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.mcgraw-
hill.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

Various adhesive
Selectins Integrins molecules

Weak binding
In some inflammatory diseases therapy is directed against
and rolling Activation and
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-γ)
 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

i va ting
Act

i bi tory
Inh

NK cell is inhibited

NO KILLING
 NK cell killer function

Depends on balanse of signals by activating and inhibitory receptors

Inhi
b itory

Acti
vatin
g

NK cell is activated
KILLING
 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
apoptosis
FasL Fas
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 Inflammation induction

Activation (IL-12 and IFN-γ) (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 a. Production of enzymes, ROS and NO
recognize
2. Epithelial cells provide chemical b. Kill our own virus-infected cells
barrier for pathogens by
3. Macrophages stimmulate inflammation c. Polysaccharide capsule production
by production of
4. Macrophages kill phagocytosed d. TNF, IL-1 and other mediators
microbes by
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 h. When a target cell does not express MHC
stimulates class I
9. Bacteria can avoid phagocytosis by i. Leukocyte migration

10. Innate immunity cells stimulate j. Peptide antibiotics production

adaptive immunity by
1.____
g 2.____
j 3.____
d 4.____
a 5.____
b 6.____
h 7.____
i 8.____
f 9.____
c 10.____
e