STRUCTURE AND DYNAMICS OF IMMUNE COMPLEXES

Project Details

Description

Immune complexes (IC) are formed in the circulation or in tissue fluids as
a consequence of the interaction between antigens and their corresponding
antibodies. Many properties of IC, including clearance from the
circulation, complement fixation, and adherence to phagocytes, depend on IC
size and composition. The chronic presence of IC has been implicated in
the pathology of several diseases including, systemic lupus erythematosus,
rheumatoid arthritis, and neoplastic disease. The demonstration that
activity which blocks the immune response to tumors can be removed by
incubation of serum with protein A has motivated studies of plasma
adsorption onto immobilized protein A in a number of tumor systems, with
excellent success reported in treatment of lymphosarcoma and leukemia in
FeLV-infected cats. Our research objectives are to: (1) determine the
parameters that govern size, composition, and structure of IC, (2)
Investigate the dependence of complex size and composition on binding and
activation of complement, (3) understand the interactions between IC and
the cells which bind them, and (4) define the reactions that occur upon
contact of IC with immunoadsorbents such as immobilized protein A and
conglutinin. Model IC constructed from two or more monoclonal antibodies
and bovine serum albumin will be characterized in terms of molecular weight
and size distribution, composition, overall structure, and mean
hydrodynamic radius using electron microscopy, quasi-elastic light
scattering, high performance size exclusion chromatography,
radioimmunoassays, and mathematical models. Purified complement components
will be incubated with model IC; the dependence of complement fixation and
activation on complex size, structure, and composition will be measured.
Similarly, IC will be incubated with macrophages and erythrocytes to
measure binding and uptake, and with immunoadsorbents to analyze adsorption
effects. These fundamental studies will provide the basis for experiments
using IC isolated from sera of FeLV-infected cats. The proposed research
will enhance our understanding of IC formation and behavior in the presence
of complement and specific cells, and will provide a rational basis for
future development and design of immunoadsorption techniques which may be
applied diagnostically or therapeutically to a variety of disease states.
StatusFinished
Effective start/end date5/1/871/31/94

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $81,692.00

ASJC

  • Medicine(all)

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