Week 4 Lecture Notes: Immune & Inflammatory Responses

Immune Response

  • 1st Line of Defense: Surface barriers (skin, mucous membranes), secretions (lysozymes, tears, gastric acid).

  • 2nd Line of Defense: Non-specific, specialized cells/processes (phagocytes, dendritic cells, NK cells, macrophages), chemicals (cytokines, histamines), acute inflammatory response.

  • 3rd Line of Defense: Specific = lymphocytes (T cells - cellular immunity, B cells - humoral immunity).

    • B-lymphocytes: antibody-mediated immunity; produce antibodies —> bind to unwanted substances against extracellular pathogens. Think: B for antibody

    • T-lymphocytes: cell-mediated immunity; defend against intracellular pathogens and cancer. —> kill off unwanted substances

Innate vs. Adaptive Immunity

  • Innate Immunity (1st & 2nd Defence):

    • Non-specific.

    • In-built; present at birth.

    • Immediate response.

    • No antibodies produced; not antigen-specific.

    • No memory.

    • Can be inherited.

  • Adaptive Immunity (3rd Line Defence):

    • Specific.

    • Acquired; develops over lifespan.

    • Slower response than innate.

    • Antigen-specific; antibodies produced.

    • Memory cells formed.

    • Cannot be inherited.

Inflammatory Response

  • Non-specific, first-line defense to cell injury.

  • Purpose: neutralise agent, prevent further damage, clean up tissue for healing.

  • Causes: trauma, heat, chemicals, infection.

  • Beneficial effects: prevents spread of damage, disposes of debris/pathogens, alerts adaptive immune system, sets stage for repair.

Types of Inflammation

  • Acute:

    • Continues until threat is eliminated (8-10 days). Think: Acute = rapid

    • Example: superficial graze.

  • Chronic:

    • Persistence of infection, antigen, or foreign body. Think: Acute = slow and dragged on

    • Dense infiltration of lymphocytes and macrophages.

    • Example: rheumatoid arthritis.

  • Granulomatous:

    • Contains infection or damaged site. Think: Trap the infection

    • Mass of immune cells (macrophages). —> isolate the irritant that cannot be eliminated

    • Example: tuberculosis granulomas.

Acute Inflammatory Response (AIR) Cardinal Signs

  • Redness: increased blood flow (vasodilation).

  • Heat: increased blood flow.

  • Swelling: increased blood and fluid (increased vessel permeability).

  • Pain: swelling activates pain receptors.

Inflammatory Chemicals and Their Roles

  • Histamine: Vasodilation, increases capillary permeability. Remember: Opens the blood vessels

  • Kinins: Vasodilation, chemotaxis of leukocytes —> migration to affected site, induce pain. Remember: Induces pain

  • Prostagladins: Neutrophil chemotaxis, induce pain (some are anti-inflammatory). Remember: Neutrophils, pain, fever and inflammation

  • Interferons: Signal viral presence to adaptive immune response. Remembers: Interfere with viruses

  • Complement: Lyses microorganisms, enhances phagocytosis, intensifies immune responses. Remember: Complement/enhance immune responses

  • Cytokines: Regulate immunological responses and cell communication. Remember: Coordinate immune response

Thermoregulation and Fever

  • Normal body temperature: 36.5C - 37.6C

  • Regulated by hypothalamus, endocrine and sympathetic nervous systems.

  • Hypothermia: Core temperature less than 36C

    • Mild: 34C - 36C

    • Moderate: 30C - 34C

    • Severe: Less than 30C

Heat Promoting Mechanisms:

  • Constriction of cutaneous blood vessels.

  • Increase in metabolic rate.

  • Shivering.

  • Thyroxine release. —> controls metabolic rate

  • Behavioral modifications (clothing, posture).

  • Hyperthermia: Elevated body temperature.

  • Fever: Abnormally high body temperature; systemic response to microorganisms.

Heat Loss Mechanisms:

  • Dilation of cutaneous blood vessels.

  • Enhanced sweating.

  • Behavioral modifications (reducing activity, seeking cooler environment).

Pathogenesis of Fever:

  • Exogenous pyrogens —> microbes outside the body; trigger release of endogenous pyrogens in leukocytes and macrophages.

  • Endogenous pyrogens —> host immune cells inside the body; act on hypothalamus.

  • Prostaglandins released, raising the body’s set point.

  • Heat-producing mechanisms activated.

Fever - Benefits:

  • Kills microorganisms.

  • Decreases iron, zinc, copper levels.

  • Prevents viral replication.

  • Improves immune response.

Fever - Risks:

  • Stress on the body; damage if sustained temperature > 41C

  • Death > 43C

  • Febrile seizures (> 39C) in young children.

Pain

  • Nociceptive pain —> pain caused by damage to the tissue; is a protective mechanism.

    • Manifestations include increased heart rate, hypertension, diaphoresis —> excessive sweating, and dilated pupils.

  • Somatic pain: skin, joints, muscles. Remember: skin, tissues, muscles

  • Visceral pain: internal organs; poorly localized. Remember: V for very deep = internal organs

  • Referred pain: felt in an area removed from origin. Remember: R for redirected

  • Chronic pain: lasts >3-6 months.

Acute vs. Chronic Pain

  • Acute Pain:

    • Identifiable precipitating event.

    • Decreases over time.

    • Sympathetic nervous system activation (increased heart rate, respiratory rate, blood pressure).

  • Chronic Pain:

    • May not be known.

    • Pain does not go away.

    • Predominantly behavioural symptoms (flat affect, decreased physical activity, fatigue).

Pain Physiology:

  • Transduction: Stimuli can cause release of sensitizing chemicals that activate nociceptors —> via conversion into electrical signals. Think: pain is created

  • Transmission: Action potential from injury site sent to spinal cord, brainstem/thalamus, then cortex. Think: pain is sent

  • Perception: Conscious experience of pain. Think: pain is felt

  • Modulation: Neurons inhibit nociceptive signals. Think: pain is managed

Pain Pathways:

  • First-order neurons (nociceptors) transmit signals from periphery to dorsal horn of spinal cord.

  • Second-order neurons (spinothalamic tract) relay information from spinal cord to hypothalamus Think: hence “spino-thalamic tract”

  • Third-order neurons (thalamocortical neurons) relay information from thalamus to cerebral cortex. Think: hence “thalama-cortical”

  • Dermatomes: area of skin supplied by a single spinal nerve.

Pain Assessment (PQRSTU):

  • P: Provoking/Palliative factors.

  • Q: Quality.

  • R: Region/Radiation.

  • S: Severity.

  • T: Timing/Duration.

  • U: Understanding.

Pain Management:

  • Non-opioids, opioids, adjuvant analgesics, NSAIDS.

  • Non-pharmacological (hot/cold packs, massage, relaxation, exercise).

WHO Analgesic Ladder:

  • Evaluate effectiveness of therapies.

  • Manage medication side effects.

  • Incorporate patient and carer education.

  • Step 1: Mild pain

    • Non-opiod analgesics

    • i.e. Paracetamol, NSAIDs

  • Step 2: Moderate pain

    • Weak opiod + non-opiod

    • i.e. Tramadol, paracetamol + codeine

  • Step 3: Severe pain

    • Strong opiod + non-opiod

    • i.e. Morphine, fentanyl, oxycodone

Antipyretics & Analgesics

Paracetamol:

  • Trade Names: Panadol, Tylenol, Panamax, Dymadon

  • Indications: Fever, mild-moderate pain

  • Mechanism of Action: Inhibits peroxidase, reducing COX activity.

  • Side Effects: Liver injury with overdose.

Ibuprofen:

  • Class: NSAID

  • Trade Names: Neurofen, Advil, Motrin, Caldolor

  • Indications: Pain (especially inflammation), fever

  • Mechanism of Action: Inhibits prostaglandin synthesis by inhibiting COX.

  • Side Effects: Nausea, GI ulceration, hypertension.

Morphine:

  • Class: Opioid analgesic

  • Trade Names: Morphine sulfate, Zomorph, Sevredol, Morphgesic, MXL, Oramorph.

  • Indications: Severe pain

  • Mechanism of Action: Acts on mu-opioid receptors in CNS.

  • Side Effects: Nausea, vomiting, drowsiness, constipation, respiratory depression.

Antiemetics

Metoclopramide:

  • Trade Names: Maxolon, Metozolv, Reglan.

  • Indications: Nausea and vomiting

  • Mechanism of Action: Blocks dopamine receptors in CTZ and increases GI motility.

  • Side Effects: Restlessness, drowsiness, diarrhea.

Ondansetron:

  • Trade Names: Zofran, APO-Ondansetron.

  • Indications: Nausea and vomiting (chemotherapy, postoperative).

  • Mechanism of Action: Blocks 5-HT3 receptors in the CTZ.

  • Side Effects: Flushing, dry mouth.

Peptic Ulcer Disease (PUD)

  • injury to the digestive tract caused by peptic acid

  • Results from imbalance betwbloatedness acid pepsin and mucosal defense barriers

  • Associated with H. pylori infection and NSAID over-use.

  • Symptoms: Epigastric pain improved with food/antacids, excessive bowel gas, and bloatedness.

  • Diagnosis: Urea breath test, stool antigen test, endoscopy with biopsy.

  • Treatment: Antibiotics (for H. pylori), proton pump inhibitors (PPIs), H2 receptor antagonists, stopping NSAIDs.

  • Complications: Gastrointestinal bleeding, perforated ulcer, gastric outlet obstruction, gastric malignancy.