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Biomedical subjects

M A Barcinski

Publications and source records attributed to M A Barcinski.

52 records · Page 3Linked to original sources

Function of macrophages in genetic control of immune responsiveness.

Macrophages serve an essential but poorly understood role in the cellular and molecular events that underlie immune competence. Antigenic proteins are now known to bind initially to macrophages prior to their recognition by T lymphocytes. Antigen uptake by macrophages is a metabolism-dependent event that results in an association of the antigen or a fragment thereof with a product of genes linked to the major histocompatibility complex of the species. For recognition of this associative form of antigen and self to result in cell proliferation, a direct physical interaction of antigen-bearing macrophage and lumphocyte must occur. Soluble forms of the altered antigen complexed to self may, however, function in nonproliferative T cell activation phenomenon. Using antigens of defined structure, it is possible to derive data which indicate that genetic control of immune responsiveness resides at the level of the antigen-presenting cell, thus indicating that these latter cells have profound discriminatory influences on host immune competence.

Animals↗

Determinant selection is a macrophage dependent immune response gene function.

Immune response (Ir) genes are linked to the species histocompatibility complex and define as yet uncharacterised phenotypic products which control the immune response to thymus dependent antigens. Antibody formation and antigen induced T lymphocyte proliferation are two examples of immune phenomena which, in vivo and in vitro, operate under Ir gene influence. To clarify their mechanism of action and cellular location, we have examined the contribution of antigen structure (amino acid sequence and conformation to Ir gene control of antigen recognition by T lymphocytes) as well as to the critical role played by the antigen presenting macrophage in expression of that control. We report that immune response gene control of antigen recognition operates at least in part at the level of the macrophage.

Animals↗

Immune response gene control of determinant selection. I. Intramolecular mapping of the immunogenic sites on insulin recognized by guinea pig T and B cells.

T-cell DNA synthesis and T-helper cell function in response to isolated insulin chains and naturally occurring insulin variants was assessed in insulin immune guinea pigs. Two distinct antigenic determinants, recognized by T cells, were defined. One localized in the B chain and the other one constituted by amino acids A8, A9, and A10 of the insulin A-chain loop. Recognition of the B-chain determinant is under the control of Ir genes linked to the strain 13 major histocompatibility complex. This was shown by studying the response to isolated insulin B chain in F1(2 x 13) guinea pigs, as well as serologically defined backcrosses and outbred animals. Insulin recognition through the A-chain loop determinant is specific for strain 2 guinea pigs. These animals recognize this region of the molecule even when displaying different amino acid sequences. The strain differences observed in those antigenic sites eliciting T-cell recognition was not found at an antibody level. No differences could be detected in the ability of the different insulin variants to inhibit the binding of 125I-labeled pork insulin to strain 2 guinea pig anti-pork insulin or to strain 13 guinea pig anti-pork insulin.

Amino Acid Sequence↗

Granulocyte-macrophage colony-stimulating factor is a growth-factor for promastigotes of Leishmania mexicana amazonensis.

In this paper we show that murine lung conditioned medium (LCM) displays, in addition to its already described colony-stimulating activity on bone marrow cells, a potent growth-stimulating activity on promastigotes of Leishmania mexicana amazonesis. Immunoprecipitation of LCM with an antibody specific for murine granulocyte-macrophage colony stimulating factor (GM-CSF) abrogates both activities, indicating that the leishmanial growth-promoting activity is due to the presence of GM-CSF on LCM. Furthermore, recombinant GM-CSF (rGM-CSF) added to the culture medium or to the immunoprecipitated LCM is able to respectively induce or to partially recover the growth-promoting activity of the LCM. Sequential in vitro passages of the parasite induces a progressive loss of sensitivity to the growth-factor. Parasite forms recently collected from lesions are significantly more responsive to the growth-factor than forms already adapted to grow in culture. Since it has been shown that several different microorganisms display receptors for vertebrate-like hormones and that GM-CSF is able to enhance a cutaneous leishmanial lesion, our results permit us to raise the hypothesis that a direct interaction between a host-derived hormone and a pathogenic microorganism can be of importance in defining the fate of an infection. The fact that GM-CSF is produced by cells that actively participate in a leishmanial infection (T-lymphocytes and macrophages) reinforces our hypothesis.

Animals↗