Innate and Adaptive Immunity: Principles and Mechanisms (Chapters 11 & 12)

Innate and Adaptive Immunity

Overview of Immune Responses

The immune system is responsible for protecting the body against pathogens through two main branches: innate immunity and adaptive immunity. Both branches work together to recognize, eliminate, and discriminate between self and foreign antigens.

• Innate Immunity: Inborn protection present in all eukaryotes; provides immediate, non-specific responses.

• Adaptive Immunity: Develops over time, is specific to particular antigens, and is only present in vertebrates.

• Key Features of Both Branches:

  • Recognize diverse pathogens

  • Eliminate identified invaders

  • Discriminate between self and foreign antigens

Comparison Table: Innate vs. Adaptive Immunity

Feature	Innate Immunity Tools	Adaptive Immunity Tools
Response time	Immediate	4–7 days (1st encounter)
Organisms that have it	All eukaryotes	Only vertebrates
Distinguishes self from foreign	Yes	Yes
Kills invaders	Yes	Yes
Effective against diverse threats	Yes	Yes
Tailors response to specific antigen	No	Yes
Remembers antigen and amplifies response upon later exposure	No	Yes

Innate Immunity

First-Line Defenses

First-line defenses aim to prevent pathogen entry and consist of physical, mechanical, and chemical barriers.

• Physical Barriers: Structures that physically block pathogen entry.

  • Epithelial cells: Line all body cavities and entrances (skin, digestive tract, airway).

  • Skin: Layer of dead epithelial cells, proteins, and lipids; water-resistant.

• Mechanical Barriers: Rinse, flush, or trap pathogens to limit their spread.

  • Tears wash debris/pathogens from eyes.

  • Urine flushes microbes out of the body.

  • Saliva rinses microbes out and limits adherence to oral tissue.

  • Mucus membranes trap microbes; mucociliary escalator sweeps away from lungs.

• Chemical Barriers: Directly attack invaders or create environments that limit pathogen survival.

  • Lysozymes: Enzymes that break down bacterial cell walls (found in tears, saliva, mucus, sweat, milk).

  • Acidic environments: Hydrochloric acid in the stomach, fatty acids in sweat and ear wax.

  • High salt environment: Skin.

  • Antimicrobial peptides (AMPs): Proteins that destroy microbes.

Antimicrobial Peptides (AMPs)

AMPs are proteins produced by leukocytes, skin, mucous membrane cells, earwax, milk, tears, and saliva. They destroy a wide spectrum of viruses, parasites, bacteria, and fungi. Defensins are a key class of AMPs that rapidly kill invaders by inserting themselves into target cell membranes.

Normal Microbiota and Immune Responses

• Hygiene Hypothesis: Suggests decreased diversity and levels of microbes in normal microbiota may negatively affect immune responses.

• Studies of germ-free animals show underdeveloped immune systems in microbe-free environments.

• Normal microbiota play a direct role in immune system development.

Second-Line Innate Defenses

Cellular and Molecular Defenses

If pathogens bypass first-line defenses, second-line defenses are activated, involving the lymphatic system, leukocytes, and molecular factors.

• Lymphatic System: Collection of tissues and organs that collect, circulate, and filter fluid (lymph) before returning it to the blood.

• Leukocytes (White Blood Cells): Essential immune system cells, including granulocytes and agranulocytes.

• Molecular Factors: Cytokines, iron-binding proteins, complement proteins.

Lymph & Lymphatic Vessels

• Lymphatic system carries lymph around the body in lymph vessels.

• Lymph is filtered to remove waste, pathogens, and toxins in lymph nodes.

• Interstitial fluid enters lymphatic capillaries and becomes lymph.

• Lymph flows toward lymph nodes, is filtered, and returns to the venous blood supply as plasma.

Primary and Secondary Lymphoid Tissues

• Primary lymphoid tissues: Site of production and maturation of leukocytes (thymus and bone marrow).

• Secondary lymphoid tissues: Filter lymph or blood (lymph nodes, spleen, mucosa-associated lymphoid tissue - MALT).

• B and T cells collect in secondary tissues to fight infections.

Self-Tolerance Screening

To prevent mature lymphocytes from attacking self-tissues, the body screens for immune cells with self-tolerance in the thymus (T cells) and bone marrow (B cells).

Leukocytes: Granulocytes and Agranulocytes

• Granulocytes: Cells with visible granules (neutrophils, eosinophils, basophils, mast cells).

• Agranulocytes: Lack visible granules (monocytes, dendritic cells, lymphocytes).

• Most leukocytes exhibit some degree of phagocytosis.

Key Phagocytes

• Neutrophils: Most numerous, multi-lobed nucleus, first responders, release AMPs, phagocytose foreign cells.

• Monocytes: Largest agranulocytes, horseshoe-shaped nucleus, mature into macrophages.

• Macrophages: Highly phagocytic, destroy a wide range of pathogens, can be fixed (reside in tissues) or wandering (roam through tissues).

• Dendritic cells: Highly phagocytic, found in most tissues, patrol and phagocytize a broad range of antigens.

Phagocytosis Steps

1. Engulfment of target (cell or virus).

2. Phagosome formation.

3. Fusion with lysosome to form phagolysosome.

4. Destruction by hydrolytic enzymes.

5. Release of waste products; display antigens on MHC I & II.

Lymphocytes: NK Cells, B Cells, and T Cells

• Natural Killer (NK) Cells: Innate, abundant in liver, protect against viruses, bacteria, parasites, and tumor cells.

• B Cells and T Cells: Adaptive, coordinate the adaptive immune response.

Molecular Second-Line Innate Defenses

General Roles

• Stimulate inflammation

• Generate fever

• Recruit leukocytes to fight infection

• Promote tissue and blood vessel repair

• Promote leukocyte and lymphatic tissue development

• Antiviral effects (interferons)

• Immune system regulation/activation

Cytokines

Cytokines are signaling proteins that allow cells to communicate, initiating and coordinating immune actions.

• Chemokines: Attract white blood cells to needed areas; induce chemotaxis.

• Interleukins (ILs): Activate adaptive and innate immune responses; stimulate hematopoiesis.

• Interferons (IFNs): Signal when pathogens or tumor cells are detected.

• Tumor Necrosis Factors (TNFs): Induce inflammation and kill tumor cells.

Iron-Binding Proteins

• Limit availability of free iron to reduce bacterial growth (e.g., transferrin, ferritin, hemoglobin, lactoferrin).

Complement System

• Over 30 different proteins work in a cascade to protect against infectious agents.

• Triggered by macrophages, neutrophils, damaged cells, blood-clotting proteins, antibody-antigen interaction.

• Functions: stimulate inflammation, tag targets for elimination (opsonization), directly kill targeted cells (cytolysis).

Inflammation and Fever

Inflammation

Inflammation is an innate immune response that develops when tissues are damaged. Its purpose is to recruit immune defenses, limit the spread of infectious agents, and deliver factors essential for tissue recovery.

• Phases of Inflammation:

  1. Vascular Changes: Release of vasoactive molecules and leukocytes; vessels dilate and become more permeable, leading to redness and heat.

  2. Leukocyte Recruitment: Chemoattractants recruit leukocytes (neutrophils, monocytes); leukocytes exit capillaries, monocytes mature into macrophages, cytokines recruit other leukocytes, causing swelling and pain.

  3. Resolution: Vessels return to normal, leukocytes die off (apoptosis), swelling is reduced as exudate is collected by lymphatic capillaries, and healing is promoted.

• Late Resolution Phase: Wound healing begins, angiogenesis builds new blood vessels, blood clots dissolve, leukocytes undergo apoptosis, pus may continue to form.

Chronic Inflammation

• Develops when inflammation persists too long.

• Not useful or protective; exacerbates tissue injury.

• Promotes atherosclerosis, certain cancers, and neurodegenerative disorders.

Fever

Fever (pyrexia) is an abnormally high systemic body temperature induced by pyrogens (fever-inducing agents such as bacterial toxins or cytokines). The hypothalamus is signaled to raise the body's baseline temperature.

• Purpose:

  • Enhances effects of interferons

  • Enhances phagocyte efficiency

  • Limits growth of certain pathogens

  • Promotes tissue repair

• Low-grade fever: 37.5°C to 38.3°C (99.5–101°F); considered protective.

• High fever: ≥40.5°C (105°F) is life-threatening; essential proteins denature, medical emergency.

• Fatal temperature: Above 43°C (109.4°F).