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.

• Innate Immunity: Rapid, nonspecific, no memory. Includes barriers, phagocytes, inflammation, and fever.

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

Blood Cell Counts and Health

White blood cell (WBC) counts are important diagnostic tools. Abnormal counts can indicate infections, immune disorders, or other health conditions.

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

• Low WBC count: May indicate viral infection, pneumonia, autoimmune disease, or cancer.

The Concept of Immunity

Definitions and Types

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

• Susceptibility: Lack of resistance to disease.

• Innate Immunity: Present at birth, rapid, nonspecific, no memory.

• Adaptive Immunity: Specific, slower, memory component, involves T and B lymphocytes.

Toll-like Receptors (TLRs) and Pathogen Recognition

Innate immune responses are triggered by protein receptors in the plasma membrane of defensive cells. Toll-like receptors (TLRs) on host cells recognize pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS), flagellin, and peptidoglycan. Binding of TLRs to PAMPs induces the release of cytokines, which regulate immune responses.

First Line of Defense: Skin and Mucous Membranes

Physical Factors

The skin and mucous membranes act as physical barriers to prevent pathogen entry. The skin consists of the epidermis (outer layer, keratinized, tightly packed cells) and the dermis (inner connective tissue layer). Shedding and dryness of skin inhibit microbial growth.

• Skin: Largest organ, physical barrier, keratinized epidermis.

• Mucous membranes: Line gastrointestinal, respiratory, and genitourinary tracts; secrete mucus to trap microbes.

• Lacrimal apparatus: Produces tears to wash microbes from the eye.

Additional Physical Defenses

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

• Earwax: Prevents entry of microbes and debris.

• Urine and vaginal secretions: Flush out microbes.

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

Chemical Factors

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

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

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

Normal Microbiota and Innate Immunity

• Microbial antagonism (competitive exclusion): Normal microbiota compete with pathogens for space and nutrients, produce substances harmful to pathogens, and alter environmental conditions.

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

• Probiotics: Live microbial cultures that confer health benefits, such as lactic acid bacteria preventing diarrhea and pathogen colonization.

Second Line of Defense: Cellular Components

Formed Elements in Blood

Blood consists of plasma and formed elements (cells and cell fragments). The main formed elements are erythrocytes (red blood cells), leukocytes (white blood cells), and platelets. All blood cells originate from stem cells in red bone marrow through hematopoiesis.

Leukocytes: Types and Functions

Leukocytes are divided into granulocytes (with visible granules) and agranulocytes (without visible 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 cell; produces antibacterial peptides
Both	Neutrophil	Granulocyte	Phagocytizes bacteria and fungi
Both	Monocyte	Agranulocyte	Precursor to macrophages; phagocytic
Both	Dendritic cell	Agranulocyte	Phagocytosis and initiation of adaptive immune responses
Both	Natural killer (NK) cell	Agranulocyte	Kills cancer cells and virus-infected cells
Adaptive	Plasma cell, B cell	Agranulocyte	Produces antibodies
Adaptive	T cells	Agranulocyte	Cell-mediated immunity

The Lymphatic System

The lymphatic system consists of lymph, lymphatic vessels, lymphoid tissue, and red bone marrow. It contains lymphocytes and phagocytic cells. Lymph carries microbes to lymph nodes, where they are destroyed by lymphocytes and macrophages.

Phagocytes and Phagocytosis

Phagocytes

Phagocytes are cells that ingest and destroy microbes and debris. Types include neutrophils, macrophages (mature monocytes), and dendritic cells. Fixed macrophages reside in tissues, while free (wandering) macrophages move to sites of infection.

Mechanism of Phagocytosis

Phagocytosis occurs in four main phases:

1. Chemotaxis: Phagocytes are attracted to microbes by chemical signals.

2. Adherence: Phagocyte attaches to the microbe's surface.

3. Ingestion: Microbe is engulfed into a phagosome; opsonization (coating with serum proteins) enhances ingestion.

4. Digestion: Microbe is destroyed inside a phagolysosome.

Inflammation

Stages and Functions

Inflammation is a local defensive response to tissue damage. The main signs are pain, redness, immobility, swelling (edema), and heat (PRISH). Functions include destroying the injurious agent, limiting its effects, and repairing tissue.

• Vasodilation: Increases blood flow to the area (redness, heat).

• Increased permeability: Allows defensive substances to enter tissues (swelling, pain).

• Chemotaxis: Attracts phagocytes to the site of injury.

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

Phagocyte Migration and Tissue Repair

• Margination: Phagocytes stick to blood vessel walls at the site of inflammation.

• Diapedesis: Phagocytes squeeze through endothelial cells to reach damaged tissue.

• Tissue repair: Final stage; stroma (supporting tissue) and parenchyma (functioning tissue) produce new cells.

Fever

Causes and Effects

Fever is an abnormally high body temperature, usually caused by infection. Cytokines trigger the hypothalamus to raise body temperature. Fever enhances immune responses and inhibits some pathogens.

• Benefits: Increases production of immune cells, inhibits growth of some microbes, speeds up tissue repair.

Antimicrobial Substances

The Complement System

The complement system is a group of over 30 proteins produced by the liver that enhance immune responses. Complement activation occurs via three pathways:

1. Classical pathway: Triggered by antibodies binding to antigens.

2. Alternative pathway: Triggered by direct interaction with pathogen surfaces.

3. Lectin pathway: Triggered by lectin binding to microbial carbohydrates.

• Outcomes: Cytolysis (cell lysis), opsonization (enhanced phagocytosis), inflammation.

• Regulation: Regulatory proteins prevent host cell damage.

• Deficiencies: Increase susceptibility to infections.

• Pathogen evasion: Capsules can prevent complement activation.

Interferons

Interferons (IFNs) are cytokines with antiviral activity. Types include:

• IFN-α and IFN-β: Produced in response to viral infection; induce antiviral proteins in neighboring cells.

• 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, inhibiting cell wall synthesis, forming pores in membranes, and destroying DNA/RNA.

Other Factors Affecting Immunity

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

• Age: Very young and elderly individuals are more susceptible to infection.

• Hygiene: Practices like handwashing reduce infection risk.