The Mechanism of Immunological Paralysis

Dresser, D. W.; Mitchison, N. A.

doi:10.1016/s0065-2776(08)60466-6

Cited by 360 publications

(153 citation statements)

References 178 publications

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“…Much evidence from in vivo experiments on tolerance has led to the generally accepted theory that the smaller the antigen molecule, the stronger is its potency to render immunocompetent cells tolerant upon direct contact (22). This is in contradiction to our findings which show that polymerized flagellin is more potent in its ability to induce tolerance in vitro than is flagellin monomer (mol wt 40,000).…”

Section: Discussioncontrasting

confidence: 99%

“…The most obvious answer derives from the well known fact that antibody may often be produced during the induction of high zone tolerance as the result of concomitant immunity (22). This phenomenon has also been reported by Ada and Parish to occur during the induction of low zone tolerance to polymerized flagellin by means of fragment A (19).…”

Section: (B) Monomer and Fragment A--monomeric Units Of The Flagellamentioning

confidence: 81%

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Antibody-Mediated Suppression of the Immune Response in Vitro

Diener

Feldmann

1970

The Journal of Experimental Medicine

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Immunological tolerance to H antigens of Salmonella adelaide may be induced in vitro by the exposure of mouse spleen cells for 6 hr to an immunogenic dose of polymerized flagellin in the presence of low concentrations of specific antibody. Such antibody-mediated tolerance requires an optimal antigen: antibody ratio for its induction. A shift in this ratio in favor of the antibody concentration results in failure of tolerance induction and leads to immune suppression commonly known as antibody-mediated feedback inhibition which is not analogous to immunological tolerance. Fragment A of flagellin fails to induce immunological tolerance in vitro. Tolerance to polymerized flagellin may however be induced in vitro, provided the spleen cells are exposed to fragment A in the presence of specific antibody for 6 hr. The results are discussed in the light of current theories of the mechanism of tolerance induction.

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Section: Discussioncontrasting

confidence: 99%

Section: (B) Monomer and Fragment A--monomeric Units Of The Flagellamentioning

confidence: 81%

Antibody-Mediated Suppression of the Immune Response in Vitro

Diener

Feldmann

1970

The Journal of Experimental Medicine

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“…Earlier reports showed that B lymphocytes tolerize [6] or anergize [16] CD8 T cells, effects obtained injecting mice with a large number (5Â10 7 ) of autologous B lymphocytes, that is a number equal to the number of B lymphocytes in the spleen. While recreating conditions of high-dose tolerance [40] those reports failed to address how B lymphocytes regulate CD8 T cells under non-physiological conditions. On the other hand, the injection of a low number of B lymphocytes expressing the H-Y minor histocompatibility antigen was shown to be immunogenic not tolerogenic [41].…”

Section: Discussionmentioning

confidence: 99%

CD8 T cell priming by B lymphocytes is CD4 help dependent

Castiglioni¹,

Gerloni²,

Cortez-Gonzalez³

et al. 2005

Eur J Immunol

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While it is generally accepted that B lymphocytes can present antigen and activate CD4 T cells, priming of CD8 T cells by B lymphocytes remains controversial. Recently, we showed that mice injected with genetically programmed B lymphocytes generate antigen specific CD4 and CD8 T cell responses in vivo that could also be induced in mice lacking functional dendritic cells. To gain further insights into the requirements for T cell priming by antigen-presenting B lymphocytes, in vitro experiments were performed using ovalbumin (OVA) and OVA-specific TCR-transgenic CD4 and CD8 T cells. We found that while B lymphocytes can directly prime CD4 T cells, the activation of CD8 T cells requires T cell help. Transfer experiments show that help can either be contact dependent or be mediated by soluble factors in the supernatants of activated OVAspecific CD4 T cells. Furthermore, the effect of activated CD4 T cells can be replaced by soluble recombinant IL-4. Collectively, the data show the existence of different requirements for priming of CD4 and CD8 T cells and point to the previously unappreciated fact that the induction of CD8 T cell responses by B lymphocytes requires T cell help.

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“…1 The present results are considered to show in a very direct way the existence of actively produced antibody molecules on the outer membranes of "immune" cells. Prellmiuary results indicate that similar antibodies exist on the surface of potential antibody-forming cells in a nonimmune animal as analyzed by antigencoated bead columns, x This would mean that, although the antigenic beadcolumns are supposedly acting through mechanisms different from those thought to participate during the induction of classical immunological tolerance (19), the practical outcome might be the same, the production of a cell population being specifically deprived of reactivity against certain antigenic specificities.…”

Section: Discussionmentioning

confidence: 99%

Cell Separation on Antigen-Coated Columns

Wigzell

Andersson

1969

The Journal of Experimental Medicine

290

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The combination of antigen and specific, predetermined antibody receptors is commonly considered a necessary prelude to the induction of detectable antibody formation. Experimental evidence supporting such a concept has been accumulating in a variety of experimental systems. Administration of antigen will sdectivdy induce DNA synthesis in a small fraction of the lymphoid cell population, that is, in the cells capable of immunological reaction against the immunogen, while leaving cells potentially reactive against other antigens largely untouched (1). The specific inhibition by haptens of the in vitro induction of a secondary response indicates that a cellassociated antibody exists in the cell population containing primed cells, the antigenbinding specificity of the receptor being virtually identical with that of the releasable antibody product of these cells (2, 3). The increase in affinity of the antibody produced with time after immunization (4, 5) and the finding that passively administered "high" affinity antibodies are more efficient as inhibitors of active antibody formation than are "low" affinity antibodies (6) are also in agreement with the ceUbound antibody concept. Cells carrying high affinity receptors would have a selective advantage at the decreasing antigen concentrations with time after immunization, explaining both the rise in affinity of antibody produced and the increasing resistance with time after immunization towards antibody-induced supression of antibody formation (7).Further support for the cell-attached receptor has come from results obtained when using immune cells in vitro where trials were made to find a correlation between affinity of antibody being produced and the concentration of antigen needed to trigger the immune cells into mitosis (8). It can be demonstrated that with increasing affinity of antibody there was a corresponding decrease in the concentration of antigen needed to induce a detectable increase in the DNA synthesis of the cell population.The exact location of the cell-associated antigen-specific receptors is unknown, although they have been assumed to be present on the surface of the potential, antibodysynthesizing cells. The small lymphocyte is a cell type considered to be of major importance for the provision of antibody-producing cells (q), and ~mmunoglobulins have been demonstrated on the outer surface of these cells having a distribution pattern suggesting active synthesis by the small lymphocyte (10).

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The Mechanism of Immunological Paralysis

Cited by 360 publications

References 178 publications

Antibody-Mediated Suppression of the Immune Response in Vitro

Antibody-Mediated Suppression of the Immune Response in Vitro

CD8 T cell priming by B lymphocytes is CD4 help dependent

Cell Separation on Antigen-Coated Columns

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