Influence of the antigenicity of target cells on the antibody-mediated cytotoxicity of nonsensitized lymphocytes

Wiedermann, G; Denk, Helmut; Stemberger, H; Eckerstorfer, R.; Tappeiner, G

doi:10.1016/s0008-8749(75)80048-7

Cited by 12 publications

(4 citation statements)

References 13 publications

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“…If completely valid, these considerations imply that antibody will not be damaging when it recognizes only a few sites, or one site, on an antigen. This proposition is consistent with studies showing a need for greater than a million hapten molecules on a single chicken red blood cell to render the red cell susceptible to anti‐hapten IgG antibody‐dependent lysis by non‐sensitized lymphocytes, in the antibody‐dependent cellular cytotoxicity reaction . There are other situations, however, where antibody may be destructive without recognizing many sites on the antigen, such as the IgG autoantibodies specific for the acetylcholine receptor seen in myasthenia gravis.…”

Section: Evolutionary Pressuressupporting

confidence: 85%

On the Mechanism Determining the Th1/Th2 Phenotype of an Immune Response, and its Pertinence to Strategies for the Prevention, and Treatment, of Certain Infectious Diseases

Bretscher

2014

Scand J Immunol

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It is well recognized that the physiological/pathological consequences of an immune response, against a foreign or a self-antigen, are often critically dependent on the class of immunity generated. Here we focus on how antigen interacts with the cells of the immune system to determine whether antigen predominantly generates Th1 or Th2 cells. We refer to this mechanism as the ‘decision criterion’ controlling the Th1/Th2 phenotype of the immune response. A plausible decision criterion should account for the variables of immunization known to affect the Th1/Th2 phenotype of the ensuing immune response. Documented variables include the nature of the antigen, in terms of its degree of foreignness, the dose of antigen and the time after immunization at which the Th1/Th2 phenotype of the immune response is assessed. These are quantitative variables made at the level of the system. In addition, the route of immunization is also critical. I describe a quantitative hypothesis as to the nature of the decision criterion, referred to as the Threshold Hypothesis. This hypothesis accounts for the quantitative variables of immunization known to affect the Th1/Th2 phenotype of the immune response generated. I suggest and illustrate how this is not true of competing, contemporary hypotheses. I outline studies testing predictions of the hypothesis and illustrate its potential utility in designing strategies to prevent or treat medical situations where a predominant Th1 response is required to contain an infection, such as those caused by HIV-1 and by Mycobacterium tuberculosis, or to contain cancers.

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Section: Evolutionary Pressuressupporting

confidence: 85%

On the Mechanism Determining the Th1/Th2 Phenotype of an Immune Response, and its Pertinence to Strategies for the Prevention, and Treatment, of Certain Infectious Diseases

Bretscher

2014

Scand J Immunol

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“…However, the number of 'foreign sites' on, for example, cancer cells is likely in the range of a few thousand [29]. Further evidence suggests that other antibody- dependent mechanisms are only effective if there is a high density of sites on the surface of the cell that are recognised by antibody [30]. Moreover, there is also evidence that CTLs, the lytic cells of cell-mediated immunity, can attack target cells with very few recognisable sites, leading to the lysis of the target cells, whereas IgG-dependent complement-mediated lysis does not occur [31].…”

Section: The Cellular Basis Of Immune Deviation and The Definition Ofmentioning

confidence: 99%

Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections

Bretsche¹,

Ismail

Menon³

et al. 2001

CMLS, Cell. Mol. Life Sci.

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The occurrence of infectious disease represents a failure of the immune system, a failure that must be prevented by effective vaccination or remedied by treatment. Vaccination against acute diseases such as smallpox and polio are very effective, due to the rapid and increased immune response of vaccinated individuals upon natural infection. In contrast, effective vaccination against intracellular pathogens that cause chronic diseases, such as the leishmaniases, tuberculosis and AIDS, has not been achieved. Clinical observations suggest cell-mediated, Th1 responses, exclusive of antibody production and the generation of Th2 cells, are optimally protective against these intracellular pathogens. Effective vaccination must ensure the generation of such a protective response. We explore here whether understanding very broad features of the regulation of the immune response can accommodate modern findings on the immunological features of these diseases, and provide a perspective within which strategies for effective vaccination and treatment can be developed.

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“…CRBC, however, were chosen as the main target for subsequent experiments on ADCC against soluble protozoal antigens, because these have been found to be particularly satisfactory substrates for coupling a protein antigen for use on a cytotoxicity assay (27). Techniques for linking antigenic determinants to cells have included direct linkage of reactive haptens to the cell surface (10,36); coupling of protein antigens through carbodiimide or bisdiazobenzidine (27); and coupling of antigens to target cells modified by chromium chloride (18), glutaraldehyde (27), or tannic acid (28). The tannic acid method was chosen in the present experiments as a simple technique which was unlikely to alter the structure of the complex and to a certain extent undefined protozoal antigens.…”

Section: Much Of the Published Work On Cellular Effec-mentioning

confidence: 99%

“…FinaUy, some comment may be made about the antigens used for study. Until now, most workers have chosen to work with common pro-on October 10, 2020 by guest http://iai.asm.org/ Downloaded from tein antigens or hapten-protein conjugates (10,18,27,36). These systems are interesting in their own right and have certain advantages; they may, for example, be radiolabeled, allowing investigations on the the number of antigenic molecules and antibody interactions required on the target cell for cytotoxcity to occur (18).…”

Section: Much Of the Published Work On Cellular Effec-mentioning

confidence: 99%

Antibody-Dependent Cell-Mediated Cytotoxicity in Cattle: Activity Against ⁵¹ Cr-Labeled Chicken Erythrocytes Coated with Protozoal Antigens

Duffus¹,

Butterworth

Wagner

et al. 1978

Infect Immun

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Bovine mononuclear cells in the presence of bovine anti-chicken erythrocyte sera at high dilutions induce release of chromium-51 from labeled chicken erythrocytes. Bovine effector cells are capable of recognizing both bovine immunoglobulin G 1 and bovine immunoglobulin G 2 ; in contrast, human effector cells only recognize immunoglobulin G 1 . Effector cell activity of bovine mononuclear cells is equally distributed between peripheral blood and spleen. As in other species, thymus and lymph node cells exert no antibody-dependent effect, although some direct cytotoxicity by lymph node cells may be observed. Antibody-dependent cell-mediated cytotoxicity against a bovine cell line can also be detected. By using a tannic acid technique, it was found that chicken erythrocytes coated with Theileria parva piroplasm antigen or with Trypanosoma rhodesiense variant-specific coat antigen form suitable targets for bovine antibody-dependent cell-mediated cytotoxicity assays. By using such targets, a moderate degree of direct cytotoxicity by bovine mononuclear cells, in the absence of antibody, is always observed; this may be reduced by choosing optimal conditions of tannic acid treatment and antigen sensitization and by the use of short incubation periods for the cytotoxicity assay. Observations have been made on the variant specificity, time course of appearance, and association with immunoglobulin G 1 of the antibody activity responsible for cell-dependent cytotoxicity against chicken erythrocytes coated with T. rhodesiense antigens. The potential usefulness of this technique in the analysis of protective immune responses against protozoal infections is discussed.

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Influence of the antigenicity of target cells on the antibody-mediated cytotoxicity of nonsensitized lymphocytes

Cited by 12 publications

References 13 publications

On the Mechanism Determining the Th1/Th2 Phenotype of an Immune Response, and its Pertinence to Strategies for the Prevention, and Treatment, of Certain Infectious Diseases

On the Mechanism Determining the Th1/Th2 Phenotype of an Immune Response, and its Pertinence to Strategies for the Prevention, and Treatment, of Certain Infectious Diseases

Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections

Antibody-Dependent Cell-Mediated Cytotoxicity in Cattle: Activity Against ⁵¹ Cr-Labeled Chicken Erythrocytes Coated with Protozoal Antigens

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Influence of the antigenicity of target cells on the antibody-mediated cytotoxicity of nonsensitized lymphocytes

Cited by 12 publications

References 13 publications

On the Mechanism Determining the Th1/Th2 Phenotype of an Immune Response, and its Pertinence to Strategies for the Prevention, and Treatment, of Certain Infectious Diseases

On the Mechanism Determining the Th1/Th2 Phenotype of an Immune Response, and its Pertinence to Strategies for the Prevention, and Treatment, of Certain Infectious Diseases

Vaccination against and treatment of tuberculosis, the leishmaniases and AIDS: perspectives from basic immunology and immunity to chronic intracellular infections

Antibody-Dependent Cell-Mediated Cytotoxicity in Cattle: Activity Against 51 Cr-Labeled Chicken Erythrocytes Coated with Protozoal Antigens

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Antibody-Dependent Cell-Mediated Cytotoxicity in Cattle: Activity Against ⁵¹ Cr-Labeled Chicken Erythrocytes Coated with Protozoal Antigens