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)

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.

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