Innate Immunity

Innate Immunity

Antigens
1. Invoke immune responses (B-cell)
2. "Antibody generators"
WBCs
1. Innate: macrophages, respond to all
2. Adaptive: B & T cells, specific response
Skin barrier
1. pH
2. Shedding
3. [NaCl]
Mucous Membranes
1. lysozyme (attack cell wall)
2. lactoferrin (sequesters Fe)
3. Lactoperoxidase (superoxide radicals)
Antimicrobial Peptides (AMPs)
1. Cationic peptides (highly conserved, damage bacteria pm)
  1. 1st class (a-helic, no cysteine, prod by macrophages)
    1. Cathelicidin (LL-37)
      1. Protect kidney in UT w/neutrophils
      2. Humans protected by zwitterionic (0 charge) membranes
  2. 2nd class: Defensins (disulfide linked, neutrophils, epithelial)
    1. Kill phagocytosed bact. by binding to membrane and forming pores for lysis
  3. 3rd class: larger, enriched for specific am. ac.
    1. Histatin
      1. In saliva, anti-fungal (c. albicans)
2. Bacteriocins
  1. Produced by normal flora
    1. Lethal to related species
      1. Colicins (E. coli) form pores & binds to specific recptors (porins)
Complement System
1. Major activities
  1. Defense against bacterial infections
  2. Crosstalk b/w innate and adaptive immunity
  3. Disposing waste
2. Opsonization
  1. Decorating microbes with "opsonins" for recognition by phagocytic cells
    1. Stimulates macrophages for phagocytosis
3. Activation of C proteins
  1. Enzymatic cleavage
    1. C#b proteins bind to complex
    2. C#a proteins diffuse to be inflammatory mediators (binds to receptor)
4. Functions
  1. Opsonization (C3b)
  2. Inflammation (C#a)
  3. Cell lysis via MAC
5. The Three Pathways
  1. Alternative
    1. Antibody-independent, initiated by foreign cell surfaces
    2. C3 cleaves to C3 convertase
      1. C3 convertase cleaves with C3 to C5 converstase
        C5 goes to be the MAC
  2. Lectin
    1. Lectin or Mannose-Binding Lecting (MBL) binds to carbohydrates
      1. 2 serine protesase (MASP-1, MASP-2)
        Activates with C3 and Lectin
        Mannose Binding Proteins (MBP) on pathogen surfaces
        Enhance phagocytosis
  3. Classical
    1. Initiated by forming Ag-Ab (Antigen-Antibody) complex
      1. Part of Acquired & not as fast
      2. Produces cleavage products that help in:
        Opsonization
        Chemotaxis
        MAC
      3. C1 is activated when bound to antibody
        Yields C2 & C4
        C4a diffuses
        C2a diffuses
        C4b and C2b become C3
6. Complement Proteins
  1. C3b
    1. Opsonin
  2. C#a
    1. Show immune cells infection site
    2. Recruit macrophages & neutrophils
  3. C5b
    1. Form MAC for lysis
Pathogen Recognition
1. Opsonin-Independent Mechanism
  1. Pathogen recognition, specific and non
  2. Mediated by:
    1. Lectin-carbohyd
    2. Protein-protein
    3. Hydrophob
    4. Pathogen-Associated Molecular Patterns (PAMPs)
      1. 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
      2. LPS in Gram -
      3. Peptidoglycan in Gram +
      4. Binding activates NFkB transcription factor (Key for Cytokine gene transcription)
        Cytokine
        Acts as signal molecule
        Recognized by receptors on immune cell
        Trigger their function
Intracellular Digestion (Phagocytosis)
1. Autophagy
  1. Tags internal microbes for destruction w/Ubiquitin
    1. Phagophore encircles
      1. Fuse with lysosome to degrade

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