Immune Function and Sleep

Immune Function and Sleep Lecture Notes

Overview of Immune Function

  • The immune system is a complex network of cells, tissues, and organs.

  • Purpose: To defend the body against harmful invaders such as:

    • Pathogens (including bacteria, viruses, fungi).

    • Cancer cells.

    • Toxins.

Functions of the Immune System

  1. Protection Against Infections

    • Detects and neutralizes harmful microorganisms and pathogens, preventing infections.

  2. Inflammatory Response

    • Triggers inflammation to heal wounds and clear damaged cells, facilitating tissue repair and recovery.

  3. Immunological Memory

    • Remembers past infections, enabling a quicker and more efficient response upon subsequent encounters with the same pathogens.

  4. Recognition and Elimination of Abnormal Cells

    • Identifies and destroys abnormal or cancerous cells to prevent malignancy.

Types of Immunity

Innate Immunity

  • Characterized by a rapid non-specific response against pathogens.

  • Key components:

    • Mucous Membranes: Serve as a protective barrier against the colonization of bacteria and microorganisms.

    • Skin: Functions as an anatomical barrier providing physical blockade against pathogens.

Adaptive Immunity

  • Involves a slower targeted response against specific pathogens.

  • Key components:

    • Blood: Contains circulating defense cells like B lymphocytes and antibodies; antibodies bind and neutralize foreign antigens.

    • Tissue: Specialized cells (e.g., T lymphocytes) that can differentiate and respond to foreign antigens.

    • Cellular Components: Includes circulating cells such as macrophages and neutrophils, crucial for initiating an immune response.

    • Bone Marrow: Source of hematopoietic stem cells, crucial for the formation of various immune cells.

Peripheral Immune Cells

  • Derived from precursor cells in the bone marrow:

    • Granulocytes: Eosinophils, basophils, and neutrophils.

    • Monocytes/Macrophages.

    • Lymphocytes: B and T cells.

    • Natural Killer (NK) Cells.

Immune Response and Sleep

  • Strong links exist between circadian rhythms and the immune system, with both innate and adaptive immune cells displaying diurnal rhythms.

  • Changes observed in immune cell responses during active and rest phases.

    • Green Arrows: Indicate increase in specific immune responses.

    • Red Arrows: Indicate decrease in specific immune responses.

Role of Microglia in the Central Nervous System (CNS)

  • Microglia: Specialized immune cells acting as the primary defense in the brain and spinal cord.

    • Functions include monitoring and responding to pathogens, damaged cells, and debris.

    • Shape changes based on functionality.

Measures of Microglia Morphology

  • Scientists measure microglial shape to determine activation.

    • Reactive Microglia: Have shorter branches and larger round cell bodies.

Impact of Sleep on Microglial Responses

  • Research measured microglia in freely moving mice using green fluorescent protein and EEG/EMG to monitor sleep/wake states.

    • During NREM (Non-Rapid Eye Movement) and REM sleep, microglial processes lengthened and the distance microglia traveled increased, indicating increased survey behavior compared to wakefulness.

Effects of Sleep Deprivation

  • Sleep deprivation causes microglia to alter to a reactive morphology, becoming activated with shorter branches and rounder shapes.

Sleep-Promoting Neurochemical Agents

  • Pro-inflammatory Cytokines: Critical signaling molecules of the innate immune system that regulate NREM sleep.

    • Examples include:

    • Interleukin-1β (IL-1 β): Induces NREM sleep and inhibits REM sleep by affecting wake-active neurons in the preoptic area.

    • Tumor Necrosis Factor-alpha (TNF-α): Stimulates IL-1 production and also increases NREM sleep.

Cytokines and Sleep Dynamics

  • Cytokines are small signaling proteins released by immune cells that stimulate the immune response and can regulate sleep.

  • Sleep, particularly slow-wave sleep, triggers cytokine release that helps coordinate immune response.

  • Conversely, infections can trigger the release of excessive cytokines (e.g., from macrophages and microglia).

Study on Cytokines

  • Acute Total Sleep Deprivation Study on adult rats showed increased cytokine levels in plasma and cerebrospinal fluid (CSF) during sleep deprivation, indicating immune signaling pathway activation.

Effects of Sleep Deprivation on Antibody Response

Influenza Vaccination Study

  • Sleep deprivation prior to immunization led to significantly fewer antibody titers, indicating weakened immune response.

Hepatitis A Vaccination Study

  • Antibody titers were significantly lower in participants who were sleep deprived the night after vaccination compared to those who slept normally.

Hepatitis B Vaccination Study

  • Participants with longer habitual sleep durations had higher antibody responses, with those sleeping more than 7 hours per night achieving greater clinical protection compared to short sleepers.

Summary of Immune Function and Sleep

  • Illustrates a bi-directional relationship between sleep and immune function:

    • Immune dysregulation can lead to disturbed sleep.

    • Sleep disturbances can exacerbate inflammatory responses and contribute to pathophysiology.

  • Under healthy conditions, sleep supports proper immune function by maintaining homeostasis and facilitating healthy cytokine production and immune cell migration.

  • Inflammatory triggers promote immune cell entry into the brain, resulting in reactive microglia and excessive cytokine production, leading to disrupted sleep, which in turn heightens inflammation and cytokine levels.