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Immune- Neuroendocrine Interactions. Behavioral Symptoms “Sickness Behavior”. Restlessness/Inability to Sleep Anxiety Anorexia- ARC Inhibits Decrease in Sex Behavior Animals also show: Reduced Exploration Reduced Learning Withdrawal from Social Interactions. Immune Overview.

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Immune- Neuroendocrine Interactions

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behavioral symptoms sickness behavior
Behavioral Symptoms“Sickness Behavior”
  • Restlessness/Inability to Sleep
  • Anxiety
  • Anorexia- ARC Inhibits
  • Decrease in Sex Behavior
  • Animals also show:
    • Reduced Exploration
    • Reduced Learning
    • Withdrawal from Social Interactions
immune overview
Immune Overview
  • Innate-Macrophages, NTK, Antigen Presenting Cells
  • Adaptive
    • Humoral- B Cells,
    • Cell-Cell
      • Cytotoxic T Cells
      • Th1
      • Th2
the immune system communicates through cytokines
The Immune System Communicates Through Cytokines
  • Macrophages- IL-1, IL-8, TNF-alpha, IL-6, IL-12
  • T Cells- IL-2, 3, 4, 5, GM-CSF, IFN-gamma, TNF-alpha, beta, FAS, IL10, TGF-beta, MCP.
endocrine systems involved
Endocrine Systems Involved
  • Hypothalamus Pituitary Adrenal Axis- Prime axis, negative feedback onto immune system
  • Hypothalamus Pituitary Gonadal Axis- LH, LHRH
  • Thyroid- GHRH
stress affects immune response
Stress Affects Immune Response

Becker, Behavioral Endocrinology,

Second Edition. Ch 10, Coe, fig 6.

where can immune system act
Where Can Immune System Act?
  • At Brain
    • Dispute over how and where IL-1 Acts.
    • PVN involved
  • Pituitary- Anterior Cultures respond to IL-1
  • Adrenal Gland- Cultures do seem to respond to high IL-1 levels.
hpa feedback onto immune
HPA feedback onto immune
  • IL-1 chief responder
  • PVH center
  • Cfos studies
  • Activity of IL-1
    • Brainstem inputs
    • Circumventricular organs
    • Endothelial- Neuropil interactions
experimental paradigms
Experimental Paradigms
  • Immunological Stressors Include
    • IL-1
    • IL-2, IL-6
    • Graft Tissue
    • Lippopolysaccharide (LPS)- Gram Negative Bacterial Extracellular Matrix
  • Measure
    • Hormone Levels
    • cFos activation
taste and superantigen pairing induce immune conditioned response
Taste and Superantigen Pairing induce Immune-Conditioned Response
  • Conditioning: CS and CSo groups got saccharin and ip SEB. P got sac and ip saline. UCS water and ip saline.
  • Evocation: CS and P sac, ip saline. CSo got water and ip saline. UCS water and ip SEB.
why does hpa have negative feedback on immune system
Why does HPA have negative Feedback on Immune System?
  • Anaphylaxis
  • Toxic Shock??? Macrophage Cytokines induce HPA activity. Not as often T-Cell cytokines/responses, ie Graft Experiments, do not induce HPA activity
  • Pathology includes, chronic stress, rundown, etc.
pvh responds to il 1
PVH Responds to IL-1

cFos activation in

PVH after IL-1 Injection

COX Inhibitor

Blocks response

pvh neuron subtypes
PVH Neuron Subtypes
  • IL-1 Activated Cell Types
  • Oxytocin
  • Vasopressin
  • Corticotropin Releasing Factor
il 1 induces crf release
IL-1 Induces CRF Release
  • A) Saline
  • B) Colchicine Control
  • C) Saline + Colchicine
  • D) IL-1 + Colchicine
crf released by il 1
CRF Released by IL-1
  • Colchicine (axonal transport inhibitor) treated ME shows that CRF magnocellular terminals are depleted by IL-1 (Berkenbosch, 1991)
  • Anti-CRF serum injected with IL-1 blocks ACTH release
il 1 other responsive nuclei
IL-1 Other Responsive Nuclei
  • BNST
  • Ventrolateral Medulla
  • Central N. of Amygdala
  • Thalamus
  • OVLT
  • AP
  • Forebrain
the vasculature endothelial responders to il 1
The Vasculature:Endothelial Responders to IL-1

Cox-2, an inflammatory protein is induced

By LPS, and IL- 1 beta.

Others argue PGE Synthase acts as a

Molecular Switch

brainstem inputs
Brainstem Inputs

Figure from Previous Studies, lesions to brainstem input eliminated

IL-1 induced cFos Expression in PVN

hpg axis
HPG Axis
  • Decreases in T leads to decreased platelette aggregation. Thromboxanes
  • IL-1 Seem to be due to Hypothalamic Response
  • However, CRF can inhibit GnRH release
hpt axis
HPT Axis

Both TSH and T4 levels decrease

After IL-1 Stressor.

immunity varies across lifespan
Immunity Varies Across Lifespan

Becker, Behavioral Endocrinology,

Second Edition. Ch 10, Coe, fig 12.