lecture 3 innate immunity
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INNATE IMMUNITY
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Evolution in the Immune System
The Red Queens Hypothesis It takes all the running you can
do, to keep in the same place. If
you want to get somewhere else,
you must run at least twice as fastas that.
Host-pathogen arms race
IMUNOLOGIE
Positive selection SurviveReproduce
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Evolution of the Immune System Invertebrates Vertebrates
Origin of adaptive immunityEvolution of allorecognition
Coelomocyte, earthworm Macrophage, human
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Immunity in multicellular organisms
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Immunity in multicellular organisms
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Evolution trends Rapid, but varying rates Convergent evolution Multigene families Polymorphism Somatic generation of diversity
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Innate and adaptive immunity
SpecificityDiversityMemoryComponents Cellular and chemical barriers Serum proteins
Cells
Comparing
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Function of the innate immune system
Initial response to pathogensStimulates adaptive immune responses
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Components Surface epithelium Effector cells (neutrophils, mononuclear phagocytes and
NK cells)Acute-phase response and complement proteins Cytokines
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Epithelial barriers
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Skin GI and respiratory tractmucosal tissue
T lymphocytes B-1 cells Mast cells
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Cells of the innate immune system Neutrophils Monocytes/macrophages Dendritic cells NK cells Lymphocyte subsets: !"-T cells, B-1 cells Mast cells Eosinophils Basophils
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Phagocytes
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Neutrophils (PMNs) Short-lived (24-48h) Recruited from
circulation to the site of
infection
Extra- and intracellularkilling
Storage granulesPrimary (azurophylic)Secondary (specific)
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New! 5.4 days (Pillay, 2004)
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Macrophages Phagocytosis Pro-inflammatory
cytokines: IL-1, IL-6, IL-8,
TNFa
Housekeeping
Activated by IFNg
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Dendritic cells Link innate and adaptive
immune responses Function asAPCs
Express PRRs
Plasmacytoid dendritic cellsare early responders to viral
infection
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Recruitment of leukocytes
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Inflammation
Pro-inflammatory cytokines
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Phagocytosis
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NK cellsAnti-viral host defense Large granular lymphocytes Kill directly Produce IFN!Activated by IL-12, IL-15 and
type I IFN
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Humoral innate immunity.
Complement system
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Humoral innate immunity The complement system Pentraxins Collectins Ficolins Cytokines of the innate immune
system
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Recognize microbial structures
CRPSerum amyloid PPTX3
Control viral infection: type 1 IFNsProinflammatory: IL-1, TNFNK cell activation: IL-12, IL-15 Macrophage activation: IFNgSynthesis of acute-phase proteins: IL-6 Control of inflammation: IL-10, TGFb
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Innate immune recognition Pattern recognition: Molecular structures unique to microorganisms (PAMPs) and not
produced by the host
Recognizes molecular structures essential for pathogen survival Encoded in germline DNA
Recognition of missing self: Inhibitory receptors (NK cells); complement factor H Recognizes stressed or injured host cells
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PRRs PRRs= cell-associated Pattern Recognition Receptors
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TLRs (Toll-like receptors) CLRs (C-type lectin receptors) Scavenger receptors NLRs (Nod-like receptors)
RLRs (RIG-I -like receptors)
Nod1Nod2
RIG-IMDA5
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Toll-like receptors (TLRs)
H.Kumar, Biochem.J.,2009
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TLRs
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Inflammasomes
H.Kumar, Biochem.J.,2009
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Summary Evolutiontrends of the immune system Functionand componentsthe innate immune system Cellsof the innate immune system Processes of innate immunity Humoral innate immunity PRRs TLRs Inflammasomes
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