Innate Immunity: Lines of Defense

Innate Immunity

• Resistance and Susceptibility: Ability to ward off disease (resistance) and vulnerability or lack of resistance (susceptibility)
• Three Lines of Defense:
• First Line of Defense: Non-specific natural barriers that restrict entry of pathogens (e.g., skin and mucous membranes)
• Second Line of Defense: Innate non-specific immune defenses that provide rapid local response to pathogens (e.g., fever, phagocytes, inflammation, and interferon)
• Third Line of Defense: Antigen-specific immune responses that specifically target and attack invaders that get past the first two lines of defense (e.g., antibodies and lymphocytes)

Mechanical Defenses

• Skin:
• Two layers: epidermis (thin outer layer of epithelial tissue) and dermis (thick inner layer of connective tissue)
• Contains Langerhans cells, dead cells, and keratin (waterproof)
• Intact skin is an effective barrier against most pathogens, but exceptions include hookworms and dermatophytes
• Mucous Membranes:
• Line gastrointestinal, genitourinary, and respiratory tracts
• Two layers: outer epithelial and inner connective layer
• Epithelial layer secretes mucus that maintains moist surfaces
• Although they inhibit microbial entry, they offer less protection than skin
• Some microorganisms can penetrate mucous membranes, such as papillomavirus and Treponema pallidum
• Other Mechanical Defenses:
• Lacrimal apparatus: continual washing and blinking prevents microbes from settling on the eye surface
• Saliva: washes microbes from teeth and mouth mucous membranes
• Mucus: traps many microbes
• Nose hair: coated with mucus, filters dust, pollen, and microbes
• Ciliary escalator: cilia on mucous membranes of lower respiratory tract move upwards towards throat at 1-3 cm/hour
• Coughing and sneezing: expel foreign objects
• Epiglottis: covers larynx during swallowing
• Urination: cleanses urethra
• Vaginal secretions: remove microbes from genital tract

Chemical Defenses

• Sebum: oily substance produced by sebaceous glands that forms a protective layer over skin
• Contains unsaturated fatty acids that inhibit growth of certain pathogenic bacteria and fungi
• pH: low, skin pH usually between 3 and 5, caused by lactic acid and fatty acids
• Perspiration: produced by sweat glands, contains lysozyme and acids
• Lysozyme: enzyme that breaks down gram-positive cell walls, found in nasal secretions, saliva, and tears
• Gastric Juice: mixture of hydrochloric acid, enzymes, and mucus, pH between 1.2 to 3, kills many microbes and destroys most toxins
• Transferrins: iron-binding proteins in blood that inhibit bacterial growth by reducing available iron

Cellular Elements of Blood

• Erythrocytes (RBC): transport O2 and CO2
• Leukocytes (WBC): various functions, including phagocytosis and antibody production
  • Granulocytes: phagocytosis (neutrophils, basophils, and eosinophils)
  • Monocytes/Macrophages: phagocytosis
  • Lymphocytes: antibody production (B cells) and cell-mediated immunity (T cells)
• Platelets: blood clotting

Second Line of Defense

• Phagocytosis: process by which phagocytes (macrophages, neutrophils, and eosinophils) engulf and digest foreign particles and microorganisms
• Phagocytes: attracted to site of infection by chemotaxis
• Stages of Phagocytosis:
  1. Chemotaxis: phagocytes are chemically attracted to site of infection
  2. Adherence: phagocyte plasma membrane attaches to surface of pathogen or foreign material
  3. Ingestion: plasma membrane of phagocytes extends projections (pseudopods) that engulf the microbe
  4. Digestion: inside the cell, phagosome fuses with lysosome to form a phagolysosome, where lysosomal enzymes kill most bacteria

Inflammation

• Triggered by: tissue damage due to infection, heat, wound, etc.
• Four Major Symptoms:
  1. Redness
  2. Pain
  3. Heat
  4. Swelling
• Functions:
  1. Destroy and remove pathogens
  2. Limit effects by confining the pathogen and its products
  3. Repair and replace tissue damaged by pathogen and its products
• Stages of Inflammation:
  1. Vasodilation: increase in diameter of blood vessels
  2. Phagocyte migration and margination
  3. Phagocytes destroy microbes, as well as dead and damaged host cells
  4. Tissue repair: dead and damaged cells are replaced

Antimicrobial Substances

• Complement System: large group of serum proteins that participate in the lysis of foreign cells, inflammation, and phagocytosis
  • Classical Pathway: initiated by an immune reaction of antibodies
  • Alternative Pathway: initiated by direct interaction of complement proteins with microbial polysaccharides
• Consequences of Complement Activation:
  1. Cytolysis: due to the formation of a membrane attack complex (MAC) that produces lesions in microbial membranes
  2. Inflammation: complement components trigger the release of histamine, which increases vascular permeability
  3. Opsonization: complement components bind to microbial surface and promote phagocytosis
• Interferons: antiviral proteins that interfere with viral multiplication
  • Alpha and Beta Interferon: produced by virus-infected cells and diffuse to neighboring cells, causing uninfected cells to produce antiviral proteins (AVPs)
  • Gamma Interferon: produced by lymphocytes, causes neutrophils to kill bacteria

Fever Response

• Fever: body temperature above 37°C or 98.7°F
• Positive Effects:
  • Enhances interferon effects
  • Tissue repair
  • Phagocytosis
  • Inhibits some microbes
• Negative Effects:
  • Causes discomfort, body aches, malaise, and fatigue
  • If fever is too high, critical proteins are denatured and nerve impulses are inhibited, resulting in hallucinations, coma, and death
• Steps of Fever Response:
  1. Phagocytes release chemical signals called pyrogens (interleukin-1, etc.) which enter bloodstream
  2. Hypothalamic thermostat is reset
  3. Hypothalamus communicates with other areas of the brain which initiate shivering, increased metabolic rate, and constriction of blood vessels of the skin
  4. Body core temperature increases until reaches the setting prescribed by the hypothalamus
  5. As infection subsides and pyrogens decrease, thermostat is reset to normal by hypothalamus

Innate Immunity

• Resistance: The ability to ward off disease, which can be further divided into nonspecific resistance and specific resistance.

Nonspecific Resistance

• First Line of Defense: Non-specific natural barriers that restrict the entry of pathogens, including:
  • Skin (epidermis and dermis)
  • Mucous membranes (gastrointestinal, genitourinary, and respiratory tracts)
  • Lacrimal apparatus (continuous washing and blinking prevents microbes from settling on the eye surface)
  • Saliva (washes microbes from teeth and mouth mucous membranes)
  • Mucus (thick secretion that traps many microbes)
  • Nose hair (coated with mucus, filters dust, pollen, and microbes)
  • Ciliary escalator (cilia on mucous membranes of the lower respiratory tract move upwards towards the throat at 1-3 cm/hour)
  • Coughing and sneezing (expel foreign objects)
  • Epiglottis (covers the larynx during swallowing)
  • Urination (cleanses the urethra)
  • Vaginal secretions (remove microbes from the genital tract)

Chemical Defenses

• Sebum: An oily substance produced by sebaceous glands that forms a protective layer over the skin, containing unsaturated fatty acids that inhibit the growth of certain pathogenic bacteria and fungi.
• pH: The skin's low pH, usually between 3 and 5, caused by lactic acid and fatty acids, which inhibits the growth of certain pathogens.
• Perspiration: Produced by sweat glands, containing lysozyme and acids that inhibit the growth of certain pathogens.
• Lysozyme: An enzyme that breaks down gram-positive cell walls, found in nasal secretions, saliva, and tears.
• Gastric Juice: A mixture of hydrochloric acid, enzymes, and mucus, with a pH between 1.2 to 3, which kills many microbes and destroys most toxins.
• Transferrins: Iron-binding proteins in blood that inhibit bacterial growth by reducing available iron.

Cellular Elements of Blood

• Erythrocytes (RBC): Responsible for transporting oxygen and carbon dioxide, with a count of 4.8-5.4 million cells/mm3.
• Leukocytes (WBC): Responsible for various functions, including phagocytosis, with a count of 5000-9000 cells/mm3.
• Neutrophils: Phagocytic cells that predominate early in infection, making up 70% of WBC.
• Basophils: Produce histamine, making up 1% of WBC.
• Eosinophils: Produce toxins against parasites and perform some phagocytosis, making up 4% of WBC.
• Monocytes/Macrophages: Phagocytic cells that make up 5% of WBC.
• Lymphocytes: Responsible for antibody production and cell-mediated immunity, making up 20% of WBC.
• Platelets: Responsible for blood clotting, with a count of 300,000 cells/mm3.

Second Line of Defense

• Phagocytosis: The process of engulfing and digesting foreign particles and microorganisms, carried out by white blood cells.
• Phagocytosis Stages: Include chemotaxis, adherence, ingestion, and digestion.

Inflammation

• Inflammation: Triggered by tissue damage due to infection, heat, or wound, resulting in four major symptoms: redness, pain, heat, and swelling.
• Inflammation Functions: Include destroying and removing pathogens, limiting the effects of infection, and repairing and replacing damaged tissue.
• Inflammation Stages: Include vasodilation, phagocyte migration and margination, and tissue repair.

Antimicrobial Substances

• Complement System: A large group of serum proteins that participate in the lysis of foreign cells, inflammation, and phagocytosis.
• Complement Activation: Can occur through the classical pathway (initiated by an immune reaction of antibodies) or the alternative pathway (initiated by direct interaction of complement proteins with microbial polysaccharides).
• Consequences of Complement Activation: Include cytolysis, inflammation, opsonization, and inactivation of complement.

Interferons

• Interferons: Antiviral proteins that interfere with viral multiplication, produced by virus-infected cells and diffusing to neighboring cells.
• Interferon alpha and beta: Produced by virus-infected cells and causing uninfected cells to produce antiviral proteins.
• Interferon gamma: Produced by lymphocytes and causing neutrophils to kill bacteria.

Fever Response

• Fever: A body temperature above 37°C or 98.7°F, which can have both positive and negative effects on the body.
• Fever Response Steps: Include phagocytes releasing pyrogens, the hypothalamic thermostat being reset, and the body core temperature increasing until it reaches the setting prescribed by the hypothalamus.

Learn about the three lines of defense in innate immunity, including non-specific natural barriers, rapid local responses, and more. Understand resistance and susceptibility to disease.