Innate Immunity: The First and Second Lines of Defense

Innate Immunity

Overview of the Immune System

Innate immunity refers to the non-specific defense mechanisms that protect the body from pathogens. These defenses are present from birth and act as the body's first and second lines of defense, responding rapidly to infection. The third line of defense, adaptive immunity, is specific and involves lymphocytes and antibodies.

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

• Second Line of Defense: Non-specific internal responses to pathogens that breach the first line.

• Third Line of Defense: Specific immune responses (adaptive immunity).

The First Line of Defense

Physical and Chemical Barriers

The first line of defense consists of external barriers and associated chemicals that prevent pathogens from entering the body.

• Normal Microbiota: Beneficial microorganisms that compete with pathogens for resources and space.

• Skin: Acts as a physical barrier; tightly packed cells, dry environment, and secretions (e.g., sebum) inhibit microbial growth.

• Mucous Membranes: Line body cavities open to the environment; trap and remove pathogens with mucus and cilia.

• Chemicals: Include lysozyme (breaks down bacterial cell walls), defensins (antimicrobial peptides), and acidic secretions.

• Processes: Shedding of skin cells, movement of mucus, and other mechanical actions remove microbes.

Comparison of Skin and Mucous Membranes

Property	Skin	Mucous Membrane
Number of Cell Layers	Many	One to a few
Cells Tightly Packed?	Yes	Yes
Cells Dead or Alive?	Outer layers dead; inner layers alive	Alive
Mucus Present?	No	Yes
Relative Water Content	Dry	Moist
Defensins Present?	Yes	With some
Lysozyme Present?	Yes	With some
Sebum Present?	Yes	No
Cilia Present?	No	Trachea, uterine tubes
Constant Shedding and Replacement of Cells?	Yes	Yes

Secretions and Activities Contributing to the First Line of Defense

System	Secretion/Activity	Function
Digestive	Saliva	Washes microbes from teeth, contains lysozyme
Digestive	Stomach acid	Destroys most ingested pathogens
Digestive	Bile, intestinal secretions	Digest and/or inhibit microorganisms
Urinary	Urine	Contains lysozyme, acidity inhibits microbes
Reproductive	Vaginal secretions	Acidity inhibits microorganisms
Cardiovascular	Coagulation	Prevents entrance of many pathogens

The Second Line of Defense

Internal Non-Specific Defenses

When pathogens bypass the first line of defense, the second line provides rapid, non-specific responses to eliminate invaders.

• Phagocytosis: Engulfment and destruction of pathogens by phagocytic cells (e.g., neutrophils, macrophages).

• Extracellular Killing by Leukocytes: Eosinophils attack parasitic helminths; natural killer (NK) cells secrete toxins onto infected or tumor cells; neutrophils can kill pathogens without phagocytosis.

• Nonspecific Chemical Defenses: Include Toll-like receptors (TLRs), NOD proteins, interferons, and the complement system.

• Inflammation: Localized response to tissue damage, characterized by redness, heat, swelling, and pain.

• Fever: Systemic response involving elevated body temperature due to pyrogens.

Phagocytosis

Phagocytosis is a multi-step process by which phagocytes ingest and destroy pathogens.

1. Chemotaxis: Movement of phagocytes toward chemical signals from pathogens or damaged tissue.

2. Adherence: Phagocyte attaches to pathogen via receptors.

3. Ingestion: Pathogen is engulfed into a phagosome.

4. Digestion: Phagosome fuses with lysosome; enzymes degrade the pathogen.

5. Elimination: Waste is expelled from the cell.

Types of Leukocytes

Leukocytes (white blood cells) are key players in innate immunity and are classified as granulocytes or agranulocytes.

• Granulocytes: Neutrophils, eosinophils, basophils

• Agranulocytes: Lymphocytes, monocytes

Each type has specialized functions in defense and immune regulation.

Extracellular Killing by Leukocytes

Some leukocytes destroy pathogens without phagocytosis.

• Eosinophils: Attack parasitic helminths by releasing toxic proteins.

• Natural Killer (NK) Cells: Secrete toxins onto the surface of virally infected cells and tumor cells, inducing apoptosis.

• Neutrophils: Can kill pathogens by releasing antimicrobial chemicals.

Nonspecific Chemical Defenses

Chemical defenses recognize and respond to pathogen-associated molecular patterns (PAMPs).

• Toll-like Receptors (TLRs): Integral membrane proteins on phagocytes that recognize PAMPs and trigger apoptosis of pathogens.

• NOD Proteins: Cytosolic proteins in phagocytes that recognize PAMPs and trigger apoptosis.

• Interferons: Protein molecules that inhibit viral replication and spread, especially effective against RNA viruses.

• Complement System: A set of serum proteins that enhance phagocytosis (opsonization), stimulate inflammation, and cause lysis of pathogens.

Classes of Interferons

Type	Principal Source	Inducing Agent	Action	Other Names
Alpha Interferon (IFN-α)	Epithelium, leukocytes	Viruses	Stimulates production of antiviral proteins	Leukocyte-IFN
Beta Interferon (IFN-β)	Fibroblasts	Viruses	Stimulates production of antiviral proteins	Fibroblast-IFN
Gamma Interferon (IFN-γ)	Activated T lymphocytes, NK lymphocytes	Adaptive immune response	Stimulates phagocytic activity of macrophages and neutrophils	Immune-IFN, macrophage activation factor

Complement System Pathways

• Classical Pathway: Triggered by antibodies bound to antigens.

• Alternative Pathway: Triggered by microbial surfaces.

• Lectin Pathway: Triggered by mannose-binding lectins on pathogens.

All pathways converge to activate complement protein C3, leading to formation of the membrane attack complex (MAC) and lysis of pathogens.

Inflammation

Inflammation is a localized response to tissue damage, characterized by redness, heat, swelling, and pain. It serves to contain infection and promote healing.

• Acute Inflammation: Rapid, short-term response to injury or infection.

• Chronic Inflammation: Long-term, persistent response that can lead to tissue damage.

Inflammatory mediators (e.g., histamine, bradykinin, prostaglandins, leukotrienes) increase blood flow and vascular permeability, allowing immune cells and antimicrobial chemicals to reach the site of infection.

Chemical Mediators of Inflammation

Type	Examples
Vasodilating Chemicals	Histamine, serotonin, bradykinin, prostaglandins
Chemotactic Factors	Fibrin, collagen, mast cell chemotactic factor, bacterial peptides
Both Vasodilating and Chemotactic Effects	Complement fragment C5a, interferons, interleukins, leukotrienes, platelet secretions

Fever

Fever is a systemic response to infection, defined as a body temperature above 37°C. It is triggered by pyrogens, which reset the hypothalamic thermostat.

• Pyrogens: Include bacterial toxins, cytoplasmic contents of bacteria released by lysis, antibody-antigen complexes, and interleukin-1.

• Benefits of Fever:

  • Enhances the effects of interferons

  • Inhibits growth of some microorganisms

  • May enhance the performance of phagocytes

Summary Table: Nonspecific Components of the First and Second Lines of Defense

First Line	Second Line
Barriers and Associated Chemicals: Skin and mucous membranes prevent entry of pathogens; chemical and mechanical actions enhance protection.	Phagocytes: Macrophages, neutrophils, and eosinophils ingest and destroy pathogens.
	Extracellular Killing: Eosinophils and NK lymphocytes kill pathogens without phagocytosis; neutrophils can also kill extracellularly.
	Complement: Components attract phagocytes, stimulate inflammation, and lyse pathogens.
	Interferons: Interfere with viral replication and stimulate immune cells.
	Antimicrobial Peptides: Kill or inhibit pathogens.
	Inflammation: Increases blood flow, capillary permeability, and migration of leukocytes; local effects include redness, heat, and swelling.
	Fever: Mobilizes defenses, accelerates repairs, and inhibits pathogens.

Additional info: The above notes expand on the provided slides and tables, integrating textbook-level explanations and definitions for clarity and completeness.