Defects in Innate Immunity: Receptors and Signaling Components

  • Nima Parvaneh
  • Joachim Roesler
  • Steven M. Holland
  • Tim Niehues
  • The innate immunity is the first line of defense against pathogens, exerting fast and effectiveresponses via preformed receptors.

  • Toll-like receptors (TLRs) recognize specific molecular patterns found in a broad rangeof microbial pathogens such as bacteria and viruses, triggering inflammatory and antiviral responses, which result in the eradication of invading pathogens.

  • Primary immunodeficiency diseases with primary defects in TLR signaling include Interleukin-1 receptor-associated kinase-4 (IRAK-4) deficiency, UNC-93B deficiency and TLR3 deficiency. These defects predispose patients to a narrow range of infections; pneumococcal infections in IRAK-4 deficiency, and herpes simplex encephalitis in UNC-93B and TLR3 deficiencies.

  • Anhidrotic ectodermal dysplasia with immunodeficiency is caused by defects in the nuclear factor NF-κB signaling. In these disorders, TLR signaling is also impaired.

  • Poor inflammatory response despite severe infection and absence of fever are characteristic of TLR defects.

  • Mendelian susceptibility to mycobacterial diseases are characterized by recurrent and severe infections caused by weakly virulent organisms, such as environmental mycobacteria and Bacille Calmette-Guérin, and is associated with impaired IL-12/Interferon-γ dependent innate immunity.

  • WHIM (warts, hypogammaglobulinemia, infections, myelokathexis) syndrome is a primary immunodeficiency disease caused by mutation of the CXCR4 chemokine receptor gene. Both innate and adaptive immunity are impaired in this disorder.

  • Epidermodysplasia verruciformis is a rare autosomal recessive disorder associated with a high risk of skin carcinoma that results from an abnormal susceptibility to infection by specific human papillomaviruses (HPVs).


Human Papilloma Virus Mycobacterial Infection Primary Immunodeficiency Disease Ectodermal Dysplasia Mycobacterial Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Nima Parvaneh
    • 1
  • Joachim Roesler
    • 2
  • Steven M. Holland
    • 3
  • Tim Niehues
    • 4
  1. 1.Department of Pediatrics Children’s Medical Center HospitalTehran University of Medical SciencesTehranIran
  2. 2.Department of PediatricsUniversity Clinic Carl Gustav CarusDresdenGermany
  3. 3.Laboratory of Clinical Infectious DiseasesNational Institute of Allergy and Infectious Diseases National Institutes of HealthBethesdaUSA
  4. 4.Immunodeficiency and Pediatric Rheumatology CenterHELIOS Clinic Krefeld Academic Hospital University of DüsseldorfKrefeldGermany

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