Week 2 - Innate Immunity and Natural Killer Cells

What is innate immunity?

Natural/native immunity present from birth; rapid, non-specific defense without prior exposure.

Where is innate immunity most active?

At anatomical entry points: skin, respiratory tract, GI tract, urogenital tract, mammary gland, ocular mucosa.

What are the three major lines of defense in immunity?

Physical barriers, innate immunity, adaptive immunity.

What are the main components of innate immunity?

Physical barriers, humoral barriers (complement, enzymes), cellular barriers (phagocytes, NK cells), commensal organisms.

What mechanical factors protect the skin?

Tight junctions between epithelial cells, keratinized surface, constant shedding of cells.

What chemical factors protect the skin?

Sebum (acidic, water-repellent), antimicrobial peptides, sweat secretions.

What microbiological factor protects the skin?

Cutaneous microflora competing with pathogens.

How does the respiratory tract clear pathogens?

Mucus secretion + mucociliary clearance (mucociliary escalator).

What disease in dogs impairs mucociliary clearance?

Ciliary dyskinesia → predisposes to respiratory infections.

What role does gastric mucosa play in defense?

Secretes HCl (pH ≤ 2), killing ingested microbes.

Which secretions physically flush microorganisms?

Milk, saliva, tears, urine.

Name antimicrobial proteins secreted by epithelia.

Lysozyme, defensins, cathelicidins, lactoferrin, lactoperoxidase.

How do defensins kill microbes?

Insert into negatively charged microbial membranes → create pores.

What cells produce defensins in the intestine?

Paneth cells.

What is the role of commensal organisms in innate defense?

Compete with pathogens for space/nutrients; influence intestinal and immune development.

What is a probiotic?

Supplementation with beneficial microbes to support commensal balance.

What are the main goals of the inflammatory response?

Neutralize pathogens, prevent systemic spread, promote tissue repair/homeostasis.

What triggers the inflammatory response?

Damaged cells release alarmins; mast cells degranulate releasing histamine; macrophages release cytokines.

What vascular changes occur during inflammation?

Vasodilation (redness, heat), increased permeability (swelling), stimulation of nerves (pain).

What cells extravasate into tissues during inflammation?

Neutrophils first, followed by monocytes (→ macrophages).

What are sentinel cells?

Early responders like macrophages, dendritic cells, mast cells.

Describe neutrophils.

Bone marrow-derived, polymorphonuclear, short-lived, first responders, phagocytic.

Where are most neutrophils sequestered in the body?

Liver, spleen, bone marrow, lungs.

What are the four stages of neutrophil adhesion and migration?

Rolling → adhesion → diapedesis (emigration) → chemotaxis.

What are PAMPs and DAMPs?

Pathogen-associated molecular patterns; Damage-associated molecular patterns.

What is the CD system in immunity?

A classification system for cell surface molecules (e.g., CD4, CD8, CD16).

What is opsonization?

Coating of microbes by opsonins (antibodies, complement, lectins) to enhance phagocytosis.

Give examples of opsonins.

Mannose-binding lectin, fibronectin, complement (C3b), antibodies (IgG).

What are Neutrophil Extracellular Traps (NETs)?

DNA strands that capture and kill microbes, preventing spread.

What is the respiratory burst?

Production of reactive oxygen species (ROS) like superoxide, hydrogen peroxide, hypochlorite.

What enzyme complex drives the respiratory burst?

NADPH oxidase (NOX).

What are the bactericidal molecules produced by neutrophils/macrophages?

ROS (O₂⁻, H₂O₂, OCl⁻), RNS (NO, peroxynitrite), antimicrobial peptides.

Compare neutrophils vs macrophages.

Neutrophils: rapid, short-lived, first line. Macrophages: long-lived, sustained, tissue repair and antigen presentation.

What are Macrophage Extracellular Traps (METs)?

DNA-protein structures similar to NETs, used to trap microbes.

What are M1 macrophages?

Pro-inflammatory, microbicidal.

What are M2 macrophages?

Anti-inflammatory, promote tissue repair.

What happens in chronic inflammation?

Persistent infection → continuous M2 polarization → fibrosis, granuloma formation.

What is SIRS (Systemic Inflammatory Response Syndrome)?

Widespread inflammation due to excess cytokines (cytokine storm) → sepsis, organ failure, death.

What is a granuloma?

Organized collection of macrophages and fibroblasts in chronic inflammation (e.g., TB).

How do macrophages remove dying neutrophils?

By efferocytosis (phagocytosis of apoptotic cells).