Innate Immunity

consists of an immediate response & induced response (which requires inflammation, due to stronger pathogens)

Immediate Response

  • complement system - consists of >30 plasma proteins (synthesized from the liver in inactive form which must be cleaved) that mediate immune functions by tagging pathogens for destruction (opsonization)

    • infection triggers complement activation following cascade

    • general rule: C → Ca (recruits phagocytes) + Cb (tags bacterium)

    • immune functions:

      • facilitates opsonization via leukocytes

      • forms pores on membrane via membrane attack complexes (MAC; aka lysis)

      • propagation of inflammation to increase permeability of blood vessels → more leukocytes

    • 3 complement activating pathways:

      • classical (pathogen’s antigen w/ protein’s antibody)

        • C1 binds to antibody that’s bound to the antigen of the pathogen, activating C1r/C1s (proteolytic enzyme)

        • MBL binds to carbohydrates (sugars) on the pathogen’s surface, activating MASPs (proteolytic enzyme)

        • C4 → C4a + C4b

        • C2 → C2a + C2b

        • C4b + C2a → C4b2a (aka C3 convertases; a proteolytic enzyme)

        • C3 → C3a + C3b (cleaved by C4b2a)

        • C4b2a + C3b → C4b2a3b (aka C5 convertases)

        • C5 → C5a + C5b (cleaved by C4b2a3b)

        • termination (C3a & C5a = inflammation; C3b = opsonization; C5b = lysis)

      • lectin (carbs & MBL “mannose binding leptin”)

        • MBL binds to carbohydrates (sugars) on the pathogen’s surface, activating MASPs (proteolytic enzyme)

        • C4 → C4a + C4b

        • C2 → C2a + C2b

        • C4b + C2a → C4b2a (aka C3 convertases; a proteolytic enzyme)

        • C3 → C3a + C3b (cleaved by C4b2a)

        • C4b2a + C3b → C4b2a3b (aka C5 convertases)

        • C5 → C5a + C5b (cleaved by C4b2a3b)

        • termination (C3a & C5a = inflammation; C3b = opsonization; C5b = lysis)

      • alternative (spontaneous back up system; low rate)

        • C3 → C3H2O via spontaneous hydrolysis

        • factor B binds to C3H2O

        • factor D cleaves off Ba → C3H2OBb (fluid-phase C3 convertase)

        • C3H2OBb cleaves off C3s → C3a + C3b

        • factor B binds to C3b

        • factor D cleaves off Ba → C3bBb (alternative C3 convertase)

        • C3bBb cleaves off C3 → C3a + C3b


  • antimicrobial peptides - soluble molecules that can kill a wide variety of pathogens

    • e.g. defensins

      • types: alpha & beta (has hydrophobic/philic regions & can neutralize toxins via production of microbes)


  • phagocytosis - cell uses outer membrane to engulf & digest large solid particles (aka receptor mediated endocytosis)

    • done by macrophages (long-lived) & neutrophils (short-lived)

    • STEPS:

      • surface sugars of a bacterium are bound by 2 c-type lectin-like domains (CTLD; specialized pattern recognition receptor)

      • macrophage ingests bacterium → degradation begins via endosome formed in macrophage

      • endosome fuses with lysosome → phagolysosome formed → further degradation


Induced Response

inflammation

recognize pathogen’s antigen (Ag) + location → induce inflammation

  • extracellular pathogen - outside of cell

    • e.g. cell-surface carb Ag recognized by macrophage receptors and killed via phagocytosis

  • intracellular pathogen - inside of cell

    • exogenous - engulfed & degraded inside vesicles (phagosomes)

    • endogenous - found & degraded in cytoplasm

    • e.g. viral infection of a [self] cell recognized by NK-cell’s receptors and is killed to prevent replication


  • pattern recognition receptor (PRR) - host sensor proteins (on immune cells or free floating) that identify molecules associated with invading microbes/cellular stress

    • recognizes:

      • pathogen-associated molecular patterns (PAMPs) which are structures found on microbes such as carbs, lipids, proteins, nucleic acid

      • damage-associated molecular patterns (DAMPs) which are endogenous molecules released from host cell under stress/damage/cell death such as heat shock proteins

    • types:

      • c-type lectin receptor (CLR) - self/nonself endo/exogenous Ag

      • nod-like receptor (NLR) - endogenous Ag

        • recognizes degraded bacterial cell walls in cyto

      • toll-like receptor (TLR) - exogenous Ag

        • structure can be homodimer (3,4,7,8) or heterodimer (1-2, 2-6) shaped like 2 horseshoes

      • rig-i-like receptor (RLR) - endogenous viral RNA

    • able to distinguish self from non-self from altered self Ag