L. Polak

Studies on Contact Hypersensitivity to Chromium in the Guinea Pig

Macrophage migration inhibition and migration inhibitory factor (MIF) production were investigated in guinea pigs sensitized to potassium dichromate. The migration of peritoneal exudate cells from hyp

Development of contact sensitivity to DNFB in guinea pigs genetically differing in their response to DNP skin protein conjugates.

Strain 13 guinea pigs sensitized either with dinitrofluorobenzene (DNFB) or with a homologous DNP skin protein conjugate (DNP-GPSP) responded equally well to both an epicutaneous test with the hapten

Differential Capacity of Macrophages from Various Sources to Act as Hapten-Specific Stimulator Cells in vitro

Lymphocytes from 2,4-dinitrochlorobenzene, contact sensitized guinea pigs show increased DNA synthesis in vitro when stimulated by dinitrophenylated macrophages. In this study, macrophage-containing cell suspensions were isolated from various sources (spleen, lungs, peritoneal cavity) and from the peritoneal cavity also after different stimuli (oil, thioglycollate, starch, lymphokines). These cells were then haptenized and investigated on their capacity to act as stimulator cells in vitro. In addition, a possible relationship between Ia-positivity of the hapten-presenting cell suspensions and the induction of DNA synthesis was studied. The results demonstrate (1) that the hapten-presenting capacity of macrophages differs with respect to the source and the way of elicitation, (2) that oil-induced peritoneal exudate cells are the most suitable stimulator cells for in vitro assays in contact sensitivity, and (3) that the cellular expression of Ia antigens is in itself no warrant for hapten-presenting capacity.

Current concept of allergic skin reactions

On the basis of literature and experimental work the present views on the mechanism of the development of allergic skin reactions of the contact type are reviewed.

Self molecules in induction of hypersensitivity and tolerance in DNCB contact sensitivity in the guinea pig.

Dinitrophenylated macrophages are efficient inducers of contact sensitivity and of tolerance to dinitrochlorobenzene, depending on the mode of application. Contact sensitivity induced by an intradermal injection of DNP-M phi is genetically restricted, whereas tolerance induced by an intravenous injection is, in guinea pigs, not under control. This tolerance is complete in the majority of animals, but is reversed by DNCB in Freunds complete adjuvant and prevented by pretreatment with cyclophosphamide. Tolerance induced by an intravenous injection of the unconjugated hapten is not reversed by DNCB in FCA, but is abrogated by an intradermal injection of DNP-M phi. This abrogation does not occur, however, when DNCB in FCA is applied simultaneously with the DNP-M phi. In further experiments, it is demonstrated that the genetic restriction of induction of contact sensitivity by DNP-M phi is on the level of antigen recognition and is not due to the nonidentity of the Ia structures on macrohages used for induction and the Ia structures involved in elicitation of contact sensitivity.

Induction and Termination of Immunological Unresponsiveness to DNCB in Guinea Pigs

Tolerance and desensitization to DNCB are based on different mechanisms. Temporary desensitization of DNCB-contact sensitive guinea pigs may be caused by a direct inactivation of specific effector cells by the intravenously injected hapten whereas in tolerance to DNCB induced by pretreatment of normal animals with DNBSO3, suppressor cell activity may account for specific unresponsiveness.

The Induction of Immunological Tolerance During the Primary Response

By injecting adult guinea pigs intravenously with dinitrochlo-robenzene sulfonate (DNBSO3) 2 to 24 h after applying a sensitizing epicutaneous dose of dinitrochlorobenzene (DNCB), the production of PCA-detectable anti-DNP antibodies and the induction of contact hypersensitivity to DNCB is strongly depressed for over 14 weeks. The proportion of animals acquiring this state of specific unresponsiveness as well as its stability against a second sensitizing attempt with DNCB alone are clearly dependent on the dose of DNBSO3 injected and on the time interval elapsing between both hapten applications. However, the tolerogenic effect of DNBSO3 is stronger when injected some weeks before sensitization. The results obtained are discussed on the basis of current concepts on the relationship between antigen and immunocompetent cells. The possibilities to interpret our findings by means of reversible blocking or affinity labelling of cellular receptors, specific annihilation of antigen-sensitive cells or immune deviation are considered.

Contact Sensitivity in Guinea Pigs: Allogeneic Reaction and Carrier Specificity in Antigenic Recognition

in the present paper it is shown that both induction and elicitation of 2,4-dinitrochlorobenzene-contact sensitivity in guinea pigs are genetically controlled. This genetic control is operating by two somehow different mechanisms. The recognition of hapten on allogeneic macrophages during the inductive phase is suppressed by the allogeneic response against these macrophages whereas the elicitation upon transfer of syngeneically primed lymphocytes is limited by the identity of at least some components of the major histocompatibility complex. This nonidentity contradicts the rule of carrier specificity, which is a requirement for all delayed type hypersensitivity reactions. Furthermore, the presentation of haptens to primed cells is less restricted than presentation of protein antigens.

Tolerance in delayed hypersensitivity

Specific immunological unresponsiveness, called tolerance, has been described in almost all immunological systems (Katz and Benacerraf, 1974; Howard and Mitchison, 1975; Nossal, 1974). It is of interest that the demonstration of tolerance in delayed hypersensitivity was one of the earliest to be reported (Sulzberger, 1929; Chase, 1946). Bumet’s formulation of the clonal selection theory (Burnet and Fenner, 1949) and Medawar’s (1958) concept of clonal deletion initiated a flood of experimental research that resulted in the general acceptance of a unifying theory of tolerance as an annihilation of the immunocompetent specific cells which was thought to be valid for all immunological systems.

Production and characterization of antisera against Guinea pig macrophage activating factor

Guinea pig lymph node cells stimulated with concanavalin A (Con-A) were used as a source of lymphokines. Purifications by molecular sizing columns yielded sufficient quantities of macrophage activating factor (MAF)-active fractions to allow immunization of rabbits. An antiserum was produced which is capable of specifically inhibiting MAF activity, as well as blocking the activity of macrophage migration inhibiting factor (MIF), but not of skin reactive factor. Antisera raised against control supernatants derived from lymph node cells not stimulated with Con-A, failed to specifically inhibit any of these lymphokines. Additionally, anti-MAF but not anti-control antibodies suppressed completely contact sensitivity to dinitrochlorobenzene.