It is the purpose of this project to answer basic questions regarding inner ear immunity: 1) Is the inner ear an immunopriviledged site; that is, does it operate under the influence of effective afferent and efferent limbs of the immune response? 2) Is the inner ear susceptible to the effects of immune complexes? 3) Can specific antibody raised against cochlear antigens be demonstrated to gain access to the inner ear and possibly affect its function? 4) Do patients suffering from sensorineural hearing losses or vertigo demonstrate a humoral or cell mediated immune response directed against the inner ear? Through primary KLH sensitizations and rechallenges of the perilymphatic compartment, endolymphatic sac and CSF, and by utilizing a sensitive radioimmunoassay for the detection of anti-KLH antibodies the magnitude of the inner ear's immune response will be determined. Also, through the use of electro-cochleography, the physiological effects of immune reactions will be monitored. Light, immunofluorescence, and electron microscopy will provide histological evidence of injury due to humoral or cell mediated responses. T and B cell adoptive transfer experiments will then be employed to further identify the cellular componente responsible for the observed response. Lastly, patients with wensorineural hearing loss or vertigo will be studied for the presence of anticochlear antibodies or lymphocyte blastogenesis to chochlear antigen during their clinical course.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS018643-03S1
Application #
3398663
Study Section
Hearing Research Study Section (HAR)
Project Start
1982-07-01
Project End
1985-11-30
Budget Start
1985-07-01
Budget End
1985-11-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Type
Schools of Medicine
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Darrow, D H; Keithley, E M; Harris, J P (1992) Effects of bacterial endotoxin applied to the guinea pig cochlea. Laryngoscope 102:683-8
Krekorian, T D; Keithley, E M; Fierer, J et al. (1991) Type B Haemophilus influenzae-induced otitis media in the mouse. Laryngoscope 101:648-56
Krekorian, T D; Keithley, E M; Takahashi, M et al. (1990) Endotoxin-induced otitis media with effusion in the mouse. Immunohistochemical analysis. Acta Otolaryngol 109:288-99
Keithley, E M; Krekorian, T D; Sharp, P A et al. (1990) Comparison of immune-mediated models of acute and chronic otitis media. Eur Arch Otorhinolaryngol 247:247-51
Harris, J P (1989) Autoimmunity of the inner ear. Am J Otol 10:193-5
Gloddek, B; Harris, J P (1989) Role of lymphokines in the immune response of the inner ear. Acta Otolaryngol 108:68-75
Berchtold, P; Harris, J P; Tani, P et al. (1989) Autoantibodies to platelet glycoproteins in patients with disease-related immune thrombocytopenia. Br J Haematol 73:365-8
Tomiyama, S; Keithley, E M; Harris, J P (1989) Antigen-specific immune response in the inner ear. Ann Otol Rhinol Laryngol 98:447-50
Takahashi, M; Peppard, J; Harris, J P (1989) Immunohistochemical study of murine middle ear and Eustachian tube. Acta Otolaryngol 107:97-103
Tomiyama, S; Harris, J P (1989) Elevation of inner ear antibody levels following direct antigen challenge of the endolymphatic sac. Acta Otolaryngol 107:202-9

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