Post on 14-Jan-2016
description
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
Principle mechanisms of innate and adaptive immunity
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
Components of innate immunity
- epithelial barriers (skin and mucosal membranes)
- humoral components (complement, cytokines etc.)
- cells (phagocytes, NK cells...)
- physical barrier
Functions of epithelia in innate immunty
- chemical barrier (production of antimicrobial peptides)
- physical barrier
Functions of epithelia in innate immunty
- intraepithelial lymphocytes
- normal bacterial flora
- chemical barrier (production of antimicrobial peptides)
- physical barrier
Functions of epithelia in innate immunty
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)
Role of phagocytes in innate immunity
Order of events in infection
1. Entry of pathogen
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
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:
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
Phagocytosis and killing of
microbes
Pathogen recognition
Zipping of membrane around microbe
Phagocytosis and killing of
microbes
Ingestion of microbe
Phagocytosis and killing of
microbes
Fusion of phagosomewith lysosome
Phagocytosis and killing of
microbes
Phagocyte activation
Phagocytosis and killing of
microbes
Killing of microbe
Phagocytosis and killing of
microbes
http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter31/animation_quiz_3.html
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...)
Inflammation induction
Proinflammatory cytokines
TNF ― Tumor Necrosis FactorIL-1 ― Interleukin-1Chemokines ― Chemotactic cytokines
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
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)
Chemokines
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
6. Pathogen elimination and/or adaptive immunity activation (dendritic cells)
- cytokines, costimulatory molecules...
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
6. Pathogen elimination and/or adaptive immunity activation
7. Tissue repair and remodeling (macrophages)
- enzymes and cytokines (growth factors, metaloproteinases...)
Role of NK cells in innate immunity
Killing of cells infected by intracellular pathogens
(eg. viruses) andtumor cells
NK – Natural killer
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)
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
Inhibitory Activating
Inhibitory
Activating
NK cell is inhibited
NO KILLING
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
Inhibitory
Activating
NK cell is activatedKILLING
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
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
Mechanism of NK cell recognition
Mechanism of NK cell recognition
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 cell
apoptosis
NK cell perforin
FasL Fas
NK cell killer function
- complement proteins (8th week seminar)
- other plasma proteins (CRP, MBL etc.)
- cytokines
Humoral mechanism of innate immunity
Cytokines in innate immunity
Inflammation induction(TNF, IL-1, chemokines...)
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...)
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
Thanks for your attention!
Questions?
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