Chemistry: molecular biology and microbiology – Spore forming or isolating process
Patent
1988-01-27
1990-02-13
Rosenberg, Peter D.
Chemistry: molecular biology and microbiology
Spore forming or isolating process
514 43, 514 45, A61K 3170
Patent
active
049006754
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to modulation of animal cellular responses, and more particularly, to modulation of antigen-specific immune and other animal cellular responses by compositions containing a low molecular weight derivative of isoxanthopterin.
BACKGROUND ART
An animal's immune system is comprised of numerous elements that act separately and/or in concert to counteract, to eliminate, or to neutralize substances that are recognized by that system as foreign to the animal host. Generally, but not necessarily, the substance recognized as foreign by the immune system has its origin exogenous to the host. Exemplary of such exogenous substances are infectious bacteria and the by-products of their cellular activity, virus particles and their proteins, proteins injected by insect stings, and the like. In autoimmune diseases, such as rheumatoid arthritis, the host's immune system perceives host-made proteins or self-made proteins as foreign.
The principal effectors of the immune system are the leukocytes, which include lymphocytes of thymic origin (T cells), lymphocytes produced in bone marrow (B cells), neutrophils which, inter alia, produce enzymes that make oxidizing agents such as hydrogen peroxide that have cytotoxic effects upon bacteria, and macrophages, which present the foreign substance or immunogen (antigen) to the T cells and B cells, as well as produce a protein designated interleuken-1 that assists T cell transformation into T helper cells and B cell and T cell proliferation. Complement, which is a complex mixture of proteins that acts in an ordered, cascading manner upon the foreign substance, also plays a major role in immune responses.
B cells can be distinguished from T cells, inter alia, by the presence of monomeric immunoglobulins (antibodies) on their surface membranes. Mature B cells secrete antibodies into their environment when properly activated.
There are five known classes of immunoglobulins, identified as IgA, IgD, IgE, IgG, and IgM on the basis of five antigenically different heavy chain proteins that make up a portion of the immunoglobulin molecule. B cells also bear non-immunoglobulin cell markers, including a complement receptor (CR), a receptor for the Fc portion of immunoglobulin (FcR), I-region associated antigens (Ia), and a set of differentiation antigens (Lyb 1-7) that are identified by antisera and other means are correlated with various aspects of B cell maturation and activation. These markers are useful in phenotypically identifying B cells and B cell subpopulations.
While the immunoglobulins act upon the foreign substances, or antigen, the T cells, and particularly helper T cells, are believed necessary to stimulate B cells to divide and to differentiate into antibody secreting cells for humoral immunity. Suppressor T cells contribute to the regulation of humoral immunity, while cytotoxic T cells and T cell mediators of delayed-type hypersensitivity are the principal effectors of cell-mediated immunity.
Murine T cells bear surface antigens designated Lyt 1, 2, and 3 as well as L3T4 that are related to T cell functions. Helper T cell precursors are of the Lyt 1.sup.+, 2.sup.-,3.sup.- L3T4.sup.4 phenotype. These cells normally participate in the activation and regulation of B cells.
Helper T cells are known to assist in activation and differentiation of immunoglobulin-secreting B cells after a first message is received by the B cells from the activating immunogenic (antigenic) agent usually presented to it after processing by an antigen-presenting cell. However, the mode by which the T cells provide help for activation and differentiation of the B cells is a matter of controversy.
The immune response exhibited by animal cells can be modified by artificial suppression (immunosuppression) or enhancement (immunopotentiation). Artifically induced immunosuppression can be achieved by six general methods: (1) administration of a suppressive dose of antigen, (2) administration of specific antisera or antibodies, (3) use of other biologic reagents such
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Rosenberg Peter D.
Scripps Clinic and Research Foundation
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