Innate Immunity: Nonspecific Defenses of the Host

Innate Immunity: Nonspecific Defenses of the Host

Overview of the Immune System

The immune system is a complex network of cells, tissues, and molecules that protects the body from pathogens. It is organized into three lines of defense, each with distinct characteristics and roles in host protection.

• First Line of Defense: Physical and chemical barriers that prevent pathogen entry.

• Second Line of Defense: Cellular and molecular responses that act rapidly upon pathogen invasion.

• Third Line of Defense: Adaptive immunity, involving highly specific responses and memory.

Immunity and Susceptibility

• Immunity: The ability of an organism to resist infection or disease by identifying and destroying pathogens.

• Susceptibility: The lack of resistance to a disease or pathogen.

Toll-like Receptors (TLRs) and Pathogen-Associated Molecular Patterns (PAMPs)

Toll-like receptors (TLRs) are proteins on immune cells that recognize pathogen-associated molecular patterns (PAMPs), which are conserved molecular structures found in many pathogens. Recognition triggers immune responses, including the release of cytokines.

• Example: TLR4 recognizes lipopolysaccharide (LPS) from Gram-negative bacteria.

Cytokines

Cytokines are small proteins released by cells that regulate the intensity and duration of immune responses. They mediate communication between cells, promote inflammation, and recruit immune cells to infection sites.

• Examples: Interleukins, interferons, tumor necrosis factors.

First Line of Defense: Physical and Chemical Barriers

Physical Factors

• Skin: Acts as a physical barrier; tightly packed cells and keratin prevent pathogen entry.

• Mucous Membranes: Line the respiratory, gastrointestinal, and genitourinary tracts; secrete mucus to trap microbes.

• Mucociliary Escalator: Cilia in the respiratory tract move mucus and trapped particles out of the lungs.

• Cerumen (Earwax): Protects the ear canal by trapping microbes and dust.

• Urine: Flow mechanically removes microbes from the urinary tract.

• Vaginal Secretions: Flush out potential pathogens from the vaginal tract.

Chemical Factors

• Sebum: Oily substance produced by sebaceous glands; inhibits microbial growth due to its acidity.

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

• Gastric Juice: Highly acidic (pH 1.2–3.0); destroys most ingested pathogens.

• Vaginal Secretions: Acidic environment inhibits microbial growth.

Role of Normal Microbiota

The normal microbiota competes with pathogens for nutrients and attachment sites, produces substances harmful to pathogens, and stimulates the immune system.

• Probiotics: Live microorganisms that confer health benefits by enhancing the normal microbiota.

• Prebiotics: Non-digestible food ingredients that promote the growth of beneficial microbes.

Second Line of Defense: Cellular and Molecular Responses

Cells of the Immune System

• Granulocytes:

  • Neutrophils: Phagocytic cells; first responders to infection.

  • Basophils: Release histamine; involved in inflammation and allergic responses.

  • Eosinophils: Combat parasites and participate in allergic reactions.

• Agranulocytes:

  • Monocytes: Differentiate into macrophages and dendritic cells in tissues.

  • Macrophages: Highly phagocytic; present antigens to T cells.

  • Dendritic Cells: Phagocytic; initiate adaptive immune responses by presenting antigens.

  • Lymphocytes: Include natural killer (NK) cells (innate immunity), B cells, and T cells (adaptive immunity).

Lymphatic System

• Anatomy: Consists of lymph, lymphatic vessels, lymph nodes, spleen, thymus, and tonsils.

• Role in Immunity: Drains interstitial fluid, transports immune cells, and filters pathogens through lymph nodes.

Phagocytosis

Phagocytosis is the process by which certain cells ingest and destroy microbes and debris.

1. Chemotaxis: Phagocytes are attracted to infection sites by chemical signals.

2. Adherence: Phagocyte attaches to the microbe.

3. Ingestion: Microbe is engulfed into a phagosome.

4. Digestion: Phagosome fuses with lysosome; enzymes digest the microbe.

Inflammation

Inflammation is a local response to tissue injury or infection, characterized by four cardinal signs:

• Redness (rubor)

• Heat (calor)

• Swelling (tumor)

• Pain (dolor)

Histamine released from damaged cells causes vasodilation, increasing blood flow and permeability.

• Acute Inflammation: Short-term, beneficial response to injury.

• Chronic Inflammation: Long-lasting, can cause tissue damage.

Steps of Inflammation:

1. Vasodilation (mediated by histamine)

2. Phagocyte migration and phagocytosis

   • Chemotaxis: Movement toward chemical signals

   • Margination: Phagocytes stick to blood vessel walls

   • Diapedesis: Phagocytes move out of blood vessels into tissues

3. Tissue repair

   • Fibrosis: Scar tissue formation

   • Regeneration: Replacement with original tissue type

Fever

Fever is a systemic response to infection, mediated by cytokines and prostaglandins that reset the hypothalamic set point.

• Symptoms: Chills, shivering (body raising temperature), crisis (body cooling down).

Complement System

The complement system is a group of proteins that enhance immune responses. It can be activated by three pathways:

• Classical Pathway: Triggered by antibodies bound to antigens.

• Alternative Pathway: Activated directly by pathogen surfaces.

• Lectin Pathway: Initiated by mannose-binding lectin binding to pathogen carbohydrates.

Outcomes of Complement Activation:

• Inflammation

• Cytolysis: Formation of membrane attack complex (MAC) that lyses pathogens.

• Opsonization: Coating of pathogens to enhance phagocytosis.

Other Antimicrobial Substances

Interferons

Interferons are cytokines that interfere with viral replication and activate immune cells.

Iron-Binding Proteins

Iron-binding proteins (e.g., transferrin, lactoferrin, ferritin, hemoglobin) sequester iron, limiting its availability to microbes. Some bacteria produce siderophores to compete for iron.

Antimicrobial Peptides (AMPs)

AMPs are small peptides produced by host cells that disrupt microbial membranes, inhibit cell wall synthesis, and neutralize toxins.

• Examples: Defensins, cathelicidins.