Innate immune system
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- See also: Immune system and Adaptive immune system
The innate immune system is comprised of the cells and mechanisms that defend the host from infection by other organisms, in a non-specific manner. This means that the cells of the innate system recognize, and respond to, pathogens in a generic way.<ref name=Alberts>Alberts, Bruce, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walters (2002). Molecular Biology of the Cell; Fourth Edition. New York and London: Garland Science. ISBN 0815332181.</ref> The innate system does not confer long-lasting or protective immunity to the host.
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[edit] Functions
The innate system is thought to constitute an evolutionarily older defense strategy, and is the dominant immune system found in plants, fungi, insects, and in primitive multicellular organisms. <ref name=Janeway>Janeway, Charles, Paul Travers, Mark Walport, and Mark Shlomchik (2001). Immunobiology; Fifth Edition. New York and London: Garland Science. ISBN 0815341016..</ref>
The major functions of the innate immune system include:
- The recruitment of immune cells to sites of infection and inflammation, through the production of chemical factors; including specialized chemical mediators, called cytokines.
- Activation of the complement cascade to identify bacteria, activate cells and to promote clearance of dead cells or antibody complexes.
- The identification and removal of foreign substances; present in organs, tissues, the blood and lymph, by specialized white blood cells.
- The activation of the adaptive immune system through a process known as antigen presentation.
[edit] Inflammation
Inflammation is one of the first responses of the immune system to infection or irritation. Inflammation is stimulated by chemical factors released by injured cells and serves to establish a physical barrier against the spread of infection, and to promote healing of any damaged tissue following the clearance of pathogens.<ref name="IandF">Stvrtinová, Viera, Ján Jakubovský and Ivan Hulín (1995). Inflammation and Fever from Pathophysiology: Principles of Disease. Computing Centre, Slovak Academy of Sciences: Academic Electronic Press.</ref>
Mechanistically, the chemicals factors produced during inflammation (histamine, bradykinin, serotonin, leukotrienes) sensitize pain receptors, cause vasodilation of the blood vessels at the scene, and attract phagocytes, especially neutrophils.<ref name="IandF"/> Neutrophils then trigger the immune system by releasing factors that summon other leukocytes and lymphocytes. The inflammatory response is characterized by the following quintet: redness (rubor), heat (calor), swelling (tumor), pain (dolor) and possible dysfunction of the organs or tissues involved (functio laesa).
[edit] Complement system
The complement system is a biochemical cascade of the immune system that helps, or “complements”, the ability of antibodies to clear pathogens or mark them for destruction by other cells. The cascade is composed of many small plasma proteins, synthesized in the liver, primarily by hepatocytes, which work together to:
- trigger the recruitment of inflammatory cells.
- "tag" pathogens for destruction by other cells by opsonizing, or coating, the surface of the pathogen.
- disrupt the plasma membrane of an infected cell, resulting in cytolysis of the infected cell, causing the death of the pathogen.
- rid the body of neutralized antigen-antibody complexes.
Elements of the complement cascade can be found in many species evolutionarily older than earlier than mammals including plants, birds, fish and some species of invertebrates. <ref name=Janeway6>Janeway CA, Jr. et al (2005). Immunobiology., 6th ed., Garland Science. ISBN 0-443-07310-4.</ref>
[edit] Cells of the innate immune response
All white blood cells (WBC) are known officially as leukocytes. Leukocytes are unlike other cells of the body, and are not exclusively associated with any organ or tissue- in fact they effectively act like independent, single-celled organisms. Leukocytes are able to move, interact, and even capture things on their own. Unlike many other cells in the body, most innate immune leukocytes cannot divide or reproduce on their own, but rely on the pluripotential hemopoietic stem cells present in the bone marrow to produce new cells.<ref name=Alberts/>
The innate leukocytes include: Natural killer cells, mast cells, eosinophils, basophils; and the phagocytic cells including macrophages, neutrophils and dendritic cells, and function within the immune system by identifying and eliminating pathogens that might cause infection.<ref name=Janeway/>
[edit] Natural killer cells
Natural killer cells, or NK cells, are a component of the innate immune system, and are distinctive in that NK cells attack host cells that have been infected by microbes, but do not attack microbes themselves. NK cells attack and destroy tumor cells, and virally infected cells, through a process known as "missing-self", a term used to describe cells with low levels of a cell-surface marker called MHC (major histocompatibility complex)—a situation which can arise due to viral infection of host cells.<ref name=Janeway6/> They were named "natural killer" because of the initial notion that they do not require activation in order to kill cells that are "missing self."
[edit] Mast cells
Mast cells are a type of innate immune cell that resides in the connective tissue and in the mucous membranes, and are intimately associated with pathogen defence, wound healing, and are often associated with allergy and anaphylaxis.<ref name="IandF"/> When activated, mast cells rapidly release characteristic granules, rich in histamine and heparin, along with various hormonal mediators, and chemokines, or chemotactic cytokines into the environment. Histamine dilates blood vessels, causing the characteristic signs of inflammation, and recruits neutrophils and macrophages.<ref name="IandF"/>
[edit] Basophils and Eosinophils
Basophils and Eosinophils are cells related to the neutrophil (see below). When activated by a pathogen encounter, basophils release histamine, are important in defense against parasites, and play a role in allergic reactions (such as asthma).<ref name=Janeway/> Upon activation, eosinophils secrete a range of highly toxic proteins and free radicals that are highly effective against bacteria and parasites, but are also responsible for most tissue damage occurring during allergic reactions. Activation and toxin release by eosiniphils is tightly regulated to prevent any inappropriate tissue destruction.<ref name="IandF"/>
[edit] Phagocytes
The word 'phagocyte' literally means 'eating cell'. These are immune cells that engulf, or eat, pathogens or particles. To engulf a particle or pathogen, a phagocyte extends portions of its plasma membrane, wrapping the membrane around the particle until it is enveloped (i.e. the particle is now inside the cell). Once inside the cell, the invading pathogen is contained inside a endosome which merges with a lysosome.<ref name=Janeway/> The lysosome contains enzymes and acids that kill and digest the particle or organism. Phagocytes generally patrol the body searching for pathogens, but are also able to react to a group of highly specialized molecular signals produced by other cells, called cytokines. The phagocytic cells of the immune system include Macrophages, Neutrophils and Dendritic cells.
Phagocytes often engulf the hosts’ own cells. When cells die, either during normal processes (called apoptosis) or due to a bacterial or viral infection of the cell, phagocytic cells are responsible for their removal from the system.<ref name=Alberts/> By helping to remove dead cells, to make room for the new healthy cells, phagocytosis is an important part of the healing process following tissue injury.[edit] Macrophages
Macrophages, from the Greek, meaning "large eating cell", are large phagocytic leukocytes, which are able to travel outside of the circulatory system by moving across the cell membrane of capillary vessels and entering the areas between cells in pursuit of invading pathogens. In tissues, organ specific macrophages are differentiated from phagocytic cells present in the blood called monocytes. Macrophages are the most efficient phagocytes, and can eat substantial numbers of bacteria or other cells.<ref name=Janeway/> The binding of bacterial molecules to receptors on the surface of a macrophage triggers it to engulf and destroy the bacteria through the generation of a “respiratory burst”. Pathogens also stimulate the macrophage to produce chemokines, which summons cells to the site of infection.<ref name=Janeway/>
[edit] Neutrophils
Neutrophils, along with two other cell types; eosinophils and basophils, are known as granulocytes or polymorphonuclear cells (PMNs), due to their distinctive lobed nuclei. Neutrophils are the most abundant type of phagocyte, normally representing 50 to 60% of the total circulating leukocytes, and are usually the first cells to arrive at the scene of infection.<ref name="IandF"/> Similar to macrophages, neutrophils destroy foreign substances or pathogens by activating a "respiratory burst". The main products of the neutrophil respiratory burst are strong oxidizing agents including hydrogen peroxide, free oxygen radicals and hypochlorite. The bone marrow of a normal healthy adult produces more than 100 billion neutrophils per day, and more than 10 times that many per day during acute inflammation.<ref name="IandF"/>
[edit] Dendritic cells
Dendritic cells (DC) are phagocytic cells present in tissues that are in contact with the external environment, mainly the skin (where they are often called Langerhans cells), the inner lining of the nose, lungs, stomach and intestines.<ref name=Alberts/> They are named for their resemblance to neuronal dendrites, but dendritic cells are in no way connected to nervous system function. Dendritic cells are very important in the process of antigen presentation (see below), and serve as a link between the innate and adaptive immune systems.
[edit] Innate immune evasion
Cells of the innate immune system effectively prevent free growth of bacteria within the body, however many species of bacteria have evolved mechanisms allowing them to evade the innate immune system<ref name="Evasion"> Kennedy, Alan. Immune Evasion by bacteria.</ref>. Some of these strategies involve:
- Inhibiting phagocytosis, by affecting the receptors that the phagocytes use to engulf bacteria, or by mimicking host cells, so that the immune system does not perceive them to be foreign (Bacteroides)
- Inhibiting the ability of the phagocyte to respond to chemokines signals (Staphylococcus aureus)
- Inhibiting the mechanisms that phagocytes use to destroy the bacteria (Mycobacterium tuberculosis), and multiplying within the phagocyte.
- Directly killing the phagocyte (M. tuberculosis, Streptococcus pyogenes and Bacillus anthracis).<ref name="Evasion"/>
[edit] See also
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Host defense in non-mammalian species
- Antimicrobial peptides are an evolutionarily conserved component of the innate immune response and are found among all classes of life.
- Pattern recognition receptors are proteins used by organisms to identify molecules associated with microbial pathogens.
- Toll-like receptors are a major class of pattern recognition receptor.
- The Complement system is a biochemical cascade of the immune system that helps clear pathogens from an organism.
[edit] References
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| Immune system |
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| Adaptive immune system | Innate immune system | Humoral immune system | Cellular immune system | Immunological tolerance | Lymphatic system | White blood cells | Antibodies | Antigen (MHC) | Complement system | Inflammation |
