Immune response major histocompatibility complex

Homo sapiens (compared to Drosophila melanogaster) Large-scale gene duplications with substantial expansion of genes involved in acquired immune response (B cells, T cells, major histocompatibility complex genes, cytokines, chemokines and their receptors), plasma proteases (complement and hemostatic proteins), proteins associated with apoptotic regulation and proteins related to neuronal network formation and electrical coupling... 

Immunoglobulins (Igs) can activate the complement system, which amplifies the immune response by enhancing chemotaxis, phagocytosis, and release of lymphokines by mononuclear cells that are then presented to T lymphocytes. The processed antigen is recognized by the major histocompatibility complex proteins on the lymphocyte surface, resulting in activation of T and B cells. 

The Major Histocompatibility Complex. The molecules making up the major histocompatibility complex (MHC) were first discovered through their ability to provoke rejection response when tissues from one individual were transplanted to another individual of the same species. Quite apart from the MHC s contribution to the difficulties of transplant surgery, in recent years it has become abundantly clear that the MHC plays a major role in the operation of T cell immunity, particularly in its function of presenting antigen to the T cell receptor. 

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. 

Fig. 11.1. Principle of an immunological synapse. Possibilities for communication between B and T cells during an immune response. Antigenic peptides are presented by the MHC complex class II at the surface of the B cell. The antigens are recognized and bound by T cell receptors of the T cell. The T cell receptor is activated and sets a signal chain in motion that leads to activation of the expression of cytokines, such as IL-2. The cytokine is secreted, and binds and activates a cytokine receptor on the B cell. TNFa is shown as another example of a ligand-receptor system. TNFa communicates, as a membrane-bound ligand, with a corresponding receptor on the surface of the B cell. The interactions shown take place in a narrow spatial region between B and T cells, which is why this system is referred to as an immunological synapse. TNF tumor necrosis factor MHC major histocompatibility complex IL-2 interleukin 2.

This provides potential defensive proteins directed at almost every imaginable invader. It also ensures that every individual has a set of proteins that labels its own cells as "self," and that virtually every individual on earth has cell surface proteins different from those of every other person. In both the innate and adaptive responses the immune system must carefully distinguish "self" from "nonself."36 37 In the innate system this discrimination developed during evolution of the host and its pathogens. In the adaptive system it depends upon interaction of the T cells with surface molecules, primarily those of the major histocompatibility complex (MHC). 

---