Lakhasly

THE ACUTE-PHASE RESPONSE

In contrast to the local effects of inflammation described earlier, the acute-phase response is a rapid, systemic increase in various plasma proteins in response to innate inflammation.Upon binding, these host proteins can enhance complement activation (see Chapter 63) and phagocytosis (i.e..Finally, many acute-phase proteins increase the migration of new neutrophils and other leukocytes from the bone marrow and enhance their homing, phagocytic, and microbicidal functions.

THE ACUTE-PHASE RESPONSE

In contrast to the local effects of inflammation described earlier, the acute-phase response is a rapid, systemic increase in various plasma proteins in response to innate inflammation. Together, these cause systemic symptoms of fever, malaise, elevated heart rate, and loss of appetite that we commonly associate with infection. As described earlier, macrophages and other cells that are triggered through their PRRs assemble inflammasomes in their cytoplasm, and these multiprotein complexes cut IL-1 from its inactive precursor into its active form before it is released. IL-6 and TNF-a are also made by macrophages in response to IL-1 and PRR stimulation.

IL-1, IL-6, and TNF-a are proinflammatory cytokines, meaning that they enhance the inflammatory response in various ways . They signal to the hypothalamus to change the body's thermostat, causing fever. They also signal to the liver hepatocytes to increase production of C-reactive protein, MBL, proteins of the complement cascade (covered in Chapter 63), ferritin, and other acute-phase proteins. Mast cells can directly sense microbial patterns through PRRs or through receptors for antibodies (i.e., IgE receptors), or can be stimulated by IL-1 to release IL-6, leukotrienes, vasoactive signals, and other proinflammatory mediators.

Some of the acute-phase proteins are anticoagulants that improve blood flow to inflamed tissues. Other acute-phase proteins, such as ferritin, sequester iron, which bacteria need for replication, or bind to the surface of bacteria and activate complement, which can kill the bacteria. For example, as mentioned earlier, MBL binds to mannan (mannose) on the surface of many bacteria, fungi, and protozoa, and C-reactive protein similarly binds to other components of the cell walls of micro-organisms. Upon binding, these host proteins can enhance complement activation (see Chapter 63) and phagocytosis (i.e.. act as opsonins). Finally, many acute-phase proteins increase the migration of new neutrophils and other leukocytes from the bone marrow and enhance their homing, phagocytic, and microbicidal functions.