Sympathetic v Parasympathetic nervous system
- SNS: fight or flight response, relax lungs, dilate eyes
- PNS: rest and digestion, vagal nerve & vagal tone often considered, slows heartbeat
- Acetylcholine (ACh)
- Epinephrine & Norepinephrine: adrenergic receptors (alpha and beta), alpha adrenergic receptors located in vasculature, GI tract.
- Beta adrenergic receptors located in heat, salivary glands, smooth muscle, and adipose tissues.
- Not: in addition to release from adrenal glands, SNS also triggers release of norepinephrine from nerve terminal with some spill over.
- Wide ranging location of receptors allow wide ranging effects of ANS.
- Blood borne chemical messengers
- Produced by endocrine glands and other organs and cells (eg heart, immune cells)
- Act on target tissues with specific hormone receptors
3 broad categories of hormones
- Steroid hormones: synthesised from cholesterol. Carried by protein. Long lasting effects. Long half life.
- Adrenal cortex hormones: glucocorticoid (cortisol) and aldosterone
- Gonadal hormones
- Protein hormones: chains of amino acids
- Short= thyrotropin releasing hormone (TRH)
- Long= growth hormone (GH)
- Amines: derivatives of amino acids
- Catecholamines: epinephrine (E), Norepinephrine (NE). High impact but tend to be short lived
- Thyroid hormone
Hormone production is regulated by
- Circadian rhythms: 24 hour rhythm guided by internal clock and by external cues
- Negative feedback: hormone inhibits release of its releasing factor. Stops release of itself at some point
Hypothalamic-pituitary-adrenal (HPA) axis
- Hypothalamus (brain- pituitary (brain)- adrenal gland (torso)
- Activated in response to stress and results in the release of glucocorticoids that serve to regulate the physiological stress response.
- A way of shutting down stress process.
- Hormonally mediated activity, so slower than neurally mediated stress responses.
H secretes releasing and inhibiting factors:-corticotrophin releasing hormone (CRH): produced by neurons in paraventrivular nucleus of hypathalamus. Acts as neurotransmitter and neuropeptide.Luteinizing hormone releasing hormone (LHRH)Thyrotopin releasing hormone (TRH)Growth hormone releasing hormone (GHRH)Growth hormone inhibiting factor (GHIF)Dopamine
HPA: pituitary gland
- Separated into anterior and posterior
- Posterior pituitary:
- Oxytocin: milk ejection, uterine contractions during labor
- Role in bonding
- Vasopressin: antidiuretic hormone
- Anterior pituitary:
- Connected to hypothalamus via system of blood vessels known as hypothalamic-hypophyseal portal system.
- Adrenocorticotrophic hormone (ACTH): secreted by corticotrophs; derived from POMC, cleaved by CRH into ACTH, beta endorphin and other peptides
CRH turns the other molecules into something else like ACTH
HPA: adrenal glands
- Adrenal medulla: secretes epinephrine and norepinephrine (catecholamines) (relevant to SNS)
- Adrenal cortex: secretes glucocorticoids, mineralocorticoids, and sex steroids (relevant to HPA)
- Up to 95% of secreted cortisol is bound to large proteins including corticosteroid binding globulin (CBG) and albunim, and carried in the body through the blood. (needs to be unbound for it to work)
- Enters all tissues: passes through parotid gland to saliva; through kidney to urine and through blood-brain barrier.
- Salivary cortisol is unbound (biologically active)
- Adrenal steroids have receptors in every nucleated cell:
- -MR (stronger affinity) compared to GR (low affinity)
- After binding, receptors moves into nucleus and regulate gene expression
Cortisol two families of functions
- 1. Metabolic and diurnal functions (sleep, metabolism). Highest wake up then going down, spikes after food
- Driven by signal and hypothalamus
- Highly sensitive to negative feedback control
- 2. Stress functions: secretion enhanced by input from amygdala
- Negative feedback less effective
- During stress, numerous effects:
- Permissive: GCs present before stressor, prime response
- Stimulating: Increases in GCs enhance effects of first wave hormone response
- Suppressive: increase in GCs rein in stress-induced defense reactions
- Preparative: modulate response to subsequent stressor.
- Enhance SNS effects on cardiovascular stress response
- Increase circulating glucose
- Overall suppress immune response, but permissive on initial activation
Acts as a break
Cortisol negative feedback loop
- Hippocampus activates hypothalamus which releases CRF, goes to anterior pituitary to release ACTH, goes to adrenal cortex and releases cortisol.
- Cortisol in addition to effects on tissues, also has negative impact on anterior pituitary and hypothalamus.
HPA axis is measured via
- Wake level and before sleep. (If slope flat, due to constant stress)
- Average 24 sample
- Urine: accumulation of cortisol in urine
- Total daily cortisol
- Overnight/24 hour cortisol
- Diurnal cortisol rhythm
- Morning rise
- Response to acute stress
- Sensitivity tests
- -> dexamethane (synthetic glucocorticoid) give it to them, see what happens when give cortisol
- -> how much less cytokines blood releases when GC is added.
- The immune system generally serves to:
- Discriminate self from non-self
- Destroy and clear foreign substances
- Ignore self, possibly destroy altered self (tumor cells)
- Antigen= any substance that can be identified by the immune system
- Pathogen: microorganisms that can cause disease when they enter the host
- Phagocytosis: ingestion of matter by cells
Innate vs adaptive immune response
- Innate: Fast, non specific. Phagocytosis, inflammation
- Adaptive: slow, specific. Recognised by B and T cells
White blood cells (WBCs)
- Also known as leukocytes
- 3 types
- 1. Granulocytes:
- Neutrophils: 50-70% of circulating WBC. Phagocytosis and activation of bacterial mechanisms.
- Eosinophils: 1-3% killing antibody-coated parasites.
- Basophils = <1%% of circulating WBC
- 2. Monocytes 1-6% of circulating WBC
- Early immune response including phagocytosis and antigen presentation.
- Macrophages are mature monocytes in tissue
- Dendritic cell: antigen uptake in peripheral sites. Antigen presentation in lymph nodes
- 3. Lymphocytes:
- 1. Natural killer (NK) cells= 5-10% of lymphocytes: plays role in innate immunity against virally infected cells
- B cells= 10-15% of lymphocytes
- T cells= 75-80% lymphocytes
- Helper T cells (CD4)
- Cytotoxic T cells (CD8) kills the bacteria
- Called t cells because produced in thymus
- Immune cells communicate with each other and with other cells by releasing soluble proteins called cytokines.
- Many different types of cytokines, produced by many different types of cells, with wide variety of biological effects, target cells, receptors, and molecular structures.
- Produced during innate and adaptive immune responses, serve to mediate and regulate immune and inflammatory responses
- Generally, cytokines are produced briefly and locally, in a self limiting manner.
- Cytokines are extremely potent, activity needs to be carefully regulated
- Typically produced rapidly and have short half life, inherently limiting effects
- Activity is modulated by:
- Receptor antagonists
- Cytokine binding serum proteins and/or soluble receptors
- Other cytokines with antagonistic effecrs
- Cytokine receptor expression.