Immune responses, chemokines

Analysis of mouse models with genetic disruption of individual chemokines or chemokine receptors has usually revealed specific phenotypes, but generally, only under stressed conditions (infection, allograft, etc.), which suggests that the full potential of chemokine-receptor redundancy may not always be realized in vivo. Instead, under normal physiological conditions and during immune responses, chemokines and chemokine receptors appear to function as a coordinated, but vulnerable, network. 

T-cells, representing the adaptive arm of the immune response, also play a critical role in atherogenesis, and enter lesions in response to the chemokines inducible protein-10 (DP-10), monokine induced by DFN-y (MIG), and DFN-inducible T-cell a-chemoattractant (I-TAC), which bind CXCR3 (a chemokine receptor containing two cysteine residues separated by one amino acid), highly expressed by T lymphocytes in the plaque. The... 

A cascade of proteins of the immune response that can be triggered by antigen-antibody complexes and by the innate immune system (e.g. exposure to microbial polysaccharides) to raise the immune response. Complement proteins can detect and bind to foreign material or immune complexes and label them for phagocytosis. They can also cause inflammation by directly degranulating mast cells and releasing chemokines to recruit other immune cells into the affected area. 

The key end result of TLR signalling is the induction of cytokines. Cytokines are proteins produced during an immune response that allow the maturation, activation and differentiation of effector cells in the immune system. The activation of NFkB and AP-1 by the MyD88 and the TREF dependent pathways leads to the production of proinflammatory cytokines such as IL-6, TNF-a and various chemokines. This pathway can also activate IRF-7 via TLR-7and TLR-9 allowing Type-I interferons to be produced. 

Neutrophils are the most abundant leukocytes in humans, comprising about two thirds of peripheral blood leukocytes. Upon tissue injury, they rapidly infiltrate injury sites and play an important role in innate immune responses. In addition, they also contribute to the development of adaptive immune responses by producing an array of cytokines and chemokines. Tissue infiltration of neutrophils is initiated by signals generated by the interaction between chemoattractants produced at sites of injury and their corresponding cell surface receptors. Classical chemoattractants, such as C5a, N-formyl-methionyl-leucyl-... 

Fig. 4. Regulation by chemokines of recruited DC-mediated immune responses, (a) The effect of CCL21 on mDC migration in liver disease model, (b) The effect of CXCL9 on pDC migration in skin infection model.

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... 

Several opiate receptors have been identified on cells of the nervous systems of animals and humans, with mu (p), kappa (k), and gamma (y) subtypes being predominant. These classical opiate receptors are G- protein coupled 7-transmembrane molecules.27 Opiates predominantly affect immune responses directly by ligation of p, k, and y opiate receptors, as well as non-classical opiate-like receptors, on immune cells and indirectly by binding to receptors on CNS cells. Studies conducted in vitro with opiate-treated immune cells demonstrated receptor-mediated reduced phagocytosis, chemotaxis and cytokine and chemokine production. These effects are linked to modulation of host resistance to bacterial, protozoan, viral and fungal infections using animal models, cell lines and primary cells. 

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