Trachoma is one of the most prevalent infectious diseases of mankind and the leading cause of blindness. However, many features of trachoma are still unexplained. On the one hand, there is appreciable evidence that local (and perhaps systemic) immune responses to chlamydial antigens are responsible for much of the pathology observed in this disease. However, there is also suggestive evidence that local and/or systemic immune responses may simultaneously afford a measure of protection against chlamydial infection. It is, therefore, the main purpose of these investigations to clarify this apparent and almost paradoxical dichotomy. The specific objectives are: 1. To characterize the various components of the local immune response in the conjunctiva to chlamydial infection. 2. to characterize the local and systemic immune mechanisms, both humoral and cell-mediated, which contribute to the resistance to chlamydial infection. 3. To investigate methods for the selective immunization to various chlamydial antigens paying particular attention to stimulation of the secretory immune system by employing enteric vaccines. The studies will be conducted in an experimental animal model of trachoma that has been developed in cynomolgus monkeys which receive repeated infections with Chlamydia trachomatis. The study will take advantage of recent advances in immunological and experimental pathologic techniques to clarify the pathogenesis of this disease. These techniques will include specific monoclonal antibodies to T-cell surface antigens and to immunoglobulin isotypes; immunoperoxidase and immunofluorescent staining methods; and the use of purified chlamydial antigens. The efficacy of various routes of immunization and the effect of different immunosuppressant agents will be studied to gain further information on the pathogenesis and to provide information on protective immunity. It is anticipated that these studies will have considerable importance not only in the fields of opthalmology and immunology but also in the wider areas of infectious disease and preventive medicine.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY003324-05
Application #
3257647
Study Section
Visual Sciences A Study Section (VISA)
Project Start
1980-04-01
Project End
1988-11-30
Budget Start
1984-12-01
Budget End
1985-11-30
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Whittum-Hudson, J A; Gerard, H C; Clayburne, G et al. (1999) A non-invasive murine model of chlamydia-induced reactive arthritis. Rev Rhum Engl Ed 66:50S-55S;discussion 56S
Balin, B J; Gerard, H C; Arking, E J et al. (1998) Identification and localization of Chlamydia pneumoniae in the Alzheimer's brain. Med Microbiol Immunol 187:23-42
Gerard, H C; Whittum-Hudson, J A; Hudson, A P (1997) Genes required for assembly and function of the protein synthetic system in Chlamydia trachomatis are expressed early in elementary to reticulate body transformation. Mol Gen Genet 255:637-42
An, L L; Hudson, A P; Prendergast, R A et al. (1997) Biochemical and functional antigenic mimicry by a polyclonal anti-idiotypic antibody for chlamydial exoglycolipid antigen. Pathobiology 65:229-40
Whittum-Hudson, J A; An, L L; Saltzman, W M et al. (1996) Oral immunization with an anti-idiotypic antibody to the exoglycolipid antigen protects against experimental Chlamydia trachomatis infection. Nat Med 2:1116-21
Nanagara, R; Li, F; Beutler, A et al. (1995) Alteration of Chlamydia trachomatis biologic behavior in synovial membranes. Suppression of surface antigen production in reactive arthritis and Reiter's syndrome. Arthritis Rheum 38:1410-7
Campos, M; Pal, S; O'Brien, T P et al. (1995) A chlamydial major outer membrane protein extract as a trachoma vaccine candidate. Invest Ophthalmol Vis Sci 36:1477-91
Beutler, A M; Schumacher Jr, H R; Whittum-Hudson, J A et al. (1995) Case report: in situ hybridization for detection of inapparent infection with Chlamydia trachomatis in synovial tissue of a patient with Reiter's syndrome. Am J Med Sci 310:206-13
Whittum-Hudson, J A; O'Brien, T P; Prendergast, R A (1995) Murine model of ocular infection by a human biovar of Chlamydia trachomatis. Invest Ophthalmol Vis Sci 36:1976-87
Beutler, A M; Whittum-Hudson, J A; Nanagara, R et al. (1994) Intracellular location of inapparently infecting Chlamydia in synovial tissue from patients with Reiter's syndrome. Immunol Res 13:163-71

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