Innate Immunity: The First Lines of Defense (Immune System Part 1)

Immune System Overview

Introduction to the Immune System

The immune system is a functional system that provides resistance to disease by defending the body against pathogens and other foreign substances. It is composed of two main intrinsic systems: the innate (nonspecific) defense system and the adaptive (specific) defense system. These systems are intertwined and work together to protect the body.

• Innate (nonspecific) defense system: Provides immediate, general protection against pathogens.

• Adaptive (specific) defense system: Provides targeted, long-term immunity against specific pathogens.

Functional Characteristics

• The immune system is not a single organ but a collection of cells, tissues, and molecules.

• Innate and adaptive defenses share some defensive molecules and pathways.

• Innate responses can alert and activate the adaptive immune system.

Innate (Nonspecific) Defense System

Lines of Defense

The innate defense system consists of two main lines of defense:

1. First Line of Defense: External body membranes, such as the skin and mucous membranes, which act as physical and chemical barriers.

2. Second Line of Defense: Internal defenses, including antimicrobial proteins, phagocytes, natural killer cells, inflammation, and fever.

These defenses inhibit the spread of invaders and are crucial for immediate protection. Inflammation is a key mechanism in the second line of defense.

Comparison of Innate and Adaptive Defenses

Innate Defenses	Adaptive Defenses
Surface barriers (skin, mucous membranes)	Humoral immunity (B cells)
Internal defenses (phagocytes, NK cells, inflammation, antimicrobial proteins, fever)	Cellular immunity (T cells)
Immediate response	Slower, specific response

Surface Barriers

Role and Mechanisms

Surface barriers are the body's first line of defense against pathogens. They include the skin and mucous membranes, which provide both physical and chemical protection.

• Acidity of skin and secretions (acid mantle): Inhibits growth of many microorganisms by creating a hostile environment.

• Enzymes: Lysozyme in saliva, respiratory mucus, and lacrimal fluid destroys bacterial cell walls, killing many microorganisms.

• Defensins: Antimicrobial peptides that disrupt microbial membranes and inhibit growth.

• Other chemicals: Lipids in sebum and dermcidin in sweat are toxic to some bacteria.

Respiratory system modifications also contribute:

• Mucus-coated hairs in the nose: Trap inhaled particles and pathogens.

• Cilia in the upper respiratory tract: Sweep dust- and bacteria-laden mucus toward the mouth for removal.

If surface barriers are breached (e.g., by cuts), internal defenses are activated to protect deeper tissues.

Internal Defenses: Cells and Chemicals

Overview

When pathogens bypass surface barriers, the body relies on internal defenses. These include various cells and chemicals that identify and eliminate invaders.

• Phagocytes

• Natural killer (NK) cells

• Inflammatory response (involving macrophages, mast cells, white blood cells, and inflammatory chemicals)

• Antimicrobial proteins (interferons and complement proteins)

• Fever

Pattern Recognition Receptors

Many innate immune cells possess pattern recognition receptors (PRRs) that detect common structures on microbes. Toll-like receptors (TLRs) are a key class of PRRs, with humans having 11 types, each recognizing different microbial components. Activation of TLRs triggers immune responses.

Phagocytes

Phagocytes are cells that engulf and digest pathogens and debris. The main types include:

• Neutrophils: Most abundant phagocytes; become phagocytic upon encountering infectious material but die after ingesting pathogens.

• Macrophages: Develop from monocytes; are robust and long-lived. Free macrophages wander through tissues, while fixed macrophages reside in specific organs (e.g., stellate macrophages in the liver, microglia in the brain).

Phagocytosis involves the following steps:

1. Phagocyte adheres to pathogen.

2. Engulfs particles, forming a phagosome.

3. Lysosome fuses with phagosome, forming a phagolysosome.

4. Enzymes digest the pathogen.

5. Residual material is expelled from the cell.

Natural Killer (NK) Cells

Natural killer (NK) cells are large granular lymphocytes that target and destroy cells lacking "self" cell-surface receptors, such as virus-infected or cancerous cells. They induce apoptosis (programmed cell death) and secrete chemicals that enhance the inflammatory response.

Inflammation: Tissue Response to Injury

Inflammation is triggered whenever body tissues are injured. It is a protective response with several benefits:

• Prevents the spread of damaging agents

• Disposes of cell debris and pathogens

• Alerts the adaptive immune system

• Sets the stage for tissue repair

The cardinal signs of acute inflammation are:

• Redness

• Heat

• Swelling

• Pain

• Impairment of function (sometimes)

Stages of Inflammation

1. Chemical release: Injured tissues and immune cells release chemicals (e.g., histamine from mast cells) into the extracellular fluid.

2. Vasodilation and increased vascular permeability: Vasodilation causes increased blood flow (hyperemia), leading to redness and heat. Increased permeability allows exudate (fluid with clotting factors and antibodies) to enter tissues, causing swelling and pain.

3. Phagocyte mobilization: Neutrophils arrive first, followed by macrophages. If pathogens are present, the complement system is activated and adaptive immunity is engaged.

Antimicrobial Proteins

Antimicrobial proteins enhance innate defenses by attacking microorganisms directly or hindering their ability to reproduce. The two most important types are interferons and complement proteins.

Interferons (IFNs)

• Family of immune-modulating proteins produced by virus-infected cells.

• Warn neighboring healthy cells, stimulating them to produce proteins that block viral replication and degrade viral RNA.

• Some interferons activate NK cells and macrophages directly.

Complement System

• Consists of about 20 blood proteins circulating in inactive form.

• Major mechanism for destroying foreign substances.

• Activation enhances inflammation and directly destroys bacteria.

• Supports both innate and adaptive immunity.

Fever

Fever is an abnormally high body temperature, representing a systemic response to infection. It is triggered when leukocytes and macrophages exposed to foreign substances release pyrogens, which act on the hypothalamus to raise the body's temperature set point.

• Moderate fever causes the liver and spleen to sequester iron and zinc, which are needed by microorganisms.

• Increases metabolic rate, accelerating tissue repair.

Summary Table: Innate Immune Defenses

Defense Type	Main Components	Function
Surface Barriers	Skin, mucous membranes, secretions	Physical and chemical barrier to entry
Internal Defenses	Phagocytes, NK cells, inflammation, antimicrobial proteins, fever	Destroy pathogens that breach surface barriers

Key Terms

• Pathogen: A microorganism that causes disease.

• Phagocytosis: The process by which a cell engulfs and digests foreign particles.

• Apoptosis: Programmed cell death.

• Pyrogen: A substance that induces fever.

• Exudate: Fluid that leaks out of blood vessels during inflammation, containing proteins and immune cells.

Additional info: The adaptive immune system (humoral and cellular immunity) will be covered in more detail in subsequent sections or lectures.