Infection and Immunity - Phagocytosis - Essay Example

?Infection and Immunity Introduction The human body has a built-in infection control and protection mechanism, one which helps protect the body from infection and helps promote health. Phagocytes, aside from other infection control mechanisms in the body, function to protect the body from harmful elements. These are white blood cells which ingest harmful particles, including bacteria and even dead or dying cells for the end purpose of protecting the rest of the body from any harm caused by such particles. This paper shall discuss the processes by which phagocytes are attracted to a site of infection and the mechanism by which they destroy foreign particles. This essay is being carried out in order to establish a clear understanding of the functionalities of phagocytes and phagocytosis, as applied to these cells and to normal body processes. Body Phagocytes are crucial cells in the fight against infection and in ensuring immunity against harmful bacteria and viruses. Phagocytes are very much developed among vertebrates and with every litre of blood, about six billion phagocytes are present (Mayer, 2006). These cells have first been discovered by Ilya Mechnikov in 1882 during his study of starfish larvae, and throughout the years, other discoveries on this cell have been made and developed by other scientists (Mayer, 2006). Aside from humans and vertebrates, phagocytes are also seen in other species, with some amoebae portraying behaviour very much like macrophage phagocytes, thereby, suggesting that phagocytes are apparent very early on in the development of living things (Janeway, 2001). Phagocytes may either be professional or non-professional based on how effective they are during phagocytosis. The professional phagocytes include the neutrophils, monocytes, macrophages, dendritic cells, and mast cells, and these cells have receptors which are highly sensitive to harmful objects or cells, including bacteria that are not normally part of the body (Ernst and Stendahl, 2006). These phagocytes are needed to fight infections and help maintain healthy cells by removing dead or dying cells (Robinson and Babcock, 1988). Where infection is present, chemicals attract the phagocytes to areas where infection is already present (Ernst and Stendahl, 2006). The chemicals may be from the bacteria itself or from the phagocytes themselves. As soon as these phagocytes come in contact with bacteria, the receptors on the surface of the phagocyte bind to them, causing the bacteria to be engulfed by the phagocyte (Janeway, 2001). The phagocytes then kill the bacteria through oxidants and nitric oxide (Fang, 2004). After the process of phagocytosis, the macrophages and dendrites usually take part in antigen presentation, where the phagocyte brings back the ingested materials to the surface. Such material is available to other cells in the immune system. The phagocytes also traverse the body’s lymph nodes where the material is displayed to the lymphocytes (Fang, 2004). These activities and processes are crucial to securing immunity. Phagocytosis involves activities, drawing out bacteria, parasites, as well as dead cells (Janeway, 2001). It takes place when bacteria or other foreign bodies bind to the receptors on the surface of phagocytes. Such phagocytes then elongate and stretch in order to engulf the bacteria or foreign object. This process usually takes place within nine minutes (Hampton, 1994). As soon as the foreign material is in the phagocyte’s phagosome, the material cannot anymore get out (Hampton, 1994). The phagosome merges with the lysosome or any granule and form into a phagolysosome. Moreover, the bacterium is also made to undergo various killing processes and in a few minutes is already dead (Hampton, 1994). Phagocytosis can take hours for dendrites and macrophages as macrophages are usually slow and untidy eaters, often regurgitating some of the materials into the system. Such undigested materials often trigger more phagocytes to engulf excess materials (Sompayrac, 2008). The phagocytes, in contrast, are big eaters and can often engulf foreign bodies whole without leaving any residues and without regurgitating these back to the tissues. These phagocytes have various receptors which are used to bind materials (Meyer, 2006). Opsonin receptors, scavenger receptors, and Toll-like receptors are just some of the receptors for phagocytes, with the opsonin receptors enhancing the breakdown of bacteria with immunoglobulin G (IgG) antibodies or complement (Meyer, 2006). Complement refers to proteins in the blood which can annihilate cells which are already meant to the destroyed (Sompayrac, 2008). The scavenger receptors attach to the molecules on the surface of bacteria and the Toll-like receptors attach to specific molecules. In attaching to Toll-like receptors, phagocytosis is often increased and prompts the phagocytes to release hormones which trigger inflammation (Mayer, 2006). Figure 1 The image above illustrates the cell and how the phagocytes engulf the bacteria or foreign body through phagocytosis. The destruction of foreign materials is the main function of phagocytes and is either apparent within the phagocyte through intracellular killing or outside through extracellular killing. After phagocytes consume bacteria or other foreign materials, their oxygen needs and intake often increase and with increase in oxygen intake, reactive molecules are often produced (Dahlgren, 1999). The compounds of the oxygen are highly toxic to the cell as well as the invader and as such are often confined inside the cell. The process of killing bacteria through reactive oxygen-filled molecules is describes as oxygen-dependent intracellular annihilation. This process has two types (Fang, 2004). The first is oxygen-based production of superoxide which uses oxygen-rich bacteria killing processes (Shatwell, 1996). This superoxide is transformed into hydrogen peroxide and superoxide dismutase. The superoxide also reacts to the hydrogen peroxide, creating hydroxyl radicals which help in the destruction of the bacteria or foreign material (Mayer, 2006). The second kind of ‘killing’ is seen with the application of the myeloperoxidase enzyme coming from the neutrophils (Klebanoff, 1999). As the granules combine with phagosome, the myeloperoxidase is then discharged into the phagolysosome using hydrogen peroxide and chlorine, soon after, hypochlorite is produced. This hypochlorite is actually used in bleaches and is toxic to bacteria. The myeloperoxidase has the heme pigment which causes the green colour in the secretions in neutrophils, including pus and sputum (Meyer, 2004). The phagocytes can attack the microbes through oxygen-independent processes, however these are not as efficient as the oxygen dependent processes (Hoffbrand, 2005). There are four main kinds of this process. The first utilizes electrically charged proteins which destroy the membrane of the bacteria or foreign material. The second type utilises the lysozymes and destroys the cell wall, and the third kind makes use of the lactoferrins, which eliminates the iron from the bacteria (Hoffbrand, 2005). Finally, the fourth kind, utilizes the protease and hydrolytic enzymes in order to ingest the proteins and kill the bacteria or foreign material (Delves, et.al., 2006). Various types of cells in the immune system follow the process of phagocytosis (Silverstein, 1995). The neutrophils enter the tissues and phagocytise the bacteria in acute inflammation; the macrophages are seen in monocytes in the blood and are seen in chronic inflammation. They also release various inflammatory paracrines. For dendritic cells, the phagocytosis in these cells is crucial in the establishment of particular immune responses. For B-lymphocytes, a limited amount of phagocytosis in these cells is often crucial to ensure that cells release the much needed antibodies (Allen and Aderem, 1996). Phagocytosis starts as the neutrophil or macrophage passes around the bacteria or foreign material and consumes it so that it becomes fully engulfed within a phagosome. The more significant challenge is in the next step where the microorganism is destroyed (Rabinovitch, 1996). Some bacteria require special mechanisms for destruction, while others can be killed through normal phagocytosis processes. The phagosome and the lysosome merge with each other creating the phagolysosome. A combination of proteins known as the phagocyte oxidase is found in the membrane of the phagolysosome and creates oxygen radicals in the phagosome (Rabinovitch, 1996). One electron is derived from NADPH (Nicotinamide adenine dinucleotide phosphate) and included in the oxygen. The result would be highly reactive molecules which are sensitive to proteins, lipids, and other molecules. The nitric oxide synthase causes the breakdown of nitric oxide, which is very much reactive to superoxide, then creating molecules which can lead to damages in the biological molecules (Parham, 2009). Lysosomes possess various proteases, which include broad spectrum elastase which is crucial in the annihilation of various types of bacteria or foreign material. On the other hand, lysozymes attack cell walls of gram-positive bacteria. For defensins and some kinds of peptides, these attack the bacterial cell membranes (Parham, 2009). Lactoferrin attaches to iron, elements which are important in bacterial growth. Other kinds of protein bind to vitamin B12 (Parham, 2009). For transporters of hydrogen ions, they cause the breakdown of phagolysosome which then causes the destruction of different types of bacteria Aside from the destruction of bacteria and other microorganisms, phagocytes release substances which gravitate to other cells and assist in establishing a strong response to infection (Han and Ravichandran, 2011). Such regulatory cells establish the immune response, and these cells or molecules are known as cytokines. These are proteins which are secreted by white blood cells, including macrophages. These cytokines act like paracrines; and these help in cell regulation and are released locally to other cells (Parham, 2009). There are times however when cytokines do not act specifically, especially if they cause fever. The secretion of the cytokines by the macrophages is very important because cytokines like the TNF-alpha and the IL-1 help ensure and facilitate the body’s immune response (Parham, 2009). They are also valuable paracrines. The TNF-alpha can also be secreted in major infections in significant quantities which can be life threatening to the host individual (Parham, 2009). Phagocytosis in immune cells are activated when the pathogen-associated molecular patterns (PAMPS) are activated, this also leads to NF-?B activation. Opsonins like C3b and antibodies often act like attachment sites and assist the phagocytosis of pathogens (Parham, 2009). With the assistance of the actin-myosin contractile system, the material is engulfed and the phagosome is then bound to the lysosome, eventually leading to its degradation. After apoptosis or cell death, the dying cells are taken up by the macrophages through efferocytosis (Parham, 2009). The dying cell presents with various intracellular molecules and these molecules are known to be receptors on the cell surface of the macrophage. Issues in dead cell clearance can sometimes be linked with impaired phagocytosis or macrophages. Where remnants of dead cells are accumulated, autoimmune disorders often become apparent (Parham, 2009). Pathogens can often avoid contact with phagocytes. They can reproduce in sites where phagocytes do not usually travel (e.g., the skin). They can also control the usual inflammatory response to infection and without such inflammatory processes, the phagocytes would not be able to respond (Valenick, et.al., 2005). Some bacteria can also trick the immune system, thinking that the bacterium is natural self bacteria. Bacteria can also avoid being engulfed when they produce proteins which protect their surfaces and interfere with phagocytosis. Common in these instances are capsules, where the bacteria encapsulate itself to protect against phagocytes (Burns and Hull, 1999). Some types of bacteria are also able to live inside phagocytes and continue to impact on the immune system. While inside the phagocyte, they stay in the cytoplasm and avoid any contact with the chemicals which destroy the phagolysosomes (Melin, et.al., 2009). Despite these methods of avoidance however, for the most part, barring any unforeseen elements in the person’s normal anatomy, the phagocytes carry out their functions efficiently and help protect the body against any bacteria and harmful foreign bodies. Conclusion Based on the above discussion, phagocytes are white blood cells which function to protect the body from infection, specifically from bacteria and other foreign materials. Phagocytes go through the process of phagocytosis with the bacteria or foreign material. This involves the process of the phagocyte stretching and then engulfing the bacteria, and trapping the bacteria inside it is then broken down. Normally, our blood contains millions of phagocytes which have receptors to bacteria and other foreign materials. When these receptors are triggered, the process of phagocytosis unfolds, thereby ensuring that the body is protected from bacteria and other harmful foreign materials. References Allen, L. and Aderem, A., 1996. Mechanisms of phagocytosis. Curr. Opin. Immunol., 8, 36–40 Burns, S. and Hull, S., 1999. Loss of resistance to ingestion and phagocytic killing by O (-) and K (-) mutants of a uropathogenic Escherichia coli O75:K5 strain. Infect. Immun., 67 (8), 3757–62 Dahlgren, C. and Karlsson, A., 1999. Respiratory burst in human neutrophils. Journal of Immunological Methods, 232 (1–2), 3–14. Delves, P., Martin, S., Burton, D., and Roit, I., 2006. Roitt's essential immunology. Malden, MA: Blackwell Publishing. Ernst, J. and Stendahl, O., 2006. Phagocytosis of bacteria and bacterial pathogenicity. New York: Cambridge University Press. Fang, F., 2004. Antimicrobial reactive oxygen and nitrogen species: concepts and controversies. Nat. Rev. Microbiol., 2 (10), 820–32. Hampton, M., Vissers, M., and Winterbourn, C., 1994. A single assay for measuring the rates of phagocytosis and bacterial killing by neutrophils. J. Leukoc. Biol., 55 (2), 147–52. Han, C., and Ravichandran, K. 2011. Metabolic Connections during Apoptotic Cell Engulfment. Cell, 147(7), 1442-5 Hoffbrand, A., Pettit, J., and Moss, P., 2005. Essential haematology. London: Blackwell Science. Janeway, C., 2001. Immunobiology: the immune system in health and disease. New York: Garland Science Klebanoff, S., 1999. Myeloperoxidase. Proc. Assoc. Am. Physicians, 111 (5), 383–89. Mayer, G., 2006. Immunology — Chapter one: innate (non-specific) immunity. Microbiology and Immunology. South Carolina: USC School of Medicine. Melin, M., Jarva, H., Siira, L., Meri, S., Kayhty, H., and Vakevainen, M., 2009. Streptococcus pneumoniae capsular serotype 19F is more resistant to C3 deposition and less sensitive to opsonophagocytosis than serotype 6B. Infect. Immun., 77 (2), 676–84. Meyer, K., 2004. Neutrophils, myeloperoxidase, and bronchiectasis in cystic fibrosis: green is not good. J. Lab. Clin. Med., 144 (3), 124–26. Rabinovitch, M., 1995. Profesional and non-professional phagocytes: an introduction. Trends Cell Biol., 5, 85–87 Robinson, J. and Babcock, G., 1998. Phagocyte function - A guide for research and clinical evaluation. New York: Wiley–Liss Shatwell, K. and Segal, A., 1996. NADPH oxidase. The International Journal of Biochemistry and Cell Biology, 28 (11), 1191–95. Silverstein, S., 1995. Phagocytosis of microbes: insights and prospects. Trends Cell Biol., 5,141– 42 Sompayrac, L., 2008. How the immune system works. Malden, MA: Blackwell Publishing. Valenick, L., Hsia, H., and Schwarzbauer, J., 2005. Fibronectin fragmentation promotes alpha4 beta1 integrin-mediated contraction of a fibrin-fibronectin provisional matrix. Experimental Cell Research, 309 (1), 48–55. Read More