Cytokines characteristics

Administering large doses of antigen leads to a decrease of specific TCR and consequently, reduced release of cytokines characteristic of Thl and Th2 lymphocytes, i.e., IL 2, IFNy, IL 5, and IL 4, as a result of clonal deletion. Among other persisting T CD4 lymphocytes, reduced IL 2 receptor expression and failure to release some cytokines (IL 2, 4, 10, and/or TGFP) is observed. As a result their response to the antigen is weaker (Cohn, 2001). 

In the absence of selective antagonists, cytokines have been classified either on the basis of common functional properties or on the stmctural characteristics of their receptors. 

Chemokines are a family of small cytokines, or proteins secreted by cells. Proteins are classified as chemokines according to shared structural characteristics such as small size (8-10 kDa in size), and the presence of four... 

In the very early phases of the acute inflammatory response most of the cells invading the damaged area are polymorphonuclear neutrophils, also denoted as PMNs, which serve as initial line of defense and source of proinflammatory cytokines. These cells, which usually live for 4-5 days, circulate in the blood until they are attracted by chemokines into injured tissues. Whereas physical injury does not recruit many neutrophils, infections with bacteria or fungi elicit a striking neutrophil response. The characteristic pus of a bacterial abscess is composed mainly of apoptotic (apoptosis) and necrotic PMNs. Emigration of neutrophils from the blood starts with a process denoted as margination where neutrophils come to lie at the periphery of flowing blood cells and adhere to endothelial cells (Fig. 1). L-Selectin is expressed... 

Goldberg-Bittman L, Sagi-Assif O, Meshel T, et al. Cellular characteristics of neuroblastoma cells regulation by the ELR -CXC chemokine CXCL10 and expression of a CXCR3-like receptor. Cytokine 2005 29 105-117. 

The presence of serum-binding proteins. Some biopharmaceuticals (including insulin-like growth factor (IGF), GH and certain cytokines) are notable in that the blood contains proteins that specifically bind them. Such binding proteins can function naturally as transporters or activators, and binding can affect characteristics such as serum elimination rates. 

Recombinant DNA technology has also facilitated detailed study of cytokine receptors. Based upon amino acid sequence homology, receptors are usually classified as belonging to one of six known superfamilies (Table 8.3). Individual members of any one superfamily characteristically display 20-50 per cent homology. Conserved amino acids normally occur in discrete bands or clusters, which usually correspond to a discrete domain in the receptor. Most receptors exhibit multiple domains. In some cases a single receptor may contain domains characteristic of two or more superfamilies. For example, the IL-6 receptor contains domains characteristic of both the haematopoietic and immunoglobulin superfamilies, making it a member of both. 

Some growth factors may be classified as cytokines (e.g. interleukins, TGF-P and CSFs). Others (e.g. IGFs) are not members of this family. Each growth factor has a mitogenic (promotes cell division) effect on a characteristic range of cells. Whereas some such factors affect only a few cell types, most stimulate growth of a wide range of cells. 

Details on the cellular immune responses occurring following the recognition of xenobiotic haptens as antigens by the immune system are described in chapters 33-35 of this volume. Ultimately, a certain combination of mediators is selectively activated and subsequently helps determine and differentiate the characteristic immune response (e.g., Thl vs. Th2). For example, dermal sensitizing chemicals (e.g., oxazolone and dinitrochlorobenzene) elicit a higher proportion of Thl cytokines such as IFNy and... 

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