Lecture 31; Psychoneuroimmunology Flashcards
What does the immune system also do?
Sense the microbial world
Parallel features to the CNS
Immune system as ‘mobile brain’ - links to CNS and alters what is going on there.
How well are the nervous system and immune system connected?
There are a large number of interconnections.
‘bi-directional information highway’
Both influence one another
What is the neuroimmune network?
Three interlinking pathways; (Highly integrated)
ANS (nerves)
Endocrine system (Hormones)
Immune system (Cytokines) (Nueroimmune hormones)
All interlinked
Note* All Primary and Secondary lymphoid organs are innervated by nerves.
Therefore how we think, feel, behave might influence all these characteristics. (Psycho-neuro-immunology)
What is sickness behaviour?
Common symptoms and behaviours;
- Dont want to exercise
- Dont want to eat
- Dont want to be social
Symptoms;
- Temperature rises
- Pain sensitivity
- Touch sensitivity
- Wish to sleep more
- Desire nurturing
- Perceptions change (tend to catastrophise things)
Is sickness unique to a pathogen or species?
No, found across all species regardless of pathogen
What was the suggested reason for these behaviours and causes of them?
Early signalling in the inflammatory response promotes these behaviours as they improve outcomes.
Promoted by inflammatory cytokines (IL-1, IL-6, TNFα)
These control the neurophysiology in an adaptive way b/c it is useful
What does IL1 do on the nervous system?
- Promotes sickness behaviours
- Increases body temperature
- Increases slow wave sleep
How does IL1 achieve this changes in the nervous system?
- Acts on vagus nerve branches
- Secreted by astrocytes and glial cells (Can act as neurotransmitter)
- Stimulates astroglial proliferation
- Neurotransmitter activity in brain
What is a medical instance where they find altered behaviour post inflammation?
Post Surgical fatigue
Subset of patients have it last far longer
Describe the post surgical fatigue study;
Colorectal surgery patients Fatigue measure (Pen and paper rubic)
24-hour abdominal drain fluid
• Cytokine concentrations (Local)
What cytokines were measured and what did they find?
TNFa
IL6
IL10
Those with higher levels of the cytokines 24hrs post operation had their post surgical fatigue last way longer.
Influence neuroimmune network for long lasting effects
Whats the take home message of the post surgical fatigue study?
More peritoneal cytokines, longer-lasting fatigue
What happens to neurons in the hypothalamus during antibody response?
Neural firing rates:
Increase during peak antibody response
What happens if neurons in the hypothalamus were electrically stimulated?
Electrical stimulation:
Enhances antibody response
What happened to immune function if the brain was lesioned?
Anterior lobe lesions:
- Depress antibody responses
- Alter NK activity
- Alter T cell function
Does the immune system affect hippocampal neurogenesis?
Immune system affects neurogenesis in the brain
i.e
- Immunodeficient = reduction in neurogenesis (thought that microglia influence neurogenesis)
- Inflammation = reduction in neurogenesis. Transition of microglia to inflammatory phenotype. (immune signalling)
- Enriched environment = increased microglia and increased neurogenesis.
What happens to the immune system of a socially inhibited individual?
Increased sympathetic nervous system (SNS) activity
Increased vulnerability
to viral infections (SNS affects immune system?)
Note***
Must be able to draw and annotate lymph node structure as well as other immune organs
Where do nerves innervated lymph nodes?
- All over
- Put particularly in the paracortical area
( T cells, Norepinephrine communicates with immune cells (esp T cells))
What was found when they combined the knowledge of sociability and nervous-immune interactions in the Rhesus macaques?
- Low sociable animals had a far higher density of SNS nerve termini in their secondary lymphoid organs.
=
Sociability affects innervation of lymph nodes
They also found higher concentration of NGF
What happens when they looked at innervation of different areas of the lymph node?
Highest innervation of the paracortical area.
Therefore low sociable macaques have greater SNS (norepinephrine) affects T cells
Therefore change in immune responsiveness
Changes in cellular balance too i.e towards TH2 (therefore more prone to viral infection)
Summerise the ANS + immune + social relationships;
Extensive innervation of lymphoid organs
Predominantly sympathetic (norepinephrine)
Terminate in T cell-rich areas
Density related to social temperament
= Psychosocial factors Immune regulation
How do corticosteroids i.e cortisol affect the neuroimmune system?
- Depress most in vivo immune responses
- Depress phagocytosis
- Inhibit macrophage activation
- Inhibit T and B cell activation in vitro
- Alter lymphocyte trafficking
- Affect thymus cell numbers
Is it just corticosteroids that does this?
No B endorphin is known to do this too.
Prolactin, growth hormone, Catecholamines, Enkephalins
how can the immune system affect the CNS?
- Histamine (Mast Cell)
- Macro (IL1,6, TNFa)
- T Cell ( IL3, IFNg, IL2)
- B cell (b endorphin, ACTH)
Summerise the neuroimmune connection;
There is a flow diagram in the slides, learn it.
Infection or tissue damage
= Proinflam cyotkines
- > Inflammation
- > Adaptive Immune response
- > HPA, Brainstem-vagus, Neocortex-Sam effects
HPA, Brainstem-vagus, Neocortex-Sam effects=
- > Cortisol (-ve, Inflam, Adaptive, Pro cyto)
- > Ach -> Adaptive
- > NE -> Adaptive
- > Energy, Temperature, behaviour change
And it is though that psychosocial factors influence the brain response. (influences recovery from infection)
What happens to people who recieve intentional wounds and were stressed vs werent.
Higher levels of proinflam cytokines of those who were stressed.
Took longer to heal too
‘Therefore perceived stress influences wound healing
