Immunogenetics of reproduction: an overview.
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Genetic linkage between the HL-A and Bf loci could be confirmed in 43 families with 168 offspring. In 4 families, 5 recombinants out of 82 informative meiotic divisions were observed (r = 6.1%). The localisation of the Bf marker system was studied in 3 families with crossovers between HL-A and MLC. From these data the following map order of human chromosome 6 can be proposed: HL-A (1st locus) -- HL-A (2nd locus)--MLC-Bf---PGM(3). The fact that important components of the classical and alternate pathway of complement activation are governed by genes closely linked with HL-A and MLC loci leads to the proposition to include the Bf system into the Major Histocompatibility Complex in man.
A purified, extracellular protein, M. W. 17500, from group A streptococci was used in an in vitro model to study genetic aspects of immune responsiveness. Peripheral blood lymphocytes from members of eight nuclear families and one kindred of three generations were isolated and purified by F-icoll-Isopaque flotation and cultured together with varying concentrations of antigen. A summary measure of the antigen response data (measured as CPM) was constructed through a weighted regression analysis of response on dose. Commingling analysis of the standardized regression coefficients provided evidence for the existence of two underlaying distributions. Segregation analysis confirmed that response to this antigen is controlled by a major gene and is inherited in an autosomal dominant manner.
The 1985 Catalog of Mapped Genes (Human Gene Mapping 8; 33) has been used to pick out the known, immunologically important genes; these are then discussed in the following order: genes controlling organs, tissues and cells of the immune apparatus, genes determining 'self' structures, genes determining the structures of immunological specificity, genes determining substances with immunoregulatory and effector properties. The symbols for the genes and the biological functions of their products are explained. The genetics of the ABO blood groups, of the HLA-system and of antibody formation are given in rather more detail.
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The major histocompatibility complex (MHC) comprises approximately one thousandth of the genome and encompasses its most polymorphic members. This diversity enables the MHC, at the population level, to counteract the extraordinarily diverse microbiological threats. Reviewed here are two separate sets of MHC class I genes: MIC and RAET1. Whilst the former are encoded within the MHC (6p21.3), the latter are located on the opposite arm of the same chromosome (6q24.2-q25.3). Differing from the prototypical class I genes in structure, transcription, diversity and potential function, they both exemplify the versatility of the MHC fold, despite convergence onto a single ligand, the activatory C-type lectin-like receptor, NKG2D. Why the immune system uses two distinct gene families to interact with a unique ligand remains a fascinating question. To answer this question, the reader will be chronologically exposed to the field whilst following a single thread, i.e. genomics and gene diversity.
Host-parasite relationships represent integrating adaptations of considerable complexity involving the host's immune capacity to both recognize and destroy the parasite, and the latter's ability to successfully invade the host and to circumvent its immune response. Compatibility in Drosophila-parasitic wasp (parasitoid) associations has been shown to have a genetic basis, and to be both species and strain specific. Studies using resistant and susceptible strains of Drosophila melanogaster infected with virulent and avirulent strains of the wasp Leptopilina boulardi demonstrate that the success of the host cellular immune response depends on the genetic status of both host and parasitoid. Immunological, physiological, biochemical, and genetic data form the bases of a two-component model proposed here to account for the observed specificity and complexity of two coevolved adaptations, host nonself recognition and parasitoid virulence.
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The association of rheumatoid arthritis (RA) with the HLA complex has been well established since 1978. But what does that mean? After reminding the reader of some existing immunological interpretations, a more recent variant is introduced. Antigens and molecular chaperones of the HSP70 family form complexes, which interact with HLA-DR beta-chains, especially of the DRB1*0401 genotype, which is the most common among patients with RA in our region. This mechanism might bring *0401(+) persons an advantage in defence against microorganisms, but a disadvantage concerning autoimmunity. Chaperone machines are upregulated in synovial tissue of RA patients. As their number and variety is huge in humans, there exist many possibilities for function, reaching from antigen presentation to immune regulation. In addition to the HLA complex, the "genetic background" plays an important role for the development of an autoimmune disease. This is demonstrated in families of patients with RA or scleroderma, where a high percentage of first degree relatives suffer from a "related" disease.
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The poultry immune system is a complex system involving many different cell types and soluble factors that must act in concert to give rise to an effective response to pathogenic challenge. The complexity of the immune system allows the opportunity for genetic regulation at many different levels. Cellular communication in the immune response, the production of soluble factors, and the rate of development of immune competency are all subject to genetic influences. The genes of the major histocompatibility complex (MHC) encode proteins which have a crucial role in the functioning of the immune system. The MHC antigens of chickens are cell surface glycoproteins of three different classes: Class I (B-F), Class II (B-L) and Class IV (B-G). The MHC antigens serve as essential elements in the regulation of cell-cell interactions. The MHC has been shown to influence immune response and resistance to autoimmune, viral, bacterial and parasitic disease in chickens. The MHC has been the primary set of genes identified with genetic control of immune response and disease resistance, but there are many lesser-characterized genes outside of the MHC that also regulate immunoresponsiveness. Polygenic control has been identified in selection experiments that have produced lines of chickens differing in antibody levels or kinetics of antibody production. These lines also differ in immunoresponsiveness and resistance to a variety of diseases. Understanding the genetic bases for differences in immunoresponsiveness allows the opportunity selectively to breed birds which are more resistant to disease. Indirect markers that can be used for this selection can include the MHC genes and immune response traits that have been associated with specific or general resistance to disease.
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