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
- are not enhanced upon repetead contact with pathogen (no memory)
- react predominantly to infectious agents
- first line of defense
- stimulate and shape adaptive imunity
Components of innate immunity
- epithelial barriers (skin and mucosal membranes)
- cells (phagocytes, NK cells...)
- humoral components (complement, cytokines etc.)
Functions of epithelia in innate immunty
- physical barrier
Functions of epithelia in innate immunty
- physical barrier
- chemical barrier
(production of antimicrobial peptides)
Functions of epithelia in innate immunty
- physical barrier
- chemical barrier
(production of antimicrobial peptides)
- intraepithelial lymphocytes
- normal bacterial flora
Cells of innate immunity
Cell type
Pricipal function(s)
Monocytes/Macrophages
Phagocytosis, inflammation,
T-cell activation, tissue repair
Neutrophils
Phagocytosis, inflammation
NK cells
Killing of infected or tumor cells
Dendritic cells
Phagocytosis, activation of naive T-cells
Mast cells
Inflammation
Eosinophils
Defense against parasites
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
- not present on human cells
Lipoproteins
Flagellin
Examples:
structures of bacterial cell wall (LPS, peptidoglycan, flagellin...)
nucleic acids of pathogens (dsRNA, unmethylated CpG dinucleotides...)
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
Phagocytosis and
killing of
microbes
Zipping of membrane
around microbe
Phagocytosis and
killing of
microbes
Ingestion of microbe
Phagocytosis and
killing of
microbes
Fusion of phagosome
with lysosome
Phagocytosis and
killing of
microbes
Phagocyte activation
Phagocytosis and
killing of
microbes
Killing of
microbe
http://highered.mcgrawhill.com/sites/0072556781/student_view0/chapt
er31/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 Factor
IL-1 ― Interleukin-1
Chemokines ― 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)
http://www.youtube.com/watch?v=WEGGMaRX8f0
http://www.youtube.com/watch?NR=1&v=DMvixApKzKs
Integrins
Selectins
Various adhesive
molecules
Weak
binding
In some
inflammatory diseases therapy is directed against
Activation and
and rolling
proinflammatory cytokines
or adhesive molecules
firm binding
Transmigration
(eg: TNF in rheumatoid arthritis or VLA-4 in multiple sclerosis)
Endothelium
Chemokines
TNF & IL-1
Arrival to the site of infection
Macrophages
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
NK – Natural killer
Killing of cells infected by
intracellular pathogens
(eg. viruses) and
tumor cells
Role of NK cells in innate immunity
NK – Natural killer
Killing of cells infected by
intracellular pathogens
(eg. viruses) and
tumor cells
Activation of
macrophages (by IFN-γ)
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
NK cell is inhibited
NO KILLING
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
NK cell is activated
KILLING
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
- activating receptors recognize stress-derrived structures on cells
(including infected and malignant cells)
- inhibitory receptors recognize MHC class one molecule
Mechanism of NK cell recognition
Mechanism of NK cell recognition
NK cell killer function
Apoptosis induction in infected and tumor cells
Killing mechanisms same as in cytotoxic T-cells
- Perforin and granzymes
- FasL and Fas
perforin
NK cell
granzymes
Infected or
tumor cell
FasL
Fas
apoptosis
Humoral mechanism of innate immunity
- complement proteins (8th week seminar)
- cytokines
- other plasma proteins (CRP, MBL etc.)
Cytokines in innate immunity
Inflammation induction
(TNF, IL-1, chemokines...)
Cytokines in innate immunity
Macrophage and NK cell
Activation (IL-12 and IFN-γ)
Inflammation induction
(TNF, IL-1, chemokines...)
Antiviral effects (IFN type I, IFN-α and IFN-β)
(eg. INF-α in HCV therapy)
Differentiation of T-cell subpopulation (eg. IL-12)
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?
1.
Receptors on innate immunity cells
recognize
a. Production of enzymes, ROS and NO
2.
Epithelial cells provide chemical
barrier for pathogens by
b. Kill our own virus-infected cells
3.
Macrophages stimmulate inflammation c. Polysaccharide capsule production
by production of
Macrophages kill phagocytosed
d. TNF, IL-1 and other mediators
microbes by
4.
5.
NK cells
e. molecules that provide “second signal”
6.
NK cells are activated
f. NK and T- cells
7.
Chemokynes are important for
g. Structures that a group of pathogens has
in common
8.
IL-12 produced by macrophages
stimulates
h. When a target cell does not express MHC
class I
9.
Bacteria can avoid phagocytosis by
i. Leukocyte migration
Innate immunity cells stimulate
adaptive immunity by
j. Peptide antibiotics production
10.
1.____
g
2.____
j
3.____
d
4.____
a
5.____
b
6.____
h
7.____
i
8.____
f
9.____
c
10.____
e