PPY 400: Unit 2 - Inflammation and Immune Pathology

PPY 400: Unit 2 - Inflammation and Immune Pathology

• Course covers Chapters 5, 6, and 4
• Topics include inflammation and the immune system

Immune System

• Structures include skin, mucous membranes, monocytes, macrophages, lymphoid system (spleen, thymus gland, lymph nodes), and bone marrow
• WBCs (leukocytes) mediate inflammation and immunity, locating and eliminating pathogens and foreign molecules
• Two defense types:
  • Innate: no prior exposure, NK cells and phagocytic cells (neutrophils and macrophages) respond to various antigens
  • Specific: more effective with repeated exposure, recognizes specific antigens, involves B cells and T cells

Inflammation

• Occurs when cells are injured, regardless of the cause, initiating a protective healing mechanism
• Purpose of inflammation:
  • Neutralize/destroy harmful invading agents
  • Limit the spread of harmful agents to other organs
  • Prepare damaged tissue for repair
• Common signs include redness, swelling, heat, pain, and loss of function. "-itis" is used to describe inflammation (e.g., tendonitis, appendicitis), but infection isn't always the cause.
• Inflammation can be caused by exogenous sources (surgery, trauma, burns) or endogenous sources (e.g., tissue ischemia from a heart attack (MI))
• Acute inflammation lasts less than two weeks, chronic inflammation is widespread, lasts longer, may cause scarring/deformity

Process of Inflammation

• Includes increased vascular permeability, recruitment and emigration of leukocytes, and phagocytosis of antigens and debris
• Immediately after injury, precapillary arterioles around the injury vasoconstrict briefly to reduce blood loss

Stages of Inflammation Process

• Increased Vascular Permeability: Histamine, prostaglandins, bradykinin, and leukotrienes released by mast cells at the injured site cause vasodilation, increasing blood flow and capillary permeability, pushing fluid into surrounding tissues, contributing to swelling, heat, redness, and pain. The accumulated fluid is called exudate.
• Emigration of Leukocytes:
  • Selectins allow neutrophils to stick to receptors along capillary walls.
  • Integrins help neutrophils to stick and roll along endothelial surfaces, enhancing binding affinity.
  • Chemokines enhance binding to help neutrophils firmly attach to vessel walls.
  • Neutrophils squeeze through interstitial fluid to inflamed tissue is called diapedesis.
  • Chemotaxis involves neutrophils being attracted by damaged tissues from chemicals (e.g., bacterial toxins, etc).
  • Neutrophils are important in phagocytosing dead tissue and producing collagenase
  • Monocytes, eosinophils, and NK cells contribute to inflammation, destroying infected tissues.
• Phagocytosis: Neutrophils and monocytes (macrophages) begin the phagocytosis process, digesting proteins via, lysozymes, neutral proteases, collagenase, elastase, acid hydrolyases
• Pus forms from a collection of dead neutrophils, bacteria, and cellular debris at the injury site
• Macrophages last longer than neutrophils, have a role in removing old neutrophils and preparing the site for healing

Acute vs. Chronic Inflammation

• Acute inflammation resolves quickly (typically less than 3 months) when tissue heals
• Chronic inflammation lasts longer than several months; can occur after expected healing time.
• Typical signs of chronic inflammation include symptoms not typically associated with an acute inflammatory response
• common causes or acute inflammation include migraines and headaches.

Other Types of Pain

• Cancer-related pain: a subcategory of chronic pain. This can involve acute pain episodes from tumor infiltration, compression, or treatment side effects.
• Neuropathic pain: a complex, disabling chronic pain resulting from nerve damage, not from stimulation of pain receptors. Causes can involve injury, surgery, high blood glucose, viruses, etc.
• Ischemic pain: a form of pain induced from a sudden or profound loss of blood flow to tissues. Often accompanied with symptoms like an aching, burning or prickling pain. The pain is often resolved as blood flow improves.
• Referred pain: Involves pain being experienced in an area different from where a tissue injury occurs because pain pathways overlap. Similar nerves are implicated in two distinct pain-related areas.

Types, Stages, and Treatments for Excessive Immune Responses (Autoimmunity and Hypersensitivity)

• Autoimmunity: Immune system attacks its own tissues due to misidentification as foreign, causing tissue damage. Autoimmune disorders are not well understood.
• Hypersensitivity: Normal immune response triggers an excessive reaction, can harm healthy tissues in response to normal stimulus.
• Common causes include allergic reactions. and food allergies
• Treatment involves immunosuppressive therapy, adjusted for each patient according to disease.
• Treatments include corticosteroids and cytotoxins to inhibit excessive immune responses or limit immune functions. Cytotoxins kill actively growing lymphocytes, and corticosteroids reduce the number of lymphocytes.

Deficient Immune Responses

• Result from reduced immune system components.
• Primary immunodeficiency disorders (PID): Congenital (at birth) or acquired (such as HIV/AIDS) issues with immune cell function
• Secondary immunodeficiency disorders: Due to non-immune system factors (e.g., malnutrition, stress, or medications).

Pain

• Pain includes physiological mechanisms, commonly known as nociception
• 4 stages of nociception:
  • Transduction
  • Transmission
  • Perception
  • Modulation

Nociception: Transduction

• Converting painful stimuli into neuronal action potentials at the sensory receptor
• Nociceptors, pain receptors in skin, muscle, connective tissues and other organs, are stimulated by noxious stimuli.
• Nociceptors convert these stimuli into action potentials
• Chemicals like potassium, hydrogen ions, lactate, histamine, serotonin, bradykinin, and prostaglandins stimulate nociceptors.

Transmission

• Movement of action potentials along sensory neurons from peripheral receptors to the spinal cord and brain
• Includes Ad and C fibers
  • Ad fibers are larger, myelinated, carry pain information quickly and localized.
  • C fibers are smaller, unmyelinated, transmit pain slowly, and encompass a wider pain area, often associated with more diffuse achy feelings.
  • Transmission can involve collateral branches spreading up and down the spinal cord via Lissauer’s Tract, leading to reflex action. Spinal neurons synapse on other neurons/interneurons. Neurotransmitters/neuropeptides, like Substance P, glutamates, GABA and cholecystokinin are released between synapses. These chemicals pass the signal on to the next neuron.
• Pain signal travels up the anterolateral tract to the brain (also known as the spinothalamic tract). Signals cross to the opposite side of the spinal cord and travel up to the brain.
  • Two divisions exist in the anterolateral tract:
    • Neospinothalamic division: Includes Ad fibers that quickly transmit localized pain information directly to thalamus for processing with limited emotional component.
    • Paleospinothalamic division: Includes C fibers that send pain information slowly to multiple widespread areas of the brain, often associated with more significant emotional responses.
      • includes areas like the reticular formation, mesencephalon (midbrain), cerebral cortex, limbic system and basal ganglia.

Perception

• Brain interprets pain signals as painful sensations
• Factors influencing pain perception include attention, distraction, anxiety, fear, prior experiences, and expectations.
• Includes the primary somatosensory cortex, association areas, frontal lobe and limbic structures

Perception of Pain

• Pain threshold: the level of painful stimulation required to be perceived (relatively similar across individuals)
• Pain tolerance: degree of pain an individual bears before seeking relief (varies significantly)
• Pain expression: how individuals communicate pain experience to others (can include facial expressions, cries, groans, etc)

Modulation

• Complex mechanism altering synaptic transmission of pain signals
• Multiple sites and varying mechanisms exist along the pathway
• Includes rubbing, shaking, or pressing to reduce painful stimulus. The gate control theory suggests larger myelinated fibers help close the gate, stopping nociceptor impulses
• Descending pathways from the brain and brainstem (e.g., Raphe magnus) can inhibit pain transmission
• Opioids (like endorphins and morphine-like drugs) inhibit the release of Substance P from nociceptors, reducing pain transmission.
• During pain and stress, the body modulates sensations via serotonin, endorphins, and norepinephrine

Nociceptive Inhibition

During pain and stress, serotonin, endorphins, and norepinephrine produce analgesic effects ("stress-induced analgesia").

• Endogenous opioids (like enkephalin) inhibit the release of Substance P, which stops pain signaling.

Explore the intricate details of inflammation and immune pathology in PPY 400. This quiz covers key concepts from Chapters 4, 5, and 6, focusing on the immune system's structure and the processes underlying inflammation. Test your knowledge on innate and specific immune responses as well as the role of various cells in defense mechanisms.