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Dive into the research topics where Susannah MacRae is active.

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Featured researches published by Susannah MacRae.


Cellular Immunology | 1982

Analysis of subpopulations of glass-adherent mouse skin cells controlling resistance/susceptibility to infection with Leishmania tropica, and correlation with the development of independent proliferative signals to Lyt-1+/Lyt-2+ T lymphocytes

Reginald M. Gorczynski; Susannah MacRae

Abstract A comparison has been made between the course of Leishmania tropica infection of BALB/ c, CBA, and (BALB/c × CBA)F1 mice in vivo and the growth of the parasite in isolated adherent skin cells in vitro. The susceptible phenotype of the BALB/c mouse was reflected in an innate susceptibility of a discrete subpopulation of adherent skin cells to permit extensive and prolonged growth and replication of the parasite in tissue culture. When cells infected in culture were used to stimulate proliferation of immune lymphocytes from “cured” mice, the skin cells of susceptible BALB/c mice were deficient in their ability to induce proliferation of lymphocytes of BALB/c, CBA, or BCF1 origin (all immunized in the appropriate bone marrow reconstituted irradiated BCF1 hosts). In contrast, these skin cells were able to induce proliferation of immune lymphocytes if the L. tropica antigen source used was a soluble excreted extract (EF), rather than that produced by a live parasite infection. Stimulation of naive lymphocytes using an infected adherent skin cell population from BALB/c mice was found to produce a cell population(s) (Thy-1.2+, Lyt-2+ and including some Lyt-1+ cells) able to inhibit subsequent sensitization of normal BCF1 lymph node cells by L. tropica antigens. The susceptibility of the BALB/c mouse in vivo thus may be attributable to the early contact of T-lymphocyte subsets in BALB/c mice with the high-antigen load maintained in this discrete skin cell population. These particular skin cells were also found to express low levels of Ia antigens.


Archive | 1984

Factors Involved in the Classical Conditioning of Antibody Responses in Mice

Reginald M. Gorczynski; Susannah MacRae; Marion Kennedy

There is a great deal of evidence to support the contention that the immune response in mammals to foreign antigens is exquisitely regulated by the immune system itself, and by factors produced by cells associated directly or indirectly with the effects of immune stimulation (1). Amongst the former we could consider the intricacies of a network model for immunoregulation (2), while amongst the latter for instance one could cite evidence for an effect of hormones, interleukins and products of arachidonic acid metabolism on immune responses (3–5), We (6) and others (7–11) have been interested, at the whole organism level, for any evidence which would support the notion that during immunomodulation, an organism can make some form of an association between non-antigenic environmental cues (a conditioned stimulus, CS) and a physiological stimulus known to perturb the immune system in a predictable way (an unconditioned stimulus, US). Thereafter presentation of the CS alone might then produce a physiological response (a conditioned response, CR) analogous to that initially evoked by the US itself (an unconditioned response, UR).


Cellular Immunology | 1982

Ontogeny of diversity in the receptor repertoire of murine cytotoxic lymphocytes: I. Comparison of recognition patterns of activated T cells of B10.D2 and B10.BR mice of different ages and analysis of changes in F1 hybrid and bone marrow radiation chimeras☆

Reginald M. Gorczynski; Marion Kennedy; Susannah MacRae

Abstract Cytotoxic T lymphocyte precursors (CTLp) from B10.D 2 , B10.BR, and (B10.D 2 × B10.BR)F 1 mice of different ages have been activated by irradiated “wild-type” H2K b antigens (from B10.A(3R) mice) under limiting dilution conditions such that cytotoxic cells in responder wells represent the progeny of a single CTLp. After expansion in the presence of IL 2 and irradiated C57B1/6Kha spleen cells the contents of each well were divided into equal aliquots and tested for lysis with a panel of selected H2K b mutant targets. As has been observed for the murine B-cell repertoire, there seems to be substantially more homogeneity in the neonatal allo-T-cell repertoire than in the adult mouse. Furthermore, while the adult F 1 repertoire is markedly distinct from that expressed by either parental T-lymphocyte pool, the neonatal repertoire apparently reflects a relatively accurate composite of each parental population, codominantly expressed. These data, combined with studies of adult bone marrow radiation chimeras, suggest that during development of the adult T-lymphocyte repertoire from the initially expressed restricted (germ-line?) recognition specificities, somatic diversification driven by environmental (MHC?) antigenic determinants occurs. In addition to this ontogenetic development, during senescence another “regulation” of the repertoire becomes apparent, and once more the heterogeneity of recognition specificities is diminished. Nevertheless, the homogeneity seen in aged mice does not represent a simple return to the expression of the limited number of allo-specificities encoded in the neonatal repertoire.


Cellular Immunology | 1981

Analysis of early events occurring during neonatal induction of tolerance to histoincompatible cells in mice.

Reginald M. Gorczynski; Barbara Khomasurya; Susannah MacRae; L. Short

Abstract Mice have been analyzed at different times post neonatal inoculation of F 1 hybrid lymphoid cells for their ability to respond to foreign MHC antigens expressed on the tolerizing cell population, and to impart that response phenotype to normal adult spleen cells. At early times following neonatal challenge with F 1 spleen cells all mice produced serum immunoglobulins of F 1 donor origin which inhibited the response of normal adult cells. The antigenic specificity of the inhibitory factors suggests a role for an antireceptor antibody in the inhibition seen, and the presence of such serum-mediated inhibition is indicative of (and may be causally related to) the late appearance of a cell-mediated suppressor mechanism in these mice.


Cellular Immunology | 1981

Macrophage heterogeneity and Ir-gene control as factors involved in the immune response of guinea pigs to infection with Leishmania enrietti☆

Reginald M. Gorczynski; Susannah MacRae; R. Kuba; Gerald B. Price

Abstract Macrophages from strains 2/N, 13/N, and (2 × 13)F 1 , guinea pigs have been fractionated by velocity sedimentation and the various subpopulations used as target cells for infection by Leishmania enrietti . The data presented show: (i) that the ability of infected macrophages to support the subsequent growth and replication of the parasite varies according to the cell subpopulation examined, (ii) that different subpopulations differ in their capacity to promote lymphocyte proliferation from lymph node cells of a guinea pig which have recovered from a primary lesion, (iii) that lymphocyte proliferation depends upon presentation of leishmanial antigens in the context of products of the original I-region-coded genes present during the initial ( in vivo ) infection and, (iv) that in immune animals, changes occur in terms of the ability of the macrophages to promote lymphocyte proliferation, but not apparently in terms of their ability to support parasite growth in vitro .


Immunopharmacology | 1984

Alterations in lymphocyte recognition repertoire during ageing. I. Analysis of changes in immune response potential of B lymphocytes from non-immunized aged mice, and the role of accessory cells in the expression of that potential

Reginald M. Gorczynski; Mei-Ping Chang; Marion Kennedy; Susannah MacRae; Karen Benzing; Gerald B. Price

The repertoire of specificities recognized by endogenous plaque-forming cells of young or aged mice has been examined, as well as the repertoire of specificities represented by mitogen-activated B cells of those animals. Significant changes occur in both polyclonal endogenous plaque-forming cells and polyclonal B cell responsiveness, as well as reactivity for antigens expressed on bromelain-treated mouse erythrocytes and mouse Ig-coupled sheep erythrocytes. Adoptive transfer experiments suggest that these changes reflect a role for the differentiative environment in the regulation of the B cell recognition repertoire. Additional analysis of changes in antigen-presenting cells in aged mice suggest that alterations in the manner of presentation of environmental antigens in vivo may control the expressed B cell repertoire. Indeed, under experimental conditions it has proven less easy to induce B cell/macrophage restriction (for antigen presentation and induction of antibody formation) in cells of old animals than in cells of younger mice.


Cellular Immunology | 1981

Alteration of allospecific T-cell receptors after differentiation from prethymic precursor cells in semiallogeneic environments

Reginald M. Gorczynski; Karen Benzing; R. Krogsrud; Susannah MacRae; Gerald B. Price

Abstract Murine bone marrow cells (strain A) have been allowed to differentiate in vivo in syngeneic (A) or semiallogeneic hosts (A × B) to produce mature splenic T lymphocytes. After stimulation of these cells with irradiated allogeneic (C) spleen cells in tissue cultures, the cytotoxic T-cell blasts (CTL) were purified by velocity sedimentation and used to immunize (A × C) F 1 hybrid mice, to produce antisera recognizing the receptor structure (for C) on the relevant A cytotoxic cells (and their precursors). Using these sera we have been able to show that the T-cell receptor for alloantigen C on strain A cytotoxic precursor lymphocytes (CTLp) seems to differ according to the host environment in which those T cells differentiate from immature bone marrow precursors.


Cellular Immunology | 1983

Recognition specificities, development, and possible biological function of natural killer cells in the mouse

Reginald M. Gorczynski; Marion Kennedy; Mei-Ping Chang; Susannah MacRae

We have used a spleen fragment assay to assess subpopulations of NK effector cells in individual mice and to analyse the patterns of inhibition of lytic activity seen in the presence of different sugars (mono-, di- and tri-saccharides). Our data suggest that during ontogeny the heterogeneity (diversity) of the NK effector population increases in a fashion which is somewhat characteristic of the individual strain under investigation. Furthermore, when a similar analysis was performed on NK cells in the spleen of lethally irradiated recipient mice receiving syngeneic or semi-allogeneic bone marrow stem cell precursors, we found that the phenotype of inhibition by different sugars was a characteristic of the bone marrow donor and not of the recipient. In so far as the assay described assesses target recognition by NK cells (and not subsequent parameters involved in the lytic event) these data can be interpreted in terms of a relative independence of the expressed recognition repertoire of NK cells from the environment in which their differentiation occurs.


Cellular Immunology | 1982

Ontogeny of diversity in the receptor repertoire of murine cytotoxic lymphocytes. II. Fine specificity of negative regulation (suppression) of the allo-receptor repertoire in congenic b10.d2 Mice.

Reginald M. Gorczynski; Marion Kennedy; Susannah MacRae

Abstract Newborn B 10.D2 mice have been inoculated with 1 × 108 hybrid lymphocytes from offspring of B10.D2 females mated with C57B1/6 males derived from various of the H2Kb mutant sublines. Lymphocytes from animals made tolerant in this fashion have been used at different times thereafter to examine the repertoire of recognition specificities available in the anti-H2Kb alloantigen repertoire. Using this protocol we have demonstrated the following: (i) that the early-appearing specificities (16 days postbirth) which we (R. M. Gorczynski, M. Kennedy, and S. MacRae, Cell Immunol.73, 44, 1982) and Sherman (L. Sherman, J. Exp. Med.155, 380, 1982; J. Immunol. 128, 1849, 1982) have suggested may represent the expression of polymorphic germ line determinants, are susceptible to modulation of expression by the introduction of specific tolerizing determinants, and (ii) that such modification of the neonatal repertoire causes changes in the adult repertoire which are not simply explained as being the adult expression of suppression induced in the neonate, but may instead reflect a modified pattern of somatic diversification from the altered neonatal repertoire.


Immunopharmacology | 1980

In vitro generation from murine bone marrow cells of accessory cells with discrete antigen presentation capacity and ability to release lymphostimulatory molecules

Reginald M. Gorczynski; Karen Benzing; Susannah MacRae; Gerald B. Price

An investigation of the immunological accessory cell function of in vitro bone marrow derived colony forming cells has been made. Data are presented to show that such cells can present immunogenic stimuli to lymphocytes and release lymphostimulatory products that in turn replace certain macrophage functions in the immune response. The appearance of these two activities is not correlated. Considerable heterogeneity exists in terms of the ability of different populations of cells to present distinct carbohydrate antigens in immunogenic form. In addition, that different macrophage cell populations can alter the affinity of antibody produced by an optimally stimulated primed spleen cell population is reported.

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Reginald M. Gorczynski

Ontario Institute for Cancer Research

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Marion Kennedy

Ontario Institute for Cancer Research

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Gerald B. Price

Ontario Institute for Cancer Research

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Barbara Khomasurya

Ontario Institute for Cancer Research

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Karen Benzing

Ontario Institute for Cancer Research

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Alastair J. Cunningham

Ontario Institute for Cancer Research

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Mei-Ping Chang

Ontario Institute for Cancer Research

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E.J. Steele

Ontario Institute for Cancer Research

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L. Short

Ontario Institute for Cancer Research

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R. Krogsrud

Ontario Institute for Cancer Research

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