Chapter 15

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Innate Immune System

Overview and General Purpose

The innate immune system is the body's first line of defense against invading pathogens. It provides immediate, non-specific responses to a wide variety of threats, including bacteria, viruses, fungi, and parasites. Unlike the adaptive immune system, the innate system does not require prior exposure to a pathogen and does not generate immunological memory.

Purpose: Prevent entry and rapidly eliminate pathogens.
Components: Physical, chemical, and biological barriers; cellular and soluble factors.
Organization: Involves barriers, recognition, alarm, inflammation, cell recruitment, and effector functions.

Comparison: Innate vs. Adaptive Immune Systems

Innate Immunity: Immediate, non-specific, no memory, uses pattern recognition (e.g., airport security).
Adaptive Immunity: Delayed, highly specific, generates memory, tailored responses (e.g., FBI investigation).

Pathogen Detection and Recognition

The innate immune system detects pathogens by recognizing Pathogen-Associated Molecular Patterns (PAMPs) using Pattern Recognition Receptors (PRRs). These receptors are found on immune cells and in soluble form in the blood.

PAMPs: Conserved molecular structures unique to microbes (e.g., bacterial cell wall components, viral RNA).
PRRs: Include Toll-like receptors (TLRs), NOD-like receptors (NLRs), and soluble factors like complement proteins.

Diagram of a bacterium, a common pathogen detected by the innate immune system

Barriers to Entry: The First Line of Defense

Physical, Chemical, and Biological Barriers

The body employs several barriers to prevent pathogen entry:

Physical: Skin, mucous membranes, cilia, tears.
Chemical: Acidic pH, enzymes (lysozyme, pepsin), bile, antimicrobial peptides (defensins).
Biological: Normal flora (commensal microbes) outcompete pathogens.

SEM image of skin surface, a physical barrier Diagram of respiratory tract showing mucous membranes and cilia

Comparison of Skin and Mucous Membranes

	Skin	Mucous Membrane
Number of Cell Layers	Many	One to a few
Cells Tightly Packed?	Yes	Yes
Cells Dead or Alive?	Outer layers: dead; inner layers: alive	Alive
Mucus Present?	No	Yes
Relative Water Content	Dry	Moist
Lysozyme Present?	Yes	With some
Defensins Present?	Yes	Yes
Sebum Present?	Yes	No
Cilia Present?	No	Trachea, uterine tubes
Constant Shedding and Replacement of Cells?	Yes	Yes

Table comparing skin and mucous membrane defenses

Secretions and Activities Contributing to Defense

Secretion/Activity	Function
Saliva	Washes microbes from teeth, gums, tongue, and palate; contains lysozyme
Stomach acid	Digests and/or inhibits microorganisms
Bile	Inhibitory to most microorganisms
Defecation, Vomiting, Urine	Eliminates microorganisms
Vaginal secretions	Acidity inhibits microorganisms
Menstrual flow	Cleanses uterus and vagina
Blood flow, Coagulation	Removes or prevents entry of pathogens

Table of secretions and activities contributing to first line of defense

Pattern Recognition and Immune Activation

Pattern Recognition Receptors (PRRs) and PAMPs

PRRs are crucial for the detection of pathogens. They recognize PAMPs, which are conserved microbial molecules not found in host cells.

Cellular PRRs: Located on the surface or inside immune cells (e.g., TLRs, NLRs).
Soluble PRRs: Circulate in blood (e.g., complement proteins).

Table of Toll-like receptors and their ligands

Toll-Like Receptors (TLRs)

TLRs are a family of PRRs that recognize specific PAMPs. They are found on the cell surface or within endosomal compartments of immune cells.

TLR	PAMP (Microbial Molecule)
TLR1	Bacterial lipopeptides and certain proteins in multicellular parasites
TLR2	Peptidoglycan, lipoteichoic acid (Gram-positive cell wall), yeast cell wall
TLR4	Lipid A in LPS (Gram-negative bacteria)
TLR5	Flagellin (bacterial flagella)
TLR3	Double-stranded RNA (viruses)
TLR7, TLR8	Single-stranded viral RNA
TLR9	Unmethylated CpG DNA (bacterial/viral DNA)

The Complement System

Activation Pathways

The complement system is a cascade of plasma proteins that enhances the ability of antibodies and phagocytic cells to clear microbes. It can be activated by three pathways:

Classical Pathway: Triggered by antibodies bound to antigens.
Alternative Pathway: Triggered directly by microbial surfaces.
Lectin Pathway: Triggered by lectin binding to microbial carbohydrates.

Diagram of complement activation pathways

Functions of Complement

Opsonization: Tags pathogens for phagocytosis.
Chemotaxis: Recruits immune cells to infection sites.
Direct Killing: Forms the Membrane Attack Complex (MAC) to lyse pathogens.

Diagram of complement cascade and MAC formation

Inflammation and Cellular Recruitment

Inflammatory Response

Inflammation is a hallmark of innate immunity, characterized by heat (calor), pain (dolor), redness (rubor), and swelling (tumor). It is triggered by cytokines and chemokines released from immune cells.

Vasodilation: Increases blood flow to the area.
Increased Permeability: Allows immune cells and proteins to enter tissues.
Extravasation: Movement of white blood cells from blood to tissues.

Recruitment of Innate Immune Cells

Key innate immune cells include neutrophils, macrophages, dendritic cells, natural killer (NK) cells, eosinophils, and basophils. Chemotactic signals and adhesion molecules guide these cells to infection sites.

Neutrophils: First responders, phagocytose bacteria, form pus.
Macrophages: Engulf pathogens, present antigens, secrete cytokines.
Dendritic Cells: Bridge innate and adaptive immunity by presenting antigens to T cells.
NK Cells: Kill virus-infected and cancerous cells.

Diagram of neutrophils and other innate immune cells

Effector Functions of Innate Immunity

Phagocytosis and Microbial Killing

Phagocytic cells (macrophages, neutrophils, dendritic cells) ingest and destroy pathogens. They may use lysosomal enzymes or generate reactive oxygen and nitrogen species (respiratory burst) for microbial killing.

Reactive Oxygen Species: Superoxide (O2-), hydrogen peroxide (H2O2), bleach (OCl-).
Antimicrobial Peptides: Defensins disrupt microbial membranes.

Diagram of phagocytosis process

Natural Killer (NK) Cells

NK cells recognize and kill infected or abnormal host cells using a balance of activating and inhibitory receptors. They are important for early defense against viruses and tumors.

The Lymphatic System and Hematopoiesis

Lymphatic System Structure and Function

The lymphatic system drains excess fluid from tissues, transports immune cells, and provides sites for immune cell interactions. It includes primary lymphoid organs (bone marrow, thymus) and secondary lymphoid organs (lymph nodes, spleen, MALT).

Lymph: Fluid containing immune cells and proteins.
Lymph Nodes: Sites for immune cell activation and proliferation.

Hematopoiesis and Leukocyte Lineages

All blood cells originate from pluripotent stem cells in the bone marrow. Major leukocyte lineages include:

Granulocytes: Neutrophils, eosinophils, basophils/mast cells.
Monocytes/Macrophages: Circulate in blood, mature in tissues.
Dendritic Cells: Antigen-presenting cells, initiate adaptive immunity.
Lymphocytes: B cells (antibody production), T cells (helper and cytotoxic), NK cells.

Summary Table: Key Innate Immune Components

Component	Function
Physical Barriers	Prevent pathogen entry (skin, mucosa)
Chemical Barriers	Destroy/inhibit microbes (acid, enzymes)
Phagocytes	Ingest and destroy pathogens
NK Cells	Kill infected/cancerous cells
Complement	Opsonization, chemotaxis, direct killing
Cytokines/Chemokines	Coordinate and recruit immune responses

Example: When bacteria breach the skin, PRRs on resident macrophages recognize PAMPs, triggering cytokine release, inflammation, and recruitment of neutrophils to eliminate the invaders.