Innate immunity
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Transcript of Innate immunity
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Innate immunity
• Properties of innate immunity• Components of innate immunity
– Epithelial barriers– Cellular mechanisms– Humoral mechanisms
• Role of innate immunity in stimulating adaptive immune response
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Principle mechanisms of innate and adaptive immunity
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Mechanisms of innate immunity
- phylogenetically older
- exist before or react immediately after contact with pathogen
- first line of defense
- are not enhanced upon repetead contact with pathogen (no memory)
- react predominantly to infectious agents
- stimulate and shape adaptive imunity
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Components of innate immunity
- epithelial barriers (skin and mucosal membranes)
- humoral components (complement, cytokines etc.)
- cells (phagocytes, NK cells...)
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- physical barrier
Functions of epithelia in innate immunty
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- chemical barrier (production of antimicrobial peptides)
- physical barrier
Functions of epithelia in innate immunty
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- intraepithelial lymphocytes
- normal bacterial flora
- chemical barrier (production of antimicrobial peptides)
- physical barrier
Functions of epithelia in innate immunty
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Cells of innate immunity
NK cells
Dendritic cells
Mast cells
Neutrophils
Monocytes/Macrophages
Phagocytosis, inflammation
Phagocytosis, inflammation,T-cell activation, tissue repair
Killing of infected or tumor cells
Eosinophils
Inflammation
Defense against parasites
Phagocytosis, activation of naive T-cells
Cell type Pricipal function(s)
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Role of phagocytes in innate immunity
Order of events in infection
1. Entry of pathogen
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Role of phagocytes in innate immunity
Order of events in infection
1. Entry of pathogen
2. Recognition of pathogen (macrophages and dendritic cells)
- molecular patterns and receptors
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Molecular patterns
Structures common for certain groups/classes of pathogens- essential for their life, replication and/or infectivity
structures of bacterial cell wall (LPS, peptidoglycan, flagellin...)
nucleic acids of pathogens (dsRNA, unmethylated CpG dinucleotides...)
- not present on human cells
Lipoproteins
Flagellin
Examples:
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Role of phagocytes in innate immunity
Order of events in infection
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen (macrophages)
- reactive oxygen species (ROS), nitric oxide (NO) and lysosomal enzymes
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Phagocytosis and killing of
microbes
Pathogen recognition
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Zipping of membrane around microbe
Phagocytosis and killing of
microbes
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Ingestion of microbe
Phagocytosis and killing of
microbes
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Fusion of phagosomewith lysosome
Phagocytosis and killing of
microbes
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Phagocyte activation
Phagocytosis and killing of
microbes
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Killing of microbe
Phagocytosis and killing of
microbes
http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_3.html
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Role of phagocytes in innate immunity
Order of events in infection
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Induction of inflammation (macrophages)
- production of pro-inflammatory cytokines (TNF, IL-1, chemokines...)
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Inflammation induction
Proinflammatory cytokinesTNF ― Tumor Necrosis FactorIL-1 ― Interleukin-1Chemokines ― Chemotactic cytokines
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Role of phagocytes in innate immunity
Order of events in infection
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Inflammation induction
5. Attraction of cells to infection site
- adhesive molecules (selectins and integrins) and chemokines
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Leukocytes arrive at the site of infection (extravasation)
Weak binding and rolling Activation and
firm binding
Endothelium
TNF & IL-1
Transmigration
Arrival to the site of infection
Selectins IntegrinsVarious
adhesive molecules
ChemokinesMacrophages
http://www.youtube.com/watch?v=WEGGMaRX8f0
http://www.youtube.com/watch?NR=1&v=DMvixApKzKs
In some inflammatory diseases therapy is directed against proinflammatory cytokines or adhesive molecules
(eg: TNF in rheumatoid arthritis or VLA-4 in multiple sclerosis)
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Role of phagocytes in innate immunity
Order of events in infection
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Inflammation induction
5. Attraction of cells to infection site6. Pathogen elimination and/or adaptive immunity activation (dendritic cells)
- cytokines, costimulatory molecules...
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Role of phagocytes in innate immunity
Order of events in infection
1. Entry of pathogen
2. Recognition of pathogen
3. Phagocytosis and killing of a pathogen
4. Inflammation induction
5. Attraction of cells to infection site6. Pathogen elimination and/or adaptive immunity activation
7. Tissue repair and remodeling (macrophages)
- enzymes and cytokines (growth factors, metaloproteinases...)
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Role of NK cells in innate immunity
Killing of cells infected by intracellular pathogens
(eg. viruses) andtumor cells
NK – Natural killer
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Role of NK cells in innate immunity
NK – Natural killer
Killing of cells infected by intracellular pathogens
(eg. viruses) andtumor cells
Activation of macrophages (by IFN-γ)
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NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
Inhibitory Activating
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Inhibitory
Activating
NK cell is inhibited
NO KILLING
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
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Inhibitory
Activating
NK cell is activatedKILLING
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
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Inhibitory Activating
- activating receptors recognize stress-derrived structures on cells (including infected and malignant cells)
- inhibitory receptors recognize MHC class one molecule
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
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Mechanism of NK cell recognition
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Mechanism of NK cell recognition
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Apoptosis induction in infected and tumor cells
Killing mechanisms same as in cytotoxic T-cells
- Perforin and granzymes
- FasL and Fas
granzymes Infected or
tumor cellapoptosis
NK cell perforin
FasL Fas
NK cell killer function
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- complement proteins (8th week seminar)
- other plasma proteins (CRP, MBL etc.)
- cytokines
Humoral mechanism of innate immunity
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Cytokines in innate immunity
Inflammation induction(TNF, IL-1, chemokines...)
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Macrophage and NK cellActivation (IL-12 and IFN-γ)
Antiviral effects (IFN type I, IFN-α and IFN-β)
Differentiation of T-cell subpopulation (eg. IL-12)
(eg. INF-α in HCV therapy)
Cytokines in innate immunity
Inflammation induction(TNF, IL-1, chemokines...)
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Role of innate immunity in
stimulation of adaptive immune
response
T or B-cells need two signals for activation
First signal antigen recognition
Second signal derrived by innate
immunity
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Thanks for your attention!
Questions?
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Peptide antibiotics productionj.Innate immunity cells stimulate adaptive immunity by
10.
Leukocyte migrationi.Bacteria can avoid phagocytosis by9.
When a target cell does not express MHC class I
h.IL-12 produced by macrophages stimulates
8.
Structures that a group of pathogens has in common
g.Chemokynes are important for7.
NK and T- cellsf.NK cells are activated6.
molecules that provide “second signal”e.NK cells5.
TNF, IL-1 and other mediatorsd.Macrophages kill phagocytosed microbes by
4.
Polysaccharide capsule productionc.Macrophages stimmulate inflammation by production of
3.
Kill our own virus-infected cells b.Epithelial cells provide chemical barrier for pathogens by
2.
Production of enzymes, ROS and NOa.Receptors on innate immunity cells recognize
1.
10.____9.____8.____7.____6.____5.____4.____3.____2.____1.____g j d a b h i f c e