Innate Immunity: Nonspecific Defenses of the Host – Study Notes

Innate Immunity: Nonspecific Defenses of the Host

Overview of Immunity

Immunity refers to the ability of an organism to resist infection or disease. The immune system is divided into two main branches: innate immunity (nonspecific, present at birth, rapid response) and adaptive immunity (specific, slower, has memory). Innate immunity provides the first and second lines of defense against pathogens, including physical barriers, cellular defenses, and chemical mediators.

The Concept of Immunity

• Immunity: Ability to ward off disease.

• Susceptibility: Lack of resistance to a disease.

• Innate Immunity: Defenses against any pathogen; rapid, present at birth.

• Adaptive Immunity: Immunity or resistance to a specific pathogen; slower to respond, has memory component.

• Cells of the innate immune system respond to pathogens and activate adaptive immunity via Toll-like receptors (TLRs) that recognize pathogen-associated molecular patterns (PAMPs).

• Cytokines are released to regulate immune responses and recruit other immune cells.

First Line of Defense: Physical and Chemical Barriers

Physical Factors

• 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 tracts from drying out.

• Lacrimal apparatus: Drains tears and washes the eye.

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

• Other mechanisms: Epiglottis, earwax, urine flow, vaginal secretions, peristalsis, defecation, vomiting, diarrhea.

Chemical Factors

• 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 microbes.

Normal Microbiota and Innate Immunity

• Normal microbiota compete with pathogens for space and nutrients (microbial antagonism).

• Produce substances harmful to pathogens and alter conditions affecting pathogen survival.

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

• Opportunistic pathogens: Normal microbiota that can cause disease under certain conditions (e.g., E. coli, S. aureus).

• Probiotics: Live microbial cultures with beneficial effects.

• Prebiotics: Nutrients that promote the growth of beneficial bacteria.

Second Line of Defense: Cellular and Chemical Responses

Formed Elements in Blood

Blood contains cells and cell fragments suspended in plasma. The main formed elements are erythrocytes (red blood cells), leukocytes (white blood cells), and platelets. All are produced in red bone marrow via hematopoiesis.

Leukocytes (White Blood Cells)

Leukocytes are classified as granulocytes or agranulocytes based on the presence of granules in their cytoplasm.

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; some are fixed in tissues, others are wandering
Both	Dendritic cell	Agranulocyte	Phagocytosis and initiation of adaptive immune responses
Both	Natural killer (NK) cell	Agranulocyte (lymphocyte)	Kills cancer and virus-infected cells
Adaptive	Plasma cell, B cell	Agranulocyte (lymphocyte)	Recognizes antigens and produces antibodies
Adaptive	T cells	Agranulocyte (lymphocyte)	Cell-mediated immunity

White Blood Cell Counts

• Normal WBC count: 5,000–10,000 WBCs per mm³ (5.0–10.0 × 10⁹/L).

• Differential WBC count indicates the relative numbers of each type of WBC.

• High WBC counts may indicate bacterial infections, autoimmune diseases, or medication side effects.

• Low WBC counts may indicate viral infections, pneumonia, severe bacterial infections, or cancers.

The Lymphatic System

The lymphatic system consists of lymph plasma, lymphatic vessels, and lymphoid organs (lymph nodes, spleen, tonsils, thymus, red bone marrow). Lymphoid tissue contains lymphocytes and phagocytic cells. Lymph carries microbes to lymph nodes where immune cells encounter and destroy pathogens.

Phagocytes and Phagocytosis

Phagocytes are cells that ingest and destroy microbes and debris. "Professional" phagocytes include neutrophils, eosinophils, and macrophages (developed from monocytes). Macrophages can be fixed (residing in tissues) or free (wandering in tissues).

Mechanism of Phagocytosis

• Chemotaxis: Chemical signals attract phagocytes to microorganisms.

• Adherence: Attachment of phagocyte to microbe, often enhanced by opsonization (coating with serum proteins such as antibodies or complement).

• Ingestion: Pseudopods engulf the microbe, forming a phagosome.

• Digestion: Lysosomes fuse with the phagosome, forming a phagolysosome where the microbe is digested.

• 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 effects of injurious agents and to repair damaged tissue.

• Signs and symptoms: pain, redness, immobility, swelling (edema), heat (PRISH).

• Acute inflammation: rapid onset, short duration.

• Chronic inflammation: slower onset, longer duration, may be severe and progressive.

Stages of Inflammation

• Vasodilation and increased vascular permeability: Blood vessels dilate and become more permeable, allowing immune cells and proteins to reach the site of injury.

• Phagocyte migration and phagocytosis: Neutrophils and monocytes migrate to the site, adhere to blood vessel walls (margination), squeeze through (diapedesis), and ingest microbes.

• Tissue repair: Damaged tissue is repaired once harmful substances are removed.

Fever

Fever is an abnormally high body temperature, usually caused by infection. Cytokines reset the hypothalamus to a higher temperature, enhancing immune responses and inhibiting pathogen growth. Complications can include tachycardia, acidosis, dehydration, seizures, and coma.

Antimicrobial Substances

The Complement System

The complement system is a group of over 30 serum proteins produced by the liver that enhance the immune system's ability to destroy microbes. Complement activation occurs via three pathways: classical, alternative, and lectin. The system leads to cytolysis, opsonization, and inflammation.

• Classical pathway: Triggered by antibodies binding to antigens.

• Alternative pathway: Triggered by complement proteins binding directly to microbial surfaces.

• Lectin pathway: Triggered by mannose-binding lectin binding to microbial carbohydrates.

Outcomes of Complement Activation

• Cytolysis: Formation of the membrane attack complex (MAC) that lyses microbes.

• Opsonization: Coating of microbes to enhance phagocytosis.

• Inflammation: Activation of mast cells to release histamine and other mediators.

• Regulation: Host cells have regulatory proteins to prevent damage.

• Some pathogens evade complement by producing capsules or other inhibitors.

Interferons

• Interferons (IFNs): Cytokines produced by host cells in response to viral infection.

• Induce production of antiviral proteins in neighboring cells, inhibiting viral replication.

• Three main types: alpha, beta, and gamma interferons.

Iron-Binding Proteins

• Host proteins (transferrin, lactoferrin, ferritin, hemoglobin) tightly bind iron to limit its availability to pathogens.

• Some bacteria produce siderophores to compete for iron.

Antimicrobial Peptides

• Short peptides produced in response to microbial molecules.

• Broad spectrum of activity: inhibit cell wall synthesis, form pores in membranes, destroy DNA/RNA.

• Examples: dermcidin, defensins, cathelicidins, thrombocidin.

Other Factors Affecting Immunity

• Genetic resistance: Some individuals have genetic traits that confer resistance (e.g., sickle cell trait and malaria).

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

• Healthy protocols: Hand hygiene, cough/sneeze etiquette, safe sex practices reduce disease risk.