Innate Immunity: Nonspecific Defenses of the Host

Innate Immunity: Nonspecific Defenses of the Host

Overview of Immunity

Immunity refers to the body's ability to resist or eliminate potentially harmful foreign materials or abnormal cells. The immune system is divided into two main branches: innate immunity (nonspecific, present at birth, rapid response) and adaptive immunity (specific, slower, memory component). Innate immunity provides the first and second lines of defense against pathogens, while adaptive immunity provides the third line of defense.

Key Differences: Innate vs. Adaptive Immunity

• Innate Immunity: Rapid, nonspecific, no memory, includes barriers (skin, mucous membranes), phagocytes, inflammation, and fever.

• Adaptive Immunity: Slower, specific to pathogens, has memory, involves lymphocytes (T cells and B cells).

First Line of Defense: Physical and Chemical Barriers

Physical Barriers

The skin and mucous membranes act as the body's primary physical barriers to infection. These structures prevent the entry of pathogens through tightly packed epithelial cells and protective secretions.

• Skin: Composed of the outer epidermis (keratinized, tightly packed cells) and inner dermis (connective tissue). Shedding and dryness inhibit microbial growth.

• Mucous Membranes: Line the gastrointestinal, respiratory, and genitourinary tracts. Secrete mucus to trap microbes and prevent drying.

• Lacrimal Apparatus: Produces tears that wash microbes from the eye surface.

• Ciliary Escalator: Cilia in the respiratory tract move mucus and trapped particles away from the lungs.

• Other Physical Factors: Earwax, urine flow, vaginal secretions, peristalsis, defecation, vomiting, and diarrhea help remove microbes from the body.

Chemical Barriers

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

• Sebum: Oily substance produced by sebaceous glands; forms a protective film and lowers skin pH (3–5).

• Lysozyme: Enzyme in sweat, tears, saliva, and urine that destroys bacterial cell walls (peptidoglycan).

• Low pH: Gastric juice (pH 1.2–3.0) and vaginal secretions (pH 3–5) inhibit microbial growth.

Role of Normal Microbiota in Innate Immunity

Normal microbiota protect the host by competing with pathogens for nutrients and space (microbial antagonism), producing substances harmful to pathogens, and altering environmental conditions. Some microbes are commensal (benefit without harming the host), while probiotics are live cultures administered for health benefits.

Second Line of Defense: Cellular Components and Processes

Formed Elements in Blood

Blood contains plasma and formed elements: erythrocytes (red blood cells), leukocytes (white blood cells), and platelets. Leukocytes are crucial for immune defense and are produced in red bone marrow via hematopoiesis.

Types of Leukocytes

Leukocytes are classified as granulocytes or agranulocytes based on the presence of cytoplasmic granules.

Innate or Adaptive	Cell Type	Description	Function
Innate	Basophil	Granulocyte	Releases histamines that cause inflammation
Innate	Eosinophil	Granulocyte	Kills parasites with oxidative burst
Innate	Mast cell	Granulocyte	Antigen-presenting cells; produce antibacterial peptides
Both	Neutrophil	Granulocyte	Phagocytizes bacteria and fungi
Both	Monocyte	Agranulocyte	Precursor to macrophages; some fixed in certain organs, others wander tissues
Both	Dendritic cell	Agranulocyte	In skin and mucosa; phagocytizes bacteria and viruses
Both	Natural killer (NK) cell	Agranulocyte	Kills cancer cells and virus-infected cells
Adaptive	Plasma cell, B cell	Agranulocyte	Recognizes antigens and produces antibodies
Adaptive	T cells	Agranulocyte	Cell-mediated immunity

Phagocytes and Phagocytosis

Phagocytes are cells that ingest and destroy microbes and debris. Major phagocytes include neutrophils and macrophages (derived from monocytes). Phagocytosis involves four main steps: chemotaxis, adherence, ingestion (often enhanced by opsonization), and digestion within phagolysosomes.

The Lymphatic System

The lymphatic system consists of lymph, lymphatic vessels, lymphoid tissue, and red bone marrow. It transports lymph (containing microbes) to lymph nodes, where lymphocytes and macrophages destroy pathogens. The system is essential for immune surveillance and fluid balance.

Inflammation

Inflammation is a local defensive response to tissue damage, characterized by pain, redness, immobility, swelling, and heat (PRISH). Its functions are to destroy or contain injurious agents and repair damaged tissue. Key mediators include histamine, kinins, prostaglandins, leukotrienes, and cytokines, which promote vasodilation and increased vascular permeability.

Vasoactive Mediator	Source	Effect
Histamine	Mast cells, basophils, platelets	Vasodilation, increased permeability
Kinins	Blood plasma	Chemotaxis, attracts neutrophils
Prostaglandins	Damaged cells	Intensify histamine/kinin effects, help phagocytes move through capillary walls
Leukotrienes	Mast cells, basophils	Increase permeability, help phagocyte attachment
Complement	Blood plasma	Stimulates histamine release, attracts phagocytes, promotes phagocytosis
Cytokines	Fixed macrophages	Vasodilation, increased permeability

Fever

Fever is an abnormally high body temperature, usually caused by infection. Cytokines trigger the hypothalamus to raise body temperature, which can inhibit pathogen growth, increase immune reactions, and speed up tissue repair. When the fever 'breaks,' vasodilation and sweating return the body to normal temperature.

Antimicrobial Substances

The Complement System

The complement system is a group of over 30 proteins that enhance immune responses. Complement activation occurs via three pathways: classical (antibody-dependent), alternative (direct pathogen contact), and lectin (mannose-binding). The main outcomes are cytolysis (cell lysis), opsonization (enhanced phagocytosis), and inflammation.

• Classical Pathway: Triggered by antibodies binding to antigens.

• Alternative Pathway: Triggered by complement proteins binding directly to pathogen surfaces.

• Lectin Pathway: Triggered by lectin binding to microbial carbohydrates.

Interferons

Interferons (IFNs) are cytokines with antiviral activity. IFN-α and IFN-β are produced in response to viral infections and induce neighboring cells to produce antiviral proteins. IFN-γ activates neutrophils and macrophages to kill bacteria.

Iron-Binding Proteins

Iron-binding proteins (e.g., transferrin, lactoferrin, ferritin, hemoglobin) sequester iron, limiting its availability to pathogens. Some bacteria produce siderophores to compete for iron.

Antimicrobial Peptides (AMPs)

AMPs are short peptides produced in response to microbial molecules. They have broad-spectrum activity, including inhibition of cell wall synthesis, pore formation, and destruction of microbial DNA/RNA.

Other Factors Affecting Resistance

• Genetic resistance: Certain genetic traits (e.g., sickle cell trait) can confer resistance to specific pathogens.

• Age: The very young and elderly are more susceptible to infection.

• Hygiene: Practices such as handwashing reduce infection risk.