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[[Image:ontdur.PNG|right|Durham Regional Municipality]]
The '''immune system''' is the collection of organs and tissues involved in the adaptive defense of a body against foreign biological material. It may be broken down into the adaptive immune system (only found in vertebrates[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=9297968]), composed of four lymphoid organs ([[thymus]], [[lymph node]]s, [[spleen]] and submucosal lymphoid nodules) and the group motile cells that are involved in the body's defense against foreign bodies. The term may also be used to refer to the totality of a body's defense systems, encompassing both the adaptive immune system and other passive defenses, such as the skin.
'''The Regional Municipality of Durham''', commonly called Durham Region (2003 population 525,000), is a regional political area located east of [[Toronto, Ontario]]. It has an area of approximately 2,500 square kilometers and includes the municipalities of [[Pickering, Ontario|Pickering]], [[Ajax, Ontario|Ajax]], [[Oshawa, Ontario|Oshawa]], [[Whitby, Ontario|Whitby]], [[Clarington, Ontario|Clarington]], [[Uxbridge, Ontario|Uxbridge Township]], [[Scugog, Ontario|Scugog Township]] and [[Brock, Ontario|Brock Township]]. Durham Region is considered part of the [[Greater Toronto Area]]. The regional seat is in [[Whitby, Ontario|Whitby]].
The region of Durham was established in [[1974]] as one of several new "regional" governments in the Province of [[Ontario]]--primarily in fast-growing urban and suburban areas. Durham Region encompasses areas that were previously part of Ontario County and Durham County.
In multicellular [[organism]]s, the immune system is an organ system that acts as a defense against foreign [[pathogen]]s (such as [[virus (biology)|viruses]], [[bacterium|bacteria]], [[parasite]]s), some [[poison]]s, as well as [[cancer]]. Components of the immune system also function in the return of extracellular fluid to the blood.
The southern portion of the region, adjacent to Lake Ontario is primarily suburban in nature, forming the eastern flank of the "905" belt of suburbs and exurbs around Toronto. The northern area encompasses rural areas and small towns.
Bacteria and monocellular organisms have an "immune system" (under the broader of the two definitions above) designed to combat [[bacteriophage]]s (viruses that infect bacteria). They do this by simultaneously expressing [[restriction enzymes]] that cut [[DNA]] at certain sequences, and enzymes that protect their own DNA from this enzyme by methylating the same sequence. Therefore, the bacterium's DNA will not be damaged by the first enzyme because of the presence of the second enzyme. However, when a bacteriophage attempts to infect this bacterium, the viral DNA has not been protected, and gets degraded by the first enzyme. While study of the bacterial immune system provides useful insights into immunology, the remainder of this article will focus on higher organisms' immune systems, particularly the human immune system.
Major employers include [[General Motors of Canada]], [[Ontario Power Generation]], [[Lakeridge Health System]], [[Durham College]], [[University of Ontario Institute of Technology]] and many smaller component and transportation firms supplying the automotive industry.
==Recognizing self and non-self==
The Canadian headquarters of [[General Motors]], [[Volkswagen]], and [[BMW]] are all located in the region. The automotive industry is especially concentrated in Oshawa.
The immune system defends the body by recognizing agents that represent ''self'' and those that represent ''non-self'', and launching attacks against harmful members of the latter group. Distinguishing between self and non-self and between harmful non-self and harmless non-self is a difficult problem, and a variety of human disorders arise from failures of discriminatory systems (see [[Immune System#Disorders of the human immune system]]).
The four separate [[public transit]] systems in the region, operated by various municipalities, are set to be amalgamated under the Region's administration at the beginning of [[2006]].
Some self/non-self discrimination is effected by hard-wired mechanisms that recognize features displayed ''only'' by pathogens. The MBL pathway of the [[complement system]], for instance, recognizes mannose sugars, which appear only in the polysaccharide coats of bacterium. The most interesting mechanisms of discrimination, however, are not hard-wired --- rather, they involve the immune system ''learning'' to recognize non-self.
Durham also has one [[Indian reserve]], [[Mississaugas of Scugog Island, Ontario|Mississaugas of Scugog Island]]
For instance, the [[plasma membrane]] of every ''nucleated'' cell contains molecules of a large [[glycoprotein]] called the [[major histocompatibility complex]] (MHC). These proteins have configurations and amino acid sequences that are unique to every individual. T cells, a group that encompasses cytotoxic T lymphocytes ([[CTL]]s), the cells that kill virally-infected cells, contain surface-mounted [[T cell receptor|receptors]] that they use to determine if a given cell is virally infected by reading the [[peptide]]s displayed on its [[MHC]] molecules. During their development, [[T cell]]s are tested for self-reactivity. If a given cell contains receptors that bind strongly to an existing molecule in the body, it is destroyed by forced [[apoptosis]], leaving behind T cells that can be safely released into the body. (This is a much-truncated picture of T cell development; see the article on [[T cells]] for more).
== External Link ==
==Structure of the immune system==
*[http://www.region.durham.on.ca Region of Durham] The Region of Durham.
Most multicellular organisms possess an immune system consisting of ''innate immunity'' which generally consists of a set of genetically-encoded responses to pathogens and does not change during the lifetime of the organism. ''Adaptive immunity'', in which the response to pathogens changes during the lifetime of an individual, appeared somewhat abruptly in [[evolutionary timeline|evolutionary time]] with the appearance of [[Chondrichthyes|cartilaginous (jawed) fish]]. Organisms that possess an adaptive immunity also possess an innate immunity and many of the mechanisms between the systems are common, so it not always possible to draw a hard and fast boundary between the individual components involved in each, despite the clear difference in operation. Higher [[vertebrate]]s and all [[mammal]]s have both an innate and an adaptive immune system.
*[http://www.durhamtourism.ca DurhamTourism.ca] Tourism guide to the region.
*[http://www.groups.yahoo.com/group/freecycledurhamregion/ Freecycle Durham Region] Home page of the Durham Region chapter of the worldwide [http://www.freecycle.org Freecycle Network]
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[[Category:Census divisions of Ontario]]
===Innate immune system===
[[pt:Municipalidade Regional de Durham]]
The adaptive immune system may take days or weeks after an initial infection to have an effect. However, most organisms are under constant assault from pathogens, which must be kept in check by the faster-acting innate immune system. Innate immunity fights pathogens using defenses that are quickly mobilized and triggered by receptors that recognize a broad spectrum of pathogens. Plants and many lower animals do not possess an adaptive immune system and instead rely on innate immunity.
The study of the innate immune system has recently flourished. Earlier studies of innate immunity utilized model organisms that lack adaptive immunity such as the plant ''[[Arabidopsis thaliana]]'', the fly ''[[Drosophila melanogaster]]'', and the worm ''[[Caenorhabditis elegans]]''. Recent advances have been made in the field of innate immunology with the discovery of the [[toll-like receptor]]s, which are the receptors in mammals that are responsible for a large proportion of the innate immune recognition of pathogens. There is strong evidence that these toll-like receptors are responsible for sensing the "pathogen-associated molecular patterns" and/or providing the "danger signal" as speculated by Janeway and Matzinger, respectively.
====Physical barrier====
The first defense includes barriers to infection such as skin and mucus coating of the gut and airways, physically preventing the interaction between the host and pathogen. Pathogens which penetrate these barriers encounter constitutively expressed anti-microbial molecules that restrict the infection.
====Phagocytic cells====
The second-line defense includes phagocytic cells, which includes [[macrophage]]s and [[neutrophil granulocyte]]s ([[Granulocyte|polymorphonuclear leukocyte]]s, PMN) that can engulf ([[phagocytose]]) foreign substances. Macrophages are thought to mature continuously from circulating monocytes.
Phagocytosis involves [[chemotaxis]], where phagocytic cells are attracted to microorganisms by means of chemotactic chemicals like microbial products, complements, damaged cells and white blood cell fragments; chemotaxis is followed by [[cell adhesion|adhesion]], where the phagocyte sticks to the microorganism. Adhesion is enhanced by opsonization, where proteins like [[opsonin]]s are coated on the surface of the bacterium. This is followed by [[ingestion]], in which the phagocyte extends projections, forming [[pseudopod]]s that engulf the foreign organism. Finally the bacterium is digested by the enzymes in the lysosome.
====Anti-microbial proteins====
In addition, anti-microbial proteins may be activated if a pathogen pass through the barrier offered by skin. There are several class of antimicrobial proteins, such as [[acute phase protein]]s ([[C-reactive protein]], for example, binds to the [[C-protein]] of ''[[Streptococcus_pneumoniae|S. pneumoniae]]'' - enhances phagocytosis and activates complement), [[lysozyme]] and the [[complement system]].
====Complement system====
The [[complement system]] is a very complex group of [[serum protein]]s which is activated in a [[cascade]] fashion. Three different pathways, the ''[[classical complement pathway|classical]]'', ''[[alternative complement pathway|alternative]]'', and ''[[mannose-binding lectin pathway|mannose-binding lectin]]'' pathways, are involved in complement activation. The first recognizes antigen-antibody complexes, the second spontaneously activates on contact with pathogenic cell surfaces, the third recognizes [[mannose]] sugars, which tend to appear only on pathogenic cell surfaces. A cascade of protein activity follows complement activation; this cascade can result in a variety of effects including [[opsonization]] of the pathogen, destruction of the pathogen by formation and activation of the [[membrane attack complex]], and inflammation.
===Adaptive immune system===
The adaptive immune system, also called the acquired immune system, ensures that most mammals that survive an initial infection by a pathogen are generally immune to further illness caused by that same pathogen. [[Vaccination]] exploits this mechanism to produce immunity by way of introducion of an attenuated pathogen. The adaptive immune system is based on immune cells called [[leukocyte]]s (or white blood cells) that are produced by [[stem cell]]s in the [[bone marrow]]. In many species, including [[mammals]], the adaptive immune system can be divided into two major sections:
* The ''[[humoral immunity|humoral immune system]]'', which acts against bacteria and viruses in the body liquids (such as [[blood]]). Its primary means of action are proteins called [[immunoglobulin]]s, also called [[antibody|antibodies]], which are produced by ''[[B cell]]s''
* The ''[[cell-mediated immunity|cellular immune system]]'', which (among other duties) destroys virus-infected cells. The functions of CMI are performed by ''[[T cell]]s'', also called ''T lymphocytes'' (T means they develop in the [[thymus]]). There are two major types of T cells:
** ''[[Cytotoxic T cell]]s'' (T<sub><small>C</small></sub> cells) recognize infected cells by using [[T-cell receptor]]s to probe the surface of other cells. If they recognize an infected cell, they release [[granzyme]]s to signal that cell to become [[apoptosis|apoptotic]] ("commit suicide"), thus killing that cell and any viruses it is in the process of creating.
** ''[[Helper T cell]]s'' (T<sub><small>H</small></sub> cells) activate infected [[macrophage]]s (cells that ingest dangerous material), and also produce [[cytokine]]s ([[interleukin]]s) that induce the [[proliferation]] of B and T cells.
** In addition, there are ''[[Regulatory T cell]]s'' (T<sub><small>reg</small></sub> cells) which are important in regulating cell-mediated immunity.
===The intersection between innate and adaptive immune systems===
Splitting the innate and adaptive immunity has served to simplify discussions of immunology. However, the systems are quite intertwined in a number of important respects.
One of the most important examples are the mechanisms of '''antigen presentation.''' After they leave the thymus, T cells require activation to proliferate and differentiate into "killer" T cells (CTLs). Activation is provided by antigen presenting cells (APCs). A major category of APCs involved in T cell activation, the [[dendritic cells]], are part of the innate immune system. Activation occurs when a DC simulatenously binds to a T "helper" cell's antigen receptor ''and'' to its CD28 receptor, which provides the "second signal" needed for DC activation. This signal is a means by which the DC conveys that the antigen is indeed dangerous, and the next encountered T "killer" cells need to be activated. This mechanism is based on antigen danger evaluation by T cells that are all belonging to the adaptive immune system. But the [[dendritic cells]] are often directly activated by engaging their [[toll like receptors]], getting their "second signal" directly from the antigen. In this way they actually recognize in "first person" the danger and direct the T killer attack.
In this way, the innate immune system plays a critical role in the activation of the adaptive immune system.
[[Adjuvant]]s, or chemicals that stimulate an immune response, provide artificially this "second signal" in procedures when an antigen that would not normally raise an immune response is artificially introduced into a host. With the adjuvant, the response is much more robust. Historically, a commonly used formula [[Freund's Complete Adjuvant]], an emulsion of oil and [[mycobacterium]]. It was later discovered that toll-like receptors, expressed on innate immune cells, are critical in the activation of adaptive immunity.
==Disorders of the human immune system==
Many disorders of the human immune system fall into two broad categories: those characterized by attenuated immune response and those characterized by overzealous immune response.
[[Immunodeficiency]] is characterized by an attenuated response. There are ''congenital'' (inborn) and ''acquired'' forms of immune deficiency. [[Chronic granulomatous disease]], in which [[phagocytes]] have trouble destroying pathogens, is an example of the former. [[AIDS]] ("Acquired Immune Deficiency Syndrome"), an [[infectious disease]], caused by the [[HIV]] virus that destroys CD4<sup>+</sup> T cells, is an example of the latter. Immunosuppressive medication intentionally induces an immunodeficiency in order to prevent [[transplant rejection|rejection]] of [[organ transplantation|transplanted organs]].
On the other end of the scale, an overactive immune system figures in a number of other disorders, particularly [[autoimmune disorder]]s such as [[lupus erythematosus]], type I [[diabetes mellitus|diabetes]] (sometimes called "juvenile onset diabetes"), [[multiple sclerosis]], [[psoriasis]], and [[rheumatoid arthritis]]. In these the immune system fails to properly distinguish between self and non-self and attacks a part of the patient's own body. Other examples of overzealous immune responses in disease include [[hypersensitivity|hypersensitivities]] such as [[allergies]] and [[asthma]].
==Further reading==
* A standard textbook on the immune system is ''Immunobiology'', by [[Charles Janeway]], et al. The paperback of the sixth edition is ISBN 0815341016. [[NCBI]] makes the 5th edition availiable electronically at [http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=imm.TOC&depth=10].
==See also==
* [[:Category:Immune system]]
* [[antigen]]/[[antigenic determinant]]/[[epitope]]/[[hapten]]/[[memory cell]]
* [[autoimmune disorder]]s
* [[CD4 receptor]]/[[CD8 receptor]]/[[perforin]]/[[apoptosis]]/[[clonal selection]]
* [[immunotherapy]]
* [[lymphatic system]]/[[lymphocyte]]
* [[macrophage]]
* [[major histocompatibility complex]]/[[class I MHC]]/[[class II MHC]]
* [[monoclonal antibody]]/[[polyclonal antibody]]
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[[Category:Immune system]]
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