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Diet and immunological memory of lines of White Leghorn chickens divergently selected for antibody response to sheep red blood cells.

Antibody responses to a first, second, and third injection with SRBC, and growth were studied in lines of White Leghorn chickens selected for high (HA) or low (LA) 5-d antibody titers to an i.v. inoculation with 0.1 mL of a 0.25% suspension of SRBC. The experiment involved parallel studies on two groups of chicks hatched from the same matings of parental lines HA and LA at a 14-d interval. Chicks of each age-line subclass were fed either a high or low nutrient density diet from hatch onwards. When chicks of Hatches 1 and 2 were 28 and 14 d of age (doa) respectively, they were injected with 0.1 mL of 0.25% suspension of SRBC, and antibody titers measured 3 and 6 d later. A second and a third injection of the same concentration of SRBC was given to chicks of each age-line-diet subclass at 10-d intervals and antibody titers measured 3 and 6 d after each injection in different chicks randomly sampled from each age-line-diet subclass. After the first injection, antibody (primary) responses of HA chicks were higher than those of LA chicks regardless of age and diet. This difference (HA > LA) observed for the primary response was seldom evident in the responses to the second (secondary) and third (tertiary) injections. Antibody responses of LA chicks after the second and third injections were anamnestic. For HA chicks given the first injection at 28 doa, neither the secondary nor tertiary responses suggested anamnestic capacities, whereas there was apparent memory exhibited by the secondary and tertiary responses of HA chicks initially injected at 14 doa. The LA chicks were significantly heavier than HA chicks at all ages. Even though the higher nutrient density diet increased BW of chicks of both lines, its effect on memory responses was sporadic. The results of this experiment show that, even though divergent selection has been successful in the primary responses, correlated responses in immunological memory were not always observed, suggesting that the two types of responses might be under different genetic control.

Animal Husbandry↗

Studies on the immune response to fixed antigens. IV. Recall of immunologic memory with fixed antigens.

The chemically modified antigens, trinitrophenylated sheep red blood cells (SRBC) and glutaraldehyde-SRBC, elicited specific secondary responses in mice but were unable to induce primary responses. They also induced specific immunologic memory. The secondary immune response was directed to the specific determinants of SRBC but not to new antigenic determinants created by the chemical modification process. The interpretation of these findings is discussed in relationship to the ability of fixed antigens to be processed by macrophages.

Animals↗

Immunosuppression in murine malaria. III. Induction of tolerance and of immunological memory by soluble bovine serum albumin.

The primary antibody response to alumadsorbed BSA was depressed when initiated during low-grade chronic Plasmodium berghei malaria in mice, as previously reported during acute P.y. yoelii infection. Induction of immunological memory by soluble polymerized BSA was abolished in both infections; in infected hosts this normally immunogenic stimulus resulted in partial tolerance. In contrast to the depression of immune response, neither infection interfered with the induction of low-zone tolerance by monomeric BSA. The rate of non-immune elimination of BSA was found to be normal during acute malaria, and only slightly reduced in chronic infection. These results may be explained in terms of abnormal antigen handling in infected mice, due to some functional defect in macrophages, although this does not seem to be a sufficient explanation for all the phenomena of malaria-associated immunosuppression.

Animals↗

Priming of immunological memory by pneumococcal conjugate vaccine in children unresponsive to 23-valent polysaccharide pneumococcal vaccine.

Pneumococcal polysaccharide vaccine (PPV) is of limited immunogenicity in infants and immunocompromised patients. Our prospective randomized controlled trial investigated whether priming with pneumococcal conjugate vaccine (PCV) induced specific immunological memory in previously nonresponders to PPV. Of a total of 33 children (2 to 18 years) with polysaccharide-specific immunodeficiency (PSI), group A (n = 16) received two doses of 7-valent PCV in a 4- to 6-week interval, and a booster dose of 23-valent PPV after one year. Group B (n = 17) received two doses of PPV in a 1-year interval exclusively. Specific antibody concentrations for serotypes 4, 5, 6B, 9V, 14, 18C, 19F, and 23F were determined (enzyme-linked immunosorbent assay) before and at 7 and 28 days after administration of the PPV booster and compared to an opsonophagocytosis assay. Of group A, 64 to 100% had antibody concentrations of > or = 1 microg/ml on day 28 after the booster versus 25 to 94% of group B. Group A had significantly higher antibody concentrations for all PCV-containing serotypes already on day 7, indicating early memory response. Antibody concentrations were in accordance with functional opsonic activity, although opsonic titers varied among individuals. Pneumococcal vaccination was well tolerated. The incidence of airway infections was reduced after priming with PCV (10/year for group A versus 15/year for group B). Following a PPV booster, even patients primarily not responding to PPV showed a rapid and more pronounced memory response after priming with PCV.

Adolescent↗

Antibody responses to antigenic determinants of influenza virus hemagglutinin. I. Thymus dependence of antibody formation and thymus independence of immunological memory.

Using immunodiffusion methods it has been shown that purified hemagglutinin (HA) extracted from two related strains of influenza A viruses (A/PR8/34 and A/FM1/47) have two distinct antigenic determinants, or groups of determinants. One determinant is cross-reactive while the other is strain-specific. Antisera raised in normal mice against HA were shown to contain two populations of antibody molecules, each directed against one of the determinants. Immunization of thymus-deprived (TXBM) mice showed a strong thymus dependence of antibody formation to HA. However, the thymus dependence of antibody formation against the cross-reactive determinant could be overcome by repeated inoculations of HA in TXBM mice, indicating a different handling of two portions of the same molecule by the immunological system. Strong, secondary-type responses to the strain-specific determinant were observed in primed thymus-deprived mice after reconstitution with virgin thymus cells, showing that specific immunological memory was elicited by this determinant despite the absence of detectable antibody secretion. These findings are interpreted as examples of immunological recognition and memory mediated by B lymphocytes and discussed in terms of mechanisms of T and B lymphocyte co-operation. It is suggested that the helper effect of T lymphocytes is exerted at a late stage in the differentiation of specific populations of B cells into antibody-secreting cells.

Animals↗

Comparison of the immunological memory after DNA vaccination and protein vaccination against anthrax in sheep.

Currently available live spore vaccines against anthrax in animals have many drawbacks, one of which is their presumed inability to induce a long lasting immunity. In the present study we compared the immunological memory after a protein vaccination with DNA vaccinations in sheep. The antigen used was the protective antigen (PA83) of Bacillus anthracis. Sheep were vaccinated three times with either PA83 plus alhydrogel, or with one of four different plasmid DNA formulations, which all encoded either the full-length PA83 or its domain 4. Two pDNA formulations included Vaxfectin adjuvant, the other two were injected in PBS without adjuvant. Initially, the antibody titres of protein vaccinated sheep were significantly higher than the titres of pDNA vaccinated sheep. After 5 months, however, the antibody titres of protein vaccinated sheep had dropped remarkably, while the titres of all four pDNA vaccinated groups were either stable or had increased. Humoral responses of sheep immunised with pDNA formulated with Vaxfectin adjuvant were higher than the responses of the corresponding groups that received pDNA in PBS only.

Animals↗

Cellular parameters of the immunological memory induced by lysozyme-LPS mixtures and complexes.

The primary antibody response to the protein antigen lysozyme can be enhanced many fold by complexing the antigen with lipopolysaccharide (LPS). This complex, as well as lysozyme/LPS admixtures, is also capable of inducing a state of lysozyme specific immunological memory. Investigation of this memory state has revealed that administration of lysozyme either admixed or complexed with LPS results in priming of both B and T lymphocytes. Adoptive transfer of secondary responsiveness from animals primed in either fashion was further found to be T cell dependent. The implications of these findings are discussed.

Animals↗

Specific IgM enhances and IgG inhibits the induction of immunological memory in mice.

The effect of priming mice with IgM anti-SRBC (sheep erythrocytes) together with SRBC or IgG anti-SRBC together with SRBC on the development and expression of memory cells was studied. Mice primed with specific IgM and SRBC showed a much more efficient secondary plaque-forming cell and serum antibody response after challenge with SRBC in an adoptive transfer system than did controls primed with SRBC only. The expression of this enhanced memory of IgM-primed spleen cells was counteracted by the high levels of internal IgG anti-SRBC (also the result of priming with IgM) when the mice, instead of being tested in adoptive transfers, were challenged directly. The antigen-specific feedback suppression of the primary antibody response by specific IgG antibodies was also seen to inhibit partially the development of memory cells. The suppressive effect on priming could be demonstrated both in adoptive transfer systems and after direct boost of the same mice that received the primary immunization. Both the IgM enhancement and the IgG suppression of memory cell development were antigen-specific, since no effect on the antibody response to a non-cross-reacting antigen, horse erythrocytes, was seen. The effect of these up- or down-regulations of immunological memory could be demonstrated after secondary injections as long as 90-280 days after priming.

Animals↗

Immunological memory for HIV-1 induced in rabbits by immune poly(A)+ RNA.

New Zealand rabbits were used to demonstrate the in vitro and in vivo transfer of reactivity, including immunological memory, to a synthetic peptide corresponding to residues 586-606 of the gp-160 protein of human immunodeficiency virus (HIV-1). The transfer were mediated by immune poly (A)+ RNA from lymphoid organs (spleen and mesenteric nodules) harvested after immunization of a sheep with the peptide (8 subcutaneous injections plus glucan and complete Freund's adjuvant using a total of 1750 micrograms peptide). Immunological reactivity was detected by the leukocyte adherence inhibition (LAI) test for cellular immunity. A dose of 150 micrograms poly(A)- RNA ml-1 10(7) leukocytes-1 or 2.0 micrograms poly(A)+ RNA ml-1 10(7) leukocytes-1 was used for in vitro transfer. For in vivo transfer the recipient rabbits received 3,000 micrograms poly(A)- RNA or 20 micrograms poly(A)+ RNA. The mean non-adherence index (NAI) obtained in vitro was 10 +/- 7 for leukocytes treated with poly(A)-RNA and 60 +/- 10 leukocytes treated with poly(A)+ RNA. The poly(A)+ RNA fraction induced a primary-like response and memory cells in vivo. The poly(A)-RNA fraction had no effect. Since sheep are refractory to, and rabbits are sensitive to HIV-1, we suggest the use of this animal model for testing the immunomodulating effect of anti-HIV-1 immune poly(A)+ RNA.

Animals↗

Surface antigens of immunocompetent cells. 3. In vitro studies of the role of B and T cells in immunological memory.

The effect of preincubation with anti-theta or anti-mouse immunoglobulin (Ig) and complement (C') on immune responsiveness of spleen cells from BALB/c mice immunized with sheep erythrocytes (SE) was investigated. Both treatments greatly depressed the remaining ability to produce a secondary response to SE in vitro. Normal BALB/c spleen cells were far less effective in reconstituting the responses of such depleted cell populations than were much smaller numbers of untreated immune spleen cells. Thymus-derived cell (T cell) memory appeared early after immunization and showed specificity for the immunizing antigens. Recombination of anti-Ig-treated with anti-theta-treated immune spleen cells resulted in virtually complete reconstitution of responsiveness. The presence of immunological memory in T cells and the nature of their surface receptors are discussed.

Animals↗

Immunologic memory cells of bone marrow origin. Increased burst size of specific immunocyte precursors.

Individual immunocompetent precursor cells of (C57BL/10 x C3H)F(1) mouse marrow generate, on transplantation, three to five times more antibody-forming cells localized in recipient spleens during secondary than during primary immune responses. The increased burst size is immunologically specific since antigens of horse and chicken erythrocytes and of Salmonella typhimurium do not cause this effect in marrow cells responsive to sheep red blood cells. Both sensitized and nonsensitized precursors require the helper function of thymus-derived cells and antigen for the final steps of differentiation and maturation. The burst size of primed precursor cells is the same after cooperative interactions with virgin or educated helper cells of thymic origin. The greater potential of these marrow precursors may be attributable to self-replication and migration before differentiation into antibody-forming descendants. In fact, the progeny cells of primed precursor units are distributed among a multiplicity of foci, whereas those of nonimmune precursors are clustered into one focus. The described properties of specifically primed marrow precursors are those underlying immunologic memory. It remains to be established whether memory cells are induced or selected by antigens and whether the thymus plays a role in this process.

Animals↗

[Dynamics of DNA synthesis and blast cell reproduction during formation of the primary immune response and immunologic memory].

A study was made of the dynamics of the DNA synthesis and of the reproduction of the blast cells in the spleen by the methods of autoradiography and radiometry under conditions of a single intervenous immunization of CBA mice with high and low doses of sheep erythrocytes. In the formation of immunological memory stimulated by a subimmunizing dose of the antigen (1-10(5) erythrocytes) cell changes were observed almost exclusively in the periarterial zone; as to the primary response caused by a high dose of the antigen (1-10(9) erythrocytes), it was accompanied by the changes in the cell composition in all the zones of the spleen under study (periarterial, mantle, embryonic centres, red pulp). The maximal accretion of the blast count was observed in the both cases on the second day after the antigen administration. Dynamics of the specific intensity of the 3H-thymidine incorporation into the tissues of the spleen showed the greatest correspondence with the dynamics of the cell changes in the periarterial zone of the spleen.

Animals↗

Persistence of antibody and immunologic memory in children immunized with hepatitis B vaccine at birth.

Forty-two healthy children immunized with a course of hepatitis B vaccine beginning at birth were tested at 6 years of age for persistence of anti-hepatitis B antibody (anti-HBs) and then given a booster dose of vaccine. Although nearly one-half had become seronegative, all retained robust immunologic memory and rapidly regained a protective anti-HBs titer of at least 10 mIU/ml after booster vaccination.

Antibodies, Viral↗

Characteristics of immunological memory in mice. I. Separate early generation of cells mediating IgM and IgG memory to sheep erythrocytes.

The kinetics of the generation of primed IgM and IgG antibody-forming cell precursors, and of helper T-cell populations, were analyzed in mice whose primary responses to high and low doses of SRBC were arrested at intervals by the immunosuppressive agents cyclophosphamide monohydrate and specific antibody. The extent to which immunological memory was established in these animals before blockade of the primary response was assessed by the hemolytic plaque assay following challenge 12 wk after priming. The presence of IgG B-memory cells and T-memory cells in suppressed mice was further investigated by the transfer into these animals of syngeneic SRBC-stimulated thymocytes or anti-theta-treated spleen cells. It was found that the progenitors of secondary IgM-synthesizing cells were primed almost immediately after injection of antigen, and that early blockade of the primary response resulted in a raised IgM response after challenge. On the other hand, priming for a secondary IgG response took at least 4 days, and was dose-dependent, although helper T populations for a secondary IgG response appeared 3 days after antigen injection. It appeared that both IgM and IgG memory cells may be considered as Y cells in terms of the X-Y-Z scheme of lymphocyte activation, but that the two populations are generated at different times after exposure to antigen. The size of either Y-cell population at any given time is dependent upon the amount of antigen available to provoke differentiation to antibody-forming Z cells, and the IgM Y-cell population in particular is likely to be depleted during the course of a normal 1 degrees response. When IgM Y cells were maintained for long periods as a result of immunosuppression, their secondary antibody response was independent of the primed T cells necessary for a secondary IgG response.

Animals↗

Leukocyte migration inhibitory factor production by activated lymphocytes representing immunological memory or virus-receptor interaction: response of T cell subsets to Epstein-Barr virus nuclear antigen, response of B cells to UV inactivated Epstein-Barr virus.

Both T and B lymphocytes are known to produce leukocyte migration inhibitory factor (LIF) after appropriate activation. We showed that EBV nuclear antigen (EBNA) triggered T cells for LIF production in an immunologically specific way: only T cells of seropositive individuals responded. Both Fc receptor positive and negative T cells produced LIF, and the presence of macrophages was necessary. The virus itself activated B cells independently of the serological status of the donors, thus the function was not based on immunological memory. This phenomenon was independent of the transforming capacity of the virus, because UV-inactivated virus also elicited LIF production by B lymphocytes. This triggering seems to be the consequence of the virus-receptor interaction on the cell surface.

Antigens, Viral↗

Prolongation of skin graft survival in mice by in vitro PUVA treatment and failure of induction of specific immunological memory by PUVA-treated grafts.

Treatment of murine skin grafts in vitro with 8-methoxypsoralen and longwave ultraviolet radiation prolonged their subsequent survival on allogeneic recipients, but not in cases where the recipients had been presensitized by a former skin graft of the same donor strain. In contrast to normal skin, grafts pretreated with 8-methoxypsoralen and longwave ultraviolet radiation were not able to induce an immunological memory as revealed by a second transplantation of normal skin. The results show that primary and secondary skin graft rejection can be affected by the combined action of psoralen and ultraviolet radiation.

Animals↗

Long-term antibody response and immunologic memory in children immunized with hepatitis B vaccine at birth.

Four hundred and fifty three healthy children immunized with a course of hepatitis B vaccine beginning at birth were tested at 10-11 years of age for persistence of anti-hepatitis B-S antigen antibody (anti-HBs); and responses of children without protective antibody to different doses of hepatitis B vaccine booster were evaluated. Although nearly 42% of them were not seroprotected, but most of boosted subjects (87.3%) retained robust immunologic memory and rapidly retained a protective anti-HBs antibody titer of at least 10 IU/L after booster vaccination.

Antibody Formation↗