Innate Immunity

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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.

Innate Immunity: First and Second Lines of Defense

FeatureInnate ImmunityAdaptive Immunity
SpecificityLow (Pattern recognition)High (Antigen-specific)
Response TimeFast (Hours)Slow (Days to weeks)
MemoryAbsentPresent (Long-term)
Key CellsPhagocytes, NK cells, Mast cellsT-lymphocytes, B-lymphocytes

Cellular Sentinels - The Immune Foot Soldiers

Cell TypeKey Identifying Feature/MarkerPrimary Function(s)
NeutrophilsMulti-lobed nucleus (3-5); MPO+, CD66b+Phagocytosis (bacteria); acute inflammation; NETs (📌 Neutrophil Extracellular Traps). First responders.
MacrophagesKidney-shaped nucleus; CD14+, CD68+; from monocytesPhagocytosis; antigen presentation; cytokine release; tissue repair.
Dendritic CellsStar-shaped; high MHC-II, CD11c+Potent APCs; link innate & adaptive immunity; T-cell activation.
NK CellsLarge granular lymphocyte; CD16+, CD56+ (CD3-)Kill tumor/virally infected cells (MHC-I independent); ADCC; IFN-γ production.
Mast CellsGranules with histamine, tryptase; c-Kit (CD117)+Allergic reactions (Type I); inflammation; parasite defense; degranulation.
EosinophilsBilobed nucleus; eosinophilic granules (MBP)Parasite defense; allergic reactions (modulate); chronic inflammation.
BasophilsBilobed/S-shaped nucleus; basophilic granules (histamine)Allergic/inflammatory reactions; parasite defense; release histamine.

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.
      TLRLigandRecognizes
      TLR2Peptidoglycan, LipoproteinsGram (+) bacteria, Fungi
      TLR3dsRNAViruses
      TLR4LPS (Endotoxin)Gram (-) bacteria
      TLR5FlagellinMotile bacteria
      TLR9Unmethylated CpG DNABacterial/Viral DNA
    • NLRs (NOD-like Receptors): Cytosolic; detect bacterial peptidoglycans, other signals.
    • RLRs (RIG-I-like Receptors): Cytosolic; detect viral RNA.

TLR signaling and PAMP recognition

  • 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. Positive and negative acute-phase reactants
  • 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.

Practice Questions: Innate Immunity

Test your understanding with these related questions

The acute inflammatory response is predominantly mediated by which type of immune cells?

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Flashcards: Innate Immunity

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_____ and VCAM-1 are cellular adhesion molecules that are upregulated on endothelium during leukocyte adhesion

TAP TO REVEAL ANSWER

_____ and VCAM-1 are cellular adhesion molecules that are upregulated on endothelium during leukocyte adhesion

ICAM-1

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