Innate Immunity

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Innate Immunity: Overview & Barriers - First Line Fortifications

  • Core Features: Rapid (minutes-hours), non-specific, no prior exposure, no memory. Germline encoded PRRs.

  • First Line Defenses: Prevent pathogen entry & colonization. Barriers are sequential.

    • Physical/Mechanical:
      • Intact Skin (keratin, desquamation).
      • Mucous Membranes (mucus, cilia, peristalsis).
      • Flushing actions (tears, saliva, urine).
    • Chemical:
      • pH: Gastric acid (pH 1-3), skin (pH ~5.5), vaginal lactic acid.
      • Antimicrobial peptides (AMPs): Defensins, Cathelicidins.
      • Enzymes: Lysozyme (tears, saliva) - targets peptidoglycan by hydrolyzing $\beta-(1,4)$ NAM-NAG bonds.
    • Microbiological:
      • Normal Flora: Competitive exclusion, bacteriocins.

⭐ Defensins and Cathelicidins are key antimicrobial peptides (AMPs) that disrupt microbial membranes.

Innate Immunity: Cellular Sentinels - The Immune Foot Soldiers

Key cells for immediate defense:

  • Phagocytes: Engulf and destroy pathogens.
    • Neutrophils (PMNs): Abundant first responders. Multi-lobed nucleus. Phagocytosis, NETosis. 📌 Neutrophils: Numerous, Nimble.
    • Macrophages: From monocytes. Phagocytosis, Ag presentation, cytokines. Tissue-specific (Kupffer cells - liver).
  • Dendritic Cells (DCs): Potent APCs; bridge innate to adaptive immunity.
  • Natural Killer (NK) Cells: Lymphoid origin, innate function. Target virus-infected & tumor cells with ↓MHC-I.

    ⭐ NK cells employ "missing-self recognition," targeting cells with reduced or absent MHC class I molecules.

  • Mast Cells & Basophils: Release histamine, mediators in allergy/inflammation.
  • Eosinophils: Combat parasites; modulate allergic inflammation.

Innate immune cells and functions against bacteria

Phagocytosis Overview:

Innate Immunity: Molecular Mediators - Chemical Warfare Crew

Key soluble factors orchestrating innate defense:

  • Cytokines:
    • Pro-inflammatory: TNF-α, IL-1, IL-6 (fever, inflammation). 📌 "Hot T-Bone stEAk": IL-1 (fever), TNF-α, IL-6 (APPs).
    • Type I IFNs (IFN-α, IFN-β): Induce antiviral state in cells.
    • IFN-γ (Type II IFN): Activates macrophages; from NK cells/T-cells.
  • Chemokines:
    • IL-8 (CXCL8): Neutrophil chemoattractant.
  • Complement System:
    • Key roles: Opsonization ($C_3b$), Inflammation ($C_3a, C_5a$), Lysis (MAC $C_5b-C_9$).
  • Acute Phase Proteins (APPs):
    • CRP: Opsonin, classical complement activation. (Produced by liver)
    • MBL: Lectin pathway activation. (Produced by liver)
  • Antimicrobial Peptides (AMPs):
    • Defensins, Cathelicidins: Direct microbicidal, membrane disruption.
  • Enzymes:
    • Lysozyme: Hydrolyzes peptidoglycan in bacterial cell walls.

⭐ Type I interferons (IFN-α, IFN-β) are crucial for inducing an antiviral state in uninfected cells, limiting viral spread.

Innate Immunity: Recognition & Response - Sensing Danger, Sounding Alarm

  • Sensing Danger (Recognition):

    • Microbial PAMPs (LPS, peptidoglycan, viral RNA) & host DAMPs (ATP, HMGB1) detected.
    • Key PRRs (Pattern Recognition Receptors):
      • TLRs (Toll-like Receptors): Surface (TLR2-peptidoglycan, TLR4-LPS, TLR5-flagellin); Endosomal (TLR3-dsRNA, TLR9-CpG DNA).
      • NLRs (NOD-like Receptors): Cytosolic. NOD1/2 (peptidoglycan); NLRP3 (inflammasome → IL-1β/IL-18 via Caspase-1).
      • RLRs (RIG-I-like Receptors): Cytosolic. RIG-I/MDA5 (viral RNA → Type I IFN via IRFs).
      • CLRs (C-type Lectin Receptors): Dectin-1 (fungal β-glucans).

    TLR4 (with CD14/MD-2) recognizes Gram-negative LPS, activating NF-κB for pro-inflammatory cytokine release (TNF-α, IL-1, IL-6).

  • Sounding Alarm (Response):

    • Signaling Pathways: NF-κB (pro-inflammatory cytokines, chemokines like CXCL8); IRFs (Type I IFNs: IFN-α/β for antiviral state).
    • Key Effector Mechanisms:
      • Inflammation: Vasodilation, ↑vascular permeability, neutrophil recruitment.
      • Phagocytosis: By macrophages/neutrophils; opsonins (C3b, IgG) enhance.
      • Antimicrobial peptides (AMPs): Defensins, cathelicidins.
      • NK cell activation.

NF-kB and IRF signaling pathways

High‑Yield Points - ⚡ Biggest Takeaways

  • Innate immunity is the rapid, non-specific first defense; lacks immunological memory.
  • Key players: phagocytes (neutrophils, macrophages), NK cells, complement, cytokines.
  • PRRs (e.g., TLRs) on innate cells detect PAMPs (e.g., LPS, viral RNA).
  • Inflammation (redness, heat, swelling, pain) is a core innate response.
  • Type I interferons (IFN-α/β) are critical for antiviral defense.
  • Complement system enhances phagocytosis, causes cell lysis (MAC), and promotes inflammation.
  • NK cells provide early defense against viral infections and tumors without prior sensitization.

Practice Questions: Innate Immunity

Test your understanding with these related questions

A researcher is studying the interactions between foreign antigens and human immune cells. She has isolated a line of lymphocytes that is known to bind antigen-presenting cells. From this cell line, she has isolated a cell surface protein that binds to class I major histocompatibility complex molecules. The continued activation, proliferation and survival of this specific cell line requires which of the following signaling molecules?

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Flashcards: Innate Immunity

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_____ are the two primary opsonins in bacterial defense, which enhances phagocytosis

TAP TO REVEAL ANSWER

_____ are the two primary opsonins in bacterial defense, which enhances phagocytosis

C3b and IgG

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