Lecture 3 Innate Immunity

8/13/2019 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

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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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Lecture 3 Innate Immunity

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