====== Innate Immunity ======

Innate immunity is the body's immediate, non-specific defense system against pathogens.

Characteristics:

  * Rapid response (minutes–hours)
  * No antigen specificity
  * No memory
  * Recognizes conserved microbial patterns

Innate immunity bridges into adaptive immunity.

See also:
  * [[immunology:adaptive_immunity|Adaptive Immunity]]
  * [[immunology:cytokines_overview|Cytokines Overview]]

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===== Core Components of Innate Immunity =====

Innate immunity consists of:

  * Physical barriers
  * Cellular defenses
  * Soluble mediators

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===== 1. Physical & Chemical Barriers =====

  * Skin
  * Mucosal epithelium
  * Tight junctions
  * Gastric acid
  * Mucus
  * Ciliary clearance
  * Antimicrobial peptides (defensins)

Barrier disruption is often the first step in infection and inflammation.

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===== 2. Pattern Recognition Receptors (PRRs) =====

Innate immune cells recognize pathogens using PRRs.

PRRs detect:

  * PAMPs (Pathogen-Associated Molecular Patterns)
  * DAMPs (Damage-Associated Molecular Patterns)

Major PRRs:

  * Toll-Like Receptors (TLRs)
  * NOD-like receptors
  * RIG-I-like receptors

Activation of PRRs leads to:

  * NF-κB activation
  * Cytokine production
  * Interferon production

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===== Toll-Like Receptors (TLRs) =====

TLRs recognize conserved microbial structures.

Examples:

  * TLR4 → LPS (Gram-negative bacteria)
  * TLR3 → Viral dsRNA
  * TLR7/8 → Viral ssRNA
  * TLR9 → Bacterial DNA

TLR activation triggers:

  * TNF-α release
  * IL-1 release
  * IL-6 release
  * Type I interferons

See:
  * [[immunology:interferons|Interferons]]
  * [[immunology:tnf_family|TNF Family]]

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===== 3. Innate Immune Cells =====

==== Neutrophils ====

  * First responders
  * Phagocytosis
  * Reactive oxygen species
  * NET formation

Dominant in acute bacterial infections.

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==== Macrophages ====

  * Tissue-resident phagocytes
  * Cytokine producers
  * Antigen presentation (bridge to adaptive immunity)

Key cytokines:
  * TNF-α
  * IL-1
  * IL-6

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==== Dendritic Cells ====

  * Professional antigen-presenting cells
  * Activate naive T cells
  * Link innate → adaptive immunity

See:
  * [[immunology:antigen_presentation_mhc|Antigen Presentation & MHC]]

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==== Natural Killer (NK) Cells ====

  * Kill virus-infected cells
  * Kill tumor cells
  * Recognize reduced MHC-I expression

Mechanism:
  * Perforin
  * Granzymes

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===== 4. Complement System =====

Complement is a plasma protein cascade that:

  * Opsonizes pathogens
  * Recruits inflammatory cells
  * Forms membrane attack complex (MAC)

Major functions:

  * C3b → Opsonization
  * C5a → Chemotaxis
  * C5b-9 → Membrane attack complex

See full page:
  * [[immunology:complement_system|Complement System]]

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===== 5. Cytokines in Innate Immunity =====

Early inflammatory cytokines:

  * TNF-α
  * IL-1
  * IL-6

Effects:

  * Fever
  * Increased vascular permeability
  * Leukocyte recruitment
  * Acute phase reactant production (CRP)

See:
  * [[immunology:cytokines_overview|Cytokines Overview]]

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===== Acute Inflammation Cascade =====

1. PRR activation
2. Cytokine release (TNF, IL-1, IL-6)
3. Endothelial activation
4. Neutrophil recruitment
5. Pathogen clearance

If dysregulated → sepsis or chronic inflammation.

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===== Pharmacologic Relevance =====

Drugs targeting innate pathways:

  * [[immunology:tnf_inhibitors|TNF Inhibitors]]
  * [[immunology:il_1_inhibitors|IL-1 Inhibitors]]
  * [[immunology:complement_inhibitors|Complement Inhibitors]]
  * NSAIDs (prostaglandin inhibition)

Innate dysregulation is central to:

  * Sepsis
  * Rheumatoid arthritis
  * IBD
  * Psoriasis

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===== High-Yield Pearls =====

  * Innate immunity is immediate and non-specific.
  * PRRs detect conserved microbial patterns.
  * TNF-α, IL-1, and IL-6 drive early inflammation.
  * Complement C3b opsonizes; C5a recruits; MAC lyses.
  * Innate immunity activates adaptive immunity via dendritic cells.