Innate Immunity: Nonspecific Defenses of the Host

Innate Immunity: Nonspecific Defenses of the Host

Overview of Immunity

Immunity refers to the ability of an organism to resist infection or disease. The immune system is divided into two main types: innate immunity and adaptive immunity. Innate immunity provides immediate, nonspecific defense against pathogens, while adaptive immunity is specific and develops over time.

• Susceptibility: The lack of resistance to a disease.

• Immunity: The ability to ward off disease.

• Innate immunity: Present at birth; provides rapid, nonspecific defense.

• Adaptive immunity: Acquired through exposure; specific to particular pathogens.

• Cytokines: Signaling proteins that regulate immune responses.

• Toll-like receptors (TLRs): Proteins on immune cells that recognize pathogen-associated molecular patterns (PAMPs).

First Line of Defense: Physical and Chemical Barriers

The first line of defense consists of physical and chemical barriers that prevent pathogens from entering the body.

Physical Factors

• Skin: The epidermis is made of tightly packed cells containing keratin, a protective protein.

• Mucous membranes: Secrete mucus to trap microbes.

• Ciliary escalator: Moves trapped microbes away from the lungs.

• Lacrimal apparatus: Washes the eye with tears.

Chemical Factors

• Saliva: Washes microbes off oral surfaces.

• Urine: Flushes microbes from the urinary tract.

• Vaginal secretions: Remove microbes from the vaginal canal.

• Sebum: Contains fungistatic fatty acids; inhibits fungal growth.

• Low pH: Skin (pH 3–5), gastric juice (pH 1.2–3.0), vaginal secretions (pH 3–5) inhibit microbial growth.

• Lysozyme: Enzyme found in perspiration, tears, saliva, and urine; breaks down bacterial cell walls.

Normal Microbiota and Innate Immunity

• Microbial antagonism/competitive exclusion: Normal microbiota compete with pathogens or alter the environment to inhibit pathogen growth.

• Commensal microbiota: Microbes benefit without harming the host.

• Opportunistic pathogens: Normally harmless microbes that can cause disease under certain conditions.

• Microbiome: The collection of all microbes living in and on the body.

Second Line of Defense: Internal Mechanisms

If pathogens bypass the first line of defense, the second line includes cellular and molecular responses.

Formed Elements in Blood

• Differential White Cell Count: Percentage of each type of white blood cell in a sample.

• Components of the Lymphatic System: Includes lymph nodes, spleen, and lymphatic vessels.

Phagocytosis

• Phagocytes: Cells that ingest microbes or particles (e.g., neutrophils, macrophages).

• Fixed macrophages: Reside in specific tissues.

• Wandering macrophages: Move throughout tissues.

• Mechanism: Chemotaxis, adherence, ingestion, digestion, elimination.

Body’s Defense Mechanisms

• Toll-like receptors (TLRs): Recognize PAMPs and induce cytokine production.

• Cytokines: Regulate immune response intensity and duration.

Inflammation

• Acute-phase proteins: Activated during inflammation (e.g., complement, cytokines, kinins).

• Vasodilation: Increases blood flow; caused by histamine, kinins, prostaglandins, leukotrienes.

• Signs: Redness, swelling, pain, heat, loss of function.

• Process: Phagocyte migration, phagocytosis, tissue repair.

• Functions: Destroy/remove injurious agents, wall off affected area, repair/replace tissue.

Fever

• Definition: Abnormally high body temperature.

• Mechanism: Hypothalamus set at 37°C; endotoxins cause phagocytes to release interleukin-1 (IL-1); prostaglandins reset hypothalamus to higher temperature.

• Body response: Increased metabolism, shivering, vasodilation, sweating.

• Advantages: Inhibits pathogen growth, speeds up tissue repair.

• Disadvantages: Can cause discomfort, excessive fever may be harmful.

Antimicrobial Substances

The body produces several substances that directly attack pathogens.

The Complement System

The complement system consists of serum proteins that are activated in a cascade to enhance immune responses.

• Activation Pathways:

  • Classical pathway: Triggered by antigen-antibody reaction.

  • Alternative pathway: Triggered by proteins C3, B, D, P and pathogen surfaces.

  • Lectin pathway: Triggered by lectin binding to pathogen carbohydrates.

• Key Complement Proteins:

  • C3b: Opsonization (enhances phagocytosis)

  • C3a, C5a: Inflammation

  • C5b, C6, C7, C8, C9: Cell lysis (membrane attack complex)

• Effects: Opsonization, cytolysis, inflammation, attraction of phagocytes.

• Bacterial Evasion: Capsules prevent complement activation; surface lipids/carbohydrates prevent MAC formation; enzymes digest C5a.

Interferons (IFNs)

• IFN-α and IFN-β: Induce cells to produce antiviral proteins that inhibit viral replication.

• Gamma IFN: Stimulates phagocytosis by neutrophils and macrophages.

Transferrins

• Transferrins: Bind serum iron, making it unavailable to microbes.

Antimicrobial Peptides

• Antimicrobial peptides: Small proteins that lyse bacterial cells.

Summary Table: Complement Pathways and Effects

Pathway	Trigger	Main Proteins	Effect
Classical	Antigen-antibody reaction	C1, C2, C4, C3	Opsonization, inflammation, cytolysis
Alternative	Pathogen surface, C3, B, D, P	C3, B, D, P	Opsonization, inflammation, cytolysis
Lectin	Lectin binding to pathogen carbohydrates	Lectin, C2, C4, C3	Opsonization, inflammation, cytolysis

Key Mechanisms and Equations

• Phagocytosis Steps: Chemotaxis → Adherence → Ingestion → Digestion → Elimination

• Complement Activation:

$\text{C3} \rightarrow \text{C3a} + \text{C3b}$

$\text{C3b} \text{ (opsonization)}$

$\text{C3a} + \text{C5a} \text{ (inflammation)}$

$\text{C5b} + \text{C6} + \text{C7} + \text{C8} + \text{C9} \rightarrow \text{Membrane Attack Complex (MAC)} \rightarrow \text{Cytolysis}$

Example: Skin as a Physical Barrier

The skin's epidermis, composed of tightly packed cells and keratin, acts as a formidable barrier to microbial invasion. Cuts or abrasions can compromise this defense, allowing pathogens to enter.

Example: Lysozyme in Tears

Lysozyme, an enzyme found in tears, breaks down the peptidoglycan in bacterial cell walls, providing chemical protection against infection.

Example: Fever Response

During infection, the body may increase its temperature to inhibit pathogen growth and enhance immune activity. This is regulated by cytokines and prostaglandins acting on the hypothalamus.

Additional info: Academic context was added to clarify mechanisms, definitions, and examples for each defense line and immune component.