Innate Immunity: Nonspecific Defenses of the Host – Study Notes

Innate Immunity: Nonspecific Defenses of the Host

Overview of Immunity

Immunity refers to the body's ability to resist or eliminate potentially harmful foreign materials or abnormal cells. The immune system is divided into innate (nonspecific) and adaptive (specific) immunity. Innate immunity provides immediate, general defense against pathogens, while adaptive immunity targets specific threats and develops memory for future responses.

• Immunity: The ability to ward off disease.

• Susceptibility: Lack of resistance to a disease.

• Innate Immunity: Defenses present at birth, acting rapidly against any pathogen.

• Adaptive Immunity: Immunity or resistance to a specific pathogen, slower to respond, with memory component.

White Blood Cell (WBC) Counts and Immunity

White blood cells (leukocytes) are crucial for immune defense. Their counts can indicate various health conditions:

• High WBC Count: May indicate bacterial infections, autoimmune diseases, or medication side effects.

• Low WBC Count: May indicate viral infections, pneumonia, autoimmune diseases, or cancers.

Recognition of Pathogens

The innate immune system recognizes pathogens using pattern recognition receptors:

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

• Binding of TLRs to PAMPs triggers the release of cytokines, which regulate immune responses.

First Line of Defense: Physical and Chemical Barriers

Physical Factors

Physical barriers prevent pathogen entry and remove microbes from body surfaces.

• Skin: Consists of the dermis (connective tissue) and epidermis (keratinized epithelial cells). Shedding and dryness inhibit microbial growth.

• Mucous Membranes: Line the gastrointestinal, respiratory, and genitourinary tracts. Mucus traps microbes and prevents drying.

• Lacrimal Apparatus: Produces tears that wash the eyes.

• Ciliary Escalator: Moves mucus and trapped microbes away from the lungs.

• Other Mechanisms: Earwax, urine flow, vaginal secretions, peristalsis, defecation, vomiting, and diarrhea help expel microbes.

Chemical Factors

Chemical barriers destroy or inhibit microbial growth.

• Sebum: Forms a protective film and lowers skin pH (3–5).

• Lysozyme: Enzyme in perspiration, tears, saliva, and urine that destroys bacterial cell walls.

• Gastric Juice: Low pH (1.2–3.0) destroys most bacteria and toxins.

• Vaginal Secretions: Low pH (3–5) inhibits microbes.

Normal Microbiota and Innate Immunity

Normal microbiota protect the host by competing with pathogens (microbial antagonism or competitive exclusion).

• Compete for space and nutrients.

• Produce substances harmful to pathogens.

• Alter environmental conditions to inhibit pathogen survival.

• Commensalism: One organism benefits, the other is unharmed.

• Probiotics: Live microbial cultures that confer health benefits.

Second Line of Defense: Cellular and Molecular Components

Formed Elements in Blood

Blood contains cells and cell fragments suspended in plasma, produced in red bone marrow via hematopoiesis.

• Erythrocytes: Red blood cells.

• Leukocytes: White blood cells.

• Platelets: Cell fragments involved in clotting.

Types of Leukocytes

• Granulocytes: Visible granules in cytoplasm.

  • Neutrophils: Phagocytic; early infection responders.

  • Basophils: Release histamine; involved in allergic responses.

  • Eosinophils: Phagocytic; toxic to parasites and helminths.

• Agranulocytes: No visible granules.

  • Monocytes: Mature into macrophages in tissues; phagocytic.

  • Dendritic Cells: Phagocytic; found in skin, mucous membranes, thymus.

  • Lymphocytes: T cells, B cells, and NK cells; key in adaptive immunity.

The Lymphatic System

The lymphatic system includes lymph, lymphatic vessels, lymphoid tissue, and red bone marrow. It transports lymphocytes and phagocytic cells, and carries microbes to lymph nodes for destruction by immune cells.

Phagocytes

Phagocytes are cells that ingest and destroy microbes.

• Fixed Macrophages: Reside in specific tissues and organs.

• Free (Wandering) Macrophages: Move throughout tissues, gathering at infection sites.

Mechanism of Phagocytosis

1. Chemotaxis: Chemical signals attract phagocytes to microbes.

2. Adherence: Phagocyte attaches to microbe surface.

3. Ingestion: Microbe is engulfed; opsonization (coating with serum proteins) enhances ingestion.

4. Digestion: Microbe is destroyed inside a phagolysosome.

Inflammation

Inflammation is a local response to tissue injury or infection, characterized by pain, redness, immobility, swelling, and heat. It aims to eliminate the cause of injury, remove damaged cells, and initiate tissue repair.

• Activates acute-phase proteins (e.g., histamine, kinins, prostaglandins, leukotrienes, cytokines) that cause vasodilation and increased blood vessel permeability.

• Phagocyte Migration: Margination (sticking to blood vessels) and diapedesis (movement through vessel walls) allow phagocytes to reach infection sites.

• Tissue Repair: Occurs after harmful substances are removed; involves repair of stroma (supporting tissue) and parenchyma (functioning tissue).

Fever

Fever is an abnormally high body temperature, regulated by the hypothalamus. Cytokines trigger the release of prostaglandins, raising the hypothalamic set point. Fever persists until cytokines are eliminated, after which vasodilation and sweating reduce temperature.

The Complement System

The complement system consists of serum proteins produced by the liver that enhance immune responses. These proteins act in a cascade (complement activation) and are designated by the letter 'C' and numbers (e.g., C1, C2, C3). Activated fragments are labeled with 'a' or 'b' (e.g., C3a, C3b).

Classical Pathway

Triggered by antibodies binding to antigens, leading to a cascade that activates C3, which splits into C3a (inflammation) and C3b (cytolysis, opsonization).

Alternative Pathway

Activated by direct interaction of complement proteins with microbial surfaces, independent of antibodies. C3 combines with factors B, D, and P, then splits into C3a and C3b.

Lectin Pathway

Initiated when macrophages ingest pathogens, releasing cytokines that stimulate the liver to produce mannose-binding lectin (MBL). MBL binds to mannose on microbes, activating C2 and C4, which then activate C3.

Outcomes of Complement Activation

• Cytolysis: Formation of the membrane attack complex (MAC) that lyses microbial cells.

• Opsonization: Coating of microbes to enhance phagocytosis.

• Inflammation: Complement proteins bind to mast cells, triggering histamine release.

• Regulation: Regulatory proteins prevent host cell damage by breaking down complement proteins.

• Deficiency: Lack of complement proteins increases susceptibility to infections.

• Pathogen Evasion: Capsules can prevent complement activation.

Other Antimicrobial Substances

Interferons (IFNs)

Interferons are cytokines with antiviral activity. IFN-α and IFN-β are produced in response to viral infections and induce neighboring cells to produce antiviral proteins (AVPs) that inhibit viral replication. IFN-γ activates neutrophils and macrophages to kill bacteria.

Iron-Binding Proteins

These proteins sequester iron, limiting its availability to microbes:

• Transferrin: Blood and tissue fluids.

• Lactoferrin: Milk, saliva, mucus.

• Ferritin: Liver, spleen, red bone marrow.

• Hemoglobin: Red blood cells.

• Bacteria produce siderophores to compete for iron.

Antimicrobial Peptides

Short peptides produced in response to microbial molecules. They inhibit cell wall synthesis, form pores in membranes, and have broad-spectrum activity.

Other Factors Affecting Innate Immunity

• Genetic Resistance: Certain genetic traits (e.g., sickle cell trait) confer resistance to specific pathogens (e.g., Plasmodium falciparum).

• Age: The very young and elderly are more susceptible to disease.

• Healthy Protocols: Observing proper hygiene and health practices supports innate immunity.