Pathogenesis Of Experimental Allergic Encephalomyelitis Research Articles

Experimental allergic encephalomyelitis in cobra venom factor-treated and C4-deficient guinea pigs.

Experimental allergic encephalomyelitis (EAE) was studied in guinea pigs with an inherited deficiency of the fourth component of complement (C4) and in guinea pigs injected with cobra venom factor to deplete the third component and late-acting components of complement. EAE was elicited by immunization with homologous spinal cord or purified basic protein. Administration of cobra factor after the injection of encephalitogenic emulsion delayed the onset and reduced the intensity of the clinical manifestations of EAE. In addition, cobra factor markedly reduced mortality during the sixty days of observation. However, pathological changes of perivascular infiltration and demyelination were similar in cobra factor-treated and untreated animals. Clinical signs of EAE an mortality in C4-deficient guinea pigs were no different from those in normocomplementemic controls. Thus, although activation of the classic complement pathway does not appear to be involved in the production of EAE in guinea pigs, our results suggest a possible role of the alternative complement pathway in the pathogenesis of EAE.

Neural Antigens and Induction of Myelination Inhibition Factor

Rabbits were sensitized or immunized with a variety of central nervous system antigens, including bovine spinal cord, bovine, monkey, human, guinea pig, rabbit and rat S myelin basic proteins, and a polypeptide derived from guinea pig basic protein. The animals were observed for development of experimental allergic encephalomyelitis, and their sera were collected at varying intervals after inoculation and evaluated for presence of precipitating anti-basic protein antibody and for their ability to inhibit myelin formation in cerebellar tissue cultures. The resulting complete dissociation between development of experimental allergic encephalomyelitis, the presence of anti-basic protein antibody and the occurrence of myelination inhibition factor suggests that myelination inhibition factor is not involved in the pathogenesis of experimental allergic encephalomyelitis, and argues against a role for anti-basic protein antibody as an antimyelin factor in vitro.

Pathogenesis of experimental allergic encephalomyelitis produced by sensitization with Bordetella pertussis mixed with brain tissue

Pathogenesis of experimental allergic encephalomyelitis produced by sensitization with Bordetella pertussis mixed with brain tissue

Dissociation of Antibody Production from Disease Suppression in the Inhibition of Allergic Encephalomyelitis by Myelin Basic Protein

Abstract Normal guinea pigs challenged with a single injection of homologous myelin basic protein (BP) in Freund's complete adjuvant develop experimental allergic encephalomyelitis (EAE) and delayed hypersensitivity to BP but only rarely develop detectable circulating anti-BP antibodies. Treatment of guinea pigs with methotrexate before and during disease induction completely blocks EAE and suppresses delayed hypersensitivity to the homologous encephalitogenic BP. In contrast, animals treated with methotrexate for 19 days and sensitized after a 2-day time lapse develop the same intensity of EAE and delayed hypersensitivity to BP as those sensitized without prior methotrexate treatment. Treatment of guinea pigs with BP in incomplete adjuvant prior to encephalitogenic challenge suppresses development of both EAE and delayed hypersensitivity and simultaneously evokes anti-BP antibodies. Combined treatment of guinea pigs with methotrexate and BP prior to challenge almost completely suppresses the induction of anti-BP antibodies but does not interfere with the protective effect of the BP injections. Thus, the EAE-resistant state induced in guinea pigs by repeated injections of BP in incomplete adjuvant is apparently not dependent on induction of anti-BP antibodies. A more reasonable explanation for the resistance to EAE is that antigen accumulation prevents development or survival of a clone of BP-sensitized cells. These observations suggest that production or prevention of disease is correlated with induction or suppression of delayed hypersensitivity to BP and not with the presence or absence of circulating antibodies to BP. Antibodies to BP appear to be a coincidental phenomenon not involved in the pathogenesis of EAE.

Role of cellular factors in the pathogenesis of experimental allergic encephalomyelitis

Role of cellular factors in the pathogenesis of experimental allergic encephalomyelitis

Suppression of experimental allergic encephalomyelitis in mice by irradiation of the target organ.

THE pathogenesis of experimental allergic encephalomyelitis (EAE) is not definitely known and yet it is frequently used as an experimental model for the study of autoimmune disease of the central nervous system. Waksman contends that the principal event giving rise to EAE after injection of the antigen is the passage of immunologically competent cells or histiocytes through small venules into the nervous system1. These cells originate in the blood stream and are held responsible for the destruction of elements containing antigen in the central nervous system by an undefined mechanism. It has been found that EAE can be suppressed, either by generalized physical or chemical cytotoxic agents, or by destruction of the regional lymph nodes draining the inoculation site2–9. This communication reports the suppressive effect of localized irradiation of the brain in mice during the induction of EAE, and compares the effect with that of total body irradiation.

Passive transfer of "allergic" encephalomyelitis with antibrain serum injected into the lateral ventricle of the brain.

IT is generally believed that experimental allergic encephalomyelitis results from an interaction between nervous tissue antigens and cells which are engaged in a delayed hypersensitive response. Although experimental allergic encephalomyelitis can be followed by circulating antibodies that react in vitro with nervous tissue constituents, all experiments designed to transfer passively experimental allergic encephalomyelitis either with sera from diseased animals or with antibrain immune sera have failed1. This has been taken as evidence that antibody does not play any significant part in the development of experimental demyelinating disease2. A possible explanation for the failure of antibrain antibodies to induce encephalomyelitic lesions may be their inability to cross the blood-brain barrier in sufficient amount. In order to test the role of antibrain antibodies in the pathogenesis of experimental allergic encephalomyelitis, guinea-pigs with a cannula inserted permanently into the lateral ventricle of the brain were used in the present experiment. Administration of serum through the cannula by-passes the blood-brain barrier, and permits direct contact of injected antibodies and nervous tissue.

Experimental allergic encephalomyelitis: the effect of 6-mercaptopurine.

1. 6-Mercaptopurine (6-MP) prevents experimental allergic encephalomyelitis (EAE) during the period of drug administration in both rabbits and guinea pigs. The disease is suppressed even when treatment is started as late as the 5th day after antigenic stimulation in guinea pigs and the 12th day in rabbits. 2. After discontinuation of 6-MP treatment, there is a latent period before the disease is noted. The length of this latent period is not modified by the duration of 6-MP treatment. 3. The effect of 6-MP on EAE is not the result of leukopenia, non-specific toxicity and debilitation, anti-inflammatory activity, or mere masking of clinical signs of the disease. It is, rather, the result of 6-MP's specific anti-immunologic activity. 4. The effects of 6-MP on antibody production, delayed hypersensitivity, and EAE are compared. This provides indirect evidence for the importance of circulating antibody in the pathogenesis of EAE. 5. The important considerations in the use of 6-MP are discussed and the possible usefulness of 6-MP in human neurologic diseases is considered.