Immunology Quiz: Immune Response Mechanisms

Learning Module 2A: Protection & Comfort

• NUR 370 is the course number
• Rebecca Young, MS, RN, CCRN is the presenter
• The module covers immune and inflammatory responses
• It discusses anti-inflammatory agents and immunizations' role in mitigating inflammation and disease prevention
• It differentiates normal and abnormal autonomic nervous system anatomy and physiology
• It determines the mechanism of action, indications, and expected/unexpected outcomes of medications affecting protection and comfort

Autonomic Nervous System

• The ANS regulates homeostasis through CNS, PNS, and endocrine responses
• Nerve impulses in the PNS travel to the thalamus, medulla, and spinal cord (CNS)
• From the CNS, impulses stimulate organs, glands, and muscles
• The ANS controls blood pressure, heart rate, respiration rate, temperature, fluid status, urinary output, and digestion

Sympathetic Nervous System

• The SNS is the "fight-or-flight" response to stressors
• CNS cells stimulate nerve ganglia in the thoracic and lumbar areas of the spinal cord
• Neurotransmitters released are primarily norepinephrine and epinephrine
• The body prioritizes systems beneficial for survival: heart rate, blood pressure, respiration rate, bronchodilation, pupil dilation, glucose breakdown
• Elimination, digestion, and reproduction slow down

Parasympathetic vs. Sympathetic Nerves

• Parasympathetic: constricts pupils, stimulates saliva, slows heartbeat, constricts airways, stimulates stomach activity, stimulates gallbladder, stimulates intestines, and contracts bladder
• Sympathetic: dilates pupils, inhibits salivation, increases heartbeat, relaxes airways, inhibits stomach activity, inhibits gallbladder, inhibits intestines, and relaxes bladder

Adrenergic/Sympathetic Receptors

• Alpha and Beta receptors respond to circulating epinephrine and norepinephrine (Alpha1, Alpha2, Beta1, Beta2)
• Receptor response varies based on neurotransmitter concentrations
• Some drugs target specific receptors, others stimulate all receptors, resulting in fewer systemic side effects

Adrenergic Agonists (Dopamine, Epinephrine)

• Mechanism of Action: Dopamine increases heart rate, blood pressure, and maintains kidney blood flow (treats shock). Epinephrine causes vasoconstriction, increased heart rate, blood pressure, and bronchodilation (treats shock and severe bronchospasm like asthma)
• Contraindications: Pheochromocytoma, tachyarrhythmias, ventricular fibrillation, and hypovolemia
• Adverse Effects: Effects on the heart (arrhythmias, hypertension, palpitations, angina, dyspnea); GI tract depression (nausea, vomiting, constipation); sympathetic stimulation (headache, sweating, feelings of tension or anxiety, piloerection)
• Pharmacokinetics: Generally administered intravenously (IV) or intramuscularly (IM)

Physiological Effects of Adrenergic Stimulation

• Specific physiological effects occur in response to stimulation of adrenergic receptors: pupils dilate, loss of lens accommodation, decreased salivation and secretions, bronchodilation, increased respiratory rate/depth, increased blood pressure, increased conduction/heart rate, vasoconstriction, and increased blood flow to muscles
• Effects on the GI tract involve decreased pancreatic and gastric secretions, decreased GI motility, and decreased perfusion/spincter contraction. Effects on urinary include decreased renal blood flow, minimal to no uterine activity, and bladder relaxation/sphincter contraction.
• Effects on the reproductive system are minimal to no uterine activity. Genital stimulation is a potential effect of the simulation. The effect on skin is vasoconstriction. Pilo-erection and sweating are also effects that could be a result of stimulation.

Nonselective Adrenergic Blocking Agents (Labetalol)

• Mechanism of Action: Blocks norepinephrine effects on alpha and beta receptors, decreasing heart rate and improving renal perfusion and blood pressure
• Contraindications: Bradycardia, Heart block, Asthma, and caution with diabetic clients (masks hypo/hyperglycemia symptoms)
• Adverse Effects: Bradycardia, hypotension, bronchospasm, and cough
• Client/Therapy Management: Monitor heart rate, blood pressure, and blood glucose levels

Effects of Nonselective Adrenergic Blockers

• Block the effects of the sympathetic nervous system
• Adverse effects include decreased glucose regulation, loss of bronchodilation, decreased venous return, lowered blood pressure, and increased gastrointestinal activity.

Parasympathetic Nervous System

• The parasympathetic nervous system is responsible for the "rest and digest" response.
• Promotes conservation of energy by slowing metabolism and function
• CNS cells in the cranium and sacral areas stimulate nerve ganglia, releasing acetylcholine
• Effects include increased motility and secretions in the GI tract, decreased heart rate, bronchoconstriction, relaxation of sphincters, and pupil constriction.

Cholinergic/Parasympathetic Receptors

• Receptors found in muscle and organs – muscarinic or nicotinic
• Varying response based on neurotransmitter concentrations
• Drugs tend to stimulate all cholinergic receptors.

Direct-Acting Cholinergic Agonists (Bethanechol)

• Mechanism of Action: Mimics acetylcholine to stimulate parasympathetic function, used for urinary retention and atonic bladder
• Contraindications: Bradycardia, hypotension, coronary artery disease
• Adverse Effects: Systemic effects of parasympathetic stimulation, including bradycardia, hypotension, heart block, and bladder spasm
• Pharmacokinetics: Usually administered orally

Effects of Direct-Acting Cholinergic Agonists

• The effects of direct-acting cholinergic agonists include pupil constriction, lens accommodation, lacrimal and salivary secretions, increased secretions, and increased heart rate/contractility/conduction, muscle/sphincter contraction, and vasodilation
• Cholinergic effects can increase secretions (salivation, bronchial secretions, etc.), increase gastrointestinal motility, contract sphincters (GI, urinary), and cause vasodilation.

Anticholinergic Agents (Atropine)

• Mechanism of Action: Blocks acetylcholine receptors, diminishing parasympathetic stimulation
• Contraindications: Glaucoma, paralytic ileus, GI obstruction, benign prostatic hypertrophy, bladder obstruction, cardiac impairments (arrhythmias, tachycardia), and myocardial infarction.
• Adverse Effects: Increased sympathetic responsiveness, blurred vision, photophobia, dizziness, and insomnia; Cardiovascular (tachycardia); Gastrointestinal (dry mouth, altered taste, and constipation); Genitourinary (hesitancy and urinary retention); and decreased sweating/heat tolerance
• Client/Therapy Management: Monitor heart rate and blood pressure, monitor neuro status.

Stress Response

• Homeostasis: Maintaining stable internal environment
• Stress responses should ideally be acute
• Chronic stress leads to immune suppression and increased energy demands.
• Body breaks down; may cause damage.
• Control systems and feedback mechanisms maintain cell function.

General Adaptation Syndrome (GAS)

• The HPA axis plays a large role in the stress response
• Alarm: sympathetic nervous system stimulation—increased heart rate, blood pressure, and epinephrine/norepinephrine/dopamine release
• Resistance: Body's most efficient defenses initiated, and cortisol decreases
• Fatigue: Prolonged or overwhelming stress depletes resources, with systemic damage occurring.

Acute Stress

• Acute and time-limited trigger
• Fight-or-flight response (SNS response)
• Symptoms include pounding headache, increased vital signs, and increased alertness.
• Blood is diverted from less essential organs
• Clients with limited coping may develop stress-related illnesses (anxiety, depression, eating disorders, sleep disorders, high blood pressure (hypertension), and migraine)

Chronic Stress

• Chronic intermittent: repeated exposure of stressors, not dissipated
• Chronic sustained: prolonged exposure to consistent stressors
• Overactive or underactive HPA axis due to neural or hormonal impairments
• Prolonged/overwhelming stressor
• Impacts include cardiac, immune, neurological, gastrointestinal, substance use, and mental health issues.

Inflammatory Response Overview

• Injury to cells or tissues triggers chemical reactions and events.
• The body's goal is to remove the invader, limit tissue damage, and restore homeostasis, occurring in two stages • Vascular Stage: Increased blood flow to injured tissues

• Cellular Stage: Leukocytes (WBCs) move into tissues

Inflammatory Response Cells

• Endothelial Cells: Line blood vessels, permitting selective permeability; vasoconstrict and vasodilate to regulate flow.
• Platelets: Release inflammatory mediators; increase vascular permeability
• Neutrophils: Phagocytic cells that destroy invaders in tissues; leukocytosis is an increased number in the blood during inflammation; lifespan of 10 hours
• Monocytes/Macrophages: Phagocytic cells that destroy invaders in tissues; produce inflammatory mediators

Inflammatory Response (Vascular Stage)

• Initial injury activates the Hageman factor (Factor XII) which triggers the kinin system and the beginning of the vascular stage
• Quick vasoconstriction, followed by vasodilation, occurs from increased blood flow, which causes redness, warmth, fluid leakage, and swelling.
• Bradykinin release causes local vasodilation, increased blood vessel permeability, and pain sensation.
• Cell membrane release arachidonic acid activates chemicals increasing inflammatory responses (prostaglandins, leukotrienes, cyclooxygenase, thromboxanes).

Inflammatory Response (Cellular Stage)

• Vessel lining changes to allow leukocytes to stop and adhere
• Leukocytes migrate from the blood vessel to the injured tissues.
• Leukocytes are drawn to the site of inflammation through chemotaxis.

Pain Summary

• Unpleasant sensation + emotional experience related to actual or potential tissue damage
• When tissues are damaged, cells release chemicals (kinins, prostaglandins) stimulating sensory nerves.
• Classifications:
• Acute pain: surgery, injury, infection
• Chronic pain: constant/intermittent
• Nociceptive pain: direct stimulus to pain receptor
• Neuropathic pain: nerve injury or dysfunction
• Psychogenic pain: emotional, behavioral, psychological factors

Patho of Pain

• Nociception: transmission of unpleasant stimuli to the brain.
• Sensory nerves (a-delta and c-fibers):
• A-delta fibers: fast, myelinated, respond quickly to acute pain
• C fibers: slow, unmyelinated, transmit persistent pain (chronic pain)
• Pain impulses from tissues/organs to the spinal cord
• Larger fibers (large fibers) carry pain information faster; conduct pressure, stretch, and vibration signals quickly. Smaller fibers are less fast.

Gate Control Theory

• Interneurons in the spinal cord can block pain impulse transmission to the brain
• A-fibers (touch fibers) compete with smaller fibers for spinal cord pathways, regulating pain transmission
• Descending impulses from the brain (e.g., cerebral cortex, limbic system, reticular activating system) contribute to modulating pain signals, along with serotonin and norepinephrine.

Pain Pathway

• Tissue injury releases inflammatory mediators, activating nerve fibers.
• Pain signals travel through the dorsal horn of the spinal cord and spinothalamic tracts.
• Reaching the reticular activating system (RAS), signals cause the brain to integrate pain information to contribute to the subjective sensation of pain

Pain Receptors

• Some receptors are specific to stimuli.
• Thermal receptors are sensitive to temperature extremes. Inflammatory mediators perpetuate a loop where the inflammatory mediators from injured tissues stimulate pain receptors, leading to more pain.

Pain Receptors (Opioid Receptors)

• Found in the central nervous system (CNS) and peripheral nerves, also found in GI cells.
• Influence pain signaling, pain modulation, and emotional responses. (modulation of pain responses to endorphins and enkephalins)

Types of Pain

• Acute Pain: Results from tissue injury; resolves once treated. Short duration.
• Chronic Pain: Persistent pain; often musculoskeletal, visceral, or vascular related; caused by stressors (emotional, mental, physical). Lacks typical sympathetic nervous system responses (e.g., decreased appetite, loss of sleep, depression).

Acute vs. Chronic Pain

• Differentiates aspects of acute and chronic pain including the onset, duration, autonomic and psychological response, and other responses

Nonpharmacologic Pain Management

• Question: Examples of nonpharmacological pain management techniques

Opioid Agonist (Morphine)

• Mechanism of Action: Binds to opioid receptors, causing analgesia, sedation, and euphoria.
• Adverse Effects: Respiratory depression, hypotension, constipation, sedation, cough suppression.
• Client/Therapy Management: Monitor sedation, respirations/oxygen saturation, constipation, and dependence.

Opioid Agonist-Antagonist (Buprenorphine)

• Mechanism of Action: Partial opioid agonist action. Stimulates opioid receptors while blocking others.
• Adverse Effects: Respiratory depression, sedation, impaired mentation; withdrawal syndrome possible with switching therapies.
• Client/Therapy Management: Monitor for respiratory rate, oxygen saturation, sedation, and dependence. Avoid sudden switching of pain management regimens.