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The immune system is often divided into two sections:
Structure Most multicellular organisms possess an "innate immune system", generally comprising a set of germ-line encoded receptors to pathogens, that does not change during the lifetime of the organism. ''Adaptive immunity'', in which the responses to pathogens change and develop during the lifetime of an individual, seems to have appeared somewhat abruptly in Evolutionary Time , with the appearance of Chondrichthyes (cartilaginous or jawed fish). Organisms that possess an adaptive immunity also possess an innate immunity, and with many of the mechanisms between the systems being common, it is 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. Innate immune system The adaptive immune system could take days or weeks after an initial infection to have an effect. However, most organisms are under constant assault from Pathogen s that must be kept in check by the faster-acting innate immune system. Innate immunity defends against pathogens by rapid responses coordinated through "innate" receptors that recognize a wide spectrum of conserved pathogenic components. Prior to jawed fish, lower animals, there is no evidence of adaptive immunity, animals therefore relied instead on their innate immunity. Plants on the other hand rely on secondary metabolites (aka. phytochemicals) to defend themselves against fungal and viral pathogens as well as insect herbivory. Plant secondary metabolites are derived through vast arrays of plant biosynthetic pathways not needed directly for plant survival, hence why they are named secondary. Plant secondary metabolism should not be confused with innate or adaptive immunity as they evolved along an entirely different evolutionary lineages and rely on entirely different signal cues, pathways and responses when compared to eachother. The innate immune system, when activated, has a wide array of effector cells and mechanisms. There are several different types of phagocytic cells, which ingest and destroy invading pathogens. The most common Phagocytes are Neutrophils , Macrophages , and Dendritic Cells . Another cell type, Natural Killer Cells are especially adept at destroying cells infected with viruses. Another component of the innate immune system is known as the Complement System . Complement proteins are normally inactive components of the blood. However, when activated by the recognition of a pathogen or antibody, the various proteins are activated to recruit inflammatory cells, coat pathogens to make them more easily phagocytosed, and to make destructive pores in the surfaces of pathogens. Research The study of the innate immune system has recently flourished. Earlier studies of innate immunity utilized Model Organism s 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 Toll-like Receptor s (TLRs) and the intracellular nucleotide-binding site leucine-rich repeat proteins (NODs), which are receptors in mammal cells that are responsible for a large proportion of the innate immune recognition of pathogens. In 1989, prior to the discovery of mammalian TLRs, Charles Janeway conceptualized and proposed that evolutionarily conserved features of infectious organisms were detected by the immune system through a set of specialized receptors, which he termed pathogen-associated molecular patterns (PAMPs) and pattern recognition receptors (PRRs), respectively. This was a remarkable insight at the time but was only fully appreciated after the discovery of TLRs by the Janeway lab in 1997. The TLRs now comprise the largest family of innate immune receptors (or PRRs). Janeway’s hypothesis has come to be known as the ‘stranger model’ and substantial debate in the field persists to this day as to whether or not the concept of PAMPs and PRRs, as described by Janeway, is truly suitable to describe the mechanisms of innate immunity. The competing ‘danger model’ was proposed in 1994 by Polly Matzinger and argues against the focus of the stranger model on microbial derived signals, suggesting instead that endogenous danger/alarm signals from distressed tissues serve as the principle purveyors of innate immune responses. Both models are supported in the current literature, with discoveries that substances of both microbial and non-microbial sources are able to stimulate innate immune responses, which has led to increasing awareness that perhaps a blend of the two models would best serve to describe the currently known mechanisms governing innate immunity. First-line defense: physical and chemical barrier The first-line defense includes barriers to infection, such as Skin and Mucus coating of the Gut and Airways , physically preventing the interaction between the host and the pathogen. Pathogens that penetrate these barriers encounter constitutively-expressed anti-microbial molecules (eg. Lysozyme ) that restrict the infection. In addition to the usual defense, the stomach secretes Gastric Acid which, apart from aiding digestive enzymes in the stomach to work on food, prevents bacterial colonization by most pathogens. Second-line defense: Phagocytic cells The second-line defense includes Phagocytic Cells ( Macrophage s and Neutrophil Granulocyte s) that can engulf ( Phagocytose ) foreign substances. Macrophages are thought to mature continuously from circulating Monocyte s. Phagocytosis involves Chemotaxis , where phagocytic cells are attracted to microorganisms by means of chemotactic chemicals such as microbial products, complement, damaged cells and White Blood Cell fragments. Chemotaxis is followed by 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 , involving Reactive Oxygen Species and Protease s. Anti-microbial proteins In addition, anti-microbial proteins may be activated if a pathogen passes through the barrier offered by skin. There are several classes of antimicrobial proteins, such as Acute Phase Protein s ( C-reactive Protein , for example, enhances phagocytosis and activates complement when it binds itself to the C-protein of '' S. Pneumoniae '' ), Lysozyme , and the Complement System . The Complement System is a very complex group of Serum Protein s, which is activated in a Cascade fashion. Three different pathways are involved in complement activation:
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 the formation and activation of the Membrane Attack Complex , and Inflammation . Interferon s are also anti-microbial proteins. These molecules are proteins that are secreted by virus-infected cells. These proteins then diffuse rapidly to neighboring cells, inducing the cells to inhibit the spread of the viral infection. Essentially, these anti-microbial proteins act to prevent the cell-to-cell proliferation of viruses. 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. The adaptive immune system is based on dedicated immune cells termed Leukocyte s (white blood cells) that are produced by Stem Cell s in the Bone Marrow , and mature in the Thymus and/or Lymph Node s. In many species, including Mammals , the adaptive immune system can be divided into two major sections:
In addition, there are Regulatory T Cell s (Treg cells) which are important in regulating cell-mediated immunity. Intersections between 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 cytotoxic ("killer") T cells (CTLs). Activation is provided by Antigen-presenting Cell s (APCs), a major category of which are the Dendritic Cells . These cells are part of the innate immune system. Activation occurs when a dendritic cell simultaneously binds itself 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 dendritic cell conveys that the antigen is indeed dangerous, and that the next encountered T "killer" cells need to be activated. This mechanism is based on antigen-danger evaluation by the T cells that belong to the adaptive immune system. But the Dendritic Cells are often directly activated by engaging their Toll-like Receptor s, 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 respect, the innate immune system therefore 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 is 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 The most important function of the human Immune System occurs at the cellular level of the blood and tissues. The Lymphatic and Blood Circulation systems are highways for specialized White Blood Cell s to travel around the body. White blood cells include B Cells , T Cells , Natural Killer Cells , and Macrophages . Each has a different responsibility, but all function together with the primary objective of recognizing, attacking and destroying Bacteria , Viruses , Cancer Cells , and all substances seen as foreign. Without this coordinated effort, a person would not be able to survive more than a few days, before succumbing to overwhelming infection. Infections set off an alarm that alerts the immune system to bring out its defensive weapons. Natural killer cells and macrophages rush to the scene to gobble up and digest infected cells. If the first line of defense fails to control the threat, Antibodies , produced by the B cells, upon the order of T helper cells, are custom-designed to hone in on the invader. Many disorders of the human immune system fall into two broad categories that are characterized by:
Other factors that affect immune response Many factors can also contribute to the general weakening of the immune system:
Pharmacology Despite high hopes, there are no Medication s that directly increase the activity of the immune system. Various forms of medication that activate the immune system may cause Autoimmune Disorder s. Suppression of the immune system is often used to control autoimmune disorders or Inflammation when this causes excessive tissue damage, and to prevent Transplant Rejection after an Organ Transplant . Commonly used Immunosuppressants include Glucocorticoid s, Azathioprine , Methotrexate , Ciclosporin , Cyclophosphamide and Mercaptopurine . In organ transplants, Ciclosporin , Tacrolimus , Mycophenolate Mofetil and various others are used to prevent organ rejection through selective T cell inhibition. See also
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