Innate Immunity

• Innate immunity is a non-specific defense mechanism used immediately or within hours of antigen exposure.
• Innate immunity is present from birth, designed to be fast (within hours), and is evolutionarily ancient, found in invertebrates like amoebae, snails, and fruit flies.
• Innate immunity responds the same way each time, uses a limited set of molecules to recognize infection, and directs the acquired/adaptive immune response

Components of Innate Immunity

• Physical/anatomical barriers include skin, GI tract, respiratory tract, and mucosal epithelia.
• Secreted compounds include antibacterial compounds, complement, natural antibodies, and cytokines.
• Cellular components include phagocytes and NK cells.

Goals of Innate Immunity

• Preventing pathogen entry is a key goal.
• Recognizing pathogens by detecting microorganisms is crucial.

Physical barriers of innate immunity

• Skin produces anti-microbial compounds and acts as a barrier.
• The GI tract uses peristalsis, hydrochloric acid production, and low pH for defense.
• Eyes use blinking and tears for mechanical and secreted protection.
• Tears, sweat, and saliva contain lysozyme that destroys bacteria walls.
• Microbial competition provides internal protection.

Immune Protection

• Physical, mechanical, and secreted mechanisms prevent pathogen entry.
• Innate immunity operates within 0-4 hours of exposure.

Recognizing Pathogens

• The innate immune response recognizes highly conserved molecular structures present in many microorganisms
• These structures are known as Pathogen-Associated Molecular Patterns (PAMPs).
• PAMPs are present in microorganisms but not the host, and are essential for the pathogen's survival.

PAMP Examples

• Lipopolysaccharide (LPS) is found in Gram-negative bacteria.
• Lipoteichoic acid is found in Gram-positive bacteria.

Recognizing Pathogens

• Pattern Recognition Receptors (PRR) enable pathogen recognition.
• Collectins are serum proteins containing collagen-like and lectin regions.
• Toll-like receptors (TLRs) are membrane receptors
• Nod-like receptors are cytoplasmic receptors

Toll-like Receptors

• Toll proteins were first identified in the fruit fly, Drosophila melanogaster.
• Mammals have at least 10 TLR homologs.

NOD-like Receptors

• NOD 1 senses γ-glutamyl diaminopimelic acid.
• NOD 2 senses muramyl dipeptide.

Effector Mechanisms

• Include complement, phagocytosis & killing, cytokines, and activation of adaptive immunity.

Complement System

• A series of proteins circulate in blood and tissue fluids.
• It operates via a cascade where one product induces the formation of the next.
• A key protein is C3, activated by C3 convertase.

Phagocytosis

• Monocytes/macrophages mature from circulating monocytes, found in large numbers in the GI tract, lung, liver, and spleen, and are relatively long-lived.
• Neutrophils are found only in blood and are short-lived.

Killing Mechanisms

• Macrophages and neutrophils use reactive oxygen and nitrogen intermediates.
• Processes include an increase in O2 uptake, the reduction of oxygen by NADPH oxidase, and DNA damage.

Cytokines

• Proteins act as "intercellular messengers," bind to specific receptors.
• Can activate or deactivate processes.
• Cytokines activating the innate immune response include IL-1 (interleukin 1), IL-6 (interleukin 6), and TNFα (tumor necrosis factor α).

Chemokines

• Cytokines with chemoattractant properties.
• Chemokines promote inflammation where cells adhere to blood vessel surfaces and migrate to infected tissue.
• IL-8 is produced by macrophages and endothelial cells.

Interferons

• Type 1 interferons (IFNα and IFNβ) are produced in response to virally infected cells.
• Interferons activate Natural Killer Cells.
• Natural Killer Cells then kill virally infected and tumor cells.
• NK cells are responsive to TNFα and IL-12, and produce IFNγ.

Adaptive Immunity

• Innate immunity is important for activating adaptive immune responses.
• Antigen presenting cells present peptide antigens to naïve T cells.

Antigen-Presenting Cells

• Macrophages, B cells and dendritic cells act as APCs
• Dendritic cells (DCs) present antigen to activate T cells.

Summary of Innate Immunity

• Innate immunity (0-4 hours) recognizes pathogens via pattern recognition and complement receptors, ingests pathogens through phagocytosis and opsonization, recruits cells through inflammation and cytokine/chemokine production, and induces specific immune responses through production of IL-12 and IFNγ with antigen processing.
• Skin prevents pathogen entry.
• Skin recognises the need to carry out PRRs
• Skin is able to Recruit the help of complement
• Skin induces adaptive immunity