Innate Immunity

Innate Immunity: First Responders & Fortresses

• Body's in-built, immediate defense system; present from birth.
• Characteristics:
  • Non-specific: Acts broadly against diverse pathogens.
  • Rapid: Mobilized within minutes to hours.
  • No immunological memory: Response intensity is consistent upon re-exposure.

Cellular Sentinels - The Immune Foot Soldiers

Molecular Alarms - PAMPs, PRRs & Messengers

• PAMPs (Pathogen-Associated Molecular Patterns): Microbial structures (e.g., LPS, peptidoglycan, dsRNA).
• DAMPs (Damage-Associated Molecular Patterns): Host molecules from stressed/damaged cells.
• PRRs (Pattern Recognition Receptors): Host sensors for PAMPs/DAMPs.
  • Toll-like Receptors (TLRs): Key membrane-bound PRRs.

    TLR	Ligand	Recognizes
    TLR2	Peptidoglycan, Lipoproteins	Gram (+) bacteria, Fungi
    TLR3	dsRNA	Viruses
    TLR4	LPS (Endotoxin)	Gram (-) bacteria
    TLR5	Flagellin	Motile bacteria
    TLR9	Unmethylated CpG DNA	Bacterial/Viral DNA

  • NLRs (NOD-like Receptors): Cytosolic; detect bacterial peptidoglycans, other signals.
  • RLRs (RIG-I-like Receptors): Cytosolic; detect viral RNA.

• Complement System: Plasma protein cascade.

-   Key Functions: Opsonization (C3b), Anaphylatoxins (C3a, C5a), MAC (C5b-9 lysis).

• Key Cytokines (Soluble Messengers):
  • TNF-α, IL-1, IL-6: Pro-inflammatory; fever, acute phase protein synthesis.
  • IL-12: Activates NK cells, promotes Th1 differentiation.
  • Type I IFNs (IFN-α, IFN-β): Antiviral state; ↑MHC I expression.

⭐ TLR4, along with MD-2 and CD14, is the primary receptor for Lipopolysaccharide (LPS) from Gram-negative bacteria, a critical trigger for septic shock.

Innate Responses - Inflammation & Action

• Inflammation:
  • Cardinal signs: Calor (heat), Rubor (redness), Tumor (swelling), Dolor (pain), Functio laesa (loss of function). 📌 Mnemonic: PRISH (Pain, Redness, Immobility, Swelling, Heat).
  • Key mediators: Histamine, prostaglandins, leukotrienes.
  • Events: Vasodilation, ↑ vascular permeability, leukocyte recruitment.
  • Acute Phase Reactants (APRs): C-Reactive Protein (CRP), Serum Amyloid A (SAA), Fibrinogen.
• Phagocytosis: Key mechanism for eliminating pathogens and debris.

• Natural Killer (NK) Cells:
  • Activation: "Missing self" hypothesis (recognize cells lacking MHC-I).
  • Killing mechanism: Release perforins (create pores) and granzymes (induce apoptosis).

⭐ C-Reactive Protein (CRP) is a major acute phase reactant; its levels can increase >1000-fold during acute inflammation, making it a sensitive marker of inflammation and infection.

High-Yield Points - ⚡ Biggest Takeaways

• Innate immunity: Rapid, non-specific, first-line defense; no immunological memory.
• Key cells: Phagocytes (Neutrophils, Macrophages), NK cells, Mast cells, Dendritic cells.
• Recognition: PAMPs (e.g., LPS) by PRRs (e.g., TLRs; TLR4 recognizes LPS).
• Complement system: Key for opsonization, MAC formation (lysis), and inflammation.
• Inflammation: Cardinal signs (rubor, calor, dolor, tumor); mediated by cytokines.
• Type I Interferons (IFN-α, IFN-β): Potent antiviral activity.