3. Pola Pengenalan Patogen

Pattern recognition by cells

of the innate immune system

KURSUS IMUNOLOGI DASAR 2012

[email protected]

1

[email protected] 2012

[email protected] 2012 2

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

Marker of self: CD47


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

Marker of self: MHC class I


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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

Documents

3. Pola Pengenalan Patogen