Innate Immunity, Inflammation and Toll-like Receptors (TLRs) Jean Maguire van Seventer, VMD Department of Environmental Health Boston University School of Public Health Overview I. Inflammation and the Immune Response II. Positive and Negative Outcomes of and Immune Response III. Toll-like Receptor (TLR) Biology IV. Innate Immunity in the CNS Appendix A Presentation 2 - van Seventer RAC-GWVI Meeting Minutes November 1-2, 2010 Page 54 of 234
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Innate Immunity, Inflammation and
Toll-like Receptors(TLRs)
Jean Maguire van Seventer, VMD
Department of Environmental HealthBoston University School of Public Health
Overview
I. Inflammation andthe Immune Response
II. Positive and NegativeOutcomes of and Immune Response
III. Toll-like Receptor (TLR) Biology
IV. Innate Immunity in the CNS
Appendix A Presentation 2 - van Seventer
RAC-GWVI Meeting Minutes November 1-2, 2010 Page 54 of 234
Overview
I. Inflammation andthe Immune Response
II. Positive and NegativeOutcomes of and Immune Response
III. Toll-like Receptor (TLR) Biology
IV. Innate Immunity in the CNS
Immune System
A system of defenses by which the body
(host)
recognizes self from non-self(foreign material)
The immune systemdestroys or neutralizes
foreign matter, both living and nonliving.
Appendix A Presentation 2 - van Seventer
RAC-GWVI Meeting Minutes November 1-2, 2010 Page 55 of 234
White Cells
White Blood Cells are Mediators ofthe Immune Response
White Blood Cell Lineages
Appendix A Presentation 2 - van Seventer
RAC-GWVI Meeting Minutes November 1-2, 2010 Page 56 of 234
The Immune Responseto Infectious Pathogens
Infectious Pathogenscutaneous/
mucosal membrane
Extracellular bacteria, parasites, fungi
Intracellular bacteria,parasites
Viruses(intracellular)
Parasitic worms(extracellular)
AdaptiveImmune Response
Innate Immune Response
Appendix A Presentation 2 - van Seventer
RAC-GWVI Meeting Minutes November 1-2, 2010 Page 57 of 234
Both Innate and Adaptive Immunity Depend on the Activities of White Blood Cells
Innate Immune Response
AdaptiveImmune Response
macrophages
neutrophils lymphocytesdendritic cells“DC”
B cell T cell
Appendix A Presentation 2 - van Seventer
RAC-GWVI Meeting Minutes November 1-2, 2010 Page 58 of 234
Innate Immune Response
AdaptiveImmune Response
- Immediate response0-96 hours
- Gradual response> 96 hours
-Targetsgroups of pathogens
-Targetsspecific pathogens
- No Memory - Memory
Pathogenic Microbes
Extracellular bacteria, parasites, fungi
Intracellular bacteria,parasites
Viruses(intracellular)
Parasitic worms(extracellular)
macrophages
cutaneous/mucosal membrane
immature dendritic cells
The Immune Response
neutrophils
monocytes
B cell
T cell
Adaptive Immune Response
lymph node
Innate Immune Response
Appendix A Presentation 2 - van Seventer
RAC-GWVI Meeting Minutes November 1-2, 2010 Page 59 of 234
Innate Immunity
The First Line of Defense
Innate Immune Cells
Appendix A Presentation 2 - van Seventer
RAC-GWVI Meeting Minutes November 1-2, 2010 Page 60 of 234
initiated when innate immune cell
Pattern Recognition Receptors
including Toll-like receptors (TLRs), Nod-like
receptors (NLRs)and RIG-like receptors (RLRs)
are triggered by microbe-specific motifs,
Pathogen-Associated Molecular Patterns(PAMPs)
Recognition of Pathogens by Innate Immune Cells
Events Elicited by Triggering of Macrophage and Neutrophil TLRs
• phagocytosis
• secretion of inflammatory cytokines
• secretion of chemokines (chemoattractants);recruitment of additional innate immune cells
Appendix A Presentation 2 - van Seventer
RAC-GWVI Meeting Minutes November 1-2, 2010 Page 61 of 234
Ilya Ilich (a.k.a. Elie) MechnikovFirst Observed Phagocytosis by Phagocytes
a fundamental process of the innate immune response
http://www.pasteur.fr/pasteur/musees
PhagocytosisMicrobe or other foreign material taken up by endocytosis
and isolated and destroyed within a phagolysosome
Vander’s Human Physiology. The McGraw-Hill Companies, Inc. , Editors
Appendix A Presentation 2 - van Seventer
RAC-GWVI Meeting Minutes November 1-2, 2010 Page 62 of 234