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Biomedical subjects

P Bretscher

Publications and source records attributed to P Bretscher.

7 recordsLinked to original sources
PubMed1986

The effect of low dose chronic intermittent parental methotrexate on delayed type hypersensitivity and acute inflammation in a mouse model.

We have shown that a regimen of low dose intermittent methotrexate (MTX), analogous to that used in the treatment of patients with rheumatoid arthritis, does have immunosuppressive effects on the induction of primary delayed type hypersensitivity in normal mice. This occurred even when the last MTX injection was 4 days before immunization. No effect was seen on established delayed type hypersensitivity or on inflammatory responses induced by carrageenan or the Arthus reaction.

Animals↗
PubMed1984

Immunologic and inflammatory responses during pregnancy.

Rheumatoid arthritis commonly improves markedly during pregnancy, and it has been suggested that this reflects a decrease in immunological or inflammatory effector mechanisms. We elicited a delayed type hypersensitivity (DTH) response to Burro RBC, by injection of primed lymphocytes and antigen into murine footpads. The swelling induced in footpads of pregnant mice was not significantly different from that seen in controls, nor was the response to a non-immunologic inflammatory stimulus, carrageenan, decreased in pregnant mice. On the other hand, a defect in the priming or induction phase of a primary DTH response was impaired in pregnancy, but whether this is relevant to the pregnancy induced remission of rheumatoid arthritis remains to be demonstrated.

Animals↗
PubMed1970

A theory of self-nonself discrimination.

1) Induction of humoral antibody formation involves the obligatory recognition of two determinants on an antigen, one by the receptor antibody of the antigen-sensitive cell and the other by carrier antibody (associative interaction). 2) Paralysis of antibody formation involves the obligatory recognition of only one determinant by the receptor antibody of the antigen-sensitive cell; that is, a nonimmunogenic molecule (a hapten) can paralyze antigen-sensitive cells. 3) There is competition between paralysis and induction at the level of the antigen-sensitive cell. 4) The mechanisms of low- and high-zone paralysis, and maintenance of the unresponsive state, are identical. 5) High-zone paralysis occurs when both the carrier antibody and the receptor antibody are saturated, so that associated interactions cannot take place. 6) The mechanisms of paralysis and induction for the carrier-antigen-sensitive cell are identical to those for the humoral-antigen-sensitive cell. 7) The formation of carrier-antigen-sensitive cells is thymus-dependent, whereas humoral-antigen-sensitive cells are derived from bone marrow. Since carrier antibody is required for induction, all antigens are thymus-dependent. 8) The interaction of antigen with the receptor antibody on an antigen-sensitive cell results in a conformational change in an invariant region of the receptor and consequently paralyzes the cell. As the receptor is probably identical to the induced antibody, all antibody molecules are expected to be able to undergo a conformational change on binding a hapten. The obligatory associated recognition by way of carrier antibody (inductive signal) involves a conformational change in the carrier antibody, leading to a second signal to the antigen-sensitive cell. 9) The foregoing requirements provide an explanation for self-nonself discrimination. Tolerance to self-antigens involves a specific deletion in the activity of both the humoral- and the carrier-antigen-sensitive cells.

Antibody Formation↗
PubMedDate not supplied

Immunotherapy of the rat 13762SC mammary adenocarcinoma by vaccinia virus augmentation of tumor immunity.

We studied whether vaccinia virus (VV) functioned as an immunogenic carrier in augmenting anti-tumor immunity in rats bearing a syngeneic metastatic tumor. The primary tumor was induced by injecting 10(6) 13762SC mammary adenocarcinoma cells subcutaneously into the right hind footpad of Fischer 344 rats. A concomitant anti-tumor response is induced by the tumor as demonstrated by the inhibited growth of a second tumor challenge given in the contralateral footpad 3-15 days later. Attempts were made to increase the concomitant immunity by injecting tumor-bearing animals intramuscularly with irradiated, VV-infected or uninfected 13762SC cells without adjuvant. Provided the immunotherapy was done within 5 days of the tumor challenge, administration of 10(6)-10(7) irradiated, VV-infected 13762SC cells resulted in significantly slower tumor growth, or led to complete tumor regression, compared to control animals given no treatment. In contrast, tumor growth in animals given only VV or given irradiated, uninfected 13762SC cells, alone or mixed with VV, was the same as that in control animals. Kinetics of early primary tumor growth were predictive of a longer-term anti-tumor effect. Rechallenge of 13762SC tumor-cured animals with either the homologous or with a heterologous syngeneic mammary adenocarcinoma showed the animals to be specifically 13762SC tumor-resistant, since only rats challenged with the heterologous mammary adenocarcinoma developed progressive tumors. We interpret these results to mean that early immunotherapy with irradiated, VV-infected 13762SC cells enhances an on-going anti-tumor immune response sufficiently to cause rejection of the primary tumor and any metastases that have occurred. We also believe that later immunotherapy with irradiated, VV-infected cells has no effect due to tumor-induced immunosuppression becoming paramount.

Adenocarcinoma↗