244
receptors with immune- and hematopoietic-related functions. The members of this
receptor family possess four conserved cysteine residues and sequence motif comprising tryptophan–serine–(any amino acid)–tryptophan–serine residues in the
extracellular domain. The class II cytokine receptors possess the conserved CCCC
motifs, but lack the WSXWS motif present in class I cytokine receptors (class I
cytokine) and lack tyrosine kinase domain for signaling activity. IL-2, IL-3, IL-4,
IL-5, IL-6, IL-7, IL-9, IL-11, and IL-12 are the ligands for class I receptors, and
IFN-α and IL-10 are the ligands for class II receptor family. TNF receptor family
allows the binding of ligands such as TNF-α and TNF-β, CD 40, and nerve growth
factor. Chemokine receptor family has the affinity toward IL-8, RANETS, MIP1
(macrophage inflammatory protein), PF4 (platelet factor), etc.
Binding of a cytokine to the respective receptors induces dimerization of the
receptor subunits, which leads to the activation of Janus kinase (JAK) by reciprocal
phosphorylation. Activated JAK phosphorylates various tyrosine residues of the
downstream signaling kinases, such as signal transducer and activator of transcription (STATs), their dimerization, and translocation to the nucleus, where they activate transcription of specific genes important in inflammation or immunomodulation.
The secretion of cytokines and chemokines from cells is a fundamental response to
injury and infection in the body. A wide range of cell types secrete cytokines including epithelial and endothelial cells. Innate immune cells such as macrophages/
monocytes, dendritic cells (DCs), natural killer (NK) cells, mast cells, eosinophils,
and neutrophils release a range of cytokines and regulate the immune response to
injury or infection. T lymphocytes are the principal immune cells that secrete
inflammatory and immunomodulatory cytokines in the adaptive immune response.
Cytokine secretion integrates innate and adaptive immunities and thus regulates the
overall immune response (Banyer et al. 2000).
Chemokines are an important class of cytokines with multiple potential. They
are obsessed with chemotactic ability. Broadly chemokines are classified on the
basis of their specificity toward receptors. The elevated levels of chemokines are
often associated with a variety of tumor malignancies and many autoinflammatory
and immune disorders as well. Chemokine receptors are considered as potent therapeutic targets in several immune disorders with inflammatory background, such as
rheumatoid arthritis (RA), inflammatory bowel disorders (IBD), allergic diseases,
and cancer. The elevated levels of chemokines are often associated with a variety of
tumor malignancies and many autoinflammatory and immune disorders as well.
10.3 Chronic Inflammation and Onset of Immune-Related
Malignancies
Chronic inflammation is an extended low-grade inflammatory response, often initiated when the acute inflammatory response fails to eliminate the invader or reestablish homeostasis. The shift from acute to chronic inflammation involves the
participation of many components of the immune system with the commencement
of adaptive immune response. Thus, chronic inflammatory response can act as a
B.C. Bhavya and M. Haridas
receptors with immune- and hematopoietic-related functions. The members of this
receptor family possess four conserved cysteine residues and sequence motif comprising tryptophan–serine–(any amino acid)–tryptophan–serine residues in the
extracellular domain. The class II cytokine receptors possess the conserved CCCC
motifs, but lack the WSXWS motif present in class I cytokine receptors (class I
cytokine) and lack tyrosine kinase domain for signaling activity. IL-2, IL-3, IL-4,
IL-5, IL-6, IL-7, IL-9, IL-11, and IL-12 are the ligands for class I receptors, and
IFN-α and IL-10 are the ligands for class II receptor family. TNF receptor family
allows the binding of ligands such as TNF-α and TNF-β, CD 40, and nerve growth
factor. Chemokine receptor family has the affinity toward IL-8, RANETS, MIP1
(macrophage inflammatory protein), PF4 (platelet factor), etc.
Binding of a cytokine to the respective receptors induces dimerization of the
receptor subunits, which leads to the activation of Janus kinase (JAK) by reciprocal
phosphorylation. Activated JAK phosphorylates various tyrosine residues of the
downstream signaling kinases, such as signal transducer and activator of transcription (STATs), their dimerization, and translocation to the nucleus, where they activate transcription of specific genes important in inflammation or immunomodulation.
The secretion of cytokines and chemokines from cells is a fundamental response to
injury and infection in the body. A wide range of cell types secrete cytokines including epithelial and endothelial cells. Innate immune cells such as macrophages/
monocytes, dendritic cells (DCs), natural killer (NK) cells, mast cells, eosinophils,
and neutrophils release a range of cytokines and regulate the immune response to
injury or infection. T lymphocytes are the principal immune cells that secrete
inflammatory and immunomodulatory cytokines in the adaptive immune response.
Cytokine secretion integrates innate and adaptive immunities and thus regulates the
overall immune response (Banyer et al. 2000).
Chemokines are an important class of cytokines with multiple potential. They
are obsessed with chemotactic ability. Broadly chemokines are classified on the
basis of their specificity toward receptors. The elevated levels of chemokines are
often associated with a variety of tumor malignancies and many autoinflammatory
and immune disorders as well. Chemokine receptors are considered as potent therapeutic targets in several immune disorders with inflammatory background, such as
rheumatoid arthritis (RA), inflammatory bowel disorders (IBD), allergic diseases,
and cancer. The elevated levels of chemokines are often associated with a variety of
tumor malignancies and many autoinflammatory and immune disorders as well.
10.3 Chronic Inflammation and Onset of Immune-Related
Malignancies
Chronic inflammation is an extended low-grade inflammatory response, often initiated when the acute inflammatory response fails to eliminate the invader or reestablish homeostasis. The shift from acute to chronic inflammation involves the
participation of many components of the immune system with the commencement
of adaptive immune response. Thus, chronic inflammatory response can act as a
B.C. Bhavya and M. Haridas