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Printable Handouts
Navigable Slide Index
- Introduction
- Innate immunity
- Classical and nonclassical NF-kappa-B pathways
- I-kappa-B-alpha mRNA and LPS injection
- I-kappa-B-alpha mRNA and cytokine injection
- Cell types responsible for NF-kappa-B activation
- Triggering inflammatory pathways in the brain
- CD14 mRNA expression wave after an LPS bolus
- Circumventricular organs
- CD14 mRNA expression wave from area postrema
- Microglia cells (1)
- Microglia cells (2)
- The wave of proinflammatory signaling in the brain
- Molecules inducing transcription activation
- Is LPS directly triggering parenchymal microglia?
- Centrally produced TNF-alpha induces signaling
- Activation of I-kappa-B-alpha and TNF-alpha
- Patterns of gene expression
- TNF-alpha i.c.v. injection
- TNF-alpha release by the resident microglia cells
- Summary of innate immune response so far
- Receptor mediating LPS effect in the brain
- Toll-like receptors
- TLR4 mediates NF-kappa-B activation
- Constitutive expression of TLR4 and CD14 in CNS
- TLR4 and CD14 in the circumventricular organs
- A family of eleven TLRs so far
- TLR2 mRNA up-regulated by gram(-) bacteria
- TLR2 mRNA expression wave after LPS injection
- TLR2 mRNA expression wave in CVO
- TLR2 mRNA in iba1-ir cells (microglia)
- Proinflammatory signaling in response to LPS
- What about intracerebral LPS?
- LPS-ir after single LPS bolus in the striatal region
- Gene expression after LPS bolus in striatal region
- Role of glucocorticoids (GCs)
- Cortison prevents TNF-alpha gene expression
- Neuroprotection or neurodegeneration?
- Neuroprotective role of innate immune response
- Role of glucocorticoids in neurodegeneration
- LPS is highly neurotoxic in RU486-treated rats
- Cytokines and GCs effect on brain tissue
- Effects of the innate immune response
- Summary
- Innate immunity in neurodegenerative disorders
- Alzheimer's disease
- Microglial migration in Tg APP23 mouse brain
- Microglial migration forming the plaque
- Chemotaxis of microglial cells throughout plaque
- Studying the origin of microglial cells
- Infiltration of bone marrow derived MG cells
- GFP expressing microglial cells
- Bone marrow derived MG cells reach the plaque
- Amount of BM derived MG cells in plaque
- Quantifying plaque data
- Recruiting factor for bone marrow derived MG cells
- Endogenous beta-amyloid activates immune cells
- Exploring the role of newly differentiating cells
- Generating triple transgenic animals
- BM-derived MG eliminate amyloid deposits in vivo
- BM-derived MG cells are competent immune cells
- BM-derived MG clear beta-amyloid
- BM-derived MG cells control plaque toxicity
- BMSCs in AD
- Using genetically modified BM-derived MG cells
- Genetically modified SCs in acute injury models
- The take home message
- Acknowledgements (1)
- Acknowledgements (2)
- Acknowledgements (3)
- Acknowledgements (4)
- Acknowledgements (5)
- Acknowledgements (6)
- Acknowledgements (7)
- Acknowledgements (8)
- Acknowledgements (9)
- Thank you
Topics Covered
- Systemic infection and blood sepsis
- Toll-like receptors and proinflammatory signaling in microglia
- Brain diseases associated with inflammation
- Innate immunity and neuroprotection
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Rivest, S. (2017, May 24). Inflammation and immune cell entry to the central nervous system [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 26, 2024, from https://doi.org/10.69645/ZNQW4132.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Serge Rivest has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
A selection of talks on Immunology
Transcript
Please wait while the transcript is being prepared...
0:04
So it is exactly the Innate immunity.
The presence of infections is recognized by receptors for
a specific event called the Pathogen-Associated Molecular Patterns or the PAMPs.
These PAMPs are produced by microorganisms,
such as bacteria, or fungi and yeast.
The recognition of these PAMPs by myeloid cells is the first step of
a complex inflammatory reactions that characterizes the innate immune response.
So the Endotoxin Lipopolysaccharide is
a major component of the outer membranes of the Gram-negative bacteria,
which is the best known target of innate recognition and induce
a robust inflammatory response by phagocytes or phagocytic cells, if you want.
We have many other PAMPs such as Peptidoglycan and so LTA from
Gram-postive bacterias which are known common structural patterns that are
recognized by host germ lines encoded receptors and induce stimulation of
the nuclear factors called NF kappa B signaling pathways and cytokine synthesis.
1:01
An NF kappa B is certainly one of
the best known signaling factors that is associated with the inflammatory response.
You have a classical NF kappa B and you have a known Classical NF kappa B pathways.
And a Classical one is clearly taking place in macrophages, dendritic cells,
monocytes and the cells that are clearly
responsible for the innate immune response and you have
a Nonclassical cell cell interactions that are critical for
the T and B cells that developments which are involved in the adaptive immunity.
Then you have the T cells,
you have the antigens interacting with the TCR and
also you have other ligands such as the LT
for Lymphotoxin or BAFF for B-cells and
activating factors which activates B receptors in B cells.
But the Classical one is really the one which is
triggered by the cytokine we just mentioned before such as TNF,
Interleukin-1 and LPS or many other PAMPs.
They triggered the NF kappa B activation by interacting with specific receptors,
express on the surface of B cells such as
Interleukin-1 receptors and you have also the Toll-like receptors, the TLR.
These receptors engaged productions of NF kappa B via
series of adaptive proteins such as myD88,
TRAF 6 and TAB, TAK and TAB.
These are the proteins which will activate phosphorylation of the complex of IKK.
Once you have phosphorylation of IkB for example,
then you have activations of the NF kappa B,
essentially, the main factors which is p50 and p65.
Then, you have translocations of the nuclear factors,
these activate a wide varieties of genes,
target genes such as genes involved in inflammations,
genes involved in the receptors productions and anti-apoptosis genes as well.
Then, this is clearly taking place within minutes,
once the ligands has been triggered the receptors.