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Host Defense Exam 2 (by Richie) > L28: Psychoimmunology > Flashcards

L28: Psychoimmunology Flashcards

1
Q

The connection of the central nervous system (CNS) to the immune system involves two pathways:

A

 Direct (neuronal)

 Indirect (neuroendocrine).

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2
Q

The most direct (neuronal) is the innervation of

A

primary (thymus, bone marrow) and secondary (e.g. spleen) lymphoid organs as well as the adrenal medulla.

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3
Q

In an indirect (neuroendocrine) manner…

A

the CNS communicates hormonally with the immune system.

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4
Q

These connections are activated by physical and/or psychological stressors that cause the release of neuropeptides and neurotransmitters in the brain such as:

A

Catecholamines
GABA
ACh
5-HT

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5
Q

These stimulate cells in the ___________ of the hypothalamus to synthesize and release _________ into the portal blood system of the pituitary.

A
  1. paraventricular nucleus (PVN)

2. corticotrophin releasing hormone (CRH)

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6
Q

In the anterior lobe of the pituitary gland, CRH stimulates the synthesis and release of ________ into the peripheral circulation.

A

adrenocorticotropic hormone (ACTH)

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7
Q

ACTH ultimately causes the release of _________ into the circulation.

A

the glucocorticoid (cortisol) from the adrenal gland (adrenal cortex)

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8
Q

Most cells of the immune system are sensitive to cortisol and are_______ in their function by cortisol.

A

inhibited

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9
Q

Bone marrow, spleen, thymus, lymph nodes are innervated primarily by ________ secreting peripheral nerves

A

NE

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10
Q

Moreover, the adrenal medulla is innervated directly by

A

sympathetic nerve fibers (with ganglia in the hypothalamus).

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11
Q

When stimulated, the hypothalamus activates the _______, which in turn trigger ________ cells of the adrenal medulla to secrete
__________

A

splanchnic nerves, chromaffin, catecholamines

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12
Q

T- and B- lymphocytes, neutrophils, mononuclear cells, and NK-cells possess receptors for ____________. Their effect on lymphoid tissue is dependent on the type of cell receiving the signal.

A

catecholamines, ACh, and neuropeptides.

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13
Q

Cortisol is best known for

A

(1) metabolic effects (increasing gluconeogenesis)
(2) anti-inflammatory effects (reducing cytokine production, T and B cell reactivity and NK cell activity)
(3) modulate the processing of information from the sense organs.

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14
Q

Epinephrine and norepinephrine act as neurotransmitters in the CNS and are released into the circulation by the adrenal medulla, which has what effect on immune cells?

A

Increases leukocyte MOBILIZATION, resulting in an increase in NK cell activity.

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15
Q

Endorphins originate from a precursor molecule called

A

pro-opiomelanocortin (POMC)

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16
Q

POMC is synthesized in the pituitary after stimulation by ____

A

CRH

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17
Q

POMC can also be synthesized outside of a. pituitary by

A

immune competent cells.

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18
Q

Endorphins play an important role in ___________.

A

analgesia and feelings of happiness (euphoria)

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19
Q

In the pituitary the POMC molecule is enzymatically split into the secretory products

A

ACTH, endorphin (and don’t forget a-MSH from endocrinology)

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20
Q

Enkephalins are produced in

A

The brain, pituitary, and adrenal gland (simultaneously with epinephrine and norepinephrine) when stimulated, and play a role in analgesia.

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21
Q

Enkephalins can bind the same receptors as

A

endorphins

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22
Q

Endorphins and enkephalins increase reactivity of what two immune cells?

A

Endorphins promote T cell reactivity and NK cell activity.

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23
Q

Endorphins act more like hormones, while enkephalins act more like

A

neurotransmitters.

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24
Q

_____ is one of the most frequently mentioned psychological factors that may modulate the immune system.

A

Stress

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25
Q

Stress is conceptualized as either a ______ or a ______.

A

Stimulus, response

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26
Q

An individual _______ a situation as either a challenge or a threat (stressor), dependent upon the individual’s ________ (resources, social support, coping abilities, etc.).

A

appraises, adaptive capabilities

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27
Q

Any demand-capability imbalance leads to

A

the perception of stress and the stress response (i.e., activation of the nervous system and the neuroendocrine pathways described above).

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28
Q

Stressors can differ in

A

type (physical or psychological), intensity, and duration (acute versus chronic).

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29
Q

2 Types of stress

A

Acute controllable emotional or mental stress.

Chronic uncontrollable negative stress.

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30
Q

The effect on circulating NK cells is reproduced by the administration of

A

epinephrine or norepinephrine.

31
Q

Catecholamine (Epi) and cortisol (Cort) induces localization of mononuclear cells to

A

the lymph nodes

32
Q

Immediate leukocyte mobilization in the circulation is due to

A

catecholamines (epinephrine and norepinephrine).

33
Q

Under the influence of catecholamines and cortisol, leukocytes redistribute to the

A

lymph nodes where they can respond quickly to antigenic (infectious) challenge.

34
Q

Redistribution to the lymph nodes is a consequence of hormonal modification of adhesion molecules on the surface of the leukocytes such as _____________, and activation of cognate adhesion molecule _________ on the surface of endothelial cells

A

CD11a, ICAM-1

35
Q

Low cortisol concentrations (as a consequence of acute stress) has an what effect on DTH (TMMI) response?

A

enhances DTH response

36
Q

High cortisol concentrations (as a consequence of acute stress) has an what effect on DTH (TMMI) response?

A

depresses DTH response

37
Q

Effect of chronic stress (extending for several days or weeks) on DTH?

A

Depresses it

38
Q

Chronic uncontrollable negative stress like caregiving to the chronically ill (e.g.
Alzheimer’s patients) can cause

A

immune suppression.

39
Q

sickness behavior symptoms

A

Symptoms like fever, headache, muscle and joint pain, diminished appetite, lethargy..

40
Q

what cytokines are associated with sickness behavior

A

IL-1, IL-6, and TNF

41
Q

Cytokines like _____________ change the firing frequencies of nerve cells in the CNS and influence the secretion of neuroendocrine factors of the hypothalamus-pituitary-adrenal gland axis, especially _____ production.

A
  1. IL1, IL6, TNF

2. ACTH

42
Q

Receptors for cytokines (eg. IL1, IL6, TNF) have been found in the

A

CNS and pituitary gland.

43
Q

In addition to making IL1, IL6, TNF, leukocytes are capable of neuropeptide and neurotransmitter production.
Activation of T- and B-lymphocytes can stimulate these cells to produce:

A

ACTH
Beta-endorphin
Enkephalins.

44
Q

The production of endorphins and enkephalins by activated immune cells may induce an

A

analgesic effect in infected tissue.

45
Q

The production of these cytokines, hormones, neurotransmitters, and neuropeptides may modulate on-going immune or inflammatory responses and may also influence/induce behavioral changes, known as

A

sickness behavior.

46
Q

Cytokines produce sickness behavior symptoms by two known means:

A
  1. Via the circulation

2. Via afferent neurons (i.e., vagal).

47
Q

Via the circulation, IL1 IL6 and TNF cytokines cross the BBB most likely through the circumventricular organs (CVO) and neurons in this area express receptors for IL- 1, TNF, and IL-6. Interaction of these cytokines with their cognate receptors results in

A

neural system activation and the production of prostaglandins.

48
Q

Via the _____ , IL-1 produced by leukocytes stimulates the related regions of the brain.

A

vagal afferents

49
Q

Thus these molecules, as part of the immune system, alert the brain to

A

infection or injury, communicating the body’s distress.

50
Q

Inflammation, mediated by IL-1, IL-6, and TNF, is necessary for protection from microbial pathogens. However, excessive production of these cytokines can result in

A

systemic inflammation that can result in organ failure and death.

51
Q

The CNS interacts with the immune system to regulate excessive inflammation via what 2 nerves?

A
  1. the efferent vagus

2. and the splenic nerve.

52
Q

Action potentials transit the splenic nerve releasing ____ , which stimulates the production of _______ by T lymphocytes (via surface beta 2 adrenergic receptors).

A

NE, ACh

53
Q

ACh interacts with macrophages (via ________ receptors) within the spleen and INHIBITS transcription of _________ (for simplicity only TNF is presented in Figure 11). Thus controlling the production of these proinflammatory cytokines.

A
  1. surface alpha 7 ACh

2. IL-1, IL-6, and TNF

54
Q

Splenic n. dumps NE on what kind of receptor, on T-lymphocytes?

A

B2AR

55
Q

Effective immune responses require significant mobilization of

A

energy and resources.

56
Q

In addition to mobilizing immune response, the immediate stress response is also associated with the mobilization of energy to enable

A

the body to deal with a threat or danger.

57
Q

In a ‘fight or flight’ situation, energy is diverted to

A

the muscles, heart rate increases, and the body is made ready for physical action and increased sensory performance.

58
Q

The mobilizations of energy for immune function and for fight or fight responses, however, are

A

roughly opposite! Energy cannot be diverted in both directions simultaneously.

59
Q

So after the immediate release of _________, which mobilize the leukocytes of the immune system, the immune response is temporarily suppressed by the slower release of _____, in order to maximize energy for the fight or flight response.

A

catecholamines, cortisol

60
Q

This is achieved by cortisol production (that is normally used by the body to ________).

A

slow down immune system activity

61
Q

This slow release of cortisol is a HIGHLY ADAPTIVE RESPONSE TO SHORT-TERM STRESSORS where the body may soon resume normal immune function. It becomes disadvantageous when _____________

A

stress responses are maintained over longer periods of time.

62
Q

Although the word ‘stress’ generally has negative connotations, stress is a familiar aspect of life, being a stimulant for some, but a burden for others. It is often overlooked that, an acute stress response can have______ (health promoting) effects.

A

salubrious

63
Q

The ________ of a stressor is thought to be important when considering its impact on individuals.

A

duration

64
Q

The timing of the stressor and the nature of the stressor (acute versus chronic) determine the __________

A

magnitude of the immune response.

65
Q

Differences exist in the ways that acute (short-term) and chronic (long-term) stressors affect the immune system. For example, chronic stress significantly _______ delayed-type hypersensitivity (DTH) responses (e.g. to skin test) and ______ leukocyte mobilization to the skin

A

suppresses, decreases

66
Q

Acute stress ______ the DTH response and increases __________ mobilization

A

enhances, mobilization.

67
Q

So although stress is typically thought to be immunosuppressive, acute stress can result in __________, but alternatively could contribute to _________

A
  1. immune enhancement that can promote protection from infections
  2. the exacerbation of immunopathology.
68
Q

In response to immunological challenge, acutely stressed individuals show …

A

significantly greater leukocyte infiltration, enhanced production of chemokines (chemoattractant proteins for leukocytes), IL-1, IL-6, TNF and IFN gamma (proinflammatory and Th1 cytokines).

69
Q

Further, acute stress enhances maturation and trafficking of _______ to sites of antigenic challenge.

A

dendritic cells (DCs)

70
Q

DCs are efficient antigen presenting cells (APCs) and these APCs effectively promote the activation and recruitment of T lymphocytes during initial antigen challenge, inducing a ______. The result would be subsequent augmentation of the immune response during secondary antigen exposure.

A

long-term increase in immunologic memory

71
Q

Thus, the evolutionarily adaptive fight-or-flight stress response may prepare the immune system for _______.

A

impending danger (e.g. infection and wounding by a predator). The result would be enhanced immunological protection from the infectious agent and more rapid healing of the wound.

72
Q

However, stress could also exacerbate a pathological condition that is worsened by an increased immune responsiveness such as

A

an autoimmune response or an inflammatory insult or disease condition.

73
Q

Moreover, inopportune stress could contribute to the ______ of a pathological or autoimmune condition if it occurred at an inopportune period of significant insult.

A

initiation

74
Q

Cytokines responsible for the fever, headache, muscle and joint pain, diminished appetite, lethargy, and weakness associated with infection are:

A. IL-1, IL-6, TNF.
B. IFN alpha, IFN beta, IFN gamma.
C. G-CSF, M-CSF, GM-CSF.
D. IL-12, IL-15, IL-18.
E. IL-4,IL-5,IL-10.
A

A

Host Defense Exam 2 (by Richie) (15 decks)

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