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
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-)

NK cell killer function

Depends on balanse of signals by activating and inhibitory receptors

Inhibitory

Activating

NK cell killer function

Depends on balanse of signals by activating and inhibitory receptors

ing
t
a
v
i
Act

ory
t
i
b
i
Inh

NK cell is inhibited
NO KILLING

NK cell killer function

Depends on balanse of signals by activating and inhibitory receptors
Inhi
bito
ry

Acti

NK cell is activated
KILLING

vatin
g

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

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-)

Inflammation induction
(TNF, IL-1, chemokines...)

Antiviral effects (IFN type I, IFN- and IFN-)

(eg. INF- 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