Innate Immunity: Nonspecific Defenses of the Host – Study Guide

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Innate Immunity: Nonspecific Defenses of the Host

Overview of Immunity

Immunity is the ability of an organism to resist infection or disease. The immune system is divided into innate immunity (nonspecific, present at birth) and adaptive immunity (specific, acquired). Innate immunity provides the first line of defense against pathogens and activates adaptive responses.

Immunity: Ability to ward off disease.
Susceptibility: Lack of resistance to disease.
Innate immunity: Rapid, nonspecific defenses present at birth.
Adaptive immunity: Slower, specific, and has memory.

Layers of immune defense against pathogens

White Blood Cell Counts and Types

White blood cell (WBC) counts are used to assess immune status. Differential counts indicate the relative numbers of each type of leukocyte, which can help diagnose infections or immune disorders.

Normal WBC count: 5,000–10,000 WBCs per mm3 or 5.0–10.0 × 109 per liter.
Neutrophils: 60–70%
Lymphocytes: 20–25%
Monocytes: 3–8%
Eosinophils: 2–4%
Basophils: 0.5–1%

Normal ranges and percentages of white blood cells

The Concept of Immunity

Cells of the innate immune system recognize pathogens via Toll-like receptors (TLRs) that bind to pathogen-associated molecular patterns (PAMPs). This triggers the release of cytokines that regulate immune responses and recruit other immune cells.

PAMPs: Molecules such as LPS, flagellin, peptidoglycan, bacterial DNA, viral DNA/RNA.
Cytokines: Signaling proteins that modulate immune responses.

First Line of Defense: Physical and Chemical Barriers

Physical Factors

The skin and mucous membranes act as physical barriers to prevent pathogen entry.

Skin: Composed of dermis (connective tissue) and epidermis (keratinized epithelial cells). Shedding and dryness inhibit microbial growth.
Mucous membranes: Line the GI, respiratory, and genitourinary tracts. Mucus traps microbes.
Ciliary escalator: Moves mucus and trapped microbes out of the lungs.
Lacrimal apparatus: Washes the eye with tears.
Other mechanisms: Earwax, urine flow, vaginal secretions, peristalsis, defecation, vomiting, diarrhea.

Chemical Factors

Chemical barriers inhibit microbial growth and destroy pathogens.

Sebum: Forms a protective film and lowers skin pH (3–5).
Lysozyme: Enzyme in perspiration, tears, saliva, urine; 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

Normal microbiota compete with pathogens and play a role in immune system development.

Microbial antagonism: Competition for space and nutrients.
Commensalism: One organism benefits, host is unharmed.
Opportunistic pathogens: E. coli, S. aureus, S. epidermidis, Enterococcus faecalis, Pseudomonas aeruginosa.
Probiotics: Live cultures with beneficial effects.
Prebiotics: Nutrients promoting growth of beneficial bacteria.

Second Line of Defense: Cellular and Molecular Responses

Formed Elements in Blood

Blood contains cells and cell fragments suspended in plasma. These include erythrocytes, leukocytes, and platelets, all produced via hematopoiesis in red bone marrow.

Hematopoiesis and blood cell lineages

Leukocytes (White Blood Cells)

Leukocytes are classified as granulocytes or agranulocytes, each with specific functions in immunity.

Granulocytes: Basophils (histamine release), eosinophils (parasite defense), mast cells (antibacterial peptides), neutrophils (phagocytosis).
Agranulocytes: Monocytes (macrophages), dendritic cells (antigen presentation), lymphocytes (T cells, B cells, NK cells).

Leukocyte types and functions Granulocyte types and functions Agranulocyte types and functions

The Lymphoid System

The lymphoid system includes lymph plasma, vessels, and organs containing lymphoid tissue. Lymph carries microbes to lymph nodes, where immune cells encounter and destroy pathogens.

Lymphoid organs: Tonsils, thymus, spleen, Peyer's patches, red bone marrow.
Lymphatic vessels: Transport lymph throughout the body.

Lymphatic system anatomy Lymphatic capillaries and fluid flow

Phagocytes and Phagocytosis

Phagocytes ingest and destroy pathogens. They include neutrophils, eosinophils, and macrophages (fixed and wandering).

Phagocytosis: Ingestion of microorganisms by phagocytes.
Neutrophils: First responders in infection.
Macrophages: Clean-up crew, dominate later in infection.

Macrophage engulfing bacterium Phases of phagocytosis

Mechanism of Phagocytosis

Phagocytosis involves several steps: chemotaxis, adherence, ingestion, and digestion.

Chemotaxis: Chemical signals attract phagocytes.
Adherence: Phagocyte attaches to microbe; opsonization enhances attachment.
Ingestion: Pseudopods engulf microbe, forming a phagosome.
Digestion: Lysosomes fuse with phagosome, forming phagolysosome; enzymes digest microbe.

Inflammation and Fever

Inflammation

Inflammation is a local response to tissue damage, characterized by pain, redness, immobility, swelling, and heat (PRISH). It functions to destroy injurious agents and repair tissue.

Acute inflammation: Rapid onset, short duration.
Chronic inflammation: Slow onset, long duration.
Stages: Vasodilation/increased permeability, phagocyte migration, tissue repair.

Process of inflammation Phagocyte migration and phagocytosis

Fever

Fever is an abnormally high body temperature, often caused by infection. Cytokines reset the hypothalamus to a higher temperature, enhancing immune function but potentially causing complications.

Benefits: Enhances phagocyte and T cell activity, increases interferon production, slows pathogen growth.
Complications: Tachycardia, acidosis, dehydration, seizures, coma.

Antimicrobial Substances

The Complement System

The complement system consists of over 30 serum proteins that enhance immune responses via cytolysis, opsonization, and inflammation. Activation occurs through three pathways: classical, alternative, and lectin.

Classical pathway: Antibody-antigen complexes activate complement.
Alternative pathway: Direct activation by microbial surfaces.
Lectin pathway: Mannose-binding lectin binds to microbial carbohydrates.

Classical pathway of complement activation Alternative pathway of complement activation Lectin pathway of complement activation

Outcomes of Complement Activation

Cytolysis: Formation of membrane attack complex (MAC) that lyses microbes.
Opsonization: Coating of microbes to enhance phagocytosis.
Inflammation: Activation of mast cells and release of histamine.
Regulation: Regulatory proteins prevent host cell damage.
Evading complement: Some pathogens avoid complement by capsules or inhibiting complement proteins.

Outcomes of complement activation: cytolysis, opsonization, inflammation

Interferons

Interferons are cytokines produced by host cells in response to viral infection. They induce antiviral proteins in neighboring cells and enhance phagocyte activity.

Types: Alpha, beta, gamma interferons.
Function: Inhibit viral replication, activate immune cells.

Iron-Binding Proteins

Host proteins bind iron tightly to limit pathogen access. Pathogens may produce siderophores to compete for iron.

Transferrin: Blood and tissue fluids.
Lactoferrin: Milk, saliva, mucus.
Ferritin: Liver, spleen, bone marrow.
Hemoglobin: Red blood cells.

Antimicrobial Peptides

Short peptides produced in response to microbial molecules. They inhibit cell wall synthesis, form pores, and destroy nucleic acids.

Examples: Dermcidin, defensins, cathelicidins, thrombocidin.

Other Factors Affecting Immunity

Genetic resistance: Sickle cell trait confers resistance to malaria.
Age: Very young and elderly are more susceptible.
Healthy protocols: Hand hygiene, cough/sneeze etiquette, safer sex practices.