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PHYSL 403/503 NEIM > Module 8 - Endocrine control of Immune Function > Flashcards

Module 8 - Endocrine control of Immune Function Flashcards

1
Q

Insulin secretion by pancreatic beta cells is primarily regulated by the _______ in the extracellular fluid bathing the beta cells

A

Insulin secretion by pancreatic beta cells is primarily regulated by the glucose level in the extracellular fluid bathing the beta cells

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2
Q

________ activation triggers increased expression of insulin receptors

A

lymphocyte activation triggers increased expression of insulin receptors

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3
Q

Other than glucose level in extracellular fluid, what modulates insulin secretion?

A

Sympathetic nerve stimulation and norepinephrine inhibit insulin production

Parasympathetic activity, growth hormone and prolactin stimulate insulin release

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4
Q

What is the purpose of increased expression of insulin receptors following lymphocyte activation in response to exposure to antigen?

A

Helps to augment glucose uptake by these immune cells which supports their metabolic needs

May also directly support growth/differentiation (eg of T-cells in response to antigen)

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5
Q

_______ has been shown to have an anti-inflammatory effect

A

Insulin

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6
Q

What is the relationship between vitamin D and the immune system?

A

Vit D deficiency is associated with impaired immune responses – increased susceptibility to infection

Vit D promotes early immune response

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7
Q

What part of immune response does Vit D contribute to?

(5)

A

Early immune response:

  • ↑ differentiation, phagocytic activity and cytotoxicity of macrophages (via ↑IL-1 prod)
  • Antibody production and fxn
  • ↑Ab receptor expression on lymphocytes
  • ↑Inflammatory response
  • Inhibits over-activity by inhibiting t-cell proliferation
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7
Q

What part of immune response does Vit D contribute to?

A

Early immune response:

  • ↑ differentiation, phagocytic activity and cytotoxicity of macrophages (via ↑IL-1 prod)
  • Antibody production and fxn
  • ↑Ab receptor expression on lymphocytes
  • ↑Inflammatory response
  • Inhibits over-activity by inhibiting t-cell proliferation
    • *
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8
Q

The _____ contains the largest population of endocrine cells in the body

A

The GI tract contains the largest population of endocrine cells in the body

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9
Q

Endocrine cells in the GIT are located among the _________

A

Endocrine cells in the GIT are located among the epithelial cells of the gut mucosa

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10
Q

Endocrine cells in the GIT release:

A

Substances that can act locally or systematically upon entering circulation

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11
Q

95% of the _____ in the body is gut-derived

A

95% of the serotonin (5-HT) in the body is gut-derived

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12
Q

Serotonin (5-HT) in the gut can induce production of ________ to promote _______

A

Serotonin (5-HT) in the gut can induce production of IL-1beta by macrophages to promote GIT/systemic inflammation

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13
Q

IL-1beta vs IL-1?

A

IL-1beta thought to be more potent proinflammatory cytokine than IL-1

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14
Q

_______ released by the stomach stimulates appetite and growth hormone release

A

Ghrelin released by the stomach stimulates appetite and growth hormone release

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15
Q

How does ghrelin provide a link between the GIT and neuroendocrine regulation of immune function?

A

Ghrelin → ↑GH release

GH has a supportive effect on immune function

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16
Q

What contributions does the cardiovascular system make to endocrine regulation?

A
  • Peptides released by heart, vascular epithelium serve as endocrine signals capable of influencing immune responses
    • (eg ANP (atrial natriuretic peptide) released in response to stretch of atrial muscle has been found in immune tissues (thymus, spleen and lymph nodes)
      • receptors for ANP found on leukocytes
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17
Q

ANP released by________ in response to _______

Role in Immune function?

A
  • Atrial natriuretic peptide released by heart, vascular epithelium in response to stretch of atrial muscle has been found in immune tissues (thymus, spleen and lymph nodes)
    • receptors for ANP found on leukocytes
    • ANP functions as a vasodilator in response to increased BP
    • Enhanced production of reactive oxygen species (ROS) by neutrophils
    • augments (↑) NK cells activity
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18
Q
  • Atrial natriuretic peptide (ANP) has been found in which 3 immune tissues?
    • receptors for ANP found on ______
A
  • Atrial natriuretic peptide (ANP) has been found in which 3 immune tissues?
    • Thymus, spleen, lymph nodes
      • receptors for ANP found on leukocytes
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19
Q

High levels of ANP have _______ effects by blocking __________

A

High levels of ANP have anti-inflammatory effects by blocking pro-inflammatory cytokine effects on vascular permeability

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20
Q

ANP modifies ______ production favouring _______ responses

Reduces ______ proliferation

A

ANP modifies cytokine production favouring anti-inflammatory responses

Reduces T-cell proliferation

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21
Q

All together, ANP supports _____ of immune responses and also functions to __________

A

All together, ANP supports initial stimulation of immune responses and also functions to contain the extent of these responses as a protective measure

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22
Q

Why is adipose tissue considered an endocrine organ?

A

Releases multitude of bioactive factors

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23
Q

White adipose tissue is predominant in adults and is composed of ______ and _______

A

White adipose tissue is predominant in adults and is composed of adipocytes and macrophages

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24
Q

White adipose tissue is a major contributor to _______ states and is a source of ________

A

White adipose tissue is a major contributor to low grade inflammatory states (characteristic of obesity) and is a source of pro-inflammatory cytokines (IL-1, IL-6, TNFalpha)

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24
Q

White adipose tissue is a major contributor to _______ states and is a source of ________

A

White adipose tissue is a major contributor to low grade inflammatory states (characteristic of obesity) and is a source of pro-inflammatory cytokines (IL-1, IL-6, TNFalpha)

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24
Q

White adipose tissue is a major contributor to _______ states and is a source of ________

A

White adipose tissue is a major contributor to low grade inflammatory states (characteristic of obesity) and is a source of pro-inflammatory cytokines (IL-1, IL-6, TNFalpha)

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25
Q

What are two hormones that stem from the adipose tissue?

A

Leptin and Adiponectin

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26
Q

Leptin from adipose tissue has what effect on immune response

A

Leptin is proinflammatory and promotes Th1 predominance

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27
Q

Effect of adiponectin from the adipose tissue on immune response?

A

Anti-inflammatory effects (release of adiponectin is inversely related to circulating IL-6 levels)

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28
Q

release of adiponectin from adipose tissue is inversely related to circulating ____ levels

A

release of adiponectin from adipose tissue is inversely related to circulating IL-6 levels

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29
Q

6 contributions to immune regulation from increased glucocorticoid levels

A
  • Inhibition of cytokine production
    • esp pro-inflammatory cytokines
  • Inhibition of lymphocyte proliferation
  • Death of immune cells
  • Lymphoid tissue involution
  • down-regulating antibody receptors on phagocytes
  • Inhibition of fever
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30
Q

Explain inhibition of lymphocyte proliferation by glucocorticoids

A
  • T-cells, NK cells, monocytes, macrophages
  • Typically occurs after inhibition of lymphokine production
  • Reduction of cell numbers not due solely to cell death
31
Q

Describe lymphoid tissue involution by glucocorticoids?

A

Death of immune cells BUT NOT stromal cells

32
Q

How do glucocorticoids down-regulate antibody receptors on phagocytes

A

via diminished release of certain cytokines (eg interferon IFN)

33
Q

How do glucocorticoids mediate inhibition of fever?

A

via diminished IL-1 production

34
Q

Inflammation can be detrimental:

  • ________ released during phagocytosis may damage healthy cells
  • Loss of fluid from the _______
    • increase ______ slowing blood flow and clogging capillaries with stagnant RBCs
    • may result in ______
A

Inflammation can be detrimental:

  • lysosomal hydrolases released during phagocytosis may damage healthy cells
  • Loss of fluid from the microvasculature
    • increase blood viscosity slowing blood flow and clogging capillaries with stagnant RBCs
    • may result in ischemia(because of decreased blood flow)
    • Compromise CV function
35
Q

_________ suppress inflammation

A

adrenal steroids suppress inflammation

36
Q

How do glucocorticoids control the extent of inflammation? (6)

A
  • Inhibition of histamine/serotonin production and release (vasodilators)
  • Stabilization of lysosomal membranes
  • Maintenance of vascular responsiveness to catecholamines
  • Inhibition of arachidonic acid formation and increased arachidonic acid metabolism
  • Inhibition of bradykinin release from damaged tissues
  • inhibition of enzymes
37
Q

Explain how glucocorticoids inhibit histamine/serotonin production and release and the result of this inhibition

A
  • From granulocytes/mast cells/macrophages
  • Thereby preventing vasodilation, diapedesis and damage to tissues and blood vessels

diapedesis=The movement or passage of blood cells, especially white blood cells

38
Q

Explain how glucocorticoids maintain vascular responsiveness to catecholamines

A
  • vasoconstriction counteracts local vasodilation caused by inflammatory mediators
    • decreases blood flow
    • limiting availability of fluid to form exudates
  • Swelling reduced because arterial constriction decreases capillary and venule pressure and facilitates reabsorption of extracellular fluid
39
Q

Describe the glucocorticoid mediated inhibition of arachidonic acid formation and increased arachidonic acid metabolism

A

Inhibition of phospholipase A2 and prostaglandin production - thereby reducing chemotaxis

40
Q

How do glucocorticoids mediate inhibition of bradykinin release from damaged tissue?

A

bradykinin triggers the complement cascade; blocking bradykinin will impair complement cascade

41
Q

How does glucocorticoids inhibition of enzymes mediate inflammation?

A

plasmin/collagenase secreted by granulocytes/mast cells/macrophages

By inhibiting plasmin/collagenase prevents damage to tissues and blood vessels

42
Q

What is glucocorticoid resistance?

A

In response to chronically elevated glucocorticoid concentrations, some immune cells (particularly those involved in inflammation) exhibit down regulation of glucocorticoid receptors (alters responses)

= decrease in sensitivity of some immune cell populations to glucocorticoid hormones that would normally terminate an inflammatory response

43
Q

Inappropriate inflammation linked to onset or progression of _________ or ________ diseases

A

Inappropriate inflammation linked to onset or progression of autoimmune or chronic diseases

44
Q

Increased sympathetic nervous system activity independently stimulates _____

A

Increased sympathetic nervous system activity independently stimulates inflammation

45
Q

Control of stress responses and in turn sympathetic NS activity and glucocorticoid levels can help preserve _____ and help maintain the _____ of glucocorticoids in controlling inflammation

A

Control of stress responses and in turn sympathetic NS activity and glucocorticoid levels can help preserve cellular glucocorticoid sensitivity and help maintain the protective effects of glucocorticoids in controlling inflammation

46
Q

How does the inhibition of histamine/serotonin production and release by glucocorticoids control inflammation?

A
  • typically released by granulocytes (like neutrophils) as well as mast cells and macrophages
  • Histamine and serotonin are vasodilators = vasodilation is a hallmark of inflammation
  • preventing his/serotonin = limit extent of vasodilation → limit the stretching of capillary walls → helps prevent diapedesis of immune cells into tissue → prevent damage to tissues and blood vessels
47
Q

How does stabilization of lysosomal membranes help in glucocorticoid-mediated control of inflammation?

A
  • Prevents release of hydrolytic enzymes from lysosomes that can damage healthy tissues
48
Q

Glucocorticoids maintain vascular responsiveness to catecholamines; how does this control inflammation?

A
  • critical
  • elicits vasoconstriction to counter local vasodilation induced by mediators like histamine and serotonin
  • vasoconstriction of arterioles reduces blood flow to downstream capillaries which reduces availability of fluid to leave the capillaries and enter the tissues as an exudate
  • Vasoconstriction - added effect of promoting fluid reabsorption from the tissues into the vasculature = relieves tissue swelling and protects Blood volume and cardiovascular function
49
Q

Glucocorticoid-mediated control of inflammation:

Inhibition of arachidonic acid formation and increased arachidonic acid metabolism:

A
  • Inhibition of Phospholipase A2 by coritsol
    • Phospholipase A2 enzyme which converts Phospholipids to Arachidonic acid
    • Arachidonic acid is converted to prostaglandins
    • Prostaglandins are notoriously involved in perpetuating inflammatory response and have variety of actions including vasodilations and participate in pain
    • THUS BY INHIBITING ARACHIDONIC ACID PRODUCTION, GLUCOCORTICOIDS INHIBIT PROSTAGLANDIN PRODUCTION
50
Q

How do aspirin-like drugs mediate inflammation?

A

These drugs block action of cyclooxygenase which is required to convert arachidonic acid to endoperoxides which are converted to prostaglandins

ie aspirin-like drugs prevent prostaglandin production

51
Q

Prostaglandins have ______ properties; reducing prostaglandin production by inhibiting arachidonic acid formation will reduce _____ migration of immune cells (hallmark of inflammation)

A

Prostaglandins have chemotactic properties; reducing prostaglandin production by inhibiting arachidonic acid formation will reduce chemotactic migration of immune cells (hallmark of inflammation)

52
Q

Glucocorticoid-mediated control of inflammation:

Bradykinin

A
  • Glucocorticoids inhibit release of bradykinin from damaged tissues
  • Bradykinin is big contributor to inflammation and pain and is a trigger for the complement cascade
  • inhibiting bradykinin → contains inflammatory response
53
Q

Glucocorticoid-mediated control of inflammation:

Inhibition of enzymes

A
  • Glucocorticoids inhibit release of certain enzymes such as plasmin and collagenase which are released by granulocytes/mast cells/macrophages
    • These enzymes have the potential to damage healthy tissues and blood vessels
54
Q

What is the main goal of glucocorticoid-mediated control of inflammation?

A

To allow the healing benefits while preventing “collatoral damage”

55
Q

In chronic stress, inflammation is heightened but glucocorticoids are also increased, why isnt inflammation suppressed?

A
  • After prolonged exposure to high [glucocorticoid], immune cells lose sensitivity to this hormone
    • Glucocorticoid receptor downregulation
      • Glucocorticoid resistance
56
Q

What is glucocorticoid resistance?

A

Chronically high [glucocorticoid] leads to downregulation of glucocorticoid receptors on immune cells → reduced sensitivity to glucocorticoids

ie decrease in sensitivity of some immune cell populations to glucocorticoid hormones that would normally terminate an inflammatory response

57
Q

What is the effect of aging on endocrine and immune systems?

A

↑age → ↓efficiency of endocrine and immune systems

58
Q

In some cases, with aging, basal levels of some hormones may NOT decline but _______ responses do decline and receptors may be _______

A

In some cases, with aging, basal levels of some hormones may NOT decline but secretory responses do decline; receptors may be downregulated

59
Q

______ and _____ cell function are not impaired by age

A

B-cell and macrophage cell function are not impaired by age

60
Q

All _____ and _____ cells exhibit reduced efficiency with respect to aging

A

All T-cells and NK cells exhibit reduced efficiency with respect to aging

61
Q

Effect of aging on the thymus?

A

During aging, the thymus undergoes progressive involution

62
Q

During aging, the thymus undergoes progressive involution

Leads to:

A

Increased incidence of infectious and neoplastic diseases in the elderly

63
Q

The thymus is a ________ gland located in the ________ above the _____

A

The thymus is a two-lobed gland located in the chest above the heart

64
Q

What are the roles of the two regions of the thymus

A
  • One in which the t-cells mature
  • one containing epithelial cells which secrete the thymus hormones
65
Q

Why is the thymus gland called the master gland of the immune system?

A

thymic hormones are essential for both cell-mediated and humoral immune responses

Facilitate production of T-cell precursors in the bone marrow

Regulated differentiation of T-cell precursors into helper, cytotoxic, or suppressor t-cells in the thymus gland

activate mature t-cells in the spleen and lymph nodes

66
Q

Five functions of thymic hormones:

A
  • Facilitate production of T-cell precursors in the bone marrow
  • Regulated differentiation of T-cell precursors into helper, cytotoxic, or suppressor t-cells in the thymus gland
  • activate mature t-cells in the spleen and lymph nodes
  • Mobilize NK cells
  • Stimulate release of cytokines
67
Q

What happens if the thymus gland is absent at birth?

A

T-cells fail to develop and the infant lacks the ability to cope with viral/bacterial infections

68
Q

How does the thymus gland change with age

A
  • Size increases until puberty
  • After puberty the thymus begins to decline in size and function
69
Q

What might be the cause of the decline in size and activity of the thymus gland after puberty?

A

The decline in size and activity of the thymus gland might be due to the immunosuppressive actions of glucocorticoids which increase with time and age

70
Q

What is thymic involution?

A

The decline of the size of the thymus gland

71
Q

How can thymic involution be reversed?

A

Can be restored by neuroendocrine manipulation such as treatment with GH or PRL

  • GH and prolactin (PRL) stimulate thymus growth and function to the point that these hormones have been referred to as “the fountain of youth”
72
Q

With advancing age, thymic involution occurs which is accompanied by:

A

With advancing age, thymic involution occurs which is accompanied by: reduction in the circulating thymic hormones

Causes gradual decline in cell-mediated immunity

Linked to increase in age-related diseases

73
Q

Explain the image:

A
  • As we move from left to right we see gradual thymic involution (top)
  • Accompanied by reduction in circulating thymic hormones (serum thymus factor)
  • Causes gradual decline in cell mediated immunity (thymus dependent immunity)
    • Linked to increase in age-related diseases (cancer and infectious disease)
      • normally low in early years save for a small blip accounting for incidence of childhood diseases
74
Q

Which three major hormones are reduced with age?

A
  • ↑age → :
    • ↓efficiency of cortisol feedback
    • ↓GH
    • ↓Gonadal steroids
75
Q

What does the decreased efficiency of cortisol feedback with aging cause?

Leads to:

Characterized by:

A
  • Leads to hypersecretion of glucocorticoid and the glucocorticoid cascade
  • Characterized by altered immune function and heightened inflammation
76
Q

Which hormone(s) are increases as age increases?

A

↑age → ↑LH/FSH

(↓immune stimulation in aging females int he absence of estrogen; increased inflammation in males)

77
Q

↑age → ↑LH/FSH

Effect?

A
  • ↓immune stimulation in aging females in the absence of estrogen
  • increased inflammation in males
78
Q

Why is there an increase in LH/FSH with age?

A

↑age → ↓gonadal steroids

  • Gonadal steroids (estrogen/testosterone) releases negative feedback of the gonadotropins (LH/FSH)
  • Low estrogen/testosterone → high LH/FSH (because reduced negative fb)

PHYSL 403/503 NEIM (3 decks)

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