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==Actions==
==Actions==
===Phagocytosis===
===Phagocytosis===
<p>Macrophages are [[Phagocytosis|phagocytic]] and take up particles and cell debris by endocytosis, as well as engulfing pathogens like bacteria through the specialist function of [[Phagocytosis|phagocytosis]]. These are then present in the macrophage inside phagosomes. Lysosomes present in the cytoplasm then bind with the phagosome and release their contents which degrade/digest its contents. The degradation of the lysosomal contents occurs in much the same way as [[Neutrophils|neutrophils]] with both oxygen-dependent and oxygen-independent mechanisms.</p>
<p>Macrophages are [[Phagocytosis|phagocytic]] and take up particles and cell debris by endocytosis, as well as engulfing pathogens like bacteria through the specialist function of [[Phagocytosis|phagocytosis]]. These are then present in the macrophage inside phagosomes. Lysosomes present in the cytoplasm then bind with the phagosome and release their contents which degrade/digest its contents. The degradation of the lysosomal contents occurs in much the same way as [[Neutrophils|neutrophils]] with both oxygen-dependent and oxygen-independent mechanisms.</p>
<p>Oxygen dependant killing requires the production of reactive oxygen species (ROS)(O<sub>2</sub><sup>-</sup>), hydrogen peroxide (OH), reactive nitrogen species (RNS) (nitric oxide (NO)) and chlorine (Cl*) free-radicals that damage bacterial membranes (OH + Cl* = HOCl (otherwise known as bleach!)) . These reactive species are generated during a burst of respiration following [[Phagocytosis|phagocytosis]] where increased amounts of oxygen are produced. Hydrochloric acid (HCl) is also produced during this process.</p>
<p>Oxygen dependant killing requires the production of reactive oxygen species (ROS)(O<sub>2</sub><sup>-</sup>), hydrogen peroxide (OH), reactive nitrogen species (RNS) (nitric oxide (NO)) and chlorine (Cl*) free-radicals that damage bacterial membranes (OH + Cl* = HOCl (otherwise known as bleach!)) . These reactive species are generated during a burst of respiration following [[Phagocytosis|phagocytosis]] where increased amounts of oxygen are produced. Hydrochloric acid (HCl) is also produced during this process.</p>
<p>Oxygen independent killing uses lysosomes, cathepsin (a protease) and other mechanisms. Lysozymes are particularly effective against gram positive bacteria as they hydrolyse the glycopeptide coating of the bacterial organisms. </p>
<p>Oxygen independent killing uses lysosomes, cathepsin (a protease) and other mechanisms. Lysozymes are particularly effective against gram positive bacteria as they hydrolyse the glycopeptide coating of the bacterial organisms. </p>
===Antigen Presentation===
===Antigen Presentation===
<p>Macrophages also act as '''antigen presenting cells''' taking antigens to lymph nodes to present to T cells. MHC II ([[Major Histocompatability Complexes|major histocompatibility complex]] II) proteins on their surface allow them to interact with helper T cells (CD4). Short peptide segments from foreign cells are presented with MHC II which activates the [[T cells|T cell]] as part of the nadaptive immune response.</p>
<p>Macrophages also act as '''antigen presenting cells''' taking antigens to lymph nodes to present to T cells. MHC II ([[Major Histocompatability Complexes|major histocompatibility complex]] II) proteins on their surface allow them to interact with helper T cells (CD4). Short peptide segments from foreign cells are presented with MHC II which activates the [[T cells|T cell]] as part of the nadaptive immune response.</p>
<p>To migrate through connective tissue they release proteases and glycoaminoglycanases.</p>
===Immune System Regulation===
Macrophages are important players in orchestrating the various parts of the immune response. Tissue macrophages are responsible for the trigger of the innate immune response to an injury by releasing pro-inflammatory [[Cytokines|cytokines]], in particular IL-1β, IL-6 and TNF-α, that are responsible for the activation of the endothelium of post-capillary venules that allows neutrophils and other immune cells to adhere and extravasate (move out of the blood). With interactions with [[Mast Cells|Mast cells]] they amplify the release of vasoactive peptides including histamine and bradykinin that are responsible for the five signs of inflammation (
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===Chemotaxis===
Macrophages are needed throughout the inflammatory response to perform their functions, with phagocytosis and the initiation of the inflammatory response by encouraging neutrophil extravasation, right through to the resolution of inflammation and/or the initiation of the adaptive immune response. At each of the stages of inflammation there are specific chemoattractants that the macrophages respond to. When the injury first occurs, it is the peptides released by bacteria (in particular formylated Met-Leu-Phe) and [[Cytokines|cytokines]] release by cells adjacent to the injury that bring the tissue macrophages into contact with the injured site. At the later stages, it is cytokines released by immune cells themselves that bring blood monocytes (blood macrophages) to the injury, beginning the adaptive immune response.
<p>To migrate through connective tissue they release proteases and glycoaminoglycanases through a process called exocytosis (granule fusion with the plasma membrane).</p>
===Role in pathology===
===Role in pathology===
<p>Macrophages are seen in both [[Acute Inflammation|acute]] and [[Chronic Inflammation| chronic inflammation]].</p> If large numbers of macrophages are found in chronic inflammatory processes, it implies the inability to eliminate the causal organism e.g. [[:Category:Mycobacterium species|Mycobacterium (TB)]], [[:Category:Actinobacillus species|Actinobacillus]], fungi, parasites and foreign bodies.
<p>Macrophages are seen in both [[Acute Inflammation|acute]] and [[Chronic Inflammation| chronic inflammation]].</p> If large numbers of macrophages are found in chronic inflammatory processes, it implies the inability to eliminate the causal organism e.g. [[:Category:Mycobacterium species|Mycobacterium (TB)]], [[:Category:Actinobacillus species|Actinobacillus]], fungi, parasites and foreign bodies.