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I Tizard

Publications and source records attributed to I Tizard.

At least 19 recordsLinked to original sources

Specificity and prevalence of natural bovine anti-alpha galactosyl (Galalpha1-6Glc or Galalpha1-6Gal) antibodies.

Immunity against the carbohydrate components of microorganisms mediated by antibodies is an important part of host defenses. Humans and closely related primates, but not other mammals, possess natural anti-Galalpha1-3Gal antibodies which also, although less avidly, react with melibiose (Galalpha1-6Glc). Using an enzyme-linked immunosorbent assay (ELISA) with melibiose-bovine serum albumin as an antigen, we analyzed bovine anti-alpha galactosyl antibodies with respect to specificity and distribution in individual animals. Inhibition assays showed that melibiose was the strongest inhibitor, followed equally by stachyose (Galalpha1-6Galalpha1-6Glcbeta1-2Fru) and raffinose (Galalpha1-6Glcbeta1-2Fru) and then by Galbeta1-6Gal, Gal, and Galalpha1-2Gal. Others, including Galalpha1-3Gal and Galalpha1-4Gal, only exhibited minor inhibition. Thus, these bovine anti-alpha galactosyl antibodies appeared to preferentially react with Galalpha1-6Glc or Galalpha1-6Gal. The distinction of this specificity from that (Galalpha1-3Gal) of human antibodies was further demonstrated by the poor reaction of bovine serum to the Galalpha1-3Gal antigen in comparison to human serum. All 27 healthy bovine serum samples of the three age groups (newborn, calf, and adult) tested contained such antibodies with titers increasing with age. The antibodies purified by affinity chromatography using a melibiose-agarose column were mainly of the immunoglobulin G (IgG) isotype with a concentration of >23 microg/ml in most samples. IgG1 was found to be the primary antimelibiose IgG isotype in all age groups by isotype-specific ELISA, but a significant increase in IgG2, an isotype more related to innate immunity, was observed in calves and adults, compared to newborns. The purified antibodies reacted with the type II bovine strain of Streptococcus agalactiae, a common pathogen of bovine mastitis. Thus, these anti-Galalpha1-6Glc or Galalpha1-6Gal antibodies in cattle might be involved in defense against microbes bearing this or the related epitopes.

Age Factors↗

Grease, anthraxgate, and kennel cough: a revisionist history of early veterinary vaccines.

In conclusion, it is remarkable just how farsighted many of the early vaccine investigators were. Jenner was apparently very comfortable with contagion and even recognized that infectious agents could gradually change and adapt to a new species. Pasteur, long before his fowl cholera experiment, dreamed that attenuation could yield safe vaccines and it took him no time at all therefore to recognize the significance of that serendipitous experiment. The fact that two other investigators were also developing anthrax vaccines simultaneously is yet another example of how the times favor certain discoveries. Finally Ferry, while constrained by the fact that he had no idea that distemper was caused by a virus, recognized well the concept of secondary infection and rationalized, not unreasonably, that his vaccine might assist in controlling this. It is also clear that we must look skeptically at the accepted historical record. Thus, it is clear that Jenner used horse-derived material as a source of vaccine material and that vaccinia may in fact be the long-lost agent of horsepox. Certainly this would not be news to many nineteenth-century investigators and veterinarians. Individuals planning to use live vaccinia in recombinant vaccines may wish to keep this in mind. Who discovered anthrax vaccine? Burdon-Sanderson clearly recognized that he could attenuate the organism. Greenfield showed that this could protect against disease although he was far from developing an effective vaccine. Poor Henri Toussaint was probably the first to develop an effective product but did not publicize his results widely. It was left to Louis Pasteur to take the risks inherent in a high-profile public experiment and win. I believe that he richly deserves the prize. Finally, who deserves the credit for distemper vaccine? First, Carré deserves much more credit than hitherto for discovering that distemper was caused by a virus. Second, Ferry, although misled by his identification of B. bronchiseptica deserves credit for realizing that his vaccine could play a role in controlling secondary infections. The true discoverer of an effective distemper vaccine was the Italian, Puntoni, but once again the publicity went to others, Laidlaw and Dunkin. Thus a pattern emerges that prior discovery matters little in the face of aggressive publicity. If nobody knows you did the experiment you might as well have never done it in the first place. Publish or perish is by no means a new phenomenon.

Animals↗

Specificity and prevalence of natural bovine antimannan antibodies.

Immune responses to the carbohydrate components of microorganisms, mediated both by antibodies and by lectins, are an important part of host defense. In the present experiments, the specificity and presence of natural bovine antibodies against mannan, a common fungal antigen, were examined by enzyme-linked immunosorbent assay (ELISA), using Saccharomyces cerevisiae mannan as an antigen. The results showed that all serum samples from animals of three age groups (newborn, calf, and adult) tested contained antimannan antibodies, and the titer of these antibodies increased significantly in adults. However, titers among individual adult cattle differed widely. Inhibition assays showed that yeast mannan was the strongest inhibitor. D-Mannose exhibited only a minor inhibitory effect at high concentrations. This suggests that most of these antibodies recognize an oligosaccharide-based epitope(s) different from those recognized by lectins. Cattle possess three serum C-type lectins (collectins) capable of recognizing mannan in a calcium-dependent manner. Addition of EDTA to the reaction did not reduce antibody binding, suggesting that the binding of these antibodies to mannan was not affected by the presence of collectin. The antibodies purified from either calf or adult serum by mannan-Sepharose affinity chromatography consisted of mainly immunoglobulin G (IgG) and a smaller amount of IgM. IgG1 was shown to be the dominant antimannan IgG isotype by isotype-specific ELISA. Together, these results demonstrate the production of natural antimannan antibodies in cattle in an age-dependent manner. These antibodies might be involved in defending the host against mannan-containing pathogens as a specific line of defense in conjunction with the innate response by lectins.

Age Distribution↗

Use of serologic testing to assess immune status of companion animals.

At the November 1997 meeting of the AVMA Council on Biologic and Therapeutic Agents, the Council recommended that the JAVMA publish an article on the current status of the use of serologic testing in an effort to assist practitioners who must make decisions regarding vaccination of companion animals (i.e., dogs, cats, and horses). It is anticipated that the peer-reviewed article provided here will be of benefit to veterinarians and will facilitate their attempts to maintain animal health through the knowledgeable use of vaccines.

Animals↗

Lectin-carbohydrate interaction in the immune system.

The immune system consists of various types of cells and molecules that specifically interact with each other to initiate the host defense mechanism. Recent studies have shown that carbohydrates and lectins (carbohydrate-binding proteins) play an essential role in mediating such interactions. Both lectins and carbohydrates are widely distributed in the mammalian tissues as well as in microorganisms. Carbohydrates, due to their chemical nature, can potentially form structures that are more variable than proteins and nucleic acids. Lectins can exist in either soluble or cell-associated form, and although overall structures vary, invariably possess carbohydrate-recognition domains (CRD) with various specificities. The interaction between lectins and carbohydrates have been shown to be involved in such activities as opsonization of microorganisms, phagocytosis, cell adhesion and migration, cell activation and differentiation, and apoptosis. The number of lectins identified in the immune system is increasing at a rapid pace. The development in this area has opened a new aspect in studying the immune system, and at the same time, provided new therapeutic routes for the treatment and prevention of disease.

Animals↗

Primary immunodeficiencies of food animals.

Although there are few, well-characterized PIDs of food animals, these diseases are important because they tend to be severe and with no cure. Most animals with PID do not receive the intensive and aggressive care required for survival: Veterinarians may be consulted only when the animals are in the terminal stages of illness; it is generally not economically practical for livestock producers or practitioners to pay for the exhaustive laboratory tests required to detect and characterize these anomalies. Another reason for the small numbers of characterized clinical cases of PID is that they are rare. It is possible, however, that intensive artificial insemination and embryo transfer could select for heterozygous carriers of these autosomal traits. As seen with bovine leukocyte adhesion deficiency, as the frequency of an allele increases in the population, the numbers of affected animals increase. Furthermore, other immunodeficient syndromes are likely to exist. Veterinarians therefore should be aware of these disorders and should seek laboratory assistance to arrive at a correct diagnosis. Because of the inheritable nature of PID, livestock producers need assistance from veterinarians to identify carriers and establish sound breeding and control programs. One positive outcome from studies of PID is that research scientists and veterinarians learn much about immune systems from these afflicted animals. In fact, these animals may become models for gene therapy or marrow reconstruction procedures.

Animals↗

Efficacy of acemannan in treatment of canine and feline spontaneous neoplasms.

Forty-three dogs and cats with spontaneous tumors were treated with the immunostimulating polysaccharide acemannan by intraperitoneal and intralesional routes of administration. Tumors from 26 of these animals showed histopathological evidence of immunological attack as shown by marked necrosis or lymphocytic infiltration. Thirteen showed moderate to marked tumor necrosis or liquefaction. Twenty-one demonstrated lymphoid infiltration, and seven demonstrated encapsulation. Twelve animals showed obvious clinical improvement as assessed by tumor shrinkage, tumor necrosis, or prolonged survival; these included five of seven animals with fibrosarcomas. It is believed that acemannan exerts its antitumor activity through macrophage activation and the release of tumor necrosis factor, interleukin-1, and interferon.

Adjuvants, Immunologic↗

Aroclor 1254 as a 2,3,7,8-tetrachlorodibenzo-p-dioxin antagonist: effects on enzyme induction and immunotoxicity.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and Aroclor 1254 induced the cytochrome P-450 dependent monooxygenases, aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) in rat hepatoma H-4-II E cells and C57BL/6J mice. It has been proposed that both Aroclor 1254 and 2,3,7,8-TCDD induce these enzymes via a common mechanism which features initial binding to the aryl hydrocarbon (Ah) cytosolic receptor protein. The major difference between these compounds was the relative potency (i.e. 2,3,7,8-TCDD much greater than Aroclor 1254). Cotreatment of rat hepatoma H-4-II E cells or C57BL/6J mice with a dose of 2,3,7,8-TCDD which submaximally induces AHH and EROD and a dose of Aroclor 1254 which exhibited little or no induction activity resulted in significant antagonism of the induction effects of 2,3,7,8-TCDD. For example, cotreatment of C57BL/6J mice with 2,3,7,8-TCDD (15 nmol/kg) and Aroclor 1254 (25, 75 and 150 mumol/kg) resulted in up to 23% antagonism of AHH induction by 2,3,7,8-TCDD. Moreover, cotreatment with a higher dose of the 2,3,7,8-TCDD agonist (30 or 50 nmol/kg) partially reversed some of the antagonism by Aroclor 1254. In vivo antagonism was observed only at Aroclor 1254/2,3,7,8-TCDD molar ratios of 1667:1, 5000:1 and 10,000:1. Administration of 2,3,7,8-TCDD (3.72 nmol/kg) to C57BL/6J mice resulted in a 76% decrease in the splenic plaque forming cell response to sheep red blood cells. This T-cell mediated immunotoxic effect of 2,3,7,8-TCDD segregates with the Ah locus. In contrast, administration of 5, 15, 75 and 150 mumol/kg of Aroclor 1254 resulted in impairment of the immune response only at the highest dose level. However, cotreatment of mice with 2,3,7,8-TCDD (3.72 nmol/kg) and Aroclor 1254 (5, 15 or 75 mumol/kg) resulted in no significant decrease in the plaque forming cell response and complete protection from the immunotoxicity of 2,3,7,8-TCDD. Cotreatment of the mice with Aroclor 1254 (75 mumol/kg) and a higher dose of the 2,3,7,8-TCDD agonist resulted in partial reversal of the protective effects of Aroclor 1254. The in vitro and in vivo data suggest that within specific antagonist/agonist dose ratios, Aroclor 1254 can antagonize at least 2 Ah receptor-mediated effects of 2,3,7,8-TCDD, namely AHH induction and immunotoxicity.

Animals↗

Serologic assays.

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Agglutination Tests↗

Influence of palmitic acid on mouse lymphocyte function in vivo and in vitro.

The effect of palmitic acid on the immune response of mice to sheep erythrocytes was studied. It was found to increase the number of background plaques in normal mice but it had no significant effect on primed cells. When given with antigen it functioned as a weak adjuvant but it had no effect on response of mouse lymphocytes to the mitogens phytohemagglutinin or bacterial lipopolysaccharide. While it is clear that palmitic acid does not have a profound effect on lymphocyte reactivity, it may have a subtle modulating influence on the immune system.

Adjuvants, Immunologic↗

Immunosuppression in experimental African trypanosomiasis. Polyclonal B-cell activation and mitogenicity of trypanosome-derived saturated fatty acids.

Changes in antibody responses in adult mice infected with Trypanosoma congolense and subsequently challenged with unrelated antigens (sheep red blood cells and pneumococcal polysaccharide) were studied. Immune responses were significantly depressed within 1 week of infection, and complete suppression of both IgM and IgG responses to both types of antigen was established 15 days after immunization. Coincidentally with the development of high parasitaemias, background IgM plaque-forming cell responses to sheep red cell antigen significantly increased in non-immunized T. congolense-infected animals. Autolysates of T. congolense and chloroform-soluble extracts of the autolyzed trypanosome were found to be mitogenic in vitro for the spleen cells of normal mice. Fractionation of these extracts by thin-layer chromatography indicated that the mitogenic activity migrated with the free fatty acids. Substitution of the relevant saturated and unsaturated free fatty acids in the autolyzed trypanosome extracts with commercial pure fatty acids in the mouse spleen cultures indicated that the mitogenicity was due to palmitic and stearic acids. It is suggested that the general immunosuppressing effect of trypanosomes may be attributed, at least in part, to the polyclonal activation, and subsequent depletion and/or clonal exhaustion of B-cells as a result of blastogenic stimulus from the parasites. This may operate, at least in part, through the generation of B-cell mitogenic saturated fatty acids.

Animals↗

Complement activating factor(s) of Trypanosoma lewisi: some physiochemical characteristics of the active components.

Of the complement activating factors present in Trypanosoma lewisi, the major component, a carbohydrate containing substance was further investigated. This component was found to have a lag time of complete activation of 2 CH50 units of bovine complement of approximately 15 minutes while 1% trypsin (a known activator of complement, used as a control system) was capable of instant consumption of a similar quantity of complement. In addition, the complement activating factor of trypanosomes was observed to be stable at 100 degrees C for 15 minutes and over a pH range of 3.0 to 11.0. Thin layer chromatography studies suggested that at least part of the active component contained lipid, perhaps indicating that it may be glycolipid in nature.

Animals↗