scholarly journals SPECIFIC IMMUNE RESPONSE GENES OF THE GUINEA PIG

1971 ◽  
Vol 134 (2) ◽  
pp. 458-470 ◽  
Author(s):  
Harry G. Bluestein ◽  
Ira Green ◽  
Baruj Benacerraf

The immunogenicity of three random copolymers of amino acids with L-glutamic acid and L-alanine (GA), L-glutamic acid and L-tyrosine (GT), or L-glutamic acid, L-alanine, and L-tyrosine (GAT), administered in complete Freund's adjuvant, was studied in several inbred and random-bred guinea pig strains. The animals were tested for delayed sensitivity and their sera were assayed for the presence of antibody directed against the immunizing polymer. All of the guinea pigs developing delayed hypersensitivity also had significant antibody levels in their sera. Inbred strain 2 guinea pigs responded to immunization with GA, but failed to form detectable responses to GT. Inbred strain 13 animals, on the other hand, responded to GT, but not to GA. The (2 x 13)F1 hybrids responded to both GA and GT with both delayed hypersensitivity and circulating antibody. Thus, the ability of these inbred guinea pigs to respond immunologically to GA or GT is controlled by distinct autosomal dominant genes. A variable percentage of random-bred guinea pigs, depending on their source as well as their strain, responded to immunization with GA and with GT. All guinea pigs, both inbred and random bred, responded to immunization with GAT. The ability to respond immunologically to GAT, therefore, does not seem to be under simple genetic control. However, the levels of anti-GAT antibody found in the sera of animals lacking the ability to respond to GA were much lower than those detected in GA responder animals.

1971 ◽  
Vol 134 (6) ◽  
pp. 1529-1537 ◽  
Author(s):  
Harry G. Bluestein ◽  
Leonard Ellman ◽  
Ira Green ◽  
Baruj Benacerraf

The ability of guinea pigs to form immune responses specific for each of the random copolymers, L-glutamic acid and L-alanine (GA) and L-glutamic acid and L-tyrosine (GT), is under the control of distinct autosomal dominant genes. By testing for the ability to respond to these copolymers among the progeny from the reciprocal backcross mating of responder (2 x 13)F1 animals with the appropriate nonresponder parental strain, we have demonstrated that different unigenic autosomal dominant traits control the ability to respond to GA and GT respectively. The data further shows that the GA gene is linked to the poly-L-lysine (PLL) gene and to the locus determining the major strain 2 histocompatibility specificities and that the GT gene is linked to the locus controlling the expression of major strain 13 histocompatibility specificities. Analysis of the inheritance of the GT and PLL genes among the offspring from a mating of responder (2 x 13)F1 guinea pigs with random-bred guinea pigs unable to respond to GT or PLL demonstrate that these genes segregate away from each other. Thus, the PLL gene and the genes to which it is linked, the GA gene and the major strain 2 histocompatibility locus, behave as alleles or pseudoalleles to the GT gene and the major strain 13 histocompatibility locus.


1974 ◽  
Vol 20 (5) ◽  
pp. 657-662 ◽  
Author(s):  
John P. Heggers ◽  
L. P. Mallavia ◽  
David J. Hinrichs

Formalinized vaccines prepared from the Nine Mile, Phase I, strain of C. burneti or purified preparations of the Phase I antigen initiate a state of delayed hypersensitivity in guinea pigs as determined by the in vitro migration inhibition system. This delayed hypersensitivity is directed against the protein as well as the carbohydrate component of the Phase I antigen. Guinea pigs that had recovered from Q-fever demonstrated a similar state of delayed hypersensitivity. Circulating antibody levels as determined by the microagglutination test were readily apparent in both infected and vaccinated animals.


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.


1958 ◽  
Vol 107 (1) ◽  
pp. 109-124 ◽  
Author(s):  
S. B. Salvin ◽  

Guinea pigs were injected in the footpads with either purified diphtheria toxoid or recrystallized egg albumin in Freund adjuvant without mycobacteria. Each guinea pig was then skin-tested only once with the specific antigen and bled for antibody determination. After injection of the sensitizing antigen, a latent period occurred during which neither sensitivity nor circulating antibody could be detected. A period of delayed sensitivity followed wherein circulating antibody could not be discerned and which could be transferred by lymph node cells. Ultimately, the Arthus type sensitivity developed, accompanied by circulating antibody. The duration and severity of reactions to homologous antigens during the last 2 phases varied with the antigen and with the dose. An increase in the sensitizing dose decreased the duration of the delayed type of allergy, a decrease in the dose prolonged the delayed type. Inclusion of mycobacterium in the sensitizing inoculum tended to introduce delayed sensitivity earlier and delay the onset of Arthus type sensitivity. When specific precipitate in antibody excess was included with the toxoid in the sensitizing dose, the onset of the Arthus phase was hastened. When lymph nodes from a large number of sensitized donors were removed during the latter part of the latent period, recipients of the cells showed a delayed type sensitivity.


1954 ◽  
Vol 11 (1) ◽  
pp. 1-NP ◽  
Author(s):  
M. F. A. WOODRUFF

SUMMARY Administration of cortisone in large dosage (20 mg daily) decreases the chances of survival of thyroid autotransplants in guinea-pigs. Despite this, cortisone may facilitate the survival of thyroid homotransplants, apparently by inhibiting the development of resistance in the host. The effect is a slight one, however, and is not apparent when transplants are made from stock donors to members of a highly inbred strain. Administration of thyrotrophin does not abolish the deleterious effect of cortisone on autotransplants, nor does it appear to facilitate the survival of homotransplants.


1964 ◽  
Vol 119 (2) ◽  
pp. 327-342 ◽  
Author(s):  
Edwin M. Lerner ◽  
Philip R. B. McMaster ◽  
Eurmal D. Exum

Experimental allergic thyroiditis produced in strain 13 histocompatible guinea pigs after a single immunization with thyroid extract and Freund's adjuvant was followed for more than 2 years. The disease appeared as early as 5 days and persisted for the entire period studied, although it regressed in the later stages. Circulating antithyroid antibody was detected at low levels as early as 7 days after immunization, and increased to a peak at the time of most severe disease. Thereafter, antibody decreased, but was still detectable in most animals as late as 2 years. There was no correlation between antibody levels and extent of disease except at the 7 week stage. Delayed sensitivity to thyroid antigen was found as early as 5 days after immunization, and appeared to precede the development of thyroiditis in many animals. It correlated closely with thyroiditis at 5 days and 7 weeks. At 6 months, the delayed skin reaction was decreased, and a modified type of reaction appeared which persisted as long as 26 months. The time relationship of delayed sensitivity, thyroiditis, and circulating antibody continue to confirm the role of delayed sensitivity in the pathogenesis of this disease. The accumulated data demonstrating production of thyroiditis without antibody, and the converse, tend to strengthen this view.


1972 ◽  
Vol 136 (6) ◽  
pp. 1545-1563 ◽  
Author(s):  
Siraik Zakarian ◽  
R. E. Billingham

Using guinea pigs of strains 2 and 13 and their F1 hybrids as experimental subjects, various lines of evidence have been obtained that in this species, as in all others tested, the only significant cellular antigens with which donor lymphocytes engage when normal and immune lymphocyte reactions are incited are radiosensitive leukocytes. Constitutive cells of the skin are unimportant. (a) The intensities of these reactions in irradiated subjects are dependent upon the peripheral leukocyte concentration. When this falls below a certain threshold no reactions are incitable. (b) Highly leukopenic animals are capable of developing immune lymphocyte transfer (ILT) reactions if normal lymphoid cells of their own genetic constitution are mixed with the putative attacking donor cells, as "supplementing antigen," before inoculation. (c) Radiation-chimeric strain 13 animals having F1 hybrid leukocytes in their bloodstream give typical ILT reactions when challenged intradermally with strain 13 anti-2 node cells. Exposure of strain 2 animals to 600 R does not prevent their becoming actively immunized if, 24 hr later, they are injected intradermally with strain 13 lymphocytes. However, this sensitization, revealed by the host's capacity to give delayed hypersensitivity reactions, wanes as leukopenia progresses. On the basis of this and other findings it is argued that the flare-up stage of the NLT reaction in preirradiated hosts is mainly an expression of host sensitivity against the transferred alien cells. Two unexpected observations have been made in the course of this study: (a) F1 hybrid animals developed what appeared to be a strong delayed hypersensitivity after intradermal inoculation with parental strain lymphoid cells or antigenic extracts prepared from them. (b) If strain 13 guinea pigs which had been sensitized against strain 2 tissue antigens by intradermal injection of lymphocytes 7 days beforehand were inoculated intravenously with strain 2 antigenic extract a significant proportion of the animals developed severe delayed necrotizing reactions, recall flares, at some or all of the healed skin inoculation sites.


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.


1936 ◽  
Vol 64 (4) ◽  
pp. 641-655 ◽  
Author(s):  
Marion C. Morris

1. Sensitized guinea pigs injected with normal rabbit or guinea pig serum previous to intravenous inoculation of antigen may be protected against a few lethal doses of antigen. The protection is greater with foreign than with homologous serum and appears to be related roughly to the amount of serum introduced. 2. Sensitized guinea pigs injected with antibody-containing serum preliminary to intravenous injection of antigen, show no greater refractoriness to anaphylaxis than do those injected with normal serum. 3. Moreover, in many instances, the injection of an excess of antibody into the circulation of sensitized guinea pigs, leads to an increased susceptibility of these animals to anaphylaxis. 4. These results indicate that an excess of circulating antibody is not responsible for a state of antianaphylaxis, but on the contrary, may contribute toward the anaphylactic reaction itself.


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