Week 3 Physiology Immune System

### Overview & Innate vs Adaptive

Why isn't the immune system a true anatomical "system"?

It's a diverse collection of cells found in blood, lymph, and tissues throughout the body that carry out immune defenses, but the cells are not anatomically connected like the organs of other body systems.

What is immunology?

The study of the physiological defenses by which the host recognizes self from non-self (foreign matter) and destroys or neutralizes that foreign matter.

What is immune privilege?

The property of certain body sites (eyes, brain/CNS, testes, placenta/fetus) where immune responses are suppressed or restricted to prevent inflammatory damage to sensitive tissue or rejection of the fetus.

By what three mechanisms do immune-privileged sites suppress local immune activity?

Physical barriers (e.g., blood-brain barrier blocking routine immune cell entry), chemical signals (local anti-inflammatory/suppressive molecules), and altered signals (fewer surface markers that would trigger immune attack).

Why are the eyes, brain/CNS, testes, and placenta each immune-privileged?

Eyes: prevents inflammation that would damage vision. Brain/CNS: shields delicate neural tissue from immune damage. Testes: protects developing sperm from autoimmune attack. Placenta/fetus: stops the mother's immune system from rejecting the fetus.

What distinguishes non-specific (innate) immunity from specific (adaptive) immunity?

Innate immunity protects against foreign substances without recognizing their specific identity; adaptive immunity depends on lymphocytes specifically recognizing a substance, followed by an attack unique to that substance.

What are the typical response timelines for innate vs. adaptive immunity?

Innate: minutes to hours. Adaptive: days to weeks.

How does the innate immune system enable the adaptive immune system?

Non-specific (innate) immune components provide instructions (via antigen presentation) that instruct and activate specific (adaptive) immunity.

### Immune Cell Types

Where are leukocytes produced, and what is their overall role?

Produced in the bone marrow; they are the primary immune defense system, patrolling in blood/tissues to detect damage, trigger inflammation, destroy pathogens, and produce antibodies.

What is the function of neutrophils, and what do they target?

The most common WBC; they rush to injury/infection sites immediately and primarily kill and eat bacteria and fungi via phagocytosis.

What two cell types make up lymphocytes, and what does each do?

B cells, which create antibodies (humoral immunity), and T cells/Natural Killer cells, which directly destroy virus-infected cells and cancer cells (cell-mediated immunity).

What do monocytes become once they enter body tissue, and what do they clean up?

They transition into macrophages; they clean up dead tissue, cellular debris, and chronic bacterial infections.

What do eosinophils target, and what other role do they play?

They destroy large foreign invaders such as parasites and worms (helminths) that are too big for phagocytosis by other cells; they also drive allergic reactions and asthma symptoms.

What is the function of basophils, and what do they release?

The rarest WBC; they release histamine during an allergic reaction, triggering inflammation and vasodilation so other immune cells can reach the site.

What does "Never Let Monkeys Eat Bananas" represent, and what is the order it encodes?

The relative proportions of WBC types from most to least abundant: Neutrophils (60%) > Lymphocytes (30%) > Monocytes (6%) > Eosinophils (3%) > Basophils (1%).

What distinguishes granulocytes from agranulocytes, and which cells belong to each group?

Granulocytes (neutrophils, eosinophils, basophils) contain visible cytoplasmic granules; agranulocytes (monocytes, lymphocytes) lack prominent granules.

What are plasma cells, where do they come from, and what is their major function?

Specialized WBCs differentiated from B lymphocytes during an immune response; located in peripheral lymphoid organs/tissues; they synthesize and secrete high volumes of antibodies.

Where do macrophages come from, and what are their three main functions?

Derived from monocytes in the bone marrow; they perform phagocytosis, present antigens to helper T cells, and secrete cytokines involved in inflammation.

Where are macrophages strategically positioned, and why?

In epithelia (skin, respiratory tract lining, digestive tract lining) — the body's external and internal surfaces most exposed to pathogen entry.

What is the function of dendritic cells, and how do they link innate to adaptive immunity?

They phagocytose pathogens in tissue, then travel to lymph nodes to present antigens to T cells, initiating the adaptive immune response.

What are mast cells, where do they reside, and what is their role?

The immune system's primary "alarm system"; reside in connective and mucosal tissues; they store and release histamine and other inflammatory chemicals.

### Cytokines

What are cytokines, and how do they act (locally vs. systemically)?

Protein messengers secreted by various immune cells (not a distinct gland) that regulate host cell division and function; most of their actions occur locally, not throughout the bloodstream, and they link immune system components together.

Name four key cytokines mentioned in this lecture.

IL-1, IL-2, IL-6, and TNF-alpha.

### Innate Defenses & Inflammation

What three categories make up non-specific (innate) immune defenses?

1) Body surface defenses, 2) inflammation, 3) interferons.

What general property do non-specific defenses recognize on an invader?

A general marker of "foreignness," such as classes of carbohydrates or lipids in microbial cell walls — not the pathogen's specific identity.

What barriers make up the body's first line of defense at its surfaces?

Intact skin, antimicrobial secretions from glands (salivary, lachrymal), sticky antimicrobial mucus lining the respiratory/GI/genitourinary tracts, nasal hairs, cough/sneeze reflexes, and stomach acid.

What triggers the "chemical alarm" step of the inflammatory sequence, and what is released?

Local tissue injury triggers mast cells to release histamine.

In the inflammatory sequence, what happens immediately after the chemical alarm (histamine release)?

Vasodilation — local blood vessels widen to increase local blood flow.

What happens to capillaries during the vascular leakage step of inflammation, and why does it matter?

Capillaries become hyperpermeable and proteins escape into tissue, which contributes to swelling and helps immune mediators reach the site.

What drives chemotaxis during inflammation?

WBCs travel along a chemical gradient (released by damaged tissue, mast cells, and complement fragments) toward the site of injury.

What is margination and diapedesis, and where does it fall in the inflammatory sequence?

The step after chemotaxis, where phagocytes roll along, adhere to, and squeeze through the vessel wall into the tissue at the injury site.

What is the final step of the inflammatory sequence, and how is it accomplished?

Pathogen clearance — active phagocytosis destroys the foreign matter.

Put the inflammatory sequence in order.

Chemical alarm (histamine release) → vasodilation → vascular leakage (protein escape) → chemotaxis → margination and diapedesis → pathogen clearance (phagocytosis).

What are the two overall functions of inflammation?

1) Destroy or inactivate foreign invaders, 2) set the stage for tissue repair.

Which three cell types are the key phagocyte mediators of inflammation?

Neutrophils, macrophages, and dendritic cells.

What are complement proteins, and where are they made?

A group of over 30 plasma proteins, primarily synthesized in the liver, that are a core part of innate immunity and allow extracellular killing of microbes without prior phagocytosis.

What is opsonization, and which complement protein is a key example?

Complement proteins like C3b coat a pathogen's surface, tagging it for recognition and destruction by phagocytes.

How do complement proteins contribute to inflammation?

Small complement fragments act as anaphylatoxins, attracting macrophages and neutrophils to the infection site and enhancing the inflammatory response.

What is the Membrane Attack Complex (MAC), and what does it do?

The terminal product of the complement cytolysis pathway; it punches holes in a pathogen's membrane, causing cytolysis and destruction of the pathogen.

Name the three core functions of complement proteins in immunity.

Opsonization, inflammation, and cytolysis (via the Membrane Attack Complex).

What are interferons, and what is their main antiviral action?

A family of cytokines released by infected cells into extracellular fluid that inhibit viral replication inside host cells and signal neighboring cells to raise their defenses.

### Adaptive Defenses

What two lymphocyte types carry out adaptive immunity, and what type of immunity does each mediate?

B cells mediate humoral immunity; T cells mediate cell-mediated immunity.

Where do B cells mature, and what do they target?

B cells mature in the bone marrow and mediate humoral immunity, targeting pathogens floating in bodily fluids.

Describe the mechanism by which an activated B cell fights a pathogen.

When a B cell recognizes a matching antigen, it clones itself and secretes antibodies into the blood, which attach to and neutralize the pathogen and mark it for destruction.

Where do T cells mature, and what do they target?

T cells mature in the thymus and mediate cell-mediated immunity, attacking cells already infected by a pathogen or that have become cancerous, via direct contact rather than circulating antibodies.

What is the difference between cytotoxic T cells and helper T cells?

Cytotoxic T cells directly destroy virus-infected or cancerous cells by inducing them to self-destruct; helper T cells don't kill directly but coordinate the broader immune response by signaling and activating other immune cells, including B cells.

Put the cell-mediated adaptive response in order.

Antigen presentation → T cell recognition → clonal expansion → target destruction → immunological memory.

In the cell-mediated response sequence, what happens right after antigen presentation?

T cell recognition — the T cell recognizes the presented antigen as foreign.

What is clonal expansion, and where does it fall in the cell-mediated response sequence?

The step after T cell recognition, where the activated T cell proliferates into many identical copies to mount an effective attack, before target destruction occurs.

What is the final stage of the cell-mediated adaptive response, and why does it matter for future infections?

Immunological memory — long-lived memory cells persist for years, allowing faster recognition and elimination if the same pathogen attacks again.

How do vaccines exploit immunological memory?

They introduce antigens (from a non-infectious version of a pathogen) that stimulate the immune system to produce antibodies and memory B/T cells, so the body responds faster and more effectively if it later encounters the real pathogen.

What is the difference between primary and secondary lymphoid organs?

Primary lymphoid organs are sites where lymphocytes are formed and mature; secondary lymphoid organs are filtering stations where mature lymphocytes are activated by antigens to launch an immune response.

A patient asks how a "real" viral infection differs from a normal localized innate + adaptive immune response. How would you explain it?

A normal response is the coordinated, self-limited innate inflammatory cascade plus a targeted adaptive attack that clears the pathogen and resolves; an unchecked/uncontrolled infection reflects the pathogen outpacing or overwhelming these defenses (e.g., evading antigen presentation or replicating faster than clonal expansion can respond), risking systemic spread.

### Factors Affecting Immune Resistance

What is the single greatest contributor to decreased infection resistance worldwide, and why?

Protein-calorie malnutrition — inadequate amino acids impair synthesis of proteins essential for immune function (e.g., antibodies).

How does pre-existing disease (e.g., diabetes mellitus) lower resistance to infection?

Pre-existing disease alters the tissue's chemical environment or interferes with blood supply, and conditions like diabetes impair normal immune/vascular function, predisposing the body to infection.

How does chronic stress affect immune resistance, and what is the key mediator?

Chronic stress triggers continuous release of cortisol, which suppresses WBC function and reduces overall antibody production.

How do positive emotions and strong social connections affect immune resistance?

They boost natural killer (NK) cell activity, enhancing the body's ability to fight viral infections.

How do depression and anxiety affect immune resistance?

They elevate baseline pro-inflammatory cytokines, causing chronic low-grade inflammation that damages healthy tissue and weakens vaccine effectiveness.

What is the "J-curve" relationship between physical activity and infection risk?

Moderate physical activity lowers infection risk below sedentary baseline, but excessive/high-intensity training raises infection risk above baseline — infection risk plotted against activity level forms a J shape.

How does sleep deprivation affect NK cell activity?

It severely drops active NK cell surveillance and reduces cytolytic activity, leaving the body more vulnerable to viruses.

What happens to cytokines during deep slow-wave sleep, and why does it matter?

Protective cytokines (IL-12, IFN-gamma) are up-regulated and pro-inflammatory cortisol is down-regulated, allowing the adaptive immune system to consolidate immunological memory.

What are the consequences of chronic sleep deprivation (

Elevated baseline systemic cytokines (IL-6, TNF-alpha) causing chronic low-grade tissue inflammation, and drastically weakened antibody responses to vaccines.

A stressed, sleep-deprived patient asks how this weakens their defenses before a pathogen even enters the blood. What's the mechanism?

Chronic stress and poor sleep elevate cortisol and pro-inflammatory cytokines systemically, which can impair body-surface barrier integrity and function (e.g., mucosal defenses) and blunt NK cell/antibody readiness — weakening defenses even before an actual exposure occurs.

### Autoimmune — SLE

What is Systemic Lupus Erythematosus (SLE), and what are its three proposed etiologic categories?

An autoimmune disease of unknown, multifactorial etiology: genetic (familial association, no single gene identified), hormonal (higher prevalence in women of childbearing age, suggesting estrogen's role), and environmental (UV radiation, smoking).

What is the first step in SLE pathophysiology, and what does it release?

Increased/dysregulated apoptosis releases nuclear components (DNA, nucleosomes) that are not cleared properly, exposing self-antigens.

In SLE pathophysiology, what happens after apoptosis/antigen exposure?

Loss of self-tolerance — autoreactive T and B lymphocytes fail to distinguish self from non-self and become activated.

What happens after loss of self-tolerance in the SLE cascade?

Autoantibody production — B cells produce large quantities of autoantibodies that bind nuclear antigens.

What happens after autoantibody production in SLE, and what hypersensitivity type does this represent?

Immune complex deposition — antibody-antigen complexes circulate and deposit in small blood vessels of tissues like kidneys, skin, and joints; this is Type III hypersensitivity.

What is the final step of the SLE cascade, and what does it cause clinically?

Inflammation and tissue damage — deposited complexes trigger the complement system, causing severe inflammation, tissue injury, and vasculitis, producing lupus's clinical symptoms.

Put the SLE pathophysiologic cascade in order.

Apoptosis/antigen exposure → loss of self-tolerance → autoantibody production → immune complex deposition (Type III hypersensitivity) → complement activation → inflammation/tissue damage (vasculitis).

Besides Type III hypersensitivity, what other hypersensitivity mechanism contributes to SLE, and what does it cause?

Type II hypersensitivity — antibodies directly bind blood cells (RBCs, platelets, WBCs), causing their destruction and resulting in conditions like hemolytic anemia and thrombocytopenia.

What is the cornerstone long-term therapy for SLE?

Hydroxychloroquine.

What SLE treatments are used for flares/major organ involvement, and for severe renal/neurologic disease?

Glucocorticoids for symptom control and flares (higher doses for nephritis/CNS disease); immunosuppressants (mycophenolate mofetil, azathioprine, cyclophosphamide) for more severe disease, especially renal or neurologic involvement.

### Exaggerated Response — Sepsis

What is sepsis/septic shock, and what are common sources/pathogens?

Life-threatening organ dysfunction caused by a dysregulated host response to infection; common sources include pneumonia, UTIs, abdominal infections, and contaminated surgical wounds/pressure ulcers; caused by gram-positive (e.g., Staph aureus) or gram-negative (e.g., E. coli) bacteria, and sometimes fungi or viruses.

What triggers the cytokine storm in sepsis, and what cytokines are involved?

Pathogens trigger macrophages to release excess TNF-alpha, IL-1, and IL-6 systemically.

What happens after the cytokine storm in the sepsis cascade?

Endothelial damage — these cytokines damage vascular endothelium, causing widespread capillary leak.

What causes the profound blood pressure drop in sepsis, and what mediates it?

Nitric oxide causes profound arterial vasodilation and vascular shunting, leading to a dramatic drop in blood pressure.

What is DIC in the context of sepsis, and what does it cause?

Disseminated intravascular coagulation — hyper-coagulation forms microvascular thrombi that plug capillaries, starving organs of oxygen; the final step of the sepsis cascade.

Put the sepsis pathophysiologic cascade in order.

Cytokine storm (excess TNF-alpha/IL-1/IL-6) → endothelial damage/capillary leak → vasodilation and shunting (via nitric oxide) → blood pressure crash → microvascular thrombi/DIC → organ ischemia.

What is the clinical presentation of early sepsis ("warm shock")?

High fever, severe tachycardia (>90 bpm), tachypnea (>20 breaths/min), flushed warm skin, and rapid capillary refill.

What is the clinical presentation of late sepsis ("cold shock")?

Persistent low blood pressure (MAP

What distinguishes "warm shock" from "cold shock" in sepsis progression?

Warm shock (early) shows fever, tachycardia, flushed/warm skin from vasodilation; cold shock (late) shows hypotension, cool/pale/mottled skin, lethargy, and oliguria as perfusion fails and the body decompensates.

What is the "sepsis bundle," and within what time window should it be initiated?

IV broad-spectrum antibiotics, fluid resuscitation (30 mL/kg), and vasopressors — initiated within 1 hour of suspected sepsis.

As a PT, what should you do if you suspect sepsis in a patient (acute care or outpatient)?

Suspend therapy immediately and call the medical team or 911 — sepsis is a medical emergency.

### Allergies & Hypersensitivity

What happens during the sensitization phase of an allergic response?

The body mistakes a harmless allergen for a threat; immune cells produce IgE antibodies, which bind to (arm) mast cells. No symptoms occur during this phase.

What triggers the effector phase of an allergic response, and what happens?

Re-exposure to the same allergen — it binds directly to the IgE antibodies already on mast cells, causing the mast cells to degranulate and release histamine, producing immediate symptoms (swelling, sneezing, airway constriction).

Put the allergic response in order from first exposure to symptomatic reaction.

Sensitization phase: allergen exposure → IgE antibody production → IgE binds/arms mast cells (no symptoms) → Effector phase: re-exposure to allergen → allergen binds mast-cell-bound IgE → mast cell degranulation → histamine release → symptoms.

What is mast cell degranulation?

The process by which mast cells break down and rapidly release chemical alarms, primarily histamine, into the body.

Compare local mast cell degranulation to systemic degranulation in scope, examples, and medical urgency.

Local: restricted to point of contact/one organ system; examples are hives, localized swelling, hay fever; non-life-threatening, manageable at home/urgent care. Systemic: widespread, affecting multiple organ systems; examples are anaphylaxis/anaphylactic shock; a medical emergency requiring immediate epinephrine.

Compare local vs. systemic mast cell degranulation in terms of blood pressure and airway effects.

Local: normal blood pressure, no widespread vascular changes; mild localized congestion or minor wheezing. Systemic (anaphylaxis): dangerously low blood pressure (hypotension) with system-wide shock; severe throat swelling that can close the airway, with extreme bronchospasm.

A patient develops hives after a bee sting versus another patient who develops throat swelling and hypotension. What's the underlying difference?

Hives reflect local mast cell degranulation confined to the skin (histamine causes local vasodilation/leakage) — not life-threatening. Throat swelling with hypotension reflects systemic degranulation (anaphylaxis) — widespread histamine release causes system-wide vasodilation/capillary leak (hypotension) and airway smooth muscle spasm (bronchospasm) — a medical emergency requiring epinephrine.