Innate Immunity

    • Clinical Correlation:
    • Low-grade or transient N. Meningococcal bacteremia is overcome by opsonization and phagocytosis, but higher grader or persistent bacteremia requires the complement system for eradication of invasive disease. 
  • Innate immunity receptors and signal transduction
    • Defects in pattern recognition receptors i.e Cellular receptor that activates innate immune system 
      • 4 types: 
        • 2 Membrane bound 
          • TLR (7 types)
          • CLR (5 types)
            • CLR are important in recognition of fungi and bacteria in the body NEJM 2011
        • 2 Cytoplasmic 
          • NLR (6 Types)
            • NLR recognizes peptidoglycan of bacterial cell wall and activate inflammasome that convert inactive IL 1 and IL 18 to active IL 1 and IL 18.
          • RIG - 1 Helicase receptors (2 Types)
            • RIG -1 helices receptors are mainly receptors for the nucleic acid of the virus NEJM 2011
      • Interaction between TLR and NOD2 is needed for effective innate immunity against mycobacteria, and staphylococci. NEJM 2011
      • Likewise, cross talk between CLR and TLR is needed for anti-fungal innate immunity NEJM 2011
    • Defect in IFN Gamma Pathway (Mycobaterial and Salmonella Susceptibility )
  • Complement Deficiencies
    • Classic, Alternate, Lectin pathways 

Molecules Great and Small: The Complement System CJSAN 2015
  • Clinical Pearls
    • Defect in MBL pathway deficiency can lead to recurrent strep bacteremia
    • Deficiency of C3 can also lead to recurrent strep bacteremia
    • Later 2 are part of innate immune system as they  act as first line defense before antibody is formed
    • IgM and IgG can only activate complement system, hence cryoglobulinemic disorders are either IgG or IgM mediated. 
    • Normal C3 does not rule out Alternate Pathway Activation.
    • In some cases, as in some cases of MPGN, immune-complex may initiate the disease process but the disease may be accelerated by alternate pathway (MPGN - A New Look at an Old Entity NEJM 2012) 

Case 3-2014: A 61-Year-Old Woman with Gastrointestinal Symptoms, Anemia, and Acute Kidney Injury (RPGN): 

Causes of RPGN
Subpages (1): Neutrophils