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Biomedical subjects

E Mozes

Publications and source records attributed to E Mozes.

At least 199 records · Page 11Linked to original sources
PubMed1976

Varied effects of polyadenylic-polyuridylic acid on immune responses.

The effect of the double-stranded synthetic polynucleotide, poly(A).poly(U), on the immune response of inbred mouse strains to multichain synthetic polypeptides was studied. Poly(A).poly(U) did not affect immune responses controlled by H-2 linked genes. Thus, when either (T,G)-A- -L or (Phe,G)-A--L were injected into high or low responder mice followed by administration of poly(A).poly(U) 24 h after immunization, no increase in the antibody titers was observed. In contrast, poly(A).poly(U) increased significantly the response to polyproline, which is controlled by a non H-2 linked gene, in low responder mice. However, the polyribonucleotide had no effect on the antibody titers of the SJL mice, the high responders to multichain polyproline. When poly(A).poly(U) was injected into DBA/1 mice following immunization with (Phe,G)-Pro- -L, the polynucleotide enhanced the low response to the Pro- -l region at the expense of the anti (Phe,G) response which is normally high in this mouse strain. In this case poly(A).poly(U) caused an intramolecular antigenic competition. The general conclusion of this study is that the chemical nature of the antigenic determinant plays an important role in determining the type of influence exerted by poly(A).poly(U).

Animals↗
PubMed1976

Role of antigenic structure in cell to cell cooperation.

Two synthetic polypeptides which differ only in the order of amino acids in their NH2-terminal side chains, namely, (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(LLys) and (Tyr-Glu-Try-Glu)-poly(DLAla)- -poly(LLys), were found to be under different genetic control. By three different in vivo systems for thymus-derived cell depletion, it was demonstrated that (Tyr-Tyr-Glu-Glu)-poly(DLAla)- -poly(LLys), which represents the random poly(Tyr,Glu)-poly(DLAla)- -poly(Lys) in the pattern of immune responses and in the quality of antibodies they elicit, is thymus-dependent whereas (Tyr-Glu-Tyr-Glu)-poly(DLAla)-poly(LLys) does not require thymus-derived cell help for efficient antibody production. Therefore, the two ordered polypeptides which are similar chemically differ in parameters, not yet determined, which affect their capability to trigger bone marrow-derived cells.

Amino Acid Sequence↗
PubMed1976

Genetic control of immune responsiveness to poly (LPro)--poly (LLys)-derived polypeptides by histocompatibility-linked immune response genes in the rat.

In rats responsiveness to branched synthetic polypeptides carrying a Pro--L backbone, such as (T,G)-Pro--L or (Phe,G)-Pro-L and to Pro--L itself is controlled by Ir genes which are linked to the major histocompatibility genes. The level of antibody production to these polypeptides does not fall into strict high or low responder categories but covers the range in between. (T,G)-pro--L and Pro--L elicit a very similar response pattern which, however, differs from that obtained with (Phe,G)-Pro--L. Anti-(T,G),Pro--L antibodies do not cross-react with (T,G)-A--L, but do so extensively with Pro--L. Anti-(Phe,G)-Pro--L antibodies show cross-reactivity to (Phe,G)-A--L only when the antibody-producing strain is a high responder to (Phe,G)-A--L. These results when considered in view of data obtained in mice on genetic control of the immune response to (T,G)-Pro--L suggest that at least two unlinked Ir genes are involved in controlling anti-Pro--L responsiveness.

Animals↗
PubMed1976

Comparison of the immune response potential of newborn mice to T-dependent and T-independent synthetic polypeptides.

Newborn mice do not, in general, produce antibodies during the 1st week of life; this inability to respond immunologically has been attributed to lack of functional macrophages and T cells. To determine whether B cells of newborn mice are functionally mature and therefore capable of producing antibodies to thymus (T) independent antigens, the response of 1-9-day-old C3H/HeJ mice injected with a thymus-independent polypeptide, poly(DTyr,DGlu)-polyDPro- -polyDLys was compared to that of their littermates injected with a thymus-dependent immunogen, poly(LTyr,LGlu)-polyLPro- -polyLLys. No antibodies were detected in 1- or 2-day-old mice immunized with the T-dependent antigen, as revealed by haemagglutination and haemolytic plaque-forming cell assays, performed 6 days after injection of the antigen. Injection of 3-day-old animals with the thymus-dependent immunogen resulted in significant immune responses which increased with age. In contrast, 1- and 2-day-old mice responded to the T-independent immunogen with high antibody levels, however, in 3-day-old injected mice, the levels were lower. When 3-day-old nude mice were injected with this antigen, no decrease in the immune response was observed. Thus, newborn mice respond immunologically to a thymus-independent antigen injected at the first 2 days after birth and the antibody levels decrease with maturation of the thymus.

Age Factors↗
PubMed1975

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).

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.

Animals↗
PubMed1975

Antigen-specific T-cell factors in the genetic control of the immune response to poly(Tyr,Glu)-polyDLAla--polyLys. Evidence for T- and B-cell defects in SJL mice.

The cellular basis of the genetic control of the immune response to poly(LTyr, LGlu)-polyDLAla--polyLLys [(T,G)-A--L] in SJL (H-2s, low responder) mice has been investigated using T-cell factors. Thymocytes of SJL origin were educated to (T,G)-A--L and tested for their ability to produce an antigen-specific factor capable of cooperating in vivo with bone marrow cells of either SJL or C3H.SW (high responder) origin. SJL T cells were found to be incapable of producing such a cooperative factor, in contrast with results previously obtained with C3H/HeJ (low responders) and C3H.SW strains. Moreover, SJL bone marrow cells did not produce an antibody response to (T,G)-A--L, even when combined with factor produced by high responder (C3H.SW) mice. Thus, both T and B cells appear to be defective in the SJL strain in the response to (T,G)-A--L.

Animals↗
PubMed1975

The effect of the thymus-independent antigens, collagen and synthetic collagen-like polypeptide, on the requirement of cell cooperation in the immune response to thymus-dependent antigens.

The effect of thymus-independent antigens on the need for cell cooperation in the immune response to thymus-dependent antigens was investigated. Irradiated recipient mice transplanted with either bone marrow cells or a mixture of bone marrow and thymus cells, were immunized with the thymus-independent antigen (Pro-Gly-Pro)n covalently conjugated to the thymus-dependent ovalbumin, or with a mixture of (Pro-Gly-Pro)n and ovalbumin. In both cases an effective response towards ovalbumin was observed in the absence of thymus cells as was found for the thymus-independent (Pro-Gly-Pro)n. The same effect on ovalbumin was demonstrated when a mixture of the thymus-independent collagen and ovalbumin was used for immunization. On the other hand, when irradiated reconstituted mice were immunized with a mixture of ovalbumin and the thymus-dependent gelatin, which is the denatured product of collagen, cell-to-cell cooperation was required for an immune response to both immunogens. The effect of (Pro-Gly-Pro)n and collagen on the response to the thymus-dependent ovalbumin in vivo was observed in in vitro experiments using sheep red blood cells (SRBC) as the immunogen as well. In the presence of reduced and carboxymethylated (RCM) Ascaris collagen and (Pro-Gly-Pro)n, nude spleen cells could produce significant numbers of plaque-forming cells towards SRBC. Thus, (Pro-Gly-Pro)n and collagen can deliver the signal required to stimulate B cells to produce antibody towards thymus-dependent antigens in the absence of T cells. In contrast to the results with (Pro-Gly-Pro)n and collagen, the thymus-independent synthetic polypeptide poly(DTyr, DGlu-)-poly(DPro)--poly(DLys) did not affect the requirement for cell cooperation of the thymus-dependent immunogens, ovalbumin and SRCB. It thus appears that the ability to substitute for T cells for antibody production towards thymus-dependent immunogens is not a general characteristic of thymus-independent antigens.

Animals↗
PubMed1975

Genetic control of the murine cell-mediated immune response in vivo. II. H-2 linked responsiveness to the synthetic polypeptide poly(Tyr,Glu)-poly(DL-Ala)--poly(Lys).

Cell-mediated immunity in response to (T,G)-A-L was studied with a radioisotopic footpad assay. It appears that in vivo cell-mediated immune responsiveness to (T,G)-A--L is linked to the H-2 complex, as was demonstrated previously for specific antibody snythesis. Evidence is presented in this report which indicates that the cell-mediated immunity measured is a function of a population of T cells. The apparent controversy between results obtained by analyzing antibody formation and cell-mediated immunity can be explained by assuming the need for cell cooperation between helper T cell and effector T cell, because efficient purely cellular immunity is analogous to T-B cell cooperation needed for antibody production.

Animals↗
PubMed1975

Lack of inverse relationship between the net charge of T-independent immunogens and the responding spleen cells.

Previous studies have demonstrated an inverse relationship between the net electrical charge of immunogens and the antibodies they elicit. This correlation was found to be expressed at the cellular level. It has been shown that thymus-derived cells may recognize immunogens on the basis of their overall electrical charge. In this study, charged T-independent copolymers composed of tyrosine, glutamic acid, and lysine of the D configuration were prepared in order to find out whether this net charge phenomenon holds also for immunogens which do not require helper T cells for generation of immune response. Spleen cells were fractionated over negatively charged glass bead columns, and their immunocompetence was tested by transferring them into irradiated recipient mice which were immunized with the dinitrophenylated acidic or basic T-independent carrier. No differences in the responsiveness to the dinitrophenyl group on either carrier could be detected in recipients of unfractionated or fractionated cells on the charged columns. Similar results were obtained with the negatively charged T-independent branched polypeptide poly-(DTyr,DGlu)-poly(DPro)--poly(DLys). Filtration of spleen cells through glass bead columns did not affect the immune response potential of the recipient mice. In contrast, a significant reduction was observed in the frequency of positive responses in recipients of filtered cells, which were immunized with the negatively charged T-dependent poly(DTyr,DGlu)-poly(DPro)--poly(DLys). Thus, the inverse net charge phenomenon holds only for T-dependent antigens.

Animals↗
PubMed1975

The nature of murine immune response to nucleic acids.

The antibody response of mice to nucleic acids appears to be genetically regulated, and may show varying patterns. SJL/J mice and AKR/Cu mice are high responders to denatured DNA complexed with MBSA and produce 7S as well as 19S antibodies. DBA/2 mice respond with low titers to this immunogen which consists of 19S antibody exclusively. C57BL/6 mice are high responders to denatured DNA, but produce only 19S antibodies. Denatured DNA-MBSA is immunogenic when injected without complete Freund's adjuvant, thereby suggesting that this antigen might be thymus independent. The pattern of immune responses of some strains to the polyribonucleotides poly(I)-poly(C) and poly(A)-poly(U) is opposite to that observed with denatured DNA. Thus, DBA/2 mice are high responders and SJL/J mice are low responders. However, the low responders SJL/J mice produce 7S as well as 19S antibody which suggests that different mechanisms operate for the regulation of immune responses to the two types of nucleic acids. Whereas no antibody is elicited upon immunization with DNA in the absence of a carrier protein, poly(A)-poly(U) and poly(I)-poly(C) are immunogenic when injected without MBSA. Immunization with complexes of the polyribonucleotides and MBSA enhanced the responses to these immunogens; however, the strain differences were not completely abolished. Poly(A)-poly(U) did not enhance the low immune responses of DBA/2 mice to denatured DNA when injected i.v. following immunization with the DNA-MBSA. However, simultaneous immunization of DBA/2 and SJL/J mice with poly(A)-poly(U) and denatured DNA-MBSA resulted in high antibody titers to both immunogens in either mouse strain.

Animals↗
PubMed1974

Antigen-specific thymus cell factors in the genetic control of the immune response to poly-(tyrosyl, glutamyl)-poly-D, L-alanyl--poly-lysyl.

The genetic control of the antibody response to a synthetic polypeptide antigen designated poly-L(Tyr, Glu)-poly-D,L-Ala--poly-L-Lys [(T, G)-A--L] has been studied in congenic high responder C3H.SW (H-2(b)) and low responder C3H/HeJ (H-2(k)) strains of mice. This response is controlled by the Ir-1 gene and is H-2 linked. The method employed was to study the ability of specifically primed or "educated" T cells of each strain to produce cooperative factors for (T, G)-A--L in vitro. Such factors have been shown to be capable of replacing the requirement for T cells in the thymus-dependent antibody response to (T, G)-A--L in vivo. The T-cell factors produced were tested for their ability to cooperate with B cells of either high or low responder origin by transfer together with bone marrow cells and (T, G)-A--L into heavily irradiated, syngeneic (for bone marrow donor) recipients. Direct anti-(T, G)-A--L plaque-forming cells were measured later in the spleens of the recipients. The results showed that (a) educated T cells of both high and low responder origin produced active cooperative factors to (T, G)-A--L, and no differences between the strains in respect to production of T-cell factors could be demonstrated; and (b) such factors, whether of high or low responder origin, cooperated efficiently with B cells of high responder origin only, and hardly at all with B cells of low responder origin. The conclusion was drawn that the cellular difference between the two strains lies in the responsiveness of their B cells to specific signals or stimuli received from T cells. As far as could be discerned by the methods used, no T-cell defect existed in low responder mice and the expression of the controlling Ir-1 gene was solely at the level of the B cells in this case.

Alanine↗
PubMed1974

Antibody response of inbred mouse strains to ordered tetrapeptides of tyrosine and glutamic acid attached to multichain polyalanine or polyproline. Tyr-Tyr-Glu-Glu is a major determinant of the random poly-(Tyr, Glu)-polyDLAla--polyLys.

Five inbred mouse strains which represent high and low responders to the random synthetic polypeptide poly(LTyr,LGlu)-polyDLAla--polyLLys, designated (T, G)-A--L, to which the immune response is controlled by an H-2-linked gene, were immunized with three ordered tetrapeptides composed of tyrosine and glutamic acid attached either to multichain poly-DL-alanine or to polyproline. Only one of the three antigenic determinants, namely tyrosyl-tyrosyl-glytamyl-glutamic acid (T-T-G-G), resembled the random peptide (T, G) in the pattern of immune responses elicited against it, and in the cross-reactivity of the specific antibodies with (T, G)-A--L. The immune response pattern to the other two ordered tetrapeptides, T-G-T-G and G-T-T-G, was different from that obtained with (T, G)-A--L, and no cross-reactivity was detected between the antibodies provoked with these peptides and (T, G)-A--L. Thus, it is suggested that T-T-G-G is a major determinant in the random (T, G)-A--L.

Alanine↗