Major histocompatibility complex genes and evidence for their occurrence in the tilapia, Oreochromis niloticus
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2-6-4 (1), CBD
3.1.2.3 Antigen presenting cellsThe activation of both the humoral and cell-mediated branches of the immune system depends on the production of lymphokines from TH cells. The TH cells can be activated following antigen recognition only when the antigen is displayed together with MHC on the surface of specialized cells called antigen-presenting cells (APCs). The antigen presenting cells include macrophages, B cells, and dendritic cells; these are distinguished by their expression of a particular type of MHC molecule. These specialized cells internalize antigen, either by phagocytosis or by endocytosis, and then re-express a part of that antigen, together with the MHC molecules, on their membrane. The TH cell then recognises the antigen associated with the MHC molecule on the membrane of the antigen-presenting cell. Antigens which are generally very large and complex, are not recognised in their entirety by T or B lymphocytes. Instead, both T and B lymphocytes recognise discrete sites on the antigen called antigenic determinants, or epitope. Epitopes are the immunologically active regions on a complex antigen, the regions that actually bind to B or T cell’s receptor. A comparison of the amino acid sequences of the VL and VH domains of B cell receptor reveal that the amino acid sequence variability is concentrated in several hypervariable regions. These regions form the antigen binding site of the antibody molecule. Because the antigen-binding site is complementary to the structure of the epitope, the hypervariable regions are also called complementary-determining regions (CDRs). The most important difference in antigen recognition by T lymphocytes and B lymphocytes is that B cells can recognise an epitope alone, whereas T cells can only recognise an epitope when it is present on the surface of a self-cell in association with an MHC molecule. For a T cell to recognise a foreign protein antigen, it must be degraded into small peptides that form physical complexes with a class I or class II MHC molecule. This conversion of proteins into MHC-associated peptide fragments is called antigen processing. Figure 3.1 presents the schematic diagram of the cellular immune system (cited from Kuby, 1997). Exogenous antigens (e.g. bacteria, parasites) are internalized by phagocytosis or endocytosis of antigen-presenting cells. Macrophages can internalize antigen by both processes, whereas most other APCs are not phagocytic or are poorly phagocytic and therefore internalize exogenous antigen only by endocytosis (either receptor-mediated endocytosis or pinocytosis). After internalized an antigen, it is degraded into peptide fragments within compartments of the endocytic processing pathway where the class II MHC molecules are expressed. The endocytic processing pathway appears to involve three increasingly acidic compartments : early endosomes (pH 6.0-6.5); late endosomes or endolysosomes (pH 5.0-6.0); and lysosomes (pH 4.5-5.0). The internalized antigen moves from early to late endosomes and finally to lysosomes, encountering hydrolytic enzymes and an increasingly low pH in each compartment. The antigen is degraded into oligopeptides in the compartments of the endocytic pathway and bind to the class II MHC molecules. The MHC class II molecule bearing the peptide is then exported to the cell surface where it is recognised by CD4+ TH cells (Lanzavecchia, 1990). CD4+ binds to the β2 domains of class II MHC molecules. After recognising and forming a complex with an antigen-MHC class II molecules, the TH cell becomes activated, begins to divide and give rise to a clone of effector cells. Each of the effector cells is specific for the same antigen-class II MHC complex. These effector cells secrete lymphokines which activate B cells. The B cells then divide and differentiate into plasma cells that secrete antibody proteins. The soluble antibody molecules bind to the antigen and neutralize them or precipitate their destruction by complement enzyme. Endogenous antigen is produced within the host cell itself. Viral proteins are synthesised within virus-infected host cells. Endogenous antigens are thought to be degraded into peptide fragments that bind to class I MHC molecules within the endoplasmic reticulum. The peptide-MHC complex is then transported to the cell membrane and recognised by CD8+ TC cells (Bjorkman and Parham, 1990). Like CD4+, CD8+ binds to the α3 domain of MHC class I molecule. After forming a complex with antigen-class I MHC molecule, TC cell proliferates and differentiates into CTL. The CTLs are activated by interaction with an antigen-MHC class I complex on the surface of an altered self-cell and kill it. In the killing process the CD8+ T cells secrete some cytotoxic substances such as perforin present in the granules, which produce lesions in the membranes of target cells and lyse them. Download 1.2 Mb. Share with your friends:
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