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Printable Handouts
Navigable Slide Index
- Introduction
- Inflammation is initiated by ‘strangers’ or ‘danger’
- PAMPs and DAMPs initiate inflammation
- The 'Danger Model' of Immunity
- Necrotic cells instigate inflammation
- PAMPs and DAMPs initiate inflammation in infectious and non-infectious settings
- Apoptosis vs. necrosis
- Necrosis promotes inflammation while apoptosis minimizes it
- Necrosis indicates a severe departure from normal tissue function
- Specifically, what are DAMPs?
- IL-1 family cytokines represent the canonical DAMPs
- The extended IL-1 cytokine family
- Members of the extended IL-1 family characteristics
- All IL-1 family members have natural receptor antagonists
- IL-1 family cytokines signal via TIR-domain
- IL-1 family cytokines engage cell surface receptors
- IL-1 family DAMPs initiate Inflammation
- TLRs and IL-1Rs promote NFkB activation
- How are IL-1 family cytokines activated upon liberation from dead cells?
- IL-1 family members possess highly disordered N-terminal pro-domains vulnerable to proteolysis
- IL-1 family cytokines require proteolytic processing
- IL-1b/IL-18 are processed via inflammasomes
- Neutrophils: first responder immune cells recruited
- Neutrophils and mast cells typically release their granule proteases into the extracellular space
- Neutrophil and Mast cell-derived proteases can process and activate most IL-1 family cytokines
- Neutrophil proteases process and activate IL-1 family DAMPs upon release via necrosis
- Neutrophil proteases serve as global regulators
- Exogenous allergen and microbial proteases can also process and activate IL-1 family cytokines
- IL-1 family cytokines serve as sentinels for multiple proteases associated with ‘danger’
- Thank you
Topics Covered
- Inflammation is initiated by ‘strangers’ or ‘danger’
- PAMPs and DAMPs initiate inflammation
- The Danger Model of Immunity
- Apoptosis vs. necrosis
- IL-1 family cytokines represent the canonical DAMPs
- Neutrophils are the first responder immune cells recruited to sites of injury or infection
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Martin, S. (2024, February 29). IL-1 family cytokines as the canonical DAMPs of the immune system [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved October 7, 2024, from https://doi.org/10.69645/GIAC9219.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
Other Talks in the Series: The Immune System - Key Concepts and Questions
Transcript
Please wait while the transcript is being prepared...
0:00
Hello, I'm Seamus Martin from
Trinity College
Dublin in Ireland.
Today, I'm going to be
talking about members of
the IL-1 cytokine family and
their role as canonical
DAMPs of the immune system.
DAMPs, as I'm going to be
talking about a lot today,
are molecules that are
essentially damage-associated
molecular patterns.
As we shall see, these are
important molecules that drive
inflammation in the context
of necrosis or tissue damage.
0:29
As you know, inflammation is
initiated by two main drivers,
either strangers in the
form of infectious agents,
such as bacteria or viruses
and the concept of PAMPs
was introduced by
Charles Janeway
about 30 years ago when he
suggested that infectious agents
all contain the so-called
pathogen-associate
molecular patterns.
These are molecules that
are effectively unique
to microbial agents that
are not present
normally in the body.
These PAMPs are essentially
interpreted by the body,
by the immune system
as being indicative
of infection or non-self.
PAMPs are introduced into the
body by infectious agents,
and then they trigger
or are sensed
by pattern recognition
receptors,
receptors that are essentially
trained to recognize PAMPs.
In the other scenario, you've
got molecules that are
indicative of danger.
As we shall see,
Polly Matzinger realized that
effectively inflammation
can be initiated
by things other than strangers,
by things other than
infectious agents.
By realizing that in the
context of sterile immunity,
where you don't have an
infectious agent in the body,
but instead, you have
tissue damage or
tissue stress caused by
either physical injury,
by toxins, noxious agents,
or things that effectively just
perturb normal
homeostasis in cells.
You have a situation
where self-molecules,
which she dubbed danger
signals at the time,
are now more commonly
called DAMPs,
or damage-associated
molecular patterns.
These self-molecules
are released from cells
or released from one
particular cellular
compartment into another,
such as released from
mitochondria into the cytosol,
and these DAMPs can also
trigger inflammation.
As we shall see,
they trigger inflammation
by being sensed by
a different type of pattern
recognition receptor,
and they are also able
to drive inflammation.
Inflammation can be initiated by
either PAMPs associated
with strangers or by
DAMPs associated with danger in
the form of tissue
damage or tissue stress.
In both cases, either PAMPs
or DAMPs can drive inflammation.