Immunochemical and Idiotypic Analyses of Immunological Components of an Immune Network in BALB/c Mice and Its Application to Anti-Dna Autoimmunity
Lacy, Michael Joseph
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https://hdl.handle.net/2142/71189
Description
Title
Immunochemical and Idiotypic Analyses of Immunological Components of an Immune Network in BALB/c Mice and Its Application to Anti-Dna Autoimmunity
Author(s)
Lacy, Michael Joseph
Issue Date
1988
Doctoral Committee Chair(s)
Voss, Edward W., Jr.
Department of Study
Microbiology
Discipline
Microbiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Health Sciences, Immunology
Abstract
The sequential occurrence of self-directed antibodies is predicted by the immune network theory of Jerne (1974). According to this theory, antibodies that are specific for the variable regions of inducing antibodies are maintained in equilibrium until the balance within the immune network is modulated by external antigen or by antibodies with active sites complementary to network-related antibodies.
Based upon the immune network theory of Jerne, immunological components characteristic of network theory models were produced in this investigation in BALB/c mice, quantitated, and characterized idiotypically and immunochemically. Quantitation of network components was achieved by affinity purification or by standard curve analysis using solid phase radioimmunoassays. In order to produce the large quantities of specific murine immunoglobulins required for quantitation and characterization, a method was developed to expand polyclonal antibody production in BALB/c mice by inducing ascites fluid. Sp2/0-Ag14 cells induced the production of ascites fluids in a predictable manner so that ascites fluid could be forced concurrently with a specific immune response. BALB/c mice were therefore immunized to develop polyclonal antibodies whose immunochemical characteristics corresponded to those described by immune network theory.
Investigations were performed by using the immune response to fluorescein hapten as an example of a diverse, well characterized response. Similar analyses were performed using immune responses to DNA antigen as representative autoimmune-like antibodies.
Several points regarding immune network characteristics were suggested by the data: (1) antibodies with specificity for external antigen can be induced by network-related immunoglobulin alone; (2) in BALB/c mice, idiotypic modulation may enrich for cross reactivities that were previously of limited occurrence; (3) use of a polyclonal idiotypic vaccine beyond a secondary response may prove unproductive or counterproductive; (4) production of antibodies specific for DNA can be induced by cross-reacting antigen, possibly in concert with polyclonal activation, or by modulation of some balance maintained by the immune system.
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