Serological Evidence of Immunity With Coexisting Sensitization in a Type of Human Allergy (Hay Fever)

Abstract

Using ragweed hay fever as the representative of a certain type of allergy we have made studies to determine if possible the mechanism of the protection afforded by specific injections thus far established only by clinical observation. 1. Blood transfusions and serum injections from clinically immune, treated patients stopped the clinical reaction in untreated patients, thus indicating a transferable immunity. 2. The amount of skin sensitizing antibody in the serum was found to be practically unchanged by specific injections. 3. Injection of allergen-antibody mixtures into normal skin showed an immediate (1 hour) reaction when sites were made if serum of untreated cases (Serum A) was used but none or slight reaction if serum of treated cases (Serum P) was used. 4. When sites made with allergen-antibody mixtures were tested after 48 hours, reactions were absent with Serum A mixtures if enough allergen had been used, but were positive with mixtures of Serum P even though a much stronger allergen was contained in the mixture. 5. The primary inhibition of reactions with mixtures including Serum P was not due to antihistamine effect nor to binding of skin sensitizing antibody nor to binding or lysis of allergen. 6. The inhibiting antibody appears to be specific. 7. These serological studies supported by transfusion experiments have been interpreted by us as showing the development under treatment of a peculiar blocking or inhibiting type of immune antibody that prevented the action of allergen on the sensitizing antibody and hence showed in the type of human allergy under consideration (hay fever) the coexistence of sensitization and immunity.

Modification of Host Responses to Bacterial Endotoxins

“…The principle of this concept is not unlike that proposed by Cooke eta/. (19) where blocking antibodies prevent the antigen from reacting with the skin sensitizing antibodies. The results used to formulate this concept will be presented and discussed in the order given above.…”

Recombinant allergens

“…The occurrence of allergen-specific antibodies that do not belong to the "reaginic" class was reported as early as 1935 (71). It was later demonstrated that certain allergen-specific IgG antibodies can inhibit anaphylactic reactions (72,73).…”

Allergen‐specific immunotherapy: from therapeutic vaccines to prophylactic approaches

“…In 1927, Black [17] reported the first attempt to use oral immunotherapy as a possible alternative to injection immunotherapy. A few years later, in 1935, Cooke et al [18] published a seminal paper: using passive serum transfer, they showed that SIT induced an allergenspecific serum factor that prevented allergen-induced skin sensitization. Injection of aqueous allergen extracts caused frequent systemic and often severe side effects.…”

“…Cooke et al [18] 1938 Adsorption of allergens onto aluminium salts for SIT Sledge [19] 1940 Blocking IgG antibodies compete with 'reagin' for specific allergen Loveless et al [20] 1954 Controlled SIT study Frankland and Augustin [21] 1970 Chemical denaturation of allergens to reduce their allergenic activity ('allergoids') Marsh et al [22] 1977 Coupling to polyethylene glycol renders allergens nonallergenic and tolerogenic Lee and Sehon [23] 1986 Sublingual immunotherapy for tolerance induction Scadding and Brostoff [24] 1996 Use of synthetic allergen-derived T-cell epitope-containing peptides for SIT Norman et al [26] 1999 Long-term clinical effects after discontinuation of SIT Durham et al [27] 2002 SIT prevents the progression towards severe allergy (rhinitis-asthma) Möller et al [28] 2004 First SIT with recombinant hypoallergenic allergen derivatives Niederberger et al [30] demonstrated that sublingual immunotherapy was a possible alternative to injection SIT for tolerance induction in allergic patients. An important advance for diagnosis of allergy and SIT was the elucidation of allergen structures and sequences by molecular cloning techniques and the production of recombinant allergens from the late 1980s [reviewed in 25].…”