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Event: 2255

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

Innate immune response, activation

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
Activation of the innate immune response
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Cellular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
small intestine

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
immune system process occurrence

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Gluten-driven immune activation leading to celiac disease KeyEvent Antonio Fernandez Dumont (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
human Homo sapiens High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Unspecific High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

An adaptive T and B cell response is only initiated after innate immune activation. While the exact nature of the agent causing innate immune activation remains unknown, it could involve exposure to viruses or bacteria, particularly when this occurs in the gastrointestinal tract, or exposure to environmental factors, such as gluten.

Certain infections may induce inflammation that promotes the activation of self-reactive B cells. Preexposure to IL-15, a cytokine upregulated in inflammatory and infectious conditions (Meresse et al., 2006; Fehniger et al., 2001), plays a key role in this process. IL-15 activates NK cells and intraepithelial lymphocytes (IELs) (CD8+ T cells), which become cytotoxic, damaging epithelial cells in the intestine. This epithelial damage allows gluten peptides to cross into the lamina propria, further perpetuating the immune response and inflammation. Nilsen et al. (1998) hypothesized that a Th1-like profile, characterized by predominantly high levels of IFNγ, results from various types of intestinal immune responses. This was recently observed in studies following intestinal astrovirus infection (Molberg et al., 1998) and in cases of cow’s milk-sensitive enteropathy. Additionally, infections can cause molecular mimicry, where pathogen-derived antigens resemble self-antigens. This can trigger an immune response that cross-reacts with the body’s own tissue, contributing to the development of autoimmune conditions such as celiac disease (Petersen et al., 2020).  

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Measured by biomarkers or functional tests. The assessment would focus on immune cell activation, cytokine production and pathogen recognition. Methods could include, flow cytometry, microscopy and staining, ELISA, RT-PC, oxidative burst assays, Toll-like receptor simuation assays.  

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Homo sapiens

References

List of the literature that was cited for this KE description. More help

  • Fehniger, T.A., and M.A. Caligiuri. (2001). Interleukin 15: biology and relevance to human disease. Blood. 97:14–32.

  • Meresse B, Curran SA, Ciszewski C, Orbelyan G, Setty M, Bhagat G, Lee L, Tretiakova M, Semrad C, Kistner E, Winchester RJ, Braud V, Lanier LL, Geraghty DE, Green PH, Guandalini S, Jabri B. (2006). Reprogramming of CTLs into natural killer-like cells in celiac disease. J Exp Med. 203:1343-1355.

  • Molberg Ø, Nilsen EM, Sollid LM, Scott H, Brandtzaeg P, Thorsby E, Lundin KEA. (1998). CD41 T-cells with specific reactivity against astrovirus isolated from normal human small intestine. Gastroenterology 114:115–122.

  • Nilsen EM, Jahnsen FL, Lundin KE, Johansen FE, Fausa O, Sollid LM, Jahnsen J, Scott H, Brandtzaeg P. (1998). Gluten induces an intestinal cytokine response strongly dominated by interferon gamma in patients with celiac disease. Gastroenterology. 115:551-563.

  • Petersen J, Ciacchi L, Tran MT, Loh KL, Kooy-Winkelaar Y, Croft NP, Hardy MY, Chen Z, McCluskey J, Anderson RP, Purcell AW, Tye-Din JA, Koning F, Reid HH, Rossjohn J. (2020). T cell receptor cross-reactivity between gliadin and bacterial peptides in celiac disease. Nat Struct Mol Biol. Jan;27(1):49-61. doi: 10.1038/s41594-019-0353-4.