7. Mechanisms of innate immunity
- phylogenetically older
- exist before or react immediately after contact with pathogen
- first line of defense
- are not enhance upon repeated contact with pathogen (no memory)
- react predominantly to infectious agents
- stimulate and shape adaptive imunity
8. Components of innate immunity
- epithelial barriers (skin and mucosal membranes)
- humoral components (complement, cytokines etc.)
- cells (phagocytes, NK cells...)
9. - intraepithelial lymphocytes
- normal bacterial flora
- chemical barrier
(production of antimicrobial peptides)
- physical barrier
Functions of epithelia in innate immunity
10. 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)
11. 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...)
12. 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:
15. 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 Integrins
Various adhesive
molecules
Chemokines
Macrophages
In some inflammatory diseases therapy is directed against
proinflammatory cytokines or adhesive molecules
(eg: TNF in rheumatoid arthritis or VLA-4 in multiple sclerosis)
16. 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)
17. NK cell killer function
Depends on balance of signals by activating and inhibitory receptors
18. NK cell is inhibited
NO KILLING
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
19. NK cell is activated
KILLING
NK cell killer function
Depends on balanse of signals by activating and inhibitory receptors
20. - activating receptors recognize stress-derived 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
22. 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
23. - complement proteins
- other plasma proteins (CRP, MBL etc.)
- cytokines
Humoral mechanism of innate immunity
24. Macrophage and NK cell
Activation (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...)
25. 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
derived by innate immunity
26. Peptide antibiotics production
j.
Innate immunity cells stimulate
adaptive immunity by
10.
Leukocyte migration
i.
Bacteria can avoid phagocytosis by
9.
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 for
7.
NK and T- cells
f.
NK cells are activated
6.
molecules that provide “second signal”
e.
NK cells
5.
TNF, IL-1 and other mediators
d.
Macrophages kill phagocytosed
microbes by
4.
Polysaccharide capsule production
c.
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 NO
a.
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
