Chemokines adaptive immunity role

Beyond roles of chemokine receptors in hematopoiesis and innate immunity, roles for chemokines in adaptive immunity emerged. Moreover, other nonleukocyte migration properties of chemokine receptors have been identified. These include roles in the biology of endothelial cells (Chapter 15), cancer (Chapter 16), smooth muscle (Chapter 11), fibroblasts (Chapter 14), stem cells (Chapter 8), and all cell types associated with nervous system tissues (Chapter 17). In many instances, broad functional overlap is evident as chemokines can direct the migration of these cells just as they do with leukocytes. In certain instances, the ability of chemokines to retain cell populations within a specific microenvironment is as important as their migration-promoting properties. However, it is also clear that migration and retention are not the sole end points. 

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-... 

Luster AD. The role of chemokines in linking innate and adaptive immunity. Curr Opin Immunol 2002 14 129-135. 

Chemokines play an essential role in linking the innate and adaptive immune responses by orchestrating leukocyte trafficking. The chemokine system consists of a group of small polypeptides and their receptors. Chemokines possess four conserved cysteines. Based on... 

It is a paradigm that a major role of proinflammatory chemokines is to mobilize innate and adaptive immune responses against infectious agents. However, some observations are difficult to reconcile with this paradigm. For example, interferons suppress the production of IL-8, and IL-8 in turn suppresses the antiviral activity of IFNa in association with a reduction... 

Chemokines induce directed chemotaxis in nearby responsive cells. They are released from various cells in response to bacteria and viruses infection and in response to agents that cause physical damage such as silica or urate crystals. The main functions of chemokines are chemoattractants for leukocytes. They help to recruit monocytes, neutrophils, and other effector cells from the blood to the sites of infection or damage. They serve to guide cells involved in innate immunity and in the adaptive immune system. Some chemokines have other roles in the development of lymphocytes, migration, and the growth of new blood vessels. 

Peters W, Dupuis M, Charo IF. A mechanism for the impaired IFN-gamma production in C-C chemokine receptor 2 (CCR2) knockout mice role of CCR2 in linking the innate and adaptive immune responses. J Immunol 2000 165 7072-7077. 

T cells are bone marro v-derived lymphocytes. There are six different types of Tcells identified in humans helper T cells (Th), cytotoxic T cells (Tc), memory T cells, regulatory T cells (Treg), natural killer T cells (NKT) and yb T cells. AD types have different roles in the adaptive immune systems and consequentiaUy distinct chemokine receptor expression patterns. 

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... 

Phage display can be adapted to investigate further the interaction between a chemokine and a CKBP such as those used in this study. The adaptation of phage display to the identification of protein pharmacophore is however Hmited to small proteins but most soluble proteins which play a role as immune messengen, cytokines, chemokines, growth factors, etc., should be susceptible to such an approach. 

Chemokines regulate the migration of cells in vivo and dysregulated expression of chemokines and their receptors are implicated in autoimmune and inflammatory diseases. Inflammatory arthritides, such as rheumatoid arthritis (RA), are characterized by the recruitment of inflammatory cells into joints. The K/BxN serum transfer mouse model of inflammatory arthritis shares many similar features with RA. In this autoantibody-induced model of arthritis, neutrophils are the critical immune cells necessary for the development of joint inflammation and damage. In this review, we describe the use of several methods to study the role of chemoattractant receptors, including chemokine receptors, on the recruitment of neutrophils into the joint in the K/BxN model of inflammatory arthritis. This includes both traditional methods, such as flow cytometry, immunohistochemistry, and enzyme assays, as well as multiphoton in vivo microscopy that we have adapted to study the role of immune cell trafficking in and around the joint in live mice. 

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