The Rôle of the "Wax" of the Tubercle Bacillus in Establishing Delayed Hypersensitivity

Abstract

One highly puzzling aspect of the phenomenon of the delayed hypersensitivity of infection, namely, the necessity for the presence of the entire organism in the tissues in order that the hypersensitive state be induced, has been dealt with in previous publications in relation to tuberculosis (1, 2). Although it is well known in the case of the tubercle bacill~s timt the protein of the organism is the antigenic component responsible for the hypersensitive state/this substance in isolated form is powerless to bring about the typical hypersensitivity which follows either infection or the injection of killed bacterial cells, and this despite the well established antigenic properties of such protein. It was demonstinted that the protein could become effective ff at the same time the animal received another component of the bacillus; i.e., the waxy lipid extractable with chloroform (3). A series of criteria established that the hypersensitive state so induced fulfills in all particulars that which follows on the heels of tuberculous infection.In work of this nature, a point of confusion may arise from the failure to distinguish--in the mind of the investigator as well as in the inductive procedures employed--the nature of delayed hypersensitivity and the basic differences segregating it from hypersensitivity of the immediate type, including anaphylaxis, Arthns reactivity, and the human "atopic" states. Briefly stated, the differences are these:1. Immediate hypersensitive reactions follow exposure to antigen within seconds or minutes. Delayed reactions require hours and progress relatively slowly.2. In immediate hypersensitivity a demonstrable humoml antibody is involved, since this will transfer the state to normal recipients. In delayed reactivity no antibody has ever been demonstrated; the only successful attempts to transfer the state have been those employing cells obtained, for example, from an induced peritoneal exuclate (4-8).

The Adjuvant Effect Of A Tubercle Bacillary Lipid On The Antibody Response Of Rabbits To Sheep Red Cells

“…These observations are contrary to other reports that injection of a tubercle bacillary wax, prepared in the same manner, together with tubercle bacillary protein, ovalbumin or picryl chloride leads to delayed type hypersensitivity to these antigens (Raffel, 1948;Raffel and Forney, 1948;Raffel et al, 1949) but to insignificant increases in complement-fixing antibody titres. Notwithstanding these as yet unresolved discrepancies it is apparent that the lipid may vary or alter the character of the immunological response as well as augment its intensity.…”

The Rôle of the "Wax" of the Tubercle Bacillus in Establishing Delayed Hypersensitivity

“…Ordinarily, contact reactions occur when sensitization has been mediated through the skin itself (e.g., chemicals, poison oak, etc.). Only occasionally will delayed hypersensitivity induced by some other route result in the sensitization of epidermal cells to contact with antigen (3,35,36). In the present experiments the route of sensitization was subcutaneous, hence there was no reason necessarily to expect the emergence of contact reactivity.…”

“…Wa~.-~The wax employed here was obtained from two strains of tubercle bacilli of human type (H37Rv and Cutter bacilli) as described in previous papers (2,3). The purified wax fraction was used.…”

“…The purified wax fraction was used. The chemical isolation procedures (11) and the precautions undertaken to assure the removal of bacterial bodies from this fraction have been described (2,3). Dr. R. J. Anderson also supplied a sample of purified wax prepared from H37 bacilli in his own laboratory; this was freed of residual bacilli by the same ultrafiltration and prolonged ultracentrifugation procedures employed with our own substances, and proved to have the same kind and degree of activity.…”

Studies on the Immunological Response to Foreign Tumor Transplants in the Mouse

“…b) The course of serum antibody production during sensitization does not run parallel to the development of delayed sensitivity (24). c) Tuberculoprotein, picryl chloride, and even egg albumen injected together with tubercle bacillary wax adjuvant elicit delayed reactivity; but when injected alone these agents induce only serum antibody (25)(26)(27). The adjuvant, though not itself antigenic, incites a granulomatous response of the type which has often been compared to the round cell infiltration of homografts (28).…”