Download 10 Recognition and elimination by innate

INNATE RECOGNITION AND
EFFECTOR MECHANISMS
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Recognition of microbes and damaged self by the
innate immune system
• Cell-associated pattern recognition receptors (PRRs)
• Extracellular PRRs
Recognition of PAMPs from different classes of microbial
pathogens
Clin. Microbiol. Rev. 2009;22:240-273
Sensing of Damage Associated Molecular Patterns
(DAMP) by PRRs and other receptors of the innate
immune system
Lancet 2011; 378: 1015–26
Cell-associated pattern recognition receptors (PRRs)
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Toll receptors activate phylogenetically conserved signal
transduction pathways
Bacterium
Fungi
Protease
LPB
LPS
Toll
DmMyD88
Spaetzle
Cactus
Dif
Tube/
Pelle
Antimicrobial peptide
Drosophila
TLR4
CD14
IkB
MyD88
IRAK
NF-kB
Pro-inflammatory cytokines
Mammals
Structure, location, and specificities of mammalian TLRs
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Signaling functions of TLRs
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Classification, protein structure, and function of the
NOD-like receptor family
Physiol Rev 2015;95:149-178
Overview of NOD-like receptor cellular pathways
Physiol Rev 2015;95:149-178
The inflammasome
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
Sensing of cytosolic nucleic acids
Front. Microbiol., 20 June 2012 | http://dx.doi.org/10.3389/fmicb.2012.00201
Membrane bound pattern-recognition
receptors
Extracellular PRRs
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
The 'missing-self' hypothesis
Limited types of defensive reactions
• Antiviral state
• Inflammation
Recognition of viral nucleic acid by RIG-1-like receptors
(RLRs) initiate an inflammatory response
Virus-infected cells produce type I interferons
Major functions of the type I interferons
Functions of NK cells
Cellular and Molecular Immunology, 7th ed., 2014 Elservier
NK cells circulate between blood and tissues
NK cells provide an early response to virus infection
Activation by type I interferon induces the proliferation
of NK cells and their differentiation into cytotoxic cells
Interaction between a macrophage and an NK cell induces
NK-cell proliferation and differentiation into effector cells
secreting interferon-γ (IFN-γ), which further activates
the macrophage
Interactions of NK cells with dendritic cells
NK cells express diverse combinations of receptors
Activation of NK cells by receptors of innate
and adaptive immunity
CD94:NKG2A recognizes complexes of HLA-E and
peptides derived from the leader sequences
of HLA-A, -B, and -C
Signals from inhibitory receptors block the signaling
pathways of NK-cell activation
Killer-cell immunoglobulin-like receptors (KIRs) bind to
the same face of the MHC class I molecule as
the T-cell receptor
NK-cell education involves balancing the signaling
pathways for inhibition and activation
NK-cell acquisition of inhibitory receptors for
self-MHC class I
NK cells are educated by inhibitory receptors that
recognize self-MHC class I