A macrophage of a mouse stretching its "arms" (Pseudopodia) to engulf two particles, possibly pathogens

Macrophages (Greek: "big eaters", from makros "large" + phagein "eat") (mø^[1]) are cells within the tissues that originate from specific white blood cells called monocytes. A mouse (plural mice) is a small Animal that belongs to one Pseudopods or pseudopodia (from the Greek word ψευδοπόδια, ψευδός "fake false" Greek (el ελληνική γλώσσα or simply el ελληνικά — "Hellenic" is an Indo-European language, spoken today by 15-22 million people mainly Monocyte is a type of Leukocyte, part of the Human body 's Immune system. Monocytes and macrophages are phagocytes, acting in both non-specific defense (or innate immunity) as well as specific defense (or cell-mediated immunity) of vertebrate animals. Phagocytes are cells that are found in the blood bone marrow and other tissues of Vertebrates. Immune system|Adaptive immune systemThe innate immune system comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner Cell-mediated immunity is an Immune response that does not involve Antibodies or complement but rather involves the activation of Macrophages Their role is to phagocytose (engulf and then digest) cellular debris and pathogens either as stationary or mobile cells, and to stimulate lymphocytes and other immune cells to respond to the pathogen. Phagocytosis is the cellular process of engulfing solid particles by the Cell membrane to form an internal Phagosome, or "food vacuole A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious A lymphocyte is a type of White blood cell in the Vertebrate Immune system.

Life cycle

When a monocyte enters damaged tissue through the endothelium of a blood vessel (a process known as the leukocyte adhesion cascade), it undergoes a series of changes to become a macrophage. Monocyte is a type of Leukocyte, part of the Human body 's Immune system. The endothelium is the thin layer of cells that line the interior surface of Blood vessels forming an interface between circulating Blood in the The blood vessels are part of the Circulatory system and function to transport Blood throughout the body Leukocyte extravasation is the movement of Leukocytes out of the Circulatory system, towards the site of tissue damage or infection Monocytes are attracted to a damaged site by chemical substances through chemotaxis, triggered by a range of stimuli including damaged cells, pathogens, histamine released by mast cells and basophils, and cytokines released by macrophages already at the site. Chemotaxis, a kind of Taxis, is the phenomenon in which bodily cells bacteria, and other single-cell or Multicellular organisms direct their movements Histamine is a Biogenic amine involved in local immune responses as well as regulating physiological function in the gut and acting as a Neurotransmitter A mast cell (or mastocyte) is a resident cell of several types of tissues and contains many granules rich in Histamine and Heparin Cytokines are a category of signalling Proteins and Glycoproteins that like Hormones and Neurotransmitters, are used extensively in cellular At some sites such as the testis, macrophages have been shown to populate the organ through proliferation.

Unlike short-lived neutrophils, the life span of a macrophage ranges from months to years.

Function

Steps of a macrophage ingesting a pathogen:
a. Ingestion through phagocytosis, a phagosome is formed
b. The fusion of lysosomes with the phagosome creates a phagolysosome; the pathogen is broken down by enzymes
c. A phagolysosome is a membrane-enclosed Organelle which is formed from the fusing of a Lysosome and a Phagosome. Waste material is expelled or assimilated (the latter not pictured)
Parts:
1. Assimilation is the process of taking digested food which is circulating the body and then using it to help rebuild cells Pathogens
2. A pathogen (from Greek πάθος pathos "suffering passion" and γἰγνομαι (γεν- gignomai (gen- "I give birth to" infectious Phagosome
3. In cell biology a phagosome is a Vacuole formed around a particle absorbed by Phagocytosis. Lysosomes
4. Lysosomes are Organelles that contain Digestive enzymes (acid Hydrolases. Waste material
5. Cytoplasm
6. The cytoplasm is the contents of a cell that is enclosed within the Plasma membrane. Cell membrane

Phagocytosis

Main article: Phagocytosis

One important role of the macrophage is the removal of necrotic debris and dust in the lungs. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer Phagocytosis is the cellular process of engulfing solid particles by the Cell membrane to form an internal Phagosome, or "food vacuole Necrosis (in Greek Νεκρός = "dead" is the name given to unnatural Death of cells and living tissue. lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive Removing dead cell material is important in chronic inflammation as the early stages of inflammation are dominated by neutrophil granulocytes, which are ingested by macrophages if they come of age (see CD-31 for a description of this process. Neutrophil granulocytes, generally referred to as neutrophils, are the most abundant type of White blood cells in humans and form an essential part of the CD31 is a Cluster of differentiation Molecule. It is also called PECAM-1 for platelet endothelial cell adhesion molecule )

The removal of dust and necrotic tissue is to a greater extent handled by fixed macrophages, which will stay at strategic locations such as the lungs, liver, neural tissue, bone, spleen and connective tissue, ingesting foreign materials such as dust and pathogens, calling upon wandering macrophages if needed.

When a macrophage ingests a pathogen, the pathogen becomes trapped in a food vacuole, which then fuses with a lysosome. In general vacuole functions include Removing unwanted structural debris Isolating materials that might be harmful or a threat to the cell Containing Lysosomes are Organelles that contain Digestive enzymes (acid Hydrolases. Within the lysosome, enzymes and toxic peroxides digest the invader. Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins However, some bacteria, such as Mycobacterium tuberculosis, have become resistant to these methods of digestion. Mycobacterium tuberculosis is the Bacterium that causes most cases of Tuberculosis. Macrophages can digest more than 100 bacteria before they finally die due to their own digestive compounds.

Role in specific immunity

Macrophages are versatile cells that play many roles. As scavengers, they rid the body of worn-out cells and other debris. They are foremost among the cells that "present" antigen; a crucial role in initiating an immune response. As secretory cells, monocytes and macrophages are vital to the regulation of immune responses and the development of inflammation; they churn out an amazing array of powerful chemical substances (monokines) including enzymes, complement proteins, and regulatory factors such as interleukin-1. A monokine is a type of Cytokine produced primarily by Monocytes and Macrophages. Interleukin-1 (IL-1 is one of the first Cytokines ever described At the same time, they carry receptors for lymphokines that allow them to be "activated" into single-minded pursuit of microbes and tumour cells. Lymphokines are a subset of Cytokines that are produced by a type of Immune cell known as a Lymphocyte.

After digesting a pathogen, a macrophage will present the antigen (a molecule, most often a protein found on the surface of the pathogen, used by the immune system for identification) of the pathogen to a corresponding helper T cell. An antigen (from antibody-generating) or immunogen is a substance that prompts the generation of Antibodies and can cause an immune response T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or The presentation is done by integrating it into the cell membrane and displaying it attached to a MHC class II molecule, indicating to other white blood cells that the macrophage is not a pathogen, despite having antigens on its surface. The major histocompatibility complex ( MHC) is a large genomic region or Gene family found in most Vertebrates It is the most gene-dense region

Eventually the antigen presentation results in the production of antibodies that attach to the antigens of pathogens, making them easier for macrophages to adhere to with their cell membrane and phagocytose. Antibodies (also known as immunoglobulins, abbreviated Ig) are Gamma globulin Proteins that are found in Blood or other Bodily In some cases, pathogens are very resistant to adhesion by the macrophages. Coating an antigen with antibodies could be compared to coating something with Velcro to make it stick to fuzzy surfaces. Velcro is a brand name of fabric hook-and-loop fasteners. It consists of two layers a "hook" side which is a piece of Fabric covered with tiny hooks

The antigen presentation on the surface of infected macrophages (in the context of MHC class II) in a lymph node stimulates TH1 (type 1 helper T cells) to proliferate (mainly due to IL-12 secretion from the macrophage). T helper cells (also known as effector T cells or Th cells) are a sub-group of Lymphocytes (a type of White blood cell or For Il-12 see also Ilyushin Il-12 Interleukin 12 ( IL-12) is an Interleukin that is naturally produced by Dendritic When a B-cell in the lymph node recognizes the same unprocessed surface antigen on the bacterium with its surface bound antibody, the antigen is endocytosed and processed. The processed antigen is then presented in MHCII on the surface of the B-cell. TH1 receptor that has proliferated recognizes the antigen-MHCII complex (with co-stimulatory factors- CD40 and CD40L) and causes the B-cell to produce antibodies that help opsonisation of the antigen so that the bacteria can be better cleared by phagocytes. CD40 is a costimulatory protein found on Antigen presenting cells and is required for their activation An opsonin is any molecule that acts as a binding Enhancer for the process of Phagocytosis, for example by coating the negatively-charged molecules on the membrane Phagocytes are cells that are found in the blood bone marrow and other tissues of Vertebrates.

Macrophages provide yet another line of defense against tumor cells and body cells infected with fungus or parasites. A fungus (ˈfʌŋgəs is a eukaryotic Organism that is a member of the kingdom Fungi (ˈfʌndʒaɪ Parasitism is a type of symbiotic relationship between Organisms of different Species. Once a T cell has recognized its particular antigen on the surface of an aberrant cell, the T cell becomes an activated effector cell, releasing chemical mediators known as lymphokines that stimulate macrophages into a more aggressive form. Lymphokines are a subset of Cytokines that are produced by a type of Immune cell known as a Lymphocyte. These activated or angry macrophages, can then engulf and digest affected cells much more readily. ^[2] The angry macrophage does not generate a response specific for an antigen, but attacks the cells present in the local area in which it was activated. ^[2]

Fixed macrophages

A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of dust is likely to occur. Each type of macrophage, determined by its location, has a specific name:

Macrophage

Investigations concerning Kupffer cells are hampered because in humans Kupffer cells are only accessible for immunohistochemical analysis from biopsies or autopsies. A dust cell (or alveolar macrophage) is a type of Macrophage found in the Pulmonary alveolus, near the Pneumocytes, but separated from the An alveolus (plural alveoli, from Latin alveolus, "little cavity" is an anatomical structure that has the form of a hollow cavity lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive A histiocyte is a cell that is part of the human Immune system. Connective tissue is one of the four types of tissue in traditional classifications (the others being epithelial, Muscle, and Nervous tissue) Kupffer cells, also known as Browicz-Kupffer cells, are specialized Macrophages located in the Liver that form part of the Reticuloendothelial system The liver is a vital organ in the human body and is present in Vertebrates and some other animals Nervous tissue is the fourth major class of Vertebrate tissue. An epithelioid cell is a Mesenchymal cell whose morphology resembles that of Epithelial cells In Medicine ( Anatomical pathology) a granuloma (classical Latin plural granulomata; modern anglicized plural granulomas, also accepted An osteoclast (from the Greek words for "bone" and "broken" is a type of Bone cell that removes Bone tissue by removing its Mineralized matrix Bones are rigid organs that form part of the Endoskeleton of Vertebrates They function to move support and protect the various organs of the body produce The spleen is an organ found in all Vertebrate animals In humans the spleen is located in the abdomen of the body where it functions in the destruction of redundant Red The kidneys are complicated organs that have numerous biological roles From rats and mice they are difficult to isolate and after purification only approximately 5 million cells can be obtained from one mouse.

Macrophages can express paracrine functions within organs that are specific to the function of that organ. In the testis for example, macrophages have been shown to be able to interact with Leydig cells by secreting 25-hydroxycholesterol, an oxysterol that can be converted to testosterone by neighbouring Leydig cells. Also, testicular macrophages may participate in creating an immune privileged environment in the testis, and in mediating infertility during inflammation of the testis.

Involvement in symptoms of diseases

Due to their role in phagocytosis, macrophages are involved in many diseases of the immune system. For example, they participate in the formation of granulomas, inflammatory lesions that may be caused by a large number of diseases. In Medicine ( Anatomical pathology) a granuloma (classical Latin plural granulomata; modern anglicized plural granulomas, also accepted

Some disorders, mostly rare, of ineffective phagocytosis and macrophage function have been described.

Macrophages are the predominant cells involved in creating the progressive plaque lesions of atherosclerosis. Atherosclerosis is a Disease affecting arterial Blood vessels It is a chronic inflammatory response in the walls of arteries in large part due to the accumulation

When fighting influenza, macrophages are dispatched to the throat. However, until the killer T cells for the flu virus are found, the macrophages do more damage than help. They not only destroy throat cells infected with the flu virus but also destroy several surrounding non-infected cells.

Macrophages also play a role in Human Immunodeficiency Virus (HIV) infection. Human immunodeficiency virus ( HIV) is a Lentivirus (a member of the Retrovirus family that can lead to acquired immunodeficiency syndrome Like T cells, macrophages can be infected with HIV, and even become a reservoir of ongoing virus replication throughout the body. T cells belong to a group of White blood cells known as Lymphocytes, and play a central role in Cell-mediated immunity.

Macrophages are believed to help cancer cells proliferate as well. They are attracted to oxygen-starved (hypoxic) tumour cells and promote chronic inflammation. Chronic Hypoxia is a pathological condition in which the body as a whole ( generalized hypoxia) or region of the body ( tissue hypoxia) is deprived of adequate Inflammation ( Latin, inflamatio, to set on fire is the complex biological response of vascular tissues to harmful stimuli such as Pathogens Inflammatory compounds such as Tumor necrosis factor (TNF) released by the macrophage activates the gene switch nuclear factor-kappa B. NF-κB ( nuclear factor-kappa B) is a protein complex that is a Transcription factor. NF-kB then enters the nucleus of a tumour cell and turns on production of proteins that stop apoptosis and promote cell proliferation and inflammation. ^[3]

Media

Related cells

• Tingible body macrophages are found in the germinal centers of lymph nodes.
• Dendritic cells (including Langerhans cells). Dendritic cells (DCs are Immune cells and form part of the Mammalian Immune system. Not to be confused with the Beta cells making up the Islets of Langerhans.
• A lipid-laden macrophage is called a foam cell. Lipids are broadly defined as any fat- Soluble ( lipophilic) naturally-occurring Molecule, such as fats oils waxes cholesterol sterols fat-soluble Foam cells are cells in an Atheroma derived from both Macrophages and Smooth muscle cells ref> which have accumulated low density lipoproteins
• A Multinucleated giant cells is a type of a macrophage seen in certain types of inflammatory diseases such as Mycoplasmal infections.

References

See also

• Oxoferin or WF 10 (TCDO)
• Immunomodulator

External links

• HIV and the Macrophage A book on the role of macrophages in AIDS pathogenesis
• Histology at BU 00704loa
• The role of macrophages in HIV pathogenesis