Mhc And

The MHC is a genetic locus which spans 4 Mb in the p21 region of chromosome 6 and is responsible for controlling the immune response. Encoded in this region are several classes of proteins referred to as HLA, which are divided into three groups: class I, class II, and class III. The HLA class I molecules are designated HLA-A, HLA-B, or HLA-C and are encoded by genes of the MHC, which participate in antigen presentation to cytotoxic T (CD8+) cells. The HLA class II molecules are designated DP, DQ, or DR and are encoded by genes of the MHC, which participate in antigen presentation to helper T (CD4+) cells. The HLA class III region is located within the HLA region because its components are related to the functions of HLA antigens, or are under control mechanisms similar to the HLA genes. HLA class III contains loci responsible for complements, hormones, and intracellular peptide processing and other developmental characteristics.1-2-1 HLA class I and class II genes play an important role in the communication between cells, determining whether transplanted tissue or bone marrow is histocompatible (accepted as self) or histoincompatible (rejected as foreign), and are thought to be functionally significant in disease susceptibility.

The expression of all MHC loci is codominant; both the set of alleles inherited from one's father and the set inherited from one's mother are expressed on each cell. In most cases, the entire linked MHC, called a haplotype, is inherited intact, without recombination.1-3-1 Research has indicated that individuals with certain allelic genotypes may be at higher risk for developing diseases affecting the immune system. Because both alleles contribute to the phenotype equally, it is important to investigate the genotypes in disease association studies rather than alleles on their own.

There are three standard levels of HLA typing: low, medium, and high. Low-resolution typing defines broad families of alleles. Medium-resolution typing helps determine that the individual has one of the many alleles within a low-resolution group and eliminates others. Highresolution typing is an effort to definitively state which allele resides at a locus for an individual.1-4-1 Solid organ transplant programs work well with low-resolution typing, whereas bone marrow programs require high resolution.

The HLA system has the greatest degree of polymorphism in the human genome. As of August 2003, there were over 1600 alleles recognized at the classical loci (Table 1).[5- Mutations and polymorphisms are constantly being identified, making HLA typing for donor and recipient matching in transplantation increasingly complex and creating the need for analytical tools to detect genetic patterns potentially related to disease. The completion of the human genome project has given scientists the ability to identify genomic variation in cells and tissues quantitatively, simultaneously, and automatically under a variety of conditions using high-throughput microarray analysis.[6-

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