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Pattern recognition by cells

of the innate immune system


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KURSUS IMUNOLOGI DASAR 2012


rina_susilowati@ugm.ac.id

rina_susilowati@ugm.ac.id 2012

The success of a healthy immune system is


the ability to distinguish between
the bodys own cell (SELF) & foreign cells (NONSELF)

rina_susilowati@ugm.ac.id 2012

Immune Cells Should Distinguish Self and non Self cells


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Receptors of Innate immunity

Receptors of Adaptive immunity

T
B
Macrophages

rina_susilowati@ugm.ac.id 2012

Dendritic
cells

Immune Cells Should Distinguish Self and non Self cells


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Injured
cells
Altered self

Pathogens
(non self)

pathogen associated
molecular patterns
(PAMPs) e.g LPS, high
mannose

damage associated
molecular patterns
(DAMPs)

Eat
me

Normal
cells (self)

self-associated molecular
patterns (SAMPs)

Eat
me

Dont
eat me

pattern recognition receptors (PRRs)


Macrophages

Macrophages

Inflammation
rina_susilowati@ugm.ac.id 2012

Macrophages

Recognition of pathogens by host cells


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PAMPs are molecular components


associated with pathogens but not
found as a part of eukaryotic cells

PRRs are receptors produced by


host cells that recognize PAMPs
http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit4/innate/pamptlr.html

rina_susilowati@ugm.ac.id 2012

Recognition of pathogens by host cells


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Clin Microbiol Rev.2009 Apr;22(2):240-73, Table of Contents.


Pathogen recognition and inflammatory signaling in innate immune defenses. Mogensen TH

TLRs: Toll-like receptors


NLRs: NOD-like receptors
RLRs: RIG-like receptors
Others
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Cellular localization of pattern-recognition receptors (PRRs)


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Clin Microbiol Rev. 2009 Apr;22(2):240-73, Table of Contents.
Pathogen recognition and inflammatory signaling in innate
immune defenses. Mogensen TH

TLRs: Toll-like receptors


NLRs: NOD-like receptors
RLRs: RIG-like receptors
Others
rina_susilowati@ugm.ac.id 2012

Toll-like receptors represent an ancient pathogenrecognition system


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Flies use Toll to


defend from
fungi

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Mammalian Toll-like receptors are activated by


many different PAMPs
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Receptor
Ligands

TLR1/TLR2 Triacyl lipopeptides


TLR2/TLR6 Diacyl lipopeptides

Lipoteichoic acid
TLR2
Lipoproteins
Peptidoglycan
Lipoarabinomannan
Porins
Envelope glycoproteins
GPI-mucin
Phospholipomannan
Zymosan

-Glycan

TLR3
dsRNA
TLR4
LPS
Envelope glycoproteins
Glycoinositolphospholipids
Mannan

HSP70

TLR5
Flagellin

TLR7/8
ssRNA
TLR9
CpG DNA
Clin Microbiol Rev. 2009 April; 22(2): 240273.

rina_susilowati@ugm.ac.id 2012

Origin(s)
Bacteria
Mycoplasma
Gram-positive bacteria
Various pathogens
Gram-positive and -negative bacteria
Mycobacteria
Neisseria
Viruses (e.g., measles virus, HSV, cytomegalovirus)
Protozoa
Candida
Fungi
Fungi
Viruses
Gram-negative bacteria
Viruses (e.g., RSV)
Protozoa
Candida
Host
Flagellated bacteria
RNA viruses
Viruses, bacteria, protozoa

Other membrane bound PRRs


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Macrophage Mannose Receptor

Cell bound C type lectin e.g DC


SIGN that binds sugar molecules
on the surface on many bacteria
and viruses.

Dectin-1
C-type lectin that binds b-glucancontaining particles including
zymosan and C. albicans

Macrophage Scavenger
Receptor (SR-A)
Recognize certain anionic
polymers and low-density
lipoproteins

rina_susilowati@ugm.ac.id 2012

Extracellular (soluble) PRRs


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Initiate complement activation


Galectins
Lectins which bind beta galactoside. As galectins are dominantly found in the lesions where pathogeninitiated tissue damage signals appear, this lectin family is also considered as potential damageassociated molecular pattern (DAMP)

Pentraxin (such as serum amyloid and C-reactive protein)


Lipid transferases peptidoglycan recognition proteins (PGRs)
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Cytoplasmic PRRs: the RIG-I-like receptors detect


cytoplasmic viral RNAs and stimulate interferon production
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RLR : RIG like receptors RIG: Retinoic acid inducible gene

Receptor

Ligands

RLRs

RIG-I
MDA5

dsRNA (short), 5triphosphate RNA


dsRNA (long)

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Origin(s)
Viruses (e.g., influenza A virus, HCV, RSV)
Viruses (picorna- and noroviruses)

Cytoplasmic PRRs: The NOD-like receptors (NLR) act as


intracellular sensors of bacterial infection
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Receptor

NLRs

NOD1

NOD2

NALP1
NALP3

Ligands
Diaminopimelic acid
MDP
MDP
ATP, uric acid crystals, RNA,
DNA, MDP

Origin(s)
Gram-negative bacteria
Gram-positive and -negative bacteria
Gram-positive and -negative bacteria
Viruses, bacteria, and host
Clin Microbiol Rev. 2009 April; 22(2): 240273.

NLR: NOD-like receptors;


NOD: Nucleotide-binding oligomerization domain
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NLR binding trigger formation of inflammasomes


leading to IL-1 secretion
Davis BK et al., 2011 Annu. Rev. Immunol. 29:707-35

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NLR: NOD-like receptors;


NOD: Nucleotide-binding oligomerization domain
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PAMPs-PRRs recognition send danger signals


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Networking by small-molecule hormones in plant immunity


Corn M J Pieterse, Antonio Leon-Reyes, Sjoerd Van der Ent & Saskia C M Van Wees
Nature Chemical Biology 5, 308 - 316 (2009) Published online: 17 April 2009

rina_susilowati@ugm.ac.id 2012

Upon pathogen attack, pathogen-associated


molecular patterns (PAMPs) activate patternrecognition receptors (PRRs) in the host,
resulting in a downstream signaling cascade that
leads to PAMP-triggered immunity
http://www.nature.com/ni/journal/v8/n1/full/ni0107-11.html

PAMPs-PRRs recognition send danger signals


Yonsei Med J. 2011 May;52(3):379-92. doi: 10.3349/ymj.2011.52.3.429.
Intrinsic and extrinsic regulation of innate immune receptors.
Jeong E, Lee JY

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Recognition of PAMPs leads to engulfment of the pathogen as


well as activation of phagocytes and initiate an
inflammatory response
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Pathogen recognition initiate activation of adaptive immune


responses
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Pathogen-induced
TLR signaling in
immature dendritic
cells
induces their
migration to
lymphoid organs
and
enhances antigen
processing

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PAMPs-PRRs signaling can be inhibited by


virulent pathogens
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Virulent pathogens acquired


effectors (purple stars) that suppress
PAMPs-triggered immunity, resulting
in host susceptibility

Networking by small-molecule hormones in plant immunity


Corn M J Pieterse, Antonio Leon-Reyes, Sjoerd Van der Ent & Saskia C M Van Wees
Nature Chemical Biology 5, 308 - 316 (2009) Published online: 17 April 2009

rina_susilowati@ugm.ac.id 2012

TLR and NLR also recognize danger-associated molecular


patterns(DAMPs) to initiate limited innate immune responses
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Damage-associated molecular patterns (DAMPs)


I. Evolutionary culprit

II. Disruption of membrane


integrity

Curr Opin Immunol.2011 Feb;23(1):41-5. Epub 2011 Jan 3.


Sialoside-based pattern recognitions discriminating
infections from tissue injuries.
Liu Y Chen GY Zheng P

rina_susilowati@ugm.ac.id 2012

Receptors/Sensors

Retroelements

ND

Mitochondria DNA

TLR9

Formyl peptides

FPRL1/2

Monosodium urate crystal

NLRP3

Uric acid

NLRP3

Cholesterol crystals

NLRP3

Alum

NLRP3

TLR and NLR also recognize danger-associated molecular


patterns(DAMPs) to initiate limited innate immune responses
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Curr Opin Immunol.2011 Feb;23(1):41-5. Epub 2011 Jan 3.
Sialoside-based pattern recognitions discriminating
infections from tissue injuries.
Liu Y Chen GY Zheng P

Sialoside-based
pattern recognition
as a negative
regulator for innate
immune responses

rina_susilowati@ugm.ac.id 2012

Marker of self: CD47


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http://www.seas.upenn.edu/~discher/research.html

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Marker of self: MHC class I


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rina_susilowati@ugm.ac.id 2012

Summary
Pattern recognition by cells of the innate immune system
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Cells of innate immune


system detect danger
signals through PAMPs or
DAMPs - PRRs
recognition

Recognition of danger
signals leads to
engulfment of pathogen
or damage cells,
inflammation and
activation of adaptive
immunity

Cells of innate immune system recognize self-associated molecular


pattern and that recognition prevent them from attacking self cells

Thank You
rina_susilowati@ugm.ac.id 2012