Lymphatic System, Barrier Defenses, and Innate Immunity - Study Notes

Innate vs Adaptive Immunity

• Innate defenses are present at birth and respond quickly but non-specifically; adaptive defenses develop with exposure and are slower but highly specific.
• Adaptive immunity relies on lymphocytes, specifically B cells and T cells, and can produce antibodies.
• Innate immunity provides local, immediate defense; adaptive can yield systemic responses via antibodies.
• Innate has no memory; adaptive develops memory after initial exposure (e.g., memory B cells and plasma cells after B cell activation).
• The adaptive response can provide targeted, enduring protection against pathogens, whereas innate provides broad, initial control.

Barriers and First-Line Defenses (Physical, Chemical, and Microbial Barriers)

• Skin as a primary impermeable barrier: keratinized, dead outer cells.
• Mucous membranes trap and help remove invaders; mucus provides lubrication and entrapment.
• Dry vs moist skin: environmental exposure and low moisture environments influence barrier effectiveness.
• Low pH and washing actions on the skin help deter microbes.
• Sebaceous glands produce oils that help protect hair follicles; sweat provides washing action.
• Oral cavity: saliva contains lysozyme, which digests bacterial cell walls; saliva is itself a mucus-like protective fluid.
• Stomach: strong hydrochloric acid denatures proteins and activates digestive enzymes; pH and acidity kill many bacteria.
• Digestive tract enzymes also contribute to microbial destruction; many bacteria are ingested with food and saliva.
• Respiratory tract: mucus traps pathogens; ciliated epithelium moves trapped material up and out (mucociliary escalator) toward the pharynx and then to the digestive tract for destruction.
• Normal flora: nonpathogenic bacteria in mucus tissues compete with pathogens and prevent colonization by occupying niches and resources.
• Overall function: barriers prevent entry and limit spread; if breached, internal defenses engage.

Cells of the Innate Immune System

• Monocytes/macrophages: circulate in blood and differentiate into tissue macrophages; key for phagocytosis and antigen presentation.
• Dendritic cells: professional antigen-presenting cells with long cytoplasmic extensions to sample and present antigens to T cells; high surface area facilitates communication with many T cells.
• Macrophages in specific organs:
  • Kupffer cells in liver
  • Alveolar macrophages in lungs
  • Histocytes in connective tissue
  • Microglia in brain
• Neutrophils: most abundant circulating phagocytes; rapid responders to inflammation; granulocytes with multi-lobed nucleus; highly potent phagocytes.
• Natural killer (NK) cells: lymphocytes that can induce apoptosis in infected or abnormal cells; act without prior exposure; provide early defense.

Phagocytosis in Detail

• Process: phagocytes recognize, engulf, and internalize invaders into vesicles (phagosomes).
• Fusion with lysosomes yields a phagolysosome where digestion occurs.
• Enzymes such as lysozyme contribute to bacterial cell-wall digestion within phagolysosomes.
• Exocytosis removes debris after digestion.
• Visual analogy: Amoeba eating paramecia demonstrates engulfment; similar steps occur in human phagocytes.
• Key terms:
  • Phagosome: vesicle containing the engulfed microbe.
  • Lysosome: vesicle containing digestive enzymes.
  • Phagolysosome: fused phagosome and lysosome where digestion occurs.
• Neutrophils often perform rapid, intense phagocytosis during acute inflammation.

Illustrative equation of phagocytosis

• $ext{Phagosome} + ext{Lysosome} <br /> ightarrow ext{Phagolysosome}$

Antigen Presentation and the Role of Dendritic Cells

• Dendritic cells’ extensions increase surface area for interactions with T cells.
• They are especially important for initiating adaptive responses by presenting processed antigens to T cells, linking innate and adaptive immunity.
• This bridging is essential for initiating targeted T cell responses and antibody production.

Natural Killer Cells and Cytotoxic T Lymphocytes

• NK cells: part of the innate branch; kill abnormal cells by inducing apoptosis without needing antigen-specific recognition.
• Mechanism: release perforin to form pores in the target cell membrane and granzymes to trigger apoptotic pathways.
• NK cell activity is influenced by recognition of MHC class I on potential target cells:
  • When a cell displays normal MHC I, NK cell activity is restrained.
  • If a cell downregulates MHC I (common in some infections and cancers), NK cells are more likely to kill it.
• Cytotoxic T lymphocytes (CD8+ T cells): recognize infected cells presenting antigen on MHC class I; dock with MHC I and deliver cytotoxic hits.
• Summary: NK cells are a backup system when MHC I is reduced or altered; cytotoxic T cells provide targeted killing when a specific antigen is presented on MHC I.

Pattern Recognition Receptors (PRRs) and Microbial Sensing

• Innate recognition relies on pattern recognition receptors (PRRs) that detect common microbial features (PAMPs).
• Examples of PAMPs:
  • Lipopolysaccharide (LPS) on certain bacteria
  • Peptidoglycan in bacterial cell walls
  • Components of bacterial flagella
• PRRs detect the presence of bacteria or fungi and raise alarm; they also detect intracellular viral features.
• Intracellular detection focuses on viruses:
  • Cells recognize viral patterns such as single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA).
  • Some viral signatures differ from host nucleic acids, enabling recognition.
  • Cells may detect differences in DNA and RNA to distinguish self from non-self.
• Note: Recognition indicates the presence of a pathogen generally, not a specific organism.

Cytokines, Chemokines, and Inflammation

• Cytokines: small, short-range signaling proteins that coordinate immune responses between nearby cells (cell-to-cell communication).
• Histamine: one example of a cytokine/mediator released by damaged cells and mast cells; contributes to inflammation and vasodilation.
• Chemokines: a subset of cytokines that direct leukocyte migration to sites of infection (chemotaxis).
• Inflammation: localized response driven by macrophages, mast cells, and injured cells releasing mediators; recruits neutrophils and other immune cells to the site of injury or infection.
• The sequence typically involves macrophages and mast cells releasing signals that call neutrophils to the area.
• Interferons (see below) are also part of the signaling milieu, especially in viral infections.

Interferons and Antiviral State

• Interferons are cytokines with a primary antiviral role; they help neighboring cells resist viral replication.
• Mechanism (conceptual): a virus-infected cell releases interferon; neighboring cells respond by entering an antiviral state (e.g., upregulating antiviral proteins).
• Consequence: neighboring cells reduce viral replication, potentially sacrificing infected cells to limit spread.
• Rationale for resting during illness: fighting infection is energetically costly and involves losing infected cells while generating new immune effectors.

Fever and Pyrogens

• Some microbes produce pyrogens that raise the hypothalamic set point, causing fever.
• Fever is beneficial when controlled, as it can accelerate immune responses and inhibit some pathogens; however, unregulated fever can be harmful.
• The inflammatory milieu and pyrogen signaling contribute to fever as part of the protective response, but excessive fever requires management.

Interplay with the Adaptive Immune System

• Innate immunity acts as a gatekeeper and teacher for the adaptive response.
• By presenting antigens (via dendritic cells) and creating an inflammatory context, innate responses help activate B and T lymphocytes.
• Adaptive immunity produces:
  • Antibodies (humoral response) by B cells; antibodies provide systemic defense.
  • T cell responses (cell-mediated) and memory formation for faster responses upon re-exposure.
• The transcript references that B cells clone into plasma cells (antibody production) and memory B cells for faster future responses.

Practical and Real-World Implications

• Innate barriers are the first line of defense; when breached, the body mounts a rapid, localized response that buys time for the adaptive system.
• Fever and fatigue reflect the body’s active battle against infection and underscore the need for rest to support immune function.
• Understanding the balance between innate and adaptive responses informs vaccine design, infection control, and therapeutic strategies.

Visual and Supplemental Resources

• The instructor references videos demonstrating phagocytosis and cellular interactions, such as amoeba engulfing paramecia, to illustrate phagocytosis steps.
• If you have early access to class Explore resources, these videos can reinforce concepts before class.

Quick Connections to Core Principles

• Barrier defenses (skin, mucus, pH, normal flora) align with foundational principles of preventing pathogen entry.
• Phagocytosis demonstrates how cells physically remove invaders and prepare antigens for adaptive presentation.
• Pattern recognition and PRRs illustrate how the innate system detects general microbial patterns rather than specific pathogens.
• The MHC system and NK cell surveillance highlight the importance of “self” identification in immune regulation and the balance between destruction of infected cells and preservation of healthy tissue.
• The transition from innate to adaptive immunity explains why early, localized inflammation precedes targeted antibody and T cell responses.

Notable Terms and Concepts to Remember

• Keratinized epidermis; Langerhans cells; sebaceous glands; sweat; lysozyme; ciliated epithelium; mucociliary escalator; normal flora.
• Phagosome, lysosome, phagolysosome; exocytosis; neutrophils; macrophages; dendritic cells; Kupffer cells; microglia; histiocytes.
• MHC Class I; cytotoxic T cells; natural killer cells; perforin; granzymes; apoptosis.
• PRRs; PAMPs; LPS; peptidoglycan; flagellin; dsRNA; ssRNA.
• Cytokines; chemokines; histamine; interferon; chemotaxis; inflammation.
• Interplay between barrier defenses and systemic immune responses.