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Toll-Like Receptors (TLR)

  • Family of receptors recognizing conserved patterns in microorganisms (PAMP on surface of pathogen); each TLR has multiple leucine-rich repeats and binds multiple PAMPs
  • TLRs primarily expressed in immune cells and serve as first line defense; activation of TLR signaling induces
       
     
    NFκB: protein complex that controls transcription of DNA
    		 
       
    expression of proinflammatory cytokines, chemokines, and plays role in adaptive immunity (dendritic cells present pathogen- derived antigen from TLR to T cells)
  • TLRs bridge innate immune system to adaptive immune system
  • TLR pathway results in NFκB activation
   
 
Table 1-9 Toll-Like Receptors (TLRs)
TLRsFunction/Association
 TLR1 Favors TH1 response and enhances TLR2 signaling
 TLR2 Required for recognition of bacterial lipopolysaccharide (LPS); associated with inflammatory acne ; of note, anti-inflammatory effect of retinoids via TLR2
 TLR3 Recognizes viral dsDNA
 TLR4 Recognizes LPS
 TLR5 Recognizes flagellin (component of bacterial flagella)
 TLR7 Recognizes viral ssRNA and triggers IFNγ production; imiquimod (type of imidazoquinoline) is a synthetic TLR7 analog (antiviral/antitumor properties)
    
 
   



   
 
Table 1-10 Antimicrobial Peptides
Antimicrobial PeptideCellular SourceExpression
Human β-defensin 1 (hBD-1)
Keratinocytes
Constitutive expression, direct chemoattractants for immature dendritic cells and memory T cells
Human β-defensin 2 (hBD-2)
Keratinocytes
Inducible with bacteria or cytokines
Human β-defensin 3 (hBD-3)
 
Keratinocytes
 
Inducible with bacteria or cytokines
Human β-defensin 4 (hBD-4)
Keratinocytes
Inducible with bacteria or cytokines
Canthelicidin (LL-37)
 
Keratinocytes, granulocytes
 
Inducible with bacteria or cytokines
Psoriasin
Keratinocytes
Inducible with bacteria or cytokines
Other peptides: antileukoprotease (ALP), dermicidin (DCD-1), lysozyme
      
     
     
  hβD-2 and LL37: ↓ levels in atopic dermatitis, ↑ levels in psoriasis  
     
     
 
   

 

 

 

 

 

 

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