scholarly journals THE COURSE OF EXPERIMENTAL AUTOALLERGIC THYROIDITIS IN INBRED GUINEA PIGS

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.

1961 ◽  
Vol 113 (4) ◽  
pp. 611-624 ◽  
Author(s):  
Philip R. B. McMaster ◽  
Edwin M. Lerner ◽  
Eurmal D. Exum

Strain 13 histocompatible guinea pigs developed allergic thyroiditis after immunization with thyroid extracts derived from the same strain or from other strains of guinea pigs. This thyroiditis appeared as early as 5 days after immunization, and by 7 weeks was uniformly present and generally severe. 7 weeks after immunization, the anti-thyroid antibody titer correlated with the presence and degree of thyroiditis. However, at certain other times after immunization, the titer did not correlate with the thyroiditis. By contrast, all animals with thyroiditis, which were skin-tested with thyroid extract, exhibited delayed hypersensitivity. Moreover, all those which failed to respond with delayed reactions, when skin-tested, had not developed thyroiditis. The present work correlates the presence of experimental allergic thyroiditis with delayed hypersensitivity.


PEDIATRICS ◽  
1981 ◽  
Vol 68 (4) ◽  
pp. 544-549 ◽  
Author(s):  
Carol J. Baker ◽  
Morven S. Edwards ◽  
Dennis L. Kasper

The role of maternally acquired antibody to native type III polysacchande of group B Streptococcus as a determinant of susceptibility for infant systemic infection was investigated. Sera from 11 1 acutely ill infants with type III group B streptococcal bacteremia and/or meningitis and their mothers, and cord sera from 45 healthy neonates and their mothers who had type III group B streptococcal vaginal colonization at delivery were studied. Sera from each of 111 acutely ill infants contained very low levels ofantibody (sjlt 1.7 µg/ml, median 0.4 µg/ml), and a significant correlation with maternal levels was tested for early onset infection (median 0.6 µg/ml; r = .76; P sjlt .01). Women whose infants remained well had antibody levels sjgt 2 µg/ml in their sera (73%) more often than those whose infants developed symptomatic infection (17%) (P sjlt .001), and the median level in their sera (12.6 µg/ml) was considerably higher. Study of sera obtained during convalescence from 86 surviving infants indicated a poor antibody response to infection. In contrast, high levels of antibody were detected in sera from each of five convalescent women with postpartum bacteremia. These data extend earlier observations suggesting the correlation between low levels of type-specific antibody in serum and risk for systemic infection with type III strains of group B streptococci.


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.


1972 ◽  
Vol 50 (6) ◽  
pp. 689-696 ◽  
Author(s):  
M. A. Barton ◽  
T. A. McPherson ◽  
R. U. Lemieux ◽  
G. O. Bain

Peptides comprising the 7–11, 11–20, and 12–20 sequences of human encephalitogenic basic protein (HEP) were synthesized by the solid-phase procedure, purified by gel-filtration and high-voltage paper electrophoresis, and characterized by amino acid analysis, thin-layer chromatography, high-voltage paper electrophoresis, and paper chromatography.The peptides were studied for the capacity to induce E.A.E. when injected with Freund's complete adjuvant (FCA) into guinea pigs. The same peptides were also studied for the capacity to inhibit development of E.A.E. in guinea pigs injected with peptide/FCA 28 days before injection with encephalitogenic HEP in FCA. The results were as follows: (1) all three peptides induced mild clinical E.A.E. but the 12–20 peptide induced severe disease in five out of 40 guinea pigs; (2) none induced histological lesions typical of E.A.E.; (3) none induced antibody reactive with 125I-HEP; (4) none induced delayed sensitivity to the homologous peptide or HEP; (5) injection of the 12–20 peptide in FCA inhibited the development of histological E.A.E. in guinea pigs injected later with HEP/FCA, whereas the 7–11 and 11–20 sequences did not; (6) humoral immunity to injection of HEP/FCA was not prevented by prior injection of the synthetic peptides in FCA.


1977 ◽  
Vol 145 (5) ◽  
pp. 1288-1298 ◽  
Author(s):  
P Chao ◽  
L Francis ◽  
E Atkins

Guinea pig periotoneal exudate (PE) cells incubated overnight in vitro with heat-killed Staphylococci released an endogenous pyrogen (EP) that could be assayed by intravenous injection in rabbits. The febrile responses were linearly related to the dosage of EP over an eightfold range. PE cells derived from guinea pigs with delayed hypersensitivity (DH) to bovine gamma globulin (BGG), also released EP when incubated with antigen in vitro. This reaction was specific and did not occur withe PE cells from normal or complete Freund's adjuvant-sensitized guinea pigs. Studies indicated that monos and/or polymorphonuclear leukocytes rather than lymphocytes were the source of EP. However, when incubated with BGG and sufficient dosages of BGG-sensitized lymphocytes, normal PE cells released EP over a 42 h period. These results suggest that antigen stimulates specifically sensitized lymphocytes to release an agent (perhaps a lymphokine) that activates phagocytic cells to release EP. This model offers unique advantages for investigating in vitro the role of the lymphocyte in antigen-induced fever in DH as well as the relationship of this lymphocyte-induced activity to other known biologic activities mediated by antigen stimulated lymphocytes.


2021 ◽  
Vol 12 ◽  
Author(s):  
Annelot C. Breedveld ◽  
Melissa M. J. van Gool ◽  
Myrthe A. M. van Delft ◽  
Conny J. van der Laken ◽  
Teun J. de Vries ◽  
...  

ObjectiveAutoantibodies are detected in most patients with rheumatoid arthritis (RA) and can be of the IgM, IgG or IgA subclass. Correlations between IgA autoantibodies and more severe disease activity have been previously reported, but the functional role of IgA autoantibodies in the pathogenesis of RA is ill understood. In this study, we explored the effect of IgA immune complexes on osteoclast mediated bone resorption.MethodsAnti-citrullinated peptide antibody (ACPA) and anti-carbamylated protein (anti-CarP) antibody levels of the IgA and IgG isotype and rheumatoid factor (RF) IgA were determined in synovial fluid (SF) of RA patients. Monocytes, neutrophils, and osteoclasts were stimulated with precipitated immune complexes from SF of RA patients or IgA- and IgG-coated beads. Activation was determined by neutrophil extracellular trap (NET) release, cytokine secretion, and bone resorption.ResultsNET formation by neutrophils was enhanced by SF immune complexes compared to immune complexes from healthy or RA serum. Monocytes stimulated with isolated SF immune complexes released IL-6 and IL-8, which correlated with the levels of ACPA IgA levels in SF. Osteoclasts cultured in the presence of supernatant of IgA-activated monocytes resorbed significantly more bone compared to osteoclasts that were cultured in supernatant of IgG-activated monocytes (p=0.0233). Osteoclasts expressed the Fc receptor for IgA (FcαRI; CD89) and Fc gamma receptors. IgA-activated osteoclasts however produced significantly increased levels of IL-6 (p<0.0001) and IL-8 (p=0.0007) compared to IgG-activated osteoclasts. Both IL-6 (p=0.03) and IL-8 (p=0.0054) significantly enhanced bone resorption by osteoclasts.ConclusionIgA autoantibodies induce release of IL-6 and IL-8 by immune cells as well as osteoclasts, which enhances bone resorption by osteoclasts. We anticipate that this will result in more severe disease activity in RA patients. Targeting IgA-FcαRI interactions therefore represents a promising novel therapeutic strategy for RA patients with IgA autoantibodies.


1951 ◽  
Vol 94 (5) ◽  
pp. 415-430 ◽  
Author(s):  
Charles K. Osgood ◽  
Cutting B. Favour

The treatment with adrenocorticotropic hormone of guinea pigs sensitized with heat-killed tubercle bacilli caused suppression of their skin reactivity to tuberculin. Similar animals treated with saline did not show this change. Normal guinea pigs treated with adrenocorticotropic hormone showed suppression of inflammation, but not necrosis, produced by intracutaneous oil of turpentine. There was slight, but probably not significant, diminution of inflammation during saline administration. Tuberculin complement-fixing antibody titers were not altered by either adrenocorticotropic hormone or saline administration. Adrenocorticotropic hormone produced marked eosinopenia and lymphopenia in guinea pigs.


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.


1953 ◽  
Vol 51 (3) ◽  
pp. 359-371 ◽  
Author(s):  
H. A. Druett ◽  
D. W. Henderson ◽  
L. Packman ◽  
S. Peacock

Experiments to determine the role of particle size in the infectivity of anthrax spores are described. Clouds of homogeneous particles were produced. The mortality-dosage curves for guinea-pigs and monkeys are given for clouds of various particle sizes. Data are given on the effect of time in the concentration-time relationship. The results are compared with those recorded by other workers on the relationship of particle size to respiratory retention.Infectivity was highest with single-spore clouds, falling off as particle size increased. Reasons are given for attributing this effect to difference in site of deposition of different-sized particles.


1962 ◽  
Vol 116 (3) ◽  
pp. 311-327 ◽  
Author(s):  
Leon W. Hoyer ◽  
Robert A. Good ◽  
Richard M. Condie

1. 6-Mercaptopurine (6-MP) prevents experimental allergic encephalomyelitis (EAE) during the period of drug administration in both rabbits and guinea pigs. The disease is suppressed even when treatment is started as late as the 5th day after antigenic stimulation in guinea pigs and the 12th day in rabbits. 2. After discontinuation of 6-MP treatment, there is a latent period before the disease is noted. The length of this latent period is not modified by the duration of 6-MP treatment. 3. The effect of 6-MP on EAE is not the result of leukopenia, non-specific toxicity and debilitation, anti-inflammatory activity, or mere masking of clinical signs of the disease. It is, rather, the result of 6-MP's specific anti-immunologic activity. 4. The effects of 6-MP on antibody production, delayed hypersensitivity, and EAE are compared. This provides indirect evidence for the importance of circulating antibody in the pathogenesis of EAE. 5. The important considerations in the use of 6-MP are discussed and the possible usefulness of 6-MP in human neurologic diseases is considered.


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