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Immune- Neuroendocrine Interactions

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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  1. Immune- Neuroendocrine Interactions

  2. 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

  3. Immune Overview • Innate-Macrophages, NTK, Antigen Presenting Cells • Adaptive • Humoral- B Cells, • Cell-Cell • Cytotoxic T Cells • Th1 • Th2

  4. 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.

  5. Endocrine Systems Involved • Hypothalamus Pituitary Adrenal Axis- Prime axis, negative feedback onto immune system • Hypothalamus Pituitary Gonadal Axis- LH, LHRH • Thyroid- GHRH

  6. Stress Affects Immune Response Becker, Behavioral Endocrinology, Second Edition. Ch 10, Coe, fig 6.

  7. 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.

  8. HPA feedback onto immune • IL-1 chief responder • PVH center • Cfos studies • Activity of IL-1 • Brainstem inputs • Circumventricular organs • Endothelial- Neuropil interactions

  9. 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

  10. 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.

  11. 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.

  12. PVH Responds to IL-1 cFos activation in PVH after IL-1 Injection COX Inhibitor Blocks response

  13. PVH Neuron Subtypes • IL-1 Activated Cell Types • Oxytocin • Vasopressin • Corticotropin Releasing Factor

  14. IL-1 Induces CRF Release • A) Saline • B) Colchicine Control • C) Saline + Colchicine • D) IL-1 + Colchicine

  15. 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

  16. IL-1 Other Responsive Nuclei • BNST • Ventrolateral Medulla • Central N. of Amygdala • Thalamus • OVLT • AP • Forebrain

  17. 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

  18. Brainstem Inputs Figure from Previous Studies, lesions to brainstem input eliminated IL-1 induced cFos Expression in PVN

  19. 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

  20. Immune Cells Secrete NE Hormones • POMC in B lymphocytes

  21. HPT Axis Both TSH and T4 levels decrease After IL-1 Stressor.

  22. Immunity Varies Across Lifespan Becker, Behavioral Endocrinology, Second Edition. Ch 10, Coe, fig 12.

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