Staphylococcal infection in guinea pigs sensitized with a commercial staphylococcal allergen

Guinea pigs, previously injected with commercial staphylococcal allergen to induce delayed hypersensitivity, were infected by the intramuscular injection of S. aureus in a nonlethal dose. For control, the animals receiving only S. aureus were used. The dynamic study of the degree of septicemia and some lymphocytic characteristics in the animals was made. The study revealed that delayed hypersensitivity did not aggravate the course of the main disease; on the contrary, it rendered protection against the subsequent infection. Increased resistance to infection was manifested by a decrease in the degree of septicemia, determined from the decreased number of colony-forming units of S. aureus in the splenic tissue as assessed by inoculation into agar, as well as from a higher level of the activation of lymphocytes as assessed by rosette formation.     

Pathogenetic significance of the immediate and delayed types of hypersensitivity reactions in the dynamics of nephritis]

Complex study of the immunologic status of rats from the first days after the injection of nephrotoxic serum up to formation of chronic renal failure in comparison with functional and morphological characteristics of the disease confirmed the hypothesis on the phasic development and different pathogenetic role of the hypersensitivity reactions of the immediate and delayed types during nephritis. Signs of the immediate hypersensitivity predominated during the initial stages of the disease; realization of this hypersensitivity is indicated both by the liberation of the mediators of the pathochemical phase and by the change of the renal processes. The development of delayed hypersensitivity reactions plays the basic role in the pathogenesis of chronic nephritis.     

不同纯度、剂量白喉类毒素对迟发型超敏反应的影响

研究不同剂量及不同白喉类毒素纯度引起的迟发型超敏反应的状况,用于指导疫苗的生产,提高疫苗的质量。以豚鼠为动物模型,采用迟发型超敏试验法,对原制白喉类毒素、精制白喉类毒素、纯化精制白喉类毒素、高纯度的精制白喉类毒素的剂量与超敏反应试验。试验结果表明,注射白喉类毒素剂量的大小与超敏反应成正相关,与纯度成负相关。剂量越大,超敏反应越强;纯度越高,超敏反应愈弱。     

The effect of sodium nucleinate on allergic and immunological reactions

Experiments on immunized rabbits and guinea pigs indicated that sodium nucleinate (SN) was capable of weakening or entirely eliminating anaphylactic and skin reactions of delayed type hypersensitivity to repeated administration of staphyloanatoxin, APDT vaccine. The findings on patients with the infectious form of bronchial asthma and chronic rheumatism showed that sodium nucleinate attenuated reactions to the subcutaneous administration of staphylococcal and streptococcal allergens. The treatment of patients suffering from infectious-allergic bronchial asthma and rheumatism with SN resulted in the recovery of deficient T cells, T-suppressors, normalization of immunoglobulin concentrations. In children with acute glomerulonephritis sodium nucleinate normalized decreased T-suppressor cells and increased IgG and circulating immune complexes (CIC), resulting in a pronounced remission of disease. The mechanism of desensitization and elimination of CIC by SN has not been explored, however, the parameters of SN-induced immunomodulation are known rather completely. It is suggested that SN brings about accumulation in the cell of cyclic AMP which diminished membrane permeability, activates monoaminooxidase resulting in the degradation of histamine and other biogenic amines, enhances the synthesis of endogenous corticosteroids with their desensitizing properties. All these effects contribute to the elimination of delayed type hypersensitivity. The role of SN in the inhibition of delayed type hypersensitivity remains obscure.     

FTY720 immunosuppression impairs effector T cell peripheral homing without affecting induction, expansion, and memory

FTY720 (2-amino-2-(2-[4-octylphenyl]ethyl)-1,3-propanediol hydrochloride) prolongs survival of solid organ allografts in animal models. Mechanisms of FTY720 immunomodulation were studied in mice infected with lymphocytic choriomeningitis virus (LCMV) to assess T cell responses or with vesicular stomatitis virus to evaluate Ab responses. Oral FTY720 (0.3 mg/kg/day) did not affect LCMV replication and specific CTL and B cells were induced and expanded normally. Moreover, the anti-viral humoral immune responses were normal. However, FTY720 treatment showed first a shift of overall distribution of CTL from the spleen to peripheral lymph nodes and lymphocytopenia was observed. This effect was reversible within 7-21 days. Together with unimpaired T and B cell memory after FTY720 treatment, this finding rendered enhancement of lymphocyte apoptosis by FTY720 in vivo unlikely. Secondly, the delayed-type hypersensitivity reaction to a viral MHC class I-presented peptide was markedly reduced by FTY720. These results were supported by impaired circulation of LCMV specific TCR transgenic effector lymphocytes in the peripheral blood and reduced numbers of tissue infiltrating CTL in response to delayed-type hypersensitivity reaction. Thirdly, in a CD8+ T cell-mediated diabetes model in a transgenic mouse expressing the LCMV glycoprotein in the islets of the pancreas, FTY720 delayed or prevented disease by reducing islet-infiltrating CTL. Thus, FTY720 effectively reduced recirculation of CD8+ effector T cells and their recruitment to peripheral lesions without affecting the induction and expansion of immune responses in secondary lymphoid organs. These properties may offer the potential to treat ongoing organ-specific T cell-mediated immunopathologic disease.     

Delayed hypersensitivity to house dust-storage mites Thyrophagus putrescentiae in experimental allergic dermatoses]

House dust mites and storage mites proved to be one of the main allergens causing hypersensitivity in atopic dermatitis in allergic patients. The authors reproduced experimental allergic dermatosis on the model of delayed type hypersensitivity in guinea pigs, caused by sensitization to the allergen from the mite's bodies Tyrophagus putrescentiae--species having wide distribution in the country. The results characteristic for T-cell type hypersensitivity have been obtained: delayed positive skin tests after 24 hours, typical histomorphological picture (strong allergic alteration, epidermis desquamation, vasculitis, dermis T-cell infiltration and spongiosis--Waksman's syndrome). It is concluded that side by side with humoral IgE-mediated reaction there is strong delayed T-cell hypersensitivity to the storage mites Tyrophagus putrescentiae.     

Studies on circulating gonococcal antibodies and antigens.

One hundred human sera obtained from acute gonococcal disease and 100 sera from nongonococcal diseases or healthy persons were concentrated four times and examined for the presence of circulating gonococcal antigens and antibodies by means of a counterimmunoelectrophoresis (CIE) and delayed hypersensitivity assay. Antibodies reacting with cytoplasmic gonococcal antigens were detected by CIE in 92% of sera received from patients suffering from acute gonococcal disease. Gonococcal antigens were found in the concentrated sera of 82.3% of patients on the basis of dermal reactions observed upon injections of these sera into the skin of rabbits sensitized with disrupted gonococci; 51.8% of the patients' sera gave delayed hypersensitivity reactions in rabbits sensitized with cytoplasmic antigens of N. gonorrhoeae. Control sera from healthy people and those with non-gonococcal diseases did not react with any of the preparations tested.     

Specific depression of delayed hypersensitivity to purified proteins, with relation to production of circulating antibody

In guinea pigs sensitized in the footpads with a purified protein, such as hen egg albumin or diphtheria toxoid, in incomplete Freund's adjuvant, delayed hypersensitivity precedes the appearance of circulating antibody. This expression of delayed hypersensitivity by skin-test declines sharply the day before circulating antibody is detected. Adoptive transfer of spleen and peritoneal exudate cells from guinea pigs showing this decline suppresses the expression of delayed hypersensitivity in already sensitized recipients. This suppression of delayed hypersensitivity is immunologically specific. The intensity of this suppression does not correlate directly with the dose of sensitizing antigen, nor does it depend directly on the amount of circulating antibody.     

The ultrastructural development of the schistosome egg granuloma in mice.

Hepatic granulomas from mice infected with Schistosoma mansoni for periods of 8 weeks to 1 year studied by electron microscopy. The different cell types present in the granulomas suggested that whilst a delayed hypersensitivity response predominated during early stages of infection an Arthus-type reaction associated with delayed hypersensitivity occurred at later stages of infection.     

Role of mediators of cellular hypersensitivity in the stimulation of the antibody formation to unrelated antigen

The effect of a concurrent delayed hypersensitivity reaction on the antibody response to sheep red cells was assessed by a plaque assay. Guinea pigs with delayed hypersensitivity to tuberculin purified protein derivative (PPD) or egg albumin showed an increased antibody response to sheep red cells when the cells were injected intravenously at the same time as PPD or egg albumin. This effect was transferred to normal guinea pigs by serum from guinea pigs with delayed hypersensitivity to PPD or egg albumin taken 24 hr after injecting the corresponding antigen. Supernatants containing migratory inhibitory factor were prepared by incubating lymphocytes from sensitized rabbits with antigen. These supernatants were injected with sheep red cells and gave rise to an enhanced plaque response. Similar results were obtained with supernatants from normal rabbit thymus cells. The role of mediators of delayed hypersensitivity in enhancing antibody formation and in T cell/B cell cooperation is discussed.     

Heterologous antigenic stimulation in induction of delayed hypersensitivity.

An influence of a delayed hypersensitive reaction to a primary antigen on the induction of delayed hypersensitivity to a second unrelated antigen was observed in guinea pigs immunized with azobenzenearsonate-N-acetyl-L-tyrosine (ABAT), and injected intradermally 3 weeks later with a mixture of ABAT and secondary antigen. Animals so treated developed delayed hypersensitivity to sheep red blood cells (SRBC) or Type II pneumococcal polysaccharide as secondary antigens, as measured by skin test reactivity and inhibition of macrophage migration, whereas ABAT unsensitized control groups did not. However, attempts to induce delayed reactivity to proteins as secondary antigens were unsuccessful. The injection of secondary antigen into a mineral oil-induced inflammatory lesion did not induce delayed hypersensitivity, suggesting that specific reactivity to ABAT is a prerequisite for heterologous induction. Possible mechanisms for the observed phenomenon, including a role for macrophages, are discussed.     

Cellular immunity in man: correlation of leukocyte migration inhibition factor formation and delayed hypersensitivity

The formation of leukocyte migration inhibition factor (MIF) by the lymphocytes of 13 normal persons immune to the protein antigen keyhole limpet hemocyanin (KLH) has been investigated. KLH-induced MIF formation expressed as percent migration was compared with delayed hypersensitivity, antibody, and in vitro lymphocyte blastogenic responses to this antigen. Individuals were studied 404–840 days (median 540 days) after their last exposure to KLH. Nine persons had delayed hypersensitivity to KLH and 10 had circulating KLH antibody. The lymphocytes of 11 showed an in vitro blastogenic response to KLH stimulation, while the lymphocytes of nine produced MIF after KLH stimulation. The mean percent migration for the subjects with KLH delayed hypersensitivity was 48.2 (range 20.4–70.4) compared with 133 (range 120–161) for the four persons who did not have KLH delayed hypersensitivity (P < 0.05). The correlation coefficient between the precent migration and delayed hypersensitivity was ?0.78 (P < 0.01). No correlation was demonstrated between migration inhibition and the other parameters of immunity.     

Comparative characteristics of the diagnostic properties of staphylococcal allergens in an experiment

The diagnostic value of five staphylococcal allergens prepared from a single S. aureus strain by different methods and in different institutions has been tested on the experimental models of delayed, immediate and mixed (immediate and delayed) hypersensitivity in guinea pigs. The advantages of the allergens prepared in Kazan (USSR) for the detection of delayed hypersensitivity and the ultrasonicated allergen, as well as the allergen made in Czechoslovakia, for the detection of immediate hypersensitivity have been noted.     

Delayed cutaneous hypersensitivity response in tetanus toxoid sensitized rhesus monkeys: predictor of anergy and value in tuberculin skin testing

The primary problem in using the tuberculin skin test in nonhuman primates is the clinical uncertainty concerning the animal's ability to elicit a delayed cutaneous hypersensitivity response. A negative tuberculin skin test can only be meaningful if the animal can produce a delayed cutaneous hypersensitivity reaction. Veterinarians deliberately sensitize animals to antigens in the form of prophylactic vaccination. Therefore, if nonhuman primates were deliberately sensitized to an antigen capable of producing a hypersensitivity response, that antigen should serve as a positive control for delayed cutaneous hypersensitivity reactions. Tetanus toxoid was chosen because repeated immunizations with this antigen is recommended routine medical practice for nonhuman primates housed outdoors. Twenty juvenile, male rhesus (Macaca mulatta) monkeys were selected for this study. The monkeys were assigned randomly to one of two groups of ten animals. The test group was vaccinated with tetanus toxoid intramuscularly at 1 month intervals for a total of three vaccinations. The control group was treated the same except saline was administered rather than tetanus toxoid. Following sensitization, the two groups of animals were challenged with tetanus toxoid intradermally. Eight of the ten monkeys in the test group responded to the tetanus toxoid while none of the control groups responded to the tetanus toxoid. Elicitation of a delayed cutaneous response in animals sensitized to tetanus antigen before challenge may serve as a positive control for delayed cutaneous hypersensitivity. This simple test may serve as a useful adjunct in making objective clinical decisions concerning anergy-suspect animals.     

The development of experimental allergic encephalomyelitis with immunizing doses of myelin basic protein.

Rabbits immunized with low (11.25 mg) and high (57.50 mg) doses of myelin basic protein from several species develop antibasic protein antibodies, delayed type hypersensitivity, and clinical and pathological signs of experimental allergic encephalomyelitis. More than 55% of rabbits immunized with relatively high doses of basic protein develop disease. The absence of circulating antibasic protein antibodies in immunorespondent animals is associated with the appearance of clinical or histological signs of experimental allergic encephalomyelitis; however, the presence of humoral antibodies did not prevent completely the development of disease. Delayed-type hypersensitivity, specific for the basic protein, appears as early as 5 days after immunization and is maintained in nondiseased and surviving animals. Neither excess encephalitogen nor encephalitogen-induced antibody is sufficient to suppress completely the eventual development of clinical or histological manifestations of disease.     

Lymphocytotoxic antibodies in cancer

Summary To study the relationship of cold-reactive lymphocytotoxic antibodies (LCA) to immune defects in cancer, LCA were measured in sera from 71 patients with different types of malignancies and 31 healthy controls. A significantly increased incidence (10 of 24) of LCA was noted in a group of patients with lymphoreticular malignancies excluding chronic lymphocytic leukemia (CLL). No significantly increased incidence of LCA was found in patients with CLL (0 of 9), melanoma (5 of 22), or carcinoma (1 of 16) as opposed to normal controls (1 of 31). In the lymphoreticular malignancy group, no correlation was noted between LCA levels and delayed hypersensitivity skin tests, skin croton oil response, total lymphocytes, T cells, or B cells. We conclude that LCA is increased in patients with certain lymphoreticular malignancies in contrast to other types of cancer. Its presence, however, is unrelated to major defects in the cell-mediated immune system seen in some of these patients.     

Functional dyspepsia and nonerosive reflux disease: clinical interactions and their implications

Functional dyspepsia or nonulcer dyspepsia, and nonerosive reflux disease (NERD) or endoscopy-negative reflux disease, are common reasons for referral to a gastroenterologist. Although there is much confusion with regard to definition, recent research would suggest that these 2 conditions are linked and may represent components in the spectrum of the same disease entity, in terms of both symptoms and pathophysiology. Several theories have been proposed regarding the etiology of these disorders, including acid exposure, visceral hypersensitivity, impaired fundal accommodation, delayed gastric emptying, and Helicobacter pylori infection.     

Immune Response against Hamster Erythrocytes in the Low-Responder Mouse Strains

Delayed hypersensitivity against hamster erythrocyte antigen was examined after sensitization with hamster erythrocytes (HRBC) in Freund's complete adjuvant (FCA). Extent of the delayed hypersensitivity was determined by the migration inhibition test, the peritoneal macrophage disappearance test and the skin test in the ear using solubilized HRBC as the test antigen. 1) Delayed hypersensitivity against HRBC developed earlier in high-responder SL mice than in low-responder C57BL/6 mice after sensitization. The period required for development of the delayed hypersensitivity in AKR mice was intermediate between periods in high-responder SL mice and low-responder C57BL/6 mice. 2) After sensitization with HRBC in FCA, a delayed hypersensitive state without detectable antibody production persisted until day 12 in high-responder SL mice and until day 16 or later in low-responder C57BL/6 mice. 3) Delayed hypersensitivity against HRBC antigen persisted even after the appearance of circulating antibody which occurred late after sensitization with HRBC in FCA or after intravenous injection of HRBC into sensitized mice.     

CD4+ TCR repertoire heterogeneity in Schistosoma mansoni-induced granulomas

The hallmark of Schistosoma mansoni infection is the formation of liver granulomas around deposited ova. The initiation of granuloma formation is T cell-dependent since granulomas are not formed in their absence. We investigated whether a few T cells arrive to initiate the inflammatory lesion and subsequently expand locally, or whether a large repertoire of systemically activated T cells home to the delayed type hypersensitivity reaction induced by the ova. The TCR repertoire of single granulomas from the same liver were analyzed by PCR using Vbeta-specific primers and CDR3 analysis. Each granuloma has a very diverse TCR repertoire indicating that most of the T cells recruited to these lesions are activated systemically. At the same time, sequence analysis of individually sized CDR3 products from single granuloma indicate that a fraction of T cells expand locally at the lesion site. Using TCR transgenic mice containing a pigeon cytochrome c-specific T cell population or lymphocytic choriomeningitis virus infection tracked with lymphocytic choriomeningitis virus-specific tetramers, we demonstrated that nonspecific T cells home to the granuloma if they are activated. However, recombinase-activating gene 2(-/-) pigeon cytochrome c-specific TCR transgenic mice fail to form granulomas in response to S. mansoni ova even after T cell activation, suggesting a requirement for egg-specific T cells in the initiation of these inflammatory lesions. Understanding the mechanism of T cell recruitment into granulomas has important implications for the rational design of immunotherapies for granulomatous diseases.     

Specific experimental therapy in sensitization to group A streptococci]

A model of delayed hypersensitivity to Streptococcus hemolyticus, group A, were obtained in guinea pigs and rabbits. Studies of spontaneous changes of the immuno-allergic reactivity revealed that after a month of sensitization there developed delayed hypersensitivity only; according to the results of late skin tests it lasted not less than 6 months (the duration of investigation). The delayed hypersensitivity component began to manifest itself in 2 1/2 to 3 months and increased later on. Specific hyposensitization was performed with streptococcus allergens differing by physico-chemical conditions, i.e. the corpuscula allergen, the one that was lysed by ultrasonic waves, and Ando-Verzhikovsky's allergen. The latter had the most intensive hyposensitizing features. Specific hyposensitization was more demonstrative after the intracutaneous long-term course injections of threshold doses. Administration of subthreshold doses, as well as subcutaneous or intravenous injections of the allergen, was ineffective.