Innate Immunity
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Contents |
Structure of the immune system
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 time with the appearance of 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 vertebrates and all mammals have both an innate and an adaptive immune system.
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 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 receptors, 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 macrophages and neutrophil granulocytes (polymorphonuclear leukocytes, 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 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.
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 proteins (C-reactive protein, for example, binds to the C-protein of S. pneumoniae - enhances phagocytosis and activates complement), lysozyme and the complement system.
Complement system
The complement system is a very complex group of serum proteins which is activated in a cascade fashion. Three different pathways, the classical, alternative, and 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 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 cell's antigen receptor and to its CD28 receptor, which provides the "second signal" needed for activation. This signal is a means by which the APC conveys that the antigen is indeed dangerous, and the T cell needs to be activated. In this way, the innate immune system plays a critical role in the activation of the adaptive immune system.
Adjuvants, or chemicals that stimulate an immune response, provide 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.
Further reading
- A standard textbook on the immune system is Immunobiology, by WikiPedia:Charles Janeway, et al. The paperback of the sixth edition is ISBN 0815341016. WikiPedia:NCBI makes the 5th edition availiable electronically at [1].
- Most of the first version of this article is derived from WikiPedia:Immune_system
- Roitt's Essential Immunolog by WikiPedia:Ivan Roitt and Peter Delves is a core student textbook, an immunology primer.
- The sample chapter "Innate Immunity" is available for download
Reviews
Hamerman JA, Ogasawara K, Lanier LL.
NK cells in innate immunity.
Curr Opin Immunol. 2005 Feb;17(1):29-35. Review. PMID: 15653307 NKref0491
Web Links
- Innate immune response @ The Biology Projekt - Immunology
- http://focosi.altervista.org/immunityinnate.html
- Nature Immunology Web Focus: Bridging innate and adaptive immunity
- University of Hartford - Innate Immunity
- InnateImmunity.net
Source
Initial version of this article from Wikipedia, the free encyclopedia. Further edited as an collaborative approach to focus on information related to Natural Killer cells and Innate Immunity.
