Week 10 lecture notes

Innate Immunity

Overview of Innate Immunity

Innate immunity refers to the non-specific defense mechanisms that come into play immediately or within hours of an antigen's appearance in the body. These defenses are present from birth and provide the first and second lines of defense against pathogens.

• Species Resistance: Most pathogens infect only certain species due to specific environmental requirements and compatible physiological processes.

• Physiological Incompatibility: Human cells may lack the correct chemical receptors or have conditions unsuitable for pathogen survival.

• Limitations: Humans do not have innate resistance to all pathogens.

The First Line of Defense

The first line of defense consists of physical and chemical barriers that prevent pathogens from entering the body.

• Structures: Skin and mucous membranes of the respiratory, digestive, urinary, and reproductive systems.

• Skin: The most significant barrier to infection, composed of two major layers:

  • Epidermis: Multiple layers of tightly packed cells; shedding of dead skin cells removes microorganisms.

  • Dermis: Contains collagen fibers that help resist abrasions.

• Clinical Relevance: Loss of skin due to burns greatly increases infection risk (e.g., 97% infection rate in deep burns).

Chemical Defenses of the Skin

• Perspiration: Secreted by sweat glands; salt inhibits pathogen growth.

• Sebum: Secreted by sebaceous glands; keeps skin pliable and lowers pH, inhibiting many bacteria.

• Lysozyme: Enzyme that destroys bacterial cell walls by cleaving peptidoglycan, especially effective against Gram-positive bacteria. Found in tears and macrophages.

Mucous Membranes

• Epithelium: Thin, living outer layer; tightly packed to prevent pathogen entry.

• Connective Layer: Supports the epithelium.

• Respiratory System: Lined with mucous membranes; goblet cells secrete mucus, ciliated cells propel mucus out of the larynx.

• Cell Shedding: Continual shedding and stem cell regeneration maintain barrier integrity.

• Dendritic Cells: Reside below the epithelium to phagocytize invaders.

• Impact of Smoking: Damages cilia, increasing infection risk.

Lacrimal Apparatus

• Produces and drains tears, bathing the eyes and washing away microbes.

• Lysozyme in tears destroys bacteria; tears are drained into the pharynx and swallowed, where bacteria are digested in the stomach.

Antimicrobial Peptides

• Present in skin, mucous membranes, and neutrophils.

• Act against a variety of microbes (bacteria, fungi, protozoa, viruses) by disrupting enzymatic activity.

Role of Normal Microbiota

• Microbial Antagonism: Normal microbiota compete with potential pathogens for nutrients and space.

• Create an environment unfavorable to pathogens, stimulate the second line of defense, and provide vitamins to the host.

The Second Line of Defense

When pathogens bypass the first line, the second line of defense, primarily involving blood components, is activated.

• Blood Components:

  • Plasma: Mostly water, contains electrolytes, dissolved gases, nutrients, proteins (including iron-binding compounds, complement proteins, antibodies).

  • Serum: Plasma without clotting factors.

  • Erythrocytes: Red blood cells; transport oxygen and carbon dioxide.

  • Platelets: Involved in blood clotting.

  • Leukocytes: White blood cells; defend against invaders. Divided into granulocytes and agranulocytes.

Iron Transport and Microbial Competition

• Transferrin: Plasma protein that transports iron, making it unavailable to microbes.

• Siderophores: Microbial proteins that bind iron, competing with host cells.

• Lactoferrin: Host protein that sequesters iron from siderophores.

Leukocyte Classification

Type	Features	Function
Granulocytes	Large granules, stain different colors	Phagocytosis, nonphagocytic killing, diapedesis
Basophils	Stain blue	Release histamine, mediate inflammation
Eosinophils	Stain red/orange	Attack parasitic worms, phagocytosis
Neutrophils	Stain lilac	Phagocytosis, NET formation
Agranulocytes	Uniform appearance	Adaptive immunity, phagocytosis
Lymphocytes	Small, round nucleus	Adaptive immunity
Monocytes	Large, kidney-shaped nucleus	Mature into macrophages

Abnormal White Blood Cell Counts

• Increased leukocytes and neutrophils: often indicate bacterial infection.

• Increased lymphocytes: often indicate viral infection.

• Increased eosinophils: may indicate parasitic worm infection.

Phagocytosis

Phagocytosis is the process by which certain cells engulf and digest foreign particles, bacteria, and dying cells.

• Phagocytes: Cells capable of phagocytosis (e.g., macrophages, neutrophils).

• Macrophages: Monocytes that leave the blood and mature in tissues; named for their location.

Steps of Phagocytosis

1. Chemotaxis: Movement toward chemical signals.

2. Adherence: Binding of phagocyte to microbe.

3. Ingestion: Extension of pseudopodia to engulf microbe into a food vesicle.

4. Maturation: Fusion of vesicles within the phagocyte with the food vesicle.

5. Killing: Digestive chemicals from vesicles destroy the microbe.

6. Elimination: Excretion of microbial remnants.

Innate Immunity Receptors and Proteins

• Toll-like Receptors (TLRs): Membrane proteins on phagocytes that bind pathogen-associated molecular patterns (PAMPs) and initiate defensive responses.

• NOD Proteins: Cytosolic proteins that bind PAMPs inside the cell.

• Interferons: Proteins released by host cells to inhibit viral spread; cause symptoms like fever and muscle aches.

• Types of interferons:

  • Type I (alpha, beta): Early response, bind neighboring cells.

  • Type II (gamma): Later response, stimulates macrophages.

Complement System

• Group of proteins that, when activated, result in lysis of foreign cells.

• Activation pathways:

  • Classical pathway

  • Alternative pathway

  • Lectin pathway

• Complement proteins act as opsonins, marking microbes for immune response.

• Host cells have proteins that prevent complement-mediated damage.

Inflammation

• Nonspecific response to tissue damage; characterized by redness, heat, swelling, pain, and loss of function.

• Caused by various factors (heat, UV, abrasions, pathogens).

• Types:

  • Acute: Develops quickly, resolves quickly.

  • Chronic: Long-lasting, may result in disease (e.g., arthritis).

• Inflammatory mediators (bradykinin, prostaglandins, leukotrienes, histamine) increase blood vessel permeability and dilation.

• Mast cells release histamine in response to complement components (C5a, C3a).

Fever

• Body temperature above 98.6°F, triggered by pyrogens acting on the hypothalamus.

• Pyrogens include bacterial toxins, cytoplasmic contents of lysed bacteria, and antibody-antigen complexes.

• Physiological effects: Increases phagocytic activity, but excessive fever can damage cells.

Nonphagocytic Killing

• Eosinophils: Attack parasitic helminths by secreting toxins; elevated counts indicate infestation.

• Natural Killer (NK) Cells: Secrete toxins onto virally infected cells and tumors; recognize stressed cells without adaptive immunity.

• Neutrophils: Produce chemicals and extracellular traps (NETs) to kill bacteria.

Summary Table: First vs. Second Line of Defense

Defense Line	Main Components	Mechanisms
First Line	Skin, mucous membranes, normal microbiota	Physical barrier, chemical defenses, microbial antagonism
Second Line	Blood components (plasma, leukocytes, platelets)	Phagocytosis, inflammation, fever, complement, nonphagocytic killing

Key Takeaways

• The body's first line of defense includes skin, mucous membranes, and normal microbiota, which block or inhibit many pathogens.

• The second line of defense involves blood components, inflammation, fever, and specialized immune cells.

• Both lines of defense are essential for preventing and controlling infections.