Fill that gap!
A model for ........ , before it was understood that MHC molecules bound peptides, essentially the model we still use today
Alloreactivity
Contrary to apoptotic cell death, necrotic cell death triggers .............. .
Danger signals. It was demonstrated in humans that DCs are able to distinguish two types of tumor cell death, with necrosis providing a critical signal (DAMPs) that will promote the initiation of immunity.
The sensing of damage signals has been associated with the constitution of ............ .
Inflammasomes. They are a multiprotein complex that contains a pattern recognition receptor (PRR) which can help induce a pro-inflammatory response.
PAMP stands for...
Pathogen-Associated Molecular Patterns
This theory claims that immune responses are triggered by ............ released by the body's own cells
Danger/Alarm signals
How does the notion of “danger” explain the immune responses to innocuous antigens such as allergens or food antigens?
It is often unclear what a “danger” is for a cell or a tissue, and how cells and tissues can “perceive” that something is dangerous
The NLRP3 inflammasome seems to be able to sense ................ molecules, or, in other words, it can be activated in the context of “sterile inflammation” and it has been implicated in various sterile inflammatory diseases, including gout, asbestosis and silicosis.
Non-microbial
DAMP stands for...
Damage-Associated Molecular Patterns
To determine why an immune response is triggered is the presence or absence of danger, not ............ vs. ...........
Dendritic Cells can be activated by ........... in the absence of ‘foreign’ products.
Damaged cells
Some studies even suggest that HSP can have a ........ as well as a pro-inflammatory role.
Regulatory role
The release of DAMPs in the extracellular milieu functions as a sign of cell death to the innate immune system, which then triggers a pro-inflammatory response. This view, which elaborates on the danger theory, has been called the .....
Hidden-self model
This model stresses that endogenous cellular alarm signals from ......... or ......... cells.
Distressed or Injured
The idea that immune responses are due to “damages” has led to several experimental investigations. Therefore, in order to assess the “Danger theory,” the main concern is to define .........
Damage signals
One of the potential key players in the Danger Signal theory are the ............ .
Heat Shock Proteins. Their expression is increased when cells are exposed to elevated temperatures or other kinds of stress. They can act as activator for APCs and act as feedback molecules.
PAMPs play an essential role in activation of ..................... , they constitute an important objection to the danger theory, which states that every immune response is due to damages.
Innate Immunity.
The Danger Model, Polly Matzinger's revolutionnary work was develloped in discussions with...
Ephraim Fuchs
Proposed Damage Signals
CD40-L TNF-α, IL-1β, IFNα Intracellular nucleotides: ATP, UTP, Long unmethylated CpG sequences, Heat shock proteins (HSP), Reactive oxygen intermediates, Vasoactive intestinal peptide (VIP), Metalloproteinase-9, Degradation products of heparan sulfate, Small breakdown products of hyaluronan
Uric acid is involved in triggering immune responses, as it is released by injured cells, stimulates dendritic cell maturation and, when co-injected with antigen in vivo, significantly enhances the generation of responses from ............. cells
CD8+ T cells
These the four following criteria to define a DAMP:
(1) a DAMP should be active as a highly purified molecule
(2) the biological activity of a DAMP should not be due to ................... molecules
(3) a DAMP should be active at concentrations that are actually present in pathophysiological situations;
(4) the selective elimination or inactivation of a DAMP should ideally inhibit the biological activity of dead cells in vitro and in vivo
Contamination with microbial