Modulation of immunity by soluble mediators

Waksman, Byron H.

doi:10.1016/0362-5478(78)90009-8

Cited by 7 publications

(8 citation statements)

References 486 publications

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“…(Table 3) and play a role as well in the peripheral inflammatory reactions of CMI [40,179]. A full list of specific and nonspecific factors is given in [178]. MK and LK spill over into the circulation and may act as systemic regulators of the immune response [-128].…”

Section: Immune Cell Interactions and Regulationmentioning

confidence: 99%

“…The use of adjuvants or of antigens with enhanced adjuvanticity commonly results in a marked increase in the number of lymphocytes within LN draining an [119,173,178,179] inoculation site, attributable both to an increased flux of lymphocytes into the nodes starting within a few minutes and to local blast transformation (and thus replication) of these cells [165] (Frost and Lance in [191]). T-lymphocytes in particular are recruited by this means [164].…”

Section: Effects On Lymphocyte Migrationmentioning

confidence: 99%

“…The helper effect of activated T-cells appears to be mediated exclusively by soluble substances which act on B-cells and signal them to proliferate and/or differentiate [178,179]. Adjuvants which induce a specific carrier effect (viruses, tuberculo-protein in CFA) induce formation of antigen-specific helper factors, which act directly on B-cells or at the surface of macrophages.…”

Section: Effects On T-lymphocytesmentioning

confidence: 99%

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Adjuvants and immune regulation by lymphoid cells

Waksman

1979

Springer Semin Immunopathol

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The modern concept of the mode of action of adjuvants has evolved in exact relation to our understanding of the lymphoid organ system and the complexity of the immune response and its regulation. In the late 60's, attention remained focussed primarily on 'the antibody response' and on the physical attributes of adjuvants which enhanced this response. A major symposium published in 1967 [145] emphasized: the value of depot formation, with slow release of antigen and development of a local granuloma; the value of particles bearing antigenic determinants; the relative merits of water-in-oil emulsions, and the usefulness of metabolizable oils; the apparent importance of lipophilic or surface active materials as adjuvants; and the striking activity of cationic quarternary ammonium compounds with long alkyl side chains.Unquestionably the first insight into the selective or differential action of adjuvants on immune responses was Dienes' demonstration in the late 20's that simple protein antigens preferentially induce CMI (cell-mediated immunity, delayed hypersensitivity) when injected into a tuberculous focus [47]. This theme was continued in the early studies of Freund's adjuvant [60] and more recent studies of tubercle bacillus derivatives such as MDP (muramyl dipeptide) [25]. White, in the 1967 symposium, demonstrated that mycobacterial adjuvants which intensified the cell-mediated response also increased 72 antibody formation relative to 71 (in the guinea pig). We now know both of these to be intensely thymusdependent responses, and current research on MDP, for example, is focussed on the action of this compound directly on various subpopulations of T-lymphocytes in culture.

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Section: Immune Cell Interactions and Regulationmentioning

confidence: 99%

Section: Effects On Lymphocyte Migrationmentioning

confidence: 99%

Section: Effects On T-lymphocytesmentioning

confidence: 99%

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Adjuvants and immune regulation by lymphoid cells

Waksman

1979

Springer Semin Immunopathol

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“…Fortunately, the kinetics of IDS release help eliminate some of the above problems. IDS is secreted by lymphocytes into supernates during the second phase of lymphocyte activation (17), ie, that associated with DNA synthesis, and is therefore present in supernates after 48 h of stimulation. Discarding supernates from the first 48 h of stimulation eliminated a plethora of factors that would interfere with purification.…”

Section: Discussionmentioning

confidence: 99%

Immuno-suppressive lymphocyte factors. I. Purification of inhibitor of DNA synthesis to homogeneity.

Jegasothy¹,

Battles²

1979

The Journal of Experimental Medicine

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Inhibitor of DNA synthesis (IDS) is a T-lymphocyte factor, whose role in immunnoregulation might be to nonspecifically suppress the immune system especially in situations where very high, prolonged tolerogenic doses of antigens are present. We have purified IDS-contained supernates of stimulated lymphocytes to homogeneity, through isoelectric focusing and Sephadex gel chromatography. IDS has an isoelectric point of 2.73-2.75 and in its monomeric form has a mol wt of 20,000 but exists in the supernate usually as an aggregated tetrameric form. Di- and trimeric forms are also seen. All forms are biologically active. Purity was confirmed by SDS gel electrophoresis and the binding of dansyl chloride to terminal or free amino groups of proteins and peptides. We have, further confirmed that pure IDS is not cytotoxic and is probably a glycoprotein whose activity depends on an intact carbohydrate moiety.

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“…Since the discovery of the first lymphokine, many others have been described [32]. At present, it is not known how many lymphokines there are and whether those that have been identified perform other tasks besides the one they have been identified in performing (e. g., IL-1 has recently been identified in regulating more functions than previously identified); thus, one lymphokine or monokine may have multiple biologic effects.…”

Section: Cytokines: the Immunomodulatorsmentioning

confidence: 99%