Pola Pengenalan Patogen

Pattern recognition by cells
of the innate immune system

1
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)
Immune Cells Should Distinguish Self and non Self cells

3
Receptors of Innate immunity
Receptors of Adaptive immunity
T
B
Macrophages
Dendritic
cells
Immune Cells Should Distinguish Self and non Self cells

4
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
Macrophages
Recognition of pathogens by host cells

5
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
Recognition of pathogens by host cells

6
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
Cellular localization of pattern-recognition receptors (PRRs)

7
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
Toll-like receptors represent an ancient pathogenrecognition system

8
Flies use Toll to

defend from
fungi
Mammalian Toll-like receptors are activated by

many different PAMPs
9
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.
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

10
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
Extracellular (soluble) PRRs

11
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)
Cytoplasmic PRRs: the RIG-I-like receptors detect

cytoplasmic viral RNAs and stimulate interferon production
12
RLR : RIG like receptors RIG: Retinoic acid inducible gene
Receptor
Ligands
RLRs
RIG-I
MDA5
dsRNA (short), 5triphosphate RNA

dsRNA (long)
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
13
Receptor
NLRs
NOD1
NOD2
NALP1
NALP3
Ligands
Diaminopimelic acid
MDP
MDP
ATP, uric acid crystals, RNA,
DNA, MDP
Origin(s)
Gram-negative bacteria
Viruses, bacteria, and host
Clin Microbiol Rev. 2009 April; 22(2): 240273.
NLR: NOD-like receptors;

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

leading to IL-1 secretion
Davis BK et al., 2011 Annu. Rev. Immunol. 29:707-35
14
NLR: NOD-like receptors;

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

15
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
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
16
Recognition of PAMPs leads to engulfment of the pathogen as

well as activation of phagocytes and initiate an
inflammatory response
17
Pathogen recognition initiate activation of adaptive immune

responses
18
Pathogen-induced
TLR signaling in
immature dendritic
cells
induces their
migration to
lymphoid organs
and
enhances antigen
processing
PAMPs-PRRs signaling can be inhibited by

virulent pathogens
19
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
TLR and NLR also recognize danger-associated molecular

patterns(DAMPs) to initiate limited innate immune responses
20
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
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
21
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
Marker of self: CD47

22
http://www.seas.upenn.edu/~discher/research.html
Marker of self: MHC class I

23
Summary
Pattern recognition by cells of the innate immune system
24
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

Pola Pengenalan Patogen

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Pattern recognition by cells

of the innate immune system

KURSUS IMUNOLOGI DASAR 2012

The success of a healthy immune system is

Immune Cells Should Distinguish Self and non Self cells

Receptors of Innate immunity

Receptors of Adaptive immunity

Immune Cells Should Distinguish Self and non Self cells

pattern recognition receptors (PRRs)

Recognition of pathogens by host cells

PAMPs are molecular components

PRRs are receptors produced by

Recognition of pathogens by host cells

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

TLRs: Toll-like receptors

Cellular localization of pattern-recognition receptors (PRRs)

TLRs: Toll-like receptors

Toll-like receptors represent an ancient pathogenrecognition system

Flies use Toll to

Mammalian Toll-like receptors are activated by

TLR1/TLR2 Triacyl lipopeptides

Other membrane bound PRRs

Macrophage Mannose Receptor

Cell bound C type lectin e.g DC

Extracellular (soluble) PRRs

Initiate complement activation

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

Cytoplasmic PRRs: the RIG-I-like receptors detect

dsRNA (short), 5triphosphate RNA

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

NLR: NOD-like receptors;

NLR binding trigger formation of inflammasomes

NLR: NOD-like receptors;

PAMPs-PRRs recognition send danger signals

Networking by small-molecule hormones in plant immunity

Upon pathogen attack, pathogen-associated

PAMPs-PRRs recognition send danger signals

Recognition of PAMPs leads to engulfment of the pathogen as

Pathogen recognition initiate activation of adaptive immune

PAMPs-PRRs signaling can be inhibited by

Virulent pathogens acquired

Networking by small-molecule hormones in plant immunity

TLR and NLR also recognize danger-associated molecular

Damage-associated molecular patterns (DAMPs)

II. Disruption of membrane

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

Monosodium urate crystal

TLR and NLR also recognize danger-associated molecular

Marker of self: CD47

Marker of self: MHC class I

Cells of innate immune

Cells of innate immune system recognize self-associated molecular

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