Specificity of a BCG-Induced Pulmonary Granulomatous Response in Rabbits

Self Cite

Fractions of the tubercle bacillus were examined for their capacity to produce an allergic pulmonary granulomatous response in rabbits. We found that emulsions containing old tuberculin and even old tuberculin alone in an emulsion could induce a pulmonary inflammatory reaction comparable in intensity to that produced with killed BCG. Emulsions lacking old tuberculin failed to produce an allergic pulmonary inflammatory response. The significance of these results in relation to immunological and nonimmunological chronic inflammation is discussed.

supporting

confidence: 64%

Section: Downloaded Frommentioning

confidence: 99%

Mycobacterial Components Responsible for the Induction of a Chronic Immunological Inflammatory Response in Rabbit Lungs

Moore

Myrvik

1974

Self Cite

“…The fact that pulmonary granuloma formation is not impaired by desensitization implies that cellular immune re-sponses, including DH, remain intact within the lung during this period. The finding that pulmonary cells obtained by savage from BCG-challenged rabbits retain their ability to produce a lymphokine (migration inhibition factor) in response to specific antigen challenge (8,17) supports this conclusion.…”

Section: Resultsmentioning

confidence: 81%

Selective suppression of granuloma formation and delayed hypersensitivity in rabbits

Schroff¹,

Heise²,

Myrvik³

et al. 1980

The relationship between dermal delayed hypersensitivity (DH) and granulomatous hypersensitivity was studied in rabbits sensitized with killed mycobacteria. Specific antigen challenge of sensitized animals resulted in extensive pulmonary granulomatous inflammation and induced suppression of both dermal DH and dermal granuloma formation. Whereas suppression of DH was concomitant with pulmonary granuloma formation, as is the case in a number of granulomatous diseases, a causal relationship between the two did not exist. Both DH and dermal granulomatous hypersensitivity were significantly suppressed whether or not the antigen challenge was of a granulomagenic (particulate) or nongranulomagenic (soluble) form. The data presented indicate that granulomatous hypersensitivity and DH are selectively suppressed with regard to different anatomical sites.Numerous human diseases are accompanied by the development of epithelioid granulomas. Immune granulomas generally are regarded to be cell mediated, as demonstrated by the ability to transfer the state of granulomatous hypersensitivity with immune lymphoid cells but not with immune serum (1). Delayed hypersensitivity (DH) also has been demonstrated to be mediated by components of the cellular immune system and its products (11,26). A striking incongruity exists in that several disease states (including sarcoidosis, lepromatous leprosy, and systemic fungal infections) are characterized by suppressed DH reactivity during periods of extensive granulomatous inflammation. In contrast, granuloma formation as a consequence of pulmonary tuberculosis and tuberculoid leprosy generally is accompanied by positive skin test responsiveness. It is not apparent how one expression of the cell-mediated immune system is suppressed while another expression of the same system apparently remains unaffected.Short-term suppression of DH can be accomplished by administration of relatively large quantities of specific antigen to previously sensitized individuals. This phenomenon has been termed desensitization by Uhr and Pappenheimer (25). A correlate of desensitization apparently exists during the latter stages of some diseases such as lepromatous leprosy, where massive antigen release is accompanied by loss of skin test reactivity to lepromin (3,21). Numerous investigators have demonstrated that the ability to elicit antigen-specific granulomas is not affected during states of antigen-induced desensitization (2,9,27). These reports all have in common the fact that DH was assessed dermally, whereas granuloma formation was evaluated at a different anatomic site, e.g., the lungs.The purpose of this investigation was to determine the relationship between DH and granuloma formation at the same anatomical location in response to similar antigens. The experimental system used in the present study has been well characterized with respect to formation of pulmonary granulomas (9,16,18). The following study is unique in that granulomas are elicited not only within internal organs, but also dermally at the sit...

“…or intratracheally (i.t.) with heat-killed BCG, they develop an extensive pulmonary granulomatous response after challenge (4,(8)(9)(10)(11). In this case, the alveolar macrophages (AM) invariably exhibit migration inhibition when harvested and tested in the capillary tube migration test (no antigen added).…”

mentioning

confidence: 99%

Induction of a macrophage migration enhancement factor after desensitization of tuberculin-positive rabbits with purified protein derivative

Gordon¹,

Takata²,

Myrvik³

1986

The production of a macrophage migration enhancement factor (MEF) has been achieved as a consequence of administering a desensitizing dose of purified protein derivative (PPD) to Mycobacterium bovis BCGsensitized rabbits. The migration-enhancing effect was first demonstrated when alveolar macrophages (AM) harvested from desensitized rabbits exhibited marked migration stimulation; whereas maximum migration enhancement was observed 8 days after the administration of PPD, migration enhancement of the AM from these rabbits persisted for up to 12 days. Sera from BCG-sensitized, PPD-desensitized animals exhibited a peak of MEF activity 4 days after desensitization. Maximal MEF activity was demonstrated in culture supernatants of nonadherent spleen cells harvested 8 days after the intravenous desensitizing dose of PPD was given. Control spleen cell culture supernatants did not produce detectable MEF. The route of desensitization with PPD was critical. When PPD was administrated intratracheally, MEF activity was not induced. The intravenous administration of BCG after PPD desensitization reversed migration enhancement to strong migration inhibition. Ammonium sulfate fractionation indicated that two fractions contained MEF activity. MEF activity was retained by dialysis membranes with a 15,000-molecular-weight cutoff but passed through dialysis membranes with a 25,000-molecular-weight cutoff. The mixture of migration inhibition factor with MEFcontaining supernatants resulted in the mutual cancellation of both activities. These observations suggest that MEF may be a modulator of macrophage effector responses mediated by migration inhibition factor.