Innate Immunity

Innate Immunity

1. Antigens

   • Invoke immune responses (B-cell)
   • "Antibody generators"

2. WBCs

   • Innate: macrophages, respond to all
   • Adaptive: B & T cells, specific response

3. Skin barrier

   • pH
   • Shedding
   • [NaCl]

4. Mucous Membranes

   • lysozyme (attack cell wall)
   • lactoferrin (sequesters Fe)
   • Lactoperoxidase (superoxide radicals)

5. Antimicrobial Peptides (AMPs)

   • Cationic peptides (highly conserved, damage bacteria pm)
     • 1st class (a-helic, no cysteine, prod by macrophages)
       • Cathelicidin (LL-37)
         • Protect kidney in UT w/neutrophils
         • Humans protected by zwitterionic (0 charge) membranes
     • 2nd class: Defensins (disulfide linked, neutrophils, epithelial)
       • Kill phagocytosed bact. by binding to membrane and forming pores for lysis
     • 3rd class: larger, enriched for specific am. ac.
       • Histatin
         • In saliva, anti-fungal (c. albicans)
   • Bacteriocins
     • Produced by normal flora
       • Lethal to related species
         • Colicins (E. coli) form pores & binds to specific recptors (porins)

6. Complement System

   • Major activities
     • Defense against bacterial infections
     • Crosstalk b/w innate and adaptive immunity
     • Disposing waste
   • Opsonization
     • Decorating microbes with "opsonins" for recognition by phagocytic cells
       • Stimulates macrophages for phagocytosis
   • Activation of C proteins
     • Enzymatic cleavage
       • C#b proteins bind to complex
       • C#a proteins diffuse to be inflammatory mediators (binds to receptor)
   • Functions
     • Opsonization (C3b)
     • Inflammation (C#a)
     • Cell lysis via MAC
   • The Three Pathways
     • Alternative
       • Antibody-independent, initiated by foreign cell surfaces
       • C3 cleaves to C3 convertase
         • C3 convertase cleaves with C3 to C5 converstase
           • C5 goes to be the MAC
     • Lectin
       • Lectin or Mannose-Binding Lecting (MBL) binds to carbohydrates
         • 2 serine protesase (MASP-1, MASP-2)
           • Activates with C3 and Lectin
             • Mannose Binding Proteins (MBP) on pathogen surfaces
               • Enhance phagocytosis
     • Classical
       • Initiated by forming Ag-Ab (Antigen-Antibody) complex
         • Part of Acquired & not as fast
         • Produces cleavage products that help in:
           • Opsonization
           • Chemotaxis
           • MAC
         • C1 is activated when bound to antibody
           • Yields C2 & C4
             • C4a diffuses
             • C2a diffuses
             • C4b and C2b become C3
   • Complement Proteins
     • C3b
       • Opsonin
     • C#a
       • Show immune cells infection site
       • Recruit macrophages & neutrophils
     • C5b
       • Form MAC for lysis

7. Pathogen Recognition

   • Opsonin-Independent Mechanism
     • Pathogen recognition, specific and non
     • Mediated by:
       • Lectin-carbohyd
       • Protein-protein
       • Hydrophob
       • Pathogen-Associated Molecular Patterns (PAMPs)
         • Detected by Pattern Recognition Receptors (PRRs)
           • Can trigger phagocytes
           • Toll Like Recptors (TLRs)
             • Signaling recptors
             • Recognize/bind unique PAMPS
               • Triggers signal to initiate host response
         • LPS in Gram -
         • Peptidoglycan in Gram +
         • Binding activates NFkB transcription factor (Key for Cytokine gene transcription)
           • Cytokine
             • Acts as signal molecule
             • Recognized by receptors on immune cell
               • Trigger their function

8. Intracellular Digestion (Phagocytosis)

   • Autophagy
     • Tags internal microbes for destruction w/Ubiquitin
       • Phagophore encircles
         • Fuse with lysosome to degrade