. It is suggested that the Ir-3 gene plays a role in the regulation of the balance stimulation and suppression according to the dose of antigen given.

scholarly journals GAMMA GLOBULIN AND ANTIBODY FORMATION IN VITRO

1967 ◽  
Vol 125 (1) ◽  
pp. 33-44 ◽  
Author(s):  
Vera J. Stecher ◽  
G. Jeanette Thorbecke
Keyword(s):  
Antibody Formation ◽  
Primary Response ◽  
Secondary Response ◽  
Detectable Effect ◽  
Complete Suppression ◽  
Similar Time ◽  
X Irradiation ◽  
Early Radiation

The present studies have shown that the influence of X-irradiation on the secondary antibody response in vitro is remarkably similar to its effect on the primary response in vivo. When sensitized tissue was first irradiated and then reexposed to antigen, the duration of the interval between irradiation and antigen addition determined the degree of inhibition of the secondary response obtained. A delay of 12 hr resulted in stronger inhibition than a delay of 6 hr, and an interval of 24 hr before reexposure to antigen caused complete suppression of antibody production to diphtheria toxoid and almost complete suppression when sheep RBC were used as the antigen. Induction of the secondary response in rabbit lymph node tissue in vitro followed by exposure to X-irradiation, revealed that immediate exposure to irradiation after antigen produced stronger inhibition of the subsequent response than irradiation on days 2–3. Irradiation on day 6 had no detectable effect. The effectiveness of the early radiation is probably due to prevention of the proliferation of the antibody-forming cells. BUDR was found to be effective at similar time periods as X-irradiation, whereas colchicine could still stop antibody formation when added late during the secondary response in vitro. It was noted that lymph nodes from some BSA-sensitized rabbits as late as 18 months after sensitization gave a response indistinguishable from a typical secondary response, even when not reexposed to antigen.

scholarly journals Brief Report: Immune Response in Mice with Plasma-Cell Tumor (X5563) Assayed by Agar Plaque Technique

Blood ◽  
1968 ◽  
Vol 31 (2) ◽  
pp. 252-257 ◽  
Author(s):  
SHINJI HIRANO ◽  
YUKIO IMAMURA ◽  
FUMIMARO TAKAKU ◽  
KIKU NAKAO
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Plasma Cell ◽  
Cellular Level ◽  
Primary Response ◽  
Cell Tumor ◽  
Secondary Response ◽  
Sheep Erythrocytes ◽  
Plasma Cell Tumor

Abstract The immune response to sheep erythrocytes in mice with the gamma-type plasma-cell tumor (X5563) was measured on a cellular level by agar plaque technique of Jerne et al. It was demonstrated that there was a reduction in the number of plaque-forming cells involved in the primary response but not in the secondary response in the mice which were immunized shortly before the inoculation of the tumor. These findings indicate that the lowered antibody response in mice with the tumor is due to a diminished number of antibody-forming cells.

scholarly journals ANTIBODY FORMATION IN VOLUNTEERS FOLLOWING INJECTION OF PNEUMOCOCCI OR THEIR TYPE-SPECIFIC POLYSACCHARIDES

1946 ◽  
Vol 83 (4) ◽  
pp. 303-320 ◽  
Author(s):  
Michael Heidelberger ◽  
Colin M. MacLeod ◽  
Samuel J. Kaiser ◽  
Betty Robinson
Keyword(s):  
Antibody Response ◽  
Antibody Formation ◽  
Unexpected Result ◽  
Human Beings ◽  
Subcutaneous Injections ◽  
Specific Antibody Response ◽  
Tentative Explanation ◽  
Normal Human ◽  
Antibody Levels ◽  
Circulating Antibody

1. A modification of the microanalytical quantitative precipitin method, five to ten times as sensitive as the older procedure, has been used to measure the type-specific antibody response in human beings. Injections of type-specific pneumococci or equivalent amounts of their type-specific polysaccharides led to comparable antibody production. In general, the few hundredths of a milligram of polysaccharides injected functioned as extraordinarily powerful antigens. 2. Subcutaneous injections of the polysaccharides were as effective as intracutaneous, and the resulting antibody levels, which were highly variable individually, remained relatively constant for 5 to 8 months, gradually tapering off during periods of observation that exceeded 2 years in some instances. 3. After the injection of several type-specific polysaccharides widely diverse combinations of selective and non-selective responses were observed. 4. Booster doses had little or no effect in increasing circulating antibody, even after 2 years. A tentative explanation is given of this unexpected result. 5. Possibly because they frequently harbor pneumococci, normal human beings appear to be in serological equilibrium with the C-antigen of pneumococcus, since in most instances the quite appreciable anti-C content of their sera remained relatively constant during periods of a year or longer. Many of the sera also contained antibody to S VII.

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