Immunogenetics is an interdisciplinary subject of immunology and genetics. It mainly studies the genetic basis of the structure and function of the immune system such as immune response and antibody immunization diversity. In addition, immunological methods are also applied to identify genetic differences between individuals (such as blood type, surface antigen, etc.) as an indicator of genetic law analysis. Immunogenetics is one of the important theoretical foundations of modern medical clinical practice. It is the theoretical basis of blood transfusion, organ transplantation, fetal incompatibility and paternity testing. It is also important for clarifying the evolution of the immune system, ethnic differences and biological evolution.
Antigen inheritance
Leukocyte antigen
In 1936, P.A. Goll detected four erythrocyte antigens in mice using rabbit anti-mouse erythrocyte serum. He crossed the antigen-positive mouse strain with the antigen-negative mouse strain, and then backcrossed the offspring to the antigen-negative mouse strain, back-crossing progeny or antigen II positive or negative. Tumors were rejected when antigens from antigen-II positive mice were transplanted to antigen II negative progeny; tumors were not rejected when transplanted to antigen II positive progeny, demonstrating that antigen II is a histocompatibility antigen (H-2) , controlled by a single gene. It was further discovered that H-2 specificity can be detected on lymphocytes, and the study of leukocyte antigens was initiated. It was later demonstrated that the histocompatibility antigen of mice is not controlled by a single gene but by several closely linked genes. Many of these genes constitute the major histocompatibility complex (MHC), which is located on mouse chromosome 17, and is divided into K, I, S, G, D/L, and T6 regions. The major histocompatibility complex of the human body is called human leukocyte antigen, or HLA for short. The composite locus that determines HLA is on the short arm of chromosome 6, and there are several seats in A, C, B, and D/DR. Each seat has many codominant multiple alleles. The corresponding gene complexes of monkeys and dogs are called RhLA and DLA, respectively.
Antigen inheritance of other animals
The proteins of various animal cells are antigenic substances, and the differences of these proteins can be detected by immunological methods, thereby revealing their genetic mechanism. For example, anti-serum using rabbit anti-grass fragments, it was found that each parasitic strain can synthesize about 10 different specific surface antigens. The double-small paramecium has s, g, and d major genes controlling its surface antigens S, G, and D. These genes are not linked. These surface antigens are controlled by nuclear genes, but their expression is affected by temperature. The s gene is expressed at 15 to 18 ° C, and the g gene is expressed when the s gene is turned off with an increase in temperature, and the d gene is expressed at a temperature of about 30 to 32 ° C. Different genotypes of different geographical distributions, such as the g genes of lines 156 and 168, can encode different antigens 156G and 168G, but when individuals of these different lines are joined to form a hybrid, although their genotypes are the same (both 156g/168g) ), the temperature conditions at the time of culture are also the same (30 ° C), but the clonal propagation line of the hybrid genus Parasitic worm belonging to the 156 strain expresses the antigen G, and the clonal propagation line of the hybrid genus of the 168 strain expresses the antigen. D. This heterozygote with the same genotype has different phenotypes under certain circumstances, and the phenomenon that can be passed through asexual reproduction is called post-genetic phenomenon. The nature of post-genetic inheritance is both a matter of genetic immunization and immunology that is not fully solved.
Antibody inheritance
Antibody molecule composition
An antibody molecule is an immunoglobulin consisting of two light chains and two heavy chains. Both the light chain and the heavy chain can be divided into a variable region (V) and a constant region (C) according to the degree of amino acid sequence variation. Higher animals and humans are capable of producing an extremely large number of immunoglobulins of different specificities. Is there so many light chain genes and heavy chain genes in every individual? This has puzzled geneticists. Burnet's clonal selection doctrine answers this question at the cellular level. According to this theory, each plasma cell can produce only one or a few antibodies, and the numerous plasma cells of an individual can produce countless kinds of antibody molecules together.
Chromosome combination
A wide variety of plasma cells are differentiated from lymphocytes. Using gene constructs, molecular hybridization and nucleotide sequence analysis techniques, it was found that the light and heavy chains of immunoglobulin molecules are encoded by several isolated gene segments or exons. On the chromosome that determines the light chain, there are four types of gene fragments of L, V, J, and C. There are about 150 kinds of V fragments (variable fragments), and about 5 types of J fragments (linking fragments), and one type of L fragment (guide fragment) and C fragment (constant fragment). During lymphocyte differentiation, these gene segments are rearranged and ligated together to be transcribed. Different combinations of rearrangements and flexibility of the V/J linker can result in approximately 7,500 (150 x 5 x 10) light chain genes. On the chromosome that determines the heavy chain, there are five kinds of gene fragments of L, V, D, J, and C. Among them, there are 1 L fragment, 80 kinds of V fragments are estimated, 50 kinds of D fragments (diversity fragments), 6 kinds of J fragments, and 8 kinds of C fragments. The V/D and D/J connectors are estimated to have 10 possibilities each. The eight C fragments determine the class of immunoglobulins, ie, lgM, lgD, lgG3, lgG1, lgG2b, lgG2a, lgE or lgA, which have the same variable region for the same antigenic determinant. The flexibility of rearrangement and adaptor can result in 2.4 million (80 x 50 x 6 x 10 x 10) heavy chain genes. The combination of light and heavy chains can produce 18 billion (750 x 2400000) immunoglobulin molecules. If you add a possible somatic mutation (estimated mutation rate is 1/10000 cells/generation), the diversity of bound antibodies can be expanded.
Although the source of antibody diversity has been described at the cellular and molecular levels, there are still many issues to be resolved. It is known that a plasma cell produces only one specific antibody molecule, and its allele is not expressed in a hybrid state. The mechanism of this allelic rejection is still unknown. The exact process for chromosomal rearrangement is now known to be rare.
No comments:
Post a Comment