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| Macrophage |
• Macrophages are tissue histiocytes or differentiated monocytes that are capable of phagocytosis.
• They also synthesize and secrete various cytokines (e.g., interleukin-1 [IL-1], tumor necrosis factor-a [TNF-a], IL-6, IL-8, and IL-12).
• High yield fact: Septic shock is caused by TNF - a released by macrophages in response to LPS.
What happens during phagocytosis?
In simple terms, phagocytosis, as the name suggests, is the process (-osis) that devours (phago-) the cell (cyto-).
Steps involved in phagocytosis of a microbe:
Chemotaxis
• It means moving towards a target microbe. (Imagine a leukocyte catching a taxi towards the microbe.)
• Chemokines are small proteins that induce directed chemotaxis. There are a wide variety of chemokines.
• Leukotriene B4, complement fragment C5a, IL-8 and the bacterial N-formyl peptides are a few examples.
• Mnemonic: Before (B4) going, make sure you can See five (C5a) clearly In Light (IL8) and form peptides (N-formyl peptides).
Attachment
• As the name suggests, in this step the phagocyte attaches to the microbe.
• Leukocytes recognize surface receptors (such as opsonins) on the microbes, and initiate the process of phagocytosis.
• Opsonization is a process in which the antibody marks the pathogen for elimination. (Opsonins make the microbe yummy for phagocytes)
Ingestion and Engulfment
• This next step includes ingesting of that microbe and enveloping it, which forms the phagosome.
• This phagocytic vacuole (phagosome), then fuses with lysosomes to form a phagolysosome.
Digestion and Degradation
• The step of degradation takes place with the help of microbicidal substances such as reactive oxygen species (ROS), nitric oxide (NO), and lysosome enzymes, which digests and kills the microbe.
There are two processes by which the phagocyte kills the microbe:
Oxygen dependent killing mechanism
• During phagocytosis, a metabolic process results in the activation of a membrane-bound oxidase (NADPH oxidase, also called phagocyte oxidase) that reduces oxygen to superoxide anion, which is extremely toxic to ingested microorganisms.
• The NADP oxidase reaction results in a transient increase in oxygen consumption by the cell, which is known as the respiratory burst. (Mnemonic: Oxidase grants super powers to oxygen. Let’s call super oxide anion – super man!)
• The superoxide anion is converted by the enzyme superoxide dismutase into H2O2. (Mnemonic: Superman is mutated by dismutase into a double-headed monster, H2O2!)
• From H2O2, a number of reactive oxygen intermediates can be formed such as hydroxyl radical, hypochlorite, and hypobromite.
Oxygen independent killing mechanism
• Activated macrophages produce lysozyme and various hydrolytic enzymes that do not require oxygen.
• Macrophages also synthesize a group of antimicrobial and cytotoxic peptides, known as defensins.
What activates the macrophages?
• Phagocytosis activates the macrophages.
• The mediators of inflammation can further enhance activity of macrophages.
• The most potent activator of macrophages is interferon gamma (IFN-Y) secreted by activated TH1 cells.
What are the different types of macrophages?
Macrophage-like cells serve different functions in different tissues and are named according to the tissue they are located in:
• Alveolar macrophages in the lung
• Histiocytes in connective tissues
• Kupffer cells in the liver
• Mesangial cells in the kidney
• Microglial cells in the brain
• Osteoclasts in bone
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• They also synthesize and secrete various cytokines (e.g., interleukin-1 [IL-1], tumor necrosis factor-a [TNF-a], IL-6, IL-8, and IL-12).
• High yield fact: Septic shock is caused by TNF - a released by macrophages in response to LPS.
What happens during phagocytosis?
In simple terms, phagocytosis, as the name suggests, is the process (-osis) that devours (phago-) the cell (cyto-).
Steps involved in phagocytosis of a microbe:
Chemotaxis
• It means moving towards a target microbe. (Imagine a leukocyte catching a taxi towards the microbe.)
• Chemokines are small proteins that induce directed chemotaxis. There are a wide variety of chemokines.
• Leukotriene B4, complement fragment C5a, IL-8 and the bacterial N-formyl peptides are a few examples.
• Mnemonic: Before (B4) going, make sure you can See five (C5a) clearly In Light (IL8) and form peptides (N-formyl peptides).
Attachment
• As the name suggests, in this step the phagocyte attaches to the microbe.
• Leukocytes recognize surface receptors (such as opsonins) on the microbes, and initiate the process of phagocytosis.
• Opsonization is a process in which the antibody marks the pathogen for elimination. (Opsonins make the microbe yummy for phagocytes)
Ingestion and Engulfment
• This next step includes ingesting of that microbe and enveloping it, which forms the phagosome.
• This phagocytic vacuole (phagosome), then fuses with lysosomes to form a phagolysosome.
Digestion and Degradation
• The step of degradation takes place with the help of microbicidal substances such as reactive oxygen species (ROS), nitric oxide (NO), and lysosome enzymes, which digests and kills the microbe.
There are two processes by which the phagocyte kills the microbe:
Oxygen dependent killing mechanism
• During phagocytosis, a metabolic process results in the activation of a membrane-bound oxidase (NADPH oxidase, also called phagocyte oxidase) that reduces oxygen to superoxide anion, which is extremely toxic to ingested microorganisms.
• The NADP oxidase reaction results in a transient increase in oxygen consumption by the cell, which is known as the respiratory burst. (Mnemonic: Oxidase grants super powers to oxygen. Let’s call super oxide anion – super man!)
• The superoxide anion is converted by the enzyme superoxide dismutase into H2O2. (Mnemonic: Superman is mutated by dismutase into a double-headed monster, H2O2!)
• From H2O2, a number of reactive oxygen intermediates can be formed such as hydroxyl radical, hypochlorite, and hypobromite.
Oxygen independent killing mechanism
• Activated macrophages produce lysozyme and various hydrolytic enzymes that do not require oxygen.
• Macrophages also synthesize a group of antimicrobial and cytotoxic peptides, known as defensins.
What activates the macrophages?
• Phagocytosis activates the macrophages.
• The mediators of inflammation can further enhance activity of macrophages.
• The most potent activator of macrophages is interferon gamma (IFN-Y) secreted by activated TH1 cells.
What are the different types of macrophages?
Macrophage-like cells serve different functions in different tissues and are named according to the tissue they are located in:
• Alveolar macrophages in the lung
• Histiocytes in connective tissues
• Kupffer cells in the liver
• Mesangial cells in the kidney
• Microglial cells in the brain
• Osteoclasts in bone
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