BIO108 Chapter 16 Non-Specific Immunity

Chapter 16: Nonspecific Immunity (Innate Immunity)

Overview of Host Defenses

Host defenses against pathogens (viruses, bacteria, fungi) are organized into multiple layers. The first and second lines of defense are nonspecific (innate), while the third line is specific (adaptive).

• Susceptibility: Lack of resistance to a disease.

• Immunity (Resistance): Ability to ward off disease.

• Nonspecific resistance: Defenses against any pathogen (innate immunity).

• Specific resistance: Immunity to a specific pathogen (adaptive immunity).

• Adaptive immunity: Slower to respond, has memory component.

First Line of Defense

Physical Factors

Physical barriers and processes prevent entry or remove microbes from body surfaces.

• Skin: Epidermis consists of tightly packed cells with keratin, a protective protein. The top layer is shed periodically, removing microbes. Dryness of skin is also protective.

• Mucous membranes: Trap microbes; mucus-coated hairs filter air.

• Ciliary escalator: Microbes trapped in mucus are transported away from lungs (1-3 cm/hr) into the stomach for destruction.

• Lacrimal apparatus: Produces tears that wash eyes and drain into the nose, diluting and removing irritants and microbes.

• Saliva: Washes away microbes, prevents colonization of teeth and mucous membranes.

• Urine: Flow prevents colonization of urethra.

• Vaginal secretions: Wash microbes out of the vaginal tract.

• Earwax: Prevents entry of microbes into the ear.

• Peristalsis, defecation, vomiting, diarrhea: Expel microbes from the gastrointestinal tract.

Chemical Factors

Chemical substances produced by the body inhibit or destroy pathogens.

• Sebum: Produced by sebaceous glands; contains bacteriostatic and fungistatic fatty acids.

• Low pH of skin (~5): Due to fatty acids and lactic acid; inhibits pathogen growth.

• Lysozyme: Enzyme in perspiration, tears, saliva, and tissue fluids; destroys microbial cell walls.

• Low pH of gastric juice (1.2–3.0): Kills microbes and toxins (except Clostridium botulinum, Staphylococcus aureus). Helicobacter pylori can neutralize acidity and cause ulcers.

Normal Microbiota

Normal microbiota protect the host by microbial antagonism (competitive exclusion).

• Compete with pathogens for nutrients and space.

• Normal vaginal microbiota inhibit Candida albicans (prevents vaginitis).

• Escherichia coli in the large intestine produces bacteriocins that inhibit Salmonella and Shigella.

• Estimated 1 × 1014 bacteria on a human body.

Second Line of Defense

Differential White Cell Count

White blood cells (WBCs) are crucial for innate immunity. Their normal ranges and percentages are:

Type	Percentage
Neutrophils	60%–70%
Lymphocytes	20%–25%
Monocytes	3%–8%
Eosinophils	2%–4%
Basophils	0.5%–1%

Normal WBC count: 5,000–10,000 per mm3 (5.0–10.0 × 109 per liter).

Hematopoiesis

Blood cells are created in red bone marrow stem cells via hematopoiesis.

• Pluripotent stem cells differentiate into myeloid and lymphoid lineages.

• Myeloid lineage: erythrocytes, platelets, mast cells, neutrophils, eosinophils, basophils, monocytes (macrophages, dendritic cells).

• Lymphoid lineage: lymphocytes (T cells, B cells, natural killer cells).

White Blood Cells

Granulocytes

• Neutrophils: Contain peroxidases, hydrolytic enzymes, and defensins; highly phagocytic; primary bacteria killers.

• Basophils: Similar to mast cells; produce histamine (vasodilator, attracts other WBCs).

• Eosinophils: Counterattack against parasitic worms; lessen allergy severity by phagocytizing immune complexes; some phagocytosis.

Agranulocytes

• Monocytes: Largest leukocytes; phagocytic as mature macrophages; leave circulation to become tissue macrophages.

• Dendritic cells: Found in skin, mucous membranes, thymus; phagocytic.

• Lymphocytes: Involved in specific (adaptive) immunity.

Phagocytes

Phagocytes are cells that ingest and destroy microbes.

• Phago-: Greek for "eat"; -cyte: Greek for "cell".

• Fixed macrophages: Residents in tissues/organs (e.g., lungs, liver, brain).

• Kupffer cells (liver) and microglia (brain) are examples of fixed macrophages.

• Free (wandering) macrophages: Roam tissues and gather at infection sites.

The Mechanism of Phagocytosis

Phagocytosis involves several steps:

• Chemotaxis: Chemical signals attract phagocytes to microorganisms.

• Adherence: Attachment of phagocyte to microbe surface.

• Ingestion: Microorganism is coated with serum proteins (opsonization) to facilitate ingestion.

• Digestion: Microbe is digested inside a phagolysosome.

• Toll-like receptors (TLRs): Host cell receptors that recognize pathogen-associated molecular patterns (PAMPs), triggering cytokine release to regulate immune responses.

Microbial Evasion of Phagocytosis

Some microbes have evolved mechanisms to evade phagocytosis.

Mechanism	Example Organism
Inhibit adherence (M protein, capsules)	Streptococcus pyogenes, Streptococcus pneumoniae
Kill phagocytes (Leukocidins)	Staphylococcus aureus
Lyse phagocytes (Membrane attack complex)	Listeria monocytogenes
Escape phagosome	Shigella
Prevent phagosome-lysosome fusion	HIV, Mycobacterium tuberculosis
Survive in phagolysosome	Coxiella burnetii (Q fever)

Inflammation

Inflammation is a local response to tissue damage or infection, characterized by:

• Redness

• Pain

• Heat (local)

• Swelling (edema)

• Loss of function

Process of Inflammation

• Damage to tissue releases chemicals (histamine, kinins, prostaglandins, leukotrienes, cytokines).

• Vasodilation and increased permeability of blood vessels allow immune cells and proteins to enter tissue.

• Abscess formation and blood clotting help contain infection.

Inflammatory Response: Edema

• Protein-rich fluid enters tissue spaces, diluting harmful substances.

• Provides oxygen and nutrients for repair.

• Clotting proteins prevent spread of bacteria.

Phagocytic Mobilization

Occurs in four main phases:

1. Leukocytosis: Neutrophils released from bone marrow.

2. Margination: Neutrophils cling to capillary walls in injured area.

3. Diapedesis: Neutrophils squeeze through capillary walls.

4. Chemotaxis: Neutrophils attracted to injury site by chemicals.

Inflammatory Mediators

• Kinins: Vasodilation, increased permeability, chemotaxis, attract neutrophils.

• Prostaglandins: Intensify effects of kinins, help phagocytes move through capillaries.

• Leukotrienes: Produced by mast cells/basophils, increase permeability, help attach phagocytes to pathogens.

• Histamine: Found in mast cells, basophils, platelets; released in response to injury.

Tissue Repair

• Repair cannot be completed until harmful substances are removed.

• Stroma: Supporting connective tissue.

• Parenchyma: Functioning part of tissue.

Fever: Abnormally High Body Temperature

Fever is a systemic response to infection, regulated by the hypothalamus.

• Normal set point: 37°C.

• Gram-negative endotoxins cause phagocytes to release interleukin-1 (IL-1).

• IL-1 triggers hypothalamus to release prostaglandins, raising body temperature.

• Body increases metabolism and shivering to raise temperature.

• When IL-1 is eliminated, temperature falls (crisis).

• Fever causes liver and spleen to reserve iron, limiting microbial growth.

The Complement System

Overview

The complement system consists of serum proteins produced by the liver that assist the immune system in destroying microbes. It acts in a cascade process called complement activation.

• Proteins designated with uppercase C and numbered (e.g., C1, C2, C3).

• Activated fragments indicated with lowercase a and b (e.g., C3a, C3b).

• Activation of one protein leads to sequential activation of others.

• Gram-negative bacteria are more susceptible to cytolysis.

Pathways of Complement Activation

Pathway	Trigger	Key Proteins
Classical	Antigen-antibody interaction	C1, C2, C4
Alternative	Microbial surface molecules	B, D, P, C3
Lectin	Mannose-binding lectin	Lectins, C2, C4

All pathways activate C3, leading to:

• Opsonization: C3b promotes phagocyte attachment to microbe.

• Cytolysis: C5b, C6, C7, C8, C9 form membrane attack complex (MAC).

• Inflammation: C3a, C5a stimulate mast cells to release histamine.

Summary Table: Outcomes of Complement Activation

Outcome	Complement Proteins Involved	Effect
Opsonization	C3b	Enhances phagocytosis
Cytolysis	C5b, C6, C7, C8, C9	Destroys pathogen cell membrane
Inflammation	C3a, C5a	Stimulates histamine release

Additional info:

• Complement system is a major effector of innate immunity and bridges to adaptive immunity.

• Deficiencies in complement proteins can lead to increased susceptibility to infections.