Lecture 2: Innate Immunitystreaming.einstein.yu.edu/docs/conferences/...Seminars in Immunology ....
Transcript of Lecture 2: Innate Immunitystreaming.einstein.yu.edu/docs/conferences/...Seminars in Immunology ....
Questions to Consider
How can the immune system detect invasion by pathogens and alert the immune system- immunological triage?
Can the immune system use pathogen profiling as a quick and dirty way to differentiate pathogens from self-antigens
Immune System Design
How can the immune system detect invasion by pathogens and alert the immune system?
Can the immune system use pathogen profiling as a quick and dirty way to differentiate pathogens from self-antigens?
How does the immune system contain pathogens?
How are immune cells directed to sites of infection?
Initiation of an Inflammatory Response
Clinical Manifestations• pain-increased vascular
diameter• redness and heat-
increased blood flow and decreased blood flow velocity
• swelling- increased vascular permeability
Initiation of an Inflammatory Response
Causes• Response to bacterial replication• Response to tissue damage• Response to macrophage mediator
release
Goals of the Inflammatory Response
Prevent the initial establishment of infection
Prevent spread of infection from invasion site
Recruit effector cells for assistance
Alert and mobilize B cells and T cells
The Innate Immune Response is the Layered Front Line of the Host Defense System Using Pattern Recognition
Far More Rapid Progression of Bacterial Infection in Mice Lacking the Innate Immune Response Than in Mice
Lacking the Adaptive Immune Response
Phagocytic Cells Express Receptors That Specifically Bind Pathogen-derived Moieties Which Can Induce
Cellular Activation and Differentiation
Bacterial Derived Factor Cellular Receptor
Glucan Glucan receptor
Mannose Mannose receptor
Lipopolysaccharide (LPS) CD14/Toll-like receptor (TLR)-4
Toll- An Important Immune Molecule In Flies
Toll, discovered in 1996, is a drosophila developmental gene
When this gene was knocked out, the fruit flies succumbed to massive fungal infection
This indicated Toll encoded an important immune molecule
Phagocytic Cells Express Receptors That Specifically Bind Pathogen-derived Moieties Which Can Induce
Cellular Activation and Differentiation
Bacterial Derived Factor
Cellular Receptor
Lipopolysaccharide (LPS)
CD14/Toll-like receptor (TLR)-4
Mannose Mannose receptor
Glucan Glucan receptor
Toll-like Receptors Recognize Unique Pathogen-associated Molecular Patterns (PAMP)
ssRNA (HIV)Gram positive bacteriaGram
negativebacteria
Seminars in Immunology 2004;16:3-9
Langerhans’ cells Provide a Link Between the Innate and Adaptive Immune Systems
Immature dendritic cells that are present in the skin
After activation, they migrate to the lymph nodes and transport skin-derived antigens
In the lymph nodes, they become activated dendritic cells and activate antigen specific lymphocytes
These cells are one way the innate immune system activates the adaptive immune response
LPS Interacts With TLR-4 Expressed by Langerhans’ Cells and Induces Their Migration to Lymph Nodes and
Differentiation Into Antigen Presenting Dendritic Cells
Binding of LPS toCD14/TLR-4
Migration intoLymph Nodes
Differentiation IntoDendritic Cells
IL-6 Produced by Monocytes Activated by Bacterial Components Stimulates the Liver to
Produce Factors That Bind to PAMPs
Monocytes Activated by Bacterial Components Secrete Cytokines Including TNF-That
Amplify the Immune Response
How Can Effector Cells be Recruited to Sites of Infection?
Local site that is infected• Requires expression of focused signals that can recruit specific
cells needed to contain infection
Effector cells• Need capacity to recognize these signals so that they can
migrate from the circulation into the inflammatory site
A Broad Range of Chemokines Selectively Induce the Migration of Different Inflammatory Cells
CXC Motif Chemokines CC Motif Chemokines
Adhesion Molecules Expressed by Epithelial Cells Bind to Other Adhesion Molecules Expressed by Inflammatory Cells
Adhesion Molecules Expressed by Epithelial Cells Bind to Other Adhesion Molecules
Expressed by Inflammatory Cells
Infected Tissues Produce IL-8 and Express Adhesion Molecules to Recruit Phagocytes Into Infected Tissues
•Infected tissues Produce IL-8 and express ICAM-1
•IL-8 induces LFA-1 expression by phagocytes
•LFA-1 binds to ICAM-1 and mediates phagocyte entry into interstitial tissues
Questions to Consider
How can the immune system detect invasion by pathogens and alert the immune system?
Can the immune system use pathogen profiling as a quick and dirty way to differentiate pathogens from self-antigens?
How does the immune system contain pathogens?
How are immune cells directed to sites of infection?