Immune system

The immune system is the system of specialised cells and organs that protect an organism from outside biological influences. In a broad sense, almost every organ has a protective function (e.g., the skin). When the immune system is functioning properly, it protects the body against bacteria and viral infections, destroying cancer cells and foreign substances. If the immune system weakens, its ability to defend the body also weakens, allowing pathogens, including viruses that cause common colds and flu, to grow and flourish in the body. The immune system also performs surveillance of tumor cells, and immune suppression has been reported to increase the risk of certain types of cancer.

Structure

Most multicellular organisms possess an "innate immune", generally comprising a set of genetically-encoded responses to pathogens, that does not change during the lifetime of the organism. Adaptive immunity, in which the response to pathogens changes during the lifetime of an individual, seems to have appeared somewhat abruptly in evolutionary time, with the appearance of chondrichthyes (cartilaginous or jawed fish).

Related Topics:
Evolutionary time - Chondrichthyes

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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 vertebrates and all mammals have both an innate and an adaptive immune system.

Related Topics:
Vertebrate - Mammal

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Innate immune system

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 wide spectrum of pathogens. Plants and many lower animals do not possess an adaptive immune system, and rely instead on their innate immunity.

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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 receptors, which are the receptors in mammal cells 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.

Related Topics:
Arabidopsis thaliana - Drosophila melanogaster - Caenorhabditis elegans - Toll-like receptor

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First-line defense: Physical 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, which penetrate these barriers, encounter constitutively-expressed anti-microbial molecules (eg. lysozyme) that restrict the infection.

Related Topics:
Skin - Mucus - Gut - Airways - Lysozyme

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Second-line defense: Phagocytic cells

The second-line defense includes phagocytic cells (macrophages and neutrophil granulocytes) that can engulf (phagocytose) foreign substances. Macrophages are thought to mature continuously from circulating monocytes.

Related Topics:
Phagocytic cells - Macrophage - Neutrophil granulocyte - Phagocytose - Monocyte

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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 opsonins are coated on the surface of the bacterium. This is followed by ingestion, in which the phagocyte extends projections, forming pseudopods that engulf the foreign organism. Finally, the bacterium is digested by the enzymes in the lysosome, involving reactive oxygen species and proteases.

Related Topics:
Chemotaxis - White blood cell - Adhesion - Opsonization - Opsonin - Pseudopod - Lysosome - Reactive oxygen species - Protease

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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 proteins (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.

Related Topics:
Acute phase protein - C-reactive protein - C-protein - S. pneumoniae - Lysozyme - Complement system

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The complement system is a very complex group of serum proteins which is activated in a cascade fashion. Three different pathways are involved in complement activation:

Related Topics:
Complement system - Serum protein - Cascade

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• classical pathway: recognizes antigen-antibody complexes;
• alternative pathway: spontaneously activates on contact with pathogenic cell surfaces; and
• mannose-binding lectin pathway: 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 the formation and activation of the membrane attack complex, and inflammation.

Related Topics:
Opsonization - Membrane attack complex - Inflammation

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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 leukocytes (white blood cells) that are produced by stem cells in the bone marrow, and mature in the thymus and/or lymph nodes. In many species, including mammals, the adaptive immune system can be divided into two major sections:

Related Topics:
Leukocyte - Stem cell - Bone marrow - Thymus - Lymph node - Mammals

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• Humoral immune system: It acts against bacteria and viruses in the body liquids (eg. blood) by means of proteins, called immunoglobulins (also known as antibodies), which are produced by B cells.
• Cellular immune system: It destroys virus-infected cells (among other duties) with T cells (also called "T lymphocytes"; "T" means they develop in the thymus). There are two major types of T cells:
• Cytotoxic T cells (T_C cells): These cells recognize infected cells by using T cell receptors to probe cell surfaces. If they recognize an infected cell, they release granzymes to trigger that cell to become apoptotic ("commit suicide"), thus killing that cell and any viruses that it is in the process of creating.
• Helper T cells (T_H cells): These cells activate infected macrophages (cells that ingest dangerous material), and also produce cytokines (interleukins) that induce the proliferation of B and T cells.

In addition, there are regulatory T cells (Treg cells) which are important in regulating cell-mediated immunity.

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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.

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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 cells (APCs), a major category of which are the dendritic cells. These cells are part of the innate immune system.

Related Topics:
Antigen-presenting cell - Dendritic cells

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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 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 respect, the innate immune system therefore plays a critical role in the activation of the adaptive immune system.

Related Topics:
Dendritic cells - Toll-like receptor

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Adjuvants, 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.

Related Topics:
Adjuvant - Freund's Complete Adjuvant - Mycobacterium

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