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- Models of Investigation
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1. Antifungal innate immunity in C. elegans
- Dr. Jonathan Ewbank
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2. The anti-microbial defense of Drosophila: a paradigm for innate immunity
- Prof. Jules Hoffmann
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3. Phagocytosis in the fruit fly, Drosophila melanogaster
- Dr. Lynda Stuart
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4. Innate immune sensing and response
- Prof. Bruce Beutler
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5. Macrophages and systems biology
- Prof. David Hume
- Cell Types and Recruitment
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6. Leukocyte recruitment in vivo
- Prof. Paul Kubes
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8. Eosinophils
- Prof. Tim Williams
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9. Dendritic cells: linking innate to different forms of adaptive immunity
- Prof. Ralph Steinman
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11. Innate-like lymphocytes 1
- Prof. Adrian Hayday
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12. Innate-like lymphocytes 2
- Prof. Adrian Hayday
- Recognition and Signaling
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13. Colony stimulating factor-1 regulation of macrophages in development and disease
- Prof. E. Richard Stanley
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14. Fc receptors: linking innate and acquired immunity
- Prof. Ken G C Smith
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15. Phagocytosis
- Prof. Joel Swanson
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16. Clearance of apoptotic cells and the control of inflammation
- Prof. Sir John Savill
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17. Signaling by innate immune receptors
- Prof. Michael Karin
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18. Nuclear receptors at the crossroads of inflammation and atherosclerosis
- Prof. Christopher Glass
- Modulation of Effector Responses
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19. Humoral innate immunity and the acute phase response 1
- Prof. Alberto Mantovani from humanitas.it
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20. Humoral innate immunity and the acute phase response 2
- Prof. Alberto Mantovani from humanitas.it
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21. Cytokines regulating the innate response
- Prof. Anne O’Garra
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22. Arginase and nitric oxide
- Dr. Peter Murray
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23. Novel lipid mediators in resolution of inflammation
- Prof. Charles Serhan
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25. Cationic peptides in innate immunity
- Dr. Dawn Bowdish
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26. Iron metabolism and innate immunity
- Prof. Tomas Ganz
- Pathogen-Host Interactions
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27. Innate recognition of viruses
- Prof. Caetano Reis e Sousa
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28. Type I interferons in innate immunity to viral infections
- Prof. Christine Biron
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29. HIV-1 and immunopathogenesis: innate immunity
- Prof. Luis Montaner
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30. Understanding and combating tuberculosis
- Prof. David Russell
-
32. Innate immunity and malaria
- Prof. Douglas Golenbock
- Health and Disease
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33. Innate immunity in children
- Prof. David Speert
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34. From bench to bedside: evolution of anti-TNFalpha therapy in rheumatoid arthritis
- Prof. Sir Ravinder Maini
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35. NOD-like receptors in innate immunity and inflammatory disease
- Prof. Gabriel Nunez
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36. Paneth cells in innate immunity and inflammatory bowel disease
- Prof. Satish Keshav
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37. Innate immunity in the brain in health and disease
- Prof. V. Hugh Perry
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38. The fate of monocytes in atherosclerosis
- Prof. Gwendolyn Randolph
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39. Macrophages, a cellular toolbox used by tumors to promote progression and metastasis
- Prof. Jeffrey Pollard
- Archived Lectures *These may not cover the latest advances in the field
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40. Monocyte/macrophages in innate immunity
- Prof. Emeritus Siamon Gordon
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41. Innate immunity in C. elegans
- Dr. Jonathan Ewbank
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43. NLR genes: infection, inflammation and vaccines
- Prof. Jenny Ting
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44. Manipulation of innate immune response: lessons from shigella
- Prof. Philippe Sansonetti
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45. Innate immunity of the lung and adaptation to air breathing at birth
- Prof. Jeffrey Whitsett
Printable Handouts
Navigable Slide Index
- Introduction
- Malaria: the facts in 2007
- The pathology of malaria is driven by cytokines
- Life cycle of the malarial parasite
- Why do humans get fever during malaria?
- The search for the "malaria toxin" (1)
- The search for the "malaria toxin" (2)
- Is it a component of the outer membrane?
- Gram negative cell envelope - LPS
- Is the malaria toxin just like LPS?
- Glycosylphosphatidyl inositol anchor (GPI)
- GPI anchors activate TLR2
- Purified P.falciparum failed to induce cytokines
- The major immune-stimulus in malaria is not GPI
- What is hemozoin?
- Pure hemozoin failed to induce cytokines
- Hemozoin levels and disease severity
- Hemozoin production
- Purification of hemozoin with a magnetic column
- Purified hemozoin
- Hypothesis (1)
- What is a Toll receptor?
- Identification of Toll receptors (1)
- "Toll"
- Toll receptor and TIR domain
- Identification of toll receptors (2)
- Toll receptor role in innate immune response (1)
- Toll receptor role in innate immune response (2)
- Toll innate immune response in humans and flies
- TLRs in humans, mice and flies
- The purple sea urchin has 222 TLRs
- Innate immune recognition system 1997
- Innate immune recognition system 2007
- Domains of TLR
- Shizuo Akira (1)
- Bacterial DNA is rich in non-methylated CpG
- Shizuo Akira (2)
- Hz activates IL1 production via TLR9/MyD88
- Activity of hemozoin is destroyed by DNase
- Thus, DNA is the cytokine inducing component
- Is the DNA on hemozoin human or malarial?
- PCR analysis shows that most DNA is malarial
- Can malaria DNA actually stimulate cells?
- The cell biology of TLR9 is complex
- TLR9 translocates to the endosome
- Does malaria DNA activate innate immunity?
- Malaria DNA is stimulatory only with DOTAP (1)
- Malaria DNA is stimulatory only with DOTAP (2)
- The malaria genome contains 269 CpG repeats
- Current hypothesis
- But, most malaria DNA is AT-rich
- Patients with malaria show IFN signature
- Hemozoin/DNA activates IFN-beta production
- Malaria genome contains the motif ATTTTTAC
- AT-rich ODN mimic malarial DNA
- AT-rich ODN activate IFN-beta production
- AT-rich ODN activate IFN independently of TLRs
- AT-rich ODN activation of IFN requires IRF1
- Is the inflammasome involved in the recognition?
- The inflammasome
- AT-rich ODN activate IL-1beta production
- Activation of IL-1beta is via caspase-1
- Malarial DNA activates the inflammasome
- Is the inflammasome involved in IFN Generation?
- Activation of IFN requires Nalp3 but not ASC
- Activation of IL-1beta requires caspase 1
- Hemozoin DNA - from phagosome to cytosol
- Leakage after phagocytosis of inert particles
- Alzheimer's disease
- Beta amyloid
- A-beta induces IL-1beta production in microglia
- Beta-amyloid causes lysosomal swelling (1)
- Beta-amyloid causes lysosomal swelling (2)
- Beta-amyloid causes lysosomal leakage
- Conclusion
- Hypothesis (2)
- Summary
- Thanks
Topics Covered
- Malaria causes systemic inflammation, morbidity and death
- Toxic mediators: GPI anchor, Hemozoin/DNA
- DNA motifs: CpG (TLR9) and AT-rich (unknown receptor)
- Mechanisms of malarial sepsis-like syndrome, cerebral malaria
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Golenbock, D. (2009, June 30). Innate immunity and malaria [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 5, 2024, from https://doi.org/10.69645/LKSO7369.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Douglas Golenbock has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.