10.4 Поліморфізм гкг

МНК є поліалельним і полігенним. Комбінація всіх алелей і локусів у комплексі називається гаплотипом.

10.5 Структура молекул гкг

10.5.1 Молукули класу і

Молекули MHC класу І експресуются на клітинній поверхні і являють собою гетеродимер, що складається з одного важкого альфа-ланцюга (45 кда), нековалентно зв'язаного з однодоменним бета-2-мікроглобуліном (12 кда), що зустрічається також у вільній формі в сироватці крові – їх називають класичними трансплатаційними антигенами.

Важкий ланцюг складається з позаклітинної частини (що утворює три домени: альфа1, альфа 2 і альфа 3 домени), трансмембранного сегменту і цитоплазматичного домену. Кожен позаклітинний домен містить приблизно 90 амінокислотних залишків.

10.5.2 Молекули класу іі

Молекули антигенів гістосумісності класу ІІ (DR, DP, DQ) також як і класу І є гетеродимерними білками, що складаються з важкого альфа-ланцюга (33-35 кДа) і легкого бета-ланцюга (28-30 кДа). Обидва ланцюги формують по два домени: альфа 1 і альфа 2, а також бета 1 і бета 2 (обидва варіабельні).

10.6 Суперродина імуноглобулінів

У систему імуноглобулінподібних гомологів включені молекули Т-клітинного антигенрозпізнаючого комплексу, молекули І і ІІ класів МНС , корецептори Т-клітин Т4 і Т8, однодоменні білки - Thy-1. Гомологічні молекули складають суперродину імуноглобулінів.

Summary

Immunogenicity is the property of a molecule that allows it to induce an immune response. Antigenicity is the ability of a molecule to react with antibody.

Haptens are molecules that are not immunogenic unless conjugated to a carrier but that are able to react with anti-hapten antibody. Using hapten-anti-hapten systems, landsteiner showed that chemical nature of the hapten affected its antigenicity.

The antigenicity of protein is determined by its sequence of amino acids as well as by its conformation. Peptide sequences with high segmental mobility are frequently antigenic.

The combined use of monoclonal antibody, computer-generated graphics, and X-ray crystallography is making molecular-antigenic mapping of complex structures possible.

Antibodies of predetermined specificity can be made by immunizing an animal with synthetic peptides. In this manner vaccines of desired specificity should be able to be made in future.

Antibodies are found in the -globulin fraction of serum and are called immunoglobulins (Ig).

Treatment of Ig with the proteolytic enzyme papaine results in Fab and Fc fragments. Fab has the Ag binding capacity of the molecule and Fc fragment binds complement.

The basic Ig monomer is composed of two heavy (H) and two light (L) chains, which are joined by, inter chain bonds. H and L chains are composed of variable and constant regions. Within the variable regions are hypervariable regions, which are also called complementarity - determining regions (CDR). Antibody diversity is generated by amino acid substitutions that occur within the hypervariable regions and result in unique antigen-binding structures.

Igs are extremely heterogeneous molecules, differing in size, charge, and antigenicity.

There are five classes, or isotypes, called IgG, IgM, IgA, IgD and IgE.

Because both H and L chains of Ig molecules consists variable and constant regions, it was proposed that the molecule is encoded by two genes. Comparing the Ig genes of embryos and antibody producing cells shows that the two gene one polypeptide hypothesis is basically correct; that is, antigen specificity comes about through the joining of gene segments in the potential antibody-forming cells. One V segment of several carried in the germ line is joined with one of several J segments to form a complete L chain V –region gene. The joining of gene segments that result in combinatorial diversification occurs at palindromic sequences in the DNA and follows the heptamer-nonamer. During an antibody response, the class of Ig switches, usually from IgM to IgG.

All methods of determining of presence, amount, or location of antigen or antibody depend on identifying or quantifying the Ag/Ab complex. Ag/Ab reactions in which the antigen is soluble form precipitates. When the Ag is particulate formation of the Ag/Ab complex results in an agglutination reaction. Modern methods of quantifying and localizing the Ag/Ab complex rely very heavily on labeling one of the reactants. Radioactive, Western blot and immunofluorescent assays are the most commonly used, but electron-dense labels are very useful in immunoelectron microscopy.

The complement system is a series of serum components that have the ability to combine with the Ag/Ab complex. The complement components act as a cascade. There are three pathways: the classical, alternate and central or common.

Hemopoiesis is the study of blood cell formation. Stem cells are assayed by an in vivo colony-forming assay and are called CFU-S (colony forming units, spleen). Each colony is derived from a single cell.

The thymus is a primary lymphoid organ composed of lymphocytes and epithelial cells. Pre-T cells enter the thymus via the blood and differentiate into thymic lymphocytes (thymocytes). Lymphocytes circulate between the blood and the lymphatic vascular systems. They leave the venous circulation to enter the lymph nodes through vessels lined with specialized endothelia, called high endothelial venules (HEV). Lymphocytes are distributed in T- and B- dependent areas of the spleen and lymph nodes.

The major histocompatibility complex (MHC) is a complex of genes that encodes molecules involved in various aspects of the immune response. Some of the Ags encoded by MHC are expressed by members of more than one haplotype and are called public specificities. Other MHC antigens are expressed only by members of given haplotype and are called private specificities.