Immune Response Genes in the Regulation of Mammalian Immunity

Berzofsky, Jay A.

doi:10.1007/978-1-4684-9933-9_10

Cited by 30 publications

(6 citation statements)

References 533 publications

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“…Several months later, these mice were shown to have no detectable residual F] lymphoid cells in the spleen, but only donor B6 cells that had repopulated the mouse. A number of groups have shown that such low responder T cells, which have matured in an Ft thymus, are tolerant to high responder alloantigens and can also cooperate with high responder B cells and APC in an antigen-specific response (2,21). To be sure that Fa as well as low responder APC were present in vivo, these mice were injected intravenously with 40 X I06 F1 SAC at the time of immunization.…”

Section: (High Responder X Low Responder)f1 Mb-immunieed T Cells Helpmentioning

confidence: 99%

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mentioning

confidence: 99%

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Genetic control of immune response to myoglobin. Ir gene function in genetic restriction between T and B lymphocytes.

Kohno¹,

Berzofsky²

1982

The Journal of Experimental Medicine

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Over the past decade, hypotheses regarding the site of Ir gene action have changed considerably (1, 2). The original, widely held concept (3) that/r genes were expressed in T cells gave way to the belief that they were expressed in antigen-presenting cells (APC) 1 of the macrophage-monocyte-dendritic cell lineage, or at the very least, in T cell-APC interactions. The B cell, which actually produces the antibodies, was given a relatively minor role. Some authors (4) presented evidence that the B cell played no role at all, that everything could be explained solely on the basis of T cell interaction with the APC. Others (5, 6) presented evidence that the B cell played a role parallel to that of the APC in that T cells were genetically restricted to interact with high but not low responder B cells as well as APC. This controversy was at least partially resolved by the discovery (7, 8) that T cell help for Lyb5-B cells was genetically restricted, whereas that for Lyb5 + B cells was not. These and related studies led to the hypothesis that, what the T cell saw first on the APC (a certain combination of antigen and Ia), it must see reproduced on the B cell to mediate help (9, 10). Most of these studies involved synthetic repeating polypeptide antigens, such as (T,G)-A--L.We have been studying the genetic control of the immune response to a natural globular protein antigen, sperm whale myoglobin (Mb), and have found that the in viva antibody response (11), the in vitro T cell response (12), and the in vitro antibody response (13) are all controlled by at least two/r genes mapping in distinct subregions, I-A and I-C, of the H-2 complex. These genetically separable genes control responses to chemically distinct determinants on the same antigen molecule (12, 13). In the case of T cell proliferation, we found that the selection of which antigenic determinant was stimulatory for (high responder × low responder)F1 T cells depended on the /r genes of the strain from which the APC were obtained (14). Thus, the Ir gene restriction of T ceI1-APC interaction led to what had been described by Rosenthal et al. (3) as "determinant selection." However, we wished to explore the cellular interactions involved in regulating antibody production rather than T cell proliferation. To do so, we recently developed (13) an in vitro culture system in which we can measure soluble Mb-specific antibody * Present address:

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Section: (High Responder X Low Responder)f1 Mb-immunieed T Cells Helpmentioning

confidence: 99%

“…

…”

mentioning

confidence: 99%

Genetic control of immune response to myoglobin. Ir gene function in genetic restriction between T and B lymphocytes.

Kohno¹,

Berzofsky²

1982

The Journal of Experimental Medicine

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“…fowl y-globulin) coupled to myoglobin, overcome the Ir gene-controlled low responsiveness. Thus, the antibody response to myoglobin controlled by Ir genes seems to be dependent on helper T cell activation, as seen in many other studies (14,15), but not known on B cell repertoire.…”

Section: Resultsmentioning

confidence: 67%

Immunization with antigen and interleukin 2 in vivo overcomes Ir gene low responsiveness.

Kawamura¹,

Rosenberg²,

Berzofsky³

1985

The Journal of Experimental Medicine

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We studied the effect of purified interleukin 2 (IL-2), made by recombinant DNA techniques, on the serum antibody response to myoglobin in high- and low-responder mice. Previous studies (6, 7) have shown that this response is controlled by H-2-linked Ir genes. The IL-2 was emulsified with the antigen in complete Freund's adjuvant to provide a sustained high local concentration. In low-responder B10.BR mice, a single dose (optimum 50,000 U) resulted in a consistent 10-50-fold increase in specific serum antibody throughout the time course of the response, from 10 d to 46 d after immunization. In contrast, no effect of IL-2 was seen in congenic high-responder B10.D2 mice. With IL-2, the low-responder mice achieved specific antibody levels comparable to those of high responders. Vehicle alone had no effect, and IL-2 alone, without antigen, did not induce myoglobin-specific antibody. No effect of IL-2 was seen in athymic nude mice of high-responder H-2 haplotype. The effect of IL-2 may be on a small number of responding T cells in the low responder mice, but it is possible that IL-2 also acts directly on B cells in a response that remains T-dependent, and therefore is not observed in athymic mice. We suggest that IL-2 may enhance suboptimal T cell help in the low responder, whereas help is not limiting in the high responder. This approach may enable the study of antibody responses in low responders otherwise too weak to analyze, and may be useful in producing antibodies to poorly immunogenic antigens. Potential clinical uses include immunization with weak antigens in normal patients, or with any antigen in certain immunodeficient patients.

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“…Indeed, many studies have looked for associations between genes involved in immunity and disease outcome (Buniello et al 2019) and it has been found that certain immune response (Ir) genes play the crucial role.This concept was discovered in the mid-1960s (McDevitt andBenacerraf, 1969) and this discovery introduced an apparently new level of antigen recognition whose diversity and specificity had to be explained in addition to those of familiar immunoglobulins. Hence immune response (Ir) genes were defined as antigenspecific genes that control the ability of an animal to raise an immune response, either humoral or cellular to a particular antigen (Berzofsky, 1980). This includes Major Histocompatibility Complex (MHC I, II and III), Interleukins (IL-6, IL-β), Tumor necrosis factor (TNF-), cluster of differentiation (CD-14) and Toll like Receptor (TLR-4), which are responsible for conferring innate immunity.…”

Section: Understanding Immunogeneticsmentioning

confidence: 99%

Livestock Breeding for Disease Resistance: A Perspective Review

Gogoi

Das

Chabukdhara

et al. 2021

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Livestock plays a momentous role in a country’s economy especially in a developing nation like India, where livelihoods of about 20.5 million people depend upon livestock and its allied sectors, suggesting that about two-third of the rural community is involved (Annual Report, 2018). The small ruminants like sheep and goat provide main source of income for many economically poor people, especially marginal and landless farmers. Similarly the role of these livestock to various pastoral communities cannot be ignored. So whenever there is a disease outbreak, the burden of huge economic loss falls on these poor livestock keepers. The traditional methods of disease management involve either treatment with antibiotics or vaccination for prevention of diseases. However, the indiscriminate use of these antibiotics has lead to antibiotic-resistant pathogens and likewise it is extremely difficult to develop vaccines against a wide range of pathogens that are frequently mutating and are caused by multi etiological factors. Hence, considering all these factors breeding of disease resistant animals becomes a top priority in this changing world. The literature is filled with references of indigenous animals and poultry being resistant to many diseases. Keeping this in view, the current review has been written to highlight sustainable and feasible methods for breeding them for disease resistance.

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Immune Response Genes in the Regulation of Mammalian Immunity

Cited by 30 publications

References 533 publications

Genetic control of immune response to myoglobin. Ir gene function in genetic restriction between T and B lymphocytes.

Genetic control of immune response to myoglobin. Ir gene function in genetic restriction between T and B lymphocytes.

Immunization with antigen and interleukin 2 in vivo overcomes Ir gene low responsiveness.

Livestock Breeding for Disease Resistance: A Perspective Review

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