240
is one of the crucial entities linking innate and adaptive immune responses and thus
imparts immunomodulatory activities in both branches of immune response.
Complement components could mediate several immune activities, including stimulation of T cells and antibody activities, removal of self-reactive B cells, and augmentation of immunologic memory. Components of the complement system are
synthesized in pro form and later activated on demand via three diverse pathways.
The antigen–antibody complex (usually IgM or IgG) initiates the classical pathway
and C5 split product is generated from C5 by C5 convertase in the classical pathway. Alternative pathway is activated by microbial surfaces and complex polysaccharides (yeast cell walls, endotoxins, or viral particles), and C3 is converted into
C3a and C3b by the C3 convertases. These split products C5b, C6, C7, C8, and C9
associate to form a macromolecular membrane attack complex (MAC) and directly
lyze the target cell by opsonization. Complement split products can carry out a
number of crucial functions such as disintegrating bacteria, damaged cells, and
immune complexes from circulation, accelerating the phagocytosis process via
opsonization, and eliciting the release of immunoregulatory molecules. Components
of the complement can be produced from many cells such as hepatocytes, monocytes, macrophages, etc. The three anaphylatoxins—C3a, C4a, and C5a—released
during the cascade of enzymatic cleavage are potential inflammatory mediators.
The anaphylatoxins mediate smooth-muscle contraction and increase vascular permeability and aid in histamine release. Extravasation and chemotaxis of leukocytes
at the inflammatory site is promoted by C3a, C5a, C5b, C3a, C5a, and C5b6.
Activation of the complement system results in influxes of fluid that carries antibodies and phagocytic cells to the site of antigen entry. Some of the active split products
of complement regulate immune response by directly or indirectly acting on the
effectors of immune response. C3a molecules suppress immune response by acting
through macrophages. C3b inhibits leukocyte extravasation, thereby directly modulating immune reactions. On the other hand, C5a augments antibody production and
also indirectly activates T-cell proliferation. The production of LPS-induced IL-6 is
found to be regulated via C5a. Similarly, complement activation is inherently regulated by interfering in the dissociation or association of C3 convertase. The key
endogenous proteins involved in the regulation of complement include factor 1,
factor H, CR1 (complement receptor 1), CR2 (complement receptor 2), MCP (membrane cofactor protein), DAF (decay acceleration factor), etc. (Sarma and Ward
2011).
10.2.2 Histamine and Its Receptors
Histamine is a potent vasoactive amine which plays a crucial function in early stages
of inflammation. It is produced by basophils and mast cells via decarboxylation of
the amino acid histidine. Its primary function is vasodilation, and thus regulates
many physiological processes involving dilation of vessels and muscles, such as
B.C. Bhavya and M. Haridas
is one of the crucial entities linking innate and adaptive immune responses and thus
imparts immunomodulatory activities in both branches of immune response.
Complement components could mediate several immune activities, including stimulation of T cells and antibody activities, removal of self-reactive B cells, and augmentation of immunologic memory. Components of the complement system are
synthesized in pro form and later activated on demand via three diverse pathways.
The antigen–antibody complex (usually IgM or IgG) initiates the classical pathway
and C5 split product is generated from C5 by C5 convertase in the classical pathway. Alternative pathway is activated by microbial surfaces and complex polysaccharides (yeast cell walls, endotoxins, or viral particles), and C3 is converted into
C3a and C3b by the C3 convertases. These split products C5b, C6, C7, C8, and C9
associate to form a macromolecular membrane attack complex (MAC) and directly
lyze the target cell by opsonization. Complement split products can carry out a
number of crucial functions such as disintegrating bacteria, damaged cells, and
immune complexes from circulation, accelerating the phagocytosis process via
opsonization, and eliciting the release of immunoregulatory molecules. Components
of the complement can be produced from many cells such as hepatocytes, monocytes, macrophages, etc. The three anaphylatoxins—C3a, C4a, and C5a—released
during the cascade of enzymatic cleavage are potential inflammatory mediators.
The anaphylatoxins mediate smooth-muscle contraction and increase vascular permeability and aid in histamine release. Extravasation and chemotaxis of leukocytes
at the inflammatory site is promoted by C3a, C5a, C5b, C3a, C5a, and C5b6.
Activation of the complement system results in influxes of fluid that carries antibodies and phagocytic cells to the site of antigen entry. Some of the active split products
of complement regulate immune response by directly or indirectly acting on the
effectors of immune response. C3a molecules suppress immune response by acting
through macrophages. C3b inhibits leukocyte extravasation, thereby directly modulating immune reactions. On the other hand, C5a augments antibody production and
also indirectly activates T-cell proliferation. The production of LPS-induced IL-6 is
found to be regulated via C5a. Similarly, complement activation is inherently regulated by interfering in the dissociation or association of C3 convertase. The key
endogenous proteins involved in the regulation of complement include factor 1,
factor H, CR1 (complement receptor 1), CR2 (complement receptor 2), MCP (membrane cofactor protein), DAF (decay acceleration factor), etc. (Sarma and Ward
2011).
10.2.2 Histamine and Its Receptors
Histamine is a potent vasoactive amine which plays a crucial function in early stages
of inflammation. It is produced by basophils and mast cells via decarboxylation of
the amino acid histidine. Its primary function is vasodilation, and thus regulates
many physiological processes involving dilation of vessels and muscles, such as
B.C. Bhavya and M. Haridas