The Cutaneous Reactivity of Guinea Pigs to Pure Protein Antigens

1964 ◽  
Vol 25 (5) ◽  
pp. 279-303 ◽  
Author(s):  
D.S. Nelson ◽  
S.V. Boyden
2000 ◽  
Vol 68 (6) ◽  
pp. 3674-3679 ◽  
Author(s):  
Oliver C. Turner ◽  
Alan D. Roberts ◽  
Anthony A. Frank ◽  
Susan W. Phalen ◽  
David M. McMurray ◽  
...  

ABSTRACT In this study, the hsp60 and hsp70 heat shock protein antigens ofMycobacterium tuberculosis were tested as potential vaccine candidates, using purified recombinant protein antigens or antigens encoded in the form of a DNA plasmid vaccine. Guinea pigs vaccinated with a mixture of the two proteins showed no evidence of resistance to low-dose aerosol challenge infection and quickly developed severe lung damage characterized by necrotizing bronchointerstitial pneumonia and bronchiolitis. As a result, we turned instead to a DNA vaccination approach using a plasmid encoding the hsp60 antigen of M. tuberculosis. Although immunogenic in mice, vaccination with plasmid DNA encoding hsp60 was not protective in that model or in the guinea pig model and again gave rise to similar severe lung damage. This study seriously questions the safety of vaccines against tuberculosis that target highly conserved heat shock proteins.


1966 ◽  
Vol 123 (6) ◽  
pp. 999-1012 ◽  
Author(s):  
Hans L. Spiegelberg ◽  
William O. Weigle

The in vivo formation and subsequent fate of complexes formed between specific rabbit γG-antibody subunits and circulating protein antigens was studied in rabbits and guinea pigs. Subunits obtained from purified antibodies were injected immediately after an injection of antigen, and the elimination from the circulation of either I*-labeled γG-subunits or labeled antigen determined. In the absence of antigen, all γG-subunits which lack the Fc fragment were rapidly eliminated. In the presence of excess antigen, F (ab')2, Fab and Fd fragments reacted with antigen and remained in the circulation as complexes which were eliminated at the same rate as the antigen. Fab hybrids containing a specific Fd fragment and a nonspecific L chain similarly reacted with antigen and remained in the circulation complexed to antigen. In contrast, L chains and Fab hybrids containing a specific L chain and a nonspecific Fd fragment did not react with antigen in vivo and were rapidly eliminated in both presence and absence of antigen. H chains remained in the circulation of rabbits in the absence of antigen, however, in the presence of antigen, more H chains which formed complexes with antigen remained in the intravascular space and were rapidly eliminated when the immune elimination of the antigen by the host occurred. Nonspecific H chains were rapidly eliminated from the circulaion of guinea pigs, whereas specific H chains remained in the circulation with the antigen. F (ab')2 fragments formed complexes with antigen near antibody equivalence and in antibody excess which were rapidly eliminated, however, less effectively than complexes formed near antibody equivalence with intact γG. Complexes formed in antibody excess between Fab fragments and H chains remained in the circulation at all concentrations studied and were eliminated at the rate of antigen. The role of the Fc fragment in the immune elimination of antigen-antibody complexes is discussed.


1958 ◽  
Vol 108 (6) ◽  
pp. 905-924 ◽  
Author(s):  
Jonathan W. Uhr ◽  
M. W. Brandriss

Guinea pigs with delayed hypersensitivity to protein antigens show a specific febrile response accompanied by a lymphopenia following injection of a desensitizing dose of specific antigen. No signs of shock are observed in highly sensitive animals following this injection. The response is not prevented in sensitive guinea pigs by inducing endotoxin tolerance or by pretreating with cortisone before specific challenge. Using a suitable antigen in sufficiently sensitive animals as little as 100 µg. can elicit a pronounced febrile response. Injection of a desensitizing dose of antigen specifically abolishes systemic as well as skin reactivity for several days. Normal or hypersensitive (delayed-type) animals passively sensitized with sufficient amounts of serum antibody show hypothermia after specific challenge and may show a delayed type of fatal shock. Differences were noted between their systemic reactivities, however, and the reactivity seen in specifically challenged tuberculous animals.


1985 ◽  
Vol 162 (2) ◽  
pp. 401-412 ◽  
Author(s):  
S Nagao ◽  
A Tanaka

In the course of studies aimed at determining whether MDP was antigenic or not, a hitherto unreported phenomenon was noticed. Injection (a provocative injection) of muramyl dipeptide (MDP) caused severe inflammation, with hemorrhage and necrosis in the footpads of guinea pigs, where tubercle bacilli in water-oil emulsion (a preparatory injection) had been injected 3-8 wk earlier. Sometimes the reaction was accompanied by generalized and fatal shock. Several related substances were tested, and only a combination of tubercle bacilli, or MDP plus proteins as the preparatory injection, and MDP as the provocative injection was found to induce this inflammatory necrotic reaction. Development of delayed hypersensitivity to protein antigens may be important for priming, but MDP and not the protein antigens provoked the reaction. This reaction was, so far, only observed in guinea pigs. Although this reaction appears to be similar to the Shwartzman reaction, the two reactions were found to differ from each other in several important points.


1982 ◽  
Vol 156 (1) ◽  
pp. 159-172 ◽  
Author(s):  
E B Mitchell ◽  
P W Askenase

Guinea pigs immunized with protein antigens emulsified with complete Freund's adjuvant (CFA) and skin tested at 3-4 wk have classical tuberculin-type delayed hypersensitivity (DH) reactions with few basophils present. However, recipients of T cells from these animals have delayed responses containing large basophil infiltrates and thus resemble basophil-rich cutaneous basophil hypersensitivity (CBH) responses that are elicited in animals immunized without CFA. This suggests that animals immunized with CFA have T cells with basophil-recruiting capacity but that this activity is suppressed. Using a transfer system, we found that immune serum from donors immunized with CFA had the ability to suppress the basophil-recruiting capacity of immune T cells. When immune serum and peritoneal exudate cells from guinea pigs immunized with CFA were co-transferred intravenously to normal recipients, the cell-mediated transfer of basophil-rich responses was suppressed. The responsible serum factor was antigen nonspecific, had an approximately 70,000 mol wt, and acted preferentially on cells from donors that express basophil-poor DH responses. Thus, tuberculin-type delayed hypersensitivity and CBH might be mediated by a common T cell, but the resulting basophil component of the delayed response depends on the modulation of T cell recruitment of basophils by factors in CFA-immune serum.


1975 ◽  
Vol 61 (1) ◽  
pp. 29-38
Author(s):  
Franco Gasparri ◽  
Emiliano Panconesi ◽  
Piero Periti

The present possibilities of clinically evaluating cell-mediated immune potential using skin reactivity to microbial protein antigens (streptokinase-streptodornase; tuberculin; formalin-killed parotitis virus) together with a contact sensitized such as dinitrochlorobenzene are examined. A single evaluation index for the set of cutireactions is proposed and, as a practical example, the delayed hypersensitivity data based on intradermal and patch tests in 41 cases of primary malignant tumor of the ovary are reported. There is a definite correlation between immune impairment and cancer spread, with a survival prognosis value even in initial cases.


1957 ◽  
Vol 105 (1) ◽  
pp. 11-24 ◽  
Author(s):  
Jonathan W. Uhr ◽  
S. B. Salvin ◽  
A. M. Pappenheimer

A general method for induction of the delayed hypersensitive state directed against single protein antigens is described. The method consists of intradermal injection of minute amounts of washed immune precipitates containing the antigen in question. Provided the specific precipitates are formed in the region of antibody excess, maximal sensitivity develops at least 2 to 3 weeks before detectable circulating antibody is formed in guinea pigs against the sensitizing antigen. Neither adjuvant nor killed acid-fast bacteria are required for induction of the delayed hypersensitive state although the degree of sensitization is considerably increased when the sensitizing material is incorporated in Freund's complete adjuvant. Characteristics of the "delayed" as opposed to the "immediate" hypersensitive states in the guinea pig are described and implications of the findings are discussed.


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