Chapter 16: Innate Immunity: Non-Specific Defenses of The Host

Chapter 16: Innate Immunity: Non-Specific Defenses of the Host

The Concept of Immunity

Immune System: Protects the human host from pathogens.
Immunity: The ability to fight off pathogens and prevent disease.
Host Resistance: Ability of a host to combat pathogens (having immunity).
Host Susceptibility: A lack of immunity (lacking resistance).
Host Defense: Ability of the host to remove pathogens and prevent disease.
- If host defenses are successful, the host is considered immune (resistant).
- If host defenses are not successful, the host becomes diseased (susceptible).

Two Types of Defenses (Immunity)

Innate Immunity vs Adaptive Immunity

Innate Immunity:
- Present at birth, provides non-specific defense against all pathogens.
- Characteristics:
  - Also known as “non-specific” immunity; does not discriminate among pathogens.
  - No specific recognition of microbes; aims to eliminate all pathogens (bacteria, viruses, fungi).
  - Lacks immunological memory since it's the first encounter.
  - Has a rapid immune response.
- Components: Composed of the 1st and 2nd lines of host defenses.
Adaptive Immunity:
- Develops later in life, is not innate.
- Characteristics:
  - Provides immunity against specific pathogens; discriminates among pathogens.
  - Specific recognition and response to particular microbes.
  - Possesses immunological memory from previous encounters with the same pathogen.
  - Slower response compared to innate immunity, but still relatively fast.
- Components: Composed of the 3rd line of host defenses.

Innate Immunity (Non-Specific Host Defenses)

1st Line of Defense

Physical Barriers
- Intact Skin:
  - Non-broken, no injuries.
  - Composed of closely packed epithelial cells, specifically flat or squamous cells.
  - Continuous layering of multiple layers at the epidermis level.
  - Keratin protein in the top layer reinforces skin and protects underlying layers (epidermis).
  - Dryness prevents moisture accumulation, which inhibits pathogen growth.
  - Shedding of the top skin layer helps remove pathogens.
Mucous Membranes:
- Epithelial layers lining gastrointestinal, respiratory, and genitourinary tracts.
- Secrete viscous fluid called mucus, trapping pathogens for removal.
Ciliary Escalators:
- Present in the respiratory tract and consists of epithelial cells with cilia.
- Cilia move in a coordinated manner to sweep mucus out of the body, facilitating expulsion through coughing or swallowing.
Lacrimal Apparatus:
- Protects the eyes through the action of tears.
- Tears provide continuous washing action that removes pathogens from the eye.
Saliva, Urine, and Vaginal Secretions:
- These fluids have flushing mechanisms that prevent pathogen accumulation by washing them away from the mouth, urethra, and reproductive tract.

1st Line of Defense: Chemical Barriers

Chemical Factors in Skin:
- Skin has a slightly acidic pH, deterring most bacteria (many prefer neutral pH).
- Salinity creates a hypertonic environment, leading to bacterial dehydration and death.
Lysozymes:
- Enzymes found in body secretions (sweat, tears, saliva) that break chemical bonds in peptidoglycan, destroying bacterial cell walls. Without peptidoglycan, bacteria are unable to maintain their structure and die.
Gastric Juices:
- Produced by the stomach, containing enzymes and acid that destroy most bacteria except for acidophiles (e.g., certain Archaea).
Blood Transferrin:
- A protein that binds to iron (Fe), removing it from circulation to reduce availability for bacterial growth.

1st Line of Defense: Biological Barriers

Normal Microbiota:
- Non-harmful microbes that reside in or on the host.
  - Commensal Microbes: Benefit themselves without benefiting or harming the host.
  - Beneficial Microbes: Provide a benefit to both the microbes and the host, e.g., Vitamin K-producing bacteria in the gut.
  - Opportunistic Microbes: Under certain conditions, these former normal microbiota can act as pathogens.
- Competitive Exclusion:
  - Also known as “microbial competition.” Normal microbiota compete with invading pathogens, leading to reduced pathogenic bacterial populations by seizing nutrients, space, and producing harmful substances.

2nd Line of Defense

Formed Elements in the Blood:
- Cells and cell fragments suspended in plasma, containing:
  - Erythrocytes (RBC): Contain hemoglobin, facilitating oxygen transport.
  - Leukocytes (WBC): Involved in immune function.
  - Thrombocytes (Platelets): Fragments involved in blood clotting.
- Created in red bone marrow from stem cells through hematopoiesis.
- Types of Leukocytes:
  - Granulocytes (BEN): Contain visible granules, including:
    - Basophils: Release histamine, playing a role in allergic responses.
    - Eosinophils: Toxic against parasites and worms.
    - Neutrophils: Phagocytic and the first responders in early infections.
  - Agranulocytes: Lack visible granules, including:
    - Monocytes: Migrate from blood to tissues to become macrophages.
    - Lymphocytes: Involved in adaptive immunity (T cells, B cells, NK cells).
Phagocytosis:
- Definition: Ingestion (engulfment) of microbes by phagocytes.
- Phagocytes are innate immune cells capable of phagocytosis, including neutrophils, macrophages, and dendritic cells.
- Mechanisms/Phases of Phagocytosis:
  - Chemotaxis: Chemical signals from pathogens attract phagocytes.
  - Adherence: Attachment of phagocyte to pathogen surface.
  - Ingestion: Endocytosis forms a phagosome that merges with lysosome to create a phagolysosome.
  - Digestion: Pathogen is digested within the phagolysosome.
- Microbial Evasion of Phagocytosis:
  - Capsules or toxins can inhibit phagocytosis.
  - Examples:
    - Streptococcus pneumoniae: Capsule makes it too large to engulf.
    - Staphylococcus: Releases leukocidins that kill phagocytes.
    - Mycobacterium: Mycolic acid inhibits lysosomal digestion, allowing bacterial growth within phagocytes.
Inflammation:
- The goal is to eliminate pathogens and facilitate healing, often involving neutrophils and macrophages.
- Signs and Symptoms:
  - Pain: Chemicals released by leukocytes damage nerve endings.
  - Redness (Erythema): Increased blood flow to the affected area.
  - Immobility: Loss of function due to tissue damage.
  - Swelling (Edema): Accumulation of fluid outside blood vessels.
  - Heat: Increased blood flow elevates temperature in the area.
Fever:
- Typically caused by bacterial infections, aiming to eliminate pathogens.
  - Toxins released by bacteria induce cytokine release from phagocytes.
  - Cytokines signal the hypothalamus to raise the body's temperature set point, leading to chills and a resultant fever.
  - As the infection resolves, the body temperature resets, leading to a decrease in temperature termed “crisis.”
- Outcomes of Fever:
  - Increased metabolic rate for enhanced ATP production.
  - Enhanced immune response, promoting phagocytic activity.
Induction of Antimicrobial Substances:
- Certain cells release proteins that help eliminate pathogens.
- Examples of Antimicrobial Substances:
  1. Complement System: Proteins that enhance the immune response through activation cascades.
    - Inactive and active complement proteins participate, with outcomes including opsonization, inflammation, and cytolysis.
  2. Interferons: Proteins released by host cells in response to pathogens that hinder viral replication.

Microbial Evasion of the Complement System

Capsule Production: Inhibits the binding of complement proteins to pathogens.
Inhibition of MAC Formation: Bacterial enzymes can prevent the assembly of the membrane attack complex.
Inactivation/Destruction of Complement Proteins: Some bacteria produce proteases to destroy complement proteins.