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Innate Immunity: Nonspecific Defenses of the Host (Chapter 16 Study Notes)

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Innate Immunity: Nonspecific Defenses of the Host

Introduction to Immunity

Immunity refers to the body's ability to ward off disease, while susceptibility is the lack of resistance to disease. The immune system is divided into innate (nonspecific) and adaptive (specific) immunity. Innate immunity provides immediate, general defense against pathogens and is present at birth, whereas adaptive immunity targets specific pathogens and develops memory for future responses.

  • Immunity: Ability to resist infection or disease.

  • Susceptibility: Increased likelihood of infection due to lack of resistance.

  • Innate Immunity: Rapid, nonspecific defense mechanisms present from birth.

  • Adaptive Immunity: Slower, specific response with memory component.

Overview of Immune Defenses

The immune system employs multiple layers of defense against pathogens (viruses, bacteria, fungi):

  • First Line: Skin, mucous membranes, and antimicrobial substances.

  • Second Line: Inflammation, fever, and phagocytes.

  • Third Line: Humoral and cellular immunity (adaptive response).

White Blood Cells and Immunity

White blood cell (WBC) counts are a key indicator of immune status. Differential counts help identify the relative abundance of each type of leukocyte, which can indicate various health conditions.

  • Normal WBC count: 4,000–11,000/μl

  • High WBC count: May indicate bacterial infection, autoimmune disease, or medication side effects.

  • Low WBC count: May indicate viral infection, severe bacterial infection, autoimmune disease, medication side effects, or cancer.

Leukocyte Type

Normal %

Neutrophils

60–70%

Lymphocytes

20–25%

Monocytes

3–8%

Eosinophils

2–4%

Basophils

0.5–1%

Physical and Chemical Barriers

Physical Factors

Physical barriers are the body's first line of defense, preventing pathogen entry.

  • Skin: Consists of the dermis (connective tissue) and epidermis (tightly packed epithelial cells with keratin). Shedding and dryness inhibit microbial growth.

  • Mucous Membranes: Line the gastrointestinal, respiratory, and genitourinary tracts. Mucus traps microbes and prevents tissue desiccation.

  • Lacrimal Apparatus: Produces tears to wash the eyes.

  • Ciliary Escalator: Moves mucus and trapped microbes away from the lungs.

  • Epiglottis: Prevents entry of microorganisms into the lower respiratory tract.

  • Earwax, urine flow, vaginal secretions, peristalsis, defecation, vomiting, and diarrhea all help expel microbes from the body.

Chemical Factors

Chemical barriers further inhibit or destroy pathogens.

  • Sebum: Forms a protective film and lowers skin pH (3–5).

  • Lysozyme: Enzyme in perspiration, tears, saliva, and urine that destroys bacterial cell walls.

  • Gastric Juice: Low pH (1.2–3.0) destroys most bacteria and toxins.

  • Vaginal Secretions: Low pH (3–5) inhibits microbial growth.

Normal Microbiota and Innate Immunity

Role of Normal Microbiota

Normal microbiota protect the host by outcompeting pathogens (microbial antagonism) and producing substances harmful to invaders. They also help develop the immune system.

  • Competitive exclusion: Outcompete pathogens for space and nutrients.

  • Production of antimicrobial substances and alteration of local conditions.

  • Commensalism: One organism benefits, the other is unharmed.

  • Opportunistic pathogens: E. coli, S. aureus, S. epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa.

  • Probiotics: Live cultures administered for health benefits.

  • Prebiotics: Nutrients that promote growth of beneficial bacteria.

Second Line of Defense: Cellular Components

Formed Elements in Blood

Blood contains cells and fragments suspended in plasma, produced by hematopoiesis in red bone marrow.

  • Erythrocytes: Red blood cells (oxygen transport).

  • Leukocytes: White blood cells (immune defense).

  • Platelets: Involved in blood clotting.

Leukocyte Types

Type

Description

Function

Neutrophils (Granulocyte)

Most abundant

Phagocytosis; first responders to infection

Basophils (Granulocyte)

Least abundant

Release histamine; allergic responses

Eosinophils (Granulocyte)

Moderate abundance

Phagocytic; toxic to parasites and helminths

Monocytes (Agranulocyte)

Differentiate into macrophages

Phagocytosis; antigen presentation

Dendritic cells (Agranulocyte)

Found in skin, mucosa, thymus

Phagocytosis; antigen presentation

Lymphocytes (Agranulocyte)

T cells, B cells, NK cells

Adaptive immunity (T/B cells), cytolysis (NK cells)

The Lymphoid System

The lymphoid system includes lymph plasma, lymphatic vessels, lymphoid tissues and organs, and red bone marrow. Lymphoid tissue contains lymphocytes and phagocytic cells. Lymph transports microbes to lymph nodes, where immune cells encounter and destroy pathogens.

Phagocytosis

Definition and Types of Phagocytes

Phagocytosis is the ingestion of microorganisms or particles by a cell. Professional phagocytes include neutrophils, eosinophils, and macrophages (derived from monocytes). Macrophages can be fixed (residing in tissues) or free (wandering in tissues).

  • Neutrophils: First responders in infection.

  • Macrophages: Arrive later, clean up debris and pathogens.

Mechanism of Phagocytosis

  1. Chemotaxis: Phagocytes are attracted to infection sites by chemical signals (microbial products, complement, damaged cells).

  2. Adherence: Phagocyte attaches to microbe via PAMPs (on microbe) and TLRs (on phagocyte). Opsonization (coating with serum proteins) enhances adherence.

  3. Ingestion: Pseudopods engulf the microbe, forming a phagosome. The phagosome acidifies (pH ~4).

  4. Digestion: Lysosomes fuse with the phagosome, forming a phagolysosome. Enzymes and toxic oxygen products digest the microbe. Indigestible material is expelled by exocytosis.

Inflammation

Definition and Functions

Inflammation is a local defensive response to tissue damage caused by infection, physical, or chemical agents. Its main functions are to destroy or limit the injurious agent and to repair damaged tissue.

  • Signs and symptoms (PRISH): Pain, Redness, Immobility, Swelling (edema), Heat.

  • Acute inflammation: Rapid onset, short duration.

  • Chronic inflammation: Slow onset, long duration, potentially severe.

Stages of Inflammation

  1. Vasodilation and Increased Permeability: Blood vessels dilate and become more permeable, allowing immune cells and proteins to reach the site. Mediators include histamine, kinins, prostaglandins, and cytokines.

  2. Phagocyte Migration and Phagocytosis: Neutrophils and monocytes migrate to the site, adhere to vessel walls (margination), and move through vessel walls (diapedesis) to phagocytose pathogens.

  3. Tissue Repair: Damaged tissue is replaced by stromal (supporting) or parenchymal (functional) cells after harmful agents are removed.

Key Mediators and Outcomes

  • Tumor necrosis factor alpha (TNF-α): Released by macrophages, stimulates acute-phase proteins (C-reactive protein, mannose-binding lectin, fibrinogen, kinins).

  • Cytokine storm: Excessive cytokine release causing tissue damage (e.g., in severe COVID-19).

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