Download - 3. Pola Pengenalan Patogen
Pattern recognition by cells
of the innate immune system
KURSUS IMUNOLOGI DASAR 2012
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The success of a healthy immune system is
the ability to distinguish between
the body’s own cell (SELF) & foreign cells (NONSELF)
Immune Cells Should Distinguish Self and non Self cells
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Receptors of Innate immunity
Macrophages Dendritic
cells
B
Receptors of Adaptive immunity
T
Immune Cells Should Distinguish Self and non Self cells
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Macrophages Macrophages Macrophages
Pathogens (non self)
Injured cells
Altered self
Normal cells (self)
pathogen associated
molecular patterns
(PAMPs) e.g LPS, high
mannose
pattern recognition receptors (PRRs)
Eat me
Eat me
Don’t eat me
self-associated molecular
patterns (SAMPs)
damage associated
molecular patterns
(DAMPs)
Inflammation
Recognition of pathogens by host cells
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http://faculty.ccbcmd.edu/courses/bio141/lecguide/unit4/innate/pamptlr.html
PRRs are receptors produced by
host cells that recognize PAMPs
PAMPs are molecular components
associated with pathogens but not
found as a part of eukaryotic cells
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Recognition of pathogens by host cells
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 receptorsNLRs: NOD-like receptorsRLRs: RIG-like receptorsOthers
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Cellular localization of pattern-recognition receptors (PRRs)
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 receptorsNLRs: NOD-like receptorsRLRs: RIG-like receptorsOthers
Toll-like receptors represent an ancient pathogen-
recognition system
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Flies use Toll to defend from
fungi
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Clin Microbiol Rev. 2009 April; 22(2): 240–273.
Mammalian Toll-like receptors are activated by
many different PAMPs
Receptor Ligands Origin(s)
TLR1/TLR2 Triacyl lipopeptides Bacteria
TLR2/TLR6 Diacyl lipopeptides Mycoplasma
Lipoteichoic acid Gram-positive bacteria
TLR2 Lipoproteins Various pathogens
Peptidoglycan Gram-positive and -negative bacteria
Lipoarabinomannan Mycobacteria
Porins Neisseria
Envelope glycoproteins Viruses (e.g., measles virus, HSV, cytomegalovirus)
GPI-mucin Protozoa
Phospholipomannan Candida
Zymosan Fungi
β-Glycan Fungi
TLR3 dsRNA Viruses
TLR4 LPS Gram-negative bacteria
Envelope glycoproteins Viruses (e.g., RSV)
Glycoinositolphospholipids Protozoa
Mannan Candida
HSP70 Host
TLR5 Flagellin Flagellated bacteria
TLR7/8 ssRNA RNA viruses
TLR9 CpG DNA Viruses, bacteria, protozoa
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Other membrane bound PRRs
Macrophage Mannose ReceptorCell bound C type lectin e.g DC –SIGN that binds sugar molecules on the surface on many bacteria and viruses.
Dectin-1C-type lectin that binds b-glucan-containing particles including zymosan and C. albicans
Macrophage Scavenger Receptor (SR-A)
Recognize certain anionic polymers and low-density lipoproteins
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Extracellular (soluble) PRRs
Initiate complement activation
GalectinsLectins which bind beta galactoside. As galectins are dominantly found in the lesions where pathogen-initiated tissue damage signals appear, this lectin family is also considered as potential damage-associated 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
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RLR : RIG like receptors RIG: Retinoic acid inducible gene
Receptor Ligands Origin(s)RLRs
RIG-I dsRNA (short), 5′-
triphosphate RNA
Viruses (e.g., influenza A virus, HCV, RSV)
MDA5 dsRNA (long) Viruses (picorna- and noroviruses)
Cytoplasmic PRRs: The NOD-like receptors (NLR) act as
intracellular sensors of bacterial infection
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Receptor Ligands Origin(s)NLRs
NOD1 Diaminopimelic acid Gram-negative bacteria
NOD2 MDP Gram-positive and -negative bacteria
NALP1 MDP Gram-positive and -negative bacteria
NALP3 ATP, uric acid crystals, RNA,
DNA, MDP
Viruses, bacteria, and host
Clin Microbiol Rev. 2009 April; 22(2): 240–273.
NLR: NOD-like receptors;
NOD: Nucleotide-binding oligomerization domain
NLR binding trigger formation of inflammasomesleading to IL-1 secretion
NLR: NOD-like receptors;
NOD: Nucleotide-binding oligomerization domain
Davis BK et al., 2011 Annu. Rev. Immunol. 29:707-3514
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Networking by small-molecule hormones in plant immunity
Corné 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 pattern-
recognition 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
PAMPs-PRRs recognition send danger signals
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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
Recognition of PAMPs leads to engulfment of the pathogen as
well as activation of phagocytes and initiate an
inflammatory response17
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Pathogen recognition initiate activation of adaptive immune
responses
Pathogen-induced TLR signaling in immature dendriticcells
induces their migration to lymphoid organs and
enhances antigen processing
PAMPs-PRRs signaling can be inhibited by
virulent pathogens
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Networking by small-molecule hormones in plant immunity
Corné 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
Virulent pathogens acquired effectors (purple stars) that suppress PAMPs-triggered immunity, resulting in host susceptibility
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Receptors/Sensors
Retroelements ND
Mitochondria DNA TLR9
Formyl peptides FPRL1/2
Monosodium urate crystal NLRP3
Uric acid NLRP3
Cholesterol crystals NLRP3
Alum NLRP3
I. Evolutionary culprit
II. Disruption of membrane
integrity
Damage-associated molecular patterns (DAMPs)
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
TLR and NLR also recognize danger-associated molecular
patterns(DAMPs) to initiate limited innate immune responses
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 innateimmune responses
SummaryPattern 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