Body's Defense Mechanisms

Overview of Body Defenses

• Numerous pathogens lead to disease in humans
• First, pathogens must access a portal of entry, penetrate the surface, and evade the body's defenses
• Two broad categories of defense are innate and adaptive
• Innate defenses are present at birth and nonspecific, without memory
• Adaptive defenses are specific with memory, developing later in life
• First line of defense includes innate barriers
• Second line of defense is an innate immune response
• Third line of defense is an adaptive immune response

The Body's First Line of Defense

• The surface environment inhibits microbes
• Barriers are non-specific
• Nutrients, temperature, and pH impact the surface environment
• Structural, mechanical, chemical, and genetic factors act as barriers

Structural Barriers

• Epithelium found internally and externally
• Two types of epithelial surfaces are skin and mucous membranes
• Epithelium constantly undergoes mitosis, replacing sloughed layers
• Microbes attached to the epithelium are lost
• Tight junctions exist between epithelial cells

Mechanical Barriers

• Removal with movement
• Mucociliary movement in the nose and throat traps microbes in mucus, cilia coughed/swallowed
• Fluid movement from urine, saliva, and tears flush microbes

Chemical Barriers

• Agents produced by surface cells
• Keratin waterproofs and dries the skin
• Perspiration from sweat glands has salt that inhibits pathogens
• Lysozymes are antibacterial, and found in saliva and tears
• Sebum, from sebaceous (oil) glands, lowers skin pH
• HCL acid lowers stomach pH to inhibit bacteria

Genetic Barriers

• Hosts are genetically immune to other hosts' diseases
• Microbes lack appropriate receptors or the ability to attack host cells
• Species specificity example is HIV versus FIV, Ebola virus, and heartworms

Survival of Normal Flora

• Normal flora survive via adjustments to attach to the surface
• Attachment is with adhesins
• Adhesins bind to complementary receptor molecules via a lock and key fit

Practice Examples

• Salt is an integument chemical barrier
• Lysozymes are a respiratory and chemical barrier
• Mucociliary movement is a respiratory and mechanical barrier
• HCL is a digestive, chemical barrier
• Urine is a urinary, chemical barrier
• Lactobacillus is an epidermis barrier
• Mitosis in the intestine is a structural barrier
• Pinworms are an intestinal, genetic barrier
• Vomiting is a digestive, mechanical barrier

Body's Second Line of Defense

• Occurs when pathogens penetrate skin or mucous membranes, bypassing initial barriers
• Innate and nonspecific immune response
• Involves 4 components: inflammation, phagocytosis, interferon, and complement, with blood involvement

Inflammation

• "Itis"
• Nonspecific response to tissue damage from trauma, wounds, or burns
• Goals are to remove the agent, keep damage local, and allow healing
• Characterized by redness, heat, swelling, and pain
• Fifth sign is loss of function like pain and swelling

Sequential Events Following Injury in Inflammation

• Vascular changes
• Edema (local)
• Fever (systemic)

Vascular Changes

• Triggered by released chemicals, which leads to dilation
• Bradykinins, prostaglandins, and histamine released
• Vasodilation produces redness and localized heat
• Delivers blood clotting proteins and leukocytes to the injury site

Edema

• Swelling
• Results from increased vascular permeability due to the same chemicals
• Increased permeability results in increased pressure from more blood

Consequences of Edema

• Swelling dilutes toxins and applies pressure to nearby nerves

Inflammation

• Vascular changes and edema lead to neutrophils and monocytes delivering to the site of infection
• Chemotactic factors recruit cells
• Diapedesis is when cells squeeze through vessel walls to enter the infection site
• Phagocytosis allows tissue repair and pathogen removal

Phagocytosis

• Cells capable of phagocytosis
• Divided into 5 stages: chemotaxis, ingestion, fusion, killing, and elimination

Phagocytosis Stages

• Chemotaxis is the recognition of the invader
• Ingestion surrounds the microbe and forms a phagosome
• Fusion occurs as a lysosome fuses with a phagosome, creating a phagolysosome
• Killing occurs as digestive enzymes destroy the microbe
• Elimination discharges debris out of cell

Fever

• Only occurs if microbe is present
• Results when systemic pyrogens trigger the hypothalamus, increasing core temperature
• There are bacterial toxins (exogenous) or phagocytes (endogenous)
• Fever makes the environment less hospitable, inhibiting microbe growth and enhancing phagocytosis

Chemical Defenses: Interferon

• Protein molecules released by host cells to inhibit the spread of viral infections nonspecifically
• Inhibits viral reproduction
• A cell releases interferon after infection to protect neighboring cells

Chemical Defenses: Complement

• Serum proteins designated numerically by order of discovery
• Three primary effects: inflammation, opsonization and MAC (cytolysis)
• C3a and C5a: promote inflammation
• C3b: promotes Opsonization
• C5b-9: Promotes MAC/Cytolysis

Interference with Phagocytes

• Microbes produce surface proteins that interfere with direct contact with phagocytes, blocking receptors or mimicking host cells.
• These Surface Proteins allow for the Third Line of Defense