Innate Immunity: Nonspecific Defenses of the Host

Overview of Immunity

Immunity refers to the ability of an organism to resist infection by pathogens such as viruses, bacteria, and fungi. The immune system is divided into innate (nonspecific) and adaptive (specific) defenses. Innate immunity provides the first line of defense and responds rapidly to a broad range of pathogens.

• Innate Immunity: Present from birth, responds quickly, and does not provide long-lasting immunity.

• Adaptive Immunity: Develops more slowly, is specific to particular pathogens, and provides memory for future responses.

Major Components of Innate Immunity

• Physical barriers: Skin, mucous membranes, and associated structures.

• Chemical barriers: Substances such as lysozyme, sebum, and acidic pH.

• Cellular defenses: Phagocytic cells (e.g., neutrophils, macrophages), natural killer cells.

• Physiological responses: Inflammation, fever.

• Normal microbiota: Compete with pathogens and modulate immune responses.

Physical Factors

Skin

The skin acts as a formidable barrier to microbial invasion due to its structure and chemical environment.

• Dermis: Inner portion made of connective tissue.

• Epidermis: Outer portion made of tightly packed epithelial cells containing keratin, a protective protein.

• Shedding and dryness of skin inhibit microbial growth.

• Intact, healthy epidermis is rarely penetrated by microbes.

Mucous Membranes

Mucous membranes line body tracts exposed to the external environment and provide both physical and chemical protection.

• Epithelial layer: Lines the gastrointestinal, respiratory, and genitourinary tracts.

• Mucus: Viscous glycoproteins that trap microbes and prevent tracts from drying out.

• Lacrimal apparatus: Drains tears and washes the eye, removing microbes.

Other Physical Factors

• Ciliary escalator: Transports microbes trapped in mucus away from the lungs.

• Epiglottis: Prevents microorganisms from entering the lower respiratory tract.

• Earwax: Prevents microbes from entering the ear.

• Urine: Cleans the urethra via flow.

• Vaginal secretions: Move microorganisms out of the vaginal tract.

• Other mechanisms: Peristalsis, defecation, vomiting, and diarrhea expel microbes from the body.

Chemical Factors

Chemical barriers enhance the effectiveness of physical barriers by creating hostile environments for pathogens.

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

• 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 microbes.

Normal Microbiota and Innate Immunity

Role of Normal Microbiota

Normal microbiota are the microorganisms that colonize the body without causing disease. They play a crucial role in defending against pathogens through microbial antagonism (competitive exclusion).

• Compete with pathogens for space and nutrients.

• Produce substances harmful to pathogens.

• Alter environmental conditions to inhibit pathogen survival.

• Prevent overgrowth of harmful microbes.

• Contribute to the development of the immune system.

Commensalism, Probiotics, and Prebiotics

• Commensalism: One organism benefits while the host is unharmed.

• Opportunistic pathogens: Some normal microbiota (e.g., E. coli, S. aureus, S. epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa) can cause disease under certain conditions.

• Probiotics: Live microbial cultures administered to exert a beneficial effect.

• Prebiotics: Chemicals (nutrients) that selectively promote the growth of beneficial bacteria.

Formed Elements in Blood

Blood Cell Types and Hematopoiesis

Blood contains cells and cell fragments suspended in plasma, all derived from hematopoietic stem cells in red bone marrow.

• Erythrocytes: Red blood cells, transport oxygen.

• Leukocytes: White blood cells, involved in immune responses.

• Platelets: Cell fragments involved in clotting.

Leukocytes (White Blood Cells)

The Lymphoid System

The lymphoid system consists of lymph plasma, lymphatic vessels, lymphoid tissues and organs, and red bone marrow. It is essential for immune cell development and for transporting microbes to lymph nodes where immune responses are initiated.

• Lymphoid tissue contains lymphocytes and phagocytic cells.

• Lymph carries microbes to lymph nodes for destruction by B and T lymphocytes, macrophages, and dendritic cells.

Phagocytes and Phagocytosis

Definition and Types

Phagocytes are cells that ingest and destroy microorganisms or other particles. "Professional" phagocytes include neutrophils, eosinophils, and macrophages (derived from monocytes).

• Fixed macrophages (histiocytes): Reside in specific tissues and organs (e.g., liver, lungs).

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

• Neutrophils are the first responders; macrophages dominate later in infection.

Mechanism of Phagocytosis

1. Chemotaxis: Chemical signals attract phagocytes to microorganisms (e.g., microbial products, complement, damaged cells).

2. Adherence: Phagocyte attaches to the microbe via PAMPs (pathogen-associated molecular patterns) binding to TLRs (Toll-like receptors). Opsonization (coating with serum proteins like antibodies or complement) enhances adherence.

3. Ingestion: Pseudopods extend to engulf the microbe, forming a phagosome. The phagosome becomes acidic (pH ~4), activating hydrolytic enzymes.

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

Key Terms and Concepts

• Pathogen-associated molecular patterns (PAMPs): Conserved microbial structures recognized by the immune system (e.g., LPS, flagellin, peptidoglycan).

• Toll-like receptors (TLRs): Host cell receptors that recognize PAMPs and trigger immune responses.

• Cytokines: Small proteins released by cells that regulate immune responses, including recruitment and activation of other immune cells.

• Opsonization: The process by which microbes are coated with molecules (opsonins) that enhance phagocytosis.

White Blood Cell Counts

• Normal WBC count: 4,000–11,000/μl

• Differential WBC count: Indicates the relative numbers of each type of white blood cell.

• High WBC count: May indicate bacterial infections, autoimmune diseases, or medication side effects.

• Low WBC count: May indicate viral infections, pneumonia, severe bacterial infections, autoimmune diseases, medication side effects, or cancers.

Summary Table: Major Innate Immune Cells

Example

Example: A neutrophil (blue) phagocytizing Aspergillus spores (red) demonstrates the process of phagocytosis, a key mechanism of innate immunity.

Additional info: These notes cover the core concepts of Chapter 16: Innate Immunity, including the structure and function of physical and chemical barriers, the role of normal microbiota, the types and functions of leukocytes, and the process of phagocytosis. This foundational knowledge is essential for understanding the body's first line of defense against infection.