scholarly journals GENETIC CONTROL OF THE IMMUNE RESPONSE

1972 ◽  
Vol 135 (1) ◽  
pp. 126-135 ◽  
Author(s):  
Graham F. Mitchell ◽  
F. Carl Grumet ◽  
Hugh O. McDevitt
Keyword(s):  
Immune Response ◽  
Cell Interaction ◽  
Primary Response ◽  
High Response ◽  
High Responder ◽  
Igg Antibody ◽  
Low Responder ◽  
Freund’S Adjuvant ◽  
Freund's Adjuvant ◽  
Synthetic Polypeptide

The effect of thymectomy on the genetically controlled murine immune response-1 (Ir-1) to the synthetic polypeptide poly-L(Tyr, Glu)-poly-D, L-Ala--poly-L-Lys [(T, G)-A--L] was studied with both aqueous and adjuvant immunization regimens. Adult thymectomy (combined with irradiation and bone marrow transfusion) did not affect the aqueous antigen-induced (IgM) primary response of either high or low responder mice, but did ablate the (IgG) secondary or tertiary response, a response which is restricted to the high responder strains. Adult thymectomy also blocked the normal high response to (T,G)-A--L in Freund's adjuvant in high responder mice and the high response to methylated bovine serum albumin (MBSA)-(T,G)-A--L in low responder mice. Neonatal thymectomy was also effective in blocking the response to (T, G)-A--L in Freund's adjuvant in high responder mice. These data are consistent with the concept that the Ir-1 gene effect is mediated via thymus cell interaction with antigen and with "B"-cells during the time of induction of IgG antibody formation.

scholarly journals GENETIC CONTROL OF THE IMMUNE RESPONSE

1972 ◽  
Vol 135 (1) ◽  
pp. 110-125 ◽  
Author(s):  
F. Carl Grumet
Keyword(s):  
Aqueous Solution ◽  
Immune Response ◽  
Antibody Production ◽  
Antibody Formation ◽  
Antigen Challenge ◽  
Igg Antibody ◽  
Igm Antibody ◽  
Low Responder ◽  
Kinetics Of ◽  
Synthetic Polypeptide

The kinetics of antibody formation after immunization with the synthetic polypeptide poly-L(Tyr, Glu)-poly-D, L-Ala--poly-L-Lys [(T, G)-A--L] in aqueous solution were studied in genetically high (H-2b) and low (H-2k) responder strains of mice. During the 1st wk after immunization both strains developed brisk primary responses consisting of IgM antibody. With subsequent antigen challenge, only the high responder mice showed immunological memory, producing high titers of IgG antibody. In contrast, the low responder mice continued to make a persistent low level of IgM antibody and appeared unreactive to secondary or tertiary antigen challenge. These data are consistent with the hypothesis that the immune response-1 gene [controlling response to (T, G)-A--L] exerts its effect on the immune response at the time of switchover from IgM to IgG antibody production.

scholarly journals CELLULAR BASIS OF THE GENETIC CONTROL OF IMMUNE RESPONSES TO SYNTHETIC POLYPEPTIDES

1970 ◽  
Vol 132 (4) ◽  
pp. 613-622 ◽  
Author(s):  
Edna Mozes ◽  
G. M. Shearer ◽  
Michael Sela
Keyword(s):  
Immune Response ◽  
Genetic Control ◽  
Relative Number ◽  
Precursor Cells ◽  
Spleen Cells ◽  
Low Responders ◽  
Synthetic Polypeptides ◽  
Low Responder ◽  
Synthetic Polypeptide ◽  
High Responders

SJL mice are high responders to the synthetic multichain polypeptide antigen (T,G)-Pro--L, whereas DBA/1 mice are low responders (10, 11). In order to determine whether the genetic control of immune response can be correlated with the number of antigen-sensitive precursor cells, spleen cell suspensions from normal and immunized SJL and DBA/1 donor mice were transplanted into lethally X-irradiated syngeneic recipients (incapable of immune response) along with (T, G)-Pro--L. Anti-(T, G)-Pro--L responses (donor-derived) were assayed in the sera of the hosts 12–16 days later. By transplanting graded and limiting numbers of spleen cells, inocula were found which contained one or a few antigen-sensitive precursors reactive with the immunogen. Using this method to estimate the relative numbers of such cells for the high responder SJL strain, one precursor was detected in ∼1.3 x 106 and ∼7.2 x 106 spleen cells from immunized and normal donors, respectively. In contrast, one precursor was detected in about 30 x 106 spleen cells from low responder DBA/1 mice, irrespective of whether the donors had been immunized. These results indicate that the genetic control of immunity to the synthetic polypeptide antigen investigated is directly correlated to the relative number of precursor cells reactive with the immunogen in high and low responder strains.

scholarly journals The immune response of allophenic mice to 2,4-dinitrophenyl (DNP)-bovine gamma globulin. I. Allotype analysis of anti-DNP antibody

1978 ◽  
Vol 147 (6) ◽  
pp. 1849-1853 ◽  
Author(s):  
CM Warner ◽  
TJ Berntson ◽  
L Eakley ◽  
JL McIvor ◽  
RC Newton
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
T Cells ◽  
B Cells ◽  
Glutamic Acid ◽  
Gamma Globulin ◽  
High Responder ◽  
Gene Control ◽  
Low Responder ◽  
Bone Marrow Chimeras

The question of whether or not lymphoid cells can cooperate across a histocompatibility difference barrier has been studied in several laboratories. Using an adoptive transfer system, Katz et al. (1) first showed that T cells from (low responder × high responder) F(1) mice, primed to the terpolymer L-glutamic acid, L-lysine, L-tyrosine (GLT), could collaborate with 2,4-dinitrophenyl (DNP)-primed B cells from a high responder, but not a low responder strain, in response to DNP-GLT. The response to GLT is under H- 2-1inked Ir gene control. In contrast, studies with mouse bone marrow chimeras have shown that T cells can interact with H-2-histoincompatible B cells in response to antigens not under Ir gene control (2-4). Another type of chimera, the allophenic mouse, has been used to study possible histoincompatible cell interactions to a number of antigens, including DNP-L- glutamic acid, L-lysine, L-alanine; L-glutamic acid, L-alanine, L-tyrosine; L-glutamic acid, L-lysine, L-phenylalanine; and poly-L (Tyr, Glu)-poly D,L- Ala-poly-L-Lys[T,G)-A-L] (5-9). The response to each of these antigens is under H-2-1inked Ir gene control. It was initially reported (8, 9) that in allophenic mice containing both high and low responder cells, the antibody to (T,G)-A-L was of both the high and low responder allotype. This was interpreted to mean that high responder T cells had cooperated with low responder B cells across a histocompatibility difference barrier in the environment of the allophenic mice. However, Press and McDevitt (10) have recently reported that additional and more accurate analyses of these allophenic mouse sera failed to detect any anti-(T,G)-A-L antibody of the low responder allotype. Moreover, in an experiment using bone marrow chimeras, there was no low responder allotype antibody produced in response to (T,G)-A- L(10). The present study was undertaken to test the immune response of allophonic mice to an antigen, DNP-bovine gamma globulin (DNP(56)BGG), known to be controlled by genes both inside and outside the H-2 complex (11, 12).(1) When high and low responder cells to DNP(56)BGG are present in allophenic mice, only antibody of the high responder allotype is produced. The results suggest that cell cooperation in allophenic mice cannot occur across a histocompatibility difference barrier in response to an antigen whose genetic control is at least partially within the H-2 complex.

scholarly journals CONTRIBUTION OF DIFFERENT CELL TYPES TO THE GENETIC CONTROL OF IMMUNE RESPONSES AS A FUNCTION OF THE CHEMICAL NATURE OF THE POLYMERIC SIDE CHAINS (POLY-L-PROLYL AND POLY-DL-ALANYL) OF SYNTHETIC IMMUNOGENS

1972 ◽  
Vol 135 (5) ◽  
pp. 1009-1027 ◽  
Author(s):  
G. M. Shearer ◽  
Edna Mozes ◽  
Michael Sela
Keyword(s):  
Bone Marrow ◽  
Immune Responses ◽  
Genetic Control ◽  
Bone Marrow Cells ◽  
Marrow Cell ◽  
High Responder ◽  
Side Chains ◽  
Low Responder ◽  
Synthetic Polypeptide ◽  
Marrow Cells

Genetic regulation of immunological responsiveness was studied at the cellular level by comparing the limiting dilutions of immunocompetent cells from spleen, thymus, and bone marrow of high and low responders as a function of the poly-L-prolyl and poly-DL-alanyl side chains of two synthetic polypeptide immunogens. The spleens of immunized and unimmunized high responder DBA/1 mice were found to contain respectively, 18- and 7-fold more limiting precursor cells specific for (Phe, G)-A--L than the spleens of SJL low responder donors. These results, using a synthetic polypeptide built on multichain poly-DL-alanine, confirm the findings reported for polypeptides built on multichain poly-L-proline (1, 2), that there is a direct correlation between immune response potential and the relative number of immunocompetent precursors stimulated. Cell cooperation between thymocytes and bone marrow cells was demonstrated for both (T, G)-Pro--L and (Phe, G)-A--L. Limiting dilutions of thymus and bone marrow cells in the presence of an excess amount of the complementary cell type indicated an eightfold lower number of detected (T, G)-Pro--L-specific precursors in DBA/1 (low responder) marrow when compared with SJL (high responder) marrow. No differences were observed in the frequency of relevant high and low responder thymocytes for the (T, G)-Pro--L immunogen. These results are similar to those reported for the (Phe, G)-Pro--L (3). In contrast to the cellular studies reported for the Pro--L series of immunogens, the marrow and thymus cell dilution experiments for (Phe, G)-A--L revealed genetically associated differences in both the marrow and thymus populations of immunocytes from high (DBA/1) and low (SJL) responders. In addition to a fivefold difference in limiting marrow cell precursors (similar to that seen in the Pro--L studies), a striking difference was observed between the helper cell activity of high responder DBA/1 and low responder SJL thymocytes. This difference was indicated by the observation that low responder thymocyte dilutions followed the predictions of the Poisson model, whereas dilutions of high responder thymocytes did not conform to Poisson statistics. Transfers of allogeneic thymus and marrow cell mixtures from DBA/1 and SJL donors confirmed the syngeneic dilution studies showing that the genetic defect of immune responsiveness to (Phe, G)-A--L is expressed at both the thymus and marrow immunocompetent cell level. The parameters presently known for genetic control of immune responses specific for (Phe, G) (Ir-1 gene) and for Pro--L (Ir-3 gene) have been compared. The Ir-1 and Ir-3 genes are not only distinct by genetic linkage tests (to H-2) (5, 6, 9), but they are also seen to be different by cellular studies. Furthermore, expression of low responsiveness within a given cell population was shown to depend on the chemical structure of the whole immunogenic macromolecule.

scholarly journals GENETIC CONTROL OF THE ANTIBODY RESPONSE TO POLY-L(TYR,GLU)-POLY-D,L-ALA--POLY-L-LYS IN C3H↔CWB TETRAPARENTAL MICE

1974 ◽  
Vol 140 (6) ◽  
pp. 1660-1675 ◽  
Author(s):  
Kathleen B. Bechtol ◽  
John H. Freed ◽  
Leonard A. Herzenberg ◽  
Hugh O. McDevitt
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Antibody Response ◽  
Genetic Control ◽  
Binding Capacity ◽  
High Responder ◽  
Total Serum ◽  
Antigen Binding ◽  
Low Responder

In order to further delineate the mechanisms underlying genetic unresponsiveness, tetraparental mice were constructed from immune response-1A gene high responder and low responder parental genotypes, then were immunized with poly-L-(Tyr,Glu)-poly-D,L-Ala--poly-L-Lys ((T,G)-A--L). An analysis of the total serum allotype mixture and of the antigen-binding capacity of the separated allotypes demonstrated that in the milieu of a tetraparental mouse, both high and low responder B cells could be stimulated equally to produce identical high titered anti-(T,G)-A--L responses. Furthermore, these studies show that effective stimulation could occur across a histocompatibility disparity.

Serological characterization of γM (19 S) and γG (7 S) rabbit antibodies in response to Entamoeba histolytica antigens

1968 ◽  
Vol 14 (12) ◽  
pp. 1317-1323 ◽  
Author(s):  
Z. Ali Khan ◽  
E. Meerovitch
Keyword(s):  
Entamoeba Histolytica ◽  
Primary Response ◽  
Complete Freund’S Adjuvant ◽  
Secondary Response ◽  
Antibody Activity ◽  
Serological Characterization ◽  
Freund’S Adjuvant ◽  
Complete Freund's Adjuvant ◽  
Freund's Adjuvant

Entamoeba histolytica (DKB strain) antigen mixed with an equal volume of complete Freund's adjuvant was injected at multiple sites into three rabbits. Primary response sera were drawn 1, 2, and 3 weeks after the first injection. Two injections of antigen were given in the fourth week, at 3-day intervals. The secondary response sera were drawn 5, 6, and 12 weeks after the beginning of immunization. A steady hemagglutination (HA) titer of 1:128 was obtained with all the three primary response sera, while the secondary response sera showed HA titers of 1:2000 to 1:8000. The 0.1 M 2-mercaptoethanol treatment of these sera reduced, but did not completely obliterate, their HA activity. The HA activity was detected in both the pooled γM and γG classes of immunoglobulins of the primary and secondary response sera; the immunoprecipitating activity was confined to the γG class. 2-Mercaptoethanol treatment completely destroyed the antibody activity of γM fractions without affecting that of the γG fraction. Repeated immunoelectrophoresis runs of the whole sera and pooled γM and γG fractions showed variable numbers of precipitin bands at the γG position but none at the γM and γA positions.

scholarly journals Prophylactic or therapeutic administration of Holarrhena floribunda hydro ethanol extract suppresses Complete Freund’s Adjuvant-induced arthritis in Sprague-Dawley rats    

2020 ◽  
Author(s):  
Stephen Antwi ◽  
Daniel Oduro-Mensah ◽  
David Darko Obiri ◽  
Clara Lewis ◽  
Ebenezer Oduro-Mensah ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Ethanol Extract ◽  
Stem Bark ◽  
Sprague Dawley ◽  
Adjuvant Induced Arthritis ◽  
Sprague Dawley Rats ◽  
Freund’S Adjuvant ◽  
Complete Freund's Adjuvant ◽  
Freund's Adjuvant

Abstract Ethnopharmacological relevance In Ghanaian folk medicine, Holarrhena floribunda has anecdotal use for the treatment of inflammatory conditions. A hydro ethanol extract of the stem bark has previously been shown to be effective in the management of acute inflammation and anaphylaxis in rodents.Aim of the study This study was aimed at evaluating the usefulness of H. floribunda stem bark hydro ethanol extract (HFE) for the management of chronic inflammation in a murine model.Materials and Methods Anti-arthritic effect of the extract was evaluated using Complete Freund’s Adjuvant-induced arthritis in male Sprague-Dawley rats. Using both prophylactic and therapeutic treatment models, parameters assessed included oedema, serology of inflammatory response, radiology, bone tissue histology and haematology. Data were analysed by ANOVA followed by Tukey’s multiple comparisons post hoc test.Results HFE at 50–500 mg/kg dose-dependently [P ≥ 0.0354 (prophylactic) and P ≥ 0.0001 (therapeutic)] inhibited swelling of the injected paw upon prophylactic [≤ 81.26 % (P < 0.0001)] or therapeutic [≤ 67.92 % (P < 0.01)] administration — and prevented spread of arthritis to the contralateral paw. Inflammation alleviation activity of HFE was further demonstrated by decrease in arthritis score, radiologic score and erythrocyte sedimentation rate. HFE at all doses significantly reduced serum IL-1α (P < 0.0197), and 500 mg/kg HFE reduced serum IL-6 (P = 0.0032). In contrast, serum concentrations of IL-10, protein kinase A and cyclic adenosine monophosphate were enhanced (P ≤ 0.0436). HFE consistently showed better prophylactic activity than when administered therapeutically.Conclusions The data demonstrate that HFE suppresses CFA-induced arthritis and modulates regulators of inflammation; including IL-1α, -6 and -10 which also play mediatory roles in several immune response pathways. These make HFE a strong candidate for development as an agent for management and modulation of inflammation and the inflammatory response, including immune response-related adverse events such as seen in severe COVID-19.

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.

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