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R N Misra

Publications and source records attributed to R N Misra.

At least 37 records · Page 2Linked to original sources

Immunopathology of the lens. I. Humoral and cellular immune responses to heterologous lens antigens and their roles in ocular inflammation.

In experimental rabbits heterologous soluble lens proteins consisting of alpha-, beta-, and gamma-crystallins were found to be antigenic; they stimulated a marked antibody response compared to a rather weak T-cell response. The serum antibodies to alpha-crystallins appeared first, to be followed by antibodies to beta- and gamma-crystallins in that order. The rabbits did not respond to heterologous gamma-crystallins unless these were injected with Freund's adjuvant containing mycobacteria. Incomplete Freund's adjuvant (i.e., without mycobacteria) was found to be an inferior immunoaccelerator so far as lens antigens are concerned. The response to lenticular antigens in both magnitude and duration varied in different rabbits, which suggested to us the important role played by a central control mechanism involving the immune response (Ir) genes. Some of the antibodies in potent lens antisera cross-reacted with mitochondria, endoplasmic reticulum (i.e., microsomes), contractile organelles, and cell nuclei. This explains for the first time at least in part the reasons for the widely observed phenomenon of the reactivity of lens antisera with ocular and extraocular structures. Antibodies to soluble lens proteins as detected by immunofluorescence and immunoperoxidase techniques were shown to be of the IgG class. Systemic heterologous immunisation followed by discission of the lens does not lead to the typical changes of phakoallergic endophthalmitis in the rabbit.

Animals↗

Immunopathology of the lens. II. Humoral and cellular immune responses to homologous lens antigens and their roles in ocular inflammation.

It has been possible for the first time to demonstrate antibodies to homologous lens proteins in rabbits without the addition of adjuvant. By means of immunofluorescence and immunoperoxidase methods it has been possible not only to show for the first time that homologous lens antibodies cross-react with extraocular tissues but that the cross-reacting antigens are related to the cell mitochondria, microsomes, and the proteins associated with contractile organelles. The rabbits did not produce antibodies to gamma-crystallins even when the whole lens homogenate was injected with Freund's complete adjuvant. This suggests that gamma-crystallins are non-antigenic in homologous situations, and this may be related to both B- and T-cell tolerance. Alternatively, the failure of gamma-crystallins to induce antibody production may be due to intermolecular antigenic competition with other crystallins. The presence of mycobacteria in an adjuvant is essential for an antibody response to be detectable by agar diffusion techniques. The response to homologous lens antigens, both in magnitude as well as in duration, varied in different rabbits, which suggested to us that a central control mechanism involving the immune response (Ir) genes may plan an important role. Antibodies to homologous lens proteins as detected by immunofluorescence and immunoperoxidase methods were shown to be of the IgG class. This is the first time that the kinetics of the immune response to the same homologous lens antigen in saline with or without incomplete or complete adjuvant has been examined and their relative merits compared. Systemic homologous immunisation followed by discission of the lens led to a marked Arthus type reaction in and around the lens, but a typical granulomatous phakoallergic endophthalmitis was not produced. It seems likely that the rabbit is not suitable for the production of an experimental model of this condition.

Adjuvants, Immunologic↗

Immunopathology of the lens. III. Humoral and cellular immune responses to autologous lens antigens and their roles in ocular inflammation.

In experimental rabbits it has been shown for the first time that autologous lens protein is antigenic when injected with Freund's complete adjuvant. Although lens haemagglutinins were detected in 6 out of 7 rabbits, in only 3 of the 6 animals did the titre reach a maximum of 1:640. A weak agar precipitation reaction was obtained with only 1 of the 3 sera. It would appear, therefore, that the passive haemagglutination test is superior for the detection of autologous lens antibodies. The response to autologous lens antigen both in magnitude as well as in duration varied in different rabbits, which suggested to us the possible role played by a central control mechanism involving the immune-response (Ir) and immune-associated (Ia) genes which are part of the major histocompatibility complex. Alternatively, this variation may be the result of an antigenic competition between various autologous crystallins. Antibodies to autologous lens protein as detected by immunofluorescence and immunoperoxidase techniques were shown to be of the IgG class. Systemic autologous immunisation produces only a mild uveitis and does not lead to a granulomatous intraocular inflammation. Intravitreal injections of autologous lens protein in pre-immunised animals, however, produced an Arthus type of acute endophthalmitis. Autologous lens antisera showed limited cross-reactivity with ocular and extraocular tissues, which could be detected only by such sensitive techniques as immunofluorescence and immunoperoxidase methods.

Animals↗