Adaptive vs Innate Immunity: Quick Overview

● Adaptive arm
○ Specific response division: targets particular pathogen
types (bacteria, viruses, fungi) and attacks in highly
specific ways to destroy that pathogen.
● Innate arm
○ Nonspecific response: does not discriminate by
attacker; responds the same way regardless of
pathogen.
○ No memory: once a pathogen is targeted and
destroyed, innate immunity does not remember it, so it
cannot adapt to target it more efficiently next time.
○ First line of defense: analogous to walls, doors,
windows, and roof of a house; provides initial barrier
before inner defenses engage.
○ Analogy recap: innate = walls/doors/windows;
adaptive = guards whose responses depend on the
attacker’s tools (knife vs gun).
External vs Internal Innate Defenses

● External division (first line of defense): skin and mucous

membranes
○ Skin
○ Epidermis: the most superficial layer of skin,
composed of epithelia; the four tissue types are
epithelia, connective, nervous, and muscle.
○ Epidermis is stratified squamous epithelium (stratified
= many layers; squamous = flat) consisting of many
layers of dead cells.
○ Dead cells slough off without compromising
protection.
○ Sebaceous oil glands: secrete oil rich in unsaturated
fatty acids, which are poor energy sources for
microbes, and create a low pH environment:
$$\mathrm{pH} \approx 3{-}5$$, inhospitable to
many microbes.
 ○ Sweat: mostly water with some salt; contributes to a
salty environment and helps wash away microbes.
○ Hair and mucus: hair (on head, eyelashes, nasal cavity)
helps trap particles; mucus traps particles; cilia in
airways beat to move trapped pathogens out (coughing
or swallowing).
○ Secretions and enzymes
○ Tears and saliva contain defensins and lysozymes that
tear apart and kill invading pathogens.
○ Eyes, nasal cavity, and oral cavity protection
○ Secretions in tears and saliva provide enzymatic
antimicrobial activity.
○ Cilia and mucus clearance
○ Inhaled particles/pathogens become trapped in mucus;
cilia move mucus to be coughed up or swallowed;
swallowed material reaches the stomach where gastric
secretions have a very low pH (gastric acid):
$$\mathrm{pH} \approx 1{-}3$$, denaturing proteins
of pathogens.
● Internal division (inside tissues and bloodstream): cellular,
chemical, and physiological responses
○ All are part of the innate system, still nonspecific and
lacking memory.
○ Three broad categories: cellular defenses, chemical
defenses, and physiological responses.
Cellular Defenses in Innate Immunity

● Phagocytic cells (phagocytes): eat and digest invading

pathogens
○ Neutrophils
○ One of the white blood cells; most abundant WBC (the
mnemonic: "Never let monkeys eat bananas" helps
remember the order; neutrophils are first responders).
○ Predominantly target bacteria; perform phagocytosis
and digestion of pathogens.
○ Macrophages
○ Also phagocytic; include wandering macrophages
(monocytes circulating in blood that migrate to
infection sites) and fixed macrophages (histiocytes)
stationed in tissues.
○ Macrophages can become antigen-presenting cells
 (APCs): they ingest pathogens and present fragments
(antigens) on their surface to alert the adaptive
immune system (T and B cells).
○ Fixed macrophage examples: histiocytes (connective
tissue), Kupffer cells (liver), alveolar macrophages
(lungs), microglia (nervous system).
○ Antigen Presentation and APCs
○ Macrophages can present pathogen-derived antigens to
adaptive immune cells, enabling targeted responses by
T and B cells.
● Natural killer (NK) cells
○ Do not require prior exposure; kill infected or
abnormal cells.
○ Mechanisms:
○ Perforins: create pores in the target cell membrane,
causing lysis due to osmotic imbalance.
○ Granzymes: enter through pores and trigger apoptosis
(programmed cell death) in the target cell.
○ Apoptosis vs necrosis
○ Apoptosis: programmed cell death with intact cell
membrane; contents are neatly degraded without
releasing harmful substances.
○ Necrosis: unregulated cell death with membrane
rupture and potential release of harmful intracellular
contents.
Chemical Defenses in Innate Immunity

● Complement proteins (≈ 30 components)

○ Cascade mechanism: one complement protein activates
the next in sequence, amplifying the response.
○ Functions: enhance phagocytosis, promote
inflammation, and contribute to lysis of pathogens;
they complement innate defenses and aid
inflammation.
● Cytokines
○ Small signaling proteins; can be glycoproteins.
○ Types mentioned: interleukins, interferons, tumor
necrosis factors (TNFs), among others.
○ Roles:
○ Interleukins: communicate between white blood cells;
for example, recruit leukocytes to sites of infection.
 ○ Interferons: released when cells are infected by
viruses; call in T cells and other components of the
adaptive immune system to attack infected cells.
○ Distinction: cytokines modulate both innate and
adaptive responses, whereas complement proteins
primarily bolster the innate response.
Physiological Responses of Innate Immunity

● Inflammation
○ Definition: damage to vascularized (blood-supplied)
tissue triggers an inflammatory response.
○ Key tissues considerations:
○ Cartilage is avascular (lacks a dedicated blood supply),
so inflammation is rare or slower there; inflammation
is important for repair but can be damaging if
prolonged.
○ Damaging event leads to release of pro-inflammatory
mediators by damaged cells:
○ Prostaglandins (from damaged cell membranes):
involved in pain and inflammation; targets of
NSAIDs.
○ Histamine (from mast cells upon allergen exposure or
immune trigger): promotes inflammation.
○ Bradykinins (triggered by tissue damage): contribute
to inflammation.
○ Vascular changes during inflammation:
○ Vasodilation: enlarging blood vessels to increase blood
flow to the area, bringing more immune cells to the
site.
○ Increased vascular permeability: makes vessel walls
more leaky to allow immune cells (e.g.,
monocytes/macrophages, neutrophils) to exit the
bloodstream and enter tissue.
○ Cardinal signs of inflammation: redness, heat, pain,
swelling.
○ Pharmacological targets:
○ NSAIDs (nonsteroidal anti-inflammatory drugs) target
prostaglandins.
○ Antihistamines target histamine.
○ Bradykinins have fewer targeted therapies, but some
approaches exist.
 ● Fever (pyrexia)
○ Pyrogens: substances that raise body temperature; can
be pathogens themselves or cytokines.
○ Mechanism: pyrogens act on the hypothalamus
(thermostat of the body) to raise the set point from a
normal value of $$T_{set} =
38^{\circ}\mathrm{C}$$ toward higher temperatures,
e.g. $$T \approx 40{-}41^{\circ}\mathrm{C}.$$
○ Physiological responses to fever:
○ Shivering: muscle contractions to generate heat when
the perceived set point is higher than actual
temperature.
○ Peripheral vasoconstriction: blood vessels near the
skin constrict to conserve heat and raise core body
temperature.
○ Benefits of fever:
○ Enhances immune cell function at higher temperatures.
○ Inhibits or reduces replication of certain pathogens.
○ Clinical question: fever management is context-
dependent; sometimes beneficial, sometimes harmful,
so decisions about treating fever are nuanced.
Practical Implications and Real-World Relevance

● Medical interventions
○ NSAIDs mitigate inflammation by inhibiting
prostaglandin synthesis.
○ Antihistamines mitigate histamine-mediated
symptoms.
● Understanding innate/adaptive differences helps in
designing treatments and vaccines.
● The innate system’s non-memory nature explains why
repeated exposures lead to stronger adaptive responses
rather than faster innate responses.
● The mucosal and skin barriers are a critical first checkpoint;
protection is multi-layered (physical barrier, chemical
barriers, and mechanical clearance via cilia and mucus).
Connections to Foundational Principles and Prior Lectures

● Innate vs adaptive immunity as complementary systems:

innate provides immediate, broad defense; adaptive offers
targeted, memory-based responses.
 ● Phagocytosis as a core cellular mechanism for initial
pathogen control and antigen processing for subsequent
adaptive responses.
● Antigen presentation by macrophages links innate and
adaptive immunity, enabling T and B cell activation.
● Inflammation as a general tissue defense mechanism that
also primes repair processes; fever as an evolutionarily
conserved host defense strategy.
● The role of chemical mediators (cytokines, complement,
prostaglandins, histamine, bradykinins) in coordinating
cellular and physiological responses.
Quick Reference: Key Terms and Concepts

● Innate immunity: nonspecific, non-memory defense system;

first line of defense.
● External innate defenses: skin, mucous membranes, hair,
mucus, secretions (tears, saliva), cilia, stomach acid.
● Internal innate defenses: phagocytes (neutrophils,
macrophages), NK cells, complement, cytokines.
● Phagocytosis: engulfing and digesting pathogens by
phagocytes.
● Antigen presenting cells (APCs): macrophages presenting
pathogen fragments to adaptive immune cells.
● NK cells: induce target cell death via perforins and
granzymes; can promote apoptosis.
● Prostaglandins, histamine, bradykinins: mediators of
inflammation.
● Vasodilation and increased vascular permeability: enable
more immune cells to reach infection sites.
● Cardinal signs of inflammation: redness, heat, pain,
swelling.
● Fever and pyrogens: hypothalamic set point raised by
pyrogens; shivering and vasoconstriction raise core
temperature; benefits include enhanced immune function
and reduced pathogen replication.
● Complement cascade: ~ vers. 30 proteins; sequential
activation; supports innate immunity and inflammation.
● Interleukins, interferons, TNF: cytokines that coordinate
innate and adaptive immune responses; interferons alert T
cells during viral infections.
● Cartilage is avascular: inflammation is rare in cartilage due
to lack of blood supply; implications for tissue repair