Innate and Adaptive Immunity Overview

Innate and Adaptive Immunity

• Innate immunity recognizes broad classes of microbes using pathogen-associated molecular patterns (PAMPs).
• Adaptive immunity is more specific, recognizing detailed microbial structures (antigens).
• Innate immunity uses about 1000 different molecular patterns (estimated) to recognize different microbes.
• Adaptive immunity is able to recognize over 10 antigens.
• Innate immunity is germline encoded, with limited receptor diversity.
• Adaptive immunity is encoded by gene segments through somatic recombination, leading to greater diversity.
• Innate immunity can discriminate self from non-self through recognition of host cells' lack of PAMPs.
• Adaptive immunity uses the process of eliminating or inactivating potentially harmful self-reactive lymphocytes to discriminate self from non-self.

Microbial Substances

• Microbial substances that stimulate innate immunity are commonly shared among different microbes.
• These patterns are termed pathogen-associated molecular patterns (PAMPs).
• PAMPs include viral nucleic acids, bacterial DNA, and LPS in gram-negative bacteria.
• The innate immune system identifies these substances as foreign.

Damage-Associated Molecular Patterns (DAMPs)

• The innate immune system can also identify endogenous molecules liberated from damaged or dying cells.
• These are called damage-associated molecular patterns (DAMPs).
• DAMPs can be a result of injuries from infections, chemical toxins, trauma, or other causes.
• DAMPs generally are not released from cells dying by apoptosis.

Pattern Recognition Receptors

• Cellular receptors for PAMPs and DAMPs are called pattern recognition receptors (PRRs).
• PRRs are found on cell surfaces, within phagocytic vesicles, and within the cytosol.
• Upon binding to PAMPs or DAMPs, PRRs initiate signal transduction pathways, triggering antimicrobial and proinflammatory functions within cells.

Toll-like Receptors (TLRs)

• Toll-like receptors (TLRs) are a critical class of PRRs, exhibiting evolutionary conservation.
• They recognize various microbial products, and molecules expressed by stressed or damaged cells.
• Humans have 10 different functional TLRs.
• TLRs include an extracellular Leucine-rich repeat (LRR) domain and an intracellular Toll/Interleukin-1 receptor (TIR) domain, initiating signaling cascades.
• TLR activation results in a series of signaling steps involving adaptor proteins and protein kinases, leading to the activation of various transcription factors (e.g., NF-κB, AP-1, IRF3, IRF7).
• These factors stimulate the production of genes crucial for inflammatory responses, including cytokines, chemokines, and endothelial adhesion molecules; and type I interferons for viral defense.
• TLR signaling initiates antimicrobial mechanisms like the respiratory burst, phagosome-lysosome fusion, and phagosome acidification.
• TLRs promote the production of β-defensins for direct microbial killing and immune response modulation.

Nod-like Receptors

• In addition to TLRs, NOD-like receptors (NLRs) are cytosolic sensors of PAMPs and DAMPs.
• They activate signal transduction pathways, promoting inflammation or type I IFN responses (antiviral).
• NLRs assemble into inflammasomes to activate caspase-1.
• Caspase-1 cleaves inactive precursors to form active pro-inflammatory cytokines IL-1β and IL-18.
• These cytokines promote inflammation and tissue remodeling.

Cytokines in Acute Inflammation

• Cytokines like IL-1, TNF-α, IL-6, IL-8, and IL-12 coordinate the initial response to infection or tissue damage.
• They can induce fever, increase vascular permeability, recruit immune cells, enhance antigen presentation, and promote various immune responses.

Inflammatory Response

• Inflammatory response involves changes to blood vessels to allow fluids and cells to reach the site of infection or injury.
• Leukocytes (WBCs) are crucial and arrive via a multi-step process:
  • Thetering and rolling, slowing leukocyte movement to adhere to endothelium..
  • Firm adhesion, involving activation and binding of integrins.
  • Transmigration, involving squeezing through the endothelium.
  • Chemotaxis, guiding the leukocytes towards the injury site.