MHC-II-antigen

The class II cytokine receptor family includes receptors for interferon a/P (lEN a/P) and y (lENy) and IL-10. lEN-y immunoreactivity has been found in neurons in the hypothalamus, cerebral cortex, mammilary nuclei, and dorsal tegmentum. Astrocytes and microglia in vitro can be stimulated to express class II histocompatibiHty complex (MHC-II) antigens by lEN-y, which may be involved in the presentation of antigen to T-ceUs by astrocytes. Thus lEN-y may be critical in CNS-immune function and dysfunction especially in regard to neuronal and gHal apoptotic processes. 

The MHC II antigen complex on the cell surface of also contains two polypeptide chains, a and /3. The extracellular polypeptide of the two chains each consists of two domains, al and a2 and pi and pi. Similar to the MHC I complex, the peptide lies in a groove between the a i and a2 domains. The structure of a human MHC II protein and the CLIP peptide is shown in Figure 35-15. As noted earlier. Recognition of the MHC Il-peptide complex by... 

Antigen-presenting cells (APCs) are cells of the immune system that are able to process and present foreign antigens to effector cells. The antigen is presented in the context of an MHC-I or MHC-II molecule on APCs in the presence of so-called costimulatory molecules to activate the effector cells. 

In the specialized environment of secondary lymphoid tissues such as lymph nodes or spleen, dendritic cells provide the requirements for naive T-lymphocytes to become activated and to proliferate. The professional antigen-presenting cells present peptides in MHC II, express costimulatory molecules, and release cytokines into the immunological synapse, which is formed by the antigen-presenting cell and the naive T-lymphocyte. Thus, cells of innate immunity initiate and facilitate the activation of naive lymphocytes, and it is easily conceivable that their cytokines and adhesion molecules will instruct the naive T-lymphocyte during activation and differentiation to T-effector cells. 

Thl Soluble Antigen presented by MHC II Clonal expansion CD4Thl Thl cells activated, release cytokines, activate macrophages, inflammation Tuberculin Rx, contact dermatitis, berylliosis... 

Th2 soluble Antigen presented by MHC II Clonal expansion CD4 Th2 Th2 cells activated Help for IgE production eosinophil and mast cell activation Chronic allergic rhinitis and asthma... 

Suda T, Sato A, Sugiura W, Chida K (1995) Induction of MHC class II antigens on rat bronchial epithelial cells by interferon-gamma and its effect on antigen presentation. Lung 173(2) 127-137. 

Communication requires a signal and a signal receiver. Signal receivers are termed receptors. We have seen two examples the antigen-specific receptors on B cells and the receptors on T cells which recognize Class II MHC processed antigen complexes on the surface of B cells, two more examples of molecular recognition. 

Figure 17.18 Roles of APC, MHC-II and T-helper cell. The APCs phagocytose bacteria, digest them, and transfer the resultant pepb des plus MHC-II proteins to the surface of APC. The role of this is to present the pepb de, as an antigen, to the Th cells. The binding activates Th cells which then secrete cytokines. The activated Th cells now proliferate to produce many more identical Th cells to bind more of the antigens on the APCs. The roles of the cytokines are discussed below.

Figure 17.36 The allergic response. A protein that enters the body is taken up by an ARC, digested and the peptides presented along with MHC-II protein on cell surface. This peptide binds to its complementary receptor on the Th2 cell, which produces cytokines that stimulate B-cells to proliferate and produce plasma cells that secrete IgE antibodies. The latter bind to mast cells. This is the process of sensitisation. Upon subsequent exposure to the antigenic protein, the antigens bind to the IgE antibodies on the mast cells to produce degranulation. This results in release of the factors that cause the allergic response. If degranulation is massive the response will be severe resulting in anaphylactic shock.

Finally, in this brief overview of lymphocyte defects, mention should be made of mutations affecting major histocompatibility-complex (MHC) Class II molecules. These mutations affect a multiprotein transcription factor complex that regulates the expression of MHC Class II molecules (121). Affected patients have undetectable levels of MHC Class II antigens HLA-DP, DQ, and DR on the surface of monocytes and B cells. Lack of these antigen-presenting molecules leads to impaired immune response. Affected individuals have moderate lymphopenia with a severely reduced number of CD4+ T cells and normal or increased numbers of CD8+ T cells. Since MHC molecules in the thymic epithelium play a key role in positive and negative selection of primitive T cells, selection of competent T cells is also affected in the absence of MHC Class II antigens. 

To initiate a T-cell immune response, antigen presenting cells have to display antigenic peptides com-plexed with the major histocompatibility complex (MHC) on their cell surface. The T-cell receptor of CDS cells is specific for the peptide-MHC class I complex while the CD4 cell receptor binds the peptide-MHC class II complex. This binding of the peptide-MHC II complex stimulates CD4 cell proliferation and subsequent lymphokine release. This CD4 cell response can initiate a delayed hypersensitivity reaction. However CD4 activation and the production of various lymphokines is also needed for the generation of cytotoxic T-cells and for the differentiation of plasma cells from B-lymphocytes and the antibody response by these plasma cells. For their role in also the humoral immune response CD4 cells are called T-helper cells. 

Inappropriate expression of class II MHC molecules on the membranes of cells that normally do not express class II MHC (eg, islet beta cells). Increased expression of MHC II may increase presentation of self peptides to T helper cells, which in turn induce CTL, TDTH, and B-lymphocyte cells that react against self antigens. 

Extracellular antigens are detected by APCs, such as lymphocytes, macrophages, and dendritic cells in interstitial fluid and blood. These detect the hapten and engulf the whole antigenic complex. Then, when inside the APC, the complex is partly dismantled and peptides attached to proteins similar to immunoglobulins, known as MHC II. The modified peptide-hapten complex is moved to the surface of the APC and presented as a complex with MHC to T-helper cells (CD4+), which activates and instructs the APC to make antibodies to the hapten and also B cells (memory cells with "memory" of the hapten) to proliferate. These events lead to types I to III responses. 

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