Innate vs. Adaptive Immunity

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Innate vs. Adaptive Immunity
Adaptive
Innate

• Primitive (found in all multicellular organisms)
• Directed towards types of molecules
• Effectors are broadly reactive
• Response is immediate
• No anamnestic responses
• Effectors epithelial cells, phagocytes,
  endothelial cells, fibroblasts

• Only in vertebrates
• Directed towards specific epitopes
• Response is slow
• Effectors are highly specific
• Memory persists
• Effectors Lymphocytes, APCs

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Adaptive Immunity
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Defects in Innate Immunity

• Chronic granulomatous disease--CGD (pyogenic
  infections, Aspergillus)
• Burns/chemotherapy Loss of barrier integrity
  (bacteria, yeasts)
• Neutropenia (bacteria, yeasts, molds)
• Rare specific defects in cytokines/receptors
  (susceptibility to particular infections)
• Complement deficiencies (meningococcus)
• Corticosteroids (Aspergillus, Candida,
  herpesviruses)

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Defects in Adaptive Immunity

• SCID--no T or B cells (severe, fatal infections)
• AIDS--loss of CD4 T cells (Intracellular
  pathogens, fungi, viruses, pyogenic infections,
  etc.)
• Transplant--immunsuppression of T cells (viral,
  fungal)
• Common Variable Immunodeficiency (decreased
  IgG)--generally mild increase in sinopulmonary
  bacterial infections
• Asplenia--encapsulated bacteria
• Corticosteroids

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Molecular features of Innate Immunity

• Certain proteins are vital to functioning of the
  innate immune system
• Both natural and acquired defects in these
  proteins give clues to their roles in defense.
• These proteins are present in a wide variety of
  species

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Normal fruit fly
Fruit fly lacking Toll
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Toll-like receptor structure
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Pattern recognition receptors
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Newly described PRRs

• TLR11--identifies uropathogenic E. coli in humans
  (not clear what molecule yet)
• Nod1--intracellular receptor with N-terminal CARD
  domain and C-terminal LRRs. Recognizes
  intracellular Shigella flexneri
• Nod2--similar to Nod1. Ligand not known, but is
  associated with Crohns disease

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TLRs and their ligands
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Interaction between TLRs and ligands
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IRAK interactions and TLR signalling
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TLR
IL-1R
cell membrane
p85
TIR domains


WM
MyD88
p110
Adaptors (Rac1, ? ceramide)
PI 3-kinase
IRAK
Pi
PI(3,4,5)- P3
TRAF-6
NIK
Akt
Erk
Pi
Bay11
Pi
IKK
Pi
I-kB
I-kB
NF-kB
NF-kB
p38
AP-1
SB
Inflammatory genes (chemokines, cytokines, etc)
NF-kB
nucleus
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NF-?B activation shown by EMSA
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FliC
TLR5
PI3K
IRAK/TRAF-6
WM
Bay11
Akt
I-?B degradation
?
p38
?
LY
NF-?B activation
NF-IL-6
AP-1
(50)
IL-8 transcription
LY
IL-8 mRNA
IL-8
degradation
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TLRs and adaptive immunityold paradigm
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Activation clonal proliferation
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New paradigm of TLR-controlled DC activity
tissue
lymph node
IL-10
No ligand
clonal deletion Treg cell
immature DC
Ag
TLR ligand
Immature DC
IL-12 TNF-? IL-6
Th1 cell
Mature DC
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Dendritic cell subsets and their TLRs