Innate Immunity: Structure and Function in Host Defense

Innate Immunity

Overview of the Immune System

The immune system is a complex network of cells, tissues, and organs that protects the body from infection and disease. It recognizes and eliminates pathogens such as bacteria, viruses, fungi, and abnormal host cells (e.g., infected or cancerous cells). The immune system is divided into two main branches:

• Innate immunity: Rapid, nonspecific response targeting shared microbial features.

• Adaptive immunity: Slower, highly specific response with memory.

Nonspecific means the response targets common microbial features rather than specific species.

Microbe–Host Interactions

Microbe–host interactions are dynamic and involve both beneficial and harmful microbes. Many microbial structures act as danger signals, alerting the immune system to potential threats.

Three Lines of Host Defense

The body employs three lines of defense against pathogens:

1. First line: Physical and chemical barriers that prevent microbial entry.

2. Second line: Innate immune defenses that respond rapidly and nonspecifically.

3. Third line: Adaptive immunity, highly specific and generates memory.

The second and third lines of defense detect conserved microbial structures such as flagella, cell wall components, and capsules.

First Line of Defense: Physical Barriers

Skin and Mucous Membranes

The skin and mucous membranes form the body's outer protective layer. The skin consists of three layers:

• Epidermis: Outermost layer; constant shedding removes attached microbes.

• Dermis: Middle layer; provides structural support.

• Hypodermis: Deepest layer; connects skin to underlying tissues.

Mucous membranes trap microbes using mucus, preventing their entry.

Cell Junctions

• Tight junctions: Seal neighboring cells together, blocking passage of microbes.

• Desmosomes: Anchor cells, providing mechanical strength.

• Gap junctions: Form channels for cell-to-cell communication.

Mucociliary Escalator

The mucociliary escalator operates in the respiratory tract. Ciliated cells move mucus upward, trapping microbes and debris, directing them toward the esophagus to be swallowed. Impaired cilia function increases infection risk.

Mechanical Flushing Actions

• Tears (eyes) and urine (urinary tract) physically remove microbes.

• Tears and saliva contain lysozyme, an enzyme that breaks down peptidoglycan in bacterial cell walls.

First Line of Defense: Chemical Barriers

Antimicrobial Peptides (AMPs)

AMPs are fast-acting, broad-spectrum molecules produced by epithelial and immune cells. They kill microbes by disrupting membranes or interfering with intracellular processes. AMPs can also recruit immune cells by triggering cytokine release.

Bacteriocins

Bacteriocins are antimicrobial peptides produced by bacteria to kill closely related bacterial species. They help beneficial microbes compete in environments such as the gut.

Defensins

Defensins are small, positively charged peptides found in skin, mucosa, and phagocytes. They kill microbes by disrupting membrane integrity and help shape early immune responses.

The Complement System

Overview

The complement system is a group of approximately 30 plasma proteins that function in a cascade. Complement enhances inflammation, opsonization, and direct killing of microbes via the membrane attack complex (MAC).

Classical Pathway

• Antibody binds pathogen → C1 activation

• Formation of C3 convertase

• C3 is cleaved into C3b (opsonization) and C3a (inflammation)

• Terminal pathway forms the MAC → cell lysis

Phagocytosis

Process and Cells Involved

Phagocytosis is the process of engulfing and destroying microbes, performed by neutrophils, macrophages, and dendritic cells. The steps are:

1. Chemotaxis: Movement toward chemical signals.

2. Adherence: Attachment to the microbe.

3. Ingestion: Engulfment of the microbe.

4. Digestion: Breakdown of the microbe.

5. Exocytosis: Expulsion of debris.

Recognition occurs through pattern-recognition receptors (PRRs) or via opsonins such as C3b.

Phagolysosome Formation

A phagosome encloses the pathogen. Fusion with a lysosome forms the phagolysosome, where acidic pH (≈ 5–5.5) activates enzymes that kill the microbe.

Opsonization

Opsonization occurs when C3b coats a microbe, increasing phagocytosis efficiency. This process is especially important for clearing encapsulated bacteria.

Acute-Phase Proteins

C-reactive Protein (CRP)

CRP is produced by the liver during inflammation. It binds to microbial surfaces, enhances complement activation, and acts as an opsonin.

Cytokines

Overview

Cytokines are small signaling proteins released by immune cells to coordinate inflammation, activation, and communication. Major groups include:

• Interleukins

• Chemokines

• Interferons

Cytokines act in autocrine, paracrine, or endocrine ways.

Interferons

• Type I interferons (IFN-α and IFN-β): Produced early during viral infection; induce an antiviral state.

• Type II interferon (IFN-γ): Primarily activates macrophages.

Inflammation

Role and Sequence

Inflammation helps control infection, recruit immune cells, and induce fever. Key mediators include histamine, prostaglandins, and cytokines. Inflammation is protective when controlled but damaging when excessive or chronic.

• Trigger: PAMPs or DAMPs

• Sensor: PRRs

• Signal: Cytokines and chemokines

• Response: Immune cell recruitment

• Resolution: Pathogen clearance and tissue repair

Innate Immune Cell Overview

Leukocytes and Hematopoiesis

Leukocytes are all white blood cells. Lymphocytes are a subset that include B cells, T cells, and NK cells. All immune cells arise from hematopoietic stem cells in the bone marrow. Lineages include myeloid and lymphoid.

Major Innate Immune Cells

• Neutrophils: First responders; phagocytosis.

• Eosinophils: Parasite defense, allergy, degranulation.

• Basophils/Mast cells: Histamine release, allergic inflammation.

• Monocytes: Differentiate into macrophages or dendritic cells.

• Macrophages: Phagocytosis, cytokine production, antigen presentation.

• Dendritic cells: Activate naïve T cells.

• NK cells: Kill virus-infected or tumor cells; detect missing self; release perforin and granzymes.

Pattern Recognition

Pattern-Recognition Receptors (PRRs)

PRRs detect PAMPs (pathogen-associated molecular patterns) and DAMPs (damage-associated molecular patterns). Major PRR families include:

• TLRs (Toll-like receptors)

• CLRs (C-type lectin receptors)

• RLRs (RIG-I-like receptors)

• NLRs (NOD-like receptors)

• ALRs (AIM2-like receptors)

Summary Table: Major Innate Immune Cells and Functions

Cell Type	Main Function	Key Features
Neutrophils	Phagocytosis	First responders to infection
Eosinophils	Parasite defense, allergy	Degranulation
Basophils/Mast cells	Allergic inflammation	Release histamine
Monocytes	Differentiation	Become macrophages or dendritic cells
Macrophages	Phagocytosis, cytokines, antigen presentation	Long-lived, tissue-resident
Dendritic cells	Activate naïve T cells	Bridge innate and adaptive immunity
NK cells	Kill virus-infected/tumor cells	Release perforin and granzymes

Example Applications

• Physical barriers: Skin prevents microbial entry.

• Phagocytosis: Neutrophils engulf bacteria during infection.

• Cytotoxic killing: NK cells destroy virus-infected cells.

Additional info: The notes above expand on the lecture handout by providing definitions, context, and examples for each major concept in innate immunity, suitable for exam preparation and self-study.