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Host Defense Exam 2 > Psychoneuroimmunology > Flashcards

Psychoneuroimmunology Flashcards

1
Q

What is psychoneuroimmunology (PNI)?

A

mechanisms by which the nervous system (including the brain, neurotransmitters and the neuroendocrine
system) and the immune system (including lymphoid organs, cell types, and cytokines) communicate with one another

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2
Q

What are the two pathways that connect the immune system to the CNS?

A

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

indirect (neuroendocrine): CNS communicates
hormonally with the immune system

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3
Q

What is the immune/CNS connection activated by, and what mediates the response?

A

physical and/or psychological stressors which cause the release of neuropeptides and neurotransmitters in the brain such as

catecholamines
GABA
serotonin
ACh

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4
Q

What does neuropeptides/transmitter release activate, and what does it release?

A

the PVN of the hypothalamus to synthesize and release CRH, stimulating release of ACTH, resulting in the release of cortisol from the adrenal cortex

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5
Q

What effect does cortisol have on the immune system?

A

most cells of the immune system are sensitive to cortisol and are inhibited in their function by it

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6
Q

What fibers stimulate the bone marrow?

A

bone marrow primarily stimulated by noradrenergic fibers

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7
Q

What fibers stimulate the thymus?

A

noradrenergic, cholinergic, and peptidergic fibers

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8
Q

What fibers stimulate the spleen?

A

spleen is strongly noradrenergic

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9
Q

What fibers stimulate the lymph nodes?

A

lymph nodes receive noradrenergic and peptidergic stimulation

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10
Q

What does the contact between lymphoid cells and nerve endings resemble?

A

it’s synaptic-like

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11
Q

What is the adrenal medulla innervated by?

A

directly innervated by sympathetic nerves with ganglia in the hypothalamus

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12
Q

What do T and B lymphocytes, neutrophils, mononuclear cells, and NK cells possess?

A

catecholamine receptors - response is dependent on the cell receiving the signal

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13
Q

What are some hormones, neuropeptides, and neurotransmitters that affect the immune system?

A

cortisol
epi and NE
beta-endorphins
enkephalins

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14
Q

How does cortisol affect the immune system?

A

metabolic effects (stimulates gluconeogenesis)

anti-inflammatory effects (reduced cytokine activity, B and T cell reactivity, and NK cell activity)

modulates the processing of info from the sense organs

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15
Q

How do epi and NE affect the immune system?

A

released into circulation by the adrenal medulla, which increases leukocyte mobilization, resulting in an increase in NK activity

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16
Q

What are endorphins derived from, and when/where are they produced?

A

derived from pro-opiomelanocortin (POMC), which is synthesized in the pituitary after CRH stimulation, but can also be synthesized by immune competent cells

In the pituitary the POMC molecule is enzymatically split into the secretory products ACTH, and endorphin.

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17
Q

What do endorphins do?

A

play a role in analgesia and feelings of happiness

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18
Q

Where are enkephalins produced?

A

brain, pituitary, and adrenal gland

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19
Q

What do enkephalins do?

A

play a role in analgesia and feelings of happiness (can bind the same opioid receptors as endorphins

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20
Q

What effect do endorphins and enkephalins have on the immune system?

A

increase T cell reactivity and NK cell activity

endorphins are more like hormones, enkephalins more like neurotransmitters

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21
Q

define the two types of stress

A

acute: controllable emotional or mental stress (skydiving)
chronic: uncontrollable negative stress (caregiving to alzheimers patient)

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22
Q

What, immunologically, occurs during acute stress?

A

an increase in circulating leukocytes, particularly NK cells

23
Q

During an acute stress response, what is the short lasting immune modulation associated with?

A

increased catecholamine levels

24
Q

What is increased during an acute response to stress?

A

HR
cortisol
epinephrine
norepinephrine

25
Q

What leukocytes are increased during acute stress?

A

CD3+ T cells

CD4+ Th cells

CD8+ cytotoxic T cells

CD16+ monocytes

CD56+ NK cells

26
Q

How can you reproduce the increase in NK cell activity that is produce by acute stress?

A

adminstration of epi/NE

27
Q

What happens to the mononuclear cell population one hour after skydiving?

A

mononuclear cell populations decrease as they localize to regional lymph nodes

28
Q

immediate leukocyte mobilization in the circulation is due to what?

A

catecholamines

29
Q

What is the effect of catecholamines and cortisol on mobilized leukocytes?

A

leukocytes redistribute to the lymph nodes

30
Q

How does redistribution of leukocytes occur?

A

a consequence of hormonal modification of adhesion molecules on the surface of the leukocytes (increased CD11a) and activation of cognate adhesion receptors on the surface of endothelial cells (ICAM-1)

31
Q

discuss leukocyte redistribution in the context of delayed type hypersensitivity reaction

A

The acute effects have a positive impact on immune function as measured by delayed type hypersensitivity (DTH) reaction to intradermal injection of antigen.

Low cortisol concentrations (as a consequence of acute stress) of 5 mg/kg markedly enhance DTH responses.

Higher concentrations of 40 mg/kg depress
DTH responses.

Chronic stress (extending for several days or weeks) actually decreases immune responsiveness as judged by DTH.

32
Q

What can chronic, uncontrollable, negative stress result in?

A

immune suppression

33
Q

What do individuals who are chronically stressed exhibit?

A

decreased cytokine production

decreased Ab production

an increase in colds

34
Q

cytokines produced as a result of an ongoing immune or inflammatory response can have a direct effect on the CNS. what are these cytokines?

A

IL-1
TNF-alpha
IL-6

35
Q

What changes do cytokines cause in the CNS?

A

firing frequency of nerve cells

influence the secretion of neuroendocrine factors in the HPA axis, especially ACTH production

36
Q

What kind of receptors have been found in the CNS and the pituitary gland?

A

receptors for cytokines

37
Q

leukocytes are capable of neuropeptide and neurotransmitter production. What does activation of B and T lymphocytes stimulate these cells to produce?

A

ACTH

beta-endorphin

enkephalins

38
Q

What is sickness behavior?

A

Activation of the immune system by an infectious agent induces the production of cytokines (IL-1, IL-6, and TNF), which in addition to activating the immune system also send signals to the CNS that modify behavior. This behavior modification is known as “sickness behavior”

39
Q

What are symptoms of sickness behavior, and what are they a consequence of?

A

fever, headache, lethargy, muscle and joint pain, diminished appetite

a consequence of cytokines IL1, 6, TNF

40
Q

how do cytokines produce the effects of sickness behavior?

A

via circulation: cytokines cross the brain blood barrier most likely through the circumventricular organs (CVO). Neurons in this area express receptors for IL1, 6, and TNF. Interaction of these cytokines with their cognate receptors results in neural system activation and the production of prostaglandins.

via afferent neurons: Via the vagal afferents, IL-1 produced by leukocytes stimulates the related regions of the brain

41
Q

what do cytokines involved in sickness behavior do as part of the immune system?

A

alert the brain to infection or injury, communicating the body’s distress.

42
Q

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

A

systemic inflammation that can result in organ failure and death

43
Q

How does the CNS interact with the immune system to regulate excessive inflammation?

A

via efferent vagus and splenic nerve

44
Q

What does the splenic nerve release, and what does it do?

A

NE, stimulates the production of ACh by T lymphocytes via surface beta 2 adrenergic receptors

45
Q

What does ACh released by splenic T lymphocytes do?

A

ACh interacts with macrophages in the spleen via surface alpha 7 ACh receptors and inhibits the production of IL1, 6, and TNF

46
Q

What does an effective immune response require?

A

Energy and resources

47
Q

What occurs during an acute stress response (fight or flight)?

A

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

48
Q

Energy mobilization has to be directed towards the immune system or towards fight/flight, but cannot be utilized maximally by both at the same time. How does the body deal with this?

A

After the immediate release of catecholamines, which
mobilize the leukocytes of the immune system, the immune response is temporarily suppressed by the slower release of cortisol, in order to maximize energy for the fight or flight response

49
Q

when does cortisol production become disadvantageous?

A

when stress responses are maintained over longer periods of time

50
Q

what effect can an acute stress response have?

A

salubrious ;)

51
Q

what determines the magnitude of an immune response?

A

timing (duration) and nature (acute vs chronic)

52
Q

The evolutionarily adaptive fight-or-flight stress response may prepare the immune system for impending danger (e.g. infection and wounding by a predator). What would be the result?

A

enhanced immunological protection from the infectious agent and more rapid healing of the wound.

53
Q

What can stress exacerbate?

A

pathological conditions that are worsened by an increased immune responsiveness such as an autoimmune response or an inflammatory insult or disease condition.

54
Q

Differences exist in the ways that acute (short-term) and chronic (long-term) stressors affect the immune system. Give an example.

A

chronic stress significantly suppresses delayed-type hypersensitivity (DTH) responses (e.g. to skin test) and decreases leukocyte mobilization to the skin.

Acute stress enhances the DTH response and increases leukocyte mobilization.

Host Defense Exam 2 (11 decks)

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