scholarly journals DELAYED HYPERSENSITIVITY TO HAPTEN-PROTEIN CONJUGATES

1962 ◽  
Vol 115 (5) ◽  
pp. 1037-1051 ◽  
Author(s):  
P. G. H. Cell ◽  
Arthur M. Silverstein

Further data have been presented showing that the specificity of the delayed hypersensitivity reaction in the guinea pig to hapten-protein conjugates involves to a considerable degree a contribution by the protein carrier. The carrier contribution is such that sensitization to guinea pig albumin-m-azobenzenesulfonate, for example, does not result in cross-reaction with conjugates of the same hapten with unrelated proteins such as ovalbumin or human gamma globulin, nor were cross-reactions observed between conjugates prepared with the same hapten, coupled to the same protein, but by two different chemical routes, such that the point of attachment of the hapten to the protein differed. It thus appears that in this system both hapten and carrier protein are necessary, but that neither alone is in general sufficient to stimulate the delayed sensitive cell. Desensitization experiments with cross-reacting hapten-protein conjugates have suggested the presence of a multiplicity of antigenic determinants participating in the elicitation of the delayed lesion, and of a concomitant development of a heterogeneity of specificities in the population of delayed sensitive cells in the sensitized animal. The data are discussed in terms of the apparent requirement of the delayed sensitivity mechanism for a larger functional antigenic determinant than that required for interaction with circulating antibodies. Some possible explanations for this difference, and some of its consequences, are discussed.

1995 ◽  
Vol 23 (5) ◽  
pp. 295-299 ◽  
Author(s):  
K. Katsuno ◽  
A. Manabe ◽  
K. Itoh ◽  
H. Hisamitsu ◽  
S. Wakumoto ◽  
...  

PEDIATRICS ◽  
1957 ◽  
Vol 20 (6) ◽  
pp. 958-965
Author(s):  
Herbert M. Porter

Immunologic studies of a patient with agammaglobulinemia are reported. The delayed type of hypersensitivity was normally produced in response to antigenic stimuli, but circulating antibodies of the gamma globulin fraction of the serum were not. It is postulated that delayed hypersensitivity is responsible for the apparent immunity developed against measles and chicken pox. The tuberculin response is independent of gamma globulin in the serum. The family tree of first cousins with congenital agammaglobulinemia is presented and supports the concept that the disease is a sex-linked recessive trait appearing only in male children.


1961 ◽  
Vol 113 (3) ◽  
pp. 571-585 ◽  
Author(s):  
P. G. H. Gell ◽  
B. Benacerraf

In earlier observations with the picryl system, it was concluded that contact sensitivity was a form of delayed (cellular) hypersensitivity to conjugates of sensitizer with autologous proteins indistinguishable in its immunological mechanism from other classical forms of delayed hypersensitivity to proteins. This conclusion has been confirmed and extended with the picryl and chlorbenzoyl chloride systems. 1. It is shown that to induce a state of contact sensitivity, the minimal necessary amounts of hapten are of the same order of magnitude, whether this hapten is conjugated with protein or the free reactive chemical itself. From this, it is evident that contamination of conjugates with small amounts of unreacted sensitizer plays no part in the induction of contact reactivity by the conjugate. With the dinitrophenyl system, no contact sensitivity could be induced by the conjugates used; possible reasons for this discrepancy are discussed. 2. Animals sensitized to contact by homologous conjugate can be completely desensitized by injections of such a conjugate in large amount; a similar injection schedule has no effect on the contact sensitivity of animals sensitized with the free reactive sensitizer. 3. The capacity of heterologous (ovalbumin) conjugates to evoke anti-hapten antibodies is shown to be greater than that of homologous (guinea pig seralbumin) conjugates: the reverse is true of their capacity to induce delayed reactivity. 4. Evidence is brought forward to suggest that in animals sensitized with homologous albumin conjugates, the specificity of the delayed reaction involves more than the hapten alone, even though the carrier protein is non-antigenic on its own. The contrast with the apparent lesser specificity of the antibodies later produced is discussed.


1955 ◽  
Vol 101 (5) ◽  
pp. 539-556 ◽  
Author(s):  
Seymour P. Halbert ◽  
Lois Swick ◽  
Constance Sonn

Using a highly concentrated and partially purified streptolysin O preparation, migrating agar precipitins have been found in 94 of 143 human sera from patients with a variety of diseases. Most of those showing no bands, had very low antistreptolysin titers. A correlation was found between the migration rates of these bands and the antistreptolysin titer. A strong trend toward a straight line relationship was apparent when the ASO titers were plotted on a logarithmic scale. In addition, a roughly positive correlation was found between the intensity of these bands and the antistreptolysin O titers. The finding of high levels of antistreptolysin O activity and slowly migrating heavy bands in normal pooled human gamma globulin supported the above observations. Very similar results were obtained with rabbit and guinea pig sera after immunization with the streptolysin O concentrates. The data strongly indicate that antistreptolysin O activity in human sera is generally due to precipitating antibody, and that non-specific inhibitors are not usually involved, even with low titered sera. Rabbit and guinea pig antisera to the oxidized inactive and to the reduced active forms of streptolysin O showed no obvious differences. Attempts to demonstrate immunological differences between the two states of streptolysin were apparently complicated by proteolysis, due to contamination of the concentrates with proteinase precursor.


1965 ◽  
Vol 121 (6) ◽  
pp. 873-888 ◽  
Author(s):  
Bernard B. Levine

Experiments carried out with several well defined antigenic systems (hapten conjugates of poly-L-lysine and guinea pig serum albumin) in guinea pigs demonstrated that: 1. Arthus reactions also manifest carrier specificity, although to a smaller extent than do delayed hypersensitivity reactions. 2. Desensitization by injection of minute doses of antigen results in moderate specific desensitization of delayed hypersensitivity without desensitization of Arthus reactivity to the same antigenic determinant. 3. Insoluble antigen-antibody complexes prepared from high affinity guinea pig antibodies can elicit specific delayed skin reactions in sensitized guinea pigs. 4. Homologous conjugates of structurally similar haptens show considerably less cross-reactivity in delayed reactions than in immediate hypersensitivity reactions to the same antigenic determinant. These experimental results are interpreted as indicating that delayed hypersensitivity reactions in the guinea pig are mediated by "antibodies" of comparatively high binding affinities. High binding affinities are achieved for these antibodies more likely by closer structural adaptation between antigen and antibody than by a larger area of specific contact.


1966 ◽  
Vol 123 (4) ◽  
pp. 585-598 ◽  
Author(s):  
Yves Borel ◽  
Marthe Fauconnet ◽  
Peter A. Miescher

Administration of DNP-BGG to newborn guinea pigs resulted, in more than half of the animals, in the specific suppression of delayed hypersensitivity to DNP-BGG and BGG, as shown after immunization with DNP-BGG in complete Freund's adjuvant. In contrast, all animals formed antibodies to DNP-BGG, whether or not delayed hypersensitivity to this antigen was present. No difference in antibody titers was found between pretreated and control animals. All animals had antibodies reacting specifically to the hapten DNP, and most of them to the carrier protein BGG, whether or not delayed hypersensitivity to the carrier protein was present. Furthermore, some animals with and without positive 24 hr skin test to DNP-BGG had antibodies with a combined hapten-carrier protein specificity to this antigen, i.e., a specificity which is similar to that of delayed hypersensitivity. Thus, delayed hypersensitivity and antibody formation to similar antigenic determinant were differently affected by injection of antigen in the neonatal period. The finding that delayed hypersensitivity and antibody formation could be dissociated by the induction of immunologic tolerance supports the assumption that delayed hypersensitivity and antibody formation are different immune processes which are not necessarily linked together.


1965 ◽  
Vol 48 (4) ◽  
pp. 425-429 ◽  
Author(s):  
Richard O. Bicks ◽  
Geron Brown ◽  
H. David Hickey ◽  
E.W. Rosenberg

Science ◽  
1956 ◽  
Vol 124 (3229) ◽  
pp. 980-981 ◽  
Author(s):  
E. JAMESON ◽  
H. AINIS ◽  
R. M. RYAN

1964 ◽  
Vol 119 (3) ◽  
pp. 409-423 ◽  
Author(s):  
Victor Nussenzweig ◽  
Baruj Benacerraf

The electrophoretic mobilities of guinea pig γ1 and γ2 antibodies bearing different specificities were compared in agar gel at pH 8.2. Specifically purified antibodies bearing the same immunological specificity showed the same electrophoretic mobility, but significant differences in mobility were observed when antibodies with certain selected different specificities were compared. The specificity of the carrier protein appeared not to affect the mobilities of antihapten antibodies. Differences in mobility have also been shown between γ1 antihapten antibodies produced by individual guinea pigs immunized concomitantly with 2,4-dinitrophenyl bovine gamma globulin and arsanilic acid azo guinea pig albumin. The differences in the net electrophoretic charge between antibodies with different specificities roughly paralleled that of their S fragments produced by papain digestion.


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