The Antibody Mechanisms of Ragweed Allergy. Electrophoretic and Chemical Studies

Abstract

Certain specific inhibiting properties of ser-m.~ from patients treated with ragweed extract were first reported in 1935 by Cooke, Bamard, Hebald, and Stull (I). They interpreted their results as "showing the development under treatment of a peculiar blocking or inhibiting type of immune body that prevented the action of allergen on the sensitizing antibody." Adequate confirmation of these findings has been forthcoming.Subsequently, Stull, Sherman, and Cooke (2) separated aqueous serum dilutions by half-saturation with ammonium sulfate into "albumin" and "globulin" and further fractionated the latter by dialysis against distilled water into waterinsoluble "euglobulin" and water-soluble "pseudoglobulin. ''t From passive transfer tests with these fractions they concluded that both sensitizing and blocking capacities were connected with "pseudoglobulin." No confusion should result from the fact that in the present work the terms "euglobulin" and "pseudoglohulin" are applied with the different meaning of "salting-out" properties essentially in accordance with Kendall's usage (3).Recently we have continued further studies to relate, if possible, both blocking and sensitizing antibody to electrophoretically defineable serum components. It was thought that such a correlation as reported in numerous publications for some precipitating and antitoxic antibodies (4--11) might also obtain for this artificially induceable "blocking" antibody.The studies here recorded indicate to us that blocking antibody is connected in large part, if not entirely, with the gamma globulin. In the three ser-m.~ studied it could not be attributed definitely to any of the other dectrophoretic components but was found predominantly in the gamma globulin. This is quite different from the results of our pre]imln~ry report on the sensitizing antibody (12), a study of which has been continued and will be amplified in a later paper.i Different meanings are appfied by various investigators to the terms %uglobulin"and "pseudoglobulin"; a precise definition should always be given, as was done in reference 2.

The Antibody Mechanism of Ragweed Allergy. Electrophoretic and Chemical Studies

“…which in most of the patterns is overlapped by a well developed unspecific delta boundary. For the further technical details see reference (7). min", 2) substantial amounts of reactivity were recovered with the "albumin" (23 and 9% respectively), 3) as measured by their "activities" the three most reactive fractions were 41-S, 55-S and 55-P, and 4) some reactivity was found with every one of the nine fractions, in both instances fraction 41-P containing least reactivity percentagewise.…”

“…Procedures and methods as described previously (5,6,7) apply to this study. Unless mentioned otherwise reactivity losses occurring in the course of serum fractiona tion were estimated.…”

Present and Future of Subcutaneous Aero-Allergen Immunotherapy

“…Cooke together with Mary Loveless have introduced the concept of specific blocking antibody: "the development under treatment of a peculiar blocking or inhibiting type of immune body that prevents the action of allergen on the sensitizing antibody" [20]. Twenty years later, Cooke confirmed his assumption that "serum factor" for inhibition was most likely gamma globulin (IgG) in electrophoretic mobility studies in ragweed-treated patients [21].…”

The Multifaceted B Cell Response in Allergen Immunotherapy

“…Since Robert Cooke’s seminal discovery in 1955 that ragweed AIT induced IgE blocking IgG [97], we have appreciated the central and multifaceted role of antibodies as effector molecules in AIT. Since then, we have gained a nuanced understanding of how different allergen-specific antibody isotypes may influence cellular aspects of allergen-specific tolerance in AIT, which are summarized in Figure 1.…”