Innate immune response

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Cell types involved in innate immunity in vertebrates .
Parent
Immune response
defense (biology)
Subordinate
Response to type I / III / γ- interferon
complement system
NK-mediated immunity
Coagulation
Melanization Plant
.
Immune response virus-induced gene silencing
Gene Ontology
QuickGO

In addition to the adaptive immune response, the innate immune response is a possible reaction of the immune system in all organisms to substances and living beings that are classified as foreign. In contrast to the adaptive response, the structure of the proteins involved is fixed in the genome and can therefore not be adapted. On the other hand, a large number of cell types and soluble factors have developed, each of which can act quickly and efficiently: Only minutes after penetration, most pathogens are recognized and attacked, and after a few hours they are completely eliminated. The innate immune response is therefore much more than just the first protective reaction in animals; as a rule, it is already effective enough to reliably ward off the majority of infections.

Components of the innate immune response in animals

The components of the innate immune system are

  • mechanical barriers designed to prevent pests from entering.
  • Cells such as granulocytes or natural killer cells ( NK cells ). They can be found in all organs.
  • Proteins that circulate in the blood plasma and serve as messenger substances or to ward off pathogens.

Mechanical and Physiological Barriers

The body's mechanical and physiological barriers are the first line of defense against pathogens. They ensure that the pathogens cannot even penetrate the body or leave it again as quickly as possible:

Cellular components

Neutrophils migrate from the blood vessel into the tissue, secreting proteolytic enzymes to break up intercellular connections (to improve their mobility) and phagocytosed bacteria

The cells of the innate immune response circulate in the blood vessels and are found in the tissues of the body. If a pathogen penetrates the body, the immune cells can fight it. Neutrophil granulocytes, monocytes / macrophages and dendritic cells can, for example, destroy the pathogen through absorption and digestion (phagocytosis) or through the production of immunomodulators and cytokines control the immune reaction of the organism and attract other immune cells to the site of inflammation.

Granulocytes

Granulocytes (from the Latin granulum : granules) make up the majority of white blood cells ( leukocytes ). They can leave the bloodstream and migrate into the tissue. Granulocytes have numerous vesicles (called vesicles or granules) in their cytoplasm , which contain aggressive substances with which pathogens can be rendered harmless.

Macrophages

Macrophages (giant eating cells) also represent part of the patrol of the immune system. Macrophages mature from monocytes (mononuclear white blood cells = mononuclear leukocytes ) that leave the bloodstream. Macrophages reside in the tissue, where they recognize and eat (phagocytize) any pathogens that have entered. If the pathogens cannot be fought by the macrophages alone, macrophages can activate the adaptive immune system. Macrophages also play a crucial role in combating and eliminating harmful substances and waste products (for example tar from cigarette smoke in the lungs), which is why they are sometimes referred to as "garbage collection from the body".

Natural killer cells

The natural killer cells (NK cells) discovered in 1975 are part of the innate immune system. NK cells are one of the first lines of defense in the fight against infection and cancer because they can destroy infected cells without first being in contact with the pathogen itself. Use them a mechanism that in the 1980s by the Swedish immunologist Klas Kärre was discovered and as " Lack of Self " (English. Missing self is called): NK cells recognize, among others, the MHC-I complex that almost occurs in all healthy body cells. If a cell is infected by viruses or if it turns into a tumor cell, the MHC-I complex on the surface may be lost. The finely balanced balance of inhibiting and activating receptor signals is shifted in favor of NK cell activation and the diseased cell falls victim to an immune reaction triggered by NK cells.

Humorous components

The humoral components of the immune system (from Latin humor "fluid") denote various plasma proteins that passively circulate in the blood or tissue fluid. In contrast to the immune cells, they are unable to actively migrate to the site of an infection.

Complement system

The complement system is part of the innate immune response; it consists of a group of over 30 plasma proteins with very different properties. Some of the proteins belonging to the complement system are, for example, proteases, which can bind to microorganisms and damage the intruder's cell walls, thereby destroying the intruder. Other proteins of the complement system, the anaphylatoxins , have a vasodilating effect and promote the inflammatory reaction. Many complement factors can also attract immune cells to the site of infection and are able to activate phagocytes, which the invaders then devour.

Interleukins

The interleukins, which belong to the cytokines, are the body's own messenger substances that are produced by the cells of the immune system. Today we already know a large number of interleukins (IL-1 to IL-35; as of November 2009), each of which acts on very different immune cells - for example, some stimulate leukocytes to grow, mature and divide or ensure that they are activated.

Plant immune response

Plants have neither an adaptive immune system nor mobile defense cells. Your immune response is based on the immune response of the affected tissue. This so-called induced defense takes place within minutes. In addition, stress signals can trigger a so-called hypersensitive reaction : cells surrounding the infection site die off more quickly, so that the pathogen is no longer given the opportunity to spread when nutrients are withdrawn.

Detection of pathogens

Pathogens have a number of unchangeable characteristics that clearly distinguish them from the body's own cells in the infected tissue. Some components of the bacterial shell (e.g. lipopolysaccharides ) or certain structural features of nucleic acids (e.g. the double-stranded RNA of some viruses) do not occur in animals or plants and can therefore easily be recognized as foreign. These features are called pathogen-associated molecular patterns (PAMPs). Immune cells recognize these PAMPs through an abundance of different membrane receptors , which are summarized under the term Pattern Recognition Receptors (PRRs). A subgroup of these receptors that is widespread in the immune system are the toll-like receptors (TLRs), which recognize the structures of almost all types of pathogens and then trigger signals which stimulate immune cells to produce cytokines and other antibodies.

Immune cells receive support in recognizing pathogens from various soluble factors. The complement system plays an important role in animals , the factors of which bind to foreign surfaces and thus mark or opsonize pathogens that have penetrated . Another form of opsonization takes place through so-called "natural antibodies" which, in contrast to the antibodies of the adaptive immune response, are formed in large quantities as a preventive measure. These opsonizations make it easier for the immune cells to recognize the marked pathogens with the help of different receptors and to phagocytize them efficiently.

It is assumed that around 90 percent of all infections can be recognized and successfully fought by the innate immune system. In the course of the phylogenetic development from simple living beings to complex organisms, these defense strategies were therefore adopted almost unchanged. For example, a comparison of the immune defense of insects with the innate part of the human immune defense reveals many similarities.

Course of the innate immune response

As different as the invading pathogens are, the course of the innate immune response is just as variable. Which cells and factors are involved, in which order they intervene and which are ultimately decisive for success, all of this depends heavily on the type and location of the respective infection. For example, if bacteria penetrate a skin wound, it is mainly macrophages that are the first to come into contact with them and initiate a defense reaction. Two processes are decisive here: the macrophages immediately begin phagocytosis and destruction of the pathogens, and at the same time they release an abundance of messenger substances that activate the surrounding cells and trigger the influx of further immune cells. One of these messenger substances is the cytokine TNF-α , which causes an inflammatory reaction in the surrounding tissue and thereby activates a large number of cells. This also includes the endothelial cells that line the inside of the blood vessels and, under normal conditions, also seal them tightly. In the presence of TNF-α, however, they move away from each other, the vessel wall becomes more permeable and allows numerous blood factors to flow out. Antibodies and complement proteins get into the tissue and opsonize the pathogens, which can then be phagocytosed more easily by macrophages.

Macrophages and neutrophils contain the inflammasome , a protein complex that is stimulated by components of bacteria or uric acid crystals. This triggers a series of reactions that ultimately lead to the activation of the proinflammatory cytokine interleukin-1β . This is secreted by the macrophages and triggers the inflammatory reaction. If the inflammasome was activated by bacterial components, the inflammatory reaction plays an important role in defense against the infection. On the other hand, if the inflammation was triggered by uric acid crystals, a gout attack occurs . The innate immune defense is also able to differentiate the body's own cells from foreign structures. For this purpose, practically every cell in the body has what is known as the main histocompatibility complex (MHC), which is the cell's “membership card”. Foreign or diseased cells that do not have the MHC are inevitably recognized and inevitably the target of a defense reaction.

Other messenger substances released by macrophages are chemokines , a group of proteins that attract other cells from the blood. First, neutrophils, also very potent phagocytes, arrive and support the macrophages in eliminating the bacteria. Monocytes also migrate , develop into macrophages on site and thus also increase the number of phagocytes. If bacteria penetrate tissue cells in order to avoid the attack of the phagocytes, these infected cells are recognized and killed by NK cells . Dendritic cells play a special role : They also phagocytize the bacteria, but then present their components on their cell surface and thus enable the activation of T cells. Should the innate immune response not be able to fight off an infection on its own, the specific immune response and thus the next phase of the defense will be initiated seamlessly.

A special case of the innate immune response is the defense against parasites, in which mast cells , eosinophils and basophils are mainly involved. These cells store toxic substances in numerous granules , and receptors for antibodies of the IgE subtype are found on their surface. However, they are dependent on the preparatory work of the specific immune system, which first notices an infestation and then produces specific IgE antibodies that bind to the parasite and opsonize it. The cells now recognize the opsonized parasite and release toxic substances in its immediate vicinity, which damage the parasite in various ways and ultimately cause it to die.

Another process that is mediated during infections is the release of antimicrobial substances by the blood platelets ( beta-lysine , acute phase proteins ), which is triggered by the coagulation of the blood . Last but not least, lactoferrin is released in the event of a germ infection and an artificial iron deficiency is caused by the retention of iron in the RES.

In general, the innate immune response reacts extremely quickly to an infection, but it does not change in the process and is just as effective - or ineffective - after a renewed infection with the same pathogen as it was the first time. An "immunological memory", which enables a more effective reaction to a new infestation and on which the protective effect of a vaccination is based, cannot be developed by the innate immune response, but remains an exclusive characteristic of the acquired immune response , but some cells of the innate immune system can be trained and respond more strongly to a second stimulus than to the first.

literature

  • Christine Schütt, Barbara Bröker: Basic knowledge of immunology. 3. Edition. Spektrum Akademischer Verlag, Heidelberg 2009, ISBN 978-3-8274-2646-8 .
  • JD Jones, JL Dangl: The plant immune system. In: Nature . Volume 444, Number 7117, November 2006, pp. 323-329. doi: 10.1038 / nature05286 . PMID 17108957 . (Review)
  • LC Van Loon: Plant Innate Immunity. Volume 51 of Advances in Botanical Research Academic Press, 2009, ISBN 978-0-12-374834-8 .
  • P. Schopfer, A. Brennecke: Plant physiology. Spektrum Akademischer Verlag, Heidelberg 2005, ISBN 3-8274-1561-6 .

Individual evidence

  1. ↑ AM Armant, MJ Fenton: Toll-like receptors: a family of pattern-recognition receptors in mammals . In: Genome Biol. No. 3 (8) , 2002, pp. reviews3011.1-reviews3011.6 . PMID 12186654
  2. ↑ C. Martinelli, JM Reichhart: Evolution and integration of innate immune systems from fruit flies to man: lessons and questions . In: J Endotoxin Res. No. 11 (4) , 2005, pp. 243-248 . PMID 16176662
  3. ^ Joost PH Drenth, Jos WM van der Meer: The Inflammasome - A Linebacker of Innate Defense . In: New England Journal of Medicine . No. 355 , 2006, pp. 730-732 . PMID 16914711
  4. ^ Sanjeev Mariathasan, Denise M. Monack: Inflammasome adapters and sensors: intracellular regulators of infection and inflammation . In: Nature Reviews Immunology . No. 7 , 2007, p. 31-40 . PMID 17186029
  5. ↑ Sadia Saeed, * Jessica Quintin, * Hindrik HD Kerstens, * NageshaA.Rao, * AliAghajanirefah, * Filomena Matarese, Shih-Chin Cheng, Jacqueline Ratter, KimBerentsen, Martijn A. van der Ent, Nilofar Sharifi, Eva M. Janssen- Megens, Menno TerHuurne, Amit Mandoli, Tom van Schaik, Aylwin Ng, FrancesBurden, Kate Downes, MattiaFrontini, Vinod Kumar, Evangelos J. Giamarellos-Bourboulis, Willem H. Ouwehand, Jos WM van der Meer, Leo AB Joosten, Cisca Wijmenga, Joost HA Martens, Ramnik J. Xavier, Colin Logie, & # 134; Mihai G. Netea, & # 134; Hendrik G. Stunnenberg & # 134 ;: Epigenetic programming of monocyte-to-macrophage differentiation and trained innate immunity . In: Science . tape 345 , no. 6204 , September 26, 2014, ISSN  0036-8075 , p. 1251086 , doi : 10.1126 / science.1251086 , PMID 25258085 , PMC 4242194 (free full text).