Immune receptors

Immune receptors that recognize the Fc (fragment, ciystallizable) of antibodies when bound to pathogen, thereby exerting effector ftmctions such as phagocytosis or antibody-dependent cell-mediated cytoxicity. 

Syk and ZAP-70 are early intermediates in the transduction of signals from immune receptors, including the B- and T-cell recqrtors for antigen, activatory natural killer-cell receptors, the mast cell and basophil receptor for IgE, and the widely distributed receptors for the Fc portion of IgG. Immune receptors control checkpoints in lymphocyte development and serve to integrate the responses of innate and acquired immunity. 

Consistent with their role as immune receptors, each human TLR is expressed by at least one subset of myeloid cells (MCs) or lymphocytes [7,8]. TLRs are also present on stromal elements like endothelium particularly after local inflammatory stimulus [9-11]. These distribution patterns can determine the physiological consequences of stimulation or antagonism, and affect the balance of toxicity versus therapeutic effect. Another consideration for medicinal chemistry is subcellular localization of TLRs. While most are expressed on the cell surface, some (TLRs 3,7,8, and 9) can localize to endosomes where they survey ingested material for ligands, so drug access to this compartment can be crucial when targeting these TLRs [12]. 

Shen, Q. FI., Saijo, Y., Mauch, S., Biskup, C., Bieri, S., Keller, B., Seki, FI., Ulker, B., Somssich, I. E. and Schulze-Lefert, P. (2007). Nuclear activity of MLA immune receptors links isolate-specific and basal disease-resistance responses. Science 315, 1098-103. 

Goldstein B, Faeder JR, Hlavacek WS (2004) Mathematical and computational models of immune-receptor signalling. Nat Rev Immunol 4 445 56... 

Figure 3 Speciai mechanisms of NHR. (a) Teiomere failure unmasks chromosome ends for fusion by NHEJ, which leads to potentially iterative cycles of breakage and fusion before ultimate stable telomere resolution. Oval, centromere rectangle, telomere, (b) Immune receptor loci contain multiple V, J, and sometimes D segments with signal sequences (triangles) that are cleaved by RAGl /2 and subjected to NHEj to generate recombined products. Engagement of an inappropriate chromosome can lead to RAGl /2-dependent chromosomal rearrangement.

Ledembi e M, Hao W, Liu Y, Walter S, Milialjevic I, Rivest S, Hartmann T, Fassbender K (2007) Innate immune receptor expression in normal brain aging. Neuroscience 146(1) 248—254. 

Collagen signals through the same pathway as that of immune receptors. It induces phosphorylation on tyrosine on Fc receptor y-chain (FcRy), the non-receptor tyrosine kinase Syk and phospholipase Cy2 (PLCy2) . 

PIchler WJ, Beeler A, Keller M, Lerch M, Posadas S, Schmid D, Spanou Z, Zawodniak A, Gerber B Pharmacological Interaction of drugs with Immune receptors the p-l concept. Allergol Int 2006 55 17-25. 

Gerber BO, Pichler WJ Noncovalent interactionsof drugs with immune receptors may mediate drug-induced hypersensitivity reactions. Aaps J 2006 8 El 60-5. 

Nevertheless, the potential for autoimmune disease would clearly exist if one considers the polyspecificity of immune recognition molecules such as B cell receptors, antibodies, T cell receptors and MHC molecules. Further, the polyspecificity of immune receptors is also able to transcend the biochemically defined classes of biomolecules. For instance, the monoclonal antibody SYA/J6 has been demonstrated to have a dual specificity, binding a specific carbohydrate or a specific peptide with comparable affinity.68 Detailed analysis of the interatomic interactions between the antibody combining site and either the carbohydrate or the peptide antigens demonstrated that functional mimicry is possible without exact structural mimicry. This example underlines the case that it is not possible to predict with certainty whether the molecular surfaces of all potentially cross-reactive epitopes, whether of foreign or self molecules, will, or will not, be able to bind to a specific antibody. 

Differential expression of the monocyte innate immunity receptor complex defining monocyte subpopulations... 

Fig. 1 The innate immunity receptor complexes in inflammation (SIRS/Sepsis) and cardiovascular disease. The basic cluster includes specific and nonspecific opsonin recognition sites (ex vivo, control) whereas Ugand-induced clustering is dependent on ligand surface composition (LPS/LTtA or ceramide/HSP70 and atherogenic LDL). (Adapted from Pfeiffer et al. 2001)...

Miller YI, Chang MK, Binder CJ, et al. (2003a) Oxidized low density lipoprotein and innate immune receptors. Curr Opin Lipidol 14 437 45... 

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