Neuroimmunomodulation strategy
Focus on enhancing ability of the host, not the pathogen
• Cannot accurately predict how cells will act, b/c denervated cells act different than when they are innervated.
Pathogen-Associated Molecular Patters (PAMPa)
- Molecules commonly seen in pathogens but not the host
- Includes pattern recognition receptors (TLR)
Opsonins
Molecules that prepare a target for being eaten
Presentation done via
- MHC I = endogenous
- MHC II = exogenous
Complement System
The poor man’s antibodies that mark targets for being eaten by phagocytes
- Chemical signals to attract phagocytes
- make Membrane Attack Complexes (MACs) which pole holes in target
commo methods of Nervous, Immune, Endocrine systems
The commonality among the systems is IMFLAMMATORY RESPONSE
- Nervous = neuropeptides
- Immune = cytokines
- Endocrine = hormones
Cytokine Theory of Disease
Health requires that cytokine production is balanced. Low levels are required to maintain homeostasis. Overproduction causes diseases
Cytokines
small proteins used for cell signaling by Immune system that include: “CLIIT”
- Chemokines
- Lymphokines = made my lymphocytes
- Interferons = made by host cells and interfere with pathogen
- Interleukins = first noticed by WBCs
- TNF = causes cell death
Factors that maintain homeostasis
- Humoral factors (glucocorticoids, anti-inflammatory cytokines)
- Cellular factors (regulatory T cells, alternatively activated macrophage)
Components of Neural Reflexes
- Sensory neurons: respond to stimuli
- Interneurons: relay stations
- Motor neurons: transmit information from CNS to periphery
Steps of Neural Reflex
- Sense pathogenic molecule, cytokines, etc
- Brainstem nuclei relay stimulation to efferent response
- Efferent response to principal organs of immune system
Vagal nerve stimulation
- Stimulation cause Vagus nerve to release acetylcholine unto Splenic Nerve
- splenic nerve and releases Norepinephrine unto Choline Acetyl Transferase (ChAT)
- ChAT releases more acetylcholine
- End result = decreases release of antibodies thus decreases allergic response
α7 nAChR (nicotinic acetylcholine receptor)
significantly inhibits cytokine release in macrophages, which are activated by exposure pathogenic product
- All APCS, B cells and T cells, and microglia have these receptors
- end result = decreases release of antibodies thus decreases allergic response
Action of α7 nAChR causes
- Inhibits cytokine release (TNF, NFkB, IL-6, IL-1β, IL-8, PGE-2)
- Decreases microbial killing
- Inhibits degranulation and food allergy
- Inhibits migration and antibody release
Pre/Post ganglionic neurotransmitters released in ANS
Preganglion: both SNS and PNS release ACh Postganglionic:
- SNS releases NE
- PSN release ACh
Adrenergic Receptors
adrenaline (Norepinephrine) binding receptors that include:
- Alpha receptors
- Beta receptors
Acetylcholine receptors
- Muscarinic: G protein complexes stimulated by cholinergic neurons in SNS and PNS. (example Sweat Glands)
- Nicotinic: Ligand gated ion channels in synapse between Pre/Post ganglionic neurons in SNS and
Muscarinic receptors
G protein complexes stimulated by cholinergic neurons in SNS and PNS. (example Sweat Glands
Nicotinic receptors
Ligand gated ion channels in synapse between Pre/Post ganglionic neurons in SNS and PNS
Nicotinic Acetylcholine receptors
- Bind acetylcholine and then change shape
- Forms an ion pore (allow Ca2+ and/or Na+ to flow through)
Migration within secondary lymphoid organs
controlled by neural signals, thus antibody secretions is within neuronal control
Relationship between cytokine level and disease
positive correlation between amount of cytokines released, and severity of disease (eventually death)
Heart rate variability (HRV)
is dependent upon balanced within the autonomic nervous system (SNS vs PNS).
- Increase HRV = increased PNS tone, because PNS wears off faster than SNS, thus continuous PNS stimulation is required
- Chiropractic care significantly improves HRV, my influencing ANS output to the heart.
Heart rate variability relationship with prognosis
heart rate variability is inversely correlated with risk of poor prognosis in cardiovascular disease, diabetes, hypertension, dyslipidemia.
• HRV is positively correlated with, longevity in cancer, better cognitive performance in Alzheimer’s disease
